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     

Vitamin D-Binding Protein Levels in Female Patients with Primary Hyperparathyroidism

ObjectiveTo determine whether low levels of vitamin D-binding protein (DBP) are related to 25-hydroxyvitamin D (25[OH]D) deficiency in female patients with primary hyperparathyroidism (PHPT).MethodsTwenty-five female patients with PHPT (serum calcium level >10.2 mg/dL and intact parathyroid hormone (iPTH) level >66 pg/mL) and 25 healthy age- and body mass index-matched female control subjects were xaminod. Serum calcium and iPTH levels were determined by commercial laboratories. Levels of 25(OH)D and 1,25-dihydroxyvitamin D (1,25[OH]₂D) were determined by radioimmunoassay, and DBP level was determined by enzyme-linked immunosorbent assay.ResultsSerum iPTH and calcium levels were higher in PHPT patients than control subjects (P<.001). Levels of 25(OH)D, albumin, and DBP were lower in the serum of PHPT patients than control subjects (P<.01). There were no significant differences in 1,25(OH)₂D and free 25(OH) D levels between PHPT patients and control subjects. DBP level was inversely correlated with calcium (r = -0.47; P<.01) and iPTH (r = −0.31; P<.05) levels. The 25(OH)D level correlated positively with both DBP (r = 0.28; P <.05) and albumin (r = 0.44; P<.05) levels.ConclusionsBoth serum 25(OH)D and DBP levels were lower in female patients with PHPT compared with control subjects. We suggest that a low DBP level contributes to the low 25(OH)D level observed in female PHPT patients. The etiology of the decrease in DBP and its relationship to calcium, 25(OH)D, and PTH levels require further investigation. (Endocr Pract. 2013;19:609-613)     

A Prospective Study of Commonly Utilized Regimens of Vitamin d Replacement and Maintenance Therapy in Adults

Objective: To determine which vitamin D dose, formulation, and schedule most effectively and safely achieves a 25-hydroxyvitamin D (25&lsqb;OH]D) level of >30 ng/mL (75 nmol/L).Methods: In this prospective study, 100 subjects from the NY Harbor HCS Brooklyn Campus, ages 25 to 85 years, with 25(OH)D <30 ng/mL (<75 nmol/L), were randomized into four groups: cholecalciferol (D3) 2,000 international units (IU) daily; D3 3,000 IU daily; ergocalciferol (D2) 50,000 IU weekly; and D2 50,000 IU twice weekly. All were supplemented with 500 mg calcium carbonate daily. 25(OH)D, parathyroid hormone (PTH), urinary calcium, urinary creatinine, and other variables were measured during 7 visits over 12 months.Results: All groups achieved a mean vitamin D level >30 ng/mL (>75 nmol/L) by visit 4 (5 months). Those receiving 50,000 IU D2 twice weekly displayed the most rapid and robust response, with 25(OH)D reaching >30 ng/mL (>75 nmol/L) after only 1 month and plateauing at 60 ng/mL (150 nmol/L) by 7 months. Although no statistically significant difference was seen in mean 25(OH)D levels between groups 1 through 3, subjects on 50,000 IU D2 weekly more consistently showed higher mean levels than either groups 1 or 2. No episodes of significant hypercalcemia occurred. There was a negative correlation in mean PTH levels and mean vitamin D levels in group 4 and all groups combined.Conclusion: All four schedules of vitamin D replacement were effective in safely achieving and maintaining 25(OH)D >30 ng/mL (>75 nmol/L). D2 50,000 IU twice weekly provided the most rapid attainment and highest mean levels of vitamin D.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; BUN = blood urea nitrogen; Ca/Cr = calcium/creatinine; D2 = ergocalciferol; D3 = cholecalciferol; IU = international units; PTH = parathyroid hormone     

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)     

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     

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     

Synthesis of vitamin D3 analogues with A-ring modifications to directly measure vitamin D levels in biological samples

C-3-substituted 25-hydroxyvitamin D₃ analogues were synthesized as tools to directly measure levels of vitamin D in biological samples. The strategy involves vinyloxycarbonylation of the 3β-hydroxy group and formation of a carbamate bond with a hydroxyl or amino group at the end of the alkyl chain. Biotinylated conjugates of synthesized derivatives were generated to be linked with vitamin D binding protein (DBP). The spacer group present in the alkyl chain is important in the binding of antibodies to the analogue–DBP complex. When compared to 25-hydroxyvitamin D₃-DBP, the binding of some antibodies to the analogue–DBP complex of the 25-hydroxyvitamin D₃ derivative 10 that posses an 8-aminoctyl alkyl chain is significantly reduced, but this analogue displaced [26,27-³H]-25-hydroxyvitamin D₃ from DBP. In contrast, the 8-hydroxyoctyl alkyl chain analogue 9 showed less displacement.     

