NREM Sleep Architecture and Relation to GH/IGF-1 Axis in Laron Syndrome

Abstract

Background: Laron syndrome (LS), known as growth hormone (GH) receptor deficiency, is a rare form of inherited GH resistance. Sleep disorders were described as a common feature of adult LS patients, while no data are available in children. Bi-directional interactions between human sleep and the somatotropic system were previously described, mainly between slow wave sleep and the nocturnal GH surge. Aims: To analyze the sleep macro- and microstructure in LS and to evaluate the influence of substitutive insulin-like growth factor 1 (IGF-1) therapy on it. Methods: Two young LS females underwent polysomnography; the first study was performed during IGF-1 therapy, the second one after a 3-month wash-out period. Results: In both patients, the sleep macrostructure showed that time in bed, sleep period time, total sleep time, sleep efficiency and rapid eye movement (REM) percentage were all increased during wash-out. The sleep microstructure (cyclic alternating pattern: CAP) showed significantly higher EEG slow oscillations (A1%) in NREM sleep, both during IGF-1 therapy and wash-out. Conclusions: Sleep macrostructure in LS children is slightly affected by substitutive IGF-1 therapy. Sleep microstructure shows an increase of A1%, probably related to abnormally high hypothalamic GHRH secretion, due to GH insensitivity.

Sleep Characteristics in Children with Growth Hormone Deficiency

“…Therefore, the results of our study show that GH secretion, CAP rate and CAP A1 subtypes (EEG slow oscillations) could be reciprocally interrelated and future studies will clarify if GH therapy is able to modify sleep microstructure in GHD children, as already found in other children with GH dysregulation such as Prader-Willy and Laron syndrome [22,48,49]. …”

“…Similarly, we observed a significantly higher percentage of A1 in 2 patients affected by Laron syndrome, concurrently with extremely high GH levels [49]. …”