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

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 METHODS: Blood samples were withdrawn at 10 minutes intervals starting at 0900 h for 24 h. GH and PRL release were quantified with deconvolution methods.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 24h 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 x 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 x 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.