Sleep disturbances, daytime sleepiness, and quality of life in adults with growth hormone deficiency

Abstract

Context: Low energy and fatigue are frequent complaints in subjects with GH deficiency (GHD). Because interrelations between sleep and GH regulation are well documented, these complaints could partly reflect alterations of sleep quality.

Objective: The objective of the study was to determine objective and subjective sleep quality and daytime sleepiness in adult GHD patients.

Subjects: Thirty patients, aged 19-74 yr, with untreated GHD (primary pituitary defects confirmed or likely in 26 patients, hypothalamic origin in four patients), and 30 healthy controls individually matched for gender, age, and body mass index participated in the study. Patients with associated pituitary deficiencies (n = 28) were on hormonal replacement therapy.

Methods: Polygraphic sleep recordings, assessment of Pittsburgh Sleep Quality Index, and Quality of Life Assessment for GHD in Adults were measured.

Results: Irrespective of etiology, GHD patients had a Pittsburgh Sleep Quality Index score above the clinical cutoff for poor sleep and lower Quality of Life Assessment for GHD in Adults scores than controls, with tiredness being the most affected domain. Patients with pituitary GHD spent more time in slow-wave sleep (SWS) and had a higher intensity of SWS than their controls. Among these patients, older individuals obtained less total sleep than controls, and their late sleep was more fragmented. Contrasting with pituitary GHD, the four patients with hypothalamic GHD had lower intensity of SWS than their controls.

Conclusions: GHD is associated with sleep disorders that may be caused by specific hormonal alterations as well as with poor subjective sleep quality and daytime sleepiness. Disturbed sleep is likely to be partly responsible for increased tiredness, a major component of quality of life in GHD.

Figure 1

Top panels, Differences (mean and sem) in total sleep time, sleep stages, and delta activity between 26 GHD patients with pure pituitary defects, pituitary defects with possible hypothalamic involvement, or childhood-onset idiopathic GHD, and their pair-matched healthy controls for the younger (n = 13) and older (n = 13) age groups. Positive values indicate higher levels in GHD patients and negative values lower levels in GHD patients. In each age group, P values denote the results of paired t tests between GHD patients and their matched controls. P ≥ 0.10 is not indicated. Bottom panels, Differences (mean and sem) in QoL scores for the five domains of the QoL-AGHDA scale between GHD patients with pure pituitary defects, pituitary defects with possible hypothalamic involvement, or childhood-onset idiopathic GHD, and their pair-matched healthy controls for the younger (n = 13) and older (n = 13) age groups. Positive values indicate higher levels in GHD patients. In each age group, P values denote the results of paired t tests between GHD patients and their matched controls. P ≥ 0.10 is not indicated.

Figure 2

Mean profiles (+sem) of absolute EEG spectral power in the delta, theta, and alpha ranges during the first four NREM-REM cycles in GHD patients with pure pituitary defects, pituitary defects with possible hypothalamic involvement, or childhood-onset idiopathic GHD (left panels), and in their healthy controls (right panels). The durations of NREM/REM cycles were normalized to account for individual differences as previously described (30). EEG delta power is a marker of the intensity of SWS and reflects an increase in the amplitude of delta waves. In conditions in which the prevalence and amplitude of EEG delta waves are markedly increased, spectral power in the adjacent theta frequency range is also generally elevated. Spectral power in the delta and alpha ranges are independent markers of the synchronization of cortical oscillations in the low- and high-frequency ranges, respectively, and these oscillations have their origin in distinct neuronal networks.

Figure 3

Differences (mean ± sem) between patients and controls in total delta activity during the first 6 h of sleep for patients with pure pituitary GHD (n = 12); patients with pituitary GHD with possible hypothalamic involvement (n = 7; spectral analysis could not be performed for one patient); patients with childhood-onset idiopathic GHD (n = 6); or patients with hypothalamic GHD (n = 4). Positive values indicate higher levels in GHD patients, negative values lower levels in GHD patients. **, P < 0.005 for difference between pure pituitary GHD and hypothalamic GHD, after controlling for age; *, P = 0.05 for difference between idiopathic GHD and hypothalamic GHD, after controlling for age.

Figure 4

Mean (+sem) of absolute EEG spectral power in the delta range during the first four NREM-REM cycles in GHD patients compared with their matched controls for the four diagnostic categories. From top to bottom, Pure pituitary GHD (n = 12), pituitary GHD with possible hypothalamic involvement (n = 7), childhood-onset idiopathic GHD (n = 6), and hypothalamic GHD patients (n = 4). As in Fig. 2, the durations of NREM/REM cycles were normalized to account for individual differences as previously described (30). Note differences of scales in the different categories. Differences in levels of delta activity across the four control groups are due to differences in sex, age, and BMI distribution. For each diagnostic category, patients and controls are pair matched for sex, age, and BMI.