What are the indications for growth hormone (GH) replacement therapy?

Indications for Growth Hormone Replacement Therapy

Growth hormone replacement therapy is indicated for pediatric patients with growth failure due to GH deficiency, chronic kidney disease (up to renal transplantation), idiopathic short stature, and Turner syndrome, and for adults with confirmed GH deficiency of either childhood or adult onset. 1

Pediatric Indications

Growth Hormone Deficiency (GHD)

• Indicated for children with documented inadequate secretion of endogenous growth hormone
• Diagnosis requires:
  • Height below 3rd percentile or height velocity below 25th percentile persisting for at least 3 months in infants or 6 months in older children 2
  • Confirmatory GH stimulation testing
  • Dosage: Up to 0.3 mg/kg/week divided into daily subcutaneous injections (up to 0.7 mg/kg/week for pubertal patients) 1

Chronic Kidney Disease (CKD)

• Indicated for growth failure associated with CKD up to the time of renal transplantation 1
• GH therapy must be stopped at the time of renal transplantation 3
• Dosage: Up to 0.35 mg/kg/week divided into daily subcutaneous injections 1
• Special considerations for dialysis patients:
  • Hemodialysis: Administer injection at night before sleep or 3-4 hours after hemodialysis
  • CCPD: Administer in morning after dialysis completion
  • CAPD: Administer in evening during overnight exchange 1

Idiopathic Short Stature (ISS)

• Defined as height SDS ≤ -2.25 with growth rates unlikely to permit attainment of normal adult height 1
• Diagnostic evaluation must exclude other causes of short stature
• Dosage: Up to 0.3 mg/kg/week divided into daily subcutaneous injections 1

Turner Syndrome (TS)

• Indicated for short stature associated with Turner syndrome
• Dosage: Up to 0.375 mg/kg/week divided into 3-7 subcutaneous injections per week 1

Adult Indications

Adult-Onset GHD

• Patients with GHD resulting from:
  • Pituitary disease
  • Hypothalamic disease
  • Surgery
  • Radiation therapy
  • Trauma 1
• Confirmation requires appropriate GH provocative testing unless patient has multiple pituitary hormone deficiencies due to organic disease 1

Childhood-Onset GHD (Transition to Adult Care)

• Patients previously diagnosed with GHD during childhood due to:
  • Congenital causes
  • Genetic causes
  • Acquired conditions
  • Idiopathic causes 1
• Re-evaluation required after growth completion:
  • GH treatment should be discontinued for at least 1 month after attainment of adult height
  • Retesting not required for patients with transcription factor mutations, more than 3 pituitary hormone deficits, or isolated GHD with identified mutation 4
  • Key predictors of persistent GHD: severity of deficiency, presence of additional pituitary hormone deficits, low IGF-I concentration, and structural hypothalamic-pituitary abnormalities 4

Monitoring and Discontinuation Criteria

Monitoring Parameters

• Height velocity (pediatric patients)
• IGF-I levels (primary biochemical marker for dose adjustment)
• Bone age via left wrist radiography (yearly in pediatric patients)
• Pubertal development (Tanner staging for children >10 years)
• Renal function (especially in CKD patients)
• Glucose metabolism
• Calcium and phosphate homeostasis 3

Discontinuation Criteria

• When epiphyses are fused in pediatric patients 1
• Height velocity drops below 2 cm/year in late-pubertal adolescents with evidence of epiphyseal closure 3
• Patient reaches genetic target height 3
• Inadequate response despite optimal dosing for at least 6 months 3
• Development of serious adverse effects:
  • Intracranial hypertension
  • Slipped capital femoral epiphysis
  • Severe secondary hyperparathyroidism
  • Unexplained decrease in eGFR in CKD patients 3

Common Pitfalls and Caveats

1. Inadequate Diagnostic Workup: Random GH measurements are not reliable for diagnosis due to pulsatile secretion pattern 5

2. Inappropriate Dosing:

   • Starting with too high a dose increases risk of side effects
   • Adult therapy should start at low doses (0.2-0.5 mg/day) and be adjusted based on IGF-I levels 4

3. Failure to Recognize Non-Responders:

   • Adequate response defined as height velocity increase >2 cm/year over baseline during first year of treatment
   • For non-responders, assess adherence, IGF-I levels, weight-adjusted dosing, and nutritional/metabolic factors 3

4. Missing Contraindications:

   • Active malignancy
   • Uncontrolled diabetes mellitus
   • Pre-existing papilledema
   • Hypersensitivity to GH or its constituents 3

5. Overlooking Special Populations:

   • Women may require higher replacement doses than men 6
   • Patients with nephropathic cystinosis have increased risk of diabetes mellitus 3