ESPE Yearbook of Paediatric Endocrinology

Brief summary: In this longitudinal study, the authors investigated the metabolic and cardiovascular health profile of 167 adults born SGA and previously treated with rhGH during a period of 12 years after therapy discontinuation. No relevant differences were found in treated SGA subjects compared with untreated SGA adults or adults born appropriate for gestational age (AGA), thus suggesting long-term metabolic and cardiovascular safety of rhGH treatment in short SGA children.

Subjects born small for gestational age (SGA) have an increased risk of cardiometabolic disorders in adulthood. Treatment with rhGH causes changes in body composition and insulin sensitivity that could have long-term effects (1–4). Postmarketing surveillance studies, including the Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) study, reported an increased risk of cardiovascular mortality in adults born SGA who were treated with rhGH during childhood (5).

In this study the metabolic and cardiovascular profile of 167 adults born SGA and previously treated with rhGH was compared with that of 219 untreated adults: 127 born SGA with either persistent short stature or spontaneous catch-up growth, and 92 born AGA. Subjects were followed-up for 12 years (from GH cessation), and data were collected at the age of 30 years. Insulin sensitivity increased significantly in adults previously treated with rhGH during the 12 years follow-up and a normal β-cell function was maintained. Fat mass, trunk fat and limb fat increased in SGA adults treated with rhGH after cessation of therapy, whereas lean body mass significantly decreased. However, these parameters did not differ from those of untreated SGA adults. All groups born SGA had significantly lower HDL cholesterol than adults born AGA. Systolic and diastolic blood pressure, visceral adipose tissue, subcutaneous adipose tissue, and liver fat fraction corrected for age, sex, and adult height SD score, were similar in all SGA and AGA groups. The prevalence of metabolic syndrome was also comparable in the different groups. In conclusion, the results of this study clearly show that rhGH therapy in SGA children is not associated with a worse cardiometabolic profile even after 12 years from cessation of treatment.

References: 1. Cutfield WS, Wilton P, Bennmarker H, et al. Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment. Lancet 2000; 355: 610–13. 2. Stanley TL, Grinspoon SK. Effects of growth hormone-releasing hormone on visceral fat, metabolic, and cardiovascular indices in human studies. Growth Horm IGF Res. 2015; 25: 59–65. 3. Pasarica M, Zachwieja JJ, Dejonge L, Redman S, Smith SR. Effect of growth hormone on body composition and visceral adiposity in middle-aged men with visceral obesity. J Clin Endocrinol Metab. 2007; 92: 4265–70. 4. Sas T, Mulder P, Hokken-Koelega A. Body composition, blood pressure, and lipid metabolism before and during long-term growth hormone (GH) treatment in children with short stature born small for gestational age either with or without GH deficiency. J Clin Endocrinol Metab. 2000; 85: 3786–92. 5. Sävendahl L, Cooke R, Tidblad A, et al. Long-term mortality after childhood growth hormone treatment: the SAGhE cohort study. Lancet Diabetes Endocrinol. 2020; 8: 683–92.