Growth Hormone Therapy for Growth Hormone Deficiency (GHD)
The primary treatment for Growth Hormone Deficiency (GHD) is recombinant human growth hormone (rhGH) administered at a dose of 0.045-0.05 mg/kg per day via subcutaneous injections. 1
Diagnosis and Indications
Growth hormone therapy is indicated for:
- Pediatric patients with growth failure due to inadequate secretion of endogenous growth hormone 2
- Growth failure associated with chronic kidney disease (CKD) up to the time of renal transplantation 1, 2
- Idiopathic short stature (ISS) defined by height SDS ≤ –2.25 2
- Short stature associated with Turner Syndrome 2
- Adult patients with childhood-onset or adult-onset GHD 2
Treatment Protocol
Dosing
- Pediatric GHD: 0.045-0.05 mg/kg per day via subcutaneous injection 1
- Growth failure with CKD: 0.045-0.05 mg/kg per day, irrespective of patient's age 1
- Administration: Daily subcutaneous injections in the evening to mimic physiological circadian rhythm 1
- Injection site: Should be changed daily to avoid lipoatrophy 1
Monitoring and Follow-up
- Clinic visits every 3-6 months (more frequently for young patients and those with advanced CKD) 1
- Monitor:
- Stature and height velocity
- Pubertal development
- Skeletal maturation (wrist radiography)
- Renal function
- Thyroid hormone levels (TSH and free T3)
- Serum glucose, calcium, phosphate, bicarbonate, and parathyroid hormone levels 1
Treatment Duration and Endpoints
Treatment should continue until:
- Epiphyseal closure is demonstrated 1
- Patient reaches genetic target height 1
- Patient reaches normal population-related adult height (above third percentile) 1
When to Discontinue GH Therapy
GH therapy should be stopped in cases of:
- Epiphyseal closure 1
- At the time of renal transplantation 1
- Persistent severe secondary hyperparathyroidism (PTH >500 pg/ml) 1
- Intracranial hypertension 1
- Slipped capital femoral epiphysis 1
- Inadequate response despite optimal nutritional and metabolic control 1
- Accelerated bone maturation 1
- Unexplained decrease in estimated glomerular filtration rate 1
Special Considerations
Post-Transplantation
For children who have received a kidney transplant and have persistent growth failure:
- Initiate GH therapy 1 year after transplantation if spontaneous catch-up growth does not occur 1
- Consider if steroid-free immunosuppression is not feasible 1
Safety and Adverse Effects
Common potential adverse effects include:
- Intracranial hypertension (rare but serious) - baseline fundoscopy recommended before initiation 1
- Glucose intolerance - close monitoring advised, especially in obese patients 1
- Secondary hyperparathyroidism - CKD-MBD should be adequately treated before GH therapy 1
Contraindications
GH therapy should not be started in:
- Patients with closed epiphyses 1
- Patients with hypersensitivity to the active substance 1
- Patients with severe secondary hyperparathyroidism (PTH >500 pg/ml) 1
- Patients with proliferative or severe non-proliferative diabetic retinopathy 1
- Patients with acute critical illness 1
- Patients with active malignancy 1
Approved Products
Both GH reference products and GH biosimilars are recommended for use in short children with CKD, as pharmacovigilance over the past decade has not identified any relevant differences in safety profiles 1.
Treatment Response Considerations
The response to GH treatment may vary based on:
- Residual renal function
- Target height
- Initial target height deficit
- Treatment duration
- Age at start of treatment (younger age associated with better response) 1
The response to GH is typically attenuated in children on dialysis compared to those with earlier stages of CKD, likely due to a higher degree of GH insensitivity 1.