Impact of GH replacement therapy on sleep in adult patients with GH deficiency of pituitary origin

Objectives: We previously reported that adult patients with GH deficiency (GHD) due to a confirmed or likely pituitary defect, compared with healthy controls individually matched for age, gender, and BMI, have more slow-wave sleep (SWS) and higher delta activity (a marker of SWS intensity). Here, we examined the impact of recombinant human GH (rhGH) therapy, compared with placebo, on objective sleep quality in a subset of patients from the same cohort. Design: Single-blind, randomized, crossover design study. Methods: Fourteen patients with untreated GHD of confirmed or likely pituitary origin, aged 22-74 years, participated in the study. Patients with associated hormonal deficiencies were on appropriate replacement therapy. Polygraphic sleep recordings, with bedtimes individually tailored to habitual sleep times, were performed after 4 months on rhGH or placebo. Results: Valid data were obtained in 13 patients. At the end of the rhGH treatment period, patients had a shorter sleep period time than at the end of the placebo period (479 +/- 11 vs 431 +/- 19 min respectively; P=0.005), primarily due to an earlier wake-up time, and a decrease in the intensity of SWS (delta activity) (559 +/- 125 vs 794 +/- 219 mu V-2 respectively; P=0.048). Conclusions: Four months of rhGH replacement therapy partly reversed sleep disturbances previously observed in untreated patients. The decrease in delta activity associated with rhGH treatment adds further evidence to the hypothesis that the excess of high-intensity SWS observed in untreated pituitary GHD patients is likely to result from overactivity of the hypothalamic GHRH system due to the lack of negative feedback inhibition by GH. European Journal of Endocrinology 168 763-770