Metabolic Health and Long-Term Safety of Growth Hormone Treatment in Silver-Russell Syndrome.

Abstract

Children with Silver-Russell syndrome (SRS) are born small for gestational age (SGA) and remain short. Growth hormone (GH) treatment improves height in short SGA children, including those with SRS. Data on metabolic health and long-term safety of GH treatment in SRS are lacking. To investigate metabolic health in SRS patients during and until 2 years after discontinuation of GH treatment. Metabolic health was assessed longitudinally at GH-start, GH-stop, 6 months, and 2 years thereafter. Twenty-nine SRS patients vs 171 non-SRS subjects born SGA. Lean body mass (LBM), fat mass percentage (FM%), insulin sensitivity (Si), β-cell function, blood pressure, and serum lipids. At GH-start [mean age (standard deviation) 5.4 (2.1) years in SRS and 6.7 (2.0) years in non-SRS (P = 0.003)], blood pressure, serum lipids, glucose, and insulin levels were similar and within normal ranges in SRS and non-SRS. LBM standard deviation score (SDS) and FM% SDS were lower than average in both groups. During treatment, LBM SDS remained stable whereas FM% SDS increased in both groups. During the 2 years after GH-stop, LBM decreased and FM% increased, whereas Si and β-cell function improved. At 2 years after GH-stop (mean age 18 years), all parameters were similar and within normal ranges in SRS and non-SRS. None of the SRS patients developed metabolic syndrome, diabetes mellitus type 2, or adverse events. GH-treated SRS patients have a similar metabolic health and safety profile as non-SRS subjects born SGA, both during and until 2 years after GH-stop.