Associations Between Vitamin D and Microvascular Complications in Middle-Aged And Elderly Diabetic Patients

Objective: The objective of this cross-sectional study was to investigate the association of serum 25-hydroxyvitamin D (25&lsqb;OH]D) levels with estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and the prevalence of diabetic retinopathy (DR) in Chinese diabetic adults.Methods: A total of 4,767 diabetic participants were enrolled from seven communities in Shanghai, China, in 2018. Participants underwent several examinations, which included the measurement of anthropometric parameters, blood pressure, glucose, lipid profiles, 25(OH)D, and ACR. DR was detected based on high-quality fundus photographs and remotely read by ophthalmologists.Results: Compared with the first 25(OH)D quartile, participants in the fourth quartile had a lower prevalence of high ACR (odds ratio &lsqb;OR], 0.77; 95% confidence interval &lsqb;CI], 0.61 to 0.96) (P for trend <.01). No association was found between 25(OH)D levels and eGFR. For DR, the OR (95% CI) for DR ranging from 0 to 4 in ordinal logistic regression associated with 25(OH)D was 0.62 (0.47 to 0.82) for the fourth 25(OH)D quartile (P for trend <.01) compared with the first quartile. These associations were all fully adjusted for confounding factors.Conclusion: Lower serum 25(OH)D concentration is significantly associated with increased ACR and higher prevalence of DR in middle-aged and elderly diabetic adults. However, the possibility of a causal relationship between 25(OH)D deficiency and diabetic microvascular complications remains to be demonstrated.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; ACR = albumin/creatinine ratio; BMI = body mass index; CI = confidence interval; DKD = diabetic kidney disease; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; OR = odds ratio; T2DM = type 2 diabetes mellitus     

Association between 25-Hydroxyvitamin D and Intact Parathyroid Hormone Levels Across Latitude among Adults with African Ancestry

Objective: To compare levels of 25-hydroxyvitamin D (25[OH]D) associated with a plateauing of intact parathyroid (iPTH) across latitudes among adults with African ancestry.Methods: This study included approximately 500 adults of African ancestry ages 25 to 45 years living in 4 sites: Chicago, Illinois (41°N), Jamaica (17°N), Ghana (6°N), and South Africa (34°S). Multivariate linear regression models, a nonlinear logistic growth curve model, and piecewise linear models with a single knot were fitted to estimate the 25[OH]D level associated with a plateauing of iPTH with adjustment for covariates. Goodness of fit was compared using computer intensive permutation tests.Results: Mean age was 34.7 (SD 6.2) years, and 46.5% were male. Within each site, the percentage of participants with an iPTH level ≥65 pg/mL was higher among females versus males and was most frequent among South African females (17.1%) and lowest among Jamaican males (0.6%). Goodness of fit tests supported linear regression as the preferred model for the association between iPTH and 25[OH]D in the 4 sites with no 25[OH]D level associated with iPTH plateauing in any site. The slope of the association between 25[OH]D and iPTH differed by latitude; it was strongest in the U.S. (β = -0.81; 95% confidence interval [CI] = -1.03, -0.59), and weakest in Jamaica (β = -0.45; 95% CI -0.71, -0.18) with covariate adjustment, but differences in slopes were small.Conclusion: The association between 25[OH]D and iPTH appears linear among adults with African ancestry regardless of latitude within a range of 25[OH]D levels between 10 and 60 ng/mL.Abbreviations:BMI = body mass indexCI = confidence intervaleGFR = estimated glomerular filtration rateiPTH = intact parathryoid hormone25[OH]D = 25-hydroxyvitamin D     

Temporal Relationship between Vitamin D Status and Parathyroid Hormone in the United States

Background

Interpretation of parathyroid hormone (iPTH) requires knowledge of vitamin D status that is influenced by season.

