Endocrine Abstracts

The classical features of Silver-Russell syndrome (SRS) appear to become less pronounced with increasing age. Small-for-gestational-age (SGA) birth is associated with adult metabolic syndrome. SRS is associated with SGA but the adult sequelae and long-term effects of childhood growth hormone (GH) treatment are unclear.

Objective: To determine the phenotype and cardio-metabolic profile in older individuals with SRS and compare individuals previously untreated with GH to those treated.

Method: UK participants aged ≥13 years with molecularly confirmed SRS were invited to a study appointment involving a medical history, examination and investigations. Height, weight and head circumference measurements were converted to standard deviation scores (SDS) using UK reference data.

Result: 33 individuals (18 females) aged 13.32-69.71 years (median 29.58) were recruited. Loss of methylation at H19/IGF2 was diagnosed in 81.8%; maternal uniparental disomy for chromosome 7 in 18.2%. 69.7% had previously been treated with GH. Median height SDS was −2.67; median weight SDS −1.72; median body mass index SDS −0.53; and median head circumference SDS −0.95. Height SDS ≤−2 was present in 60.6%. Asymmetry and relative macrocephaly were present in 66.7% and 57.6% respectively. Blood glucose concentration ≥6.1 mmol/L was present in 20.0% (6/30); type 2 diabetes mellitus (n=3), impaired fasting glycaemia (n=2) and impaired glucose tolerance (n=1). Treatment for hypertension (n=2) and hypercholesterolaemia (n=2) was observed. 15.4% (4/26) met criteria for diagnosis of metabolic syndrome. Hypertriglyceridaemia was present in 16.1% (5/31) overall; in 44.4% (4/9) in GH-untreated versus 4.5% (1/22) of GH-treated individuals (P=0.017). Median waist-to-hip ratios in females and males aged ≥18 years were 0.83 and 0.93 respectively.

Conclusion: Relative macrocephaly in older individuals with SRS was less prevalent than in childhood. Metabolic syndrome and hypertriglyceridaemia were more prevalent than previously reported. Historical GH treatment was associated with improved triglyceride levels, suggesting a beneficial longterm effect after treatment discontinuation.