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

Fibroblast growth factor 23 (FGF23) promotes phosphaturia and suppresses 1,25-dihydroxyvitamin D [1,25(OH) 2 D] production. PTH also promotes phosphaturia, but, in contrast, stimulates 1,25(OH) 2 D production. The relationship between FGF23 and PTH is unclear, and the acute effect of pharmacologically dosed PTH on FGF23 secretion is unknown. Twenty healthy men were infused with human PTH(1-34) ] at 44 ng/kg/h for 24 h. Compared with baseline, FGF23, 1,25(OH) 2 D, ionized calcium (iCa), and serum N-telopeptide (NTX) increased significantly over the 18-h hPTH(1-34) infusion (p < 0.0001), whereas serum phosphate (PO 4 ) transiently increased and then returned to baseline. FGF23 increased from 35 ± 10 pg/ml at baseline to 53 ± 20 pg/ml at 18 h (p = 0.0002); 1,25(OH) 2 D increased from 36 ± 16 pg/ml at baseline to 80 ± 33 pg/ml at 18 h (p < 0.0001); iCa increased from 1.23 ± 0.03 mM at baseline to 1.46 ± 0.05 mM at hour 18 (p < 0.0001); and NTX increased from 17 ± 4 nM BCE at baseline to 28 ± 8 nM BCE at peak (p < 0.0001). PO 4 was 3.3 ± 0.6 mg/dl at baseline, transiently rose to 3.7 ± 0.4 mg/dl at hour 6 (p = 0.016), and then returned to 3.4 ± 0.5 mg/dl at hour 12 (p = 0.651). hPTH(1-34) infusion increases endogenous 1,25(OH) 2 D and FGF23 within 18 h in healthy men. Whereas it is possible that the rise in PO 4 contributed to the observed increase in FGF23, the increase in 1,25(OH) 2 D was more substantial and longer sustained than the change in serum phosphate. Given prior data that suggest that neither PTH nor calcium stimulate FGF23 secretion, these data support the assertion that 1,25(OH) 2 D is a potent physiologic stimulator of FGF23 secretion.

Hereditary angioedema (HAE) is a rare autosomal dominant disease that commonly manifests with episodes of cutaneous or submucosal angioedema and intense abdominal pain. The condition usually presents due to a deficiency of C1 esterase inhibitor (C1-INH) that leads to the overproduction of bradykinin, causing an abrupt increase in vascular permeability. A less-understood and less-common form of the disease presents with normal C1-INH levels. Symptoms of angioedema may be confused initially with mast cell-mediated angioedema, such as allergic reactions, and may perplex physicians when epinephrine, antihistamine, or glucocorticoid therapies do not provide relief. Similarly, abdominal attacks may lead to unnecessary surgeries or opiate dependence. All affected individuals are at risk for a life-threatening episode of laryngeal angioedema, which continues to be a source of fatalities due to asphyxiation. Unfortunately, the diagnosis is delayed on average by almost a decade due to a misunderstanding of symptoms and general lack of awareness of the disease. Once physicians suspect HAE, however, diagnostic methods are reliable and available at most laboratories, and include testing for C4, C1-INH protein, and C1-INH functional levels. In patients with HAE, management consists of acute treatment of an attack as well as possible short- or long-term prophylaxis. Plasma-derived C1-INH, ecallantide, icatibant, and recombinant human C1-INH are new treatments that have been shown to be safe and effective in the treatment of HAE attacks. The current understanding of HAE has greatly improved in recent decades, leading to growing awareness, new treatments, improved management strategies, and better outcomes for patients.

SummaryBackground and objectives Fibroblast growth factor 23 is a phosphate-and vitamin D-regulating hormone. The objective of this study was to determine the effect of ergocalciferol administration on fibroblast growth factor 23 levels in healthy vitamin D-deficient subjects.Design, setting, participants, & measurements In this 12-week trial conducted in a clinical research center, 18-to 45-year-old subjects (n=90) with 25-hydroxyvitamin D levels #20 ng/ml (by chemiluminescent immunoassay) were randomized to weekly ergocalciferol treatment of 50,000 international units or placebo, while consuming a self-selected diet. Changes in fibroblast growth factor 23, 25-hydroxyvitamin D (by liquid chromatography/ tandem mass spectroscopy), 1,25-dihydroxyvitamin D, parathyroid hormone, and serum phosphate were measured.Results Mean 25-hydroxyvitamin D (P,0.0001), 1,25-dihydroxyvitamin D (P=0.01), and fibroblast growth factor 23 (P=0.003) increased in the treatment versus placebo group. In the treatment group, 25-hydroxyvitamin D increased from 1867 to 40612 ng/ml at week 4 (P,0.0001) and remained stable at 43612 ng/ml at week 12 (P,0.0001); 1,25-dihydroxyvitamin D increased from 42617 to 52618 pg/ml at week 4 (P,0.001) and then remained stable, and fibroblast growth factor 23 increased from 43617 to 60633 pg/ml at week 8 (P=0.001) and 74642 pg/ml at week 12 (P,0.0001). Urinary phosphate excretion increased within the treatment group, but parathyroid hormone and serum phosphate were unchanged.Conclusions Ergocalciferol administration increases circulating fibroblast growth factor 23. When measuring fibroblast growth factor 23, concurrent 25-hydroxyvitamin D measurements should be obtained, because vitamin D deficiency may lower circulating fibroblast growth factor 23 levels.