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Role of plasmapheresis in the management of severe amiodarone-induced hyperthyroidism refractory to conventional medical treatment
Papel de la plasmaféresis en el manejo del hipertiroidismo severo inducido por amiodarona y refractario a tratamiento médico convencional
Belén García Izquierdoa,
Corresponding author
belengarciaizquierdo@gmail.com

Corresponding author.
, Macarena Contreras Anguloa, Laura Armengod Graoa, Álvaro García Garcíab, Pedro Iglesiasa
a Servicio de Endocrinología y Nutrición, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
b Servicio de Hematología y Hemoterapia, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Amiodarone is a class III antiarrhythmic drug widely used in our setting for the treatment of cardiac arrhythmias&#46; It is a benzofuran derivative with high iodine content&#44; which can have a bearing on thyroid function at different levels &#40;hypophysis&#44; thyroid and peripheral receptors&#41;&#46; In many cases&#44; it can modify the circulating concentrations of thyroid hormones and be accompanied by both hypo- and hyperthyroidism&#44; although the majority of patients remain euthyroid&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The first-line treatment of amiodarone-induced hyperthyroidism is fundamentally medical with synthetic antithyroid drugs In the case of Type 1 thyrotoxicosis &#40;iodine induced&#41;&#44; or with glucocorticoids in type II &#40;owing to glandular destruction&#41;&#46; Other less conventional drugs include potassium perchlorate and cholestyramine&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> Plasmapheresis has occasionally been used in cases of intolerance to antithyroid drugs&#44; refractory hyperthyroidism&#44; and to achieve euthyroidism prior to thyroidectomy&#44; though clinical experience is scant&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We present the case of a patient with structural cardiopathy with severe amiodarone-induced hyperthyroidism refractory to medical treatment which required a high number of plasmapheresis cycles prior to definitive treatment with thyroidectomy&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">53-year-old male with Arterial hypertension&#44; dyslipidaemia&#44; obesity&#44; sleep apnoea syndrome&#44; and persistent anticoagulated atrial fibrillation&#44; owing to which he had received treatment with amiodarone &#40;200&#8239;mg&#47;day&#41; over 3 years&#44; with the suspension thereof in the 2 months prior to admission&#44; at which time it was replaced by bisoprolol&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The patient was admitted for a preferential coronary angiography owing to chest pain with elevated markers of cardiac damage&#44; which turned out to be normal&#46; A study with transthoracic echocardiography was completed&#44; showing a severely dilated right ventricle and data on severe pulmonary hypertension&#44; as well as the existence of a superior sinus venosus atrial septal defect&#44; with indication of non-urgent surgical closure&#46; During admission&#44; a severe overt hyperthyroidism was discovered &#40;TSH&#8239;&#60;&#8239;0&#46;01&#8239;&#956;IU&#47;mL&#44; normal range &#91;NR&#93;&#58; 0&#46;35&#8211;5&#46;0&#59; Free T4 &#91;FT4&#93; 10&#46;03&#8239;ng&#47;dl&#44; NR&#58; 0&#46;7&#8211;1&#46;98&#44; and Free T3 &#91;FT3&#93; 9&#46;3&#8239;pg&#47;mL&#44; NR&#58; 2&#46;3&#8211;4&#46;2&#41; one week before the catheterisation was to be performed&#44; without having previously presented exposure to iodised contrast agents&#46; Clinically&#44; he did not report palpitations&#44; tremor&#44; nervousness&#44; or any other symptom of thyroid hyperfunction&#46; He presented with good blood pressure and heart rate control with beta blockers&#46; A grade 2 goitre&#44; with no nodules was palpable&#46; The thyroid echography showed a normal-sized gland with decreased vascularisation&#46; The thyroid autoimmunity study was negative and the Interleukin-6&#44; normal &#40;&#60;2&#46;7&#8239;pg&#47;mL&#44; NR&#58; 0&#46;0&#8211;4&#46;4&#41;&#46; In light of these findings and suspected amiodarone-induced hyperthyroidism&#44; treatment was started with metimazol &#40;30&#8239;mg&#47;day&#41; and prednisone &#40;60&#8239;mg&#47;day&#41;&#46; During admission&#44; the patient presented increasing serum levels of thyroid hormones&#44; which made it necessary to increase the dose of metimazol &#40;45&#8239;mg&#47;day&#41; and prednisone &#40;90&#8239;mg&#47;day&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Acholestyramine &#40;16&#8239;g&#47;day&#41; and potassium perchlorate &#40;800&#8239;mg&#47;day&#41; were also associated&#46; Despite this and&#44; after supervising the proper adherence to the treatment&#44; after three weeks the severe hyperthyroidism persisted &#40;TSH&#8239;&#60;&#8239;0&#46;01&#8239;&#956;IU&#47;mL&#44; FT4 11&#46;92&#8239;ng&#47;dl and FT3 9&#46;76&#8239;pg&#47;mL&#41; with the diagnosis of severe amiodrone-induced hyperthyroidism refractory to high doses of metimazol&#44; corticosteroids&#44; cholestyramine and potassium perchlorate being established&#44; owing to which total thyroidectomy was proposed as definitive treatment&#46; After discussing the case in a multi-disciplinary session with Cardiac Surgery&#44; Cardiology&#44; Anaesthesia&#44; General Surgery and Endocrinology&#44; it was decided to first perform a total thyroidectomy and&#44; secondly&#44; the closure of the ASD&#46; With the aim of reducing perioperative cardiovascular risk&#44; treatment with plasmapheresis was initiated with the aim of achieving euthyroid status&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The plasmapheresis sessions consisted of mixed plasma exchanges of albumin&#47;plasma of 1&#46;5 volumes in each session&#44; performed by the Haematology Department using an apheresis machine&#46; By way of complications&#44; the patient presented various episodes of skin rash which required prophylactic antihistamine treatment with each exchange&#46; During the