Stratakis Constantine A
Section on Endocrinology and Genetics, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Pediatr Endocrinol Rev. 2006 Apr;3 Suppl 2:333-8.
Children with Cushing syndrome (CS), whether CS is iatrogenic or caused by endocrine tumors, have short stature and suffer from excess adiposity and lower bone mineral density. These clinical observations are well entrenched in the minds of pediatricians and pediatric endocrinologists. It is then surprising when one discovers that patients with cortisol-secreting adrenal tumors actually do not have completely suppressed growth hormone levels unless they are obese. Adequate adrenocortical glucocorticoid secretion is necessary for normal function of the somatotropic axis, at least in rodents. Furthermore, glucocorticoids appear to play a regulatory role in skeletal bone accumulation that goes far beyond the well known suppressive effects of excess cortisol on osteoblastic function. To add to the complexity, endocrine and paracrine cortisol levels and actions depend much on the activity of metabolizing enzymes, such as 11-beta-hydroxysteroid dehydrogenase type-1 and CYP3A. The text that follows reviews the complex and dynamic state of the relationship between two of the most important hormones that regulate growth and development in childhood as revealed from clinical, physiologic, and basic science studies. The message is clear: although excess cortisol inhibits growth and the skeleton, normal cortisol levels are part of the mix that ensures both normal growth hormone secretion and bone accumulation in childhood.
患有库欣综合征（CS）的儿童，无论CS是医源性的还是由内分泌肿瘤引起的，都身材矮小，存在肥胖问题且骨矿物质密度较低。这些临床观察结果在儿科医生和儿科内分泌学家的脑海中根深蒂固。然而，当人们发现分泌皮质醇的肾上腺肿瘤患者实际上除非肥胖，否则生长激素水平并未完全受到抑制时，就会感到惊讶。至少在啮齿动物中，充足的肾上腺皮质糖皮质激素分泌对于生长激素轴的正常功能是必要的。此外，糖皮质激素似乎在骨骼积累中发挥着调节作用，这远远超出了过量皮质醇对成骨细胞功能的众所周知的抑制作用。更复杂的是，内分泌和旁分泌皮质醇水平及作用很大程度上取决于代谢酶的活性，如11-β-羟基类固醇脱氢酶1型和CYP3A。以下文本回顾了临床、生理学和基础科学研究揭示的儿童生长发育过程中两种最重要激素之间复杂而动态的关系。信息很明确：虽然过量皮质醇会抑制生长和骨骼发育，但正常的皮质醇水平是确保儿童期正常生长激素分泌和骨骼积累的因素之一。
