The relationship between PTH and 25-hydroxy vitamin D early in pregnancy

Objective Measure serum PTH and 25(OH)D in a cross‐sectional sample of pregnant women at 11th through 13th weeks’ gestation to examine vitamin D status and consider implications. Design Observational: we retrieved residual sera stored at ?20 °C after routine first trimester Down’s syndrome screening, distributed over 12 months. Patients 430 African American women and 586 Caucasian women. Measurements PTH and 25‐hydroxy vitamin D [25(OH)D] immunoassays. Results PTH medians were: 1·33 pmol/l (African American women); 1·20 pmol/l (Caucasian women) (t = 0·43, P = 0·7). Concentrations were highest in winter and decreased significantly in spring, fall, and summer. There was a direct PTH/weight relationship in Caucasian (t = 3·12, P < 0·002), but not African American women (t = 1·34, P = 0·18). Median 25(OH)D concentrations were 47·5 nmol/l (African American women) and 65 nmol/l (Caucasian women) (t = 13·7, P < 0·001). Concentrations were lowest in winter and rose significantly in spring, fall, and summer. Reciprocal 25(OH)D/weight relationships existed for both racial groups (t = ?4·31 P < 0·001; t = 4·54, P < 0·001, respectively). Among 68 Caucasian women who smoked, median PTH and 25(OH)D concentrations were somewhat lower (P = ns). In separate regression models with PTH and 25(OH)D [dependent variables] and season, weight and smoking [independent variables], the only qualifying interactive term was in the Caucasian PTH model (season*1/weight). A regression model applied to adjusted scatter plots of PTH vs 25(OH)D indicated a weak relationship. Conclusions The PTH/25(OH)D relationship is weaker during early pregnancy than in non‐pregnant adults, making it unreliable for estimating vitamin D sufficiency. A suitable reference point for sufficiency might be the maternal 25(OH)D level considered sufficient for adequate transfer to neonates.     

Hypovitaminosis D and parathyroid hormone response in the elderly: effects on bone turnover and mortality

Objective To investigate whether absence of secondary hyperparathyroidism in the presence of hypovitaminosis D has altered bone turnover, fracture risk and mortality. Design A prospective cohort study. Patients A total of 1280 older men and women living in residential care facilities. Measurements We measured baseline serum 25‐hydroxyvitamin D (25OHD), serum intact PTH, serum amino‐terminal propeptide of type I collagen (PINP) and serum carboxy‐terminal telopeptide of type I collagen (CTX‐I). Deaths and fractures were recorded prospectively. Results Hypovitaminosis D (25OHD < 39 nmol/l) and absence of secondary hyperparathyroidism (PTH > 7·0 pmol/l) in the presence of hypovitaminosis D were common in this sample with a prevalence of 77·5% and 53·3%, respectively. In the presence of hypovitaminosis D, residents showing a hyperparathyroid response (n = 406) had significantly higher serum bone turnover markers than individuals with serum PTH levels ≤ 7·0 pmol/l (termed ‘low vitamin D, normal PTH’, n = 463). After adjusting for risk factors, mortality was significantly higher in the secondary hyperparathyroidism group than in the ‘low vitamin D, normal PTH’ group [hazard ratio (HR) = 1·35, 95% confidence interval (CI) 1·12–1·64; P = 0·002]. All residents with serum PTH levels ≤ 7·0 pmol/l (n = 603) were similar with regard to both bone turnover and mortality, independent of their actual vitamin D status. Conclusion Absence of secondary hyperparathyroidism in the presence of hypovitaminosis D appears to be common in the frail elderly and is associated with longer survival, similar to that observed in vitamin D‐replete elderly subjects.     

Relationship of vitamin D and parathyroid hormone with obesity and body composition in African Americans