Objective

Characterize the temporal relationship between 25-hydroxyvitamin D₃ levels [25(OH)D₃] and intact iPTH for several seasons, by gender and latitude in the U.S. and relate 25-hydrovitamin D₂ [25(OH)D₂] levels with PTH levels and total 25(OH)D levels.

Method

We retrospectively determined population weekly-mean concentrations of unpaired [25(OH)D₂ and 25(OH)D₃] and iPTH using 3.8 million laboratory results of adults. The 25(OH)D₃ and iPTH distributions were normalized and the means fit with a sinusoidal function for both gender and latitudes: North >40, Central 32–40 and South <32 degrees. We analyzed PTH and total 25(OH)D separately in samples with detectable 25(OH)D₂ (≥4 ng/mL).

Findings

Seasonal variation was observed for all genders and latitudes. 25(OH)D₃ peaks occurred in September and troughs in March. iPTH levels showed an inverted pattern of peaks and troughs relative to 25(OH)D₃, with a delay of 4 weeks. Vitamin D deficiency and insufficiency was common (33% <20 ng/mL; 60% <30 ng/mL) as was elevated iPTH levels (33%>65 pg/mL). The percentage of patients deficient in 25(OH)D₃ seasonally varied from 21% to 48% and the percentage with elevated iPTH reciprocally varied from 28% to 38%. Patients with detectable 25(OH)D₂ had higher PTH levels and 57% of the samples with a total 25(OH)D > 50 ng/mL had detectable 25(OH)D₂.

Interpretation

25(OH)D₃ and iPTH levels vary in a sinusoidal pattern throughout the year, even in vitamin D₂ treated patients; 25(OH)D₃, being higher in the summer and lower in the winter months, with iPTH showing the reverse pattern. A large percentage of the tested population showed vitamin D deficiency and secondary hyperparathyroidism. These observations held across three latitudinal regions, both genders, multiple-years, and in the presence or absence of detectable 25(OH)D₂, and thus are applicable for patient care.     

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     

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 system in iguanian lizards

The apparent plasma concentration of vitamin D binding protein (DBP) in an iguanian lizard, Pogona barbata, and the affinity of this protein for 25-hydroxyvitamin D₃ (25(OH)D₃), 25-hydroxyvitamin D₂ (25(OH)D₂), and 1,25-dihydroxyvitamin D₃ (1,25(OH)D₃) was found to resemble more closely that of the domestic hen than that of the human. The characteristics of Pogona DBP, the pattern of vitamin D metabolites derived from injected radioactive vitamin D₃ and the plasma concentrations of endogenous 25-hydroxyvitamin D (25(OH)D) in a range of iguanian lizards have been examined. The findings suggest that 25-hydroxyvitamin D (25(OH)D) is the major metabolite of vitamin D, and that it may represent the storage form of vitamin D in these species in the same way as in mammals. High concentrations of vitamin D within iguanian embryos and egg yolks suggest a role for this compound in embryogenesis in these species, and perhaps indicates that there is a mechanism for vitamin D delivery to eggs comparable to that found in the domestic chicken.     

The Relationship Between Serum 25-Hydroxyvitamin D and Glucose Homeostasis in Obese Children and Adolescents in Zhejiang,China

Objective: Evidence of the association between vitamin D, insulin resistance, and oral disposition index (oDI) in obese children and adolescents is limited. To fill this research gap, we measured serum 25-hydroxyvitamin D (25&lsqb;OH]D) levels in obese children and analyzed the relationship between serum 25(OH)D levels and glucose homeostasis.Methods: Altogether, 348 obese and 445 nonobese children and adolescents (age, 6 to 16 years) were enrolled in this study. Obese children were divided into 4 subgroups: normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG and IGT (IFG+IGT) according to oral glucose tolerance test results. We measured serum 25(OH)D levels and calculated the homeostasis model assessment (HOMA) of insulin resistance (IR), the whole-body insulin sensitivity index (WBISI), and the disposition index.Results: The levels of 25(OH)D in the obese group were significantly lower than in the nonobese group; serum 25(OH)D level in the NGT subgroup was higher than those of the other 3 subgroups, and it was significantly inversely correlated with logHOMA-IR (r = -0.090; P = .045) and positively correlated with logWBISI and logHOMA-oDI (r = 0.091, P = .049; and r = 0.108, P = .046, respectively). Obese patients with vitamin D deficiency thus have a significantly higher risk of disturbances in glucose metabolism.Conclusion: 25(OH)D deficiency or insufficiency is quite common in obese children and adolescents in Zhejiang, China. Obese patients with 25(OH)D deficiency (<30 nmol/L) are shown to be at higher risk for abnormal glucose metabolism.Abbreviations: 25(OH)D = 25-hydroxyvitamin D ΔI₃₀/ΔG₃₀ = insulinogenic index BMI = body mass index CI = confidence interval HbA_1c = hemoglobin A_1c HOMA = homeostasis model assessment I_F = fasting insulin IFG = impaired fasting glucose IGT = impaired glucose tolerance IR = insulin resistance NGT = normal glucose tolerance oDI = oral disposition index OGTT = oral glucose tolerance test WBISI = whole-body insulin sensitivity index     

