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In humans, growth hormone (GH) and cortisol are secreted in a pulsatile fashion and a mutual bidirectional interaction between the GH/insulin-like growth factor (IGF)-I axis and hypothalamic-pituitary-adrenal (HPA) axis has been established. Classic congenital adrenal hyperplasia (CAH) is characterized by a defect in the synthesis of glucocorticoids and often mineralocorticoids, and adrenal hyperandrogenism. In view of the sexually dimorphic pattern in GH secretion, we investigated the GH-cortisol bihormonal secretory dynamics in male and female children with classic CAH. Thirty-eight children with classic 21-hydroxylase deficiency (M: 13, F: 25; age range: 6.1-18.8 yr) were studied prospectively. Serum GH and cortisol concentrations were determined at 20 min intervals for 24 hours. The irregularity of GH and cortisol pattern was assessed using approximate entropy (ApEn), a scale- and model-independent statistic. The synchrony of joint GH-cortisol dynamics was quantified using the cross-ApEn statistic. Cross-correlation analysis of GH and cortisol concentrations was computed at various time lags covering the 24-h period. There was no gender difference in mean 24-hour serum GH (males vs females: 5.25 +/- 4.72 vs 4.44 +/- 2.64 mIU/l) or cortisol (156.2 +/- 44.6 vs 172.0 +/- 58.5 nmol/l) concentrations. For GH, ApEn values were significantly higher in females (0.66 +/- 0.14) than in males (0.53 +/- 0.16) (p = 0.009). No difference in cortisol ApEn values was noted between sexes (0.53 +/- 0.21 vs 0.54 +/- 0.12). Cross-ApEn values of paired GH-cortisol, with cortisol leading GH, were significantly higher in females (0.94 +/- 0.14) than in males (0.83 +/- 0.20) (p = 0.03). These findings suggest that females with classic 21-hydroxylase deficiency have a more irregular pattern of GH secretion and a more asynchronous joint GH and cortisol dynamics than their male counterparts.

Original publication




Journal article


J Pediatr Endocrinol Metab

Publication Date





1119 - 1130


Activity Cycles, Administration, Oral, Adolescent, Adrenal Hyperplasia, Congenital, Adrenocorticotropic Hormone, Androstenedione, Biometry, Body Mass Index, Child, Drug Administration Schedule, Female, Fludrocortisone, Human Growth Hormone, Humans, Hydrocortisone, Male, Prospective Studies, Pulsatile Flow, Sex Characteristics, Statistics as Topic, Steroid 21-Hydroxylase, Time Factors