Association of 25-hydroxyvitamin D and parathyroid hormone with the metabolic syndrome in black South African women.

The relationship between 25 hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and metabolic traits appear to differ among ethnicities and may be influenced by obesity. The aim of the study was to examine the association of serum 25(OH)D or PTH with metabolic syndrome (MetS) while controlling for adiposity in black women. Using a cross-sectional study design, 209 urban black women aged ≥ 43 years from the North West Province, South Africa, were included. Multiple regression models were used to explore the relationship between 25(OH)D or PTH and body composition. To explore the association between 25(OH)D or PTH and MetS, a separate variable was created including at least 3 of the MetS criteria, but excluding elevated waist circumference as a diagnostic criterion in a logistic regression model. The majority of the women (69.9%) were overweight or obese and 65.5% of the women had excessive adiposity using the age-specific cut-off points for body fat percentage. All body composition variables were positively associated with PTH, whereas body mass index and waist circumference, but not body fat percentage, had negative associations with 25(OH)D also after adjusting for confounders. Before and after adjusting for age, body fat, habitual physical activity, tobacco use, season of data collection, and estimated glomerular filtration rate, neither 25(OH)D nor PTH showed significant associations with MetS. Although PTH was positively associated and 25(OH)D was negatively associated with adiposity in black women, there was no association between either 25(OH)D or PTH and MetS in this study population, nor did adiposity influence these relationships.

Demographic, dietary, and biochemical determinants of vitamin D status in inner-city children.

BACKGROUND: Reports of clinical rickets are particularly evident in minority infants and children, but only limited analyses of vitamin D are available in this demographic group. OBJECTIVE: We sought to characterize circulating 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and their determinants, including circulating parathyroid hormone (PTH), total alkaline phosphatase activity (ALP), calcium, and phosphorus, in minority infants and children. DESIGN: We obtained demographic information and blood samples for measurement of PTH, ALP, 25(OH)D, and 1,25(OH)(2)D in >750 6-mo- to 3-y-old children. Dietary intake data were obtained and analyzed. RESULTS: The mean (±SD) 25(OH)D concentration was 66 ± 22 nmol/L (26.3 ± 8.7 ng/dL). A total of 15% of children had 25(OH)D concentrations less than the recommended target threshold of 50 nmol/L. Combined elevations of PTH and ALP occurred in only 2.5% of children. Determinants of 25(OH)D included vitamin D intake, age (decreasing with age), skin type (greater concentrations in lighter-skinned children than in darker-skinned children), formula use (higher intakes), season (greater concentrations in the summer and fall than in the winter and spring), and, inversely, PTH. The mean 1,25(OH)(2)D concentration was 158 ± 58 pmol/L (60.6 ± 22.5 pg/mL), which was consistent with a reference range of 41-274 pmol/L or 15.7-105.5 pg/mL. Determinants for 1,25(OH)(2)D were age (decreasing with age), sex (greater concentrations in girls than in boys), skin type (greater concentrations in lighter-skinned children than in darker-skinned children), and, inversely, serum calcium and phosphorus. CONCLUSIONS: Although 15% of subjects were vitamin D insufficient, only 2.5% of subjects had elevations of both PTH and ALP. The greater 25(OH)D concentrations observed with formula use confirm that dietary vitamin D fortification is effective in this demographic group. Circulating 1,25(OH)(2)D is higher in infants than in older children and adults and, in contrast to 25(OH)D, is not directly correlated with nutrient intakes.

Impact of race on hyperparathyroidism, mineral disarrays, administered vitamin D mimetic, and survival in hemodialysis patients.

Blacks have high rates of chronic kidney disease, are overrepresented among the US dialysis patients, have higher parathyroid hormone levels, but greater survival compared to nonblacks. We hypothesized that mineral and bone disorders (MBDs) have a bearing on survival advantages of black hemodialysis patients. In 139,328 thrice-weekly treated hemodialysis patients, including 32% blacks, in a large dialysis organization, where most laboratory values were measured monthly for up to 60 months (July 2001 to June 2006), we examined differences across races in measures of MBDs and survival predictabilities of these markers and administered the active vitamin D medication paricalcitol. Across each age increment, blacks had higher serum calcium and parathyroid hormone (PTH) levels and almost the same serum phosphorus and alkaline phosphatase levels and were more likely to receive injectable active vitamin D in the dialysis clinic, mostly paricalcitol, at higher doses than nonblacks. Racial differences existed in mortality predictabilities of different ranges of serum calcium, phosphorus, and PTH but not alkaline phosphatase. Blacks who received the highest dose of paricalcitol (>10 µg/week) had a demonstrable survival advantage over nonblacks (case-mix-adjusted death hazard ratio = 0.87, 95% confidence level 0.83-0.91) compared with those who received lower doses (<10 µg/week) or no active vitamin D. Hence, in black hemodialysis patients, hyperparathyroidism and hypercalcemia are more prevalent than in nonblacks, whereas hyperphosphatemia or hyperphosphatasemia are not. Survival advantages of blacks appear restricted to those receiving higher doses of active vitamin D. Examining the effect of MBD modulation on racial survival disparities of hemodialysis patients is warranted.

