Treatment of primary hyperaldosteronism | Medicina Clínica (English Edition)

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"documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2020;155:299-301" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "Editorial article" "titulo" => "Coronavirus infection in cancer patients, last update" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "299" "paginaFinal" => "301" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Infección por coronavirus en pacientes oncológicos, evidencias a fecha de hoy" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Miguel Borregón Rivilla, Katherin Aly Martínez Barroso" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Miguel" "apellidos" => "Borregón Rivilla" ] 1 => array:2 [ "nombre" => "Katherin Aly" "apellidos" => "Martínez Barroso" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775320304516" "doi" => "10.1016/j.medcli.2020.05.028" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775320304516?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020620304265?idApp=UINPBA00004N" "url" => "/23870206/0000015500000007/v1_202010060722/S2387020620304265/v1_202010060722/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Treatment of primary hyperaldosteronism" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "302" "paginaFinal" => "308" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Marta Araujo-Castro" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Marta" "apellidos" => "Araujo-Castro" "email" => array:1 [ 0 => "marta.araujo@salud.madrid.org" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Unidad de Neuroendocrinología, Servicio de Endocrinología y Nutrición, Hospital Universitario Ramón y Cajal, Madrid, Spain" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento del hiperaldosteronismo primario" ] ] "textoCompleto" => "IntroductionPrimary hyperaldosteronism (PHA) includes a number of disorders in which there is an unusual elevation of aldosterone in natremia, a relatively autonomous and independent aldosterone production of the renin-angiotensin-aldosterone system, and a non-suppression of aldosterone in response to sodium overload.<a class="elsevierStyleCrossRef" href="#bib0295">1</a> This inappropriately high production of aldosterone causes hypertension, cardiovascular damage, sodium retention, suppression of renin concentrations, and increased potassium excretion, which if prolonged and severe leads to hypokalemia.<a class="elsevierStyleCrossRef" href="#bib0295">1</a>PHA is underdiagnosed, and represents between 6% and 18% of the causes of HT according to the different studies, depending on the population studied and the diagnostic criteria used.<a class="elsevierStyleCrossRefs" href="#bib0300">2,3</a> Its correct identification is important, taking into account that PHA is associated with greater cardiovascular, cerebrovascular and renal morbidity and mortality than essential HT in subjects matched by age, sex and the same degree of HT.<a class="elsevierStyleCrossRef" href="#bib0310">4</a> Compared with patients with essential HT, a 6.5 times higher risk of non-fatal myocardial infarction is described; 12.1 times higher atrial fibrillation and 4.2 times higher stroke.<a class="elsevierStyleCrossRef" href="#bib0310">4</a> It is therefore essential to introduce specific treatment to reduce the negative impact of this condition, particularly on the cardiovascular system.There is consensus that drug therapy is the choice for patients with PHA due to bilateral disease.<a class="elsevierStyleCrossRefs" href="#bib0295">1,2,5</a> The main debate lies in what is the most appropriate treatment for patients with unilateral forms of PHA, whether medical or surgical. Various studies<a class="elsevierStyleCrossRefs" href="#bib0320">6–8</a> have shown that both drug therapy with mineralocorticoid receptor antagonists (MRA) and unilateral adrenalectomy, when performed appropriately, generally leads to resolution of hypokalaemia, improvement or resolution of HT and cardiovascular and renal parameters. However, the risks and benefits of both treatments and the conditions that must be met for the correct selection of the most appropriate treatment must be weighed. In the case of adrenalectomy, it is generally essential to have the results of a properly performed adrenal vein catheterization (AVC), which is not always easy. The potential risks associated with adrenalectomy, such as adrenal haemorrhage, among others, must also be weighed. On the other hand, the proven efficacy and safety of drug therapy must be taken into account, and its careful consideration in special situations such as pregnancy, familial hyperaldosteronism and elderly PHA patients (>65 years).This review mentions the main data that exist in favour of drug therapy in PHA; it discusses some special situations where drug therapy is considered to be particularly of first choice. The main studies comparing drug therapy and surgical treatment in PHA are also reviewed.Adrenal vein catheterizationNeed for adrenal vein catheterization to select the appropriate treatmentBearing in mind the limitations of imaging tests in order to select patients who could benefit from surgical treatment, it will be essential to carry them out in most cases.<a class="elsevierStyleCrossRefs" href="#bib0295">1,9,10</a> However, it could be avoided in younger patients (age <35 years) with spontaneous hypokalaemia, a significant excess of aldosterone, and unilateral adrenal lesions with radiological characteristics compatible with a cortical adenoma in the adrenal computed tomography (CT).<a class="elsevierStyleCrossRefs" href="#bib0295">1,11</a>The limitations associated with imaging tests include:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•That small adenomas can easily be interpreted as hyperplasia or, on the contrary, that areas of hyperplasia can be interpreted as microadenomas.</li><li class="elsevierStyleListItem" id="lsti0010">•That non-functioning adrenal incidentalomas are common in patients >50 years,<a class="elsevierStyleCrossRef" href="#bib0350">12</a> therefore, an adrenal adenoma may not correspond to Conn's disease in the context of PHA, especially as age advances.</li><li class="elsevierStyleListItem" id="lsti0015">•That there are many microadenomas that due to their small size will not be visible on CT or magnetic resonance imaging (MRI).</li></ul>In the different series that evaluate the efficacy of imaging tests in the PHA localization study, there are very low concordances.<a class="elsevierStyleCrossRefs" href="#bib0335">9,10,13–17</a> For example, in the series by Young et al.,<a class="elsevierStyleCrossRef" href="#bib0335">9</a> of the 203 PHA patients who underwent AVC and CT, this was clarifying only in 53% of the cases, and there were 25% of patients who underwent unnecessary surgery based on its findings. The concordance was even lower in the series by Zhu et al.,<a class="elsevierStyleCrossRef" href="#bib0360">14</a> 50.5%. These data are described in the meta-analysis by Kempers et al.,<a class="elsevierStyleCrossRef" href="#bib0355">13</a> which includes 950 patients; it focused on the usefulness of CT and MRI in PHA and found that these tests led to an incorrect diagnosis in 37.8% of patients. However, in the most recent radiological series, the rate of correct diagnosis increases; using specific adrenal protocols, with 3–1mm slice CT, diagnostic accuracy increases up to 100% in patients <35 years and 87% in subjects between 35 and 40 years.<a class="elsevierStyleCrossRef" href="#bib0345">11</a> On the other hand, there are ancillary tests such as 19-norcholesterol scintigraphy or 11C-metomidate PET-CT, with promising results.<a class="elsevierStyleCrossRef" href="#bib0380">18</a>Limitations of adrenal vein catheterizationAVC is an invasive and complex procedure, which requires an experienced team, consisting of at least one or two interventional radiologists, and an endocrinologist or nephrologist.<a class="elsevierStyleCrossRef" href="#bib0385">19</a> In addition, preparation is required before the procedure, and antihypertensive drugs must be adjusted, which is not always easy since patients with PHA often have refractory HT, difficult to manage and with associated cardiovascular disease. MRA drugs should be discontinued at least 6 weeks before, and amiloride 2 weeks prior to the procedure.<a class="elsevierStyleCrossRef" href="#bib0385">19</a> Additionally, hypokalaemia must be corrected before the procedure since hypokalaemia reduces aldosterone secretion, which can lead to false negatives.<a class="elsevierStyleCrossRef" href="#bib0385">19</a> Generally, hospitalization of the patient is recommended, taking into account that the rupture of the adrenal vein can occur suddenly in the 24–48h after the procedure is performed.<a class="elsevierStyleCrossRef" href="#bib0390">20</a>To all these requirements, it must be added that the canalization of the right adrenal vein is difficult due to its limited length and size, its acute angle with the inferior vena cava (IVC), which presents direct drainage into the IVC or small accessory hepatic vein, its various anatomical variants and that, when the patient is in the supine position, is compressed by the IVC.<a class="elsevierStyleCrossRef" href="#bib0395">21</a> If we also aim at performing a simultaneous bilateral catheterization, considered as of choice, the degree of difficulty increases<a class="elsevierStyleCrossRef" href="#bib0385">19</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Experience in adrenal vein catheterizationAs previously mentioned, a multidisciplinary team is needed, but also one that is made up of professionals who are experts in the technique. To obtain adequate results a learning curve is required.<a class="elsevierStyleCrossRefs" href="#bib0400">22,23</a> The importance of this learning is well illustrated in the study by Siracuse et al.,<a class="elsevierStyleCrossRef" href="#bib0405">23</a> in which the rate of selective catheterization increases as experience is gained, from 58% (2007–2010) to 82% (2011–2012). But these data are not those found in routine clinical practice, and even in reference centres, catheterization is not always performed. For example, in the Adrenal Vein sampling International Study(AVIS Study),<a class="elsevierStyleCrossRef" href="#bib0410">24</a> a multicenter study of hypertension management carried out in reference centres around the world, there were sites in which catheterization was performed in only 19% of the patients. On the other hand, in those centres where catheterization is performed routinely, the overall rate of catheterization and adequate localization was only 30.5%.<a class="elsevierStyleCrossRef" href="#bib0415">25</a>Potential risks of adrenal vein catheterizationThe risk of complications is low, 0.2–10%, and among the most important is the rupture of the adrenal vein whose risk is inversely related to the number of procedures performed by the interventional radiologist.<a class="elsevierStyleCrossRef" href="#bib0390">20</a> Adrenal haemorrhage can occur as a consequence of a ruptured adrenal vein or, less commonly, from a dissection, infarction, or thrombosis of the same.<a class="elsevierStyleCrossRef" href="#bib0410">24</a>Difficulties in interpreting the results of adrenal vein catheterizationIn addition to the above, there is the difficulty that if, despite all the above-mentioned limitations, the AVC is achieved, its interpretation is not easy. There is no consensus on the criteria that should be used to assess its efficacy, which complicates its interpretation. In addition, there are various options regarding the procedure protocol, without consensus on which is the best option.<a class="elsevierStyleCrossRef" href="#bib0410">24</a>Unilateral adrenalectomy in PHAResults of adrenalectomyA surgeon with experience in laparoscopic adrenalectomy must be available to obtain good surgical outcomes. And in terms of its efficacy, it is far from ideal. After an adrenalectomy, although a significant percentage experience improvement in blood pressure control,<a class="elsevierStyleCrossRef" href="#bib0420">26</a> 50–60%<a class="elsevierStyleCrossRefs" href="#bib0425">27,28</a> remain hypertensive, and even up to 70%, according to some series, such as the one published in JAMA of Surgery in 2019<a class="elsevierStyleCrossRef" href="#bib0430">28</a> in a cohort of 435 patients with PHA who underwent unilateral adrenalectomy and in the World J Surgery 2020 in 190 patients,<a class="elsevierStyleCrossRef" href="#bib0435">29</a> among other.<a class="elsevierStyleCrossRef" href="#bib0440">30</a> Some studies have reported non-cure rates of up to 80%.