Low Urine Calcium Excretion in African American Patients with Primary Hyperparathyroidism

ObjectiveTo evaluate the prevalence of low urine calcium excretion in African American patients with primary hyperparathyroidism (PHPT), a common disorder associated with bone and renal complications, and to assess the distinction between PHPT and familial hypocalciuric hypercalcemia (FHH), a rare benign genetic disease.MethodsWe conducted a retrospective study on a cohort of 1,297 patients in whom a 24-hour urine study was performed for measurement of urine calcium and creatinine. PHPT was diagnosed if the serum calcium concentration was ≥ 10.5 mg/dL and intact parathyroid hormone (PTH) was ≥ 40 pg/mL. Patients receiving medications that affect urine calcium or with glomerular filtration rate ≤ 30 mL/min were excluded.ResultsNinety-six patients satisfied the diagnostic criteria for PHPT. The African American (n = 70) and non-African American (n = 26) patients did not differ in their mean age, body mass index, glomerular filtration rate, serum PTH, 25-hydroxyvitamin D levels, and 24-hour urine creatinine values. Median values of urine calcium/creatinine (mg/g) were 122 for African American versus 214 for non-African American patients (P = .006). Thirty-one of 70 African American patients (44%) had a urine calcium/creatinine ratio ≤ 100 mg/g, whereas only 2 of 26 non-African American patients (8%) had this value (P = .001).ConclusionThe prevalence of low urine calcium excretion among African American patients with PHPT is unexpectedly high. A threshold of 100 mg/g urine calcium/ creatinine identified 44% of such patients with PHPT as having FHH in this cohort. Therefore, other clinical criteria and laboratory variables should be used to distinguish PHPT from FHH in African American patients with PTH-dependent hypercalcemia. (Endocr Pract. 2011;17: 867-872)     

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)     

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)     

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)     

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)     

Effect of Vitamin D Therapy on Bone Turnover Markers in Postmenopausal Women with Osteoporosis and Osteopenia

ObjectiveTo (7) assess the rate of reduction in bone turnover with vitamin D and bisphosphonate therapies and (2) evaluate the clinical utility of bone-specific alkaline phosphatase (BSAP) in monitoring treatment response.MethodsWe retrospectively reviewed medical records of patients with newly diagnosed osteopenia and osteoporosis from 2002 to 2009 at Loyola University Medical Center. A cohort of postmenopausal women with hip or spine T-scores of less than -1, normal serum creatinine, and no prior vitamin D or bisphosphonate therapy was divided into vitamin D-deficient (n = 29) and vitamin D-sufficient (n = 13) groups. Vitamin D-deficient patients received high-dose vitamin D, whereas vitamin D-sufficient patients received orally administered bisphosphonates. BSAP levels at baseline and 1 year were compared.Resultsvitamin D therapy in the group with vitamin D deficiency led to a 26.7% decrease in BSAP (P < .01). Bisphosphonate therapy in the vitamin D-sufficient group led to a 32.7% decrease in BSAP (P = .01). The magnitude of BSAP change in the 2 study groups (6.74 ± 6.48 μg ∕ L and 8.72 ± 9.94 μgZL) did not differ significantly (P = .45).ConclusionThe results of this study suggest that correction of vitamin D deficiency in patients with osteopenia and osteoporosis can lead to a decrease in bone turnover as measured by BSAP and that the magnitude of this reduction is similar to that achieved with orally administered bisphosphonates. (Endocr Pract. 2011;17:873-879)     

Ethnicity,Clothing Style,and Body Mass Index are Significant Predictors of Vitamin D Insufficiency in Germany

