Firek A F, Kao P C, Heath H
Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
J Clin Endocrinol Metab. 1991 Mar;72(3):541-6. doi: 10.1210/jcem-72-3-541.
The cause of hypercalcemia in familial benign hypercalcemia (FBH; also called familial hypocalciuric hypercalcemia) is unclear, although it is PTH dependent. It is also uncertain how plasma PTH levels are related to the severity of biochemical abnormalities in FBH. Because the PTH-related peptide (PTHrP) has many PTH-like actions, it might have a role in the hypercalcemia of FBH. Thus, we studied 29 patients with FBH from 11 families, 29 age- and sex-matched controls, and 42 patients with primary hyperparathyroidism (1 degree HPT), measuring PTH with a highly sensitive two-site immunochemiluminometric assay and the hypercalcemic tumor factor PTH-related peptide (PTHrP) with an extraction/concentration RIA. Plasma PTH values were elevated in 86% of 1 degree HPT patients (36 of 42), but in only 20% of FBH patients, (6 of 29). Plasma PTHrP was elevated in 1 FBH patient, and the group mean value was normal. Plasma PTH was positively correlated with calcium (Ca) in 1 degree HPT (r = 0.66; P less than 0.0001) and in FBH (r = 0.53; P less than 0.004), but the slopes of the regressions were markedly different: 1 degree HPT, 6.72; FBH, 1.61 (P less than 0.0001). There was a negative correlation between PTH and phosphorus (P) in 1 degree HPT (r = -0.39; P less than 0.01) and in FBH (r = -0.41; P less than 0.03), but, again, the slopes differed greatly: 1 degree HPT, -6.57; FBH, -1.95 (P less than 0.0001). There were no correlations between PTHrP and Ca or between PTH and PTHrP. The sums and products of PTH and PTHrP were not better correlated with Ca than PTH alone. Thus, PTH values are lower at given Ca and P levels in patients with FBH than in those with 1 degree HPT, suggesting that PTH is more effective in raising Ca and lowering P in FBH than in 1 degree HPT. The enigma of FBH remains: what molecular defect can simultaneously cause parathyroid cell insensitivity to Ca, enhanced renal tubular reabsorption of Ca, increased renal rejection of P, and enhanced or retained sensitivity to PTH?
家族性良性高钙血症（FBH，也称为家族性低钙尿性高钙血症）中高钙血症的病因尚不清楚，尽管它依赖甲状旁腺激素（PTH）。目前也不确定FBH患者血浆PTH水平与生化异常严重程度之间的关系。由于甲状旁腺激素相关肽（PTHrP）具有许多类似PTH的作用，它可能在FBH的高钙血症中起作用。因此，我们研究了来自11个家族的29例FBH患者、29例年龄和性别匹配的对照以及42例原发性甲状旁腺功能亢进症（1度HPT）患者，采用高灵敏度的双位点免疫化学发光分析法测定PTH，并用提取/浓缩放射免疫分析法测定高钙血症肿瘤因子甲状旁腺激素相关肽（PTHrP）。1度HPT患者中86%（42例中的36例）血浆PTH值升高，但FBH患者中仅20%（29例中的6例）升高。1例FBH患者血浆PTHrP升高，该组平均值正常。1度HPT患者（r = 0.66；P < 0.0001）和FBH患者（r = 0.53；P < 0.004）中血浆PTH与钙（Ca）呈正相关，但回归斜率明显不同：1度HPT为6.72；FBH为1.61（P < 0.0001）。1度HPT患者（r = -0.39；P < 0.01）和FBH患者（r = -0.41；P < 0.03）中PTH与磷（P）呈负相关，但斜率也有很大差异：1度HPT为-6.57；FBH为-1.95（P < 0.0001）。PTHrP与Ca之间或PTH与PTHrP之间无相关性。PTH和PTHrP的总和及乘积与Ca的相关性并不比单独的PTH更好。因此，在给定的Ca和P水平下，FBH患者的PTH值低于1度HPT患者，这表明PTH在FBH中升高Ca和降低P的作用比在1度HPT中更有效。FBH的谜团依然存在：什么样的分子缺陷能同时导致甲状旁腺细胞对Ca不敏感、肾小管对Ca的重吸收增强、肾脏对P的排泄增加以及对PTH的敏感性增强或保持不变？