<a class="elsevierStyleCrossRef" href="#bib0420">26</a>Several factors associated with the persistence of HT after adrenalectomy have been described, such as the coexistence of a family history of HT,<a class="elsevierStyleCrossRefs" href="#bib0445">31,32</a> which is present in approximately 60% of subjects with PHA; the need for more than two drugs to control BP,<a class="elsevierStyleCrossRefs" href="#bib0445">31,33</a> which occurs in more than half of the patients; and HT duration for more than five years,<a class="elsevierStyleCrossRefs" href="#bib0450">32,33</a> a very common situation, taking into account that delay in diagnosis is common. There are other factors such as male sex and overweight, associated with a poor surgery outcome, common in patients with PHA.<a class="elsevierStyleCrossRef" href="#bib0450">32</a> For example, the Primary Aldosteronism Surgical Outcome (STEP)<a class="elsevierStyleCrossRef" href="#bib0460">34</a> study, in a cohort of 699 patients who underwent PHA, found that women had a greater probability of biochemical cure (OR 2.25; 95% CI 1.40–3.62) than men and also young people (OR 0.95 per extra year, 0.93–0.8) and those who needed fewer drugs preoperatively to control BP (p<0.001). These results reflect the importance of the need and the value of the establishment of specific HT units, where these patients are adequately guided from the beginning and early diagnoses of patients with PHA are carried out to reduce the number of cases with limited cure possibilities after adrenalectomy.Risks of unilateral adrenalectomyAmong the risks associated with unilateral adrenalectomy are postoperative hyperkalaemia which, although it is transient and easily manageable in 16% of patients, there is 5% with chronic hyperkalaemia and some cases of potentially lethal hyperkalaemia with figures up to 7.0nmol/L.<a class="elsevierStyleCrossRef" href="#bib0465">35</a> Several factors associated with an increased risk of postsurgical hyperkalaemia have been identified, such as age greater than 53, HT with more than nine years of progression, the presence of adrenal lesions >2cm and deterioration of renal function, all of them relatively common in patients with PHA.<a class="elsevierStyleCrossRefs" href="#bib0465">35,36</a>Another of the classical potential risks of surgery in PHA is the deterioration of renal function after the intervention. It seems to be related to the resolution of the hyperfiltration state associated with PHA after surgery.<a class="elsevierStyleCrossRef" href="#bib0475">37</a> A recent meta-analysis,<a class="elsevierStyleCrossRef" href="#bib0480">38</a> which includes a total of 6056 patients with PHA, found a decrease in glomerular filtration of 11mL/min after adrenalectomy. Among the risk factors for impaired kidney function are age (OR=6.37, p=0.0006), and preoperative aldosterone levels (OR=3.12; p=0.0209) and potassium (OR=2.87; p=0.0010), as these factors increase, the risk of impaired kidney function increases.<a class="elsevierStyleCrossRef" href="#bib0485">39</a>There are other more uncommon and less reported complications, such as the potential deterioration of the lipid profile, described in up to 68.4% of patients in Kaga's series, and the development of new onset dyslipidaemia by 46%.<a class="elsevierStyleCrossRef" href="#bib0490">40</a> To all this are added the risks inherent to the intervention, such as bleeding, bruising, and so on. However, it should be noted that the risks inherent in laparoscopic adrenalectomy are few and uncommon. In addition, there are other emerging minimally invasive techniques, such as percutaneous ablation of adrenal adenomas, reporting rates of improvement and cure of HT in 75.5% of patients,<a class="elsevierStyleCrossRef" href="#bib0495">41</a> which could represent a definitive treatment in patients with PHA who refuse surgery or are not candidates for it.Drug therapy for PHAIndicationsThe treatment of PHA is aimed at the prevention of morbidity and mortality derived from hypertension, the correction of hypokalaemia, and the avoidance of organ damage associated with excess aldosterone.<a class="elsevierStyleCrossRefs" href="#bib0295">1,5</a> Several studies have demonstrated that MRA are effective in controlling blood pressure (BP) and protecting against specific organ damage due to excess aldosterone.<a class="elsevierStyleCrossRefs" href="#bib0295">1,42–44</a>The classical indications for drug therapy include bilateral hyperplasia, hereditary forms, unilateral adenomas with high surgical risk, rejection of surgery by the patient, medical contraindication for surgery, the inability to perform an AVC, advanced age and not having a clear diagnosis in catheterization. All this represents more than 70% of PHA cases, as potential candidates for first-line drug therapy<a class="elsevierStyleCrossRef" href="#bib0315">5</a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Available drugsThe drugs available to us are mainly spironolactone and eplerenone, but if these cannot be used or are not sufficient, there are other options (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>SpironolactoneIt is considered the first-line drug in PHA. It is an MRA, but it also blocks the production of androgens and progesterone, which explains part of its side effects, which are gynecomastia in men and menstrual disorders in women, side effects depending on the dose used.<a class="elsevierStyleCrossRef" href="#bib0295">1</a> Jeunemaitre et al.<a class="elsevierStyleCrossRef" href="#bib0515">45</a> reported an incidence of gynecomastia of 6.9% with doses of <50mg/day and 52% with doses >150mg/day, after 6 months of treatment.The starting dose of spironolactone is 12.5–25mg/day in a single daily dose, and the maximum recommended doses of 400mg/day.<a class="elsevierStyleCrossRefs" href="#bib0295">1,46</a> It is recommended to take it with a meal rich in fat as it has been shown to significantly improve its oral bioavailability (up to 90%).<a class="elsevierStyleCrossRef" href="#bib0525">47</a> Spironolactone is converted in the liver into two active metabolites, 7α-thio-methylpyronolactone and canrenone, which are responsible for the persistence of the pharmacological effect, and therefore the possibility of administering it only once a day.<a class="elsevierStyleCrossRef" href="#bib0530">48</a>It is considered a powerful drug to control blood pressure (BP), lowers systolic pressure by 40–60mmHg and diastolic pressure at 10–20mmHg, obtaining figures of (BP) <140/90 in 50% of patients when used as monotherapy.<a class="elsevierStyleCrossRef" href="#bib0535">49</a> Some factors associated with a greater response to spironolactone have been identified, such as the degree of renin suppression (the greater the suppression, the greater the response) and the degree of aldosterone production (the greater the aldosterone production, the greater the response).<a class="elsevierStyleCrossRef" href="#bib0540">50</a> On the other hand, some studies identify the response to spironolactone as a predictive marker of response to adrenalectomy.<a class="elsevierStyleCrossRef" href="#bib0545">51</a>EplerenoneIn the event that there are side effects with spironolactone, or when it cannot be used for other reasons, eplerenone, a selective mineralocorticoid receptor antagonist that hardly exerts antagonistic effects on the androgen and progesterone receptor, could be used, thus lacking the same side effects associated with the use of spironolactone.<a class="elsevierStyleCrossRef" href="#bib0530">48</a>In contrast, it is less potent than spironolactone and its half-life is shorter, 6–8h, so it must be administered twice a day, compared to the daily administration of spironolactone.<a class="elsevierStyleCrossRef" href="#bib0530">48</a>The main differences between spironolactone and eplerenone are that spironolactone is administered every 24h and eplerenone every 12h; eplerenone is metabolized by the liver through cytochrome PY3A4, therefore it interacts with other drugs such as digoxin and non-pharmacological methods, and is contraindicated in patients with severe liver cirrhosis (Child C)<a class="elsevierStyleCrossRefs" href="#bib0520">46,48</a> (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).Other treatmentsIf these two drugs fail to achieve adequate BP control, or they cannot be used, there are other alternatives such as amiloride, thiazides, calcium channel blockers and angiotensin converting enzyme inhibitors (ACEI), among others.<a class="elsevierStyleCrossRef" href="#bib0535">49</a> Low doses of a thiazide diuretic drug, triamterene or amiloride may be added to try to avoid high doses of spironolactone, which can cause side effects.<a class="elsevierStyleCrossRef" href="#bib0295">1</a>Drug therapy versus surgical treatment in PHAThere are several studies that analyze the differences in the degree of control of hypertension, improvement of cardiovascular and renal parameters between drug therapy and surgical treatment, without finding significant differences between the two. Among them we find the work of Catena et al., of 2007,<a class="elsevierStyleCrossRef" href="#bib0320">6</a> in which the evolution of cardiovascular parameters is analyzed based on long-term echocardiographic data in a cohort of 24 patients undergoing adrenalectomy and 30 undergoing spironolactone. Significant improvements are found in the degree of control of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in both groups, with no relevant differences in both arms of treatment, and in the degree of improvement of long-term left ventricular hypertrophy (LVH).Another study published in 2008,<a class="elsevierStyleCrossRef" href="#bib0325">7</a> in which only patients undergoing adrenalectomy were analyzed, found that, in patients with long-standing HT, with evidence of vascular remodelling, or both, the chances of cure after adrenalectomy are especially low. This prospective study of 50 PAHs who underwent surgery found a cure rate of 29.5%, and a cut-off value of 9.12% for the mean/arterial lumen ratio provided a sensitivity of 64% and a specificity of 100% for the identification of post-adrenalectomy cure and a cut-off value of 38 months for the duration of HT provided a sensitivity of 49% and a specificity of 100%.Results with greater strength can be obtained from a meta-analysis published in 2015<a class="elsevierStyleCrossRef" href="#bib0330">8</a> which includes four studies with a total of 178 patients in the adrenalectomy arm and 177 in the drug therapy arm. No significant differences were found in LVH improvement between drug therapy and surgical treatment, or in the long term, both drug therapy (−7.1±4.8%) and surgical treatment (−12.5±5.1%) reduced the LV mass index, so the authors conclude that both treatments were equally effective in achieving the primary objective.In another study aimed at analysing glucose tolerance and insulin sensitivity, in a series of 47 patients, 20 undergoing adrenalectomy and 27 undergoing drug therapy, significant improvements were found in the insulin response to glucose overload, in the glucose-insulin ratio and in the HOMA index in both, the drug therapy and the surgical treatment group, without finding significant differences between the two.<a class="elsevierStyleCrossRef" href="#bib0550">52</a>In a cohort of 48 patients treated with spironolactone at mean doses of 33.3mg/day, spironolactone reduced SBP from 149.3 to 126.2 and DBP from 88.2 to 78.3at one year of treatment, and of 81% of patients with LVH, 92% had a significant improvement in the degree of hypertrophy, and 41% achieved normal values. The authors conclude that, in patients with PHA, low doses of spironolactone achieved a significant improvement in LVH.<a class="elsevierStyleCrossRef" href="#bib0555">53</a>Another study<a class="elsevierStyleCrossRef" href="#bib0560">54</a> analyzed the changes in the carotid intima-media thickness in a cohort of 42 patients, 21 in the drug therapy arm and 21 in the surgical one. Reductions in the carotid intima-media of a similar degree were observed in the treatment groups at 6 years of follow-up. Although the magnitude of improvement in the first year was significantly greater in the adrenalectomy group (by 70%; p<0.05); the difference (by 27%) became non-significant at six years. The authors conclude that, in the long term, spironolactone in patients with PHA achieved a significant reduction in intima-media thickness, comparable to that produced by adrenalectomy in unilateral forms.From what we can see with these examples, there is a lot of evidence that does not demonstrate greater efficacy of surgical treatment compared to drug therapy, neither in the improvement of LVH, the parameters of glucose metabolism nor in the carotid intima-media thickness.However, some of the studies focused on cost/benefit analysis comparing both treatments estimate a saving of Canadian $ 31,132 per patient in favour of surgical treatment compared to long-term drug therapy.