ObjectiveTo analyze risk factors for vitamin D insufficiency in Germany with respect to ethnicity, sex, and clothing style.MethodsWe analyzed the routine diagnostic workups of 1,231 adult (45.9 ± 17.9 years old) German (n = 1,034) and Turk residents (n = 197) referred with nonspecific symptoms to the Thyroid Centers at St. Elisabeth-Hospital in Dorsten, Germany and Bottrop, Germany to assess for metabolic diseases. All subjects underwent a routine examination that consisted of a questionnaire, lab tests for 25-hydroxyvitamin-D (25OHD), and thyroid profile. Turk females with traditional clothing (headscarf and covered legs and arms) were considered to wear “covered clothing.” Logistic-regression was performed to identify factors that could predict vitamin D deficiency (< 20 ng/ mL) and insufficiency (20-30 ng/mL).ResultsVitamin D insufficiency was seen in 33% of Germans and 74.1% of Turks, and vitamin D deficiency was present in 11.3% and 44.2% of Germans and Turks, respectively (P < .001). The mean 25OHD value in Turk females with covered clothes was lower than that in Turk females with conventional clothing (16.3 ± 12.3 vs. 27.2 ± 15.8, P < .001). Vitamin D insufficiency was present in 86.0% of Turk females with covered clothing versus 62.8% with conventional clothing (odds ratio [OR] = 3.6, P = .002). Ethnicity, body mass index (BMI), and clothing style were significant predictors of vitamin D deficiency and insufficiency by logistic regression (P < .001).Conclusions(1) Vitamin D insufficiency among Turk residents in Germany is higher compared to Germans. The highest prevalence was present in Turk females with covered clothing. (2) Monitoring vitamin D in Turk residents in Germany is warranted. (3) Vitamin D supplements and access to facilities with sunlight exposure for females with covered clothing and all individuals with poor diets or limited access to sun exposure may prevent future health burden due to vitamin D insufficiency. (Endocr Pract. 2015; 21:122-127)     

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.     

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     

Impact Of Ethnic Background On Clinical Characteristics And Cardiovascular Risk Factors Among Patients With Primary Hyperparathyroidism

Objective: To compare initial laboratory values and cardiovascular risk factors (CRF) among patients with primary hyperparathyroidism (PHPT) of different ethnic backgrounds.Methods: In this retrospective study, we reviewed 500 charts of PHPT patients who presented at Robert Wood Johnson University Hospital from January 2000 to December 2013. Among these patients were 46 African Americans (AA), 31 Asians (A), 19 Hispanics (H), and 404 Caucasians (C). The following characteristics were compared between the groups: age; body mass index (BMI); levels of serum calcium, intact parathyroid hormone (iPTH), 25-OH vitamin D, and 24-hour urine calcium; and parathyroid adenoma weight. Presence of CRF including BMI, diabetes mellitus, hypertension, and hyperlipidemia were also recorded for comparison. Associations of adenoma weight and several other parameters were also assessed.Results: Among different ethnic groups, AA patients with PHPT had higher iPTH levels compared to the A and C groups (P<.05), while 25-OHD levels were lower in the AA compared to the A and C groups (P<.05). Adenoma weight was significantly greater in AA than in C and A PHPT patients (P<.01). Adenoma weight was positively correlated with iPTH levels (r = 0.493, P <.001) and serum calcium levels (r = 0.255, P<.01). The group BMIs were C: 29.5 ± 6.9, AA: 33.8 ± 10, A: 24.7 ± 3.3, and H: 30.2 ± 6.6. AA patients had a lower rate of renal stones (9%) compared to other groups (21–29%, P<.05).Conclusion: The results of our study indicate that AA patients with PHPT presented with a more severe PHPT profile but had lower 24-hour urine calcium and fewer renal stones. AA patients with PHPT also had higher prevalence of CRF when compared to A and C.Abbreviations:A = AsianAA = African AmericanC = CaucasianCRF = cardiovascular risk factorsH = HispaniciPTH = intact parathyroid hormonePHPT = primary hyperparathyroidismPTH = parathyroid hormone     

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)     

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)     

