Serum 25-Hydroxyvitamin D Deficiency; A Risk Factor for Chronic Kidney Disease in Ambulatory Indigent Patients

ObjectiveTo assess whether 25-hydroxyvitamin D (25[OH]D) deficiency is a risk factor for chronic kidney disease (CKD) in ambulatory indigent patients.MethodsData for all serum 25(OH)D concentrations measured during 2010 in our ambulatory nondialysis-dependent patients were analyzed along with CKD-related parameters. Patients were stratified into groups based on 25(OH)D levels of < 10, 10 to 19, 20 to 29, and ≥ 30 ng/mL. CKD was defined by estimated glomerular filtration rate (eGFR; Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI] equation) and abnormal urine protein to creatinine ratios. CKD-associated parameters included serum parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25[OH]₂D), alkaline phosphatase, albumin, corrected calcium, and total CO₂ levels.ResultsA total of 2,811 patients had 25(OH)D levels measured. Patients with 25(OH)D levels < 10 ng/mL had significantly increased relative risk (RR) of an eGFR < 15 mL/min/1.73 m² (RR, 4.0), an eGFR of 15 to 29 mL/min/1.73 m² (RR, 2.6), urine protein to creatinine ratio > 3.5 g/g (RR, 5.6), and serum PTH > 100 pg/mL (RR, 2.8) compared to patients with a 25(OH)D level ≥ 30 ng/mL. Patients with 25(OH)D levels of 10 to19 ng/mL had significantly increased RR of a urine protein to creatinine ratio > 3.5 g/g (RR,4.8) and serum PTH > 100 pg/mL (RR, 1.5) compared to patients with 25(OH)D levels ≥ 30 ng/mL.Conclusion25(OH)D deficiency (< 10 ng/mL) was associated with reduced eGFR, nephrotic-range proteinuria, and increased PTH levels in our population of ambulatory urban indigent patients. (Endocr Pract. 2014;20:236-243)     

Vitamin D,Parathyroid Hormone,and Serum Lipid Profiles in a Middle-Aged and Elderly Chinese Population

ObjectivesTo explore the associations of serum vitamin D and parathyroid hormone (PTH) levels with serum lipid profiles and the risk of hyperlipidemia in a middle-aged and elderly population.MethodsA population-based cross-sectional study was conducted in the spring of 2012 among 1,203 Chinese participants, aged 52 to 101 years. 25-Hydroxyvitamin D [25(OH)D] was measured by chemiluminescence assay. (PTH) levels were measured with an electrochemilumines-cence immunoassay (ECLIA) method.ResultsA total of 1,203 participants, including 526 women (43.7%), were evaluated in 2012. The median concentrations of serum 25(OH)D and PTH for the entire group were 17.3 ng/mL and 38.3 pg/mL, respectively. Serum 25(OH)D and PTH levels were not independently associated with serum total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels in a multivariate adjusted linear regression analysis of 1,027 participants not receiving antihyperlipidemic treatment (P > .05). In logistic regression analyses, serum 25(OH)D and PTH lev-els were not associated with a risk of hyperlipidemia after adjustment for age, sex, heavy drinking, smoking, diabetes, obesity, family history of hyperlipidemia, body mass index (BMI), physical activity, glomerular filtration rate (GFR), fasting glucose, high-sensitivity Creactive protein (hsCRP), calcium, and hemoglobin.ConclusionsSerum 25(OH)D and PTH levels are not independently associated with serum lipid levels or an increased risk of hyperlipidemia in a middle-aged and elderly Chinese population. (Endocr Pract. 2014;20: 556-565)     

Prevalence and Predictors Ofvitamin D Deficiency in Healthy Adults

ObjectiveVitamin D deficiency is highly prevalent in high-risk patient populations, but the prevalence among otherwise healthy adults is less well-defined. The goal of this study was to determine the prevalence and predictors of low 25-hydroxyvitamin D [25(OH)D] levels in healthy younger adults.MethodsThis was a cross-sectional study of 634 healthy volunteers aged 18-50 years performed between January, 2006 and May, 2008. We measured serum 25(OH) D and parathyroid hormone and recorded demographic variables including age, sex, race, and use of multivitamin supplements.ResultsThirty-nine percent of subjects had 25(OH)D ≤ 20 ng/mL and 64% had 25(OH)D ≤ 30 ng/mL. Predictors of lower 25(OH)D levels included male sex, black or Asian race, and lack of multivitamin use (P < 0.001 for each pre dictor). Seasonal variation in 25(OH)D levels was present in the overall cohort but was not observed in multivita min users. Lower 25(OH)D levels were associated with increased risk of elevated parathyroid hormone. Regression models predicted 25(OH)D levels ≤ 20 or ≤ 30 ng/mL with areas under the receiver operating characteristic curves of 0.76 and 0.80, respectively.ConclusionLow 25(OH)D levels are prevalent in healthy adults and may confer risk of skeletal disease. Black and Asian adults are at increased risk of deficiency and multivitamin use appears partially protective. Our models predicting low 25(OH)D levels may guide decision-making regarding whom to screen for vitamin D defi ciency. (Endocr Pract. 2012;18:914-923)     

