Scientific letter
A remarkable cause of endocrine hypertension
Una causa singular de hipertensión endocrina
Miguel Paja-Fano
, Adela-Leire Martínez-Martínez, Andoni Monzón-Mendiolea, Javier Espiga-Alzola
Corresponding author
Servicio de Endocrinología, Hospital Universitario de Basurto, OSI Bilbao-Basurto, Osakidetza, Bilbao, Spain
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"paginaInicial" => "683" "paginaFinal" => "685" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Miguel Paja-Fano, Adela-Leire Martínez-Martínez, Andoni Monzón-Mendiolea, Javier Espiga-Alzola" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Miguel" "apellidos" => "Paja-Fano" "email" => array:1 [ 0 => "miguel.pajafano@osakidetza.eus" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Adela-Leire" "apellidos" => "Martínez-Martínez" ] 2 => array:2 [ "nombre" => "Andoni" "apellidos" => "Monzón-Mendiolea" ] 3 => array:2 [ "nombre" => "Javier" "apellidos" => "Espiga-Alzola" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Endocrinología, Hospital Universitario de Basurto, OSI Bilbao-Basurto, Osakidetza, Bilbao, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Una causa singular de hipertensión endocrina" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 572 "Ancho" => 750 "Tamanyo" => 70955 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Abdominal CT scan in arterial phase showing an enhanced-uptake right adrenal mass measuring 6<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>cm in size, with numerous internal blood vessels.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The detection of an adrenal gland neoplasm in the study of arterial hypertension (AHT) opens up a wide range of diagnostic possibilities, potentially as a cause of or independent from AHT itself. We report a case with this association, with a peculiar diagnostic trajectory and an exceptional final diagnosis.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 29-year-old woman was referred to the nephrology clinic after the detection of AHT due to headaches starting one year ago. She had undergone surgery at 5 years of age due to left pyeloureteral stenosis, and reported recent pollakiuria with nocturia. She provided a primary care report with mean daytime and nocturnal blood pressure (BP) values of 154/100 and 140/90<span class="elsevierStyleHsp" style=""></span>mmHg, respectively. The laboratory tests requested by her primary care physician revealed low serum potassium levels in two determinations (3.49 and 3.12<span class="elsevierStyleHsp" style=""></span>mEq/l), with normal renal function. The expanded study in the Nephrology Department revealed low plasma renin activity (0.2<span class="elsevierStyleHsp" style=""></span>ng/ml/h) with normal-low aldosterone levels (7.3<span class="elsevierStyleHsp" style=""></span>ng/dl), normal urinary catecholamines and a CT angiographic scan evidencing a hypervascular right adrenal mass measuring 6<span class="elsevierStyleHsp" style=""></span>cm in diameter (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). After consulting the Endocrinology Department, the study was further expanded with fractionated urinary metanephrines, urinary 3-methoxytyramine and urinary free cortisol – all of them yielding normal values – in addition to ACTH (34.5<span class="elsevierStyleHsp" style=""></span>pg/ml) and plasma dehydroepiandrosterone (DHEA) (1.31<span class="elsevierStyleHsp" style=""></span>μg/ml), as well as serum chromogranin A and testosterone – all of which proved normal. Upon assessment in the clinic with these results, the patient presented no menstrual disorders or hirsutism, denied regular intake of liquorice, and had a normal phenotype. Preferential surgery was indicated in view of the size of the tumor, and the serum samples stored in the hospital serum repository were used for simultaneous measurement of intermediate metabolites of steroidogenesis in the core laboratory. Surgery took place one week later via subcostal laparotomy due to the potential malignancy of the lesion. The right adrenal gland was removed, weighing 87.1<span class="elsevierStyleHsp" style=""></span>g and containing a 6.5<span class="elsevierStyleHsp" style=""></span>cm homogeneous, solid non-encapsulated tumor with a thin, compressed adrenal tissue component. The pathology study revealed tumor growth with a trabecular and tubular-pseudoglandular pattern, with no mitoses, necrosis, calcification or vascular invasion. Immunohistochemistry proved positive for melan-A, inhibin and CKA1-AE3, and negative for chromogranin, S100, CEA, EMA and <span class="elsevierStyleItalic">renal cell marker</span>. All these data were consistent with adrenal gland adenoma, with Ki67<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>2%. The results of the pending tests were received after the operation, revealing deoxycorticosterone acetate (DOCA) levels almost 16 times above the upper limit of normal (ULN) (237.9<span class="elsevierStyleHsp" style=""></span>ng/dl; ULN: 15), with normal 11-deoxycortisol and corticosterone concentrations. Evaluation after 15 days showed BP to have normalized, the polyuria had disappeared, and the serum potassium concentration was normal (4.32<span class="elsevierStyleHsp" style=""></span>mEq/l). One month after surgery, serum testing showed normal DOCA values (7.1<span class="elsevierStyleHsp" style=""></span>ng/ml), with still low renin activity levels. Two and a half years after surgery, the patient remains asymptomatic, with normal PA and no surgical site lesions in the abdominal MRI study.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The possibility of a secondary form of AHT should be considered in the presence of certain clinical symptoms, mainly headache, tachycardia or excessive perspiration suggesting catecholamine excess, or laboratory changes – particularly spontaneous hypopotassemia.