Effect of vitamin D nutrition on disease indices in patients with primary hyperparathyroidism.

In patients with primary hyperparathyroidism, the size of the adenoma is a major determinant of biochemical indices, disease severity, and manner of presentation. However, the large variation in adenoma weight, both within and between populations and a steady decline in parathyroid adenoma weights over time remain largely unexplained. Based on the results in a small number of patients almost two decades ago we proposed that vitamin D nutritional status of the patient explains both the disease manifestations and much of the variation in adenoma size. Accordingly, we examined the relationship between vitamin D nutrition, as assessed by serum levels of 25-hydroxyvitamin D, and parathyroid gland weight, the best available index of disease severity, in a large number of patients (n = 440) with primary hyperparathyroidism. A significant inverse relationship was found between serum 25-hydroxyvitamin D level and log adenoma weight (r = -0.361; p < 0.001). Also, the adenoma weight was significantly related directly to serum PTH, calcium, and alkaline phosphatase as dependent variables. In patients with vitamin D deficiency (defined as serum 25-hydroxyvitamin D levels 15 ng/mL or lower), gland weight, PTH, AP, and adjusted calcium were each significantly higher than in patients with 25-hydroxyvitamin D levels of 16 ng/mL or higher, but serum 1,25-dihydroxyvitamin D levels were similar in both groups. We interpret this to mean that suboptimal vitamin D nutrition stimulates parathyroid adenoma growth by a mechanism unrelated to 1,25-dihydroxyvitamin D deficiency. We conclude that variable vitamin D nutritional status in the population may partly explain the differences in disease presentation.

Deliberate total parathyroidectomy: a potentially novel therapy for tumor-induced hypophosphatemic osteomalacia.

BACKGROUND: Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic metabolic bone disorder that can be cured by removing or ablating the offending tumor. However, when the tumor cannot be localized, lifelong therapy with oral phosphate and calcitriol or cinacalcet with close monitoring is required. CASE REPORT: A 56-year-old man was diagnosed with TIO in 1990. Initial therapy consisted of oral phosphate and calcitriol with symptomatic and biochemical improvement and healing of osteomalacia. Eight years later, hypercalcemic hyperparathyroidism developed, requiring subtotal parathyroidectomy with a transient increase in serum phosphate and normalization of serum calcium and PTH. Recurrent hypercalcemic hyperparathyroidism developed after 10 years of medical therapy. A deliberate total parathyroidectomy produced a prompt rise in serum phosphate into the normal range > 3.0 mg/dL and remained normal during the next 4 years of follow-up, despite continued very high serum fibroblast growth factor-23 levels throughout the 23-year follow-up. CONCLUSION: We report an unusual case of a TIO patient with long-term follow-up who developed recurrent hypercalcemic hyperparathyroidism on long-term oral phosphate therapy. Deliberate total parathyroidectomy normalized serum phosphate despite persistently elevated fibroblast growth factor-23 levels. Total parathyroidectomy offers a potentially novel therapy in some patients with TIO in whom medical therapy is not feasible or the tumor is unresectable.

The effect of endogenous parathyroid hormone in iliac bone structure and turnover in healthy postmenopausal women.

Little is known about the effect of endogenous parathyroid hormone (PTH) on the skeleton in postmenopausal women without hyperparathyroidism. In this study, the effects of PTH on bone were investigated in iliac crest biopsies obtained from 37 healthy white postmenopausal women aged 50-73 years. The results showed that neither cancellous nor cortical bone structure changed with serum PTH levels. In cancellous bone, bone formation (wall thickness, osteoid surface, osteoblast surface, mineralizing surface, and mineral apposition rate) and turnover (bone formation rate at the surface, volume levels, and activation frequency) variables increased with increasing serum PTH levels (all p < 0.05) in univariate analysis. Multiple linear regressions, adjusted for serum 25-OHD, calcium, alkaline phosphatase, age, and BMI, showed that serum PTH level was independently associated with wall thickness, osteoid surface, osteoblast surface, mineralizing surface, and bone formation rate (all p < 0.05). In cortical bone, no histomorphometric variable was correlated with PTH levels. On the endosteal surface, some of the bone formation (osteoid surface, osteoblast surface, mineralizing surface) and turnover (bone formation rate at the bone surface levels and activation frequency) variables were positively correlated with PTH levels (all p < 0.05). None of these variables could be independently predicted by PTH status. We conclude that in healthy postmenopausal women endogenous PTH has a positive effect on bone formation on the cancellous surface. The effects of PTH on the endosteal surface are probably confounded by other factors.

