To evaluate the impact on the somatotropic axis of endogenous cortisol excess in the absence of primary pituitary disease, we investigated spontaneous 24-h GH secretion in 12 adult patients with ACTH-independent hypercortisolism. Plasma GH concentration profiles (10 min samples) were analyzed by deconvolution to reconstruct secretion and approximate entropy to quantitate orderliness of the release process. Comparisons were made with a BMI- , age- and gender-matched control group and an age- and gender-matched group of lean controls. GH secretion rates did not differ from BMI-matched controls, but was 2-fold lower compared with lean subjects, mainly caused by a 2.5-fold attenuation of the mean secretory burst mass (P = 0.001). In hypercortisolemic patients, GH secretion was negatively correlated with BMI (R = -0.55, P = 0.005), but not with cortisol secretion. Total serum IGF-I concentrations were similar in the 3 groups. Approximate entropy was increased in patients with Cushing's syndrome compared with both control groups (vs. BMI-matched P = 0.04; vs. lean P = 0.001), denoting more irregular GH secretion patterns. ApEn in patients correlated directly with cortisol secretion (R = 0.77, P = 0.003). Synchrony between cortisol and GH concentration series were analyzed by cross-correlation, cross-ApEn and copulsatility analyses. Patients showed loss of pattern synchrony compared with BMI-matched controls, but copulsatility was unchanged. We conclude that hyposomatotropism in primary adrenal hypercortisolism is only partly explained (~30%) by increased body weight, and that increased GH secretory irregularity and loss of synchrony suggests altered coordinate regulation of GH release.