Background Obesity disproportionately affects African Americans (AA) (especially women), and is linked to depressed 25‐hydroxyvitamin D (25‐OH D) and elevated parathyroid hormone (PTH). The relationship of 25‐OH D and PTH with body composition and size in AA is not well known. Objective To determine the relationship of 25‐OH D and PTH levels with body composition and anthropometric measures. Design A cross‐sectional study was conducted in 98 healthy, overweight, adult AA enrolled in an NIH/NIEHS‐sponsored weight loss/salt‐sensitivity trial. Measurements Multivariable linear regression analyses were used to explore the relationship of 25‐OH D and PTH with body composition, determined by dual‐energy X‐ray absorptiometry, and anthropometric measures. Body composition and size were contrasted across vitamin D/PTH groups using general linear models: (i) normal (25‐OH D >50 nmol/l, PTH ≤65 pg/ml), (ii) low 25‐OH D and normal PTH and (iii) low 25‐OH D and high PTH. Results Age, gender and season‐adjusted regression analyses showed that PTH was directly correlated with total (P = 0·02), truncal (P = 0·03) and extremity (P = 0·03) fat mass, while 25‐OH D was inversely related to truncal fat mass (P = 0·02). Total fat mass in groups 1–3, respectively, was 30·0, 34·0 and 37·4 kg (P = 0·008); truncal fat mass was 13·4, 15·9 and 17·6 kg (P = 0·006) and extremity fat mass was 15·8, 16·9 and 19·7 kg (P = 0·02). Lean mass did not differ across the three groups. Conclusions Our findings show that lower 25‐OH D and raised PTH are both correlated, though in opposite directions, with fat mass, fat distribution and anthropometric measures in adult AA.     

Skeletal consequences of familial hypocalciuric hypercalcaemia vs. primary hyperparathyroidism

Objectives Bone metabolism is only superficially described in familiar hypocalciuric hypercalcaemia (FHH). We describe and compare biochemical and osteodensitometric variables in FHH and primary hyperparathyroidism (PHPT) and assess whether they can improve the diagnostic discrimination between the groups. Design Cross‐sectional. Patients Sixty‐six FHH patients with known calcium‐sensing receptor (CASR) gene mutations and 147 PHPT patients. Measurements We determined calcium, creatinine, phosphate, magnesium, parathyroid hormone (PTH), 25OHD, 1,25(OH)₂D and alkaline phosphatase (AP) in plasma, NTx/creatinine ratio in urine and calculated the calcium/creatinine clearance ratio (CCCR). We performed dual energy X‐ray absorptiometry at the lumbar spine, hip, forearm and whole body. Results When compared with normal controls, the FHH patients had increased levels of PTH and AP with normal U‐NTx and regional Z‐scores. Increased phenotypic expression of CASR mutations in terms of hypercalcaemia was associated with higher lumbar spine bone mineral density, but not with bone markers. FHH were younger and leaner than the PHPT patients. They had comparable plasma Ca²⁺ and 25OHD, but lower levels of PTH, 1,25(OH)₂D, AP and U‐NTx. They had higher Z‐scores in the hip and in the forearm. We achieved the best discrimination between groups by multiplying CCCR with AP, 1,25(OH)₂D and PTH, but the difference between the area under the curves by receiver operating characteristic analysis remained insignificant. Conclusion Familiar hypocalciuric hypercalcaemia is associated with increased PTH and AP compared to normal controls, but not with bone loss irrespective of the severity of the CASR mutations. A multiplicative model including CCCR, AP, 1,25(OH)₂D and PTH insignificantly improved the power of the CCCR to differentiate between FHH and PHPT. However, we still recommend CASR gene analysis in patients with a CCCR <0·020.     

Determinants of plasma PTH and their implication for defining a reference interval

Background To improve the diagnostic sensitivity of PTH measurements, more data on the upper limit of the reference interval for PTH levels were requested at a recent international consensus conference. As PTH levels vary inversely with plasma 25‐hydroxyvitamin D (25OHD) levels and as vitamin D insufficiency is widespread, particular attention should be given to the influence of low vitamin D levels on the PTH reference interval. Aim, design and methods In a cross‐sectional design, including 2316 women aged 17–84, we determined 95% reference interval using a nonparametric approach and studied the effects of potential predictors on plasma PTH levels. Results PTH was a positive function of age, body weight and BMI and inversely associated with total daily calcium intake, smoking, plasma calcium levels and 25OHD levels, all of which explained 16% of the variability in plasma PTH levels. The threshold value for 25OHD levels below which PTH levels started to rise was 82 nmol/l. Plasma PTH levels varied inversely with the seasonal variations in 25OHD levels. Mean PTH level was 4·1 pmol/l with a reference interval equal to 2·0–8·6 pmol/l. Restricting the population in whom the reference interval was calculated to only women with 25OHD levels above 30 or 100 nmol/l lowered the upper limit of the reference interval to 8·4 and 7·1 pmol/l, respectively. Similar, stratification according to age, body mass index, smoking and calcium intake had only minor impact on the reference interval. Conclusion Indices with known effects on plasma PTH levels have only a minor impact on the upper levels of the normative reference interval in women with intact renal function.     

