Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited

OBJECTIVES: Sunlight exposure of the skin is known to be the most important source of vitamin D. The aims of this study were: (i) to estimate vitamin D status amongst sunlight-deprived individuals (veiled Arab women, veiled ethnic Danish Moslem women and Danish controls); and (ii) through food intake analysis to estimate the oral intake of vitamin D necessary to keep a normal vitamin D status in sunlight-deprived individuals. DESIGN: Cross-sectional study amongst randomly selected Moslem women of Arab origin living in Denmark. Age-matched Danish women were included as controls. To control for racial differences, a group of veiled ethnic Danish Moslem women (all Caucasians) was included. SETTING: Primary Health Care Centre, City Vest and Department of Endocrinology and Metabolism C, University Hospital of Aarhus, Aarhus Amtssygehus, Aarhus, Denmark. SUBJECTS: Sixty-nine Arab women (60 veiled, nine non-veiled) and 44 age-matched Danish controls were randomly selected amongst patients contacting the primary health care centre for reasons other than vitamin D deficiency. Ten ethnic Danish Moslem women were included through a direct contact with their community. MAIN OUTCOME MEASURES: Serum levels of 25-hydroxyvitamin D were used as estimates of vitamin D status. Intact parathyroid hormone (PTH) was used to control for secondary hyperparathyroidism. Alkaline phosphatase and bone-specific alkaline phosphatase were used as markers for osteomalacic bone involvement. Oral intake of vitamin D and calcium were estimated through a historical food intake interview performed by a trained clinical dietician. RESULTS: Veiled Arab women displayed extremely low values of 25-hydroxyvitamin D: 7.1 +/- 1.1 nmol L-1, compared with 17.5 +/- 2. 3 (P < 0.002) in ethnic Danish Moslems and 47.1 +/- 4.6 (P < 10-17) in Danish controls. PTH was increased amongst veiled Arab women: 15. 6 +/- 1.8 pmol L-1, compared with 5.7 +/- 1.4 in ethnic Danish Moslems and 2.7 +/- 0.3 (P < 10-6) in Danish controls. The vitamin D intake (including food supplementation) was very low amongst Arab women: 1.04 microg day-1, compared with 13.53 amongst ethnic Danish Moslems and 7.49 amongst Danish controls (P < 0.0005). CONCLUSIONS: Severe vitamin D deficiency is prevalent amongst sunlight-deprived individuals living in Denmark. In veiled Arab women, vitamin D deficiency is the result of a combination of limitations in sunlight exposure and a low oral intake of vitamin D. The oral intake of vitamin D amongst veiled ethnic Danish Moslems was, however, very high, at 13.53 microgram (approximately 600 IU), but they were still vitamin D-deficient. Our results suggest that the daily oral intake of vitamin D in sunlight-deprived individuals should exceed 600 IU; most probably it should be 1000 IU day-1 to secure a normal level of 25-hydroxyvitamin D. This finding is in contrast with the commonly used RDA (recommended daily allowance) for adults in Europe: 200 IU day-1.     

CASR基因新发变异致新生儿重症甲状旁腺功能亢进症1例报告

新生儿重症甲状旁腺功能亢进症是一种罕见的危及生命的疾病,在新生儿期表现为严重的高钙血症、甲状旁腺功能亢进和骨质减少。患儿,女,14日龄,生后4天起病,表现为高胆红素血症、纳差、反应差、肌张力低下,严重的高钙血症和甲状旁腺功能亢进。基因检测显示,CASR基因存在未报道过的c.888C > A (p.Ser296Arg)(来源于父亲)、c.1576G > T (p.Glu526Ter)(来源于母亲)复合杂合变异。患儿经多次唑来膦酸静脉滴注,吸吮力、反应及肌张力有好转,血钙开始明显下降但一周后又升高。生后54天患儿行一侧甲状旁腺切除术,血钙有所下降,于生后64天出院。生后17月随访,患儿体格和神经发育迟缓。NSHPT由CASR基因失活变异引起,表现为严重的高钙血症和甲状旁腺功能亢进,伴生长发育迟缓。甲状旁腺全切除术是首选治疗手段,双膦酸盐可能具有一定的疗效。     

钙性尿毒症性小动脉病(附3例报告)

目的：通过3例钙化防御（钙性尿毒症性小动脉病）病例总结，介绍钙化防御的诊断、预防及治疗。方法：回顾性总结3例尿毒症继发性甲旁亢并发的钙化防御。结果：例1在手部、双肘、头部及背部出现网状紫斑及多发性皮下肿块。例2在脚趾根部出现痛性网状紫斑及皮肤溃疡。例3表现为足跟部及脚趾痛性网状紫斑和干性坏死。X线照片3例均显示病变附近软组织钙化或血管钙化。例1接受甲状旁腺内酒精注射治疗后，继发性甲旁亢得到控制，皮下肿块及软组织钙化基本消失。例2应用低钙透析液透析后溃疡面缩小，例2和例3作了坏死组织切除，最后死亡。结论：钙化防御一旦发生，预后不良，值得国内同道加以注意。     

