[The effects of amiodarone on the thyroid]. / Trastornos tiroideos por amiodarona.

BACKGROUND: Amiodarone is a drug widely used for the treatment of arrhythmias. In 16% of amiodarone-treated patients it causes changes in the thyroid function. The aim of this study was to determine the importance of amiodarone-induced thyroid dysfunction in the population of Navarre, studied between 2001 and 2007. METHODS: We present a retrospective study that considers the characteristics of 182 amiodarone-treated patients with thyroid dysfunction who had been referred to our Institute. We determined a series of biochemical and instrumental investigations (measurement of thyrotrophin, free thyroid hormones and thyroid autoantibodies; thyroid sonography and thyroid scintigraphy uptake). RESULTS: Screening of the thyroid function, recommended before starting amiodarone treatment, was carried out in only 20.9 % of the patients. Forty-one percent of patients developed amiodarone induced hypothyroidism; in 76% of them the drug was withdrawn. Hypothyroidism appears after 21 (+/- 12) months of amiodarone treatment. Forty-eight point six developed permanent hypothyroidism. This group of patients had higher serum levels of TSH (thyrotropin) and were treated for less time with amiodarone. Fifty-nine percent of patients developed amiodarone induced thyrotoxicosis; 59.4 % were diagnosed with thyrotoxicosis (AIT) type 1, 30.6% AIT type 2 and the remaining 10 % were diagnosed with mixed thyrotoxicosis. Thyrotoxicosis appears after 29.5 (+/- 17) months of amiodarone treatment. The serum levels of free thyroxine were significantly higher in the AIT type 2 than in the AIT type1. All patients were treated with antithyroid drugs and/or corticoids. Some patients were admitted to hospital due to the severity of their illness. CONCLUSIONS: In our study, amiodarone induced thyrotoxicosis was more frequent than hypothyroidism (59% vs 41%) because Navarre is an iodine-deficient area. It is necessary to control the thyroid function after 2-3 years of amiodarone treatment.

The malignant potential of a succinate dehydrogenase subunit B germline mutation.

Familial catecholamine secreting tumors have been associated with multiple endocrine neoplasia type 2, Von Hippel-Lindau disease and neurofibromatosis type 1. In the last years, mutations of genes encoding subunits B, C and D of the succinate dehydrogenase have been discovered as other causes of pheochromocytomas and paragangliomas. We diagnosed a malignant retroperitoneal paraganglioma in a 64-yr-old man with bone metastasis in 2001. Two years later a retroperitoneal benign paraganglioma was found and resected in his 32-yr-old daughter. Thus we diagnosed in this family a paraganglioma syndrome. We performed molecular genetic analyses of the genes SDHB, SDHC, and SDHD. We detected in the SDHB gene the mutation SDHB c. 558-3 C> G affecting the splice site of exon 5. In a second daughter the mutation was also detected, thorough clinical investigation revealed normal results. We conclude that the SDHB mutation predisposes to abdominal extra-adrenal and potential malignant pheochromocytoma with incomplete penetrance.

[Paraneoplastic hormonal syndromes]. / Síndromes hormonales paraneoplásicos.

We can define paraneoplastic syndromes as a combination of effects occurring far from the original location of the tumour and independently from the local repercussion of its metastases. Paraneoplastic hormonal syndromes depend on the secretion of hormonal peptides or their precursors, cytokines and, more rarely, thyroidal hormones and Vitamin D, which act in an endocrine, paracrine or autocrine way. Sometimes, paraneoplastic syndromes can be more serious than the consequences of the primary tumour itself and can precede, develop in parallel, or follow the manifestations of this tumour. It is important to recognise a paraneoplastic hormonal syndrome for several reasons, amongst which we would draw attention to three: 1) It can lead to the diagnosis of a previously undetected, underlying malign or benign neoplasia; 2) It can dominate the clinical picture and thus lead to errors with respect to the origin and type of primary tumour; and 3) It can follow the clinical course of the underlying tumour and thus be useful for monitoring its evolution. The molecular mechanisms responsible for the development of these syndromes are not well-known, but it is believed that they might be inherent to the mutations responsible for the primary tumour or depend on epigenetic factors such as methylation. In this review, we consider the following paraneoplastic hormonal syndromes: malign hypercalcaemia, hyponatraemia (inappropiate secretion of the antidiuretic hormone), ectopic Cushing's syndrome, ectopic acromegaly, hypoglycaemia due to tumours different from those of the islet cells and paraneoplastic gynaecomastia; we make a brief final reference to other hormones (calcitonin, somatostatin, and VIP).