Predisposition to vitamin D deficiency osteomalacia and rickets in females is linked to their 25(OH)D and calcium intake rather than vitamin D receptor gene polymorphism

Background Osteomalacia (OSM) and rickets are widely prevalent in developing countries especially in females. The factors associated with such predisposition are not known. Objectives To identify nutritional, endocrine and genetic factors related to calcium and vitamin D metabolism that are associated with OSM/rickets in females. Subjects and methods We studied 98 patients with OSM or rickets and their relatives including male and female sibs and parents (n = 221) for the presence of biochemical OSM {low serum 25‐hydroxyvitamin D [25(OH)D], raised intact PTH (iPTH) and raised alkaline phosphatase} and associated nutritional and genetic factors. Polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) was used for genotyping vitamin D receptor (VDR) (BsmI and FokI) and PTH gene (BstBI and DraII) single nucleotide polymorphisms (SNPs) in 74 families. The differences in the factors associated with calcium and vitamin D among the different groups were analysed by analysis of variance (ANOVA). Logistic regression analysis and the transmission disequilibrium test (TDT) were carried out to assess association between nutritional and genetic factors, and the disease, respectively. Results Most of the patients were female (91·8%). The mean serum 25(OH)D level of the female patients was comparable to that of the female sibs (14·4 ± 5·7 vs. 18·3 ± 9·7 nmol/l). The frequency of biochemical OSM was fivefold higher in female than in male sibs (24·4%vs. 4·9%). Female sibs also had significantly lower 25(OH)D, dietary calcium intake and sunshine exposure than male sibs. The frequency of biochemical OSM was comparable between mothers and fathers. The odds of biochemical OSM in the family members was reduced by 11% per 15‐min daily sunshine exposure [odds ratio (OR) = 0·89, 95% confidence interval (CI) = 0·81–0·98, P = 0·02] and decreased by 20% per 100 mg dietary calcium intake (OR = 0·80, 95% CI = 0·67–0·96, P = 0·02). VDR/PTH gene SNPs showed no association with OSM/rickets on TDT analysis. Conclusion Among the immediate family members of patients with OSM/rickets, female sibs have features of biochemical OSM in up to 24·4%. Female sibs, unlike male sibs, share with patients features of markedly low serum 25(OH)D levels, poor dietary calcium intake and poor exposure to sunshine. Genetic factors such as VDR and PTH gene SNPs were not associated with OSM/rickets.     

Correlation between plasma calcium, parathyroid hormone (PTH) and the metabolic syndrome (MetS) in a community-based cohort of men and women

Context In recent years, an association has been noted between several abnormalities that characterize the metabolic syndrome (MetS) and primary hyperparathyroidism (pHPT). These abnormalities include dyslipidaemia, obesity, insulin resistance and hypertension. The correlations between plasma calcium, parathyroid hormone (PTH) and the variables in the MetS in a normal population are still unclear. Objective To describe correlations between plasma calcium and PTH and the various abnormalities present in the MetS in a healthy population. Design We studied 1016 healthy individuals from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) population of 70 years old, by means of plasma analyses of calcium, PTH, creatinine, lipids, insulin and glucose, as well as by standardized blood pressure measurements. Further, body mass index (BMI) and waist circumference were determined. Results The more National Cholesterol Education Program (NCEP) criteria for the MetS that were met, the higher the s‐PTH and albumin‐corrected s‐calcium. Further, positive correlations between plasma calcium and BMI (P = 0·0003), waist circumference (P = 0·0009) and insulin resistance (P = 0·079) were found. PTH and BMI (P < 0·0001), waist circumference (P < 0·0001), systolic blood pressure (P = 0·0034), diastolic blood pressure (P = 0·0008), serum triglycerides (P = 0·0003) and insulin resistance (P = 0·0003) were positively correlated, whereas serum high density lipoproteins (HDL) (P = 0·036) and PTH were negatively correlated. Conclusions We conclude that PTH correlates with several of the metabolic factors included in the MetS within a normocalcaemic population. In addition, individuals with mild pHPT present significantly more NCEP criteria for MetS. We postulate that increased levels of PTH in pHPT may be associated with the increased cardiovascular morbidity and mortality seen in pHPT.     