Vitamin D deficiency and hyperparathyroidism in relation to ethnicity: a cross-sectional survey in healthy adults.

BACKGROUND: The study of vitamin D status at population level gained relevance since vitamin D deficiency was recently suggested to trigger chronic disease. AIM OF THE STUDY: We aimed to describe vitamin D status, its association with bone and mineral metabolism and risk factors for deficiency in adults over 40 years in Belgium. METHODS: We conducted a cross-sectional survey in a stratified random sample of 401 subjects aged between 40 and 60 years living in Brussels, and drawn from 4 different ethnic backgrounds: autochthonous Belgian, Moroccan, Turkish and Congolese. 25-Hydroxyvitamin D (25OHD), parathyroid hormone (PTH), osteocalcin, C-telopeptide and bone mineral density was measured. RESULTS: Three-hundred and six subjects (77%) showed 25OHD concentrations below 50 nmol/l,135 (34%) below 25 nmol/l and 18 (5%) below 12.5 nmol/l. The proportion of subjects with vitamin D deficiency was four times greater amongst those of Moroccan or Turkish descent compared with those of Congolese or Belgian descent. Moroccan subjects showed a significant higher PTH and bone marker concentrations compared to Belgian. Ethnicity, season and sex were independently associated with vitamin D deficiency in multivariate analysis. CONCLUSION: The prevalence of vitamin D deficiency is very high amongst the adult population of Brussels but immigrants are at greater risk. Given the established link between population health and adequate vitamin D status, a policy of vitamin D supplementation should be considered in these risk groups.

Race and sex: predictors of the severity of hyperparathyroidism in peritoneal dialysis patients.

BACKGROUND: Uraemic hyperparathyroidism remains a common clinical problem. Conversely, oversuppression of parathyroid hormone (PTH), particularly in diabetic patients on peritoneal dialysis, has been implicated in low bone turnover disease. Race may also be an important factor determining susceptibility to hyperparathyroidism and the different forms of renal osteodystrophy. These compounding factors that might influence the severity of hyperparathyroidism have been studied in US dialysis and predialysis populations. Dialysis-dependant Africans and Afro-Caribbeans (AC) are known to have higher circulating PTH concentrations than comparable Caucasians (C) but Indo-Asians (IA) living in temperate climates have not been studied. METHODS: We performed a cross-sectional study of all patients undergoing peritoneal dialysis at St Bartholomew's and The Royal London Hospital on 1 May 2000. The highest historical recorded PTH was recorded with concurrent biochemical and demographic details. Regression models were used for the analysis of covariance and separate manova was performed incorporating the factors that were shown on univariate analysis to be significant. RESULTS: The current study confirmed that in 50 AC patients on peritoneal dialysis, the mean (+/- SEM) peak PTH concentration (93.9 +/- 9.3 pmol/L) was higher than in 148 C (56.7 +/- 4.3 pmol/L) and 67 IA (60.2 +/- 5.7 pmol/L), P < 0.0001 and P < 0.002, respectively. This is despite there being no significant difference in serum calcium concentrations and AC having a lower serum phosphate concentration at the time of peak hyperparathyroidism. There was no significant difference in mean peak PTH concentration between C and IA. Females were also found to have higher peak PTH concentrations, but the presence of diabetes did not influence the peak PTH concentration in this study. CONCLUSION: Although we have demonstrated that patients of African (but not Asian) descent undergoing peritoneal dialysis have more severe hyperparathyroidism than Caucasians, other studies suggest that Afro-Americans develop low bone turnover at higher PTH. This would suggest that PTH values should be interpreted with care and that bone biopsies to determine histology remain important. It may emerge that there are different optimal PTH concentrations according to race.

Is there a racial difference in presentation of primary hyperparathyroidism?

Nearly 50,000 new cases of primary hyperparathyroidism (PHPT) are diagnosed annually in the United States. Most information about the disease focuses on the white population. We evaluated African American (AA) and white patients at our tertiary care university medical center to determine whether there was a racial difference in presentation of PHPT. A retrospective chart review of patients treated surgically for PHPT between 1997 and 2002 was performed. Demographic data, laboratory values, objective symptoms, surgical procedure, and histologic findings were recorded. The AA participants were matched to whites by age and gender. The effect of race was adjusted for the matching variables by including them in regression models. ANOVA chi2 tests were performed on the race effects. Thirty-six (14.4%) of the 286 patients treated for PHPT at Wake Forest University Baptist Medical Center during this 5-year period were AA. There was no difference in serum calcium or presence of objective symptoms, but PTH levels were significantly higher for blacks (207.5 vs 143.5 pg/mL; P = 0.02). In our study, AA patients had significantly higher parathyroid hormone levels at time of surgical intervention but did not present with a difference in symptoms or more advanced disease. Further research is recommended to characterize ethnic differences in patients with PHPT.

