Endocrine Abstracts

Resistance to thyroid hormone is a dominantly inherited condition of impaired tissue responsiveness to the action of thyroid hormone. Thyroid hormone levels are elevated with failure to suppress TSH.The presentation is highly variable. In individuals with generalized resistance to thyroid hormone (GRTH) appear to have eumetabolic state with compensatory high thyroid hormone levels. In contrast, those who appear to have hyper metabolic features but may have similar thyroid hormone and TSH levels are classified as selective pituitary resistance to thyroid hormone (PRTH).

The case presented with symptoms of Attention Deficit Hyperactivity Disorder since birth, childhood asthma and recurrent sinusitis. He was diagnosed hyperthyroidism at age 29 when thyroid function tests showed total T4 201 nmol/l (60–140), total T3 3.6 nmol/l (1.3–3), thyroid hormone distribution index 2.2 (2) and free thyroxine index 4.4 (1.3–3.2). Clinically he was thyrotoxic with a small goitre. Initially he was treated with carbimazole followed by sub total thyroidectomy after 18 months for uncontrolled thyrotoxic symptoms. Histology showed thyroid hyperplasia. He was started on thyroxine for post op hypothyroidism 10 years later. At age 54, he was referred to the endocrine clinic with thyrotoxic symptoms for several years with TSH 12.1 miu/l, Free T4 28.9 pmol/l and total T3 2.7 nmol/l.He was tachycardic and had a small diffuse goitre. Thyroid antibodies were negative. TSH- oma was excluded with normal MRI pituitary and alpha subunit.TSH concentration increased after TRH administration. Sequencing of thyroid hormone receptor β gene showed heterozygous mutation for P453T. One of his children (29 female), who has the same phenotype is awaiting genetic evaluation.

Conclusion: Although this man has had features of PRTH through out his life, a diagnosis was delayed for many years, partly due to a lack of sensitive TSH assay, but also having high index of suspicion for this rare disorder.