Savage M O, Scommegna S, Carroll P V, Ho J T F, Monson J P, Besser G M, Grossman A B
Department of Endocrinology, St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK.
Horm Res. 2002;58 Suppl 1:39-43. doi: 10.1159/000064767.
Growth is disturbed by adrenal hypersecretion of androgens or cortisol. Androgen excess in virilizing adrenal tumours causes advanced growth and bone age. In 9 girls with virilizing tumours, mean heights at diagnosis and final heights were 1.23 +/- 0.42 and 1.3 +/- 0.37 SDS respectively. In poorly controlled CAH, excess androgens cause early epiphyseal fusion and adult short stature. Increased growth occurs only after 18 months of age, even in untreated CAH, i.e. hydrocortisone >10 mg/m(2)/day is not generally required and may suppress infantile growth, affecting childhood and adult height. Growth was studied in 19 patients, aged 6.4-17.8 years, with Cushing's disease (CD). At diagnosis, mean height SDS was -1.81 (1.2 to -4.17), 53% < -1.8 SDS, height velocity in 6 was 0.9-3.8 cm/year and mean BMI SDS 2.29 (0.7-5.06). From 1983 to 2001, CD was cured in 18 patients (61%) by transsphenoidal surgery (TSS) alone and 39% by TSS plus pituitary irradiation (RT). In 13 patients, growth hormone (GH) was assessed by ITT/glucagons at 1-108 months after cure. Four had severe GH deficiency (<9 mU/l), 7 subnormal (10-29 mU/l) and 2 normal (>30 mU/l) GH status. Subnormal GH was present in 7 subjects >2 years after TSS or RT cure. In 10 subjects, aged 12.9 +/- 3.4 years, growth after cure was studied for 9.1 +/- 5.0 years. Nine had no catch-up growth in the interval of 0.3-1.1 years after cure (mean HV 5.3 +/- 2.4 cm/year). All these had GH deficiency peak GH 0.5-20.9 mU/l, and received hGH 2.7 mg/m(2)/week, 3 with GnRHa. All 10 showed long-term catch-up growth with mean delta SDS at diagnosis (Ht SDS-target Ht SDS) -1.72 +/- 1.26 improving to -0.83 +/- 1.08 (p = 0.0005) at latest of final Ht. At diagnosis, virilization was present in 82% of 17 patients with CD. Mean SDS values of serum androstenedione, DHEA-S and testosterone were normal, i.e. 0.72 (-2.9 to 3.0), -0.8 (6.0 to 2.2), 0.7 (-7.9 to 9.5) respectively, whereas SHBG was reduced at -2.1 (-5.3 to 1.2), increasing free androgen levels. Bone age (BA) was delayed (mean 1.46 years) in 14/16 patients, suggesting cortisol excess contributed more then androgen effect to skeletal maturation. In conclusion, most paediatric patients with CD had subnormal linear growth with delayed BA. After cure by TSS or pituitary irradiation, GH deficiency was frequent and persisted for many years. Treatment with hGH induced significant long-term catch-up growth leading to reasonable final height.
肾上腺雄激素或皮质醇分泌过多会干扰生长。导致男性化的肾上腺肿瘤中雄激素过多会使生长加速和骨龄提前。在9例患有男性化肿瘤的女孩中，诊断时的平均身高和最终身高的标准差评分（SDS）分别为1.23±0.42和1.3±0.37。在控制不佳的先天性肾上腺皮质增生症（CAH）中，雄激素过多会导致骨骺过早融合和成年后身材矮小。即使是未经治疗的CAH，生长加速也仅在18个月龄后出现，即一般不需要氢化可的松>10mg/m²/天，且这可能会抑制婴儿期生长，影响儿童期和成年后的身高。对19例年龄在6.4至17.8岁的库欣病（CD）患者进行了生长研究。诊断时，平均身高SDS为-1.81（范围为1.2至-4.17），53%<-1.8 SDS，6例患者的身高增长速度为0.9至3.8cm/年，平均体重指数SDS为2.29（范围为0.7至5.06）。从1983年到2001年，18例患者（61%）仅通过经蝶窦手术（TSS）治愈CD，39%通过TSS加垂体放疗（RT）治愈。在13例患者中，在治愈后的1至108个月通过胰岛素耐量试验（ITT）/胰高血糖素评估生长激素（GH）。4例严重生长激素缺乏（<9mU/l），7例生长激素水平低于正常（10至29mU/l），2例生长激素水平正常（>30mU/l）。TSS或RT治愈后超过2年，7例患者生长激素水平低于正常。在10例年龄为12.9±3.4岁的患者中，对治愈后的生长情况进行了9.1±5.0年的研究。9例患者在治愈后的0.3至1.1年期间没有追赶生长（平均身高增长速度为5.3±2.4cm/年）。所有这些患者均有生长激素缺乏，峰值生长激素为0.5至20.9mU/l，并接受了2.7mg/m²/周的重组人生长激素（hGH）治疗，3例同时使用促性腺激素释放激素类似物（GnRHa）。所有10例患者均出现长期追赶生长，诊断时的平均SDS差值（身高SDS-目标身高SDS）为-1.72±1.26，在最终身高时改善为-0.83±1.08（p=0.0005）。在17例CD患者中，82%在诊断时有男性化表现。血清雄烯二酮、硫酸脱氢表雄酮（DHEA-S）和睾酮的平均SDS值正常，分别为0.72（范围为-2.9至3.0）、-0.8（范围为6.0至2.2）、0.7（范围为-7.9至9.5），而性激素结合球蛋白（SHBG）降低至-2.1（范围为-5.3至1.2），增加了游离雄激素水平。16例患者中有14例骨龄延迟（平均1.46岁），提示皮质醇过多对骨骼成熟的影响大于雄激素。总之，大多数儿童CD患者线性生长低于正常且骨龄延迟。通过TSS或垂体放疗治愈后，生长激素缺乏很常见且持续多年。hGH治疗可诱导显著的长期追赶生长，使最终身高达到合理水平。
