Prader-Willi syndrome: who can have growth hormone?

Abstract

Growth hormone (GH) is licensed for treatment for Prader-Willi syndrome (PWS) for improvement of body composition,1(-)3 height velocity, mobility, behaviour and quality of life.4 Recent case reports, however, have pointed out the occurrence of sudden death during initiation of GH, mainly during sleep and possibly related to severe obesity and sleep-disordered breathing (SDB).5(-)15 Concerns for an increased mortality in PWS children starting GH therapy led to a call for cessation of its use. Children with PWS are at risk of developing SDB secondary to both deficient autonomic sleep control and upper airway obstruction (UAO). It has been suggested that GH exacerbates pre-existing gas-exchange deficiencies in three ways: (a) by stimulation of adenotonsillar hypertrophy;16 17 (b) by a rise in basal metabolic rate with a resultant rise in oxygen demand;18 and (c) by normalisation of previously decreased hydration with augmentation of volume load.19 Are we withholding GH therapy, a treatment known to be of benefit in PWS, without adequate evidence to justify our actions? We consider it safe to treat severely obese children with GH once SDB is addressed using respiratory support such as continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP). In this paper, we evaluate the current evidence for the use of GH in PWS from a respiratory bias and propose a pathway for the identification and monitoring of these "at risk" patients.

Uso de hormônio de crescimento na síndrome de Prader-Willi

“…Por outro lado, como a obesidade é o fator que levará tais pacientes a óbito, deve-se atuar para evitar ou, pelo menos, dificultar o excessivo ganho de peso comumente visto nesta condição clínica. Com o tratamento, também ocorre melhora da massa óssea e do perfil lipídico dos pacientes (5,20).…”

“…Por outro lado, como a obesidade é o fator que levará tais pacientes a óbito, deve-se atuar para evitar ou, pelo menos, dificultar o excessivo ganho de peso comumente visto nesta condição clínica. Com o tratamento, também ocorre melhora da massa óssea e do perfil lipídico dos pacientes (5,20).Em um estudo randomizado de 91 pacientes pré-púberes com PWS (42 lactentes, 49 crianças de 3 a 14 anos), houve aumento do SDS de altura de -2,3 para -0,4 após dois anos de tratamento com hrGH, enquanto em um grupo de crianças não-tratadas não se verificou alteração do SDS de altura. A massa magra aumentou e a porcentagem de gordura corpórea reduziu, apesar de não se normalizar completamente.…”

Specialty Drugs for the Treatment of Short Stature in Children—Pros, Cons, and Perspectives for the Future

“…46 In overweight patients with Prader-Willi syndrome, rhGH therapy was associated with sudden respiratory death, possibly related to airway obstruction. [47][48][49][50] Because of this association, sleep studies and airway assessments are recommended before initiating rhGH in patients with Prader-Willi syndrome. 50 Despite the apparently good safety record, the risks may be condition-specific (e.g.…”

“…[47][48][49][50] Because of this association, sleep studies and airway assessments are recommended before initiating rhGH in patients with Prader-Willi syndrome. 50 Despite the apparently good safety record, the risks may be condition-specific (e.g. Prader-Willi syndrome), and there are substantial limitations to available evidence.…”

The growth hormone receptor mediated oncogenesis

“…Other evidence implicates GH in reproduction, regulation of immune function, mental health and aging (Savine & Sonksen, 2000;. The anabolic actions of GH can be beneficial in patients with chronic illness such as those suffering from post-surgical stress, AIDS and Prader-Willi syndrome (Napolitano et al, 2008;Stafler & Wallis, 2008). GH has been reported to accelerate wound healing in surgical and burn patients (Saito, 1998) and also prevent autoimmune diabetes in non-obese diabetic mice models (Villares et al, 2013).…”