Endocrine Abstracts

Case report: A 29-year old Caucasian male was referred to our Endocrinology Outpatient Clinic following a recent admission after an episode of collapse when he was noted to have abnormal thyroid function tests: fT₄ 32.6 (7.5–21.1) pmol/l, TSH 6.41 (0.34–5.6) mU/l. These were repeated and again showed elevated fT₄ 26.9 pmol/l and normal TSH 2.29 mU/l. He reported some tremor of both hands but denied palpitations. He was clinically euthyroid but periodically had hypothyroid symptoms with lack of energy. There were no thyroid eye disease and no history of neck pain or swelling. He was otherwise fit and well. His sister had hypothyroidism.

Repeat TFTs at another laboratory using different assay showed similar results, thereby excluding thyroid antibody assay interference. Thyroid peroxidase antibodies were slightly raised at 362 IU/ml whilst thyrotropin-binding inhibiting immunoglobulins were negative. TSH alpha subunit was normal and pituitary MRI scan did not show any pituitary abnormality, suggesting TSHoma unlikely. Further questioning revealed that his sister was diagnosed with hypothyroidism since childhood and had suffered short stature.

Subsequently, samples were sent for thyroid hormone receptor gene defect and he was noted to be heterozygous for an autosomal dominant THRB C.958C>Tp.(Arg320Cys) mutation. He required no treatment with regards to his thyroid status and was referred to the clinical genetics service for family screening.

Discussion: This was the first case of resistance to thyroid hormone (RTH) diagnosed in our service. The case highlights the differential diagnosis of raised free thyroid hormone levels together with non-suppressed TSH secretion, which can be the result of assay interference with heterophile antibodies, TSHoma or thyroid hormone resistance. This inherited syndrome is characterised by reduced tissue responsiveness to thyroid hormone. The clinical presentation is highly variable, ranging from isolated biochemical abnormalities to a spectrum of mixed hypo-hyperthyroid signs and symptoms, even among affected siblings carrying the same mutation. It should be appropriately investigated in order to make the correct diagnosis and avoid unnecessary treatment.