<a class="elsevierStyleCrossRef" href="#bib0565">55</a> Another fact that supports the selection of surgical treatment as a choice for younger patients.Special situations regarding PHAGlucocorticoid-remediable hyperaldosteronismGlucocorticoid-remediable hyperaldosteronism or familial hyperaldosteronism type 1,<a class="elsevierStyleCrossRefs" href="#bib0295">1,56</a> treatment with long-acting glucocorticoids, either dexamethasone or prednisone is considered the treatment of choice. It should be given in the evening to suppress the morning peak in adrenocorticotropic hormone (ACTH), and the goal is to normalize BP and potassium levels. The mean starting doses are 0.125–0.25mg/day of dexamethasone or 2.5–5mg/day of prednisone. In some cases, the association with spironolactone, eplerenone or other drugs may be necessary for adequate blood pressure control.<a class="elsevierStyleCrossRef" href="#bib0295">1</a> In children, glucocorticoid dose should be adjusted according to age and weight, and if the association with antihypertensive drugs is necessary, eplerenone is considered the choice to avoid the antiandrogenic effects of spironolactone that could affect growth (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Primary hyperaldosteronism in the elderlyAnother section to highlight is PHA in the elderly. In these patients there is hardly any previous literature on AVC, so the distribution of unilateral and bilateral forms in this age group is unknown. On the other hand, these patients have a higher risk of non-cure after adrenalectomy and of surgical complications.<a class="elsevierStyleCrossRef" href="#bib0575">57</a> A recent study<a class="elsevierStyleCrossRef" href="#bib0575">57</a> with a cohort of 1691 young patients and 411 patients older than 65 years who underwent adrenalectomy, found that the cure rate is lower in the older group (36 vs. 18%, p=0.005), and that the risk of hyperkalaemia (5 vs. 15%, p=0.002) and renal function deterioration (12 vs. 27%, p<0.001) is higher. The authors conclude that adrenalectomy was useful in elderly patients in terms of biochemical cure and reduction of antihypertensive treatment, but remission of hypertension was limited in this population. And that special caution should be exercised due to the risk of postoperative renal failure and hyperkalaemia (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).Primary hyperaldosteronism during pregnancyDrug therapy with alpha-methyldopa is considered the treatment of choice in PHA during pregnancy.<a class="elsevierStyleCrossRef" href="#bib0580">58</a> The doses used range between 250 and 3000mg/day. Labetalol could be used as a second-line in doses of 100–2400mg/day. Spironolactone is contraindicated due to the risk of feminization if the offspring is male, and with eplerenone there are few studies. Surgical treatment would be reserved for hypertension refractory to drug therapy and in the second trimester of pregnancy (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).ConclusionsCT and MRI are not useful for the diagnosis of PHA location, which leads to having to perform CVA on most patients in order to select those who could benefit from surgical treatment. However, it should be taken into account that AVC is a complex, invasive procedure, with little experience and little success, with catheterization rates of 30.5%, even in centres considered to be of reference. On the other hand, its results are difficult to interpret due to the lack of consensus in the cut-off points of the different parameters that evaluate its efficacy.The cure rate after adrenalectomy ranges from 30% to 50% in the different series. It is a technique that is not exempt from risks, among which the frequency of hyperkalaemia in 16% and the development of chronic renal disease in up to 20% stand out.Considering the different causes of PHA, drug therapy is considered of choice in more than 70% of PAHs. There are safe and effective drugs, especially spironolactone, which, although associated with gynecomastia, is an enormously powerful antihypertensive. Several studies have observed similar results for localized PHA, in terms of improvement in LVH, carotid intima-media thickness, and SBP and DBP between drug therapy and surgical treatment. Medical treatment is also generally considered of choice during pregnancy, in those over 65 years of age and in familial types.All things considered, there are strong grounds for making drug therapy in PHA the general recommendation. However, in young patients with unilateral hyperaldosteronism and low surgical risk, and in sites with interventional radiologists who are experts in AVC, with high catheterization rates and low risk of complications, who have a surgical team with extensive experience in adrenal pathology, surgical treatment should be considered as the first option. On the other hand, surgical treatment appears to be more cost-effective, especially in young patients.Conflict of interestsThe author declares that there is no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1394838" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1278406" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1394839" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1278405" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Adrenal vein catheterization" "secciones" => array:1 [ 0 => array:3 [ "identificador" => "sec0015" "titulo" => "Need for adrenal vein catheterization to select the appropriate treatment" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Limitations of adrenal vein catheterization" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Experience in adrenal vein catheterization" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Potential risks of adrenal vein catheterization" ] 3 => array:2 [ "identificador" => "sec0035" "titulo" => "Difficulties in interpreting the results of adrenal vein catheterization" ] ] ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Unilateral adrenalectomy in PHA" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Results of adrenalectomy" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Risks of unilateral adrenalectomy" ] ] ] 7 => array:3 [ "identificador" => "sec0055" "titulo" => "Drug therapy for PHA" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Indications" ] 1 => array:3 [ "identificador" => "sec0065" "titulo" => "Available drugs" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Spironolactone" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "Eplerenone" ] 2 => array:2 [ "identificador" => "sec0080" "titulo" => "Other treatments" ] ] ] ] ] 8 => array:2 [ "identificador" => "sec0085" "titulo" => "Drug therapy versus surgical treatment in PHA" ] 9 => array:3 [ "identificador" => "sec0090" "titulo" => "Special situations regarding PHA" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0095" "titulo" => "Glucocorticoid-remediable hyperaldosteronism" ] 1 => array:2 [ "identificador" => "sec0100" "titulo" => "Primary hyperaldosteronism in the elderly" ] 2 => array:2 [ "identificador" => "sec0105" "titulo" => "Primary hyperaldosteronism during pregnancy" ] ] ] 10 => array:2 [ "identificador" => "sec0110" "titulo" => "Conclusions" ] 11 => array:2 [ "identificador" => "sec0115" "titulo" => "Conflict of interests" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-03-25" "fechaAceptado" => "2020-04-29" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1278406" "palabras" => array:5 [ 0 => "Primary hyperaldosteronism" 1 => "Adrenal vein sampling" 2 => "Adrenalectomy" 3 => "Spironolactone" 4 => "Eplerenone" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1278405" "palabras" => array:5 [ 0 => "Hiperaldosteronismo primario" 1 => "Cateterismo de venas adrenales" 2 => "Adrenalectomía" 3 => "Espironolactona" 4 => "Eplerenona" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Primary aldosteronism is associated with higher cardiovascular and renal morbidity and mortality than essential hypertension in age- and sex-matched patients with the same degree of blood pressure elevation. Therefore, it is essential to establish a specific treatment to avoid the deleterious effects of aldosterone excess. Although adrenalectomy is generally considered the treatment of choice in cases of primary aldosteronism due to unilateral disease, several aspects and circumstances should be taken into account that may make medical treatment more appropriate. Among them, in this review we mention the limited experience and efficacy, and the potential risks of adrenal vein sampling; the risks and low efficacy of adrenalectomy; the high safety and efficacy of medical treatment and some special situations such as primary aldosteronism during pregnancy, in patients of advanced age or hereditary forms of primary aldosteronism, in which medical treatment is considered especially indicated as the first line therapy. The main studies comparing medical and surgical treatment in primary aldosteronism are also discussed." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El hiperaldosteronismo primario (HAP) se asocia con una mayor morbimortalidad cardiovascular y renal que la hipertensión arterial (HTA) esencial, a misma edad, sexo y grado de HTA. Por ello, es esencial instaurar un tratamiento específico para aminorar los efectos deletéreos del exceso de aldosterona. Aunque se considera que la adrenalectomía es generalmente el tratamiento de elección en los casos de HAP por enfermedad unilateral, se deben tener en cuenta varios aspectos y circunstancias que pueden hacer más adecuado el tratamiento médico. Entre ellos, en esta revisión se mencionan, la limitada experiencia y eficacia, y los riesgos del cateterismo de venas adrenales; los riesgos y baja eficacia de la adrenalectomía; la elevada seguridad y eficacia del tratamiento médico y algunas situaciones especiales como el embarazo, la edad avanzada o las formas familiares, en las que el tratamiento médico se considera especialmente indicado como primera línea. También se comentan los principales estudios que comparan el tratamiento médico y quirúrgico en el HAP." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Araujo-Castro M. Tratamiento del hiperaldosteronismo primario. Med Clín. 2020;155:302–308." ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "BP: blood pressure; CT: computed tomography; AVC: adrenal vein catheterization; [L cortisol]: cortisol concentration on the catheter side; [IVC cortisol]: cortisol concentration in the inferior vena cava; [ALDL]: aldosterone concentration on the catheter side; [ALDIVC]: concentration of aldosterone in the inferior vena cava; [Non-dominant ALD]: concentration of aldosterone on the non-dominant side; [Non-dominant cortisol]: cortisol concentration on the non-dominant side; [Dominant ALD]: concentration of aldosterone on the dominant side; [Dominant Cortisol]: cortisol concentration on the dominant side." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pre-procedure preparation (weeks prior to AVC) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Correct hypokalaemia and BP control.• Discontinue spironolactone and eplerenone 6 weeks before and amiloride 2 weeks before. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pre-procedure conditions (day/s prior to AVC) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Contrast CT: anatomy and anatomical relationships of the right adrenal vein.• Serum aldosterone, renin and potassium levels lab tests.• Perform in the morning (avoid ACTH fluctuations).• Control pain and emotional stress (reduce activation of the hypothalamic-pituitary-adrenal axis).• Supine position 1h before the procedure. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intra-procedure conditions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Evaluate adequate catheterization: CT, rapid cortisol immunoassays \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protocols \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Sequential catheterization with ACTH (infusion 50μ/h or bolus of 250μg).• Sequential catheterization with metoclopramide (few studies).• Sequential catheterization without ACTH.• Simultaneous bilateral catheterization (without ACTH). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AVC interpretation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Selectivity index=[cortisol L]/[cortisol IVC]<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>• Relative secretion index=[ALDL]/[cortisol L][ALDVCI]/[cortisol IVC]• Contralateral suppression index=[Non-dominant ALD]/[Non-dominant cortisol][ALDVCI]/[cortisol IVC]• Lateralization index=[Dominant ALD]/[Dominant cortisol]<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a>[Non-dominant ALD]/[Non-dominant cortisol] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Post-procedure conditions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Admission 24–48h (risk of adrenal vein rupture)• Control of constants and pain, mainly \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2393798.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Use cut-off points of 2 for AVC without ACTH and 3 for AVC with ACTH (ideally, use reference laboratory cut-off points)." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Use a cut-off point of between 2 and 4 in AVC without ACTH and 2.6 and 4 in AVC with ACTH." ] ] ] "descripcion" => array:1 [ "en" => "Preparation, protocols and interpretation of adrenal vein catheterization." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "PHA, primary hyperaldosteronism; Surg, surgical." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Entity \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Proportion of patients with PHA \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sporadic bilateral hyperplasia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60–65% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hereditary forms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–2% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unilateral adenomas with high surg. risk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–2% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Contraindication for surgery \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–5% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patient rejection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not reported \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No clear diagnosis in catheterization \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30–70% of catheterizations \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Advanced age (>65 years)<a class="elsevierStyleCrossRef" href="#bib0575">57</a>,<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5–10% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pregnancy<a class="elsevierStyleCrossRef" href="#bib0580">58</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.8% of pregnancies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No possibility of catheterization \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Variable according to site \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2393797.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "Relative indication, depending on the risk-benefit balance, and consider the time of HT progression and other factors associated with a lower probability of cure after adrenalectomy" ] ] ] "descripcion" => array:1 [ "en" => "General indications for drug therapy in primary hyperaldosteronism." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "CYP3A4, cytochrome P450 3A4." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Spironolactone \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Eplerenone \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Half-life \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24–58h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3–6h \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bioavailability \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increase with high-fat meals \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not affected by ingestion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Active metabolites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes: canrenone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Elimination \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Renal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Liver \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Drug interaction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes (CYP3A4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Contraindications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HyperkalaemiaAddison's diseaseConcomitant use with eplerenone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe liver cirrhosisHyperkalaemiaUse of strong CYP3A4 inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Posology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Every 24h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Every 8–12h \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Starting dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.5/25mg/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50mg/day \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Maximum dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">400mg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100mg \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Side effects \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gynecomastia, erectile dysfunction, and sexual anaesthesia (males); menstrual disturbances (women) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not described \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pregnancy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Contraindicated (Category D) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">With caution (category B) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Breastfeeding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Avoid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Avoid \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2393799.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Drug therapy in primary hyperaldosteronism.<a class="elsevierStyleCrossRef" href="#bib0520">46</a>" ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "PHA: primary hyperaldosteronism; FH: family history; HT: arterial hypertension; CYP11B1/CYP11B2: cytochrome P450 B1/B2; ALD: aldosterone." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Glucocorticoid-remediable hyperaldosteronism \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hyperaldosteronism in >65 years \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hyperaldosteronism in pregnancy \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prevalence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1% PHA.<a class="elsevierStyleCrossRef" href="#bib0295">1</a> Most common cause of monogenic HT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5–10%<a class="elsevierStyleCrossRef" href="#bib0575">57</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.8% of pregnancies<a class="elsevierStyleCrossRef" href="#bib0580">58</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Suspicious diagnosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Children or young adults with severe and/or refractory HT and FH of HT or early haemorrhagic stroke \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refractory/resistant HT and/or hypokalaemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Difficult to control HT, preeclampsia, hypokalaemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Specific diagnosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Genetic study for mutations in CYP11B1/CYP11B2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increases the risk of false positives in the aldosterone/renin ratio \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical suspicion + elevated aldosterone and suppressed renin. Do not perform confirmation test<a class="elsevierStyleCrossRef" href="#bib0580">58</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Special considerations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High risk of haemorrhagic stroke (18%, mean age=32 years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age is a risk factor for non-cure after adrenalectomy<a class="elsevierStyleCrossRefs" href="#bib0450">32,33</a> and increased risk of hyperkalaemia and deterioration of renal function after surgery<a class="elsevierStyleCrossRef" href="#bib0575">57</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Physiological activation of the renin angiotensin aldosterone system during pregnancy. Oestrogens and progesterones counteract the action of ALD \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dexamethasone 0.125–0.25mg/day or prednisone 2.5–5mg/day, at night \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Spironolactone or Eplerenone as 1st line \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Methyldopa 250–3000mg/day.Second-line: labetalol 100–2400mg/day \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2393800.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Special situations in primary hyperaldosteronism." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:58 [ 0 => array:3 [ "identificador" => "bib0295" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The management of primary aldosteronism: Case detection, diagnosis, and treatment: An endocrine society clinical practice guideline" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.W. 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Treatment of primary hyperaldosteronism

Tratamiento del hiperaldosteronismo primario

Marta Araujo-Castro

Unidad de Neuroendocrinología, Servicio de Endocrinología y Nutrición, Hospital Universitario Ramón y Cajal, Madrid, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Primary hyperaldosteronism &#40;PHA&#41; includes a number of disorders in which there is an unusual elevation of aldosterone in natremia&#44; a relatively autonomous and independent aldosterone production of the renin-angiotensin-aldosterone system&#44; and a non-suppression of aldosterone in response to sodium overload&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a> This inappropriately high production of aldosterone causes hypertension&#44; cardiovascular damage&#44; sodium retention&#44; suppression of renin concentrations&#44; and increased potassium excretion&#44; which if prolonged and severe leads to hypokalemia&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">PHA is underdiagnosed&#44; and represents between 6&#37; and 18&#37; of the causes of HT according to the different studies&#44; depending on the population studied and the diagnostic criteria used&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">2&#44;3</span></a> Its correct identification is important&#44; taking into account that PHA is associated with greater cardiovascular&#44; cerebrovascular and renal morbidity and mortality than essential HT in subjects matched by age&#44; sex and the same degree of HT&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">4</span></a> Compared with patients with essential HT&#44; a 6&#46;5 times higher risk of non-fatal myocardial infarction is described&#59; 12&#46;1 times higher atrial fibrillation and 4&#46;2 times higher stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">4</span></a> It is therefore essential to introduce specific treatment to reduce the negative impact of this condition&#44; particularly on the cardiovascular system&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">There is consensus that drug therapy is the choice for patients with PHA due to bilateral disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">1&#44;2&#44;5</span></a> The main debate lies in what is the most appropriate treatment for patients with unilateral forms of PHA&#44; whether medical or surgical&#46; Various studies<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">6&#8211;8</span></a> have shown that both drug therapy with mineralocorticoid receptor antagonists &#40;MRA&#41; and unilateral adrenalectomy&#44; when performed appropriately&#44; generally leads to resolution of hypokalaemia&#44; improvement or resolution of HT and cardiovascular and renal parameters&#46; However&#44; the risks and benefits of both treatments and the conditions that must be met for the correct selection of the most appropriate treatment must be weighed&#46; In the case of adrenalectomy&#44; it is generally essential to have the results of a properly performed adrenal vein catheterization &#40;AVC&#41;&#44; which is not always easy&#46; The potential risks associated with adrenalectomy&#44; such as adrenal haemorrhage&#44; among others&#44; must also be weighed&#46; On the other hand&#44; the proven efficacy and safety of drug therapy must be taken into account&#44; and its careful consideration in special situations such as pregnancy&#44; familial hyperaldosteronism and elderly PHA patients &#40;&#62;65 years&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">This review mentions the main data that exist in favour of drug therapy in PHA&#59; it discusses some special situations where drug therapy is considered to be particularly of first choice&#46; The main studies comparing drug therapy and surgical treatment in PHA are also reviewed&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Adrenal vein catheterization</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Need for adrenal vein catheterization to select the appropriate treatment</span><p id="par0025" class="elsevierStylePara elsevierViewall">Bearing in mind the limitations of imaging tests in order to select patients who could benefit from surgical treatment&#44; it will be essential to carry them out in most cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">1&#44;9&#44;10</span></a> However&#44; it could be avoided in younger patients &#40;age &#60;35 years&#41; with spontaneous hypokalaemia&#44; a significant excess of aldosterone&#44; and unilateral adrenal lesions with radiological characteristics compatible with a cortical adenoma in the adrenal computed tomography &#40;CT&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">1&#44;11</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The limitations associated with imaging tests