Evaluation of Vitamin D Repletion Regimens to Correct Vitamin D Status in Adults

ObjectiveTo determine the efficacy and safety of commonly prescribed regimens for the treatment of vitamin D insufficiency.MethodsWe performed a retrospective analysis of 306 consecutive patients who were prescribed ergocalciferol (vitamin D₂) for correction of vitamin D insufficiency at the Atlanta Veterans Affairs Medical Center between February 2003 and May 2006. Serum levels of parathyroid hormone, 25-hydroxyvitamin D (25-OHD), and calcium were compared before and after treatment with ergocalciferol. Patients who did not have a 25-OHD determination (n = 41) were excluded from analysis. Vitamin D deficiency, insufficiency, and sufficiency were defined as a serum 25-OHD level of < 20 ng/mL, 21 to 29 ng/mL, and > 30 ng/mL, respectively.ResultsWe identified 36 discrete prescribing regimens. The 3 most common regimens were ergocalciferol 50,000 IU once weekly for 4 weeks followed by 50,000 IU once monthly for 5 months (n = 48); ergocalciferol 50,000 IU once monthly for 6 months (n = 80); and ergocalciferol 50,000 IU 3 times weekly for 6 weeks (n = 27). Each of these 3 treatments significantly increased serum 25-OHD (P < .01), but vitamin D sufficiency was achieved in only 38%, 42%, and 82% of study subjects, respectively. Regimens with > 600,000 IU of ergocalciferol given for a mean of 60 ± 40 days achieved sufficiency in 64% of cases, without vitamin D toxicity.ConclusionIn this study, regimens that contained at least 600,000 IU of ergocalciferol appeared to be the most effective in achieving vitamin D sufficiency. Guidelines for the treatment of vitamin D insufficiency in healthy adults should be developed. (Endocr Pract. 2009;15:95-103)     

Effect of High-Dose Vitamin D Repletion on Glycemic Control in African-American Males with Prediabetes and Hypovitaminosis D

Objective: This double-blind, randomized, controlled trial evaluated whether 12 months of high-dose vitamin D2 supplementation improved insulin sensitivity and secretion and glycemic status.Methods: African-American males (AAM) with prediabetes (glycosylated hemoglobin [A1C] 5.7-6.4%), hypovitaminosis D (25-hydroxyvitamin D [25OHD] 5-29 ng/mL), and prevalent medical problems were supplemented with vitamin D3 (400 IU/day) and then randomized to weekly placebo or vitamin D2 (50,000 IU). The primary outcome was the change in oral glucose insulin sensitivity (OGIS, from an oral glucose tolerance test [OGTT]) after 12 months of treatment. Secondary outcomes included other glycemic indices, A1C, and incident diabetes.Results: Baseline characteristics were similar in vitamin D-supplemented (n = 87) and placebo (n = 86) subjects completing the trial with average concentrations 14.4 ng/mL, 362 mL × min^-1 × m^-2, and 6.1% for 25OHD, OGIS and A1C, respectively. After 12 months, the vitamin D-supplemented group had a change in serum 25OHD +35 versus +6 ng/mL for placebo, P<.001; OGIS +7.8 versus -16.0 mL × min^-1 × m^-2 for placebo, P = .026; and A1C -0.01 versus +0.01% for placebo, P = .66. Ten percent of subjects in both groups progressed to diabetes. A posthoc analysis of participants with baseline impaired fasting glucose (IFG) showed that more subjects in the vitamin D subgroup (31.6%) than placebo (8.3%) returned to normal glucose tolerance, but the difference did not reach significance (P = .13).Conclusion: The trial does not provide evidence that 12 months of high-dose D2 repletion improves clinically relevant glycemic outcomes in subjects with prediabetes and hypovitaminosis D (NCT01375660).Abbreviations: AAM = African-American males A1C = glycosylated hemoglobin BMI = body mass index D2 = ergocalciferol D3 = cholecalciferol IFG = impaired fasting glucose IGT = impaired glucose tolerance JBVAMC = Jesse Brown VA Medical Center OGIS = oral glucose insulin sensitivity index OGTT = oral glucose tolerance test 25OHD = 25-hydroxyvitamin D VHA = Veterans Health Administration     

Safety of Vitamin D Replacement in Patients with Primary Hyperparathyroidism and Concomitant Vitamin D Deficiency

