Vitamin D, PTH and calcium levels in pregnant women and their neonates

Objectives To determine the prevalence of vitamin D deficiency in pregnant women and their neonates and to examine factors associated with vitamin D deficiency. Design and patients Population‐based study of pregnant women and their neonates from South‐eastern Sydney, Australia. Measurements Serum 25 hydroxy‐vitamin D (25‐OHD), PTH, calcium, albumin, phosphate and alkaline phosphatase were measured in women at 23–32 weeks gestation and on cord blood at delivery. Maternal skin phototype was recorded using the Fitzpatrick scale. Results Vitamin D deficiency (defined as 25‐OHD ≤ 25 nmol/l) was found in 144 of 971 (15%) women and 98 of 901 (11%) neonates. Median 25‐OHD was 52 nmol/l (range 17–174) in mothers and 60 nmol/l (17–245) in neonates. Maternal 25‐OHD levels varied by season, with lowest levels in late winter/early spring (P < 0·001). Factors associated with maternal vitamin D deficiency in multiple logistic regression were (OR, 95% CI): maternal birthplace outside Australia: 2·2 (1·4–3·5, P = 0·001), dark skin phototype: 2·7 (1·6–4·5, P < 0·001), wearing a veil: 21·7 (11·7–40·3, P < 0·001) and younger maternal age: 0·93 (0·89–0·97, P = 0·001). Maternal vitamin D deficiency increased the risk of neonatal vitamin D deficiency (OR 17·2, 95% CI 8·8–34·3) and birth weight was lower among infants of deficient vs. sufficient mothers: mean (SD) 3245 g (545) vs. 3453 g (555), P < 0·001. Conclusions Vitamin D deficiency is common among pregnant women; immigrant, veiled and dark skinned women are at greatest risk. Maternal vitamin D deficiency increases the risk of neonatal vitamin D deficiency and lower birth weight.     

Relationships among vitamin D levels, parathyroid hormone, and calcium absorption in young adolescents

BACKGROUND: Evidence suggests that vitamin D status in adults, as assessed by serum 25-hydroxyvitamin D (25-OHD), is positively associated with calcium absorption fraction and inversely associated with serum PTH. Few comparable pediatric data exist. OBJECTIVES: The objective of this study was to evaluate the relationships among vitamin D status, PTH, and calcium absorption in midpubertal boys and girls. METHODS: Calcium absorption was measured as part of an evaluation of the effects of prebiotics (inulin-type fructans) using a stable isotope method in 93 young adolescents, 12.7 +/- 1.0 yr of age, receiving diets averaging approximately 900 mg/d calcium. RESULTS: A significant positive relation to calcium absorption was found for serum 1,25-dihydroxyvitamin D (P = 0.048) and PTH (P = 0.007), but not for 25-OHD (P = 0.77). PTH was significantly inversely related to 25-OHD and was positively related to serum 1,25-dihydroxyvitamin D and osteocalcin. PTH was marginally significantly inversely related to lumbar spinal, but not whole body, bone mineral density. CONCLUSIONS: These data suggest that in adolescents, especially in the presence of vitamin D insufficiency, PTH secretion increases to adapt to higher rates of bone formation associated with growth. This results in higher serum 1,25(OH)2D concentrations and increased calcium absorption results. Vitamin D status, as reflected by the serum 25-OHD level, is not closely related to calcium absorption. Whether adaptation to low serum 25-OHD is adequate under physiologically stressful situations, including those leading to very low serum 25-OHD levels, is unknown.     