Low Free (But Not Total) 25-Hydroxyvitamin D Levels in Subjects with Normocalcemic Hyperparathyroidism

Objective: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevated parathyroid hormone (PTH) levels with persistently normal calcium levels. The diagnosis of NPHPT assumes the absence of secondary causes of elevated PTH levels. The objective of the current study was to examine levels of free 25-hydroxyvitamin D (25&lsqb;OH]D) in NPHPT subjects and healthy controls.Methods: Ten NPHPT subjects and 20 controls who were age, sex, race, and body mass index (BMI) matched were examined. The diagnosis of NPHPT was made if subjects had (1) a serum calcium level of 8.6 to 10.4 mg/dL, total 25(OH)D 30 to 40 ng/mL, and intact PTH (iPTH) ≥66 pg/mL; and (2) normal renal and liver function. Serum total 25(OH)D levels were measured by radioimmunoassay, and free 25(OH)D levels were determined using an enzyme-linked immunoassay.Results: Mean age of NPHPT subjects was 59.9 ± 5.4 years, and mean BMI was 28.4 ± 2.3 kg/m², which was not significantly different from the mean age and BMI of the control subjects. Mean total 25(OH)D level was 31.9 ± 1.7 ng/mL in NPHPT subjects and did not differ from that of the controls (32.7 ± 3.3 ng/mL; P = .52). However, mean free 25(OH)D was 5.0 ± 0.9 pg/mL in NPHPT subjects, which was 20% lower compared to the mean of the controls (6.2 ± 1.3 pg/mL; P = .013). Serum iPTH levels were inversely correlated with levels of measured free 25(OH)D (r = -0.42; P<.05) but did not correlate with levels of total 25(OH)D (r = -0.14; P>.10).Conclusion: Measured free 25(OH)D levels are lower in NPHPT subjects than in healthy control subjects. We suggest that some NPHPT subjects may actually have secondary hyperparathyroidism based on their free 25(OH) D levels.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; CV = coefficient of variation; DBP = vitamin D–binding protein; iPTH = intact parathyroid hormone; NPHPT = normocalcemic primary hyperparathyroidism     

Hiperparatiroidismo secundario en el cáncer de próstata avanzado

Background and ObjectiveHigh parathyroid hormone (PTH) concentrations are associated with increased bone resorption and bone matrix degradation. Some studies show elevated PTH concentrations and hypocalcemia in patients with advanced prostate carcinoma, although the pathophysiological significance of these findings is not well defined.Materials and methodsWe performed a retrospective study of 60 patients diagnosed with advanced prostate cancer (44 nonmetastatic and 16 metastatic) treated with androgen deprivation. In all patients, PTH, calcium, phosphorus, 25 (OH) vitamin D and prostate-specific antigen (PSA) were determined. Bone scintigraphy had previously been performed.ResultsIn patients with bone metastases, mean concentrations were as follows: calcium 9.19 mg/dl, phosphorus 3.47 mg/dl, 25 (OH) vitamin D 13.85 ng/ml, PTH 66.8 pg/ml and total PSA 101.27 ng/ml. For those without bone metastases, the results were calcium 9.39 mg/dl, phosphorus 3.38 mg/dl, 25 (OH) vitamin D 20.50 ng/ml, PTH 52.23 pg/ml and total PSA 2.52 ng/ml. PTH levels were significantly higher in patients with prostate cancer and bone metastases than in those without metastases (p=0.03). Vitamin D levels were also significantly lower in this group (p=0.03). There were no differences in other values.ConclusionsThe present study found increased PTH concentrations in patients with advanced prostate cancer. This finding could be useful to predict disease progression.     