ObjectiveTo evaluate the safety of vitamin D replacement in patients with vitamin D deficiency and primary hyperparathyroidism.MethodsRetrospective chart review of 35 patients from our endocrine clinic, age 22 to 89 years, diagnosed with primary hyperparathyroidism and vitamin D deficiency, and treated with either 1,000 to 2,000 international units (IU) of vitamin D daily or 50,000 IU of vitamin D weekly for 5 months. Data were collected before and after treatment on serum calcium, 25-hydroxyvitamin D (25-OH D), intact parathyroid hormone (iPTH), phosphorus, alkaline phosphatase, nephrolithiasis, fractures, and osteoporosis.Results25-OH D increased significantly, from a baseline of 14.65 ± 6.57 ng/mL to 42.17 ± 12.98 ng/ mL after weekly treatment with 50,000 IU of vitamin D (P<.0001), and from 22.42 ± 5.47 ng/mL to 33.33 ± 6.39 ng/mL following daily treatment with 1,000 to 2,000 IU of vitamin D (P<.0001). Pre- and posttreatment unadjusted serum calcium remained stable in the high-dose group (10.80 ± 0.43 mg/dL vs. 10.72 ± 0.67 mg/dL; P = .47), but decreased slightly in the low-dose group (10.76 ± 0.58 mg/dL vs. 10.11 ± 0.54 mg/dL; P = .0007). After adjusting for age, sex, vitamin D, and PTH levels, the small calcium difference in the low-dose group became statistically insignificant. Treatment with either high or low doses of vitamin D did not significantly change iPTH levels. Creatinine remained stable in all patients, and no new cases of nephrolithiasis were reported.ConclusionReplacing vitamin D in mild primary hyperparathyroidism is safe, effective, and does not increase calcium to dangerous levels. (Endocr Pract. 2013;19:420-425)     

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)     

Comparison of Vitamin D Replacement Strategies with High-Dose Intramuscular or Oral Cholecalciferol: A Prospective Intervention Study

Objective: To ascertain the frequency of correction of vitamin D deficiency (VDD) with single or multiple doses of oral (PO) and intramuscular (IM) administration of 2 high-dose preparations of vitamin D₃ (VD₃).Methods: This was a prospective intervention study conducted in an ambulatory care setting. One hundred participants with VDD (25-hydroxy vitamin D &lsqb;25-OHD] <20 ng/mL) were randomized to receive a dose of 600,000 or 200,000 IU of VD₃ via a PO or IM route. The main outcome measure was serum 25-OHD levels at 2, 4, and 6 months after the intervention.The same dose was repeated in participants if 25-OHD remained <30 ng/mL at 2 and 4 months.Results: At 2 months, VDD was corrected in 93.8% of participants in Group 1 (600,000 IU IM); 83.3% in Group 2 (600,000 IU PO), 87.5% in Group 3 (200,000 IU IM), and 70.6% in Group 4 (200,000 IU PO). The mean changes from baseline in vitamin D levels at 2 months were 29.6 ± 13.7, 19.8 ± 12.3, 18.3 ± 10.6, and 13.7 ± 7.8 ng/mL in Groups 1, 2, 3, and 4, respectively. The mean levels remained significantly higher from baseline in all groups at all time points during the 6 months of observation. The mean 25-OHD level achieved in Group 1 was significantly higher than all other groups at 6 months.Conclusion: Two months after the intervention, VDD was corrected in more than 70% of participants with a single dose of either 600,000 or 200,000 IU given PO or IM.Abbreviations: ALT = alanine transaminase IM = intramuscular iPTH = intact parathyroid hormone IQR = interquartile range 25-OHD = 25 hydroxyvitamin D PO = oral VD₃ = vitamin D3 (cholecalciferol) VDD = vitamin D deficiency VDI = vitamin D insufficiency     

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)     

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)     

The Vitamin D Dose Response in Obesity

ObjectiveThe prevalence of vitamin D inadequacy is high in obese individuals. Determining the response of serum 25-hydroxyvitamin D (25[OH]D) to vitamin D₃ supplementation in obese and nonobese individuals may lead to concurrent recommendations for optimal vitamin D intake in these populations. The objective of this study was to determine the dose response of vitamin D₃ in subjects with a body mass index ≥ 35 kg/m².MethodsRandomized, double-blind, placebo-controlled study. This study is an extension of our previous study of vitamin D dosing in healthy adults. After an assessment of baseline 25(OH)D levels, participants were randomized to a vitamin D supplementation arm (100 μg daily if baseline 25[OH]D was < 50 nmol/L, or 50 μg daily if baseline 25[OH]D was ≥ 50 nmol/L) or placebo arm. Subjects with baseline 25(OH)D level ≥ 80 nmol/L were excluded from the study. Two months following randomization, a repeat 25(OH)D measurement was done.ResultsFinal analysis included 25 subjects (14 placebo, 11 active). At 2 months, serum 25(OH)D concentration increased to a mean of 75 nmol/L in the active group. Mean slope (i.e., vitamin D₃ response), defined as 25(OH) D change/baseline dose, was 0.398 nmol/L/μg/day.ConclusionThe dose response of vitamin D₃ (slope) in obese subjects was significantly lower (P < .03) at 0.398 nmol/L/μg/day compared to the slope in the previous study of healthy subjects (0.66 nmol/L/μg/day). These results suggest that obese individuals may require 40% higher vitamin D intake than nonobese individuals to attain the same serum 25(OH)D concentration. (Endocr Pract. 2014;20:1258-1264)     

