Familial hypocalciuric hypercalcemia (FHH) type 1, caused by a heterozygous inactivating mutation of the gene encoding the calcium-sensing receptor (CaSR), is characterized by mild to moderate hypercalcemia, hypocalciuria and inappropriately normal or elevated parathyroid hormone (PTH). FHH must be differentiated from primary hyperparathyroidism (PHPT) because parathyroidectomy is ineffective in the former. Herein, we report a 39-year-old male patient with a 13-year history of asymptomatic PTH-dependent hypercalcemia (mean calcium of 2.88 mmol/l; reference range 2.15-2.55 mmol/l) and calcium-tocreatinine clearance ratio (Ca/Cr) ranging from 0.007 to 0.0198, which is consistent with either FHH or PHPT. Although a family history of hypercalcemia was negative, and PET-CT with fluorocholine was suggestive of a parathyroid adenoma, genetic analysis of the CaSR gene identified a heterozygous inactivating mutation NM_000388.4:c.1670G>A p. (Gly557Glu) in exon 6 and a polymorphism NM_000388.4:c.1192G>A p. (Asp398Asn) in exon 4. The G557E mutation has been previously reported in a Japanese family in which all family members with the mutation had Ca/Cr below 0.01 consistent with FHH. The biochemical profile of FHH and PHPT may overlap. Our FHH patient with a G557E CaSR mutation illustrates that the differential diagnosis can be difficult in an index case with no family history, (false) positive parathyroid imaging and higher calciuria than expected for FHH. Calcium intake, vitamin D status and bone resorption might have contributed to the Ca/Cr variations over a 13-year clinical follow up. This case thus emphasizes the irreplaceable role of genetic testing of the CaSR gene when clinical evaluation is inconclusive., Kateřina Zajíčková, Marcela Dvořáková, Jitka Moravcová, Josef Včelák, David Goltzman., and Obsahuje bibliografii
The metabolic pathways that contribute to maintain serum calcium concentration in narrow physiological range include the bone remodeling process, intestinal absorption and renal tubule resorption. Dysbalance in t hese regulations may lead to hyper - or hypocalcemia. Hypercalcemia is a potentionally life -threatening and relatively common clinical problem, which is mostly associated with hyperparathyroidism and/or malignant diseases (90 %). Scarce causes of hypercalce mia involve renal failure, kidney transplantation, endocrinopathies, granulomatous diseases, and the long -term treatment with some pharmaceuticals (vitamin D, retinoic acid, lithium). Genetic causes of hypercalcemia involve familial hypocalciuric hypercalc emia associated with an inactivation mutation in the calcium sensing receptor gene and/or a mutation in the CYP24A1 gene. Furthermore, hypercalcemia accompanying primary hyperparathyroidism, which develops as part of multiple endocrine neoplasia (MEN1 and MEN2), is also genetically determined. In this review mechanisms of hypercalcemia are discussed. The objective of this article is a review of hypercalcemia obtained from a Medline bibliographic search., I. Žofková., and Obsahuje bibliografii
Inconclusive preoperative imaging is a strong predictor of multiglandular parathyroid disease (MGD) in patients with primary hyperparathyroidism (PHPT). MGD was investigated in a cohort of 17 patients with PHPT (mean age 64.9 years, total calcium 2.75 mmol/l and parathyroid hormone (PTH) 113.3 ng/l) who underwent 18F-fluorocholine PET/CT (FCH) imaging before surgery. The initial MIBI SPECT scintigraphy (MIBI) and/or neck ultrasound were not conclusive or did not localize all pathological parathyroid glands, and PHPT persisted after surgery. Sporadic MGD was present in 4 of 17 patients with PHPT (24 %). In 3 of 4 patients with MGD, FCH correctly localized 6 pathological parathyroid glands and surgery was successful. Excised parathyroid glands were smaller (p <0.02) and often hyperplastic in MGD than in single gland disease. In two individuals with MGD, excision of a hyperplastic parathyroid gland led to a false positive decline in intraoperative PTH and/or postoperative serum calcium. Although in one patient it was associated with partial false negativity, parathyroid imaging with FCH seemed to be superior to neck ultrasound and/or MIBI scintigraphy in MGD.
18F-fluorocholine positron emission tomography/computed tomography (FCH) was performed after inconclusive neck ultrasound and 99Tc-sestaMIBI SPECT (MIBI) scintigraphy in patients with primary hyperparathyroidism (PHPT) to localize abnormal parathyroid glands before surgery. The results were retrospectively evaluated and compared to postoperative histopathological findings. 13 patients with PHPT were enrolled (mean age 64.3 years, preoperative calcium 2.74 mmol/l and parathyroid hormone 114.6 ng/l). FCH localized hyperfunctioning parathyroid glands in 12 patients of 13 (per patient sensitivity 92 % and positive predictive value (PPV) 100 %). Fourteen parathyroid lesions (11 adenomas, 3 hyperplastic glands) were resected with a mean size of 11.9 mm (per lesion sensitivity 93 % and PPV 81 %). Four adenomas and one hyperplastic gland were composed of only chief cells, whereas five lesions contained both chief and oxyphil cells. In three patients an exclusively oxyphil adenoma was found, surprisingly with negative MIBI scintigraphy in spite of a high mitochondria content in the oxyphil parathyroid cells. 12 of 13 patients had thyroid disease. In our limited study sample, FCH correctly identified parathyroid adenomas and/or hyperplastic glands in 92 % of patients with previously inconclusive conventional imaging. Unlike MIBI, FCH successfully localized small, hyperplastic and multiple hyperfunctioning parathyroid glands, irrespective of their histopathological composition., K. Zajíčková, D. Zogala, J. Kubinyi., and Obsahuje bibliografii