Influencia del inmunoensayo empleado en la determinación de vitamina D sérica

IntroductionSerum 25-hydroxyvitamin D [25(OH)D] levels are the best indicator of vitamin D levels in the body. Precision, reproducibility, and lack of standardization are the main problems in such measurements. The aim of this study was to compare the 25(OH)D levels measured using Elecsys Vitamin D Total (Roche) and ADVIA Centaur Vitamin D Total (Siemens).Material and methods25(OH)D levels were tested in 166 patients using both methods. Patients were subsequently divided into two groups: a «supplemented group» consisting of patients receiving vitamin D supplements, and an «untreated group» consisting of the rest of patients.Results25(OH)D mean levels measured by the Roche and Siemens methods in the overall group were 33.6 ± 16.0 and 19.8 ± 12.4 ng/mL respectively. 54.2% of patients were receiving vitamin D supplements. In this group, mean 25(OH)D levels measured by the Roche and Siemens methods were 40.6 ± 14.5 and 25.4 ± 13.1 ng/mL respectively. In the untreated group, the respective values were 24.9 ± 13.2 and 12.8 ± 6.6 ng/mL. Prevalence of vitamin D deficiency (serum 25(OH)D levels less than 20 ng/mL) was higher in samples analyzed using the Siemens method (60.2%) as compared to those tested using the Roche method (23.5%).ConclusionThe assays evaluated are not comparable to each other. Laboratory specialists should inform clinicians of the features of the method used for measuring 25(OH)D because this will have a direct impact on interpretation of the results and medical decisions.     

Determinants of Circulating 25-Hydroxyvitamin D and bone Mineral Density in Young Physicians

ObjectiveTo examine determinants of serum 25-hydroxyvitamin D [25(OH)D] and bone mineral density (BMD) in young physicians, a group not well studied previously.MethodsWe analyzed data from a questionnaire completed by young physicians as well as results of serum 25(OH)D, serum parathyroid hormone, and BMD measurements.ResultsAmong 104 study subjects, 42% were white, 46% were Asian, 12% were “other” (10 Hispanic and 2 African American subjects), and 75% were women. The mean age and body mass index (BMI) were 28.1 years and 23.0 kg/m², respectively. White subjects had a higher mean serum 25(OH)D level (27.3 ng/mL) than did Asian subjects (15.9 ng/mL) and other subjects (22.3 ng/mL) (P < .0001). White subjects tended to have higher Z-scores than Asian subjects and other subjects for the hip (P = .06), trochanter (P = .08), and lumbar spine (P = .08). The serum 25(OH)D level was negatively associated with serum parathyroid hormone (r = -0.44; P < .01) but not with BMD. The prevalence of vitamin D insufficiency [serum 25(OH)D < 30 ng/mL, 77% for the entire group] was higher (P < .01) in Asian subjects (93%) than in white subjects (61%) and other subjects (73%). Significant determinants of serum 25(OH)D included age, ethnicity, exposure to sunlight, use of vitamin D supplements, and family history of osteoporosis (P < .05 for all), and together with sex, calcium supplements, exercise, and BMI, these factors explained 49% of serum 25(OH)D level variability. Significant determinants of low BMD (osteopenia plus osteoporosis, prevalence 37.5%) included sex (P = .002) and BMI (P < .0001) but not serum 25(OH)D; Asian ethnicity reached borderline significance (P = .088). Age, sex, ethnicity, smoking, and BMI explained 20% to 30% of the Z-score variations.ConclusionIn young physicians with a healthful lifestyle, determinants of low serum 25(OH)D and BMD included modifiable risk factors. Vitamin D insufficiency and low BMD could be important contributors to future osteoporotic fractures in this population. (Endocr Pract. 2012;18:219-226)     

Differencesin-Vitamin-D3-Dosing-Regimens in a Geriatric Community-Dwelling Population

ObjectiveThe adequate dose of vitamin D supple mentation for community-dwelling elderly people has not been thoroughly investigated. This study aims to determine the efficacy of a low-dose and a higher dose of vitamin D₃ in maintaining 25-hydroxyvitamin D [25(OH)D] levels at or above 30 ng/mL.MethodsThis was a single site, double-blind, ran domized exploratory clinical trial that enrolled adults 65 years of age and older. Within strata of baseline 25(OH) D levels (< 30 versus ≥ 30 ng/mL) subjects were random ized in a 1:2 ratio to receive either 400 or 2,000 IU vitamin D₃ daily for 6 months. The main outcome measures were changes in serum 25(OH)D levels according to baseline 25(OH)D levels and dose of vitamin D3.ResultsAt baseline, 41 of 105 participants (39%) had low 25(OH)D levels (< 30 ng/mL). After 6 months of vitamin D₃ supplementation, 21 of 32 participants (66%) receiving 400 IU and 14 of 59 participants (24%) receiving 2,000 IU of vitamin D₃ still had low 25(OH)D levels. Thelargest increases in serum 25(OH)D levels were observed in subjects with baseline levels < 30 ng/mL who received 2,000 IU of vitamin D daily.ConclusionRegardless of baseline 25(OH)D level, in persons 65 years of age and older, 6-month vitamin D₃ supplementation with 400 IU daily resulted in low 25(OH) D in most individuals, while 2,000 IU daily maintained 25(OH)D levels within an acceptable range in most people on this regimen. (Endocr Pract. 2012;18:847-854)     