Severe vitamin D deficiency in Arab-American women living in Dearborn, Michigan.

OBJECTIVE: To determine the prevalence and degree of 25-hydroxyvitamin D deficiency in a group of Arab-American women in the largest, most-concentrated Arab-American settlement in the United States and to search for correlations with dress, diet, and use of vitamin D-fortified foods and vitamin supplements. METHODS: In this cross-sectional study, Arab-American women, 18 years and older, who attended an ethnic market on April 7 or 14, 2007, were recruited. Participants were interviewed by bilingual English- and Arabic-speaking investigators using a semi-structured interview to assess dress; demographic variables; medical history; medication use; clinical symptoms associated with vitamin D deficiency (eg, joint or bone pain, muscle weakness); and dietary intake of vitamin D from fortified orange juice, milk, and vitamin supplementation. Blood samples were drawn to measure concentrations of serum calcium, creatinine, phosphorus, alkaline phosphatase, parathyroid hormone, and 25-hydroxyvitamin D. Participants were initially divided into 2 groups based on whether the woman was veiled and further subdivided into 3 groups on the basis of vitamin D intake from supplemented food sources (milk or vitamin D-fortified orange juice) and vitamin pills: unveiled, veiled and taking supplements, and veiled and taking no supplements. RESULTS: Eighty-seven women participated. Serum 25-hydroxyvitamin D levels were uniformly low, with the highest levels in the unveiled group (median [interquartile range]) (8.5 ng/mL [5.75-13.5 ng/mL]) followed by the veiled, supplemented group (7 ng/mL [4-11.5 ng/mL]) and the veiled, unsupplemented group (4 ng/mL [2-6.8 ng/mL]). 25-Hydroxyvitamin D levels were lower in women with less experience in the United States and in those with less education. Vitamin D-fortified orange juice consumption had a greater positive predictive effect on serum 25-hydroxyvitamin D levels than either milk or vitamin pills and may possibly serve as a surrogate marker for vitamin D awareness. CONCLUSIONS: Vitamin D deficiency, as assessed by 25-hydroxyvitamin D concentrations, is endemic in a sample of Arab-American women living in Dearborn, Michigan. These findings potentially identify an important health problem in the largest, most-concentrated Arab-American population in the United States.

Treatment of vitamin D depletion after Roux-en-Y gastric bypass: a randomized prospective clinical trial.

BACKGROUND: A high prevalence (60%) of vitamin D (VitD) depletion, defined as a serum 25-hydroxyvitamin D level of < or =20 ng/mL, is present in preoperative morbidly obese patients. Despite daily supplementation with 800 IU VitD and 1500 mg calcium after Roux-en-Y gastric bypass (RYGB), VitD depletion persists in almost one half (44%) of patients. However, the optimal management of VitD depletion after RYGB and the potential benefits of such treatment are currently unknown. METHODS: A total of 60 VitD-depleted morbidly obese women were randomly assigned to receive 50,000 IU of VitD weekly after RYGB (group 1; n = 30) or no additional VitD after RYGB (group 2; n = 30). All patients received a daily supplement of 800 IU VitD and 1500 mg calcium. The serum calcium, parathyroid hormone, 25-hydroxyvitamin D, bone-specific alkaline phosphatase, urinary N-telopeptide, and bone mineral density were measured preoperatively and 1 year after RYGB. Questionnaires were used to assess other potential sources of VitD, including sunlight exposure and ingestion of VitD-containing foods/liquids. RESULTS: At 1 year after RYGB, VitD depletion and mean 25-hydroxyvitamin D level had improved significantly in group 1 (14% and 37.8 ng/mL, respectively) compared with the values in group 2 (85% and 15.2 ng/mL, respectively; P <.001 for both). A significant 33% retardation in hip bone mineral density decline (P = .043) and a significantly greater resolution of hypertension was seen in group 1 (75% versus 32%; P = .029). No significant adverse effects were encountered from pharmacologic VitD therapy. CONCLUSION: The results of our study have shown that 50,000 IU of VitD weekly after RYGB safely corrects VitD depletion in most women, attenuates cortical bone loss, and improves resolution of hypertension.

