Overnight Growth Hormone Secretion in Achondroplasia: Deconvolution Analysis, Correlation with Sleep State, and Changes after Treatment of Obstructive Sleep Apnea

The normal profile for overnight GH secretion in achondroplasia has not been previously studied. Factors that have been shown to influence GH secretion include age, obesity, sleep state, and the presence of obstructive sleep apnea (OSA). We assessed GH levels in a group of subjects with achondroplasia, during overnight polysomnography. Nineteen subjects with achondroplasia were studied at 11.3 y of age (median 6.7, range 1.8-30.9). Levels of GH were measured using time-resolved immunofluorometric assay(DELFIA, Pharmacia Biotech Inc.) and analyzed by a deconvolution method. Five subjects were restudied after treatment for OSA. Secretion rates of GH were greater in slow wave (SWS) and rapid eye movement (REM) sleep than in stage one and two (SI-II = light non-REM) sleep (p < 0.01). Total overnight GH secretion decreased with increasing age (r2 = 0.22 p < 0.04). Neither the frequency of arousals, frequency of sleep state transitions nor the severity of OSA correlated with measures of GH secretion. Levels of IGF-I correlated independently with age, body weight(percent ideal), and GH secretion rate (r2 = 0.76,p < 0.001). In a group of five subjects treated for OSA, improved respiratory distress index and reduced sleep state transitions were not associated with significant changes in GH secretion rate by sleep stage; SWS[from 0.62 ± 0.28 mIU/L/min to 1.02 ± 0.25 mIU/L/min (NS)] and SI-II sleep [from 0.26 ± 0.07 mIU/L/min to 0.60 ± 0.16 mIU/L/min(NS)]. However, in those five subjects, a GH secretion peak during the first 2 h of SWS was initially absent, appearing only after treatment of OSA (1.09± 0.38 mIU/L/min) compared with (2.40 ± 0.59 mIU/L/min(p = 0.01)). A profile of overnight GH secretion is presented for subjects with achondroplasia.