What are the side effects of recombinant human Growth Hormone (GH) injections?

From the Guidelines

Growth hormone injections can cause rare but significant side effects, including glucose intolerance and increased cranial pressure, which should be carefully weighed against the benefits of treatment. When considering the potential side effects of growth hormone injections, it is essential to prioritize morbidity, mortality, and quality of life as the primary outcomes. According to the most recent and highest quality study available, 1, the adverse effects of growth hormone treatment are rare and include glucose intolerance and increased cranial pressure.

The study published in Nature Reviews Nephrology in 2019 1 provides valuable insights into the potential side effects of growth hormone injections in children with chronic kidney disease. The authors recommend that children with stage 3–5 CKD or those on dialysis older than 6 months of age should be candidates for GH therapy if they have persistent growth failure. However, they also emphasize the importance of informing patients and their families about the potential adverse effects of GH treatment before initiation.

Some key points to consider when evaluating the side effects of growth hormone injections include:

• The expected increase in final height after 2–5 years of GH treatment amounts to approximately 7.2 cm 1
• The benefits of GH treatment with respect to increased stature must be weighed against the burden of daily subcutaneous injections on an individual basis 1
• Adverse effects of GH treatment are rare and include glucose intolerance and increased cranial pressure 1
• Patients and their families should be informed before initiation of GH therapy that individual growth responses differ widely 1

Another study published in the same journal in 2019 1 provides further information on the potential adverse events associated with growth hormone treatment. The authors report that the adverse effects of GH are similar across different dosages and to those reported by participants in untreated control populations. However, they also emphasize the importance of monitoring the effect of long-term treatment and assessing registry data to fully understand the potential risks and benefits of GH therapy.

In terms of specific side effects, the evidence suggests that:

• Glucose intolerance is a potential side effect of growth hormone injections 1
• Increased cranial pressure is a rare but significant side effect of growth hormone injections 1
• Other potential side effects, such as malignancy, slipped capital femoral epiphysis, avascular necrosis, pancreatitis, rapid progression of CKD, acute allograft rejection, or fluid retention, have not been significantly associated with GH therapy in large cohorts of pediatric CKD patients 1

From the Research

Side Effects of Growth Hormone Injections

• The use of growth hormone (GH) at replacement doses in children with GH deficiency has resulted in rare and generally reversible adverse effects 2.
• The long-term administration of pharmacologic GH doses to short, mostly non-GH-deficient children must, however, still be viewed with caution, as long-term complications cannot as yet be fully evaluated 2.
• In adults, GH deficiency causes a distinct syndrome with significant morbidities, including increased total and visceral fat, decreased muscle mass and aerobic capacity, affective disturbances, abnormal lipids, and increased vascular mortality, all of which are ameliorated with GH replacement 3.
• Hormonal side effects are minimized by stepwise dose titration in adult GH dosing 3.
• Lingering concerns remain regarding the possibility of increased cancer risk with long-term treatment, but this hazard has not been unequivocally demonstrated 3.
• Daily recombinant human GH (rhGH) is currently approved for use in children and adults with GH deficiency (GHD) in many countries with relatively few side-effects 4.
• Long-acting GH (LAGH) analogs may pose potential clinical issues in terms of dose initiation, therapeutic monitoring, incidence and duration of side-effects, and long-term safety 4.

Common Side Effects

• Increased concentrations of fasting and postprandial lipids, coagulation factors, and several independent cardiovascular risk factors have been reported in GH-deficient children and adolescents and appear to improve with GH administration 2.
• Decreased bone mineral densities have been reported in GH-deficient children and adolescents and appear to improve with GH administration 2.
• Abnormal body composition, excess body fat, and a decrease in the extracellular water volume have been reported in adults with GH deficiency 5.
• Lipid abnormalities, decreased insulin sensitivity, and a decreased fibrinolysis have been reported in adults with GH deficiency 5.