ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 4.6 | DOI: 10.1530/ey.18.4.6

Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; Pediatric Endocrinology Unit, Karolinska University Hospital, Solna, Sweden.

Lancet Diabetes Endocrinol. 2020;8(8):683–692. doi: 10.1016/S2213-8587(20)30163-7. PMID: 32707116

SAGhE is a large independent European consortium including eight different countries (Belgium, France, Germany, Italy, The Netherlands, Sweden, Switzerland, and the UK) which was set up to evaluate the long-term safety of rhGH in a large cohort (>24 000) of young adult patients treated during childhood (1). In this report, overall and cause-specific mortality was assessed by comparison to general population data to calculate standardized mortality ratios (SMR). Patients were subdivided into different risk groups: 1) low-risk, further subdivided in group 1a (isolated GHD, idiopathic short stature (ISS) or mild skeletal dysplasia) and group 1b (small for gestational age (SGA); 2) intermediate-risk, including multiple pituitary hormone deficiencies and specific syndromes (Turner, Noonan, Down, etc.), and 3), high-risk, history of malignancies or chronic renal failure. The follow-up was >400 000 patient-years (to age 25 years).

In group 1a, all-cause mortality was not significantly increased. In group 1b, mortality risk was significantly increased (SMR 1.5, 95%CI 1.1–1.9) although this result was mainly driven by the French sub-cohort. Mortality risk was also significantly increased in the intermediate and high-risk groups. Notably, mortality from diseases of the circulatory and hematological systems was increased in all risk groups.

This large long-term independent study confirms earlier data from post-marketing surveillance studies indicating no significant effect of childhood rhGH therapy on overall mortality in patients with isolated growth hormone deficiency or idiopathic short stature. Whether the increased mortality observed in subjects born SGA should be attributed to rhGH treatment during childhood is open to debate, as it may be due to their inherent cardiometabolic risk (2),(3) or to the genetic cause underlying small size at birth (4). Consistent with this, mortality was not associated with mean daily or cumulative doses of rhGH for any of the risk groups.

Overall, these data are reassuring, however prolonged long-term surveillance of patients treated with rhGH in childhood is still needed as mortality from cardiovascular and hematological diseases in all treated groups was higher than the general population.

Reference: 1. Swerdlow AJ, Cooke R, Beckers D, Borgstrom B, Butler G, Carel JC, et al. Cancer Risks in Patients Treated With Growth Hormone in Childhood: The SAGhE European Cohort Study. J Clin Endocrinol Metab. 2017;102(5):1661–72.2. Barker DJ. Fetal origins of coronary heart disease. BMJ. 1995;311(6998):171–4.3. Risnes KR, Vatten LJ, Baker JL, Jameson K, Sovio U, Kajantie E, et al. Birthweight and mortality in adulthood: a systematic review and meta-analysis. Int J Epidemiol. 2011;40(3):647–61.4. Wit JM, van Duyvenvoorde HA, van Klinken JB, Caliebe J, Bosch CA, Lui JC, et al. Copy number variants in short children born small for gestational age. Horm Res Paediatr. 2014;82(5):310–8.

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