Carroll P V, Monson J P, Grossman A B, Besser G M, Plowman P N, Afshar F, Savage M O
Department of Endocrinology, St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK.
Clin Endocrinol (Oxf). 2004 Feb;60(2):169-74. doi: 10.1046/j.1365-2265.2003.01922.x.
Although Cushing's disease (CD) rarely occurs in childhood, affected children commonly fail to achieve predicted adult height. Hypercortisolaemia results in reduced GH secretion and GH-deficiency may persist or demonstrate delayed recovery after successful treatment of CD in adults. Whether recovery of spontaneous GH secretion occurs following treatment of childhood CD has yet to be established.
We performed a retrospective analysis of the GH status of 13 children (10 males; 12.8 +/- 1.0 years, mean +/- SE) who had undergone successful treatment of CD that occurred prior to the completion of linear growth. Each underwent transsphenoidal hypophysectomy, resulting in satisfactory control of glucocorticoid levels in 7/13 (54%). The remaining six patients (46%) received fractionated external beam irradiation (4500 Gy). At the time of GH assessment, circadian dynamics of cortisol were normal in eight patients and five were receiving titrated glucocorticoid replacement.
GH status was assessed using the peak response to a provocative stimulus. Eleven out of 13 underwent testing with insulin-induced hypoglycaemia (nadir plasma glucose </= 2.2 mmol/l) and glucagon provocation was used in 2/13. Severe GH-deficiency was defined as a peak GH response < 9 mU/l, and a normal response as > 30 mU/l. Intermediate values were taken to represent subnormal GH status. Assessment of GH status was performed 39 +/- 10 months (median +/- SE) following successful treatment (range 9-108 months).
Using these criteria 4/13 (31%) patients had severe GH-deficiency. Only 2/13 (15%) had a normal response. 7/13 (54%) achieved peak GH levels in the subnormal range. Those with multiple pituitary hormone deficiencies were most likely to have lower peak GH levels, but there was no clear effect of pituitary irradiation or relationship between duration post cure and peak GH response.
GH-deficiency is common and may persist for many years following successful treatment of CD prior to completion of linear growth. External radiotherapy does not necessarily result in severe GH-deficiency in the short term. Assessment of GH status and consideration of GH treatment should be considered following treatment of CD in childhood and adolescence in order to maximize the opportunities to achieve a satisfactory final adult height. In those with subnormal GH responses, continued assessment is necessary to determine whether the GH axis subsequently recovers or if these patients develop features of the adult GH-deficiency syndrome.
虽然库欣病（CD）在儿童期很少见，但患病儿童通常无法达到预测的成人身高。高皮质醇血症导致生长激素（GH）分泌减少，GH缺乏可能持续存在，或在成人CD成功治疗后显示延迟恢复。儿童CD治疗后自发性GH分泌是否恢复尚未确定。
我们对13名儿童（10名男性；平均年龄12.8±1.0岁，均值±标准误）的GH状态进行了回顾性分析，这些儿童在骨骼线性生长完成前患CD并接受了成功治疗。每名儿童均接受了经蝶窦垂体切除术，13例中有7例（54%）糖皮质激素水平得到满意控制。其余6例患者（46%）接受了分次外照射（4500戈瑞）。在进行GH评估时，8例患者皮质醇的昼夜节律正常，5例正在接受调整剂量的糖皮质激素替代治疗。
采用激发刺激的峰值反应评估GH状态。13例中有11例接受了胰岛素诱发低血糖试验（最低血浆葡萄糖≤2.2 mmol/L），13例中有2例采用胰高血糖素激发试验。严重GH缺乏定义为GH峰值反应<9 mU/L，正常反应为>30 mU/L。中间值代表GH状态低于正常。在成功治疗后39±10个月（中位数±标准误）（范围9 - 108个月）进行GH状态评估。
根据这些标准，13例中有4例（31%）患者存在严重GH缺乏。只有2例（15%）反应正常。13例中有7例（54%）GH峰值水平处于低于正常范围。患有多种垂体激素缺乏的患者最有可能具有较低的GH峰值水平，但垂体照射没有明显影响，治愈后持续时间与GH峰值反应之间也没有明确关系。
GH缺乏很常见，在骨骼线性生长完成前成功治疗CD后可能持续多年。外照射放疗短期内不一定导致严重GH缺乏。在儿童和青少年CD治疗后，应考虑评估GH状态并考虑GH治疗，以最大程度增加实现满意最终成人身高的机会。对于GH反应低于正常的患者，需要持续评估以确定GH轴随后是否恢复，或者这些患者是否会出现成人GH缺乏综合征的特征。