Calcium,Parathyroid Hormone,and Vitamin D in Patients with Primary Hyperparathyroidism: Normograms Developed from 10000 Cases

ObjectiveTo better define the typical and atypical biochemical profiles of patients with surgically proven primary hyperparathyroidism.MethodsIn this single-center, prospectively conducted study of consecutive patients with surgically proven primary hyperparathyroidism over a 7-year period, we analyzed serum calcium, parathyroid hormone, and 25-hydroxyvitamin D concentrations.ResultsA total of 10 000 patients were included, and more than 210 000 calcium, parathyroid hormone, and 25-hydroxyvitamin D values were evaluated. Both calcium and parathyroid hormone levels demonstrated a Gaussian distribution with the average calcium concentration being 10.9 ± 0.6 mg/dL and the average parathyroid hormone concentration being 105.8 ± 48 pg/mL. The average highest calcium and parathyroid hormone concentrations were 11.4 ± 0.7 mg/dL and 115.3 ± 50 pg/mL, respectively. At least 1 calcium value of 11.0 mg/dL was seen in 87% of patients, but only 21% had 1 or more calcium value above 11.5 mg/dL. Only 7% had a single serum calcium level reaching 12.0 mg/dL. Normocalcemic hyperparathyroidism was seen in just under 3% of patients who had identical findings at surgery. An average parathyroid hormone concentration less than 65 pg/mL was seen in 16%, with 10% of patients who had no high parathyroid hormone values. The average 25-hydroxyvitamin D concentration was 22.4 ± 9 ng/mL, with levels decreasing as calcium levels increased (P < .001); 36% had 25-hydroxyvitamin D levels below 20 ng/mL.ConclusionsPatients with PHPT present with a number of distinct biochemical profiles, but as a group, they present with a near-normal Gaussian distribution of both calcium and parathyroid hormone levels. Either serum calcium or parathyroid hormone remained normal in 13% of patients, yet the findings at surgery are similar to those of patients with elevated calcium or parathyroid hormone. Low 25-hydroxyvitamin D is an expected finding in patients with PHPT, decreasing as serum calcium levels increase. (Endocr Pract. 2011;17:384-394)     

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.     

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     

Primary Hyperparathyroidism During Pregnancy: A Case Series of 8 Patients

Objective: Due to a lack of typical clinical manifestations and physiologic changes in calcium metabolism during pregnancy, primary hyperparathyroidism (PHPT) during pregnancy is commonly underdiagnosed, and treatment during this unique period presents a clinical challenge. Hence, the aim of the present study was to summarize the cases of 8 pregnant patients with PHPT who were treated at our center to provide better clinical insight into this condition.Methods: Our study comprised a retrospective analysis of 8 pregnant PHPT patients and a control group of 22 age-matched, nonpregnant PHPT patients during the same period. Clinical manifestations, biochemical indices, pathologic types, therapeutic strategies, and pregnancy outcomes were compiled, and 25 patients were screened for germline mutations in the MEN1, CDC73, and CaSR genes.Results: The most-common symptoms in the pregnancy group involved the gastrointestinal tract (GIT) in 7/8 cases (87.5%), followed by urinary system involvement (50%) and joint pain (50%). In contrast, GIT symptoms in the control group were significantly less common (31.82%; P = .012). There was a trend of more-severe elevation of serum parathyroid hormone levels in the control group compared to that in the pregnancy group (P = .053). No differences were found in blood-ionized calcium, phosphate, or alkaline phosphatase levels between the two groups. In the pregnancy group, the serum albumin-corrected calcium level was reduced from 3.42 ± 0.66 mmol/L to 2.89 ± 0.46 mmol/L (P = .025) after hydration and medical treatment. Six patients, three of whom were in the second trimester of pregnancy, underwent parathyroidectomy, and 3 patients were after childbirth or had induced labor. Postoperative serum calcium levels were reduced to within the normal range. Fetal/neonatal complications were observed in 4 of 5 patients who had not received surgical treatment during pregnancy. In addition, 2 of 5 pregnant PHPT patients were found to carry MEN1 mutations, whereas no mutations were detected in any of the 20 nonpregnant patients.Conclusion: In this case series of PHPT during pregnancy, the most-common complaint of GIT symptoms may be easily confused with pregnancy reactions, which might contribute to the under- or misdiagnosis of this clinical entity. Patients who did not receive surgical treatment during pregnancy had high incidences of fetal/neonatal complications and worse pregnancy outcomes.Abbreviations: CaSR = calcium-sensing receptor; CDC73 = cell division cycle 73; GIT = gastrointestinal tract; MEN = multiple endocrine neoplasia; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; SCa = serum calcium     