A CARBOXY-TERMINAL SPECIFIC ASSAY FOR HUMAN PARATHYROID HORMONE

An homologous carboxy-terminal specific immunoradiometric assay for human parathyroid hormone (PTH) has been developed which uses an antiserum raised in a goat against intact human PTH. This assay has been applied to the measurement of circulating PTH in man; the reference preparation was a 53–84 fragment prepared from native human parathyroid hormone. PTH was detectable in all the normal subjects studied (range 0·1–0·79 ng/ml) and elevated concentrations were found in a group of patients with primary hyperparathyroidism (range 0·82–25·5 ng/ml). Carboxy-terminal hormone concentrations were particularly raised in uraemic subjects (range 1–02–52–5 ng/ml) but some patients with vitamin D deficient osteomalacia had concentrations within the normal range (0·5–2·4 ng/ml). All patients with pseudohypoparathyroidism had elevated concentrations (range 1·0–2·8 ng/ml) and in patients with idiopathic or surgical hypoparathyroidism the concentration ranged from undetectable to 0·4 ng/ml. These results have been compared with those obtained using an amino-terminal specific assay. In normal subjects carboxy-terminal immuno-reactive hormone concentrations were, on average, three times higher than those measured in the amino-terminal assay (C:N ratio 3·28). In patients with secondary hyperparathyroidism this ratio was dependent on renal function and the plasma calcium concentration. The disappearance of endogenous carboxy-and amino-terminal PTH from the circulation of a patient with primary hyperparathyroidism was studied. Amino-terminal reactive PTH disappeared much more rapidly (t½= 1·5 min) than carboxy-terminal hormone (t½= 2·75 h). It is hoped that the carboxy-terminal specific assay described here will be of value in the further study of the secretion and metabolism of PTH.     

Hyperparathyroidism secondary to hypovitaminosis D in hypoalbuminemic is less intense than in normoalbuminemic patients: a prevalence study in medical inpatients in southern Brazil

Hypovitaminosis D has been reported in tropical countries, but this hormone has seldom been studied in Brazil. Our purpose was to study the prevalence of hypovitaminosis D in patients hospitalized in internal medicine wards in Southern Brazil. Possible associated factors were studied. We studied 81 adult patients in early spring. Mean serum 25(OH)D was 12±8.57 ng/mL; hypovitaminosis D was severe (<10 ng/mL) in 27 (33.3%) patients, and moderate (≥10 ng/mL and <20 ng/mL) in 36 (44.5%) patients. Clinical evaluation did not yield any data associated with hypovitaminosis D. Serum 25(OH)D levels of up to 20 ng/mL were associated with decreased mean serum total calcium (p=0.001), ionized calcium (p=0.01), and phosphorus (p=0.044) levels, and increased mean serum PTH level (p=0.001). In a multiple regression model, serum PTH level was independently affected by serum total calcium (p=0.01), phosphorus (p=0.009), and albumin (p=0.009) levels. Hypovitaminosis D patients had lower mean serum albumin levels (p=0.004), and serum 25(OH)D levels were directly correlated to serum albumin levels (p<0.0001). Albumin influenced independently PTH response to hypovitaminosis D; normoalbuminemic hypovitaminosis D patients had higher mean serum PTH than hypoalbuminemic patients. Conclusion: Hypovitaminosis D prevalence was very high in medical inpatients in Southern Brazil, in early spring. Nevertheless, secondary hyperparathyroidism was less intense in hypoalbuminemic hypovitaminosis D patients suggesting that in these patients free serum 25(OH)D was closer to normal.     

Vitamin D deficiency in veterans with chronic spinal cord injury

Chronic spinal cord injury (SCI) is associated with osteopenia, increasing the prevalence of long-bone fractures, Although disuse may be the primary cause of osteopenia, identification of any additional mechanisms of bone loss may lead to potential therapeutic interventions. We investigated the relationships of serum calcium (Ca), phosphorus (PO₄), albumin, alkaline phosphatase (AIk P), and parathyroid hormone (PTH) with serum 25-hydroxyvitamin D [25(OH)D] in 100 subjects with chronic SCI and 50 control, subjects. In a subgroup of 50 subjects with SCI and 50 control subjects, we correlated these parameters with serum 1,25-dihydroxyvitamin D [1,25(OH)₂D]. Mean ages for the group with SCI and the controls were the same. In subjects with SCI, the duration of injury was 20 ± 1 years (mean ± SD). Thirty-two of 100 subjects with SCI, as compared with eight of 50 controls, had serum 25(OH)D levels less than the normal range (χ² = 4.36, P < .05). In subjects with SCI, a negative correlation was demonstrated between serum 25(OH)D and PTH (r = .29, P < .005). Mean serum 1,25(OH)₂D levels were significantly elevated in subjects with SCI as compared with controls (61 ± 21 v 46 -+ 18 pg/mL, P < .0005). Twenty of 50 subjects with SCI had serum 1,25(OH)₂D levels greater than 62 pg/mL, as compared with 10 of 50 controls (χ² = 4.76, P < .05). A positive correlation was found between serum PTH and 1,25(OH)₂D in subjects with SCI and controls (r = .41, P < .005 and r = .30, P < .05, respectively). Twelve subjects with SCI had serum PTH levels greater than the normal range. In this high-serum PTH subgroup, serum 25(OH)D concentration was significantly lower (P < .05) and serum 1,25(OH)₂D and AIk P concentrations were significantly higher (P < .005 and P < .05, respectively) as compared with the subgroup with serum PTH values within the normal range. In subjects with SCI, 17 had a serum Ca concentration less than 8.5 mg/dL. In persons with SCI, depressed levels of serum 25(OH)D, as well as other factors, may result in forces inclined to reduce the serum calcium concentration. A state of mild secondary hyperparathyroidism may result, thus increasing the conversion of serum 25(OH)D to 1,25(OH)₂D. These data suggest that in chronic SCI subjects, as in the general population, secretion of PTH and the increase of circulating 1,25(OH)₂D are subject to control by negative-feedback mechanisms. Higher levels of serum PTH would be expected to accelerate bone resorption of a skeleton already regionally osteoporotic as a consequence of the bone mineral loss due to acute immobilization.     

