Pettifor J M, Bikle D D, Cavaleros M, Zachen D, Kamdar M C, Ross F P
University of the Witwatersand, Johannesburg, South Africa.
Ann Intern Med. 1995 Apr 1;122(7):511-3. doi: 10.7326/0003-4819-122-7-199504010-00006.
To determine the serum level of free 1,25-dihydroxyvitamin D [1,25-(OH)2D] in patients with vitamin D toxicity and to assess the in vitro effect of differing concentrations of vitamin D metabolites on the free serum levels of 1,25-(OH)2D.
11 patients (age range, 8 to 69 years) were studied 10 to 40 days after hospitalization for hypercalcemia.
Serum total 25-hydroxyvitamin D (25-OHD) and 1,25-(OH)2D levels were measured by radioreceptor assays. The percentage of free 1,25-(OH)2D was measured by centrifugal ultrafiltration isodialysis and was used to calculate actual free 1,25-(OH)2D levels. In the in vitro studies, vitamin D metabolites [25-OHD; 24,25-(OH)2D; 25,26-(OH)2D; and 25-OHD-26,23 lactone] were added to normal serum in concentrations expected to occur with vitamin D toxicity. The percentage of free 1,25-(OH)2D was measured by isodialysis.
All patients presented with marked hypercalcemia (mean calcium level, 3.99 +/- 0.33 mmol/L). Serum 25-OHD levels ranged from 847 to 1652 nmol/L, and total 1,25-(OH)2D levels (mean, 106 +/- 86 pmol/L) were elevated in only three patients. The percentage of free 1,25-(OH)2D (mean, 1.023% +/- 0.366%) was elevated in all nine patients in whom it was measured. Actual free 1,25-(OH)2D levels (mean, 856 +/- 600 fmol/L) were elevated in six of the nine patients. Total 1,25-(OH)2D levels were correlated with 25-OHD levels (r = 0.66; P = 0.03), whereas total and free 1,25-(OH)2D levels were highly correlated (r = 0.957; P < 0.001). In the in vitro studies, the percentage of free 1,25-(OH)2D increased after 25-OHD or 24,25-(OH)2D was added.
Although the patients had normal or near-normal total 1,25-(OH)2D values, most patients had elevated free 1,25-(OH)2D levels. These findings suggest that elevated free 1,25-(OH)2D levels might play a role in the pathogenesis of hypercalcemia in vitamin D toxicity.
测定维生素D中毒患者血清中游离1,25 - 二羟基维生素D[1,25-(OH)₂D]水平，并评估不同浓度维生素D代谢产物对血清中游离1,25-(OH)₂D水平的体外影响。
1）对意外摄入兽用维生素D浓缩剂后因维生素D中毒住院患者的病例研究，以及2）体外实验，向正常血清中添加不同浓度的维生素D代谢产物，并观察其对游离1,25-(OH)₂D百分比的影响。
11例患者（年龄范围8至69岁）在因高钙血症住院10至40天后接受研究。
通过放射受体分析法测定血清总25 - 羟基维生素D（25 - OHD）和1,25-(OH)₂D水平。通过离心超滤等渗透析法测量游离1,25-(OH)₂D的百分比，并用于计算实际游离1,25-(OH)₂D水平。在体外研究中，将维生素D代谢产物[25 - OHD；24,25-(OH)₂D；25,26-(OH)₂D；以及25 - OHD - 26,23内酯]以预期在维生素D中毒时出现的浓度添加到正常血清中。通过等渗透析法测量游离1,25-(OH)₂D的百分比。
所有患者均出现明显高钙血症（平均钙水平，3.99±0.33 mmol/L）。血清25 - OHD水平在847至1652 nmol/L之间，仅3例患者的总1,25-(OH)₂D水平（平均，106±86 pmol/L）升高。在测量的9例患者中，游离1,25-(OH)₂D的百分比（平均，1.023%±0.366%）均升高。9例患者中有6例的实际游离1,25-(OH)₂D水平（平均，856±600 fmol/L）升高。总1,25-(OH)₂D水平与25 - OHD水平相关（r = 0.66；P = 0.03），而总1,25-(OH)₂D水平与游离1,25-(OH)₂D水平高度相关（r = 0.957；P < 0.001）。在体外研究中，添加25 - OHD或24,25-(OH)₂D后，游离1,25-(OH)₂D的百分比增加。
尽管患者的总1,25-(OH)₂D值正常或接近正常，但大多数患者的游离1,25-(OH)₂D水平升高。这些发现表明，游离1,25-(OH)₂D水平升高可能在维生素D中毒高钙血症的发病机制中起作用。