Serum nuclear factor IB as a novel and noninvasive indicator in the diagnosis of secondary hyperparathyroidism

BackgroundChronic renal failure (CRF) referred to chronic progressive renal parenchymal damage caused by various causes, with metabolite retention and imbalance of water, electrolyte, and acid‐base balance as the main clinical manifestations. Secondary hyperparathyroidism (sHPT) was a common complication in maintenance hemodialysis patients with CRF. Nuclear factor IB (NFIB) was a newly found tumor suppressor gene in various cancers. The present study aimed to illustrate the role of NFIB in sHPT clinical diagnosis and treatment response.MethodsA retrospective, case‐control study, including 189 patients with sHPT and 106 CRF patients without sHPT, compared with 95 controls. Serum NFIB and 1,25(OH)₂D₃ levels were measured by RT‐qPCR and ELISAs, respectively. ROC analysis was conducted to verify the diagnostic value of NFIB in sHPT. Spearman''s correlation analysis was conducted to verify the association between NFIB and bone mineral density (BMD) scores. After 6 months of treatment, the variance of NFIB and 1,25(OH)₂D₃ in different groups was recorded.ResultsThe expression of NFIB was significantly lower in serum samples from sHPT and non‐sHPT CRF patients, compared to controls. Clinicopathological information verified sHPT was associated with NFIB, parathyroid hormone (PTH), serum calcium, serum phosphorus, time of dialysis, and serum 1,25(OH)₂D₃ levels. Spearman''s correlation analysis illustrated the positive correlation between NFIB levels and BMD scores. At receiver operator characteristic (ROC) curve analysis, the cutoff of 1.6508 for NFIB was able to identify patients with sHPT from healthy controls; meanwhile, NFIB could also discriminate sHPT among CRF patients as well (cutoff = 1.4741). Furthermore, we found that during 6 months of treatment, NFIB levels were gradually increased, while PTH and serum P levels were decreased.ConclusionsSerum NFIB was a highly accurate tool to identify sHPT from healthy controls and CRF patients. Due to its simplicity, specificity, and sensitivity, this candidate can be proposed as a first‐line examination in the diagnostic workup in sHPT.     

继发性甲状旁腺功能亢进症术后低钙血症相关因素分析

目的 探讨继发性甲状旁腺功能亢进症（SHPT）患者术后发生低钙血症的相关因素。方法 回顾性分析62例接受了双侧甲状旁腺全切除术+前臂甲状旁腺自体移植术的SHPT患者的临床资料,包括性别、年龄、透析类型、透析时间、体质量、术前术后生化指标等。采用多因素Logistic回归分析模型分析术后发生低钙血症的独立危险因素。结果 所有患者术中切除甲状旁腺后15 min 甲状旁腺激素（PTH）水平均下降80%以上,术后24 h PTH水平降至20 ~ 30 pg/ml;血钙水平于术后24 h明显下降,48 h降至低值。多因素Logistic回归分析结果显示透析方式（OR = 0.173,P = 0.038）、术前PTH水平（OR = 1.003,P < 0.001）、术前肌酐水平（OR = 1.004,P = 0.001）是术后低钙血症的独立影响因素。结论 腹透透析方式、术前PTH水平偏高、术前肌酐水平偏低是甲状旁腺全切除术+前臂甲状旁腺自体移植术后出现低钙血症的独立危险因素。     

Metastatic microcalcification in the lungs and stomach due to hyperparathyroidism: A case report

We present a case of a 34-year-old man who was admitted to our hospital with a six-month history of nausea and vomiting that had worsened over the past two weeks. Diagnosis of primary hyperparathyroidism (PHPT) due to a single parathyroid adenoma was confirmed by laboratory results and imaging but following pharmacological therapy the patient developed a dry cough. Single-photon emission tomography/computed tomography (SPECT/CT) with technetium-99m-diphosphonate (^99mTc-MDP) was used to assist in the diagnosis and results showed diffuse metastatic microcalcification in the lungs and stomach. The patient underwent right parathyroidectomy and ^99mTc-MDP SPECT/CT scan six months later showed a significantly reduced radioactive distribution in the lungs and none in the stomach. Diffuse metastatic microcalcification in the lungs and stomach due to PHTP is rare and can easily be misdiagnosed.     