include&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0035" class="elsevierStylePara elsevierViewall">That small adenomas can easily be interpreted as hyperplasia or&#44; on the contrary&#44; that areas of hyperplasia can be interpreted as microadenomas&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0040" class="elsevierStylePara elsevierViewall">That non-functioning adrenal incidentalomas are common in patients &#62;50 years&#44;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">12</span></a> therefore&#44; an adrenal adenoma may not correspond to Conn&#39;s disease in the context of PHA&#44; especially as age advances&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0045" class="elsevierStylePara elsevierViewall">That there are many microadenomas that due to their small size will not be visible on CT or magnetic resonance imaging &#40;MRI&#41;&#46;</p></li></ul></p><p id="par0050" class="elsevierStylePara elsevierViewall">In the different series that evaluate the efficacy of imaging tests in the PHA localization study&#44; there are very low concordances&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">9&#44;10&#44;13&#8211;17</span></a> For example&#44; in the series by Young et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">9</span></a> of the 203 PHA patients who underwent AVC and CT&#44; this was clarifying only in 53&#37; of the cases&#44; and there were 25&#37; of patients who underwent unnecessary surgery based on its findings&#46; The concordance was even lower in the series by Zhu et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">14</span></a> 50&#46;5&#37;&#46; These data are described in the meta-analysis by Kempers et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a> which includes 950 patients&#59; it focused on the usefulness of CT and MRI in PHA and found that these tests led to an incorrect diagnosis in 37&#46;8&#37; of patients&#46; However&#44; in the most recent radiological series&#44; the rate of correct diagnosis increases&#59; using specific adrenal protocols&#44; with 3&#8211;1<span class="elsevierStyleHsp" style=""></span>mm slice CT&#44; diagnostic accuracy increases up to 100&#37; in patients &#60;35 years and 87&#37; in subjects between 35 and 40 years&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">11</span></a> On the other hand&#44; there are ancillary tests such as 19-norcholesterol scintigraphy or 11C-metomidate PET-CT&#44; with promising results&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">18</span></a></p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Limitations of adrenal vein catheterization</span><p id="par0055" class="elsevierStylePara elsevierViewall">AVC is an invasive and complex procedure&#44; which requires an experienced team&#44; consisting of at least one or two interventional radiologists&#44; and an endocrinologist or nephrologist&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">19</span></a> In addition&#44; preparation is required before the procedure&#44; and antihypertensive drugs must be adjusted&#44; which is not always easy since patients with PHA often have refractory HT&#44; difficult to manage and with associated cardiovascular disease&#46; MRA drugs should be discontinued at least 6 weeks before&#44; and amiloride 2 weeks prior to the procedure&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">19</span></a> Additionally&#44; hypokalaemia must be corrected before the procedure since hypokalaemia reduces aldosterone secretion&#44; which can lead to false negatives&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">19</span></a> Generally&#44; hospitalization of the patient is recommended&#44; taking into account that the rupture of the adrenal vein can occur suddenly in the 24&#8211;48<span class="elsevierStyleHsp" style=""></span>h after the procedure is performed&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">20</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">To all these requirements&#44; it must be added that the canalization of the right adrenal vein is difficult due to its limited length and size&#44; its acute angle with the inferior vena cava &#40;IVC&#41;&#44; which presents direct drainage into the IVC or small accessory hepatic vein&#44; its various anatomical variants and that&#44; when the patient is in the supine position&#44; is compressed by the IVC&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">21</span></a> If we also aim at performing a simultaneous bilateral catheterization&#44; considered as of choice&#44; the degree of difficulty increases<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">19</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Experience in adrenal vein catheterization</span><p id="par0065" class="elsevierStylePara elsevierViewall">As previously mentioned&#44; a multidisciplinary team is needed&#44; but also one that is made up of professionals who are experts in the technique&#46; To obtain adequate results a learning curve is required&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">22&#44;23</span></a> The importance of this learning is well illustrated in the study by Siracuse et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">23</span></a> in which the rate of selective catheterization increases as experience is gained&#44; from 58&#37; &#40;2007&#8211;2010&#41; to 82&#37; &#40;2011&#8211;2012&#41;&#46; But these data are not those found in routine clinical practice&#44; and even in reference centres&#44; catheterization is not always performed&#46; For example&#44; in the <span class="elsevierStyleItalic">Adrenal Vein sampling International Study</span><span class="elsevierStyleItalic">&#40;AVIS Study&#41;</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">24</span></a> a multicenter study of hypertension management carried out in reference centres around the world&#44; there were sites in which catheterization was performed in only 19&#37; of the patients&#46; On the other hand&#44; in those centres where catheterization is performed routinely&#44; the overall rate of catheterization and adequate localization was only 30&#46;5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Potential risks of adrenal vein catheterization</span><p id="par0070" class="elsevierStylePara elsevierViewall">The risk of complications is low&#44; 0&#46;2&#8211;10&#37;&#44; and among the most important is the rupture of the adrenal vein whose risk is inversely related to the number of procedures performed by the interventional radiologist&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">20</span></a> Adrenal haemorrhage can occur as a consequence of a ruptured adrenal vein or&#44; less commonly&#44; from a dissection&#44; infarction&#44; or thrombosis of the same&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">24</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Difficulties in interpreting the results of adrenal vein catheterization</span><p id="par0075" class="elsevierStylePara elsevierViewall">In addition to the above&#44; there is the difficulty that if&#44; despite all the above-mentioned limitations&#44; the AVC is achieved&#44; its interpretation is not easy&#46; There is no consensus on the criteria that should be used to assess its efficacy&#44; which complicates its interpretation&#46; In addition&#44; there are various options regarding the procedure protocol&#44; without consensus on which is the best option&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">24</span></a></p></span></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Unilateral adrenalectomy in PHA</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Results of adrenalectomy</span><p id="par0080" class="elsevierStylePara elsevierViewall">A surgeon with experience in laparoscopic adrenalectomy must be available to obtain good surgical outcomes&#46; And in terms of its efficacy&#44; it is far from ideal&#46; After an adrenalectomy&#44; although a significant percentage experience improvement in blood pressure control&#44;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">26</span></a> 50&#8211;60&#37;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">27&#44;28</span></a> remain hypertensive&#44; and even up to 70&#37;&#44; according to some series&#44; such as the one published in <span class="elsevierStyleItalic">JAMA of Surgery</span> in 2019<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">28</span></a> in a cohort of 435 patients with PHA who underwent unilateral adrenalectomy and in the <span class="elsevierStyleItalic">World J Surgery</span> 2020 in 190 patients&#44;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">29</span></a> among other&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">30</span></a> Some studies have reported non-cure rates of up to 80&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">26</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Several factors associated with the persistence of HT after adrenalectomy have been described&#44; such as the coexistence of a family history of HT&#44;<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">31&#44;32</span></a> which is present in approximately 60&#37; of subjects with PHA&#59; the need for more than two drugs to control BP&#44;<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">31&#44;33</span></a> which occurs in more than half of the patients&#59; and HT duration for more than five years&#44;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">32&#44;33</span></a> a very common situation&#44; taking into account that delay in diagnosis is common&#46; There are other factors such as male sex and overweight&#44; associated with a poor surgery outcome&#44; common in patients with PHA&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">32</span></a> For example&#44; the <span class="elsevierStyleItalic">Primary Aldosteronism Surgical Outcome &#40;STEP&#41;</span><a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">34</span></a> study&#44; in a cohort of 699 patients who underwent PHA&#44; found that women had a greater probability of biochemical cure &#40;OR 2&#46;25&#59; 95&#37; CI 1&#46;40&#8211;3&#46;62&#41; than men and also young people &#40;OR 0&#46;95 per extra year&#44; 0&#46;93&#8211;0&#46;8&#41; and those who needed fewer drugs preoperatively to control BP &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; These results reflect the importance of the need and the value of the establishment of specific HT units&#44; where these patients are adequately guided from the beginning and early diagnoses of patients with PHA are carried out to reduce the number of cases with limited cure possibilities after adrenalectomy&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Risks of unilateral adrenalectomy</span><p id="par0090" class="elsevierStylePara elsevierViewall">Among the risks associated with unilateral adrenalectomy are postoperative hyperkalaemia which&#44; although it is transient and easily manageable in 16&#37; of patients&#44; there is 5&#37; with chronic hyperkalaemia and some cases of potentially lethal hyperkalaemia with figures up to 7&#46;0<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">35</span></a> Several factors associated with an increased risk of postsurgical hyperkalaemia have been identified&#44; such as age greater than 53&#44; HT with more than nine years of progression&#44; the presence of adrenal lesions &#62;2<span class="elsevierStyleHsp" style=""></span>cm and deterioration of renal function&#44; all of them relatively common in patients with PHA&#46;<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">35&#44;36</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Another of the classical potential risks of surgery in PHA is the deterioration of renal function after the intervention&#46; It seems to be related to the resolution of the hyperfiltration state associated with PHA after surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">37</span></a> A recent meta-analysis&#44;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">38</span></a> which includes a total of 6056 patients with PHA&#44; found a decrease in glomerular filtration of 11<span class="elsevierStyleHsp" style=""></span>mL&#47;min after adrenalectomy&#46; Among the risk factors for impaired kidney function are age &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#46;37&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0006&#41;&#44; and preoperative aldosterone levels &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;12&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0209&#41; and potassium &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;87&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0010&#41;&#44; as these factors increase&#44; the risk of impaired kidney function increases&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">39</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">There are other more uncommon and less reported complications&#44; such as the potential deterioration of the lipid profile&#44; described in up to 