Primary hyperparathyroidism in a patient with familial hypocalciuric hypercalcaemia due to a novel mutation in the calcium-sensing receptor gene

Abstract

We describe the clinical and genetic findings in pedigree with a novel mutation in the calcium sensing receptor (CaSR) gene and the unusual coexistence of primary hyperparathyroidism (HPT) and familial hypocalciuric hypercalcaemia (FHH) and its clinical management. The occurrence of both FHH and primary HPT in the same patient has been described rarely. Our pedigree has a novel mutation in the CaSR gene. Parathyroidectomy led to a reduction, but not normalization of the calcium levels in the patient identified as having HPT. The coexistence of HPT and FHH was considered in this patient as her calcium and PTH levels were rising with time. Surgical resection of her parathyroid adenoma resulted in reduction of her calcium levels to above normal and significant reduction in her symptoms of fatigue and low mood.

Multiple endocrine neoplasia phenocopy revealed as a co‐occurring neuroendocrine tumor and familial hypocalciuric hypercalcemia type 3

“…This is in contrast to FHH1 patients who in general are asymptomatic 7. Reports of coexisting FHH1 and PHPT have previously been published 27, 28, 29. It may therefore be considered whether the index patient had developed PHPT superimposed on his inherited FHH3, which is supported by the histopathological findings showing multiple gland affection with both adenoma and hyperplasia.…”

Collision Diagnoses: Primary Hyperparathyroidism Layered on Familial Hypocalciuric Hypercalcemia

“…CASR mutations result in loss of function of the calcium-sensing receptor (CaSR) protein. The CaSR is located in the parathyroid glands (acting to regulate PTH secretion) and kidneys (modulating renal tubular calcium re-absorption), resulting in tightly regulated serum calcium levels (2). Loss of CaSR function causes a shift of the calcium set point (resulting in mild to moderate hypercalcemia), higher calcium levels necessary to suppress PTH secretion (manifesting as nonsuppressed to slightly elevated PTH levels), and increased calcium re-absorption in the kidney (exhibited by relative hypocalciuria) (1).…”

“…Surgery is contra-indicated as it does not resolve the hypercalcemia, nor does it provide any other clinical benefit. PHPT is caused by the inappropriate secretion of PTH by parathyroid glands despite the presence of hypercalcemia (2). Eighty-five percent of the time, this is the result of autonomous production by a single parathyroid adenoma, 10% by double adenomas, and 5% by four-gland hyperplasia (3).…”

Italian Society of Endocrinology Consensus Statement: definition, evaluation and management of patients with mild primary hyperparathyroidism

“…Nonetheless, this distinction is mandatory since asymptomatic FHH does not need follow-up or treatment. However, it should be highlighted that cases of coexisting PHPT and FHH have been recently described [19].…”