The resistance of parathyroid cells to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in uremic hyperparathyroidism is thought to be caused, in part, by a 1,25(OH)2D3 receptor (VDR) deficiency in the parathyroids. However, results of biochemical studies addressing VDR numbers in the parathyroids are controversial. Several studies have found VDR content to be decreased in the parathyroids of uremic patients and animals, while others have found no such decrease in the parathyroids of uremic animals.To clarify the role of VDR, we investigated VDR distribution in surgically-excised parathyroids obtained from chronic dialysis patients by immunohistochemistry. We classified the parathyroids as exhibiting nodular or diffuse hyperplasia. Our studies demonstrated a lower density of VDR in the parathyroids showing nodular hyperplasia than in those showing diffuse hyperplasia. Even in the parathyroids showing diffuse hyperplasia, nodule-forming areas were present; these areas were virtually negative for VDR staining. A significant negative correlation was found between VDR density and the weight of the parathyroids. These findings indicate that the conflicting results of biochemical studies may be caused by the heterogeneous distribution of VDR; the decreased VDR density in parathyroids may contribute to the progression of secondary hyperparathyroidism and to the proliferation of parathyroid cells that is seen in uremia. (J. Clin.
In the present study, the role of vitamin D in the regulation of estrogen synthesis in gonads was investigated. Vitamin D receptor null mutant mice showed gonadal insufficiencies. Uterine hypoplasia and impaired folliculogenesis were observed in the female, and decreased sperm count and decreased motility with histological abnormality of the testis were observed in the male. The aromatase activities in these mice were low in the ovary, testis, and epididymis at 24%, 58%, and 35% of the wild-type values, respectively. The gene expression of aromatase was also reduced in these organs. Elevated serum levels of LH and FSH revealed hypergonadotropic hypogonadism in these mice. The gene expressions of estrogen receptor alpha and beta were normal in gonads in these mice. Supplementation of estradiol normalized histological abnormality in the male gonads as well as in the female. Calcium supplementation increased aromatase activity and partially corrected the hypogonadism. When the serum calcium concentration was kept in the normal range by supplementation, the aromatase activity in the ovary increased to 60% of the wild-type level, but LH and FSH levels were still elevated. These results indicated that vitamin D is essential for full gonadal function in both sexes. The action of vitamin D on estrogen biosynthesis was partially explained by maintaining calcium homeostasis; however, direct regulation of the expression of the aromatase gene should not be neglected.
A nationwide epidemiologic survey of idiopathic hypoparathyroidism and pseudohypoparathyroidism was conducted in 1998 to clarify the prevalence of the two disorders in Japan. From a total of 14,100 departments of pediatrics, internal medicine, neurology, and endocrinology in whole Japan, 2952 (20.9%) study departments were selected at random. Of these departments receiving the first questionnaire, 1855 (62.8%) responded. From these departments 390 patients with idiopathic hypoparathyroidism and 203 with pseudohypoparathyroidism who visited the hospitals in 1997 were reported. The total numbers of patients were estimated to be 900 (690-1100) for idiopathic hypoparathyroidism and 430 (330-520) for pseudohypoparathyroidism (95% confidence intervals in parentheses). Using these data, the period prevalence of the diseases were 7.2 (5.5-8.8) per million population in idiopathic hypoparathyroidism, and 3.4 (2.6-4.2) in pseudohypoparathyroidism (95% confidence intervals in parentheses).
Objective: The international, first-line diagnostic test for adult GH deficiency is the insulin tolerance test (ITT), which is contraindicated in some patients due to severe adverse events. Alternatives such as GH-releasing hormone combined with arginine or GH-releasing peptides (GHRP) have been proposed. We validated the use of GHRP-2 for diagnosing adult GH deficiency (GHD). Methods: Seventy-seven healthy subjects and 58 patients with peak GH!3 mg/l by ITT were enrolled. After overnight fasting, a 100 mg dose of GHRP-2 was administered intravenously; blood samples were taken during the subsequent 2 h and GH measured by immunoradiometric assay. Results: Serum GH peak occurred within 60 min after GHRP-2 administration in all subjects. GH responses to GHRP-2 were not affected by gender, but were slightly lower in elderly subjects and those with adiposity, although these did not influence diagnosis of GHD. Repeated tests showed favourable reproducibility. Peak GH concentrations after GHRP-2 were significantly (P!0.001) lower in patients (1.36G2.60 mg/l) than the healthy group (84.6G60.9 mg/l) with no difference between hypothalamic and pituitary diseases. Serum GH concentration at the point where sensitivity of response crossed with specificity ranged from 15 to 20 mg/l. A cut-off value of 15 mg/l for diagnosing GHD with GHRP-2 corresponded to the diagnostic value of 3 mg/l in the ITT. Conclusions: The GHRP-2 provocative test showed favourable reproducibility and was mildly influenced by age and adiposity. Severe GH deficiency could be diagnosed with high reliability using a 15 mg/l (9 mg/l when GH calibrated with recombinant World Health Organization 98/574 standard) cut-off for peak GH concentration.
Objective: Although there are a few reports on GH therapy in achondroplasia, these were based on a small sample and/or short-term observation. To clarify the effectiveness of GH treatment on short stature in achondroplasia and hypochondroplasia, a long-term treatment study in a larger number of patients was performed. Method: Forty-two children (16 males and 26 females, age 3±14 years) with achondroplasia were examined in this study. Initially, we evaluated hypothalamic±pituitary function and point mutation analysis as previously reported. After the evaluation, the children were treated with GH for more than 2 years; then post-treatment growth velocity and body proportion parameters were determined. Results: The 35 typical variants of our achondroplasia patients showed previously reported point mutation in the ®broblast growth factor receptor 3 gene. The annual height gain during GH therapy was signi®cantly greater than that before therapy (3:9 6 1:0 cm/year before treatment vs 6:5 6 1:8 cm/year for the ®rst year and 4:6 6 1:6 cm/year for the second year of treatment). The body disproportion had not been aggravated during the treatment period. Conclusion: We conclude that GH might be bene®cial in the treatment of short stature in children with achondroplasia in the ®rst 2 years of treatment. European Journal of Endocrinology 138 275±280
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