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     

Effectiveness and Outcomes of Current Practice in Treating Vitamin D Deficiency in Patients Listed for Liver Transplantation

Objective: Vitamin D deficiency is prevalent in cirrhotic patients awaiting liver transplantation (LT). Optimal vitamin D management for these patients remains undefined. We sought to determine the effectiveness of our practice in addressing vitamin D deficiency in LT patients.Methods: This retrospective study included 127 patients who received a first LT between July 2010 and July 2011. Outcomes measured included readmission rates, fractures, and functional status post-LT. 25-Hydroxyvitamin D (25-OH D) deficiency was stratified as: mild (20–30 ng/mL), moderate (15–19.9 ng/mL), and severe (<15 ng/mL). We estimated the amount of vitamin D supplementation required for each patient.Results: At LT evaluation, 107 patients (84%) had vitamin D deficiency, and 74% remained vitamin D deficient at LT. Only 62% received vitamin D supplementation pre-LT. Moderate and severe deficiencies were less common at LT and rare 4 months post-LT. There was an association between improvement in vitamin D deficiency category at LT and increased vitamin D (>400,000 IU total) supplementation (P = .004). We found no association between vitamin D deficiency at LT and functional status, fractures, or readmissions post-LT. Patients receiving induction immunosuppressant therapy with basiliximab had a significantly greater degree of worsening in bone mineral density (BMD) post-LT.Conclusion: Moderate-to-severe vitamin D deficiency was very prevalent in a cohort of patients undergoing evaluation for LT. Deficiency was improved with increased vitamin D replacement therapy. Vitamin D deficiency at LT was not associated with worse bone or functional outcomes post-LT. The influence of basiliximab on bone health post-LT requires further evaluation.Abbreviations: 25-OH D = 25-hydroxyvitamin D BMD = bone mineral density BMI = body mass index CI = confidence interval LT = liver transplantation MELD = Model for End-Stage Liver Disease PTH = parathyroid hormone     

Hashimoto Thyroiditis not Associated with Vitamin D Deficiency

Objective: Vitamin D deficiency is associated with several autoimmune diseases. This study assessed whether vitamin D deficiency is associated with Hashimoto thyroiditis (HT).Methods: Two groups of patients were selected for which serum 25-hydroxyvitamin D (25(OH)D) levels had been measured: (1) a study group of patients diagnosed with HT as indicated by thyroid antibodies, and (2) a healthy control group. Each group was separated by sex and then controlled for age and body mass index (BMI). Groups' mean 25(OH)D levels were compared by analysis of variance (ANOVA), and percent frequencies of vitamin D sufficiency, insufficiency, and deficiency were compared with a Z-test. The correlations between 25(OH)D levels and thyroid antibodies and thyroid-stimulating hormone (TSH) levels were also tested.Results: The mean 25(OH)D levels for the HT and control groups were significantly different in females (30.75 vs. 27.56 ng/mL, respectively) but not in males (14.24 vs. 13.26 ng/mL). HT females had a higher rate of vitamin D sufficiency (51.7% vs. 31.1%) and a lower rate of insufficiency (48.3% vs. 68.9%) relative to control females. No such differences were found in the male groups. None of the females were vitamin D deficient, but almost all males were. A significant (P = .016) positive correlation (r_s = 0.436) between 25(OH)D and TPOAb was observed in males.Conclusion: HT is not associated with higher rates of vitamin D deficiency relative to a control group.Abbreviations:BMI = body mass indexHT = Hashimoto thyroiditis25(OH)D = 25-hydroxyvitamin DTgAb = thyroglobulin antibodyTSH = thyroid-stimulating hormoneTPOAb = thyroid-peroxidase antibodyVDR = Vitamin D receptor     

Seasonal Variation Of Vitamin D And Serum Thyrotropin Levels And Its Relationship In A Euthyroid Caucasian Population

