Endocrine Abstracts

Introduction: While most common aetiologies accounting for hyperthyroidism are straightforward and respond predictably to treatment, a subset provides diagnostic or therapeutic challenge. We report such a case.

Case report: A 26-year-old Afro-Caribbean male presented with symptoms of thyrotoxicosis. FT4 was 50 (12–20 pmol/l), FT3 11.5 (3–8 pmol/l) and TSH 5.38 (0.27–4.20 mU/l). He had diffuse non-tender thyromegaly without eye signs. Thyroid antibody was negative. Three months later he felt better on Carbimazole 30 mg but complained of lethargy and weight gain. FT4 was now 15, FT3 12.3, TSH 69.6 mU/l. Carbimazole was therefore discontinued.

10 months later he presented with tremor and palpitations on 20 mg of Carbimazole. He insisted good compliance with medication. FT4 was 36, FT3 was 12.3 and TSH was 11.87 μ/l. Carbimazole was increased to 30 mg.

Short synacthen test and pituitary function was unremarkable. MRI of the pituitary ruled out TSH-secreting adenoma. 1 year after presentation FT4 was 22, FT3 11.7 and TSH 20.58 μ/l. Carbimazole was withdrawn.

Differential diagnoses considered were assay artefact, interfering antibodies to FT4 and Resistance to Thyroid Hormone (RTH). The former two were excluded by testing in multiple laboratories. Genetic testing revealed heterozygosity for a mutation in the thyroid receptor (TR)-β gene (targeted to exons 7, 8, 9 and 10). Patient later disclosed about an aunt in Jamaica with persistent hyperthyroidism on high doses of carbimazole.

Discussion: RTH is a rare, inherited condition of reduced responsiveness of target tissue to thyroid hormone. Incidence is estimated to be 1 case per 40 000 live births and clinical presentation is highly variable. Characteristically FT4 and FT3 are raised with an unsuppressed TSH. Diagnosis can be challenging and other common differentials need to be excluded. It is important to consider this diagnosis in a young person with family history and persistently unsuppressed TSH with raised FT3/FT4.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.