ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 4.5 | DOI: 10.1530/ey.18.4.5

ESPEYB18 4. Growth and Growth Factors Growth Hormone Therapy: Safety (4 abstracts)

4.5. Long-term safety of growth hormone treatment in childhood: two Large observational studies: nordiNet IOS and ANSWER

Sävendahl L , Polak M , Backeljauw P , Blair JC , Miller BS , Rohrer TR , Hokken-Koelega A , Pietropoli A , Kelepouris N & Ross J

Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.

J Clin Endocrinol Metab. 2021 May 13;106(6):1728–1741. doi: 10.1210/clinem/dgab080. PMID: 33571362

This report gathered data from two large observational studies (NordiNet International Outcome Study and ANSWER Program) aimed at assessing the incidence of adverse drug reactions (ADRs), serious adverse events (SAEs), and their relation with rhGH dose. The whole study cohort included 37,702 subjects, with >130,000 patient-years follow-up. As in previous studies, subjects were stratified into different risk groups according to underlying diagnosis: low-risk (68.4%; comprising isolated GHD, SGA children, and ISS); intermediate-risk (27.5%; multiple pituitary hormone deficiencies, Turner and other syndromes), and high-risk (4.1%, malignancies and syndromes with high risk of malignancy).

As expected, the incidence of adverse events was lowest in the low-risk group. The most frequent ADRs and SAEs included “nervous system disorders” (such as headache) and “musculoskeletal and connective tissue disorders” (such as arthralgia and scoliosis). Among the low-risk group, the incidence of SAEs was significantly higher in SGA children. Perhaps counter-intuitively, GH dose was inversely associated with AE incidence rates. This finding is likely explained by the practice to prescribe lower GH doses to patients considered at higher risk of AEs. No case of cerebral hemorrhage and no increase in mortality risk was observed.

It has to be pointed out that this study reports with events occurring during GH treatment, whereas SAGhE (see paper 4.6) analyzed events occurring in young adults who had received GH treatment during childhood. The lack of long-term follow-up limits the potential of this study to capture the risk of developing non-communicable diseases (eg, diabetes, cardio-vascular morbidity, neoplasms or neurodegenerative diseases).