Comparative Effects of Etelcalcetide and Maxacalcitol on Serum Calcification Propensity in Secondary Hyperparathyroidism: A Randomized Clinical Trial

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Hyperparathyroidism secondary to hypovitaminosis D in hypoalbuminemic is less intense than in normoalbuminemic patients: a prevalence study in medical inpatients in southern Brazil

Hypovitaminosis D has been reported in tropical countries, but this hormone has seldom been studied in Brazil. Our purpose was to study the prevalence of hypovitaminosis D in patients hospitalized in internal medicine wards in Southern Brazil. Possible associated factors were studied. We studied 81 adult patients in early spring. Mean serum 25(OH)D was 12±8.57 ng/mL; hypovitaminosis D was severe (<10 ng/mL) in 27 (33.3%) patients, and moderate (≥10 ng/mL and <20 ng/mL) in 36 (44.5%) patients. Clinical evaluation did not yield any data associated with hypovitaminosis D. Serum 25(OH)D levels of up to 20 ng/mL were associated with decreased mean serum total calcium (p=0.001), ionized calcium (p=0.01), and phosphorus (p=0.044) levels, and increased mean serum PTH level (p=0.001). In a multiple regression model, serum PTH level was independently affected by serum total calcium (p=0.01), phosphorus (p=0.009), and albumin (p=0.009) levels. Hypovitaminosis D patients had lower mean serum albumin levels (p=0.004), and serum 25(OH)D levels were directly correlated to serum albumin levels (p<0.0001). Albumin influenced independently PTH response to hypovitaminosis D; normoalbuminemic hypovitaminosis D patients had higher mean serum PTH than hypoalbuminemic patients. Conclusion: Hypovitaminosis D prevalence was very high in medical inpatients in Southern Brazil, in early spring. Nevertheless, secondary hyperparathyroidism was less intense in hypoalbuminemic hypovitaminosis D patients suggesting that in these patients free serum 25(OH)D was closer to normal.     

Paricalcitol for Secondary Hyperparathyroidism in Renal Transplantation

Secondary hyperparathyroidism contributes to post-transplant CKD mineral and bone disorder. Paricalcitol, a selective vitamin D receptor activator, decreased serum parathyroid hormone levels and proteinuria in patients with secondary hyperparathyroidism. This single-center, prospective, randomized, crossover, open-label study compared the effect of 6-month treatment with paricalcitol (1 μg/d for 3 months and then uptitrated to 2 µg/d if tolerated) or nonparicalcitol therapy on serum parathyroid hormone levels (primary outcome), mineral metabolism, and proteinuria in 43 consenting recipients of renal transplants with secondary hyperparathyroidism. Participants were randomized 1:1 according to a computer-generated sequence. Compared with baseline, median (interquartile range) serum parathyroid hormone levels significantly declined on paricalcitol from 115.6 (94.8–152.0) to 63.3 (52.0–79.7) pg/ml (P<0.001) but not on nonparicalcitol therapy. At 6 months, levels significantly differed between treatments (P<0.001 by analysis of covariance). Serum bone-specific alkaline phosphatase and osteocalcin decreased on paricalcitol therapy only and significantly differed between treatments at 6 months (P<0.001 for all comparisons). At 6 months, urinary deoxypyridinoline-to-creatinine ratio and 24-hour proteinuria level decreased only on paricalcitol (P<0.05). L3 and L4 vertebral mineral bone density, assessed by dual-energy x-ray absorption, significantly improved with paricalcitol at 6 months (P<0.05 for both densities). Paricalcitol was well tolerated. Overall, 6-month paricalcitol supplementation reduced parathyroid hormone levels and proteinuria, attenuated bone remodeling and mineral loss, and reduced eGFR in renal transplant recipients with secondary hyperparathyroidism. Long-term studies are needed to monitor directly measured GFR, ensure that the bone remodeling and mineral effects are sustained, and determine if the reduction in proteinuria improves renal and cardiovascular outcomes.     

继发性甲状旁腺功能亢进患者甲状旁腺切除术后重度低钙血症相关因素分析

目的：探讨继发性甲状旁腺功能亢进（SHPT）患者甲状旁腺切除术后重度低钙血症（SHC）相关因素,进而建立SHC防治策略。方法回顾性分析2012年3月—2014年5月在我院行甲状旁腺切除治疗的S H P T病例资料。行单因素及多因素分析明确S HC的独立影响因素,确定定量因素界值。结果共收集88例病例资料,术后发生S HC46例（52.3％）。单因素分析显示年龄、ALP、iPTH、切除的甲状旁腺数（RTPN）具有统计学显著差异,多因素分析显示年龄、iPTH、RTPN≥4为SHC的独立影响因素,确定的界值为年龄48岁（PPV68.8％,NPV67.5％）和iPT H 1750 pg／ml（PPV85.4％,NPV87.5％）。结论年龄、甲状旁腺激素水平、甲状旁腺切除数量为SHPT患者甲状旁腺切除术后SHC的独立影响因素。选择性地对高危患者实施静脉补钙,选择合理的手术方式,可作为防治S HC的初步策略。