Endocrine Abstracts

Introduction: Resistance to thyroid hormone beta is a genetic disease defined by impaired sensitivity of target tissue to thyroid hormone caused by mutation of thyroid hormone receptor beta gene, appearing with an incidence of 1/40,000. The characteristic biochemical profile of resistance to thyroid hormone is elevated serum thyroid hormone level and inappropriate serum level of thyrotropin (TSH) which is normal or elevated. Clinical picture is variable ranging from asymptomatic patients to patients with signs of overt hyperthyroidism or hypothyroidism. Diagnosis of resistance to thyroid hormone beta is confirmed by genetic testing. In 15% of patients with characteristic biochemical profile for resistance to thyroid hormone beta (after exclusion of other possible causes: laboratory interference, familial dysalbuminemic hyperthyroxinemia, TSH-secreting pituitary tumor) no mutation of thyroid hormone receptor beta gene is found. In such cases the disorder is called resistance to thyroid hormone in the absence of thyroid hormone receptor mutation.

Case report: A 55-year-old male was referred to the thyroid department because of imbalance between serum levels of TSH, free thyroxine (fT4) and free triiodothyronine (fT3): TSH 1.03 mIU/l (0.59-4.23 mIU/l), fT4 35.0 pmol/l (11.3-18.8 pmol/l), and fT3 9.98 pmol/l (3.79-6.05 pmol/l), respectively. Antibodies against thyroid peroxidase, thyroglobulin and TSH receptor were negative, level of thyroglobulin was normal, level of sex hormone binding globulin was normal 60 nmol/l (13-71 nmol/l). Ultrasound examination showed an enlarged (48 mL) thyroid gland with multiple small nodules, scintigraphy with Technetium-99m showed a nonhomogenous uptake in thyroid gland. Mutation of thyroid hormone receptor beta gene was excluded, as well as laboratory interferences, TSH-secreting pituitary tumor and familial dysalbuminemic hyperthyroxinemia as possible causes of imbalance between TSH and thyroid hormones. The patient reported palpitations and excessive sweating. Therefore, therapy with a beta blocker was initiated which partially improved the symptoms.

Conclusion: Resistance to thyroid hormone in the absence of thyroid hormone receptor mutation is a rare condition that can only be diagnosed by exclusion of other possible causes (resistance to thyroid hormone beta, laboratory interferences, TSH-secreting pituitary tumor, familial dysalbuminemic hyperthyroxinemia). Diagnosis can be further complicated by coexistent thyroid disease. Treatment, if needed, is individually tailored (beta blockers, radioiodine therapy, thyroidectomy).