How do corticosteroids (CS) affect growth hormone (GH) production?

From the Guidelines

Corticosteroids suppress growth hormone production through multiple mechanisms, including inhibition of growth hormone-releasing hormone secretion and enhancement of somatostatin release, leading to reduced GH production and impaired GH receptor signaling. When administered at pharmacological doses, corticosteroids like prednisone, dexamethasone, and hydrocortisone interfere with the hypothalamic-pituitary axis, directly reducing GH production from the pituitary gland 1. Additionally, corticosteroids impair GH receptor signaling in target tissues and reduce insulin-like growth factor-1 (IGF-1) production, further diminishing growth effects. This suppression is dose-dependent and more pronounced with longer treatment durations, particularly concerning in children where it can lead to growth impairment. The effect is most significant with daily dosing regimens rather than alternate-day therapy. Growth velocity typically recovers after discontinuation of corticosteroids, though catch-up growth may be incomplete if treatment occurred during critical growth periods.

Mechanisms of Suppression

• Inhibition of growth hormone-releasing hormone (GHRH) secretion
• Enhancement of somatostatin release
• Impaired GH receptor signaling in target tissues
• Reduced insulin-like growth factor-1 (IGF-1) production

Clinical Implications

• Children on long-term corticosteroid therapy for conditions like asthma, juvenile arthritis, or inflammatory bowel disease often experience growth delays and may require growth monitoring during treatment 1.
• Steroid minimization protocols can help mitigate growth failure in pediatric renal transplant recipients, with a significant increase in height SDS in the steroid avoidance group 1.
• Growth hormone therapy can be beneficial for short prepubertal renal transplant recipients, with a significantly higher growth velocity and mean height SDS difference compared to the control group 1.

Recommendations

• Corticosteroids should be used with caution in children, particularly during critical growth periods, and growth monitoring should be performed regularly.
• Steroid minimization protocols should be considered for pediatric renal transplant recipients to mitigate growth failure.
• Growth hormone therapy should be considered for short prepubertal renal transplant recipients who do not achieve expected catch-up growth with steroid minimization or for whom steroid withdrawal is not feasible.

From the Research

Effects of Corticosteroids on Growth Hormone Production

• Corticosteroids have been shown to suppress growth hormone (GH) production, leading to growth suppression in children 2, 3, 4, 5.
• The potency of different corticosteroids in suppressing growth varies, with dexamethasone and betamethasone being nearly 18 times more potent than prednisolone 2.
• Administration of small doses of prednisolone (10-15 mg/day) can help minimize growth suppression 2.
• Alternate day treatment with corticosteroids can also help reduce growth suppression 2.

Reversal of Corticosteroid-Induced Growth Suppression with GH Therapy

• GH therapy has been shown to reverse the growth-suppressing effects of corticosteroids in children 3, 4, 5.
• Studies have demonstrated that GH therapy can increase growth rates, improve height SD scores, and enhance linear growth in children treated with corticosteroids 3, 4.
• The response to GH therapy is negatively correlated with the dose of corticosteroids, with higher doses resulting in a reduced response to GH therapy 3.

Mechanism of Corticosteroid-Induced Growth Suppression

• Corticosteroids interfere with the GH-insulin-like growth factor-I (IGF-I) axis, leading to reduced production of local IGF-I and increased apoptosis in growth plate chondrocytes and osteoblast cell lines 5.
• The Janus kinase (JAK)-2/signal transducers and activators of transcription (STAT)-5 pathway is involved in the interaction between corticosteroids and the GH receptor 5.
• GH can partly counterbalance the negative effects of corticosteroids on growth, both in vitro and in vivo 5.

Clinical Implications

• GH therapy may be beneficial in treating children on chronic corticosteroids, both as a growth-promoting agent and as an anabolic agent on whole body protein and bone 4.
• Longer-term studies are needed to better define the safety and efficacy of GH therapy in this context 4.
• The use of GH therapy in corticosteroid-treated children should be carefully considered, taking into account the potential benefits and risks, as well as the individual child's needs and circumstances 6.