68&#46;4&#37; of patients in Kaga&#39;s series&#44; and the development of <span class="elsevierStyleItalic">new onset</span> dyslipidaemia by 46&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">40</span></a> To all this are added the risks inherent to the intervention&#44; such as bleeding&#44; bruising&#44; and so on&#46; However&#44; it should be noted that the risks inherent in laparoscopic adrenalectomy are few and uncommon&#46; In addition&#44; there are other emerging minimally invasive techniques&#44; such as percutaneous ablation of adrenal adenomas&#44; reporting rates of improvement and cure of HT in 75&#46;5&#37; of patients&#44;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">41</span></a> which could represent a definitive treatment in patients with PHA who refuse surgery or are not candidates for it&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Drug therapy for PHA</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Indications</span><p id="par0105" class="elsevierStylePara elsevierViewall">The treatment of PHA is aimed at the prevention of morbidity and mortality derived from hypertension&#44; the correction of hypokalaemia&#44; and the avoidance of organ damage associated with excess aldosterone&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">1&#44;5</span></a> Several studies have demonstrated that MRA are effective in controlling blood pressure &#40;BP&#41; and protecting against specific organ damage due to excess aldosterone&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">1&#44;42&#8211;44</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The classical indications for drug therapy include bilateral hyperplasia&#44; hereditary forms&#44; unilateral adenomas with high surgical risk&#44; rejection of surgery by the patient&#44; medical contraindication for surgery&#44; the inability to perform an AVC&#44; advanced age and not having a clear diagnosis in catheterization&#46; All this represents more than 70&#37; of PHA cases&#44; as potential candidates for first-line drug therapy<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">5</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Available drugs</span><p id="par0115" class="elsevierStylePara elsevierViewall">The drugs available to us are mainly spironolactone and eplerenone&#44; but if these cannot be used or are not sufficient&#44; there are other options &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Spironolactone</span><p id="par0120" class="elsevierStylePara elsevierViewall">It is considered the first-line drug in PHA&#46; It is an MRA&#44; but it also blocks the production of androgens and progesterone&#44; which explains part of its side effects&#44; which are gynecomastia in men and menstrual disorders in women&#44; side effects depending on the dose used&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a> Jeunemaitre et al&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">45</span></a> reported an incidence of gynecomastia of 6&#46;9&#37; with doses of &#60;50<span class="elsevierStyleHsp" style=""></span>mg&#47;day and 52&#37; with doses &#62;150<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; after 6 months of treatment&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The starting dose of spironolactone is 12&#46;5&#8211;25<span class="elsevierStyleHsp" style=""></span>mg&#47;day in a single daily dose&#44; and the maximum recommended doses of 400<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">1&#44;46</span></a> It is recommended to take it with a meal rich in fat as it has been shown to significantly improve its oral bioavailability &#40;up to 90&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">47</span></a> Spironolactone is converted in the liver into two active metabolites&#44; 7&#945;-thio-methylpyronolactone and canrenone&#44; which are responsible for the persistence of the pharmacological effect&#44; and therefore the possibility of administering it only once a day&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">48</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">It is considered a powerful drug to control blood pressure &#40;BP&#41;&#44; lowers systolic pressure by 40&#8211;60<span class="elsevierStyleHsp" style=""></span>mmHg and diastolic pressure at 10&#8211;20<span class="elsevierStyleHsp" style=""></span>mmHg&#44; obtaining figures of &#40;BP&#41; &#60;140&#47;90 in 50&#37; of patients when used as monotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">49</span></a> Some factors associated with a greater response to spironolactone have been identified&#44; such as the degree of renin suppression &#40;the greater the suppression&#44; the greater the response&#41; and the degree of aldosterone production &#40;the greater the aldosterone production&#44; the greater the response&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">50</span></a> On the other hand&#44; some studies identify the response to spironolactone as a predictive marker of response to adrenalectomy&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">51</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Eplerenone</span><p id="par0135" class="elsevierStylePara elsevierViewall">In the event that there are side effects with spironolactone&#44; or when it cannot be used for other reasons&#44; eplerenone&#44; a selective mineralocorticoid receptor antagonist that hardly exerts antagonistic effects on the androgen and progesterone receptor&#44; could be used&#44; thus lacking the same side effects associated with the use of spironolactone&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">48</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">In contrast&#44; it is less potent than spironolactone and its half-life is shorter&#44; 6&#8211;8<span class="elsevierStyleHsp" style=""></span>h&#44; so it must be administered twice a day&#44; compared to the daily administration of spironolactone&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">48</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">The main differences between spironolactone and eplerenone are that spironolactone is administered every 24<span class="elsevierStyleHsp" style=""></span>h and eplerenone every 12<span class="elsevierStyleHsp" style=""></span>h&#59; eplerenone is metabolized by the liver through cytochrome PY3A4&#44; therefore it interacts with other drugs such as digoxin and non-pharmacological methods&#44; and is contraindicated in patients with severe liver cirrhosis &#40;Child C&#41;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">46&#44;48</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Other treatments</span><p id="par0150" class="elsevierStylePara elsevierViewall">If these two drugs fail to achieve adequate BP control&#44; or they cannot be used&#44; there are other alternatives such as amiloride&#44; thiazides&#44; calcium channel blockers and angiotensin converting enzyme inhibitors &#40;ACEI&#41;&#44; among others&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">49</span></a> Low doses of a thiazide diuretic drug&#44; triamterene or amiloride may be added to try to avoid high doses of spironolactone&#44; which can cause side effects&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a></p></span></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Drug therapy versus surgical treatment in PHA</span><p id="par0155" class="elsevierStylePara elsevierViewall">There are several studies that analyze the differences in the degree of control of hypertension&#44; improvement of cardiovascular and renal parameters between drug therapy and surgical treatment&#44; without finding significant differences between the two&#46; Among them we find the work of Catena et al&#46;&#44; of 2007&#44;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">6</span></a> in which the evolution of cardiovascular parameters is analyzed based on long-term echocardiographic data in a cohort of 24 patients undergoing adrenalectomy and 30 undergoing spironolactone&#46; Significant improvements are found in the degree of control of systolic blood pressure &#40;SBP&#41; and diastolic blood pressure &#40;DBP&#41; in both groups&#44; with no relevant differences in both arms of treatment&#44; and in the degree of improvement of long-term left ventricular hypertrophy &#40;LVH&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Another study published in 2008&#44;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">7</span></a> in which only patients undergoing adrenalectomy were analyzed&#44; found that&#44; in patients with long-standing HT&#44; with evidence of vascular remodelling&#44; or both&#44; the chances of cure after adrenalectomy are especially low&#46; This prospective study of 50 PAHs who underwent surgery found a cure rate of 29&#46;5&#37;&#44; and a cut-off value of 9&#46;12&#37; for the mean&#47;arterial lumen <span class="elsevierStyleItalic">ratio</span> provided a sensitivity of 64&#37; and a specificity of 100&#37; for the identification of post-adrenalectomy cure and a cut-off value of 38 months for the duration of HT provided a sensitivity of 49&#37; and a specificity of 100&#37;&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Results with greater strength can be obtained from a meta-analysis published in 2015<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">8</span></a> which includes four studies with a total of 178 patients in the adrenalectomy arm and 177 in the drug therapy arm&#46; No significant differences were found in LVH improvement between drug therapy and surgical treatment&#44; or in the long term&#44; both drug therapy &#40;&#8722;7&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;8&#37;&#41; and surgical treatment &#40;&#8722;12&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;1&#37;&#41; reduced the LV mass index&#44; so the authors conclude that both treatments were equally effective in achieving the primary objective&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">In another study aimed at analysing glucose tolerance and insulin sensitivity&#44; in a series of 47 patients&#44; 20 undergoing adrenalectomy and 27 undergoing drug therapy&#44; significant improvements were found in the insulin response to glucose overload&#44; in the glucose-insulin <span class="elsevierStyleItalic">ratio</span> and in the HOMA index in both&#44; the drug therapy and the surgical treatment group&#44; without finding significant differences between the two&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">52</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">In a cohort of 48 patients treated with spironolactone at mean doses of 33&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; spironolactone reduced SBP from 149&#46;3 to 126&#46;2 and DBP from 88&#46;2 to 78&#46;3<span class="elsevierStyleHsp" style=""></span>at one year of treatment&#44; and of 81&#37; of patients with LVH&#44; 92&#37; had a significant improvement in the degree of hypertrophy&#44; and 41&#37; achieved normal values&#46; The authors conclude that&#44; in patients with PHA&#44; low doses of spironolactone achieved a significant improvement in LVH&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">53</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Another study<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">54</span></a> analyzed the changes in the carotid intima-media thickness in a cohort of 42 patients&#44; 21 in the drug therapy arm and 21 in the surgical one&#46; Reductions in the carotid intima-media of a similar degree were observed in the treatment groups at 6 years of follow-up&#46; Although the magnitude of improvement in the first year was significantly greater in the adrenalectomy group &#40;by 70&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#59; the difference &#40;by 27&#37;&#41; became non-significant at six years&#46; The authors conclude that&#44; in the long term&#44; spironolactone in patients with PHA achieved a significant reduction in intima-media thickness&#44; comparable to that produced by adrenalectomy in unilateral forms&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">From what we can see with these examples&#44; there is a lot of evidence that does not demonstrate greater efficacy of surgical treatment compared to drug therapy&#44; neither in the improvement of LVH&#44; the parameters of glucose metabolism nor in the carotid intima-media thickness&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">However&#44; some of the studies focused on cost&#47;benefit analysis comparing both treatments estimate a saving of Canadian &#36; 31&#44;132 per patient in favour of surgical treatment compared to long-term drug therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">55</span></a> Another fact that supports the selection of surgical treatment as a choice for younger patients&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Special situations regarding PHA</span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Glucocorticoid-remediable