Endocrine Abstracts

Herein, we report currently a 39-year old male with a 13-year history of asymptomatic hypercalcemia (mean 2.88 mmol/l; reference range 2.15–2.55 mmol/l) and mildly elevated parathyroid hormone (mean 68.7 ng/l; reference range 15–65 ng/l). Initially, in years 2007–2010 his laboratory picture was compatible with the diagnosis of Familial hypocalciuric hypercalcemia (FHH) with calcium-to-creatinine clearance ratio (Ca/Cr) between 0.008–0.009.Genetic testing was not available at that time. The differential diagnosis from primary hyperparathyroidism (PHPT) was complicated by the fact that there was no other family member with documented hypercalcemia. Between years 2014–2016 his follow up was interrupted. When he came in 2017, his Ca/Cr has almost doubled (0.014–0.019), whereas serum calcium has remained at a constant and moderately elevated level. To rule out a parathyroid adenoma, the patient underwent Tc-sestamibi scintigraphy (negative) and PET-CT with fluorocholine revealing an active focus bellow the left thyroid lobe. The neck ultrasound did not find any lesion corresponding to an enlarged left lower parathyroid gland. The Calcium-sensing receptor gene sequencing was finally carried out and identified a heterozygous missense mutation in exon 6 (c.1670G>A, p.Gly557Glu). This mutation has been previously reported in a Japanese family. Unlike our proband, all family members with G557E mutation had Ca/Cr lower than 0.01 in line with FHH. Although bone densitometry showed normal bone mineral density (BMD) in our male patient, there was a significant decrease in BMD between years 2009–2017 (22% at the femoral neck, 14% at total hip and 4.5% at lumbar spine). The documented bone loss corresponded to annual BMD % change of 2.75 at the femoral neck, 1.75 at total hip and 0.6 at lumbar spine. The patient did not have any other obvious reasons for bone resorption (no medication, normal body mass index, no endocrinopathy, vitamin D sufficiency) and it remains to be elucidated.

The biochemical profile of FHH and PHPT may overlap. The present FHH patient illustrates that the differential diagnosis can be difficult in an index case with (false) positive parathyroid imaging. Moreover, his Ca/Cr fluctuated in a large range (0.007–0.0198).Calcium intake, vitamin D status and bone resorption might have contributed to the patient Ca/Cr variations in 10-year clinical follow up.

Supported by MZ ČR - RVO (Institute of Endocrinology - EU, 00023761)