Supplemental vitamin D increases serum cytokines in those with initially low 25-hydroxyvitamin D: A randomized,double blind,placebo-controlled study

The purpose of this study was to determine if vitamin D status before supplementation influences the cytokine response after supplemental vitamin D. Forty-six reportedly healthy adults (mean(SD); age, 32(7) y; body mass index (BMI), 25.3(4.5) kg/m²; serum 25-hydroxyvitamin D (25(OH)D), 34.8(12.2) ng/mL) were randomly assigned (double blind) to one of three groups: (1) placebo (n = 15), or supplemental vitamin D (cholecalciferol) at (2) 4000 (n = 14) or (3) 8000 IU (n = 17). Supplements were taken daily for 35 days. Fasting blood samples were obtained before (Baseline, Bsl) and 35-days after (35-d) supplementation. Serum 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), cytokines, and intact parathyroid hormone with calcium were measured in each blood sample. Supplemental vitamin D increased serum 25(OH)D (4000 IU, ≈29%; 8000 IU, ≈57%) and 1,25(OH)D (4000 IU, ≈12%; 8000 IU, ≈38%) without altering intact parathyroid hormone or calcium. The vitamin D metabolite increases in the supplemental vitamin D groups (n = 31) were dependent on initial levels as serum 25(OH)D (r = −0.63, p < 0.05) and 1,25(OH)D (r = −0.45, p < 0.05) at Bsl correlated with their increases after supplementation. Supplemental vitamin D increased interferon (IFN)-γ and interleukin (IL)-10 in subjects that were vitamin D insufficient (serum 25(OH)D < 29 ng/mL) compared to sufficient (serum 25(OH)D ⩾ 30 ng/mL) at Bsl. We conclude that supplemental vitamin D increase a pro- and anti-inflammatory cytokine in those with initially low serum 25(OH)D.     

Vitamin d status and its relationship with bone mineral density and parathyroid hormone in southeast asian adults with low bone density

ObjectiveTo investigate the vitamin D sufficiency status and the relationships among serum 25-hydroxyvitamin D [25(OH)D] levels, intact parathyroid hormone (iPTH) levels, and bone mineral density (BMD) in patients attending an osteoporosis clinic in Singapore.MethodsIn total, 193 adults with or without prevalent fragility fractures and with low BMD at the femoral neck, total hip, or lumbar spine underwent assessment. Multivariate regression models were used to investigate the relationships among serum 25(OH)D, iPTH, and BMD.ResultsThe mean values (standard deviation) for age of the patients and serum 25(OH)D level were 61 (14) years and 26.05 (7.97) ng/mL, respectively. In 72% of patients, serum 25(OH)D levels were below 30 ng/mL. There was no association between 25(OH)D levels and BMD at the femoral neck, total hip, or lumbar spine(P = .568, .461, and .312, respectively). Serum iPTH levels were negatively associated with BMD at the total hip(P = .035) and the lumbar spine (P = .019). At levels < 30 ng/mL, 25(OH)D was negatively associated with iPTH (P = .036).ConclusionAmong this Southeast Asian population of patients with low BMD, no direct relationship between serum 25(OH)D levels and BMD was observed. A negative correlation existed, however, between iPTH and 25(OH)D at serum 25(OH)D concentrations < 30 ng/mL, and serum iPTH levels showed a significant negative association with BMD at the total hip and lumbar spine. These significant negative associations between iPTH levels and BMD at the total hip and lumbar spine underscore the critical role of this hormone in bone metabolism and health. (Endocr Pract. 2011;17:226-234)     

Association of Low Serum 25-Hydroxyvitamin D Levels in Pregnancy with Glucosehomeostasis and Obstetric And Newborn Outcomes