Importance of low serum intact parathyroid hormone as a predictor of mortality in hemodialysis and peritoneal dialysis patients: 14 years of prospective observation.

Excess parathyroid hormone (PTH) has long been considered detrimental to the health of patients with end-stage renal disease. PTH has been implicated as a multisystem uremic toxin, and hyperparathyroidism can be a debilitating complication in dialyzed patients. We have studied prospectively the relationship of enrollment serum intact PTH and various demographic characteristics and other biochemical parameters to all-cause mortality in 345 hemodialysis (HD) and 277 peritoneal dialysis (PD) patients. We monitored the patients for 14 years. Observed survival and survival after adjustment for age, race, gender, months on dialysis at enrollment, diabetic status, and nutritional markers were significantly better for patients with enrollment PTH greater than 200 pg/mL than for patients with PTH 65 to 199 pg/mL and patients with PTH less than 65 pg/mL. Enrollment serum PTH was an independent predictor of survival in HD and PD patients. For HD patients, age and months on HD at enrollment were associated inversely with PTH level, whereas black race, creatinine, and phosphorus were associated directly with PTH. For PD patients, age, diabetes, and months on PD at enrollment were inverse predictors, whereas black race, albumin, creatinine, and phosphorus were associated positively with PTH. Lower than expected levels of PTH in uremic patients is associated with increased mortality. We hypothesize that inadequate protein intake or phosphorus intake or both result in impaired development of the expected secondary hyperparathyroidism and in the excess mortality risk inherent with malnutrition.

Vitamin D receptor gene polymorphism detected by digestion with Apa I influences the parathyroid response to extracellular calcium in Japanese chronic dialysis patients.

BACKGROUND: To play its physiological role, 1,25(OH)2D3 must bind to a specific vitamin D receptor (VDR) in the nucleus. We have previously reported that VDR gene polymorphism influences the parathyroid function in patients with end-stage renal disease (ESRD). In the present study, we have investigated the relationship between the parathyroid responsiveness and VDR gene polymorphism, as detected by the Apa I restriction enzyme, by changing the concentration of Ca2+ in the dialysate. METHODS: 58 Japanese ESRD patients undergoing renal replacement therapy in our institution were evaluated. Genomic DNA was extracted from peripheral leukocytes and digested at the intron between exon 8 and exon 9 of the VDR gene using Apa I enzyme. Then alleles were classified into genotype A (undigested allele) and genotype a (digested allele). Extracellular ionized calcium ([Ca2+]e), serum phosphate, and intact parathyroid hormone (PTH) were measured before and after each hemodialysis (HD) session with dialysates having different concentrations of Ca2+ (1.5 or 1.25 mmol/l). The significance of differences in statistical analyses was defined within confidence limits of 5.0%. RESULTS: The AA, Aa, and aa genotypes were observed in 7/58 patients (12.1%), 23/58 patients (39.6%), and 28/58 patients (48.3%), respectively. The PTH reduction after HD with the 1.5-mmol/l Ca dialysate did not differ significantly between group AA+Aa and group aa. On the other hand, the PTH increase was significantly higher in group aa than in group AA+Aa after HD with the 1.25-mmol/l Ca dialysate (p = 0.0107), despite a similar PTH level before HD. Similarly, the percent increase of PTH after HD with the 1.25-mmol/l Ca dialysate was significantly higher (p = 0.0112) in group aa (50.2 +/- 9.4%) than in group AA+Aa (19.7 +/- 7.2%). There were no significant differences between the two groups in [Ca2+]e nor in serum phosphorus (Pi) before and after HD with either dialysate. Group AA+Aa and group aa did not show statistically significant differences in age, female/male ratio, ratio of diabetic nephropathy, or dialysis period. CONCLUSIONS: The study results showed that the patients in group aa were more sensitive to changes in [Ca2+]e than those in group AA+Aa. Moreover, they suggested that the VDR gene polymorphism may affect parathyroid responsiveness to changes in [Ca2+]e, which in turn may influence onset and progression of hyperparathyroidism in ESRD patients.

Mapping the gene for hereditary hyperparathyroidism and prolactinoma (MEN1Burin) to chromosome 11q: evidence for a founder effect in patients from Newfoundland.

An autosomal dominant syndrome of prolactinomas, carcinoids, and hyperparathyroidism was described in four Newfoundland kindreds in 1980 and in one kindred from the Pacific Northwest in 1983. Because this syndrome shares many features with multiple endocrine neoplasia type 1, the gene for which maps to proximal chromosome 11q, we performed linkage studies with chromosome 11 markers in prolactinoma families to determine whether the two genes map to the same location. All proximal chromosome 11q markers gave positive LOD scores, and no recombinants were seen with PYGM (LOD score 15.25, recombination fraction .0). All affected individuals from Newfoundland shared the same PYGM allele, providing evidence for a founder effect. The disease in the Pacific Northwest kindred cosegregated with a different PYGM allele.