Discrepant influence of vitamin D status on parathyroid hormone and bone mass after two years of calcium supplementation

Objective To investigate the influence of vitamin D status on parathyroid hormone and bone mass after a 2‐year supplementation of calcium alone. Patients and Methods Randomized, double‐blind, placebo‐controlled clinical trial, in healthy postmenopausal women without osteoporosis: three hundred and thirty‐six subjects aged 60–97 years were studied and randomized to receive elemental calcium 500 mg/day (n = 175) or placebo (n = 161) for 2 years. Measurements Changes in parathyroid hormone (PTH) and bone mineral density (BMD) from baseline and vitamin D status. Values are presented as means ± SD. Results After 2 years, subjects with calcium supplementation had significant decrease in plasma PTH level (4·4 ± 1·7 vs 4·7 ± 1·9 pmol/l, P < 0·01), improved lumbar BMD (1·031 ± 0·12 vs 1·004 ± 0·12 g/cm², P < 0·001) and total hip BMD (0·890 ± 0·10 vs 0·883 ± 0·10 g/cm², P < 0·001) without change in femoral neck BMD. In the placebo group, PTH level significantly increased (4·8 ± 1·6 vs 4·5 ± 1·5 pmol/l, P < 0·001), lumbar BMD slightly increased (1·027 ± 0·14 vs 1·018 ± 0·14 g/cm², P < 0·001), total hip and femoral neck BMD decreased (0·876 ± 0·11 vs 0·887 ± 0·11 g/cm², P < 0·001 and 0·783 ± 0·10 vs 0·798 ± 0·10 g/cm², P < 0·001, respectively). When subjects were classified according to baseline 25‐hydroxyvitamin D [25(OH)D] levels into those with 25(OH)D in the lower tertile (lowVitD) and those in the middle and upper tertiles combined (normVitD). The degree of PTH suppression after calcium supplementation was significantly higher in the normVitD compared to the lowVitD groups (?5·6 ± 26·7%vs 1·3 ± 27·2%, P < 0·05). No effect of vitamin D status on the change in lumbar BMD after calcium supplementation was demonstrated. Despite the higher suppression of PTH, there was a slight decrease in femoral neck BMD after calcium supplementation in the normVitD group while femoral neck BMD was more or less maintained in the lowVitD group (?0·6 ± 3·2%vs 0·5 ± 2·9%, P < 0·05). Conclusion Calcium supplementation appears to affect femoral bone mass less in Thai postmenopausal women with adequate vitamin D status, despite higher suppression of PTH.     

A COMPARISON OF NEPHROGENOUS CYCLIC AMP, TOTAL URINARY CYCLIC AMP AND THE RENAL TUBULAR MAXIMUM REABSORPTIVE CAPACITY FOR PHOSPHATE IN THE DIAGNOSIS OF PRIMARY HYPERPARATHYROIDISM