Rapid determination of 25-hydroxy vitamin D3 in swine tissue using an isotope dilution HPLC-MS assay

A rapid method for quantification of 25-hydroxy vitamin D3 in different swine tissues based on isotope dilution HPLC-MS has been developed and validated. Six times deuterated analyte is used as internal standard. The method is fast and can be performed with only 1 g sample. Sample preparation for kidney, liver, muscle and spleen requires only homogenisation and extraction with methanol. An additional enzymatic digest is required for skin, and clean-up of the extract by solid-phase extraction (SPE) is used for adipose tissue and skin. The lower limit of detection varies from 1 ng/g (muscle) to 5 ng/g (adipose and skin). The method has been successfully applied to various tissue samples of pigs fed for 119 days either 2000 IU of vitamin D3 or 50 μg of 25-hydroxy vitamin D3 per kg feed. For animals ingesting 25-OH-D3 supplements the highest tissue contents were observed in the skin (24.8 ± 3.5 ng/g), followed by kidney (14.2 ± 1.5 ng/g), liver and muscle (5.7 ± 0.6 ng/g). The 25-OH-D3 content in the skin was significantly higher in animals ingesting 2000 IU/kg of vitamin D3 (39.5 ± 13.4 ng/g). Levels in selected tissues of some animals were below the lower limit of quantification. No measurable amounts of 25-OH-D3 were found in spleen, abdominal fat and subcutaneous fat of the animals of both groups as well as in the liver, kidney and muscle of the animals ingesting 2000 IU/kg of vitamin D3.     

Podocyte as A Potential Target of Inflammation: Role of Pioglitazone Hydrochloride in Patients With Type 2 Diabetes

ObjectiveTo observe the effects of pioglitazone hydrochloride on urinary sediment podocalyxin and monocyte chemoattractant protein-1 (MCP-1) excretion in patients with type 2 diabetes and to explore its possible renoprotective mechanisms.MethodsNinety-eight patients with uncontrolled type 2 diabetes, who were previously prescribed metformin, acarbose, or both, were randomly assigned to a DP group (add-on pioglitazone; n = 49) or a DS group (add-on sulfonylurea; n = 49).ResultsAfter 12 weeks of treatment, both add-on pioglitazone therapy (the DP group) and add-on sulfonylurea therapy (the DS group) demonstrated a similar improvement in fasting blood glucose and hemoglobin A_1c, but systolic and diastolic blood pressure declined significantly in only the DP group. Moreover, the DP group showed significantly better efficacy in reducing urinary MCP-1 excretion in comparison with the DS group. Furthermore, both urinary albumin and urinary sediment podocalyxin excretion decreased significantly in the DP group but not in the DS group. The urinary sediment podocalyxin to creatinine ratio had a positive correlation with urinary albumin to creatinine ratio (r = 0.624; P < .01) and urinary MCP-1 to creatinine ratio (r = 0.346; P < .01).ConclusionPioglitazone treatment revealed a podocyte-protective capacity in patients with type 2 diabetes, and the underlying mechanisms may be partly attributed to its effective suppression of excessive local renal inflammation. (Endocr Pract. 2012;18:493-498)     

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)