hyperaldosteronism</span><p id="par0195" class="elsevierStylePara elsevierViewall">Glucocorticoid-remediable hyperaldosteronism or familial hyperaldosteronism type 1&#44;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">1&#44;56</span></a> treatment with long-acting glucocorticoids&#44; either dexamethasone or prednisone is considered the treatment of choice&#46; It should be given in the evening to suppress the morning peak in adrenocorticotropic hormone &#40;ACTH&#41;&#44; and the goal is to normalize BP and potassium levels&#46; The mean starting doses are 0&#46;125&#8211;0&#46;25<span class="elsevierStyleHsp" style=""></span>mg&#47;day of dexamethasone or 2&#46;5&#8211;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day of prednisone&#46; In some cases&#44; the association with spironolactone&#44; eplerenone or other drugs may be necessary for adequate blood pressure control&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a> In children&#44; glucocorticoid dose should be adjusted according to age and weight&#44; and if the association with antihypertensive drugs is necessary&#44; eplerenone is considered the choice to avoid the antiandrogenic effects of spironolactone that could affect growth &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Primary hyperaldosteronism in the elderly</span><p id="par0200" class="elsevierStylePara elsevierViewall">Another section to highlight is PHA in the elderly&#46; In these patients there is hardly any previous literature on AVC&#44; so the distribution of unilateral and bilateral forms in this age group is unknown&#46; On the other hand&#44; these patients have a higher risk of non-cure after adrenalectomy and of surgical complications&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">57</span></a> A recent study<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">57</span></a> with a cohort of 1691 young patients and 411 patients older than 65 years who underwent adrenalectomy&#44; found that the cure rate is lower in the older group &#40;36 vs&#46; 18&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41;&#44; and that the risk of hyperkalaemia &#40;5 vs&#46; 15&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41; and renal function deterioration &#40;12 vs&#46; 27&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; is higher&#46; The authors conclude that adrenalectomy was useful in elderly patients in terms of biochemical cure and reduction of antihypertensive treatment&#44; but remission of hypertension was limited in this population&#46; And that special caution should be exercised due to the risk of postoperative renal failure and hyperkalaemia &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Primary hyperaldosteronism during pregnancy</span><p id="par0205" class="elsevierStylePara elsevierViewall">Drug therapy with alpha-methyldopa is considered the treatment of choice in PHA during pregnancy&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">58</span></a> The doses used range between 250 and 3000<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; Labetalol could be used as a second-line in doses of 100&#8211;2400<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; Spironolactone is contraindicated due to the risk of feminization if the offspring is male&#44; and with eplerenone there are few studies&#46; Surgical treatment would be reserved for hypertension refractory to drug therapy and in the second trimester of pregnancy &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conclusions</span><p id="par0210" class="elsevierStylePara elsevierViewall">CT and MRI are not useful for the diagnosis of PHA location&#44; which leads to having to perform CVA on most patients in order to select those who could benefit from surgical treatment&#46; However&#44; it should be taken into account that AVC is a complex&#44; invasive procedure&#44; with little experience and little success&#44; with catheterization rates of 30&#46;5&#37;&#44; even in centres considered to be of reference&#46; On the other hand&#44; its results are difficult to interpret due to the lack of consensus in the cut-off points of the different parameters that evaluate its efficacy&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">The cure rate after adrenalectomy ranges from 30&#37; to 50&#37; in the different series&#46; It is a technique that is not exempt from risks&#44; among which the frequency of hyperkalaemia in 16&#37; and the development of chronic renal disease in up to 20&#37; stand out&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Considering the different causes of PHA&#44; drug therapy is considered of choice in more than 70&#37; of PAHs&#46; There are safe and effective drugs&#44; especially spironolactone&#44; which&#44; although associated with gynecomastia&#44; is an enormously powerful antihypertensive&#46; Several studies have observed similar results for localized PHA&#44; in terms of improvement in LVH&#44; carotid intima-media thickness&#44; and SBP and DBP between drug therapy and surgical treatment&#46; Medical treatment is also generally considered of choice during pregnancy&#44; in those over 65 years of age and in familial types&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">All things considered&#44; there are strong grounds for making drug therapy in PHA the general recommendation&#46; However&#44; in young patients with unilateral hyperaldosteronism and low surgical risk&#44; and in sites with interventional radiologists who are experts in AVC&#44; with high catheterization rates and low risk of complications&#44; who have a surgical team with extensive experience in adrenal pathology&#44; surgical treatment should be considered as the first option&#46; On the other hand&#44; surgical treatment appears to be more cost-effective&#44; especially in young patients&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflict of interests</span><p id="par0230" class="elsevierStylePara elsevierViewall">The author declares that there is no conflict of interest&#46;</p></span></span>"
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        0 => array:3 [
          "identificador" => "xres1394838"
          "titulo" => "Abstract"
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              "identificador" => "abst0005"
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        1 => array:2 [
          "identificador" => "xpalclavsec1278406"
          "titulo" => "Keywords"
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          "titulo" => "Resumen"
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            0 => array:1 [
              "identificador" => "abst0010"
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          ]
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        3 => array:2 [
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          "titulo" => "Palabras clave"
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        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Adrenal vein catheterization"
          "secciones" => array:1 [
            0 => array:3 [
              "identificador" => "sec0015"
              "titulo" => "Need for adrenal vein catheterization to select the appropriate treatment"
              "secciones" => array:4 [
                0 => array:2 [
                  "identificador" => "sec0020"
                  "titulo" => "Limitations of adrenal vein catheterization"
                ]
                1 => array:2 [
                  "identificador" => "sec0025"
                  "titulo" => "Experience in adrenal vein catheterization"
                ]
                2 => array:2 [
                  "identificador" => "sec0030"
                  "titulo" => "Potential risks of adrenal vein catheterization"
                ]
                3 => array:2 [
                  "identificador" => "sec0035"
                  "titulo" => "Difficulties in interpreting the results of adrenal vein catheterization"
                ]
              ]
            ]
          ]
        ]
        6 => array:3 [
          "identificador" => "sec0040"
          "titulo" => "Unilateral adrenalectomy in PHA"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Results of adrenalectomy"
            ]
            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Risks of unilateral adrenalectomy"
            ]
          ]
        ]
        7 => array:3 [
          "identificador" => "sec0055"
          "titulo" => "Drug therapy for PHA"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Indications"
            ]
            1 => array:3 [
              "identificador" => "sec0065"
              "titulo" => "Available drugs"
              "secciones" => array:3 [
                0 => array:2 [
                  "identificador" => "sec0070"
                  "titulo" => "Spironolactone"
                ]
                1 => array:2 [
                  "identificador" => "sec0075"
                  "titulo" => "Eplerenone"
                ]
                2 => array:2 [
                  "identificador" => "sec0080"
                  "titulo" => "Other treatments"
                ]
              ]
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Drug therapy versus surgical treatment in PHA"
        ]
        9 => array:3 [
          "identificador" => "sec0090"
          "titulo" => "Special situations regarding PHA"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0095"
              "titulo" => "Glucocorticoid-remediable hyperaldosteronism"
            ]
            1 => array:2 [
              "identificador" => "sec0100"
              "titulo" => "Primary hyperaldosteronism in the elderly"
            ]
            2 => array:2 [
              "identificador" => "sec0105"
              "titulo" => "Primary hyperaldosteronism during pregnancy"
            ]
          ]
        ]
        10 => array:2 [
          "identificador" => "sec0110"
          "titulo" => "Conclusions"
        ]
        11 => array:2 [
          "identificador" => "sec0115"
          "titulo" => "Conflict of interests"
        ]
        12 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-03-25"
    "fechaAceptado" => "2020-04-29"
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      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1278406"
          "palabras" => array:5 [
            0 => "Primary hyperaldosteronism"
            1 => "Adrenal vein sampling"
            2 => "Adrenalectomy"
            3 => "Spironolactone"
            4 => "Eplerenone"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1278405"
          "palabras" => array:5 [
            0 => "Hiperaldosteronismo primario"
            1 => "Cateterismo de venas adrenales"
            2 => "Adrenalectom&#237;a"
            3 => "Espironolactona"
            4 => "Eplerenona"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Primary aldosteronism is associated with higher cardiovascular and renal morbidity and mortality than essential hypertension in age- and sex-matched patients with the same degree of blood pressure elevation&#46; Therefore&#44; it is essential to establish a specific treatment to avoid the deleterious effects of aldosterone excess&#46; Although adrenalectomy is generally considered the treatment of choice in cases of primary aldosteronism due to unilateral disease&#44; several aspects and circumstances should be taken into account that may make medical treatment more appropriate&#46; Among them&#44; in this review we mention the limited experience and efficacy&#44; and the potential risks of adrenal vein sampling&#59; the risks and low efficacy of adrenalectomy&#59; the high safety and efficacy of medical treatment and some special situations such as primary aldosteronism during pregnancy&#44; in patients of advanced age or hereditary forms of primary aldosteronism&#44; in which medical treatment is considered especially indicated as the first line therapy&#46; The main studies comparing medical and surgical treatment in primary aldosteronism are also discussed&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El hiperaldosteronismo primario &#40;HAP&#41; se asocia con una mayor morbimortalidad cardiovascular y renal que la hipertensi&#243;n arterial &#40;HTA&#41; esencial&#44; a misma edad&#44; sexo y grado de HTA&#46; Por ello&#44; es esencial instaurar un tratamiento espec&#237;fico para aminorar los efectos delet&#233;reos del exceso de aldosterona&#46; Aunque se considera que la adrenalectom&#237;a es generalmente el tratamiento de elecci&#243;n en los casos de HAP por enfermedad unilateral&#44; se deben tener en cuenta varios aspectos y circunstancias que pueden hacer m&#225;s adecuado el tratamiento m&#233;dico&#46; Entre ellos&#44; en esta revisi&#243;n se mencionan&#44; la limitada experiencia y eficacia&#44; y los riesgos del cateterismo de venas adrenales&#59; los riesgos y baja eficacia de la adrenalectom&#237;a&#59; la elevada seguridad y eficacia del tratamiento m&#233;dico y algunas situaciones especiales como el embarazo&#44; la edad avanzada o las formas familiares&#44; en las que el tratamiento m&#233;dico se considera especialmente indicado como primera l&#237;nea&#46; Tambi&#233;n se comentan los principales estudios que comparan el tratamiento m&#233;dico y quir&#250;rgico en el HAP&#46;</p></span>"
