Endocrine Abstracts

Resistance to thyroid hormone (RTH) is a rare cause of abnormal thyroid biochemistry. Coexistence with autoimmune thyroid disorders such as Graves’ disease is exceedingly uncommon. We present a 44-year-old woman with a longstanding history of palpitations, anxiety, increased bowel frequency, and heat intolerance without weight loss, despite a good appetite. History includes rheumatoid arthritis, and family history was notable for autoimmune thyroid disease and type 1 diabetes. Initial evaluation revealed low TSH (0.03 mU/l) and markedly elevated FT4 (75 pmol/l), leading to a presumptive diagnosis of Graves’ disease. She was treated with carbimazole but has lost follow-up. Upon re-presentation in 2018, with persistent symptoms, laboratory tests revealed unsuppressed TSH (1.2 mU/l), elevated FT4 (35.4 pmol/l), positive TSH receptor antibodies (1.6 IU/l) and thyroid peroxidase antibodies. Thyroid ultrasound showed diffuse heterogeneity and increased vascularity. Given the paradoxically normal TSH in the context of high FT4, TSH-secreting pituitary adenoma and RTH were considered. Over the years, thyroid function tests continued to demonstrate elevated free thyroid hormones (FT4 38.5) with inappropriately normal TSH levels (TSH 0.89). Part of the workup included Alpha-subunit 0.2 IU/l(Normal 0-1), SHBH 85 nmol/l(Normal 32-128), and Genetic testing ultimately confirmed a heterozygous pathogenic variant in the THRB gene (c.1357C>A; p. Pro453Thr), consistent with RTH. Management included symptomatic control with propranolol. However, subsequent symptoms exacerbation with suppressed TSH levels (<0.01) and rising FT4(53.6), suggesting relapse of Graves’ disease. Antithyroid therapy was reintroduced, aiming to normalise TSH rather than free thyroid hormone to avoid overtreatment and hypothyroidism. This case highlights the diagnostic and therapeutic challenges posed by the rare coexistence of RTH and Graves’ disease. It emphasises the need for individualised treatment strategies focused on TSH targets rather than the normalisation of free hormone levels in such complex endocrine disorders.