Kautzky-Willer A, Pacini G, Niederle B, Schernthaner G, Prager R
Second Medical Clinic, University of Vienna, Austria.
Clin Endocrinol (Oxf). 1992 Aug;37(2):147-55. doi: 10.1111/j.1365-2265.1992.tb02299.x.
Primary hyperparathyroidism (pHPT) is associated with hypertension, hyperinsulinaemia, and insulin resistance. The present study investigated the causes of these metabolic disturbances by quantifying insulin sensitivity and glucose effectiveness, and by assessing the time course of beta-cell insulin secretion and hepatic insulin extraction, during a dynamic condition such as after an intravenous glucose load. In addition, we evaluated the possible link between metabolic disorders and high blood pressure.
We studied 16 patients with pHPT, before and 12 weeks after parathyroidectomy; eight of these patients were re-evaluated one year after surgery. The control group consisted of 18 healthy volunteers.
All subjects underwent an oral and a frequently sampled intravenous glucose tolerance test. The data from the intravenous glucose tolerance test were analysed by means of the minimal model technique which yields relevant parameters to comprehend the metabolic status of the single individual.
The glucose intolerance condition was characterized by a severely impaired insulin sensitivity in pHPT (3.2 +/- 0.5 vs 9.5 +/- 1.5 x 10(4)/min/(microU/ml) of control subjects; P < 0.001), as well as by a reduced glucose effectiveness, (0.02 +/- 0.002 vs 0.03 +/- 0.003/min of control subjects; P < 0.04). Total insulin secretion during the 4 hours of the test was almost twofold elevated in comparison to the control subjects (32795 +/- 4769 vs 16864 +/- 1850 pM, P < 0.004) and its basal component significantly correlated with the high blood pressure. Hepatic extraction of insulin was significantly increased in pHPT (85 +/- 2 vs 76 +/- 2%, P < 0.03), possibly as a compensatory mechanism of hypersecretion, which however did not prevent peripheral hyperinsulinaemia in pHPT. Patients with pHPT were divided into two subgroups with normal and impaired glucose tolerance. The patients with impaired glucose tolerance had a significant reduction of first phase insulin response, although their basal and stimulated insulin levels were higher. Tissue insulin sensitivity and glucose effectiveness did not significantly differ between the two subgroups. After surgery, all the biochemical parameters (former hypercalcaemia, hypophosphataemia, elevated parathormone levels) were normalized, insulin sensitivity significantly improved (6 +/- 1 x 10(4)/min/(microU/ml), P < 0.001), whereas glucose effectiveness remained completely unchanged. Basal and stimulated insulin responses were insignificantly lowered after surgery, and hepatic extraction did not change either.
Patients with pHPT exhibited decreased insulin sensitivity and insulin hypersecretion. The latter is only partially ameliorated by increased hepatic insulin extraction. After surgery, although the biochemical abnormalities were fully reversible, the metabolic changes improved only partially.
原发性甲状旁腺功能亢进症（pHPT）与高血压、高胰岛素血症及胰岛素抵抗相关。本研究通过在静脉葡萄糖负荷等动态情况下定量胰岛素敏感性和葡萄糖效能，并评估β细胞胰岛素分泌及肝脏胰岛素摄取的时间进程，来探究这些代谢紊乱的原因。此外，我们还评估了代谢紊乱与高血压之间可能存在的联系。
我们研究了16例pHPT患者，分别在甲状旁腺切除术前及术后12周进行观察；其中8例患者在术后1年进行了重新评估。对照组由18名健康志愿者组成。
所有受试者均接受了口服及频繁采样的静脉葡萄糖耐量试验。静脉葡萄糖耐量试验的数据采用最小模型技术进行分析，该技术可得出相关参数以了解个体的代谢状态。
葡萄糖不耐受情况的特征为pHPT患者的胰岛素敏感性严重受损（3.2±0.5 vs对照组9.5±1.5×10⁴/min/(μU/ml)；P<0.001），同时葡萄糖效能降低（0.02±0.002 vs对照组0.03±0.003/min；P<0.04）。试验4小时内的总胰岛素分泌相较于对照组几乎升高了两倍（32795±4769 vs 16864±1850 pM，P<0.004），其基础成分与高血压显著相关。pHPT患者的肝脏胰岛素摄取显著增加（85±2 vs 76±2%，P<0.03），这可能是一种高分泌的代偿机制，然而这并未阻止pHPT患者外周血胰岛素水平升高。pHPT患者被分为糖耐量正常和受损的两个亚组。糖耐量受损的患者尽管基础及刺激后的胰岛素水平较高，但第一相胰岛素反应显著降低。两个亚组之间的组织胰岛素敏感性和葡萄糖效能无显著差异。术后，所有生化参数（既往的高钙血症、低磷血症、甲状旁腺激素水平升高）均恢复正常，胰岛素敏感性显著改善（6±1×10⁴/min/(μU/ml)，P<0.001），而葡萄糖效能则完全未变。术后基础及刺激后的胰岛素反应略有降低，肝脏摄取也未改变。
pHPT患者表现出胰岛素敏感性降低及胰岛素分泌过多。后者仅通过肝脏胰岛素摄取增加得到部分改善。术后，尽管生化异常完全可逆，但代谢变化仅部分得到改善。
