Effects of Growth Hormone Substitution Therapy on Cognitive Functioning in Growth Hormone Deficient Patients: A Functional MRI Study

Abstract

Patients with childhood-onset growth hormone (GH) deficiency (GHD) show impairments in mood and cognitive functioning which may resolve following GH substitution. Brain functional magnetic resonance imaging (fMRI) during performance of a memory task was used to assess the cerebral activity of such patients. Thirteen childhood-onset GHD patients (mean age 27.3 ± 6.9 years) were included in a double-blind, placebo-controlled study. The effects of 6 months of GH replacement or placebo therapy were studied using neuropsychological tests and fMRI. One patient was excluded from the study due to noncompliance with the protocol. Six months of GH substitution in these GHD patients resulted in improved memory functioning, both for long-term and working memory. fMRI showed activations during the working memory task in prefrontal, parietal, motor, and occipital cortices, as well as in the right thalamus and anterior cingulate cortex. Decreased activation in the ventrolateral prefrontal cortex was observed after GH treatment as compared with placebo treatment, indicating decreased effort and more efficient recruitment of the neural system involved. It can be concluded that GH treatment for 6 months improved the long-term as well as the working memory in patients with GHD, and this was associated with decreased brain activation in the ventrolateral prefrontal cortex. GH substitution in GHD patients is beneficial for cognitive functioning, the effects of which can be visualized by means of neuroimaging.

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

“…In childhood or adult-onset GHD because of pituitary dysfunction, a decline in neurocognitive functionalities like cognition, memory, motivation, attention, and sleep, and overall quality of life (QoL) have been observed. GH replacement therapy showed significant improvements in these variables (254,285,286,287,288,289,290,291,292). Similar observations were also made following GH treatment in patients with Prader-Willi syndrome (293).…”

Cognition in the adult with childhood-onset GH deficiency

“…A fMRI study performed by Arwert et al showed that 6 months of GH substitution therapy in 13 CO-GHD adults improved both long-term and working memories (27). Furthermore, they demonstrated an increase in efficiency of working memory-associated cortical regions in the GH-treated patients when compared with the placebo group.…”

Peripheral administration of GH induces cell proliferation in the brain of adult hypophysectomized rats

“…The use of GH therapy in adult GH-deficient humans has been shown to ameliorate these conditions (McGauley 1989, Bengtsson et al 1993, Deijen et al 1998, Arwert et al 2006. Further, GH improves spatial memory in experimental hypopituitary rats (Le Grevès et al 2006).…”