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Recombinant GH appears effective for Prader-Willi syndrome
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The use of recombinant human growth hormone in patients with Prader-Willi syndrome has been met with concern about potential adverse events. To justify this therapeutic approach, 43 experts and clinical representatives formulated a consensus guideline for the use of growth hormone therapy in this patient population.
According to participants of the 2011 GH in Prader-Willi syndrome clinical care guidelines workshop, the first five items listed in the summary of clinical care guidelines for recombinant human GH (rhGH) therapy in patients with the rare genetic disorder are as follows:
- After genetic confirmation of the diagnosis of Prader-Willi syndrome, rhGH treatment should be considered and, if initiated, continued for as long as demonstrated benefits outweigh the risks.
- GH stimulation testing should not be required as part of the therapeutic decision-making process in infants and children with Prader-Willi syndrome.
- Adults with Prader-Willi syndrome should have an evaluation of the GH/insulin-like growth factor axis before rhGH treatment.
- Before initiation of rhGH therapy, patients with Prader-Willi syndrome should have a genetically confirmed diagnosis and expert multidisciplinary evaluation.
- Exclusion criteria for starting rhGH in patients with Prader-Willi syndrome include severe obesity, uncontrolled diabetes, untreated severe obstructive sleep apnea, active cancer and active psychosis.
The use of rhGH should be considered for patients with genetically confirmed Prader-Willi syndrome, combined with dietary, environmental and lifestyle interventions, researchers wrote. However, clinical outcome priorities should vary based on age and presence of physical, mental and social disability.
Finally, the researchers report that treatment should continue for as long as clinicians find that the benefit outweighs the risk and that cognitive impairment should not be a barrier to treatment. These clinical care guidelines are only a part of the consensus created by the workshop participants. For more information, see the full consensus statement published in the Journal of Clinical Endocrinology and Metabolism.
Disclosure: See the study for a full list of disclosures.
Perspective
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Aaron Carrel, MD
The Growth Hormone Research Society Consensus Guidelines for Growth Hormone therapy in Prader-Willi syndrome (PWS) provides a valuable appraisal of the literature in the challenging area of hGH therapy in PWS. The guidelines are thorough and clear. They (1) provide a detailed summary of clinical care guidelines; (2) encourage multidisciplinary evaluation of patients with PWS prior to, and during, hGH therapy; (3) address important areas unique to PWS; and (4) highlight priority areas for future PWS research.
The breadth of the topics critically reviewed is impressive, but even more valuable is the inclusion of the issues that are often left unaddressed: barriers to intervention that may be present in children with physical, mental or social disabilities, and the unique value that hGH therapy may provide for children with PWS. The guidelines reinforce that the literature demonstrates strong evidence for benefits in treating patients with PWS, include body composition (increased muscle, decreased fat, increased bone density) as well as improved motor development, and some limited evidence of improved cognition. The consensus guidelines make clear that cognitive impairment of the patient should not be a barrier to treatment. Often in the consideration of hGH therapy a cost/benefit analysis is undertaken by the treating physicians. The guidelines appropriately acknowledge risks with hGH, but in light of the many documented benefits, these risks may be appropriately taken in perspective.
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Moris A. Angulo, MD
I applaud the team effort to conclude with important consensus guidelines for growth hormone therapy in children and adults with Prader-Willi syndrome. In a 2008 study by de Lind van Wijngaarden et al, there was a high prevalence (60%) of central adrenal insufficiency (CAI) after overnight single-dose metyrapone tests in children with Prader-Willi syndrome.
The authors suggest obtaining critical blood samples for measurement of cortisol and ACTH levels if possible during an acute illness and suggestive symptomatology, and assessing adrenal glucocorticoid response to provocative testing where indicated. However, two subsequent studies by Nyunt et al and Farholt et al found normal cortisol responses to both low- and high-dose synacthen testing and insulin tolerance testing.
In our experience at Winthrop University Hospital and other clinical investigators, premature adrenarche occurs in over 60% of children with Prader-Willi syndrome in which the adrenal androgen response is mostly due to ACTH, thus whether CAI is a true issue for individuals with Prader-Willi syndrome remains uncertain. Patients should be counseled about symptoms consistent with adrenal insufficiency and educated about the best course of action and treatment should these symptoms occur.
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