What is the recommended treatment protocol for confirmed growth‑hormone deficiency in children and adults, including dosing, monitoring, and contraindications?

Growth Hormone Deficiency Treatment Protocol

For confirmed growth hormone deficiency, initiate recombinant human growth hormone at 0.045-0.05 mg/kg/day via daily subcutaneous injection in the evening, with dose adjustments every 3-6 months based on body weight and clinical response. 1

Dosing Protocol

Pediatric Patients

• Standard dose: 0.045-0.05 mg/kg/day (equivalent to 28-30 IU/m²/week) administered as daily subcutaneous injections 1
• Pubertal patients: May require up to 0.7 mg/kg/week divided daily for optimal response 2
• Dose calculation: Multiply patient's current weight by 0.045-0.05 mg to determine daily dose (e.g., 40 kg patient = 1.8-2.0 mg/day) 3
• Dose adjustments: Recalculate based on body weight at regular intervals (every 3-6 months) 1

Higher doses (56 IU/m²/week) show no additional benefit over standard dosing, while lower doses (14 IU/m²/week) result in 1.18 cm/year less height velocity 1

Adult Patients

Two dosing approaches are acceptable 2:

Weight-based regimen:

• Starting dose: ≤0.006 mg/kg/day 2
• Maximum dose: 0.025 mg/kg/day (age ≤35 years) or 0.0125 mg/kg/day (age >35 years) 2

Non-weight-based regimen:

• Starting dose: 0.2 mg/day (range 0.15-0.30 mg/day) 2
• Increase by 0.1-0.2 mg/day every 1-2 months based on clinical response and IGF-1 levels 2
• Older patients require lower starting doses and smaller increments due to increased adverse effect susceptibility 2
• Obese patients are more prone to adverse effects with weight-based dosing 2
• Estrogen-replete women may require higher doses than men; oral estrogen increases dose requirements 2

Administration Technique

• Timing: Evening injections before bedtime to mimic physiological circadian GH secretion 1, 3
• Route: Daily subcutaneous injection (bioavailability ~80%, Tmax 3-6 hours, half-life 2-3 hours) 1
• Injection sites: Rotate daily among thighs, abdomen, buttocks, and upper outer arms to prevent lipoatrophy 1, 3, 2
• Self-administration: Encourage children aged 8-10 years to self-inject with adequate training and adherence monitoring 1

Monitoring Requirements

Clinical Visits Every 3-6 Months 1, 4

Monitor the following parameters:

• Growth parameters: Height, height velocity, pubertal development 1, 4
• Skeletal maturation: Wrist radiography for bone age 1
• Thyroid function: TSH and free T3 1
• Metabolic parameters: Serum glucose, calcium, phosphate, bicarbonate 1
• Parathyroid hormone levels (especially in CKD patients) 1
• IGF-1 levels: To assess adherence if height velocity increases <2 cm/year over baseline in first year 1

Baseline Assessment

• Fundoscopy: Mandatory before initiating therapy to establish baseline for intracranial hypertension monitoring 1, 3

Contraindications

Absolute contraindications include 1:

• Active malignancy
• Closed epiphyses (pediatric patients)
• Acute critical illness
• Proliferative or severe non-proliferative diabetic retinopathy

Relative contraindications requiring treatment delay 1:

• Slipped capital femoral epiphysis
• Avascular necrosis
• Severe glucose intolerance or uncontrolled diabetes
• Pancreatitis
• Severe secondary hyperparathyroidism (PTH >500 pg/ml in CKD patients) 1
• Acute allograft rejection (transplant patients)
• Significant fluid retention

Duration of Treatment

• Pediatric patients: Continue until epiphyseal closure (final height achieved) or until renal transplantation in CKD patients 2, 5
• Adult patients: Long-term replacement therapy based on clinical response and IGF-1 normalization 2
• Treatment typically lasts 5+ years in pediatric populations to achieve normal adult height 5

Common Pitfalls and Management

Poor First-Year Response (<2 cm/year increase over baseline)

Evaluate 1:

• Adherence: Measure serum IGF-1 levels
• Hypothyroidism: Check thyroid function
• Malnutrition: Assess nutritional status
• Advanced bone age: Review skeletal maturation
• GH antibodies: Consider antibody testing

Intracranial Hypertension

• Occurs rarely (3/1,376 CKD patients in registry data) 1
• Perform immediate fundoscopy if persistent headache or vomiting develops 1, 3
• May occur even after GH discontinuation 1

Glucose Intolerance

• Insulin secretion increases during first year and hyperinsulinemia persists long-term 1
• Risk is higher in obese patients 1, 3
• Monitor glucose closely in high-risk populations (obesity, nephropathic cystinosis) 1
• Treatment for ≤5 years typically does not adversely affect glucose tolerance in most patients 1

Secondary Hyperparathyroidism (CKD patients)

• GH may directly stimulate parathyroid gland or affect calcium/phosphate homeostasis 1
• Adequately treat CKD-MBD before initiating GH 1
• Withhold GH if PTH >500 pg/ml; reinstitute when PTH returns to target range 1

Lipoatrophy

• Prevented by daily rotation of injection sites 1, 3, 2
• Inspect injection sites regularly

Product Selection

Both reference GH products and biosimilars are appropriate for use, as 10+ years of pharmacovigilance data show no relevant safety differences 1