Cortisol and growth hormone: clinical implications of a complex, dynamic relationship

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.