medwireNews: Receiving treatment with recombinant human growth hormone (rhGH) in childhood is unlikely to be associated with an increased risk for mortality in the long term, show the results of the full SAGhE cohort.

Some patients did have an increased mortality risk, but this was related to their underlying condition, report Lars Sävendahl (Karolinska University Hospital, Stockholm, Sweden) and co-researchers in The Lancet Diabetes & Endocrinology.

In a linked commentary, Stephen Shalet, from The Christie Hospital in Manchester, UK, describes the findings as “reassuring, both for clinicians and the families of those treated with recombinant human growth hormone during childhood.”

The SAGhE cohort included 24,232 patients from Belgium, France (which contributed 42.6% of the cohort), Germany, Italy, the Netherlands, Sweden, Switzerland and the UK, all of whom had been treated with rhGH at any time between its introduction in 1984–1986 and 2007–2009, regardless of treatment duration.

Because rhGH is indicated for some endocrine conditions that are associated with increased mortality risk, the researchers categorised patients according to their highest-risk underlying condition.

The lowest-risk category comprised patients with isolated GH deficiency, idiopathic short stature and mild skeletal dysplasia, and this group had a standardised mortality ratio (SMR) of 1.1, which was not significantly increased versus the general population. There was also no association between mortality risk and the mean daily or cumulative dose of rhGH.

The next risk category contained only children born small for gestational age, and this group had a significantly increased SMR of 1.5, but this was driven by the French subcohort and was not seen for the other countries combined. There was no association between cumulative rhGH dose and mortality risk, but there was a significantly increased SMR of 2.7 associated with the highest mean daily dose category (≥50 μg/kg).

The medium-risk group included multiple pituitary hormone deficiency; syndromes such as Turner, Noonan and Prader-Willi; severe cerebral malformation; and long-term steroid use due to chronic inflammatory disease. The high-risk group included all malignancies and syndromes with a known risk for malignancy, chronic renal failure and children who had undergone transplantation.

For these medium- and high-risk groups, the SMRs were a significantly increased 3.8 and 17.1, respectively, with no differences between France and the other countries. Mortality did not relate to rhGH dose and was highest in patients with multiple underlying diagnoses.

Looking at the lowest-risk group in more detail, the team found that the SMRs were significantly elevated for diseases in blood and blood-forming organs (SMR=8.2), diseases of the circulatory system (SMR=2.4) and cerebrovascular disease (SMR=4.7). Children born small for gestational age also had an increased SMR for diseases of the circulatory system (SMR=3.7).

All but one of the 19 low-risk patients who died of a circulatory cause had been given an rhGH dose within the approved range, with the other being given a higher dose of 61.9 μg/kg per day.

There was no indication of an increased risk of mortality due to neoplasms, which has been a specific concern.

“[T]his European collaborative study found no significant increase in overall mortality in low-risk patients with isolated growth hormone deficiency or idiopathic short stature, although the possibility of certain cause-specific cardiovascular and haematological mortality risks remains”, conclude the researchers.

They stress that “although our cohort of treated patients is large, mortality in this age group is rare, leading to wide [confidence intervals] and uncertainty for certain point estimates of SMR.”

By Eleanor McDermid

medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group

Lancet Diabetes Endocrinol 2020; 8: 683–692
Lancet Diabetes Endocrinol 2020; 8: 651–652

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