The thyroid hormone, parathyroid hormone and vitamin D associated hypertension

Thyroid disorders and primary hyperparathyroidism have been known to be associated with increases in blood pressure. The hypertension related to hypothyroidism is a result of increased peripheral resistance, changes in renal hemodynamics, hormonal changes and obesity. Treatment of hypothyroidism with levo-thyroxine replacement causes a decrease in blood pressure and an overall decline in cardiovascular risk. High blood pressure has also been noted in patients with subclinical hypothyroidism. Hyperthyroidism, on the other hand, is associated with systolic hypertension resulting from an expansion of the circulating blood volume and increase in stroke volume. Increased serum calcium levels associated with a primary increase in parathyroid hormone levels have been also associated with high blood pressure recordings. The mechanism for this is not clear but the theories include an increase in the activity of the renin-angiotensin-aldosterone system and vasoconstriction. Treatment of primary hyperparathyroidism by surgery results in a decline in blood pressure and a decrease in the plasma renin activity. Finally, this review also looks at more recent evidence linking hypovitaminosis D with cardiovascular risk factors, particularly hypertension, and the postulated mechanisms linking the two.     

Serum concentrations of vitamin D and parathyroid hormone and prevalent metabolic syndrome among adults in the United States

Background: Some reports suggest that concentrations of vitamin D are inversely, whereas concentrations of parathyroid hormone (PTH) are directly, associated with prevalent metabolic syndrome. Because of lingering uncertainty about these associations, we examined the cross‐sectional associations between serum concentrations of 25‐hydroxyvitamin D₃ and PTH with metabolic syndrome in a representative sample of adults in the US. Methods: We used data from 1705 participants in the 2005–2006 National Health and Nutrition Examination Survey. Vitamin D was measured by radioimmunoassay, whereas PTH was measured using an electrochemiluminescent process. Results: The mean concentration of vitamin D for participants with and without metabolic syndrome was 20.3 and 22.9 ng/mL, respectively (P = 0.001). The mean concentration of PTH for participants with and without metabolic syndrome was 44.5 and 41.0 pg/mL, respectively (P = 0.002). The age‐adjusted mean concentrations of vitamin D (P for linear trend <0.001) decreased linearly, whereas PTH (P for linear trend = 0.002) increased linearly, as the number of components of metabolic syndrome increased. After adjusting for age, gender, physical activity, urinary albumin creatinine ratio, and concentrations of C‐reactive protein and calcium, concentrations in the highest quintile of vitamin D [prevalence ratio (PR) = 0.59; 95% confidence interval (CI) 0.44–0.79], but not PTH (PR = 1.18; 95% CI 0.97–1.43), was significantly associated with prevalent metabolic syndrome. Conclusion: Concentrations of vitamin D, but not PTH, were significantly associated with prevalent metabolic syndrome among US adults.     

Diurnal rhythm of plasma 1,25-dihydroxyvitamin D and vitamin D-binding protein in postmenopausal women: relationship to plasma parathyroid hormone and calcium and phosphate metabolism

OBJECTIVE: Diurnal variations in plasma levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) have previously only been investigated in young individuals, and these studies have failed to demonstrate a diurnal rhythm. We have studied whether plasma levels of 1,25(OH)(2)D and vitamin D-binding protein (DBP) vary in a diurnal rhythm in postmenopausal women. METHODS: Blood and urine were sampled with 2- and 4-h intervals in order to assess diurnal variations in plasma levels of 1,25(OH)(2)D, DBP and parathyroid hormone (PTH), as well as in plasma levels and urinary excretion rates of calcium and phosphate. Additionally, the free 1,25(OH)(2)D index was calculated (the molar ratio of 1,25(OH)(2)D to DBP). RESULTS: Plasma 1,25(OH)(2)D exhibited a diurnal rhythm (P<0.01) with a nadir in the morning (99+/-12 pmol/l), followed by a rapid increase to a plateau during the day (113+/-13 pmol/l, i.e. 14% above nadir level; P=0.005). A similar pattern of variation was found in plasma levels of DBP with peak levels 15% above nadir levels (P<0.01). The free 1,25(OH)(2)D index did not vary in a diurnal rhythm. PTH and plasma levels and urinary excretions of calcium and phosphate exhibited a diurnal pattern of variation. The diurnal rhythm of DBP was correlated with the rhythm of 1,25(OH)(2)D (r=0.47, P<0.01) and plasma albumin (r=0.76, P<0.01). Moreover, the rhythm of plasma calcium and PTH varied inversely (r=-0.36, P=0.02). CONCLUSIONS: With the disclosure of a diurnal rhythm of total plasma 1,25(OH)(2)D, all major hormones and minerals related to calcium homeostasis have now been shown to exhibit diurnal variations. In clinical studies, the diurnal variations of 1,25(OH)(2)D and DBP must be considered, i.e. blood sampling must be standardised according to the time of day.     