ObjectiveTo evaluate the association of maternal serum 25-hydroxyvitamin D (25[OH]D) status with glucose homeostasis and obstetric and newborn outcomes in women screened for gestational diabetes mellitus (GDM).MethodsConsecutive women were screened for GDM at 24 to 28 weeks’ gestation during the months of maximal sunlight exposure in Spain (June through September). Serum 25(OH)D levels and parameters of glucose homeostasis were measured. Outcomes of the delivery and newborn were collected.ResultsTwo hundred sixty-six women were screened. Vitamin D deficiency (25[OH]D < 20 ng/mL) was observed in 157 women (59%). We observed an inverse correlation between 25(OH)D levels and hemoglobin A_1c, homeostasis model assessment of insulin resistance, serum insulin, and fasting and 1-hour oral glucose tolerance test glucose levels (P <.001). With a 25(OH)D concentration less than 20 ng/mL, the odds ratios were 3.31 for premature birth (95% confidence interval, 1.52-7.19; P <.002) and 3.93 for cesarean delivery (95% confidence interval, 2.00-7.73; P <.001). A 25(OH)D concentration of 20 ng/mL had 79% sensitivity and 51% specificity for cesarean delivery and 80% sensitivity and 45% specificity for premature birth. The cutoffs with the best combination of sensitivity and specificity were 16 ng/mL for cesarean delivery (62.9% sensitivity and 61.2% specificity) and 14 ng/mL for premature birth (66.7% sensitivity and 71.0% specificity).ConclusionsIn the population we sampled, vitamin D deficiency is very common during pregnancy. Lower 25(OH)D levels are associated with disorders of glucose homeostasis and adverse obstetric and newborn outcomes.(Endocr Pract. 2012;18:676-684)     

Vitamin D Status and Its Seasonal Variability in Healthy Young Adults in an Asian Indian Urban Population

ObjectiveTo assess the vitamin D status and its seasonal variability in healthy young adults in Chandigarh, a city in northern India.MethodsThe history was elicited and examination was performed pertaining to metabolic bone disease in 329 young adults (18 to 25 years of age) at the end of summer and 237 subjects from the same cohort at the end of winter. The calcium profile, 25-hydroxyvitamin D [25(OH)D], and intact parathyroid hormone were measured during both the seasons.ResultsAmong the young adults in this study cohort, 25(OH)D sufficiency (≥ 30 ng/mL) was found in 72.5% in summer and in 50.7% in winter. A significantly higher number of men were 25(OH)D sufficient in comparison with women in summer (P = .001). The mean (standard deviation) serum 25(OH)D levels were significantly higher at the end of summer—52.9 (33.7) ng/mL—in comparison with that at the end of winter—31.8 (21.1) ng/mL; P < .001. The intact parathyroid hormone levels were significantly lower in the 25(OH)D-sufficient group (P = .001) and began to increase at 25(OH)D levels below 25 ng/mL. The serum 25(OH)D levels correlated positively with the duration of exposure to sunlight during summer (r = 0.111; P = .05) and also the calcium intake during summer (r = 0.129; P = .03).ConclusionVitamin D sufficiency may be a reality with a combination of young skin, optimal and effective exposure to sunlight, and adequate calcium intake. (Endocr Pract. 2011;17:185-191)     

Improvement in Pancreatic β-Cell Function with Vitamin D and Calcium Supplementation in Vitamin D-Deficient Nondiabetic Subjects

ObjectiveThere are varied reports on the effect of vitamin D supplementation on β-cell function and plasma glucose levels. The objective of this study was to examine the effect of vitamin D and calcium supplementation on β-cell function and plasma glucose levels in subjects with vitamin D deficiency.MethodsNondiabetic subjects (N = 48) were screened for their serum 25-hydroxyvitamin D (25-OHD), albumin, creatinine, calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone (PTH) status. Subjects with 25-OHD deficiency underwent a 2-hour oral glucose tolerance test. Cholecalciferol (9,570 international units [IU]/day; tolerable upper intake level, 10,000 IU/day; according to the Endocrine Society guidelines for vitamin D supplementation) and calcium (1 g/day) were supplemented.ResultsThirty-seven patients with 25-OHD deficiency participated in the study. The baseline and postvitamin D/calcium supplementation and the difference (corrected) were: serum calcium, 9 ± 0.33 and 8.33 ± 1.09 mg/dL (− 0.66 ± 1.11 mg/dL); 25-OHD, 8.75 ± 4.75 and 36.83 ± 18.68 ng/mL (28.00 ± 18.33 ng/mL); PTH, 57.9 ± 29.3 and 36.33 ± 22.48 pg/mL (− 20.25 ± 22.45 pg/mL); fasting plasma glucose, 78.23 ± 7.60 and 73.47 ± 9.82 mg/dL (− 4.88 ± 10.65 mg/dL); and homeostasis model assessment-2–percent β-cell function C-peptide secretion (HOMA-2–%B C-PEP), 183.17 ± 88.74 and 194.67 ± 54.71 (11.38 ± 94.27). Significant differences were observed between baseline and post-vitamin D/calcium supplementation serum levels of corrected calcium (Z, − 3.751; P < .0001), 25-OHD (Z, − 4.9; P < .0001), intact PTH (Z, − 4.04; P < .0001), fasting plasma glucose (Z, − 2.7; P < .007), and HOMA-2–%B C-PEP (Z, − 1.923; P < .05) as determined by Wilcoxon signed rank test. Insulin resistance as measured by HOMA was unchanged.ConclusionOptimizing serum 25-OHD concentrations and supplementation with calcium improves fasting plasma glucose levels and β-cell secretory reserve. Larger randomized control studies are needed to determine if correction of 25-OHD deficiency will improve insulin secretion and prevent abnormalities of glucose homeostasis. (Endocr Pract. 2014;20:129-138)     