KDIGO Categories of Glomerular Filtration Rate and Parathyroid Hormone Secretion in Primary Hyperparathyroidism

Objective: The recent Fourth Workshop on the Management of Asymptomatic primary hyperparathyroidism (PHPT) maintained the threshold of 60 mL/min for decreased renal function, below which surgery is recommended. This study investigated the relationship between different stages of renal insufficiency and parathyroid hormone (PTH) levels in an updated case series of PHPT patients.Methods: This was a retrospective, cross-sectional study involving 379 consecutive PHPT patients. Biochemical evaluation included total and ionized serum calcium, phosphate, creatinine, immunoreactive intact PTH, and 25-hydroxyvitamin D₃ (25[OH]D₃) levels in the fasting state. Glomerular filtration rate (GFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.Results: Mean CKD-EPI estimated GFR was 81.9 ± 20.3 mL/min/1.73 m², and median GFR was 84.0 mL/min/1.73 m² (interquartile range, 26.8 mL/min/1.73 m²). The patients were divided into 5 groups according to the Kidney Disease: Improving Global Outcomes 2012 guidelines: group 1 with normal or increased GFR (>90 mL/min/1.73 m²); group 2 with mild GFR decrease (60 to 89 mL/min/1.73 m²); group 3a with mild to moderate GFR decrease (45 to 59 mL/min/1.73 m²); group 3b with moderate to severe GFR decrease (30 to 44 mL/min/1.73 m²); and group 4 with severe GFR decrease (<30 mL/min/1.73 m²). Among the 5 groups of patients, serum calcium levels were different (P = .025), whereas 25(OH)D₃ levels were not (P = .36). PTH levels were comparable across groups 1 through 3a, but they were significantly higher in groups 3b and 4 (P<.0001).Conclusion: In our series of PHPT patients, PTH levels did not rise as a result of renal impairment until GFR decreased below 45 mL/min/1.73 m².Abbreviations: 25(OH)D₃ = 25-hydroxyvitamin D₃ CKD-EPI = Chronic Kidney Disease-Epidemiology Collaboration GFR = glomerular filtration rate K/DOQI = National Kidney Foundation Disease Outcomes Quality Initiative KDIGO = Kidney Disease: Improving Global Outcomes MDRD = Modification of Diet in Renal Disease PHPT = primary hyperparathyroidism PTH = parathyroid hormone     

The Associations Between Hypovitaminosis D,Higher Pth Levels With Bone Mineral Densities,And Risk Of The 10-Year Probability Of Major Osteoporotic Fractures In Chinese Patients With T2Dm

Objective: In the current study, we investigated the vitamin D status, and its relationships with parathyroid hormone (PTH) levels, bone mineral density (BMD), and the 10-year probability of fractures in Chinese patients with type 2 diabetes mellitus (T2DM).Methods: This was a cross-sectional study of 785 patients. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). Serum levels of 25-hydroxyvitamin D (25(OH)D) and intact PTH were also quantified. The 10-year probability of fracture risk (major osteoporotic fracture &lsqb;MOF] and hip fracture &lsqb;HF]) was assessed using the fracture risk assessment tool (FRAX).Results: The prevalence of vitamin D deficiency was 82.3%, and the mean 25(OH)D level was 36.9 ± 15.2 nmol/L. The adequate group had higher BMDs at the FN and TH and lower MOF risk than the inadequate groups. Lower 25(OH)D was associated with higher PTH (r = -0.126, P<.001). PTH was negatively correlated with BMDs at 3 sites and positively correlated with MOF and HF, but this relationship disappeared in the adequate subgroup. Multivariate stepwise regression analysis revealed that PTH was the determinant of MOF (standard β = 0.073, P = .010) and HF (standard β = 0.094, P = .004).Conclusion: Our results identified a significantly high rate of vitamin D deficiency among Chinese patients with T2DM. PTH is an important risk factor responsible for the higher 10-year probability of osteoporotic fractures in diabetic patients, especially in those with lower vitamin D levels.Abbreviations: AKP = alkaline phosphatase; ALB = serum albumin; BMD = bone mineral density; BMI = body mass index; Ca = calcium; CKD = chronic kidney disease; Cr = creatinine; FN = femoral neck; FRAX = fracture risk assessment tool; HbA1c = glycated hemoglobin A1c; HF = hip fracture; L2-4 = lumbar spine; MOF = major osteoporotic fracture; 25(OH)D = 25-hydroxyvitamin D; P = phosphorus; PTH = parathyroid hormone; T2DM = type 2 diabetes mellitus; TH = total hip; UA = uric acid     

