Endocrine Abstracts

Introduction: Primary hyperparathyroidism (PHPT) is an endocrine condition in which autonomous excessive secretion of parathyroid hormone (PTH) results in hypercalcaemia. In approximately 80% of cases the aetiology is due to a single parathyroid adenoma, the remainder are due to hyperplasia of more than one gland. Familial Hypocalciuric Hypercalcaemia (FHH) is an autosomal dominant, inactivating mutation of the calcium-sensing receptor, causing a right-shift in the concentration-response curve, and producing biochemistry similar to PHPT.¹ Although usually benign, it can cause pancreatitis. More than 75% of cases are due to the following genotypes, in descending order of incidence, CASR, AP2S1, GNA11: FHH 1, 3, and 2, respectively.

Case details: We report the case of a 53-year South Asian male, referred with hypercalcaemia. Serum adjusted calcium was 2.71 mmol/l, PTH 4.5 pmol/l, FE_Ca 0.014, and 24h urine calcium 6.08 mmol; a previous 24h urine calcium was 8.76 mmol (normal 2.5-7.5). The patient had a history of renal stones, enough to cause hydro-uretero-nephrosis. Therefore, despite the equivocal biochemistry, it was felt that this was in keeping with PHPT. Dual-modality imaging did not reveal a discrete adenoma and so 4-gland exploration was undertaken with the removal of three glands, which had features of hyperplasia and was in keeping with the negative results of imaging; peak pre-operative PTH was 13.2, dropping to 4.4 pomol/l after surgery. Due to recurrence of hypercalcaemia and the equivocal FE_Ca, genetic testing was undertaken and showed the patient to be heterozygote FHH2 (GNA11).

Discussion: PHPT and FHH occurring in the same patient is rare, but has been reported.² A FE_Ca <0.02 should prompt consideration of FHH, but this patient presented with renal stone disease, more in keeping with primary hyperparathyroidism. Therefore, an operative approach was valid and there may have been reduced penetrance of the pathological variant of FHH. Where these conditions co-exist, surgery can reduce the level of hypercalcaemia and treatment choice should be based on presence of end-organ effects²; an alternative approach is to use cinacalcet, a calcimetic agent.¹

References: 1. Lee JY, Shoback DM. Familial hypocalciuric hypercalcemia and related disorders. Best Pract Res Clin Endocrinol Metab. 2018 Oct; 32(5): 609-619.

2. Frank-Raue K et al. Inactivating calcium-sensing receptor mutations in patients with primary hyperparathyroidism. Clin Endocrinol (Oxf). 2011 Jul; 75(1): 50-5.