Endocrine Abstracts

Introduction: Thyroid hormone resistance due to a TRα mutation is rare and only recently described. We report a case of primary hyperparathyroidism in an adult patient with a known TRα mutation.

Case presentation: A 60 year old female was referred with hypercalcaemia and hyperparathyroidism that persisted despite correction of vitamin D deficiency. Parathyroid hormone levels continued to be elevated or inappropriately normal with hyper- or normo-calcaemia. She had a normal range urinary calcium excretion and normal renal ultrasound. DEXA scan showed osteoporosis. Sestamibi scan failed to localise a parathyroid adenoma. ‘Primary hypothyroidism’ was identified at a young age (3 years) and she received continuous thyroid hormone replacement. As both of her children developed early life hypothyroidism; genetic assessment was performed leading to diagnosis of thyroid hormone resistance syndrome due to thyroid hormone receptor alpha mutation (heterozygous A263V mutation in the THRA gene). Her condition presenting as selective thyroid hormone resistance and hypothyroidism, she was continued on L-T₄. She declined surgical exploration without prior localization of the parathyroid lesion, and as she does not have symptoms of hypercalcaemia she remains under surveillance and is being investigated for genetic causes of hypercalcamia (including calcium sensing receptor CaSR gene mutation) and possible molecular pathogenesis that links between thyroid hormone resistance and hypercalacaemia.

Conclusion: While thyroid hormone receptor alpha mutation is a rare genetic mutation; the combination of primary hyperparathyroidism and thyroid hormone resistance is very rare and an underlying genetic pathogenesis linking the two is yet to be determined.

Keywords: Thyroid hormone resistance, TRα, hypercalcaemia, hyperparathyroidism.