Toogood A A, Shalet S M
Department of Endocrinology, Christie Hospital National Health Service Trust, Manchester, United Kingdom.
J Clin Endocrinol Metab. 1999 Jan;84(1):131-6. doi: 10.1210/jcem.84.1.5408.
Adults over the age of 60 yr with organic disease of the hypothalamic-pituitary axis have a 90% reduction in GH secretion. This is distinct from the hyposomatotropism associated with increasing age and results in a significant reduction in serum insulin-like growth factor I (IGF-I), an increase in fat mass, abnormal bone turnover, and an adverse lipid profile compared with those in healthy subjects of the same age. These findings suggest that the elderly with organic GH deficiency might benefit from GH replacement therapy. However, the dose of GH required to maintain serum IGF-I levels in the normal range while minimizing side-effects in this group of patients is unknown. We have studied 12 patients with organic GH deficiency, aged 62.4-85.2 (median, 67.9 yr), each treated with three doses of GH (0.167, 0.33, and 0.5 mg/day). Each dose was administered for 12 weeks. The serum IGF-I level rose in a dose-related manner over the course of the study (P < 0.0001). From a baseline median (range) IGF-I concentration of 101 (49-148) microg/L to 149 (49-227) microg/L at 12 weeks (P = 0.003 vs. baseline), 200 (70-453) microg/L at 24 weeks (P = 0.002 vs. baseline; P = 0.04 vs. 12 weeks), and 239 (122-502) microg/L at 36 weeks (P = 0.002 vs. baseline; P = 0.07 vs. 24 weeks). The age-specific IGF-I SD score exceeded normal in two subjects taking 0.33 mg/day and in six subjects taking 0.5 mg/day. Serum IGF-binding protein-3 also rose over the course of the study (P < 0.001); however, the greatest increase occurred during the first 12 weeks, after which the IGFBP-3 level plateaued. Body composition changed significantly during the study, with a fall in fat mass (P = 0.0003) and an increase in lean body mass (P = 0.0001). GH was well tolerated in this elderly group, all of whom completed the study. Three patients developed side-effects while taking 0.5 mg/day; two developed headaches, and one developed arthralgia. This study has demonstrated that the GH replacement dose in elderly subjects is considerably lower than that required by younger adults with GH deficiency. In 50% of the subjects a dose of 0.5 mg/day was excessive, whereas 83% maintained their serum IGF-I within normal limits while taking 0.33 mg/day. No patient exhibited a supranormal IGF-I level on 0.17 mg/day.
60岁以上患有下丘脑 - 垂体轴器质性疾病的成年人，其生长激素（GH）分泌减少90%。这与随年龄增长出现的生长激素分泌不足不同，与同龄健康受试者相比，会导致血清胰岛素样生长因子I（IGF - I）显著降低、脂肪量增加、骨转换异常以及血脂谱不良。这些发现表明，患有器质性GH缺乏的老年人可能从GH替代治疗中获益。然而，在该组患者中，将血清IGF - I水平维持在正常范围同时使副作用最小化所需的GH剂量尚不清楚。我们研究了12例患有器质性GH缺乏的患者，年龄在62.4 - 85.2岁（中位数为67.9岁），每人接受三种剂量的GH治疗（0.167、0.33和0.5毫克/天）。每种剂量给药12周。在研究过程中，血清IGF - I水平呈剂量相关方式升高（P < 0.0001）。从基线中位数（范围）IGF - I浓度101（49 - 148）微克/升，在12周时升至149（49 - 227）微克/升（与基线相比，P = 0.003），24周时为200（70 - 453）微克/升（与基线相比，P = 0.002；与12周相比，P = 0.04），36周时为239（122 - 502）微克/升（与基线相比，P = 0.002；与24周相比，P = 0.07）。在服用0.33毫克/天的两名受试者和服用0.5毫克/天的六名受试者中，年龄特异性IGF - I标准差评分超过正常范围。血清IGF结合蛋白 - 3在研究过程中也升高（P < 0.001）；然而，最大增幅发生在最初12周，之后IGFBP - 3水平趋于平稳。在研究期间身体成分发生了显著变化，脂肪量减少（P = 0.0003），瘦体重增加（P = 0.0001）。该老年组对GH耐受性良好，所有患者均完成了研究。三名患者在服用0.5毫克/天时出现副作用；两名出现头痛，一名出现关节痛。这项研究表明，老年受试者的GH替代剂量远低于年轻的GH缺乏成年人所需的剂量。在50%的受试者中，0.5毫克/天的剂量过高，而83%的受试者在服用0.33毫克/天时将血清IGF - I维持在正常范围内。没有患者在服用0.17毫克/天时出现IGF - I水平超正常的情况。
