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Hypocalciuric Hypercalcaemia (hypocalciuric + hypercalcaemia)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Normalization of serum calcium by cinacalcet in a patient with hypercalcaemia due to a de novo inactivating mutation of the calcium-sensing receptor

JOURNAL OF INTERNAL MEDICINE, Issue 2 2006
H. J. L. M. TIMMERS
Abstract. Familial benign hypocalciuric hypercalcaemia (FHH) results from a heterozygous inactivating mutation of the calcium-sensing receptor (CaR) and is characterized by hypercalcaemia, hypocalciuria and inappropriately normal plasma levels of parathyroid hormone. In a minority of patients, a loss of function mutation of the CaR results in severe hypercalcaemia associated with complications for which no effective surgical or medical treatment is available. We investigated the effects of the calcimimetic agent cinacalcet, an allosteric modulator of the CaR, in a 26-year-old man presenting with hypercalcaemia due to a de novo inactivating mutation of the CaR. Complicating features were recurrent psychosis and progressive severe osteoporosis. A single dose of either 30 or 60 mg of cinacalcet resulted in a 63,88% decline in plasma parathyroid hormone levels within 2 h of administration of the agent, reverting to baseline levels after 12 h. Normalization of serum calcium was more gradual but sustained for up to 12 months of treatment with a maintenance twice-daily oral dose of 60 + 30 mg cinacalcet. In addition to its beneficial effects in primary and secondary hyperparathyroidism, cinacalcet may open new therapeutic avenues in the management of a subset of patients with severe hypercalcaemia due to inactivating mutations of the CaR. [source]

Neonatal severe hyperparathyroidism associated with a novel de novo heterozygous R551K inactivating mutation and a heterozygous A986S polymorphism of the calcium-sensing receptor gene

CLINICAL ENDOCRINOLOGY, Issue 3 2007
Judit Tõke
Summary Introduction, Neonatal severe hyperparathyroidism (NSHPT) is induced by inactivating mutations of human calcium-sensing receptor (CaSR). Only three heterozygous de novo inactivating mutations of CaSR causing NSHPT have been described. We report the case of a now 11-year-old boy with NSHPT and we characterize a novel inactivating mutation along with the results of some functional analyses. Patient and methods, As a neonate the patient presented the clinical syndrome of NSHPT. At 6 years of age persisting hypercalcaemia without clinical symptoms was documented, and the patient remained completely symptom free without parathyroid surgery until his present age of 11 years. The entire coding region of the CaSR gene of the patient and his family members was sequenced. Functional investigation was performed in HEK-293 cells, transiently transfected with wild type and mutant CaSR plasmid constructs. Results, Sequence analysis revealed a novel de novo heterozygous mutation at codon 551 (AGG,AAG), predicting a change of arginine to lysine (R551K) and a known heterozygous polymorphism (A986S) on the same allele, which was inherited from the father. We demonstrated that the novel R551K mutation significantly reduced the calcium sensitivity of CaSR (EC50: from 3·38 ± 0·62,6·10 ± 0·83 mmol/l), which was not alleviated by the simultaneous presence of A986S polymorphism. Conclusions, We present the fourth NSHPT case induced by a novel de novo heterozygous inactivating mutation (R551K) of the CaSR gene. The disease gradually reverted to a symptomless, benign condition resembling familial hypocalciuric hypercalcaemia without any surgical intervention. [source]

Novel mutation of the calcium sensing receptor gene in familial hypocalciuric hypercalcaemia and neonatal severe hyperparathyroidism

CLINICAL ENDOCRINOLOGY, Issue 6 2006
Simone Caixeta de Andrade
No abstract is available for this article. [source]

Impaired GH secretion to provocative stimuli in two families with hypocalciuric hypercalcaemia

CLINICAL ENDOCRINOLOGY, Issue 5 2003
Elisabetta Cecconi
Summary objective, To determine whether hypercalcemia per se might be responsible for an impairment in GH secretion. design, Prospective study. patients, Six subjects of two unrelated families with familial hypocalciuric hypercalcaemia (FHH), an autosomal dominant disorder due to inactivating mutations in the calcium receptor gene, leading to an increase in serum calcium levels and inappropriately normal serum PTH concentrations. Forty normal subjects, matched for sex and age served as controls. measurements, Serum GH concentrations were measured after GHRH-Arginine (GHRH-Arg) stimulation test; serum IGF-I, ACTH, cortisol, FT4, FT3, TSH, PRL, LH, FSH levels were measured under basal conditions. results, All subjects (two male, four female, age range 24,74 years) had increased serum ionized calcium levels (range 1·36,1·56 mmol/l) and five of six patients had normal PTH levels (range for all patients was 14,68 ng/l). Basal serum GH concentrations ranged from 0·1 to 7·0 µg/l. Mean serum GH secretory peak after GHRH-Arg stimulation test was reduced in five subjects (mean 9·3 ± 3·6 µg/l, P < 0·006 vs. Controls, mean 67·0 ± 44·0 µg/l, cut-off, 16·0 µg/l) and normal in one subject (38·7 µg/l). However, serum IGF-I levels were reduced only in two patients (29 and 57 µg/l) and normal in four subjects (range 127,208 µg/l). The basal secretion of the other anterior pituitary hormones was within their normal ranges. conclusions, The results of the present study support the concept that elevated serum calcium levels impair GH secretion. However, the clinical relevance of GH deficiency in FHH remains to be elucidated. [source]