Endocrine manifestations and management of Prader-Willi syndrome

Abstract

Prader-Willi syndrome (PWS) is a complex genetic disorder, caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13. In infancy it is characterized by hypotonia with poor suck resulting in failure to thrive. As the child ages, other manifestations such as developmental delay, cognitive disability, and behavior problems become evident. Hypothalamic dysfunction has been implicated in many manifestations of this syndrome including hyperphagia, temperature instability, high pain threshold, sleep disordered breathing, and multiple endocrine abnormalities. These include growth hormone deficiency, central adrenal insufficiency, hypogonadism, hypothyroidism, and complications of obesity such as type 2 diabetes mellitus. This review summarizes the recent literature investigating optimal screening and treatment of endocrine abnormalities associated with PWS, and provides an update on nutrition and food-related behavioral intervention. The standard of care regarding growth hormone therapy and surveillance for potential side effects, the potential for central adrenal insufficiency, evaluation for and treatment of hypogonadism in males and females, and the prevalence and screening recommendations for hypothyroidism and diabetes are covered in detail. PWS is a genetic syndrome in which early diagnosis and careful attention to detail regarding all the potential endocrine and behavioral manifestations can lead to a significant improvement in health and developmental outcomes. Thus, the important role of the provider caring for the child with PWS cannot be overstated.

Review of growth hormone therapy in adolescents and young adults with Prader–Willi syndrome

“…there have been no controlled trials evaluating the optimal investigations required before and during GH treatment in PWS during adolescence, although it is thought that this should be similar to adolescents with GHD. Currently, it is recommended that an evaluation of the GH/IGF-1 axis should be made before initiating GH [46]. This is to provide baseline information before starting treatment and also to serve as a guide in terms of GH dosing, for example GH-sufficient patients may require higher doses than those with GH insufficiency.…”

Prader willi syndrome- A case report

“…1 PWS is a two-staged disorder with a hypotonic early infantile phase and an obese childhood phase. The infantile phase is characterized by failure to thrive, delayed milestones, seizures, fair skin and eyes.…”

Prader–Willi syndrome: clinical problems in transition from pediatric to adult care

“…20 Available data indicate that some degree of CAI may be part of the PWS phenotype in the transitional period, although clinically relevant adrenal failure in PWS subjects appears to be rare. 21 CAI has recently been hypothesized to be responsible of increased risk of sudden death in PWS, particularly during episodes of stress and infections. There are a number of features that support the view that CAI may form part of the PWS spectrum: the well-known hypothalamic dysfunction with multiple hormone deficiencies in PWS consistent with hypothalamic-hypophyseal brain imaging and histological anomalies; the observation of an altered adrenocorticotropic hormone (ACTH) adrenal response in some PWS children; the autopsy finding of hypoplastic adrenal glands in PWS patients dying suddenly; and the description of a previous death case with a proven poor cortisol response after an ACTH test.…”

“…There are a number of features that support the view that CAI may form part of the PWS spectrum: the well-known hypothalamic dysfunction with multiple hormone deficiencies in PWS consistent with hypothalamic-hypophyseal brain imaging and histological anomalies; the observation of an altered adrenocorticotropic hormone (ACTH) adrenal response in some PWS children; the autopsy finding of hypoplastic adrenal glands in PWS patients dying suddenly; and the description of a previous death case with a proven poor cortisol response after an ACTH test. 21,22 In any case, hydrocortisone treatment should be considered when clinically indicated and confirmed by hormonal tests.…”

“…Therefore, the patients are given stress doses of hydrocortisone to be kept at home and to be taken when necessary, and we recommend the administration of a perioperative stress dose of steroids during surgery. 21 Hypothyroidism is not common in PWS, but thyroidstimulating hormone and thyroid hormones should be measured regularly. Similar to other endocrinopathies in PWS, the etiology of hypothyroidism is believed to be central in Research and …”