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

Background: Patients 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.

Method: Two-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.

Results: Total (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.

Conclusions: Compared 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.