Thyroid hormone resistance with succinate dehydrogenase-B gene mutation

Abstract

Resistance to thyroid hormone (RTH) is characterized by non-suppressed TSH concentration despite high T4 and/or T3 levels.1 Resistance may develop at any steps in the hormone receptor binding, signaling, or intracellular thyroid hormone metabolism process. The disease is caused by mutations in the thyroid hormone receptor beta (THRB) in the majority of cases.2 Mutations in other genes have been associated with RTH, including thyroid hormone receptor alpha (THRA), Monocarboxylate transporter-8 (MCT8), and selenocysteine insertion sequence binding protein 2 (SECISBP2).2, 3 After clinical and laboratory examinations, genetic screening of other family members is necessary in suspicious cases. Succinate dehydrogenase subunit B (SDHB) is a well-known gene related to pheochromocytoma and extra-adrenal paragangliomas in the head and neck.4-6 The patient as well as his two children who have been diagnosed with RTH, all are found to have SDHB mutations that are functionally significant. This is the first report an SDHB mutation has been recorded in an RTH case in the medical literature. A 50-yearold man evaluated preoperatively for nasal surgery showed hyperthyroidism, and he was prescribed methimazole orally. An ultrasound of his enlarged thyroid gland revealed a 13 mm haloed cystic necrotic nodule. The nodule was diagnosed as Bethesda IV suspicious for follicular neoplasia after a fine-needle aspiration biopsy. His laboratory findings were FT3:13.7 pmol/L (3.1-6.8), FT4: 20.5 pmol/L (12-22), and TSH:1.0 mIU/mL (0.27-4.2). He was planned for a total thyroidectomy in the euthyroid state and referred to our department. He had mild hyperthyroid symptoms, including excessive sweating and agitation. He was shorter than the population’s average height. He had a goiter and tachycardia on his physical examination. On repeated testing, his laboratory findings revealed a high FT3 level. Antibody interaction misleading results in polyethyleneglycol precipitated thyroid hormones were investigated, and comparable results were found. Scintigram and negative thyroid auto-antibodies ruled out Graves’ disease. Normal anterior pituitary hormone levels and a hypophysial MRI ruled out a pituitary adenoma. Drug-induced hyperthyroidism and acute non-thyroidal disease were not taken into consideration. His brother, his son, and his daughter had incompatible thyroid hormone concentrations as the index case (Table I).