Association of parathyroid adenoma and familial hypocalciuric hypercalcaemia in a teenager

Abstract

Objective: Familial hypocalciuric hypercalcaemia (FHH) is clinically characterized by mild to moderate parathyroid hormone (PTH)-dependent hypercalcaemia, autosomal dominant pattern of inheritance, and normal to frankly reduced urinary calcium excretion in spite of a high serum calcium (clearance (Ca)/clearance (Cr)!0.01). FHH has a benign course and should be differentiated from primary hyperparathyroidism. It is usually caused by a heterozygous loss-of-function mutation in the calciumsensing receptor gene (CASR). Design: We report the case of a 16-year-old patient with hypercalcaemia and a mixed family history of parathyroid adenoma and mild hypercalcaemia. Serum calcium was 14 mg/dl with a serum iPTH of 253 pg/ml. Results: A neck 99m Tc-sesta MIBI tomoscintigraphy showed a definite hyperactivity in the left upper quadrant. A surgical four-gland exploration confirmed a single parathyroid adenoma. After surgical resection of a left superior parathyroid adenoma, the patient's hypercalcemia improved but did not normalize, returning to a level typical of FHH. An inactivating mutation in exon 4 of the CASR gene, predicting a p.Glu297Lys amino acid substitution was found. Conclusions: Thus, this 16-year old patient presented with the association of FHH and a single parathyroid adenoma. The young age of the patient and the association of parathyroid adenoma and FHH in his grandmother argue for a causal link between CASR mutation and parathyroid adenoma in this family. This case contributes to illustrate the expanding clinical spectrum of CASR loss-of-function mutations.

Mutations of calcium-sensing receptor gene: two novel mutations and overview of impact on calcium homeostasis

“…On the other hand, activating mutations have been described in the context of ADH and type V Bartter syndrome (see http://www.casrdb.mcgill.ca). Taking into account the last 6 years, about 36 CASR gene mutations have been described (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38), with 34 being inactivating and two activating. Among them, most have been found in exons 4 and 7.…”

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.…”

Primary Hyperparathyroidism in Children and Adolescents

“…Further confusion between FHH and PHPT derives from recent reports of the development of classic parathyroid adenomas and symptomatic PHPT in some teens and adults with FHH, however. 38,39 Multiple endocrine neoplasia, or MEN1 (OMIM 131099), is the most common cause of inherited PHPT. PHPT is present in more than 90% of patients, and diffuse hyperplasia or multiple adenomas are more common than solitary adenomas.…”