A determination was made of total urinary adenosine 3′-5′cyclic monophosphate (UcAMP), nephrogenous cyclic AMP (NcAMP) excretion and also of the renal tubular maximum reabsorptive capacity for phosphate T_mPO₄/GFR (all expressed as a function of the glomerular filtrate) in fourteen patients with primary hypercalcaemic hyperparathyroidism and twelve control normal subjects. The hyperparathyroid patients gave a mean excretion of UcAMP (7·0 ± 45·68 nmol/100 ml GF; mean ± SEM), NcAMP (6·19 ± 0·64 nmol/100 ml GF) which were significantly greater (P < 0·001) than those of normal controls, (2′45 ± 0·15nmol/100 ml GF and 1·25 ± 0·12nmol/100 ml GF) respectively. The difference between the patients and controls for the maximum renal tubular reabsorptive capacity for phosphate (T_mPO₄/GFR) (patients 0·55 ± 0·04, controls 1·05 ± 0·05 mmol/l GFR) was also highly significant (P<0·001). Statistical evaluation of the results obtained from the patients with primary hyperparathyroidism revealed that there was a positive correlation between the level of plasma calcium and immunoreactive parathyroid hormone (PTH) (r=+0·46), NcAMP(r=+0·337), UcAMP (r=+0·36), and an inverse correlation with the T_mPO₄/GFR (r=?0·62). There was also a positive correlation between plasma immunoreactive PTH and NcAMP(r=+0·31), and UcAMP(r=+0·35), and an inverse correlation with the T_mPO₄/GFR (r=?0–39). Successful removal of a single parathyroid adenoma in six patients was associated with a highly significant fall in the excretion of UcAMP, NcAMP, and a rise in the T_mPO₄/GFR (P<0·005). The combination of a low T_mPO₄/GFR and a high excretion of UcAMP or NcAMP in the presence of hypercalcaemia is highly suggestive of primary hyperparathyroidism in the absence of clinical evidence of malignant disease.     

ORIGINAL ARTICLE: Association between 25‐hydroxyvitamin D,somatic muscle weakness and falls risk in end‐stage renal failure

Objective Suboptimal levels of 25‐hydroxyvitamin D (25OHD) are common in haemodialysis patients (Chronic Kidney disease‐5D: CKD‐5D) and may be associated with reduced muscle strength and increased falls risk. We tested the hypothesis that 25OHD levels may be independently associated with falls risk in CKD‐5D. Background Supplementation with calcium and cholecalciferol reduces hip and other nonvertebral fractures in elderly individuals, and this effect may in part be attributable to reduction in falls frequency. The relationship between 25OHD and falls risk has not been investigated in CKD‐5D. Design and Patients This is a cross‐sectional study of 25 CKD‐5D patients with predialysis 25OHD, 1,25‐dihydroxyvitamin D (1,25(OH)₂D) and intact parathyroid hormone (iPTH) measurement. Falls risk was assessed by quadriceps muscle strength, FallsScreen^© test (FST), Berg Balance Scale (BBS), timed ‘up and go’ (TUG) test, Modified Barthel Index (MBI) and Falls Efficacy Scale (FES). Results Mean age was 69·8 ± 12·1 years, and median time on dialysis was 3·1 years. Median 25OHD level was 55·3 nmol/l (range 20·8–125·8 nmol/l). Muscle strength was significantly positively correlated with 25OHD (P = 0·024) but not with 1,25(OH)₂D (P = 0·477) or PTH (P = 0·461). Statistically significant correlation between 25OHD levels and FST (P = 0·028) plus MBI (P = 0·0046) was noted. No significant correlation was detected between falls risk and 1,25(OH)₂D or PTH. Conclusions Suboptimal levels of 25OHD in CKD‐5D are associated with reduced quadriceps muscle strength and increased falls risk. 25OHD may be more important than the active renal metabolite 1,25(OH)₂D for muscle strength with implications for vitamin D choice and goals of supplementation. Further investigation is required to examine effectiveness of calciferol supplementation on the incidence of falls in CKD‐5D.     

ORIGINAL ARTICLE: The association of serum vitamin D level with presence of metabolic syndrome and hypertension in middle‐aged Korean subjects

Objective: To examine the association of serum vitamin D level with metabolic syndrome (MetS) and hypertension (HTN) in middle‐aged Korean subjects. Design and subjects: We conducted a population‐based, cross‐sectional survey of 1330 participants aged over 40 years (median age 65·8 years) in Chungju, Korea, in 2007. The 324 subjects, who were normotensive in 2003 and who attended a follow‐up visit 4 years later, were included in an analysis of the association of serum vitamin D level with the risk of HTN. Measurements: Serum 25‐hydroxy‐vitamin D [25(OH)D] and PTH were measured in a central laboratory, using chemiluminescence assays. Results: The overall prevalence of the MetS in participants of this study was 45·3%. After adjusting for various covariates, subjects in the highest quintile group (61·4–116·8 nmol/l) compared with the lowest quintile group (10·0–29·7 nmol/l) of 25(OH)D had an odds ratio (OR) for having MetS of 0·35 (95% confidence intervals, CI, 0·22–0·56; P for trend <0·001). The median level of 25(OH)D was 46·8 nmol/l among 324 subjects who were normotensive in 2003. After multiple adjustment, the OR was substantially higher for new HTN (OR 2·74; 95% CI 1·40–5·34) in subjects with serum 25(OH)D levels below the median value compared with those above median. The inverse associations of vitamin D and MetS/HTN were unchanged after adjustment for PTH and serum calcium levels. There was no association between PTH and MetS. Conclusions: We found a strong inverse association of 25(OH)D levels with MetS and HTN in this middle‐aged Korean population. Having vitamin D deficiency was associated with an increased risk of having MetS and HTN in this demographic group.     