Asymptomatic Primary Hyperparathyroidism Exists in North India: Retrospective Data from 2 Tertiary Care Centers

Objective: Primary hyperparathyroidism (PHPT) has evolved into an asymptomatic disease in the west. In contrast, classic symptoms of PHPT have been reported to be common in the east. Here we describe clinical and biochemical profiles of patients diagnosed with PHPT between 2009 and 2012.Methods: This was a retrospective study conducted at 2 tertiary care centers in north India. All patients who underwent evaluation and surgery for primary hyperparathyroidism (PHPT) from January 2009 to December 2012 were included.Results: A total of 50 patients were studied between 2009 and 2012. Among them 31 (62%) were symptomatic and 19 (38%) were asymptomatic. The mean age (SD) was 48.3 (15.8) years, and the female to male ratio was 1.9:1. None of the patients had brown tumors or bone deformities. The asymptomatic group had significantly lower median adenoma weight (0.57 vs. 3.4 g, P<.05), a higher mean age (57.3 vs. 42.8 years, P<.05), and a lower median intact parathyroid hormone (iPTH) level (254.5 vs. 295 pg/mL, P<.05) compared to the symptomatic group. Adenoma weight was positively correlated with baseline serum calcium, iPTH, and alkaline phosphatase (ALP) levels.Conclusion: The asymptomatic form of PHPT was found in a significant percentage of north Indian patients in this study. Asymptomatic PHPT patients were older in age and had lower parathyroid adenoma weights and iPTH levels compared to symptomatic PHPT patients. Positive correlations were found between parathyroid adenoma weight and serum calcium, iPTH, and ALP levels.Abbreviations: ALP = alkaline phosphatase iPTH = intact parathyroid hormone MIBI = 2-methoxyisobutylisonitrile 25(OH)D = 25-hydroxyvitamin D3 PHPT = primary hyperparathyroidism PTH = parathyroid hormone     

Kidney mitochondrial metabolism of 25-hydroxyvitamin D3,: Evaluation of in vitro cation modulation

Oxidative phosphorylation and 1 α,25-dihydroxyvitamin D₃ [lα,25-(OH)₂D₃]synthesis in isolated mitochondria were decreased by the addition of strontium. Calcium effected a similar inhibition of 1α,25-(OH)₂D₃ synthesis which correlated with cation-induced mitochondrial swelling. The ultrastructural changes were found to be a consequence of experimental conditions and not a prerequisite for suppressed 1α,25-(OH)₂D₃ synthesis. Dietary administration of strontium or calcium also resulted in a decreased rate of 1α,25-(OH)₂D₃ synthesis; however, the decrease in 1-hydroxylase activity was accompanied by an induction of mitochondrial 25-hydroxyvitamin D₃ 24-hydroxylase activity. Such an in vivo-prompted mitochondrial response occurred in the absenee of morphological changes or extensive loss of oxidative phosphorylation activity. In contrast, no induction of 24-hydroxylase activity could be observed in acute studies using isolated mitochondria. Therefore, the in vitro action of calcium and strontium does not appear to reflect the in vivo mechanism whereby the cations act to change renal 25-hydroxyvitamin D₃ (25-OHD₃) hydroxylation. Results from in vitro studies corcerning the action of calcium to alter renal 25-OHD₃ metabolism should be interpreted in light of the cation's capacity to decrease oxidative phosphorylation and the subsequent intramitochondrial generation of NADPH.     

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)     

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)