Endocrine Abstracts

Prader–Willi syndrome (PWS) is a complex genetic disorder caused by the absence of normal activity in the paternally expressed genes from chromosome 15q11–q13. PWS is characterised by hyperphagia, muscular hypotonia, developmental and cognitive delays, behavioural problems and endocrine abnormalities. Obesity and short stature are common.

Endocrine deficiencies: The combination of the phenotype and reduced GH and IGF1 levels indicates a dysfunction in the GH/IGF1 axis. The degree of GH deficiency varies from mild to severe. GH treatment initiated during childhood normalises skeletal growth, improves body composition and optimizes mental and motor development. GH treatment with doses normalising IGF1 in adults with PWS improves body composition and to some degree quality of life (QoL) and physical fitness. GH treatment is safe but glucose metabolism must be continuously monitored especially in obese patients and in patients with heredity for diabetes, in addition to monitoring serum IGF-I and sleep related breathing disorders.

Incomplete sexual development is frequently seen in PWS. The majority has clinical and laboratory measurements demonstrating hypogonadism, which can be of both primary gonadal and hypothalamic origin. Sex-steroid treatment might be beneficial. Fertility has not been reported in PWS men while five pregnancies have been reported in PWS women.

Central adrenal insufficiency has been hypothesized to be responsible of an increased risk of sudden death in PWS. Available data indicate that some degree of central adrenal insufficiency may be part of PWS phenotype, although clinically relevant adrenal failure in PWS subjects appears to be rare. Adrenal insufficiency and hydrocortisone treatment should be considered whenever clinically indicated.

Hypothyroidism has been reported more frequently in children than in adults with PWS, and TSH and thyroid hormones should be followed regularly.

Conclusion: PWS in adults and children is associated with documented endocrine insufficiencies which should be monitored and treated.