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.     

Vitamin D status, physical performance and body mass in patients surgically cured for primary hyperparathyroidism compared with healthy controls - a cross-sectional study

Objective Low plasma 25‐hydroxyvitaminD (25OHD) levels, reduced muscle strength and increased body mass index (BMI) are well‐known characteristics of primary hyperparathyroidism (PHPT). Mechanisms for low 25OHD levels, increased BMI and potential changes after parathyroidectomy are unknown. Muscle strength is reported to increase following surgical cure, but whether the improvement corresponds to healthy controls’ performances remains largely unknown. Patients We studied 51 patients with former PHPT [mean age 61(36–77) years] successfully treated by surgery [mean time since operation 7·4(5–15) years] and 51 sex‐ and age‐matched controls. Measurements Physical performance include “repeated chair stand” (RCS), “timed up and go” (TUG), muscle strength [hand grip, elbow flexion/extension and knee flexion/extension (60°/90°)], postural stability, biochemistry and anthropometric indices. Results Forty‐one cases had pathologically verified adenoma, three had hyperplasia and three had uncertain diagnosis whereas four had missing data. Dietary calcium intake, vitamin D supplementation and biochemistry including PTH and 25OHD levels did not differ between groups. Former patients had significantly higher BMI (28·8 ± 6·0 kg/m²) than controls (26·0 ± 4·7kg/m²). Muscle pain was more frequently reported by cases than controls, and cases performed RCS slower than controls (P = 0·02). Furthermore, female cases had lower muscle strength in knee flexion 60° (P = 0·02) and 90° (P = 0·05). Former patients no longer differed from controls after adjustment for BMI. Conclusion Following cure, 25OHD levels are normalized suggesting 25OHD insufficiency is not a constitutional characteristics in patients with PHPT. Increased BMI seems to be sustained. Whether this is caused by decreased muscle strength or reduced muscular performance causes adiposity needs further investigations.     

Very low or undetectable intact parathyroid hormone levels in patients with surgically verified parathyroid adenomas

Objectives To report and explore potential reasons for undetectable or low‐normal serum intact PTH levels in patients with surgically verified primary hyperparathyroidism with parathyroid adenomas, review the relevant literature, and offer suggestions for management of such patients occasionally encountered in clinical practice. For future research, to help understand mechanisms underlying ‘undetectable’ or inappropriately low serum intact PTH levels. Methods Serum intact PTH levels were measured pre‐ and postoperatively by immunochemiluminescent assay (ICMA) and the results were confirmed by at least two repeated measurements on different occasions in each patient. Patients We encountered two unusual patients with primary hyperparathyroidism who had suggestive biochemical and/or clinical features of primary hyperparathyroidism. However, serum intact PTH levels were either very low or undetectable in the context of hypercalcaemia, with no other obvious cause. A ^99mTc sestamibi scan showed increased uptake in one of the parathyroid glands, suggesting a single adenoma in each case that was confirmed at surgery. Results In the first patient, from India, mean ± SD serum calcium was 2·6 ± 0·32 mmol/l (reference range 2·12–2·74 mmol/l) with intact PTH of 0·11 pmol/l (reference range 1·1–7·59 pmol/l). In the second patient, from the USA, mean ± SD serum calcium and intact PTH were 2·9 ± 0·07 mmol/l (reference range 2·17–2·51 mmol/l) and 1·35 pmol/l (reference range 1·1–7·59 pmol/l), respectively. Following curative parathyroidectomy, serum calcium levels normalized in both patients. By contrast, serum intact PTH levels, which were either suppressed or very low before surgery, rose into the low‐normal reference range in all patients. Conclusions When the clinical suspicion is high, the diagnosis of primary hyperparathyroidism should be pursued despite suppressed or low‐normal serum intact PTH levels after carefully excluding other causes of hypercalcaemia. Further research on various intact PTH molecular species secreted by parathyroid adenomas or post‐translational changes in the intact PTH molecule that might interfere with in vitro measurements should be undertaken to understand the precise reason(s) for such anomalous findings.     