Objective: It is unclear whether seasonal variations in vitamin D concentrations affect the hypothalamo-pituitary-thyroid axis. We investigated the seasonal variability of vitamin D and serum thyrotropin (TSH) levels and their interrelationship.Methods: Analysis of 401 patients referred with nonspecific symptoms of tiredness who had simultaneous measurements of 25-hydroxyvitamin D3 (25&lsqb;OH]D3) and thyroid function. Patients were categorized according to the season of blood sampling and their vitamin D status.Results: 25(OH)D3 levels were higher in spring-summer season compared to autumn-winter (47.9 ± 22.2 nmol/L vs. 42.8 ± 21.8 nmol/L; P = .02). Higher median (interquartile range) TSH levels were found in autumn-winter (1.9 &lsqb;1.2] mU/L vs. 1.8 &lsqb;1.1] mU/L; P = .10). Across different seasons, 25(OH)D3 levels were observed to be higher in lower quartiles of TSH, and the inverse relationship was maintained uniformly in the higher quartiles of TSH. An independent inverse relationship could be established between 25(OH)D3 levels and TSH by regression analysis across both season groups (autumn-winter: r = -0.0248; P<.00001 and spring-summer: r = -0.0209; P<.00001). We also observed that TSH varied according to 25(OH)D3 status, with higher TSH found in patients with vitamin D insufficiency or deficiency in comparison to patients who had sufficient or optimal levels across different seasons.Conclusion: Our study shows seasonal variability in 25(OH)D3 production and TSH secretion in euthyroid subjects and that an inverse relationship exists between them. Further studies are needed to see if vitamin D replacement would be beneficial in patients with borderline thyroid function abnormalities.Abbreviations: 25(OH)D2 = 25-hydroxyvitamin D2; 25(OH)D3 = 25-hydroxyvitamin D3; AITD = autoimmune thyroid disease; FT4 = free thyroxine; TFT = thyroid function test; TSH = thyrotropin; UVB = ultraviolet B     

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)     

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)     

Long-Term Bioavailability of Single Doses of Intramuscular Vitamin D2

Objective: We sought to determine the long-term bioavailability of single doses of intramuscular (IM) vita-min D₂ (D₂) in healthy adults.Methods: Forty healthy volunteers with hypovitaminosis D received a single dose of 200,000, 400,000, or 600,000 IU intramuscular D₂ or no treatment. Levels of 25-hydroxyvitamin D₂ (25&lsqb;OH]D₂) and 25-hydroxyvitamin D₃ (25&lsqb;OH]D₃) in serum were measured by liquid chromatography-tandem mass spectrometry. Vitamin D binding protein (DBP) and intact parathyroid hormone (iPTH), bone turnover markers (BTMs), and serum and urinary calcium were also measured.Results: After a single dose of D₂ injection, the level of 25(OH)D₂ increased slowly and reached a plateau at 8 weeks. The plateau remained stable for 12 weeks. The mean increase in 25(OH)D₂ was 6.8, 9.6, or 15.6 ng/mL after injection of 200,000 IU, 400,000 IU, or 600,000 IU D₂. Although endogenous 25(OH)D₃ levels were reduced by IM D₂, the total 25(OH)D levels increased by 5.0, 7.0, or 10.3 ng/mL in average after injection of 200,000 IU, 400,000 IU, or 600,000 IU D₂. The iPTH levels were also decreased by IM D₂. However, levels of serum calcium, BTMs, and DBP and urinary calcium were not altered by IM D₂.Conclusion: A single dose of 200,000 IU, 400,000 IU, or 600,000 IU IM D₂ raises total 25-hydroxyvitamin D levels by 5.0, 7.0, or 10.3 ng/mL on average for at least 12 weeks and reduces iPTH and endogenous 25(OH)D₃ levels without affecting levels of serum calcium, BTMs, DBP, and urinary calcium.     

