Maghnie M, Strigazzi C, Tinelli C, Autelli M, Cisternino M, Loche S, Severi F
Department of Pediatrics, University, IRCCS Policlinico S. Matteo, Pavia, Italy.
J Clin Endocrinol Metab. 1999 Apr;84(4):1324-8. doi: 10.1210/jcem.84.4.5614.
GH secretion was reevaluated after completion of GH treatment at a mean age of 19.2 +/- 3.2 yr in 35 young adults with childhood-onset GH deficiency (GHD). The patients were subdivided into 4 groups according to their first pituitary magnetic resonance imaging (MRI) findings: group I, 11 patients with isolated GHD (IGHD) and normal pituitary volume (280 +/- 59.4 mm3); group II, 7 patients with IGHD and small pituitary gland (163.1 +/- 24.4 mm3; P = 0.0009 vs. group I); group III, 13 patients (5 with IGHD and 8 with multiple pituitary hormone deficiency) with congenital hypothalamic-pituitary abnormalities such as pituitary hypoplasia (95.8 +/- 39.3 mm3; P < 0.00001 vs. group I and P = 0.003 vs. group II), pituitary stalk agenesis, and posterior pituitary ectopia; and group IV, 4 patients with multiple pituitary hormone deficiency secondary to craniopharyngioma. Pituitary MRI and GH secretory status were reevaluated after GH withdrawal using arginine, insulin induced-hypoglycemia, and sequential arginine-insulin tests. Serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were determined at the time of retesting and 6, 12, and 24 months after discontinuation of treatment in the patients with permanent GHD and after 6 months in those with normal GH responses to stimulation. The patients in groups I and II showed a normal response to stimulation after completion of GH treatment regardless of pituitary size, whereas all patients in groups III and IV still had a GH response of less than 3 microg/L to any of the tests. Pituitary volume normalized in 6 of 7 patients in group II, whereas in all patients in group III MRI studies confirmed the initial findings. Mean IGF-I and IGFBP-3 concentrations at the time of retesting were significantly higher in groups I and II than in groups III and IV. In patients of groups III and IV, mean IGF-I was significantly decreased after 6 and 12 months, whereas IGFBP-3 was significantly decreased 12 months after treatment withdrawal. Our results confirm that a high proportion of children with IGHD and normal or small pituitary show normalization of GH secretion at the completion of GH treatment, whereas GHD is permanent in all patients with pituitary hypoplasia, pituitary stalk agenesis, and posterior pituitary ectopia. IGF-I and IGFBP-3 determinations shortly after GH withdrawal had limited value in the diagnosis of GHD of childhood onset associated with congenital hypothalamic-pituitary abnormalities, but became accurate after 6-12 months. We suggest that patients with GHD and congenital hypothalamic-pituitary abnormalities do not require further investigation of GH secretion, whereas patients with IGHD and normal or small pituitary gland should be retested well before the attainment of adult height.
在平均年龄为19.2±3.2岁时，对35例儿童期起病的生长激素缺乏症（GHD）的年轻成人完成生长激素治疗后，重新评估生长激素分泌情况。根据首次垂体磁共振成像（MRI）结果，将患者分为4组：第一组，11例孤立性生长激素缺乏症（IGHD）且垂体体积正常（280±59.4立方毫米）的患者；第二组，7例IGHD且垂体小（163.1±24.4立方毫米；与第一组相比P = 0.0009）的患者；第三组，13例（5例IGHD和8例多种垂体激素缺乏症）有先天性下丘脑 - 垂体异常，如垂体发育不全（95.8±39.3立方毫米；与第一组相比P < 0.00001，与第二组相比P = 0.003）、垂体柄缺如和垂体后叶异位的患者；第四组，4例继发于颅咽管瘤的多种垂体激素缺乏症患者。在停用生长激素后，使用精氨酸、胰岛素诱发低血糖和序贯精氨酸 - 胰岛素试验重新评估垂体MRI和生长激素分泌状态。在重新检测时以及永久性GHD患者停药后6、12和24个月以及生长激素对刺激反应正常的患者停药后6个月测定血清胰岛素样生长因子I（IGF - I）和IGF结合蛋白 - 3（IGFBP - 3）。第一组和第二组的患者在完成生长激素治疗后，无论垂体大小，对刺激均显示正常反应，而第三组和第四组的所有患者对任何一项试验的生长激素反应仍小于3微克/升。第二组7例患者中有6例垂体体积恢复正常，而第三组所有患者的MRI研究均证实了最初的结果。重新检测时，第一组和第二组的平均IGF - I和IGFBP - 3浓度显著高于第三组和第四组。在第三组和第四组患者中，6个月和12个月后平均IGF - I显著降低，而停药12个月后IGFBP - 3显著降低。我们的结果证实，高比例的IGHD且垂体正常或小的儿童在完成生长激素治疗后生长激素分泌恢复正常，而所有垂体发育不全、垂体柄缺如和垂体后叶异位的患者GHD是永久性的。生长激素停用后不久测定IGF - I和IGFBP - 3对诊断与先天性下丘脑 - 垂体异常相关的儿童期起病的GHD价值有限，但6 - 12个月后变得准确。我们建议，患有GHD和先天性下丘脑 - 垂体异常的患者不需要进一步调查生长激素分泌情况，而IGHD且垂体正常或小的患者应在达到成人身高之前进行重新检测。