Effect of gastric bypass surgery on vitamin D nutritional status.

BACKGROUND: We previously reported a 60% prevalence of vitamin D (VitD) depletion, defined as a 25-hydroxyvitamin D (25-OHD) level of < or =20 ng/mL, in morbidly obese patients preoperatively. We now report the effect of gastric bypass (GB) on the VitD nutritional status in these patients. METHODS: We prospectively studied 108 morbidly obese patients who had undergone GB. Routine postoperative supplementation consisted of 800 IU VitD and 1500 mg calcium daily. Serum calcium, parathyroid hormone, and 25-OHD were measured before and 1 year after GB. RESULTS: The mean patient age was 46 +/- 9 years, 93% were women, and 72% were white. Preoperatively and at 1 year postoperatively, the prevalence of VitD depletion and hyperparathyroidism (HPT) and the mean 25-OHD level was 53% and 44%, 47% and 39%, and 20 and 24 ng/mL, respectively. One year after GB, the percentage of excess weight loss was 67% and demonstrated significant correlations both positively with 25-OHD and inversely with parathyroid hormone. At both intervals, blacks had a greater incidence of VitD depletion than did whites, and, at 1 year after GB, HPT was more common in patients with VitD depletion (55% versus 26%, P = .002). CONCLUSION: With customary supplementation, VitD nutrition is improved after GB, but VitD depletion persists in almost one half of patients, and blacks are at a significantly greater risk than whites. HPT did not improve, and those with VitD depletion had a significantly greater rate of HPT. Additional prospective studies are needed to determine how to optimize VitD nutrition and avoid potential long-term skeletal complications after GB.

Prevalence of vitamin D depletion among morbidly obese patients seeking gastric bypass surgery.

BACKGROUND: Abnormalities in calcium and vitamin D metabolism have been reported after bariatric surgery. The purpose of this study was to evaluate vitamin D nutritional status among morbidly obese patients before gastric bypass surgery. METHODS: We prospectively studied 279 morbidly obese patients seeking gastric bypass surgery for vitamin D nutritional status as assessed by serum 25-hydroxyvitamin D level. In addition, serum samples were analyzed for calcium, alkaline phosphatase (AP), intact parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D. RESULTS: Mean patient age was 43 +/- 9 years; 87% of the study patients were women, and 72% were white. Serum calcium and AP levels were normal in 88% and 89% of the patients, respectively. Vitamin D depletion, defined as serum 25-hydroxyvitamin D level

Analytical and clinical validation of the 25 OH vitamin D assay for the LIAISON automated analyzer.

OBJECTIVE: Methods to assess serum 25 OH vitamin D have improved in accuracy, precision, and ease of use. We describe the analytical and clinical validation of an automated, antibody- and microparticle-based, chemiluminescent immunoassay method for the determination of 25 OH vitamin D. DESIGN AND METHODS: The LIAISON 25 OH Vitamin D assay is a rapid automated method with first results available in 40 min, and a subsequent throughput of 180 samples per hour. Assay performance characteristics of precision and recovery were determined according to the National Committee for Clinical Laboratory Standards (NCCLS) protocols. Analytical and functional sensitivity were determined according to standard protocols. Samples for method comparison studies were obtained from routine clinical samples submitted for 25 OH Vitamin D determination or from apparently healthy normal volunteers. RESULTS: The detection limit for this assay was <2.0 nmol/L across three lots of materials. Functional sensitivity (inter-assay imprecision <20%) was 17.5 nmol/L. Total imprecision (CV) was <15% at 42.5-137.5 nmol/L. Mean (SD) recovery was 101% (13%). The assay was linear on dilution. Comparison with radioimmunoassay (RIA) yielded acceptable correlation (r = 0.88) and clinical equivalence in the range from 37.5 to 150 nmol/L. CONCLUSIONS: The LIAISON 25 OH Vitamin D assay is a rapid, accurate, and precise tool for the measurement of 25 OH vitamin D.