Correlating Pre-Operative Vitamin D Status with Post-Thyroidectomy Hypocalcemia

Objective: To examine the relationship between pre-operative vitamin D status and post-thyroidectomy hypocalcemia.Methods: Retrospective study examining 264 total and completion thyroidectomies conducted between 2007 and 2011. Subjects included had a recorded 25-hydroxyvitamin D (25[OH]D) level within 21 days prior to or 1 day following surgery, did not have a primary parathyroid gland disorder, and were not taking 1,25-dihydroxyvitamin D₃ (calcitriol) prior to surgery. Some subjects were repleted with vitamin D pre-operatively if a low 25(OH)D level (typically below 20 ng/mL) was identified. Pre-operative 25(OH)D, concurrent neck dissection, integrity of parathyroid glands, final pathology, postoperative parathyroid hormone (PTH), calcium nadir and repletion, and length of stay were examined.Results: The mean pre-operative 25(OH)D for all subjects was 25 ng/mL, and the overall rate of post-operative hypocalcemia was 37.5%. Lower pre-operative 25(OH)D did not predict postoperative hypocalcemia (P =.96); however, it did predict the need for postoperative 1,25-dihydroxyvitamin D₃ administration (P =.01). Lower postoperative PTH levels (P =.001) were associated with postoperative hypocalcemia.Conclusion: Pre-operative 25(OH)D did not predict a postoperative decrease in serum calcium, although it did predict the need for 1,25-dihydroxyvitamin D₃ therapy in hypocalcemic subjects. We recommend that 25(OH)D be assessed and, if indicated, repleted pre-operatively in patients undergoing total thyroidectomy.Abbreviations: 25(OH)D = 25-hydroxyvitamin D PTH = parathyroid hormone     

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)     

Low Maternal Vitamin D Status during the Second Trimester of Pregnancy: A Cross-Sectional Study in Wuxi,China

BackgroundVitamin D deficiency is common in pregnant women, but an optimal serum vitamin D level during pregnancy has not been determined and remains an area of active research. Vitamin D data from large populations of pregnant Chinese women are still limited.ObjectiveTo evaluate the vitamin D status of women in Eastern China during the second trimester of pregnancy.MethodsA hospital-based, cross-sectional, observational study. Serum 25-hydroxyvitamin D [25(OH)D] concentration was measured in samples from 5823 pregnant women in Wuxi City, China (latitude: 31.5o N), from January 2011 to June 2012.ResultsThe median serum 25(OH)D concentration was 34.0 nmol/L [2.5 nmol/L 25(OH)D = 1 ng/mL 25(OH)D]. Vitamin D deficiency [defined as 25(OH)D < 30 nmol/L according to the Institute of Medicine (National Academy of Sciences, Washington, D.C., USA)] or inadequacy [25(OH)D of 30–49.9 nmol/L] was identified in 40.7% and 38.0% of the women, respectively. Only 0.9% had a 25(OH)D level ≥ 80.0 nmol/L, which is the concentration recommended as adequate by the Endocrine Society (Washington, D.C., USA). Compared with older women, younger women were more likely to be deficient in vitamin D. There were significant differences in the 25(OH)D levels according to season. The 25(OH)D levels reached peak values in September and were correlated with (r = 0.337, P < 0.001), and fluctuated with, average monthly air temperatures.ConclusionsThere is a high prevalence of Vitamin D deficiency among pregnant Chinese women, and 25(OH)D levels varied according to season and air temperature. The results of this study also suggest that currently there is a big gap between the levels of Vitamin D detected in pregnant Chinese women and the levels recommended by the Endocrine Society.     

Tibial Tenderness Identifies Secondary Hyperparathyroidism Responding to High-Dose Vitamin D in Pakistani Women

ObjectiveTo assess the utility of anterior tibial tenderness (ATT) measured by visual analogue scoring (VAS) as a clinical diagnostic tool for vitamin D deficiency in a high-risk population of Pakistani women.MethodsATT was measured by VAS in 75 premenopausal women age 17 to 56 years (mean, 41.3 years) with generalized aches and pains and calcium <11 mg/dL (normal, 8 to 11 mg/dL) who were seen at a tertiary care center in Lahore, Pakistan. This was followed by administration of 1.8 million units of vitamin D3 in divided doses. ATT, vitamin D, and parathyroid hormone (PTH) levels were checked before and after the injections. Correlation between ATT, vitamin D, and PTH, as well as changes in ATT, vitamin D, and PTH following supplementation were determined.ResultsPre-intervention average calcium and vitamin D were 9.3 mg/dL (range, 8 to 10.3 mg/dL) and 12.1 ng/mL (range, 1.5 to 32.6 ng/mL), respectively. Seventy-four percent of the participants (53/75) had vitamin D deficiency and elevated PTH (>60 pg/mL). Mean PTH was 81.6 pg/mL (range, 29.1 to 370 pg/mL). Changes in ATT correlated strongly (r = 0.422; P = .013) with changes in PTH. Following supplementation, there was significant improvement in ATT (P<.01) and vitamin D level (P<.01), with a decrease in PTH level (P<.01).ConclusionATT is a valid clinical diagnostic measure of vitamin D deficiency in South Asian women. (Endocr Pract. 2013;19:596-601)