Vitamin D deficiency among pregnant women and their newborns in Isfahan, Iran

BACKGROUND AND AIMS: Vitamin D deficiency is one of the major health problems and unexpectedly has a high prevalence in sunny countries (e.g. Middle East). In this study we determined the prevalence of vitamin D deficiency in pregnant women and their newborns in Isfahan, a sunny city in Iran. METHODS: In a cross-sectional study, 88 newborns born in Beheshty hospital, affiliated to Isfahan University of Medical Sciences (August-September, 2005) and their mothers were studied. Their data were collected by questionnaires and blood sampling was done to measure serum alkaline phosphatase (ALP), calcium, phosphorus, 25 (OH) vitamin D and parathormone (PTH). Vitamin D deficiency defined as levels of 25 (OH) D < 20 and < 12.5 ng/ml for mothers and newborns, respectively and local cut-offs defined as levels in which mean serum PTH started to increase. RESULTS: The prevalence of vitamin D deficiency according to 25 (OH) D < 20 ng/ml in mothers and < 12.5 ng/ml in newborns was 5.7% and 4.5%, respectively. According to local cut-offs (35 ng/ml for mothers and 26 ng/ml for newborns) 26.1% of mothers and 53.4% of newborns were vitamin D deficient. CONCLUSION: According to local definition, vitamin D deficiency is a health problem in pregnant women and their newborns in this sunny city.     

Alterations in calcium, vitamin D, and parathyroid hormone physiology in normal men with aging: relationship to the development of senile osteopenia

The effects of aging on calcium and bone metabolism have not been systematically examined in men. To identify age-related alterations in vitamin D and PTH physiology and to assess their impact on skeletal health, we studied 62 normal men, aged 30-92 yr. The men were in excellent health, and none had any evidence of metabolic bone disease and/or known risk factors for osteopenia. Serum 25-hydroxyvitamin D (25OHD) concentrations declined steadily with advancing age (r = -0.47; P less than 0.001), and there was a corresponding decline in serum 24,25-dihydroxyvitamin D [24,25-(OH)2D] levels (r = -0.41; P less than 0.001). Serum 1,25-(OH)2D concentrations, however, did not vary over this age range (r = -0.07; P = NS). Plasma PTH levels increased with aging (r = -0.24; P less than 0.001), and there was a concomitant increase in urinary cAMP excretion (r = 0.38; P less than 0.001). Renal function (creatinine clearance) clearly declined with increasing age (r = -0.71; P less than 0.001). In conjunction with these changes in calcium metabolism, radial and vertebral bone mineral content declined. Whereas the fall in radial bone mineral content (single photon absorptiometry) at both proximal and distal sites was slight, there was a marked decrease in vertebral bone mineral content, as measured by quantitative computed tomography (r = -0.72; P less than 0.0001). The fall in vertebral bone mineral content correlated well with the declines in serum 25OHD and 24,25-(OH)2D concentrations (r = 0.47; P less than 0.001 and r = 0.51; P less than 0.001, respectively) and with the decline in renal function (r = 0.46; P less than 0.001). Multiple regression analysis revealed that the effects of aging on bone mineral content could be accounted for in large part by concomitant changes in mineral metabolism. Both the decline in renal function and the fall in serum 24,25-(OH)2D levels were closely associated with the fall in bone mineral content. These results indicate that a decline in renal function and alterations in vitamin D metabolism occur with aging in normal men. These changes contribute to, if not cause, the associated decline in skeletal mineral content in aging men.     

