Endocrine Abstracts

Introduction: Prader–Willi syndrome (PWS) is a complex genetic disorder caused by the absence of normal activity in the paternally expressed genes from the chromosome 15q11–q13. PWS is typically characterised by hyperphagia, muscular hypotonia, developmental and cognitive delay, behavioural problems and endocrine abnormalities. Obesity and short stature are common. Controlled studies of hormonal treatment in the transition period are not available.

Endocrine insufficiencies: 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 insufficiency. GH treatment initiated during childhood normalises skeletal growth, improve body composition and optimize 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 performance. 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 IGF1 and sleep related breathing disorders.

Incomplete sexual development is frequently seen in PWS. The majority has clinical and laboratory measurements demonstrating hypogonadism, and 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 recently been hypothesized to be responsible of 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 when clinically indicated.

Hypothyroidism is not common in PWS, but TSH and thyroid hormones should be followed regularly.

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