Vitamin D Insufficiency is Associated With Reduced Parasympathetic Nerve Fiber Function in Type 2 Diabetes

ObjectiveVitamin D insufficiency is prevalent in subjects with type 2 diabetes mellitus (T2DM) and is associated with peripheral neuropathy. However, there are little data regarding vitamin D status in patients with cardiovascular autonomic neuropathy. Our objective was to evaluate the association of cardiovascular autonomic function, 25-hydroxyvitamin D (25[OH]D) insufficiency (i.e., levels < 30 ng/mL), and multiple metabolic parameters in subjects with T2DM.MethodsWe examined 50 individuals with T2DM. Cardiovascular autonomic function (i.e., parasympathetic function) was assessed by RR-variation during deep breathing (i.e., mean circular resultant [MCR] and expiration/inspiration [E/I] ratio). Metabolic parameters included measures of adiposity, glycemic control, insulin resistance, calcium metabolism, and 25(OH)D.ResultsParticipants with 25(OH)D insufficiency (n = 26) were younger (66 ± 9 vs. 60 ± 10 years, P < .05), more insulin resistant, had a higher body mass index (BMI) and lower adiponectin levels. The MCR (39.5 ± 26.3 vs. 27.6 ± 17.2, P < .01) and E/I ratio (1.21 ± 0.17 vs. 1.15 ± 0.09, P < .01) were lower for those with 25(OH)D insufficiency after controlling for age. A stepwise selection procedure regressing MCR and E/I ratio on a number of metabolic parameters resulted in a model identifying age and 25(OH)D insufficiency as significant determinants for both measures. The interaction of age × 25(OH)D insufficiency was also included (MCR model, R² = 0.491, P < .001; E/I ratio, R² = 0.455, P < .001). Neither glycemic control nor other metabolic parameters were selected.ConclusionOur results suggest that 25(OH)D insufficiency is associated with reduced parasympathetic function, with a stronger association in younger persons with T2DM. Studies are needed to determine if vitamin D supplementation into the sufficient range could prevent or delay the onset of cardiovascular autonomic dysfunction. (Endocr Pract. 2015;21:174-181)     

Treatment with 50000 IU Vitamin D2 Every Other Week and Effect on Serum 25-Hydroxyvitamin D2, 25-Hydroxyvitamin D3, and Total 25-Hydroxyvitamin D in Aclinical Setting

ObjectiveTo examine the effect of 50 000 IU-vitamin D₂ supplementation in a clinical setting on serum total 25-hydroxyvitamin D (25[OH]D), 25-hydroxyvitamin D₂ (25[OH]D₂), and 25-hydroxyvitamin D₃ (25[OH]D₃).MethodsThis retrospective cohort study was performed in an urban tertiary referral hospital in Boston, Massachusetts. Patients who had been prescribed 50 000 IU vitamin D₂ repletion and maintenance programs were identified through a search of our electronic medical record. Baseline and follow-up total serum 25(OH)D, 25(OH)D₂, and 25(OH)D₃ levels were compared.ResultsWe examined the medical records of 48 patients who had been prescribed 50 000 IU vitamin D₂ in our clinic. Mean ± standard deviation baseline total 25(OH) D was 31.0 ± 10.6 ng/mL and rose to 48.3 ± 13.4 ng/mL after treatment (P <.001). 25(OH)D₂ increased from 4.2 ± 4.3 ng/mL to 34.6 ± 12.3 ng/mL after treatment (P <.001), for an average of 158 days (range, 35-735 days). Serum 25(OH)D3 decreased from 26.8 ± 10.8 ng/mL to 13.7 ± 7.9 ng/mL (P <.001).ConclusionsFifty thousand IU vitamin D₂ repletion and maintenance therapy substantially increases total 25(OH)D and 25(OH)D2 despite a decrease in serum 25(OH)D3. This treatment program is an appropriate and effective strategy to treat and prevent vitamin D deficiency.(Endocr Pract. 2012;18:399-402)     