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Such electrolyte alterations, in the absence of gastrointestinal losses or iatrogenic losses due to the use of diuretics, suggest possible mineralocorticoid excess. The most common underlying cause in this context is primary aldosteronism,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> characterized by autonomous aldosterone secretion in a unilateral adenoma or secretion by both glands in the case of bilateral hyperplasia. The other variants, including unilateral hyperplasia, multiple adenomas, aldosterone-producing carcinomas (isolated or co-secreted with other steroids) and genetic forms, are much less common. In all these presentations, renin (activity or mass measurement) is low or suppressed, with normal or high aldosterone levels (usually >15<span class="elsevierStyleHsp" style=""></span>ng/dl), not suppressible with saline overload. Another form of apparent mineralocorticoid excess occurs with severe hypercortisolism due to overwhelming of the glucocorticoid receptors and escape from inactivation by 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), usually associated with malignant ectopic ACTH production and without a Cushing phenotype because of the explosiveness of the course of the disorder.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Excessive liquorice intake, through blockade of the same inactivating enzyme, causes cortisol at physiological concentrations to activate the mineralocorticoid receptor, with consequent renin suppression, saline retention, and excessive urinary potassium excretion.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> This same genetic-based mechanism underlies the so-called apparent mineralocorticoid excess syndrome due to heterozygous 11ß-HSD2 enzyme mutations.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Non-tumoral excess of other precursors of steroidogenesis as a cause of mineralocorticoid excess can be found in pediatric patients, associated to congenital enzyme deficiencies, particularly 11ß-hydroxylase,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> with an excess of 11-deoxycortisol and DOCA (both exerting a mineralocorticoid effects), and in defects in androgen synthesis (17α-hydroxylase and 17,20-lyase) – with associated gonadal alterations.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> An excess of precursors of steroidogenesis associated to neoplastic conditions without Cushing syndrome is exceptional, and is dependent upon the level and intensity of enzyme blockade within the tumor tissue. This can be evaluated by chromatography, showing the secretion profile of each tumor. The condition is usually associated to adrenal gland carcinomas,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and exceptionally to adrenal adenomas – unilateral (as in our case)<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> or bilateral.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Our patient had a number of very unusual characteristics, particularly the surprising detection of an adrenal tumor with isolated DOCA production, and especially the fact that this was a benign neoplasm despite its size and radiological appearance. The difference between an adrenal adenoma and carcinoma depends on not entirely precise criteria before surgery; careful surgical dissection in cases with potential malignancy is therefore crucial. Clinical, biochemical and radiological reversal after surgery confirmed the tumor origin of DOCA, with no other elevated steroidogenic metabolite, indicative of selective production of this hormone within an adenoma that appeared radiologically aggressive in view of its size and vascularization.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In conclusion, a new case of adrenal tumor producing DOCA has been described, with the peculiarity of its benign nature, favorable course and the absence of hypersecretion of other steroid metabolites.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Authorship</span><p id="par0025" class="elsevierStylePara elsevierViewall">Miguel Paja: study conception and design, and writing of the manuscript. Adela L. Martínez: data collection and interpretation. Andoni Monzón: data collection and interpretation. Javier Espiga: patient care and clinical monitoring, and critical review of the article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Authorship" ] 1 => array:2 [ "identificador" => "xack500067" "titulo" => "Acknowledgments" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Paja-Fano M, Martínez-Martínez A-L, Monzón-Mendiolea A, Espiga-Alzola J. Una causa singular de hipertensión endocrina. Endocrinol Diabetes Nutr. 2020;67:683–685.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 572 "Ancho" => 750 "Tamanyo" => 70955 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Abdominal CT scan in arterial phase showing an enhanced-uptake right adrenal mass measuring 6<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>cm in size, with numerous internal blood vessels.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Endocrine hypertension: a practical approach" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 1 | 1 | 2 |
| 2024 October | 17 | 4 | 21 |
| 2024 September | 59 | 9 | 68 |
| 2024 August | 33 | 7 | 40 |
| 2024 July | 23 | 5 | 28 |
| 2024 June | 22 | 12 | 34 |
| 2024 May | 7 | 4 | 11 |
| 2024 April | 11 | 5 | 16 |
| 2024 March | 14 | 4 | 18 |
| 2024 February | 16 | 2 | 18 |
| 2024 January | 9 | 2 | 11 |
| 2023 December | 15 | 2 | 17 |
| 2023 November | 28 | 4 | 32 |
| 2023 October | 22 | 1 | 23 |
| 2023 September | 18 | 1 | 19 |
| 2023 August | 10 | 2 | 12 |
| 2023 July | 9 | 2 | 11 |
| 2023 June | 19 | 0 | 19 |
| 2023 May | 41 | 1 | 42 |
| 2023 April | 48 | 3 | 51 |
| 2023 March | 40 | 1 | 41 |
| 2023 February | 17 | 3 | 20 |
| 2023 January | 4 | 1 | 5 |
| 2022 December | 19 | 2 | 21 |
| 2022 November | 13 | 4 | 17 |
| 2022 October | 14 | 10 | 24 |
| 2022 September | 6 | 5 | 11 |
| 2022 August | 9 | 6 | 15 |
| 2022 July | 10 | 7 | 17 |
| 2022 June | 6 | 6 | 12 |
| 2022 May | 5 | 7 | 12 |
| 2022 April | 10 | 9 | 19 |
| 2022 March | 23 | 9 | 32 |
| 2022 February | 6 | 4 | 10 |
| 2022 January | 14 | 3 | 17 |
| 2021 December | 9 | 12 | 21 |
| 2021 November | 9 | 11 | 20 |
| 2021 October | 10 | 7 | 17 |
| 2021 September | 10 | 11 | 21 |
| 2021 August | 6 | 0 | 6 |
| 2021 July | 6 | 4 | 10 |
| 2021 June | 13 | 5 | 18 |
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