维生素 D 充足的绝经后低骨量和特发性继发性甲状旁腺功能亢进症妇女中，甲状旁腺激素刺激 1,25-二羟维生素 D 生成减少。
Reduced parathyroid hormone-stimulated 1,25-dihydroxyvitamin d production in vitamin d sufficient postmenoposual women with low bone mass and idiopathic secondary hyperparathyroidism.
机构信息
University of Maryland School of Medicine, Baltimore, MD 21201, USA.
出版信息
Endocr Pract. 2013 Jan-Feb;19(1):91-9. doi: 10.4158/EP12151.OR.
OBJECTIVE
Distinguishing secondary hyperparathyroidism (sHPT) from eucalcemic primary hyperparathyroidism (EC-pHPT) is important. The objective of this study was to measure parathyroid hormone (PTH)-stimulated production of 1α,25-dihydroxyvitamin D (1,25[OH]2D) in early postmenopausal patients with idiopathic sHPT, who also fit the criteria for EC-pHPT, compared to age-matched controls.
METHODS
In this pilot case-control study, postmenopausal women aged 44 to 55 years with normal serum calcium (Ca), glomerular filtration rate (GFR) ≥65 mL/min, and 25-hydroxyvitamin D (25[OH]D) ≥75 nmol/L (30 ng/mL) were given an 8 hour infusion of PTH(1-34), 12 pmol/kg/h. Patients (n = 5) had elevated PTH, normal 1,25(OH)2D, and no hypercalciuria. Controls (n = 5) had normal PTH. At baseline, 4, and 8 hours, serum Ca, creatinine (Cr), phosphorus (P), 1,25(OH)2D, fibroblast growth factor (FGF23), and 24,25(OH)2D as well as urine Ca, P, Cr, and cAMP/GFR were measured. The fractional excretion of calcium (FeCa) and tubular reabsorption of phosphorus (TMP)/GFR were calculated.
RESULTS
Patients had lower 1,25(OH)2D levels (± SD) than controls at 4 (39.8 ± 6.9 versus 58.8 ± 6.7; P = .002) and 8 hours (56.4 ± 9.2 versus 105 ± 2.3; P = .003) of PTH infusion, attenuated after adjusting for higher body mass index (BMI) in patients (P = .05, .04), respectively. The 24,25(OH)2D levels were lower in patients than controls (1.9 ± 0.6 versus 3.4 ± 0.6, respectively; P = .007). No differences were seen in serum Ca or P, urine cAMP/GFR, TRP/GFR, FeCa, or PTH suppression at 8 hours (patients 50%, controls 64%).
CONCLUSION
Vitamin D sufficient patients who fit the criteria for EC-pHPT had reduced PTH-stimulated 1,25(OH)2D compared to controls, partially attributable to their higher BMI. Other causes of reduced 1,25(OH)2D production ruled out were excessive catabolism of vitamin D metabolites, elevated FGF23, and CYP27B1 mutation. Elevated BMI and idiopathic reduced PTH-stimulated 1,25(OH)2D production should be considered in the differential of sHPT.
目的
区分继发甲状旁腺功能亢进症（sHPT）和无高钙血症的原发性甲状旁腺功能亢进症（EC-pHPT）很重要。本研究的目的是测量在符合 EC-pHPT 标准的绝经后妇女中，甲状旁腺激素（PTH）刺激产生的 1α,25-二羟维生素 D（1,25[OH]2D），这些妇女患有特发性 sHPT，并与年龄匹配的对照组进行比较。
方法
在这项初步病例对照研究中，年龄在 44 至 55 岁之间的绝经后妇女，血清钙（Ca）正常（Ca）、肾小球滤过率（GFR）≥65mL/min，25-羟维生素 D（25[OH]D）≥75nmol/L（30ng/mL），给予 PTH（1-34）8 小时输注，12pmol/kg/h。患者（n=5）的 PTH 升高，1,25（OH）2D 正常，无高钙尿症。对照组（n=5）的 PTH 正常。在基线、4 小时和 8 小时，测量血清 Ca、肌酐（Cr）、磷（P）、1,25（OH）2D、成纤维细胞生长因子 23（FGF23）和 24,25（OH）2D 以及尿 Ca、P、Cr 和 cAMP/GFR。计算钙的分数排泄（FeCa）和磷的管状重吸收（TMP）/GFR。
结果
与对照组相比，患者在 PTH 输注 4 小时（39.8±6.9 与 58.8±6.7；P=0.002）和 8 小时（56.4±9.2 与 105±2.3；P=0.003）时的 1,25（OH）2D 水平较低，在调整患者较高的体重指数（BMI）后，这种差异减弱（P=0.05，P=0.04）。与对照组相比，患者的 24,25（OH）2D 水平较低（分别为 1.9±0.6 和 3.4±0.6，P=0.007）。两组在 8 小时时的血清 Ca 或 P、尿 cAMP/GFR、TRP/GFR、FeCa 或 PTH 抑制率均无差异（患者为 50%，对照组为 64%）。
结论
符合 EC-pHPT 标准的维生素 D 充足的患者与对照组相比，PTH 刺激的 1,25（OH）2D 减少，部分原因是其 BMI 较高。已排除其他导致 1,25（OH）2D 生成减少的原因，包括维生素 D 代谢物的过度代谢、FGF23 升高和 CYP27B1 突变。在 sHPT 的鉴别诊断中，应考虑 BMI 升高和特发性 PTH 刺激的 1,25（OH）2D 生成减少。
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