Cholecalciferol (Vitamin D3) Therapy and Vitamin D Insufficiency in Patients with Chronic Kidney Disease: A Randomized Controlled Pilot Study

ObjectiveTo investigate the efficacy of cholecalciferol (vitamin D3) in raising serum 25-hydroxyvitamin D (25[OH)]D) levels and reducing parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD).MethodsIn this double-blind, randomized controlled pilot study, participants with CKD stage 3 and 4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m²), vitamin D insufficiency (serum 25[OH]D < 30 ng/mL), and serum intact PTH levels > 70 pg/mL were randomly assigned to receive either 50 000 IU of cholecalciferol or placebo once weekly for 12 weeks. Primary outcomes (25[OH]D and PTH levels) were measured at baseline, week 6, and week 12. Secondary outcomes (1,25-dihydroxvitamin D and bone turnover markers) were measured at baseline and week 12. Because of skewed data distribution, statistical analyses were performed on a logarithmic scale. The difference between the group means was exponentiated to provide the geometric mean ratio. A linear mixed model using an unstructured variance-covariance matrix was used to examine change in the primary and secondary outcomes over time.ResultsGeometric mean serum 25(OH)D concentrations of the study groups were similar at baseline (P = .77). At week 6, a significant difference between the treatment and placebo groups was detected (P = .001); this difference was maintained at week 12 (P = .002). Among cholecalciferol- treated participants, serum 25(OH)D concentration increased on average from 17.3 ng/mL (95% confidence interval [CI], 11.8-25.2) at baseline to 49.4 ng/mL (95% CI, 33.9-72.0) at week 12. As-treated analysis indicated a trend toward lower PTH levels among cholecalciferol-treated participants (P = .07).ConclusionWeekly cholecalciferol supplementation appears to be an effective treatment to correct vitamin D status in patients with CKD. (Endocr Pract. 2008;14:10-17)     

A new, vitamin D-based, multidimensional nomogram for the diagnosis of primary hyperparathyroidism

ObjectiveTo refine the diagnostic criteria for primary hyperparathyroidism (1°HPT) to identify atypical patients, in whom serum calcium, parathyroid hormone (PTH), or both are within the “normal” range.MethodsTotal serum calcium, intact PTH, and 25-hydroxyvitamin D [25(OH)D] levels were measured in patients with 1°HPT and healthy patient groups. Multivariate analysis of healthy patient data first identified factors that significantly affected PTH levels and defined a new PTH reference range with a mathematical model. That nomogram was then validated for prediction of atypical 1°HPT in patients with surgically confirmed disease.ResultsOn multivariate analysis, calcium (P = .0002), 25(OH)D (P < .0001), and age (P = .015) independently affected PTH. With these variables, we created a 4-dimensional nomogram that distinguished normal patients from those with hyperparathyroid states. Mathematically, this nomogram predicts 1°HPT when the measured serum PTH value is higher than PTH calculated by the following formula: PTH (pg/mL) = 120-[6 × calcium (mg/dL)]-[0.52 × 25(OH)D (ng/mL)] + [0.26 × patient age (years)]. When applied to our surgical group of patients, this nomogram successfully identified 100% of patients (238 of 238) with classic 1°HPT, 84% (64 of 76) with normocalcemic 1°HPT, and 54% (20 of 37) with 1°HPT and normal PTH.ConclusionThis study uniquely defines a patientspecific upper limit of normal for PTH based on the readily available variables of serum calcium, 25(OH)D, and patient age. Our nomogram may allow for more rapid definitive diagnosis and treatment of 1°HPT in patients with atypical presentations. (Endocr Pract. 2012;18:124-131)     

