Growth hormone and prolactin are secreted more irregularly in patients with Cushing's disease

Abstract

OBJECTIVE To investigate whether the spontaneous secretion of growth hormone and prolactin in adult patients with pituitary‐dependent Cushing's disease is decreased. PATIENTS Fourteen adult patients (9 women, 5 men; age: 34 ± 3.4 years, mean ± SEM) with pituitary‐dependent Cushing's disease and 14 controls matched for age, gender and body mass index were studied. METHODS Blood samples were withdrawn at 10 minutes intervals starting at 0900 h for 24 h. GH and PRL release were quantified with deconvolution methods. The regularity of GH and PRL release was measured with approximate entropy statistics. RESULTS The number of GH secretory events per 24 h was higher in patients than in controls: 19 ± 1.3 vs. 14 ± 1.5 peaks per 24 h, respectively (P = 0.020). GH secretion rate was about one quarter lower in patients (ns), and the 24 h secretion of PRL was unchanged. Total GH production correlated negatively with the urinary excretion of free cortisol (R = 0.729, P = 0.005) and with the plasma cortisol production rate (R = 0.613; P = 0.026). The orderliness of GH and PRL secretion was appraised with the approximate entropy statistic (ApEn). For GH secretion ApEn(1,20%) in patients was 0.952 ± 0.084 vs. 0.404 ± 0.047 in controls, P = 1.17 × 10−4, pointing to a markedly disordered secretion in patients. Similar results were obtained for PRL secretion: patients: 1.586 ± 0.063 vs. 1.003 ± 0.068 in controls, P = 3.67 × 10−5. No statistically significant differences in secretory dynamics were demonstrated between the 10 patients with a microadenoma and the four with a macroadenoma. CONCLUSION The amount of GH released spontaneously into the circulation in adult patients with pituitary‐dependent Cushing's disease is inversely related to the degree of cortisol hypersecretion. However, except for severe hypercortisolism, GH secretion is relatively preserved. In addition, secretion of GH and PRL is remarkably disordered in patients with Cushing's disease. Since we could not detect differences in GH and/or PRL secretory dynamics between patients with a microadenoma and those harboring a macroadenoma, we speculate that an intrapituitary paracrine mechanism and/or elevated cortisol feedback effects may be responsible for the evident disruption of GH and PRL secretion patterns.

Plasma profiles of adrenocorticotropic hormone, cortisol, α-melanocyte-stimulating hormone, and growth hormone in dogs with pituitary-dependent hyperadrenocorticism before and after hypophysectomy

“…Dogs with PDH and humans with Cushing's disease secrete less GH in pulses than healthy individuals (Veldman et al 2000, Lee et al 2003. The same was observed in the present study, although no statistical significance was reached.…”

“…PDH caused by an adenoma in pars intermedia is often characterized by highly elevated plasma concentrations of a-melanocyte-stimulating hormone (a-MSH) and strong resistance to dexamethasone suppression (Peterson et al 1986, Rijnberk et al 1988b, Bosje et al 2002. In Cushing's disease, there are not only alterations in ACTH secretions but also in the secretion of other pituitary hormones (van den Berg et al 1997, Roelfsema et al 1998, Veldman et al 2000. In dogs with PDH, these changes may include basal levels, response to stimulation (Meij et al 1997b), as well as the pulsatile release pattern that is characteristic of pituitary hormone secretion (Kemppainen & Sartin 1984, Brabant et al 1992, Kooistra et al 1997a, Kooistra & Okkens 2001, Corrada et al 2003, Lee et al 2003.…”

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

“…A conspicuous and specific observation was the decreased regularity of GH secretion measured using ApEn, as previously described in patients with ACTH-producing pituitary adenomas (17). The degree of irregularity of GH release in patients with adrenal cortisol excess was significantly greater than that estimated in obese controls.…”

“…In a previous study in patients with pituitary-dependent hypercortisolism, the 24-h GH secretion was negatively correlated to urinary cortisol excretion, and the GH secretion regularity was significantly decreased (17). Hypothetically, the GH secretory abnormalities could be the result of the presence of the pituitary adenoma itself, a tumoral product acting as a paracrine signal on the somatotrope, or the result of cortisol excess per se on the somatotropic axis.…”

“…The prime issue is whether such patients display low-amplitude and/or disorderly GH secretion compared with BMI-matched controls, as we previously found in pituitary-dependent hypercortisolism (17).…”