      ]
    ]
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; Araujo-Castro M&#46; Tratamiento del hiperaldosteronismo primario&#46; Med Cl&#237;n&#46; 2020&#59;155&#58;302&#8211;308&#46;</p>"
      ]
    ]
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        "etiqueta" => "Table 1"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">BP&#58; blood pressure&#59; CT&#58; computed tomography&#59; AVC&#58; adrenal vein catheterization&#59; &#91;L cortisol&#93;&#58; cortisol concentration on the catheter side&#59; &#91;IVC cortisol&#93;&#58; cortisol concentration in the inferior vena cava&#59; &#91;ALDL&#93;&#58; aldosterone concentration on the catheter side&#59; &#91;ALDIVC&#93;&#58; concentration of aldosterone in the inferior vena cava&#59; &#91;Non-dominant ALD&#93;&#58; concentration of aldosterone on the non-dominant side&#59; &#91;Non-dominant cortisol&#93;&#58; cortisol concentration on the non-dominant side&#59; &#91;Dominant ALD&#93;&#58; concentration of aldosterone on the dominant side&#59; &#91;Dominant Cortisol&#93;&#58; cortisol concentration on the dominant side&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pre-procedure preparation &#40;weeks prior to AVC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8226; Correct hypokalaemia and BP control&#46;&#8226; Discontinue spironolactone and eplerenone 6 weeks before and amiloride 2 weeks before&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pre-procedure conditions &#40;day&#47;s prior to AVC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8226; Contrast CT&#58; anatomy and anatomical relationships of the right adrenal vein&#46;&#8226; Serum aldosterone&#44; renin and potassium levels lab tests&#46;&#8226; Perform in the morning &#40;avoid ACTH fluctuations&#41;&#46;&#8226; Control pain and emotional stress &#40;reduce activation of the hypothalamic-pituitary-adrenal axis&#41;&#46;&#8226; Supine position 1<span class="elsevierStyleHsp" style=""></span>h before the procedure&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intra-procedure conditions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8226; Evaluate adequate catheterization&#58; CT&#44; rapid cortisol immunoassays&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Protocols&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8226; Sequential catheterization with ACTH &#40;infusion 50<span class="elsevierStyleHsp" style=""></span>&#956;&#47;h or bolus of 250<span class="elsevierStyleHsp" style=""></span>&#956;g&#41;&#46;&#8226; Sequential catheterization with metoclopramide &#40;few studies&#41;&#46;&#8226; Sequential catheterization without ACTH&#46;&#8226; Simultaneous bilateral catheterization &#40;without ACTH&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AVC interpretation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8226; <span class="elsevierStyleItalic">Selectivity index</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#91;cortisol L&#93;&#47;&#91;cortisol IVC&#93;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&#8226; <span class="elsevierStyleItalic">Relative secretion index</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#91;ALDL&#93;&#47;&#91;cortisol L&#93;&#91;ALDVCI&#93;&#47;&#91;cortisol IVC&#93;&#8226; <span class="elsevierStyleItalic">Contralateral suppression index</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#91;Non-dominant ALD&#93;&#47;&#91;Non-dominant cortisol&#93;&#91;ALDVCI&#93;&#47;&#91;cortisol IVC&#93;&#8226; <span class="elsevierStyleItalic">Lateralization index</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#91;Dominant ALD&#93;&#47;&#91;Dominant cortisol&#93;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&#91;Non-dominant ALD&#93;&#47;&#91;Non-dominant cortisol&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Post-procedure conditions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8226; Admission 24&#8211;48<span class="elsevierStyleHsp" style=""></span>h &#40;risk of adrenal vein rupture&#41;&#8226; Control of constants and pain&#44; mainly&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Use cut-off points of 2 for AVC without ACTH and 3 for AVC with ACTH &#40;ideally&#44; use reference laboratory cut-off points&#41;&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Use a cut-off point of between 2 and 4 in AVC without ACTH and 2&#46;6 and 4 in AVC with ACTH&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Preparation&#44; protocols and interpretation of adrenal vein catheterization&#46;</p>"
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          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">PHA&#44; primary hyperaldosteronism&#59; Surg&#44; surgical&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Entity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Proportion of patients with PHA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sporadic bilateral hyperplasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#8211;65&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hereditary forms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Unilateral adenomas with high surg&#46; risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Contraindication for surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patient rejection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not reported&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No clear diagnosis in catheterization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#8211;70&#37; of catheterizations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Advanced age &#40;&#62;65 years&#41;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">57</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8211;10&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pregnancy<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">58</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;8&#37; of pregnancies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No possibility of catheterization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Variable according to site&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            0 => array:3 [
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Relative indication&#44; depending on the risk-benefit balance&#44; and consider the time of HT progression and other factors associated with a lower probability of cure after adrenalectomy</p>"
            ]
          ]
        ]
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">General indications for drug therapy in primary hyperaldosteronism&#46;</p>"
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        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">CYP3A4&#44; cytochrome P450 3A4&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Spironolactone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Eplerenone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Half-life&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#8211;58<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#8211;6<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bioavailability&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increase with high-fat meals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not affected by ingestion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Active metabolites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&#58; canrenone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Elimination&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liver&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Drug interaction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes &#40;CYP3A4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Contraindications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HyperkalaemiaAddison&#39;s diseaseConcomitant use with eplerenone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe liver cirrhosisHyperkalaemiaUse of strong CYP3A4 inhibitors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Posology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Every 24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Every 8&#8211;12<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Starting dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;5&#47;25<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maximum dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">400<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Side effects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gynecomastia&#44; erectile dysfunction&#44; and sexual anaesthesia &#40;males&#41;&#59; menstrual disturbances &#40;women&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not described&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pregnancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Contraindicated &#40;Category D&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">With caution &#40;category B&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Breastfeeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Avoid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Avoid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Drug therapy in primary hyperaldosteronism&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">46</span></a></p>"
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        "etiqueta" => "Table 4"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">PHA&#58; primary hyperaldosteronism&#59; FH&#58; family history&#59; HT&#58; arterial hypertension&#59; CYP11B1&#47;CYP11B2&#58; cytochrome P450 B1&#47;B2&#59; ALD&#58; aldosterone&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Glucocorticoid-remediable hyperaldosteronism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hyperaldosteronism in &#62;65 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hyperaldosteronism in pregnancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prevalence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#37; PHA&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a> Most common cause of monogenic HT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8211;10&#37;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">57</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;8&#37; of pregnancies<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">58</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Suspicious diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Children or young adults with severe and&#47;or refractory HT and FH of HT or early haemorrhagic stroke&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refractory&#47;resistant HT and&#47;or hypokalaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Difficult to control HT&#44; preeclampsia&#44; hypokalaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Specific diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genetic study for mutations in CYP11B1&#47;CYP11B2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increases the risk of false positives in the aldosterone&#47;renin <span class="elsevierStyleItalic">ratio</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical suspicion &#43; elevated aldosterone and suppressed renin&#46; Do not perform confirmation test<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">58</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Special considerations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">High risk of haemorrhagic stroke &#40;18&#37;&#44; mean age<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>32 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age is a risk factor for non-cure after adrenalectomy<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">32&#44;33</span></a> and increased risk of hyperkalaemia and deterioration of renal function after surgery<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">57</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Physiological activation of the renin angiotensin aldosterone system during pregnancy&#46; Oestrogens and progesterones counteract the action of ALD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dexamethasone 0&#46;125&#8211;0&#46;25<span class="elsevierStyleHsp" style=""></span>mg&#47;day or prednisone 2&#46;5&#8211;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; at night&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Spironolactone or Eplerenone as 1st line&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Methyldopa 250&#8211;3000<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46;Second-line&#58; labetalol 100&#8211;2400<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Special situations in primary hyperaldosteronism&#46;</p>"
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