Vitamin D insufficiency in diabetic retinopathy

ObjectiveTo assess the relationship between vitamin D status and diabetic retinopathy.MethodsA clinic-based, cross-sectional study was conducted at Emory University, Atlanta, Georgia. Overall, 221 patients were classified into 5 groups based on diabetes status and retinopathy findings: no diabetes or ocular disease (n = 47), no diabetes with ocular disease (n = 51), diabetes with no background diabetic retinopathy (n = 41), nonproliferative diabetic retinopathy (n = 40), and proliferative diabetic retinopathy (PDR) (n = 42). Patients with type 1 diabetes and those taking > 1,000 IU of vitamin D daily were excluded from the analyses. Study subjects underwent dilated funduscopic examination and were tested for hemoglobin A_1c, serum creatinine, and 25-hydroxyvitamin D [25(OH)D] levels between December 2009 and March 2010.ResultsAmong the study groups, there was no statistically significant difference in age, race, sex, or multivitamin use. Patients with diabetes had lower 25(OH)D levels than did those without diabetes (22.9 ng/mL versus 30.3 ng/mL, respectively; P < .001). The mean 25(OH)D levels, stratified by group, were as follows: no diabetes or ocular disease = 31.9 ng/mL; no diabetes with ocular disease = 28.8 ng/mL; no background diabetic retinopathy = 24.3 ng/ mL; nonproliferative diabetic retinopathy = 23.6 ng/mL; and PDR = 21.1 ng/mL. Univariate analysis of the 25(OH) D levels demonstrated statistically significant differences on the basis of study groups, race, body mass index, multivitamin use, hemoglobin A_1c, serum creatinine level, and estimated glomerular filtration rate. In a multivariate linear regression model with all potential confounders, only multivitamin use remained significant (P < .001).ConclusionThis study suggests that patients with diabetes, especially those with PDR, have lower 25(OH)D levels than those without diabetes. (Endocr Pract. 2012; 18:185-193)     

Greater Than Age-Predicted Functional Deficits In Older Patients with Primary Hyperparathyroidism

ObjectiveTo compare the functional capacity of “asymptomatic” patients with primary hyperparathyroidism (PHPT) with normative values of healthy age-matched subjects.MethodsEighteen asymptomatic patients with PHPT met the study inclusion criteria: age > 55 years, serum calcium concentration elevated ≤ 1 mg/dL above normal, inappropriate elevation of parathyroid hormone (PTH) level, and no objective symptoms of PHPT. Functional capacity was assessed by (1) a 6-minute walk test, (2) time to complete 2 sit-to-stand maneuvers, (3) gait velocity, and (4) forward reach. Serum calcium, 25-hydroxyvitamin D, and PTH levels were measured by standard laboratory assays. Functional outcomes of the study patients were compared with age-matched normative values (unpaired t test) and correlated with these biomarkers. Because these patients often have weakness, fatigue, and malaise, we hypothesized that their functional capacity would be compromised relative to that of healthy, age-matched persons.ResultsThe mean age of the patients was 65.6 years, and the mean serum calcium, PTH, and 25-hydroxyvitamin D levels (and standard deviations) were 10.36 ± 0.37 mg/dL, 122.22 ± 39.54 pg/mL, and 44.4 ± 14.27 ng/mL, respectively. Relative to normative values of healthy, agematched subjects, these patients had comparable 6-minute walk distances but required a 37% longer time to complete a repeated sit-to-stand maneuver (P < .05), demonstrated a 52% slower gait speed (P < .001), and had a greater forward reach (P = .05).ConclusionOur findings suggest that older asymptomatic patients with PHPT may have significant functional deficits that can affect their safety and quality of life. Therefore, their functional capacity should be routinely evaluated, and identified deficits should be treated with appropriate interventions. (Endocr Pract. 2012;18: 450-455)     

Plasma osteopontin in acute liver failure

BackgroundOsteopontin (OPN) is a novel phosphoglycoprotein expressed in Kupffer cells that plays a pivotal role in activating natural killer cells, neutrophils and macrophages. Measuring plasma OPN levels in patients with acute liver failure (ALF) might provide insights into OPN function in the setting of massive hepatocyte injury.MethodsOPN levels were measured using a Quantikine® ELISA assay on plasma from 105 consecutive ALF patients enrolled by the US Acute Liver Failure Study Group, as well as controls including 40 with rheumatoid arthritis (RA) and 35 healthy subjects both before, and 1 and 3 days after undergoing spine fusion (SF) surgery as a model for acute inflammation.ResultsMedian plasma OPN levels across all etiologies of ALF patients were elevated 10- to 30-fold: overall median 1055 ng/mL; range: 33–19,127), when compared to healthy controls (median in pre-SF patients: 41 ng/mL; range 2.6–86.4). RA and SF post op patients had elevated OPN levels (37 ng/mL and 198 ng/mL respectively), well below those of the ALF patients. Median OPN levels were highest in acetaminophen (3603 ng/mL) and ischemia-related ALF (4102 ng/mL) as opposed to viral hepatitis (706 ng/mL), drug-induced liver injury (353 ng/mL) or autoimmune hepatitis (436 ng/mL), correlating with the degree of hepatocellular damage, as reflected by aminotransferase values (R value: 0.47 for AST, p < 0.001).ConclusionsOPN levels appeared to correlate with degree of liver necrosis in ALF. Very high levels were associated with hyperacute injury and good outcomes. Whether OPN exerts a protective effect in limiting disease progression in this setting remains uncertain.