Increased prevalence of primary hyperparathyroidism in treated breast cancer.

Hypercalcemia occurring in patients with advanced breast cancer (BC) is generally due to osteolytic metastases or to the activity of circulating tumor-derived products. In these conditions, the production of endogenous PTH is reduced. The frequency of hypercalcemia due to primary hyperparathyroidism in breast cancer is unknown. We examined the occurrence of primary hyperparathyroidism in a large group of women with treated BC. A total of 100 consecutive women aged 28-80 years with treated breast cancer were enrolled. One hundred and two healthy age-matched women and 60 age-matched female patients with differentiated thyroid carcinoma examined before thyroidectomy were used as controls. Intact serum PTH and serum calcium were measured in all patients and controls. Hypercalcemia associated with elevated serum PTH concentration indicating primary hyperparathyroidism was found in 7 BC patients (7%) and in none of healthy women or patients with thyroid cancer. The pre-operative staging of BC patients with primary hyperparathyroidism was I in six and II in one of them, and no patient had evidence of distant metastases. A parathyroid adenoma was found in all 6 BC patients submitted to neck exploration, one patient refused surgery. Serum calcium and PTH concentrations returned to normal levels after surgery. Two BC patients had increased serum PTH and normal calcium concentrations. One of them had low serum 25-hydroxyvitamin D [25(OH)D]. One patient with spread bone metastases had neoplastic hypercalcemia with undetectable serum PTH concentration. All remaining 90 BC patients had serum calcium and PTH concentrations within normal limits, but their mean (+/-SD) values (9.6+/-0.5 mg/dl for serum calcium, 38.0+/-16.4 mg/dl for serum PTH ) were slightly but significantly greater than in normal controls (9.3+/-0.5 mg/dl, p=0.003 and 27.9+/-10.6 pg/ml, p=0.0001, respectively) and in patients with thyroid cancer (9.2+/-0.6 mg/dl, p=0.001 and 26.2+/-11.0 pg/ml, p=0.001), with no relationship with clinical staging or anti-tumor therapy. In conclusion: 1) an increased frequency of parathyroid adenoma was found in BC patients with mildly aggressive neoplastic disease; 2) in BC patients with no evidence of primary hyperparathyroidism mean serum PTH and calcium concentrations were significantly greater than in healthy controls and in patients with thyroid carcinoma; and 3) this finding was unrelated to clinical staging or anti-tumor therapy. Thus, primary hyperparathyroidism should be considered as a possible cause of hypercalcemia in patients with non-aggressive breast cancer. We suggest that serum PTH should be determined in all BC patients with increased serum calcium concentration, especially in those with no evidence of metastatic disease.     

Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D

Vitamin D requirements are thought to vary with age, but there is little comparative evidence for this. One goal in establishing a vitamin D requirement is to avoid secondary hyperparathyroidism. We studied 1741 euthyroid, thyroid clinic outpatients without evidence of calcium abnormalities, ranging in age from 19 to 97 yr, whose serum and urine had been analyzed for calcium, vitamin D, and parathyroid status. We found no effect of age on the 25-hydroxyvitamin D [25(OH)D] concentration associated with specific vitamin D intakes, and there was no relationship between 25(OH)D and 1,25hydroxyvitamin D [1,25(OH)2D]. In every age group, serum 1,25(OH)2D declined with increasing creatinine (P < 0.001). What changed with age included creatinine, which correlated with 25(OH)D (r = 0.146, P < 0.001) only in the youngest age group (19-50 yr) but not in the older age groups (P > 0.1). Creatinine did not correlate with PTH in the youngest age group, but the relationship became significant as age increased (e.g. for the elderly, r = 0.365, P < 0.001). Linear regression of log PTH vs. log 25(OH)D agreed with the natural shape of the relationship observed with scatterplot smoothing, and this showed no plateau in PTH as 25(OH)D increased. We compared PTH concentrations among age groups, based on 20 nmol/liter increments in 25(OH)D. Mean PTH in adults older than 70 yr was consistently higher than in adults younger than 50 yr (P < 0.05 by ANOVA and Dunnett's t test). PTH levels of the elderly who had 25(OH)D concentrations greater than 100 nmol/liter matched PTH of younger adults having 25(OH)D concentrations near 70 nmol/liter. This study shows that all age groups exhibit a high prevalence of 25(OH)D insufficiency and secondary hyperparathyroidism. Older adults are just as efficient in maintaining 25(OH)D, but they need more vitamin D to produce the higher 25(OH)D concentrations required to overcome the hyperparathyroidism associated with their diminishing renal function.