What are the recommended types of growth hormone replacement therapy for patients with growth hormone deficiency, considering factors such as age, weight, and medical history?

Types of Growth Hormone Replacement Therapy

All growth hormone replacement products are recombinant human growth hormone (rhGH, also called somatropin), administered as daily subcutaneous injections, with emerging long-acting formulations now available for weekly dosing. 1, 2

Standard Daily Formulations

Recombinant Human Growth Hormone (Somatropin)

• All currently approved products contain the same active ingredient—recombinant human growth hormone (somatropin)—which is bioidentical to endogenous GH. 1, 3
• Both reference products and biosimilars of somatropin are recommended for use, as they demonstrate equivalent efficacy and safety profiles. 4
• The standard formulation requires daily subcutaneous injections, typically administered at night to mimic the physiological circadian rhythm of endogenous GH secretion. 4, 5, 2

Delivery Systems and Devices

• Multiple delivery devices are available, including prefilled pens (such as Norditropin FlexPro) that do not require reconstitution and offer flexible storage features. 3
• Injection sites must be rotated daily to prevent lipoatrophy, a common complication of repeated injections at the same site. 4, 5, 2

Dosing Protocols by Indication

Pediatric Growth Hormone Deficiency

• Standard dosing: 0.16-0.24 mg/kg/week (equivalent to approximately 0.023-0.034 mg/kg/day), divided into 6-7 daily injections. 1
• Alternative formulation (Nutropin AQ): Up to 0.3 mg/kg/week for prepubertal patients, with higher doses up to 0.7 mg/kg/week for pubertal patients. 2

Specific Pediatric Conditions

• Prader-Willi Syndrome: 0.24 mg/kg/week divided over 6-7 days, though treatment can begin as early as 2-3 months of age despite FDA approval only for children >2 years. 6, 1
• Small for Gestational Age: Up to 0.48 mg/kg/week divided over 6-7 days. 1
• Turner Syndrome: 0.33-0.375 mg/kg/week divided over 6-7 days. 1, 2
• Idiopathic Short Stature: Up to 0.47 mg/kg/week divided over 6-7 days. 1, 2
• Chronic Kidney Disease (Stage 3-5): Up to 0.35 mg/kg/week, with treatment initiated only after addressing metabolic acidosis, malnutrition, and mineral bone disorders. 6, 2

Adult Growth Hormone Deficiency

• Weight-based dosing: Start at ≤0.04 mg/kg/week (approximately 0.006 mg/kg/day), with gradual increases every 4-8 weeks based on IGF-1 levels and clinical response. 1, 2
• Non-weight-based dosing: Start at 0.2 mg/day (range 0.15-0.3 mg/day), increased gradually every 1-2 months by increments of 0.1-0.2 mg/day. 2
• Maximum doses vary by age: up to 0.025 mg/kg/day for patients ≤35 years old, or 0.0125 mg/kg/day for patients >35 years old. 2

Long-Acting Formulations

Somatrogon (Weekly Injection)

• Somatrogon is a long-acting GH analog administered once weekly, designed to reduce treatment burden and improve adherence compared to daily injections. 7
• Phase II and III clinical trials demonstrate that once-weekly somatrogon is noninferior to once-daily somatropin in terms of efficacy, safety, and tolerability for pediatric GH deficiency. 7
• This formulation addresses the challenge of low adherence to daily rhGH treatment, which can result in suboptimal effectiveness throughout childhood. 7

Somapacitan (Weekly Injection)

• Somapacitan is the first long-acting GH preparation approved for adult GH deficiency in the United States, Europe, and Japan. 8
• Administered once weekly via subcutaneous injection, reducing treatment burden for adults requiring GH replacement. 8
• Physicians must understand the pharmacokinetic and pharmacodynamic differences between long-acting preparations, as variations in half-life prolongation technologies affect dosing and monitoring strategies. 8

Key Considerations for Product Selection

Efficacy Across Formulations

• All somatropin products demonstrate similar efficacy when dosed appropriately, with GH-deficient children reaching nearly normal final heights, though typically still below their genetic target heights. 9
• Long-term administration improves body composition, muscle strength, quality of life, bone mass, and lipoprotein patterns in both children and adults. 9, 10

Safety Profile

• Adverse effects are generally rare and reversible at replacement doses, but include intracranial hypertension, fluid retention, glucose intolerance, worsening of scoliosis, and slipped capital femoral epiphysis. 3, 11
• Long-acting formulations show comparable safety profiles to daily formulations in clinical trials. 7, 8

Monitoring Requirements

• IGF-1 levels should be measured at least twice yearly to guide dosing and maintain physiological levels, regardless of formulation used. 4, 5
• Clinical consultations every 3-6 months should assess height, growth velocity, pubertal development, skeletal maturation, thyroid function, and metabolic parameters. 4, 5, 11

Common Pitfalls to Avoid

• Do not initiate any GH formulation in patients with closed epiphyses, active malignancy, acute critical illness, or severe secondary hyperparathyroidism (PTH >500 pg/ml). 6, 4, 5
• In Prader-Willi Syndrome, perform polysomnography before and 6-10 weeks after starting GH therapy, regardless of age, due to risk of obstructive sleep apnea and adenotonsillar hypertrophy. 6
• Ensure adequate treatment of hypothyroidism, malnutrition, metabolic acidosis, and mineral bone disorders before initiating GH therapy, as these factors limit treatment response. 6, 11
• For post-transplant patients, wait at least 1 year after kidney transplantation before initiating GH therapy. 6