Is safety of childhood growth hormone therapy related to dose? Data from a large observational study

Abstract

Objective: Concerns have been raised of increased mortality risk in adulthood in certain patients who received growth hormone treatment during childhood. This study evaluated the safety of growth hormone treatment in childhood in everyday practice.

Long‐term safety of growth hormone—A combined registry analysis

“…ANSWER 28,29 and NordiNet ® IOS, 28,30,31 with focus on key AEs ( Table 1). The most recent data from these registries on the tolerability profile of GH are summarized in Table S1.…”

“…71 Analysis of NordiNet ® IOS data, with a total treatment exposure of over 53 500 patient-years, identified no AEs related to stroke, subarachnoid or intracerebral haemorrhage. 30 Although no other specific analyses of the risk of intracranial haemorrhage were identified, the reported incidence appears low. Recent data from a large national registry suggest that radiotherapy for nonfunctioning pituitary adenoma, a frequent cause of AO-GHD, may increase the cerebrovascular event risk in men but not women, an observation that warrants further research.…”

“…71 Analysis of long-term safety data for 13 834 paediatric patients enrolled in NordiNet ® IOS, with a total treatment exposure of 53 575 patient-years, identified no serious AEs, serious adverse drug reactions or drug reactions related to stroke, subarachnoid or intracerebral haemorrhage. 30 Although data from HypoCCS indicated no increased risk of mortality or incidence of cancer, stroke or MI in adult patients with GHD who had previously been treated for GHD in childhood, 34 data from KIMS indicated that cerebrovascular mortality was elevated in GH-treated patients, but to a lower level than reported in the literature in non-GH-treated patients with GHD. 36 However, data from both KIMS 36 and HypoCCS 72 strongly indicated that factors such as an underlying diagnosis of craniopharyngioma or previous Cushing's disease may adversely impact on risk for cerebrovascular disease in patients with hypopituitarism treated with GH.…”

Growth Hormone Treatment for Short Stature in the USA, Germany and France: 15 Years of Surveillance in the Genetics and Neuroendocrinology of Short-Stature International Study (GeNeSIS)

“…Safety data from large, well-designed, observational studies, such as GeNeSIS, are increasingly being requested by clinicians and regulatory authorities and provide long-term data for specific safety-related questions that cannot be obtained in randomised controlled trials [33-37]. Data from such observational studies support the known safety profile of GH [12, 35, 38-40]. Among the three countries, the types of adverse events reported (both SAEs and TEAEs) were similar, although for children in France and girls with a diagnosis of Turner syndrome in all countries events appeared to be more frequently reported.…”

Incidence of diabetes mellitus and neoplasia in Japanese short-statured children treated with growth hormone in the Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS)

“…Treatment of short-statured children with recombinant human GH is associated with significant improvements in growth, leading to attainment of normal or near-normal final height ( 3 , 4 ). Treatment with GH also has a beneficial impact on body composition ( 5 ), and GH is considered to be well tolerated, with few reported adverse reactions ( 3 , 4 , 6 , 7 ).…”