procedure&#44; a slight tendency towards anaemisation was observed &#40;nadir of haemoglobin 11&#46;2&#8239;g&#47;dl&#44; NR&#58; 12&#46;0&#8211;17&#46;0&#8239;g&#47;dl&#59; after the 11th session of plasmapheresis&#44; 13 days after its commencement&#41; which required no treatment&#46; An asymptomatic hypocalcaemia was also observed&#44; despite intravenous supplementation with calcium gluconate &#40;nadir of 7&#46;6&#8239;mg&#47;dl&#59; NR&#58; 8&#46;7&#8211;10&#46;3&#8239;mg&#47;dl&#41;&#46; All of these complications were resolved after concluding the plasmapheresis&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Given the difficulty to attain a reduction in circulating thyroid hormones&#44; a total of 17 were performed prior to surgery&#46; At no time was the additional medical treatment suspended&#44; although the dose of prednisone was reduced to 40&#8239;mg&#47;day&#46; Serum levels of thyroid hormones were also determined on 5 occasions before and after the session of plasmapheresis&#44; achieving a reduction of their levels in the extraction sample immediately post-plasmapheresis &#40;FT4 pre- vs&#46; post-plasmapheresis 7&#46;89&#8239;&#177;&#8239;2&#46;48 vs&#46; 4&#46;58&#8239;&#177;&#8239;1&#46;35&#8239;ng&#47;dl&#44; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;009&#59; reduction of 41&#46;9&#37; and FT3 pre- vs&#46; post-plasmapheresis 8&#46;60&#8239;&#177;&#8239;2&#46;46 vs&#46; 8&#44;24&#8239;&#177;&#8239;2&#46;17&#8239;pg&#47;mL&#44; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;157&#59; reduction of 4&#46;1&#37;&#41;&#44; with a further increase on the day after plasmapheresis &#40;FT4 following day 6&#46;73&#8239;&#177;&#8239;1&#46;07&#8239;ng&#47;dl&#44; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;001&#59; increase of 46&#46;94&#37; and FT3 following day 8&#46;25&#8239;&#177;&#8239;2&#46;15&#8239;pg&#47;mL&#44; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;950&#59; increase of 0&#46;1&#37;&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Finally&#44; total thyroidectomy was performed 40 days after the initial diagnosis of hyperthyroidism&#44; without incident&#46; The thyroid profile prior to surgery was TSH 0&#46;01&#8239;&#956;IU&#47;mL&#44; FT4 4&#46;33&#8239;ng&#47;dl and FT3 4&#46;95&#8239;pg&#47;mL&#46; On the day immediately after&#44; a reduction in the FT4 to 3&#46;88&#8239;ng&#47;dl was noted&#44; falling to values of 1&#46;98&#8239;ng&#47;dl 3 days after the intervention&#46; Given the absence of post-surgical complications&#44; and the rapid normalisation of the thyroid hormones&#44; the patient was discharged with hormone replacement therapy with 150&#8239;&#181;g of levothyroxine a day&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Therapeutic plasma exchange &#40;TPE&#41; Is a treatment rarely used for the control of hyperthyroidism&#46; The Blood Bank &#40;Haematology and Haemotherapy Department&#41; was responsible for its implementation&#44; requiring for the procedure afferent and efferent lines connected to the apheresis equipment&#46; Its usefulness is based on the binding of T3 and T4 to plasma proteins that are eliminated&#46; By decreasing their plasma concentration&#44; the hormonal concentration is reduced &#40;principally T4&#44; with a lower free fraction&#41;&#46; Additionally&#44; by using fresh plasma as replacement fluid&#44; these proteins are applied allowing the binding of the free hormone&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Its indication in hyperthyroidism is not clearly established&#46; Some authors consider that TPE could be useful in the thyrotoxic storm&#44; in cases of intolerance or refractoriness to conventional treatments&#44; and as preoperative preparation&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> its most frequent indication being Graves&#39; disease&#44; followed by amiodarone-Induced hyperthyroidism&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Its complications include bleeding&#44; infection&#44; arterial hypotension&#44; hypocalcaemia and skin reactions&#46; The most serious correspond to disseminated intravascular coagulation or pulmonary thromboembolism&#44; with a mortality &#60;1&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> In our patient&#44; all the complications were mild and self-limiting&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Although there are studies in which 4&#8211;6 TPE sessions were necessary for normalising thyroid hormones<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;11</span></a> in our case&#44; this rose to 17&#46; The analytical alteration was clearly more pronounced in the other series&#44; with exposure to the iodinated contrast agents of the catheterisation also possibly making control more difficult&#46; After reviewing the literature&#44; this case would seem to be the greatest number of plasmapheresis that have been received before definitive treatment&#46; Moreover&#44; each session significantly reduced the FT4&#44; practically without affecting the FT3&#59; however&#44; this reduction was transient&#44; with a significant increase after 24&#8239;h&#44; which justified the repetition of sessions&#46; During the evolution&#44; it was difficult to discern the net effect of the drug therapy and the plasmapheresis in controlling the hyperthyroidism&#46; Although there was no reduction in thyroid hormones until the TPE was started&#44; which could reflect the efficacy of this technique&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion&#44; plasmapheresis would seem to be an effective alternative in those cases of severe amiodarone-induced hyperthyroidism refractory to conventional medical treatment at maximum doses as preparation for definitive treatment with surgery&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that no type of funding was received for this research&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare that there are no conflicts of interest in relation to this article&#46;</p></span></span>"
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