Thyroid hormone and parathyroid hormone competing to maintain calcium levels in the presence of vitamin D deficiency.

Weight loss and bone disease in the elderly are very often attributed to malignancy. Rarely, benign treatable conditions may be overlooked. Thyrotoxicosis, a benign treatable condition, needs to be excluded in such patients. The diagnosis may be delayed, since the symptoms are often subtle, and secondary complications including bone disease (osteoporosis) are therefore more frequent at the time of presentation. The case presented here illustrates this well, and also highlights the value of measuring vitamin D levels in such patients. The most interesting aspect of this case was the reciprocal relationship between thyroxine and parathyroid hormone observed in maintaining calcium homeostasis in this thyrotoxic patient with low vitamin D levels.     

Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women

Calcium supplementation is effective in reducing blood pressure in various states of hypertension, including pregnancy-induced hypertension and preeclampsia. In addition, calcitropic hormones are associated with blood pressure. The hypothesis is that short-term therapy with calcium and vitamin D(3) may improve blood pressure as well as secondary hyperparathyroidism more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D(3) (cholecalciferol) and calcium on blood pressure and biochemical measures of bone metabolism were studied. The sample consisted of 148 women (mean +/- SD age, 74 +/- 1 yr) with a 25-hydroxycholecalciferol (25OHD(3)) level below 50 nmol/L. They received either 1200 mg calcium plus 800 IU vitamin D(3) or 1200 mg calcium/day. We measured intact PTH, 25OHD(3), 1,25-dihydroxyvitamin D(3), blood pressure, and heart rate before and after treatment. Compared with calcium, supplementation with vitamin D(3) and calcium resulted in an increase in serum 25OHD(3) of 72% (P < 0.01), a decrease in serum PTH of 17% (P = 0.04), a decrease in systolic blood pressure (SBP) of 9.3% (P = 0.02), and a decrease in heart rate of 5.4% (P = 0.02). Sixty subjects (81%) in the vitamin D(3) and calcium group compared with 35 (47%) subjects in the calcium group showed a decrease in SBP of 5 mm Hg or more (P = 0.04). No statistically significant difference was observed in the diastolic blood pressures of the calcium-treated and calcium- plus vitamin D(3)-treated groups (P = 0.10). Pearson coefficients of correlation between the change in PTH and the change in SBP were 0.49 (P < 0.01) for the vitamin D(3) plus calcium group and 0.23 (P < 0.01) for the calcium group. A short-term supplementation with vitamin D(3) and calcium is more effective in reducing SBP than calcium alone. Inadequate vitamin D(3) and calcium intake could play a contributory role in the pathogenesis and progression of hypertension and cardiovascular disease in elderly women.     

Serum parathyroid hormone (PTH) in pregnant women determined by an immunoradiometric assay for intact PTH

Most studies of circulating PTH levels using traditional RIAs have supported the concept of physiological hyperparathyroidism of pregnancy, with pregnant women having serum immunoreactive PTH levels significantly higher than those in nonpregnant subjects. However, such RIAs are insensitive and often detect inactive PTH fragments, so that the correlation between PTH immunoreactivity and bioactivity is poor. Employing a new intact PTH immunoradiometric assay (Allegro-Nichols), we reassessed the effects of pregnancy on parathyroid function. The mean serum PTH level in 81 pregnant women was 14.4 +/- 6.3 (+/- SD) compared to 24.8 +/- 9.0 ng/L in 11 normally cycling nonpregnant women (P less than 0.001). The mean serum total and ionized calcium levels in the 2 groups were similar. In 5 of the pregnant women, serum bioactive PTH, determined by cytochemical bioassay, was slightly lower (7.7 +/- 3.4 ng/L) than in normal individuals (11.1 +/- 1.9 ng/L). Our findings suggest, in contrast with the results of most previous studies, that serum intact PTH may decline during pregnancy.