Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: results of a 2-year crossover GH trial

Abstract

BackgroundPatients with Prader-Willi syndrome (PWS) have a cognitive impairment. Growth hormone (GH) treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH) might deteriorate their GH-induced improved cognition, while continuation might benefit them. We, therefore, investigated the effects of placebo versus GH administration on cognition in young adults with PWS who were GH-treated for many years during childhood and had attained AH.MethodTwo-year, randomized, double-blind, placebo-controlled cross-over study in 25 young adults with PWS. Cross-over intervention with placebo and GH (0.67 mg/m2/day), both during 1 year.ResultsTotal (TIQ), verbal (VIQ) and performance IQ (PIQ) did not deteriorate during 1 year of placebo, compared to GH treatment (p > 0.322). Young adults with a lower TIQ had significantly more loss of TIQ points during placebo versus GH, in particular VIQ decreased more in those with a lower VIQ. The effect of placebo versus GH on TIQ, VIQ and PIQ was not different for gender or genotype.ConclusionsCompared to GH treatment, 1 year of placebo did not deteriorate cognitive functioning of GH-treated young adults with PWS who have attained AH. However, patients with a lower cognitive functioning had more loss in IQ points during placebo versus GH treatment. The reassuring finding that 1 year of placebo does not deteriorate cognitive functioning does, however, not exclude a gradual deterioration of cognitive functioning on the long term.Trial registration ISRCTN24648386, NTR1038, Dutch Trial Register, www.trialregister.nl. Registered 16 August 2007.

Time for a general approval of growth hormone treatment in adults with Prader–Willi syndrome

“…Moreover, it has been shown that GH treatment improved mental and cognitive function [ 14 ] and other studies have reported a better quality of life with GH treatment although caregivers/relatives were less optimistic in another study [ 19 ]. A significant impairment in psychosocial function in adults was noted when GH treatment was discontinued [ 14 ], while no change was seen in young adults [ 20 ]. Nevertheless, in PWS an integrated assessment of the patient is crucial in both considering a decision on the start of and in the evaluation of the effect of GH treatment, as also concluded in a large, recent study of 140 young adults with PWS [ 21 ].…”

Prevalence of growth hormone (GH) deficiency in previously GH‐treated young adults with Prader‐Willi syndrome

“…We cannot, however, exclude that GH treatment stimulates GH secretory cells in the pituitary and that this GH effect persists, even after GH treatment is discontinued. This hypothesis is supported by a recent RCT, which showed that one year of placebo in previously GH‐treated young adults with PWS did not deteriorate cognitive functioning and might suggest that the neurotropic effects of long‐term GH during childhood last into adulthood …”

Effects of growth hormone-replacement therapy in patients with Prader-Willi syndrome - review of recent clinical trials

“…Moreover, as for the cessation of GH treatment, some authors seem to highlight no deterioration in cognitive functioning in patients who attained adult height after GH-treatment. This kind of retrogressions can be observed among patients with lower IQ levels [27]. Nonetheless, in our research we did not come across on any clinical trials with more than one-year-long observations.…”