Growth hormone secretion in primary adrenal Cushing's syndrome is disorderly and inversely correlated with body mass index

Abstract

. Growth hormone secretion in primary adrenal Cushing's syndrome is disorderly and inversely correlated with body mass index. Am J Physiol Endocrinol Metab 288: E63-E70, 2005. First published August 24, 2004; doi:10.1152/ajpendo.00317.2004.-To evaluate the impact on the somatotropic axis of endogenous cortisol excess in the absence of primary pituitary disease, we investigated spontaneous 24-h growth hormone (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 body mass index (BMI)-, age-, and gender-matched control group and an age-and gender-matched lean control group. GH secretion rates did not differ from BMI-matched controls but were twofold lower compared with lean subjects, mainly due to a 2.5-fold attenuation of the mean secretory burst mass (P ϭ 0.001). In hypercortisolemic patients, GH secretion was negatively correlated with BMI (R ϭ Ϫ0.55, P ϭ 0.005) but not cortisol secretion. Total serum IGF-I concentrations were similar in the three groups. Approximate entropy (ApEn) was increased in patients with Cushing's syndrome compared with both control groups (vs. BMI-matched, P ϭ 0.04; vs. lean, P ϭ 0.001), denoting more irregular GH secretion patterns. ApEn in patients correlated directly with cortisol secretion (R ϭ 0.77, P ϭ 0.003). Synchrony between cortisol and GH concentration series was analyzed by cross-correlation, cross-ApEn, and copulsatility analyses. Patients showed loss of pattern synchrony compared with BMImatched controls, but copulsatility was unchanged. We conclude that hyposomatotropism in primary adrenal hypercortisolism is only partly explained (ϳ30%) by increased body weight and that increased GH secretory irregularity and loss of synchrony suggest altered coordinate regulation of GH release. cortisol; entropy; adrenal adenoma CUSHING'S SYNDROME is characterized by increased cortisol secretion and is caused by ACTH-dependent cortisol excess (Cushing's disease or the rare ectopic tumoral ACTH production syndrome) or by ACTH-independent cortisol excess. The latter syndrome is caused by a unilateral adenoma (seldom a carcinoma) and less frequently by ACTH-independent bilateral macronodular adrenal hyperplasia (AIMAH). The latter syndrome is characterized by bilateral nodular enlargement of the adrenal glands and clinical and biochemical signs of cortisol excess with low or undetectable ACTH concentrations (25). The detrimental metabolic consequences of chronic cortisol excess are manifold and include loss of lean body mass, increased adiposity, bone loss, and repression of the thyrotropic, gonadotropic, and somatotropic axes. Indeed, the diminished growth hormone (GH) response to various stimuli, including insulin-induced hypoglycemia, GH-releasing hormone (GHRH), growth hormone secretagogues (GHS), and ghrelin, is well described in pituitary-dependent hyperco...

Overtrained horses alter their resting pulsatile growth hormone secretion

“…ApEn quantities the orderliness of the subordinate (ϭ nonpul- satile) secretory GH patterns. A larger GH ApEn value denotes greater irregularity and has been reported during puberty and in patients with acromegaly and Cushing's disease (41,48). Decreased regularity could reflect impaired coordinate control of GH secretion by GH-releasing hormone (GHRH), somatostatin, GH, and/or IGF-I.…”

Management of Cushing syndrome in children and adolescents: experience of a single tertiary centre

“…A referral bias leading to increased 7 7 prevalence of non-pituitary CS in our institution may explain this difference in clinical presentation. While pure cortisol-secreting pituitary CD would inhibit growth (cortisol suppresses GH production [37], combined with a possible pituitary mass effect leading to GH deficiency), adrenal CS tumors cosecreting androgens would promote growth and hence stature would be less affected. In a previous series of 72 children with CD, growth retardation was present in 82%, hypertension in 46% and striae in 40% [2].…”

Metabolic comorbidities in Cushing's syndrome

“…Data from the KIMS database showed that GH deficient (GHD) patients with a previous history of CD had the same characteristics in terms of body composition and lipid levels but a higher prevalence of diabetes, hypertension, bone fractures and lower BMD, as well as a more impaired quality of life compared to GHD patients with other aetiologies (148). As GCs significantly impact on adiposity and BMI, which in turn can affect GH secretion, BMI alone can only partially explain GH impairment in CS patients (149).…”