Childhood Human Growth Hormone Therapy Not Linked to Increased Mortality

July 23, 2020

New research suggests risk of mortality associated with recombinant human growth hormone was linked to underlying diagnosis, not cumulative treatment or mean doses.

Long-term follow-up of patients from the Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) consortium indicates treatment recombinant human growth hormone during childhood was not associated with increased mortality in some pediatric patients.

Results of the analysis indicate all-cause mortality was associated with underlying diagnosis and treatment with recombinant human growth hormone therapy was not associated with increased all-cause mortality in children with isolated growth hormone deficiency or idiopathic short stature.

“This 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,” wrote study investigators. “For patients with an inherent increased mortality risk, we found that increased mortality rates are probably related to the underlying diagnosis.”

Using the entire dataset from the SAGhE consortium, which included 8 European countries and more than 20,000 patients, investigators designed their study to assess all-cause and cause-specific mortality in young adults treated with recombinant human growth hormone during childhood.

For the purpose of analysis, investigator classified patients into 4 distinct risk groups based on underlying diagnosis for recombinant human growth hormone treatment. Risk group 1a included isolated growth hormone deficiency, idiopathic short stature, and mild skeletal dysplasia. Risk group 1b was short stature in children born small for gestational age. Risk group 2 included severe cerebral malformation, short stature and severe extracerebral malformations, clinically defined syndromes, severe chronic pediatric diseases, long-term steroid use in chronic inflammatory diseases, benign pituitary tumors, and Cushing’s syndrome. Risk group 3 included all malignancies Langerhans cell histiocytosis, chronic renal failure, after bone marrow or solid transplantation, and syndromes with down increased risk for malignancies.

Of note, risk group 1a and risk group 1b were considered low risk, group 2 was considered moderate risk, and group 3 was considered high risk. Of the 24,232 patients included in the study, 13145 were classified as being low risk, 7188 were classified as moderate risk, 3587 were classified as high risk, and 312 were not classifiable.

Upon analysis, patients in risk group 1a did not experience an increase in overall mortality with results indicated a standardized mortality rate (SMR) of 1.1 (SMR, 1.1; 95% CI, 0.9-1.3). In risk group 1b, overall mortality significantly increased when analyzed for all countries (SMR, 1.5; 95% CI, 1.1-1.9) but this association failed to reach statistical significance when excluded France from the analyses (SMR, 1.2; 95% CI, 0.8-1.9).

In both risk group 2 (SMR, 3.8; 95% CI, 3.3-4.4) and risk group 3 (SMR, 17.1; 95% CI, 15.6-18.7), overall mortality was increased. Of note, investigators pointed out the risk was similar in analyses assessing the France cohort and 7 other countries separately.

When assessing individual diagnoses from the low risk group, investigators unearthed multiple associations between underlying diagnosis and mortality. Results indicated patients with isolated growth hormone deficiency or idiopathic short stature were not associated with an increase in all-cause mortality (SMR, 1.1; 95% CI, 0.9-1.3) Investigators also found recombinant human growth hormone therapy was associated with increased all-cause mortality in patients born small for gestational age, but this result was driven mainly by the French cohort.

Additionally, results indicated mortality was not associated with mean daily or cumulative doses of recombinant human growth hormone fort any risk groups and mortality from diseases of the circulatory and hematological systems were increased in all risk groups.

This study, “Long-term mortality after childhood growth hormone treatment: the SAGhE cohort study,” was published in The Lancet Diabetes & Endocrinology.