What peptide therapies are suitable for children with low percentile growth due to conditions like growth hormone deficiency?

Recombinant Human Growth Hormone (rhGH) for Pediatric Low Percentile Growth

Recombinant human growth hormone (somatropin) is the primary peptide therapy approved for children with low percentile growth, with specific indications including growth hormone deficiency, idiopathic short stature, chronic kidney disease, and Turner syndrome. 1

FDA-Approved Indications for Pediatric Growth Failure

Growth Hormone Deficiency (GHD)

• Indicated for children with inadequate endogenous GH secretion causing growth failure 1
• Dosing: Up to 0.3 mg/kg/week divided into daily subcutaneous injections 1
• In pubertal patients, dosing may increase to 0.7 mg/kg/week divided daily 1
• Treatment continues until epiphyseal closure 1

Idiopathic Short Stature (ISS)

• Approved for children with height ≤ -2.25 standard deviation score (below approximately 1st percentile) with growth rates unlikely to reach normal adult height 1
• Requires exclusion of other treatable causes of short stature 1
• Epiphyses must remain open 1
• Dosing: Up to 0.3 mg/kg/week divided into daily subcutaneous injections 1

Chronic Kidney Disease (CKD)

• Recommended for children with stage 3-5 CKD or on dialysis who have height below the 3rd percentile AND height velocity below the 25th percentile 2
• Other treatable risk factors (malnutrition, metabolic acidosis, mineral bone disorder) must be adequately addressed first 2
• Dosing: Up to 0.35 mg/kg/week divided into daily subcutaneous injections 1
• Continue until renal transplantation 1
• Post-transplant: Initiate GH therapy 1 year after transplantation if spontaneous catch-up growth does not occur 2

Turner Syndrome

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

Critical Pre-Treatment Requirements

Diagnostic Workup Must Exclude Other Causes

• Screen for hypothyroidism (TSH, free T4) as this is a reversible cause that must be treated first 3
• Celiac disease screening (tissue transglutaminase IgA, total IgA) 3
• Complete blood count to identify chronic anemia 3
• Basic metabolic panel and liver function tests to exclude chronic kidney or liver disease 3
• Girls require karyotype to rule out Turner syndrome, which is frequently missed 3
• SHOX gene testing if skeletal findings suggest mutations (short forearms, Madelung deformity) 3

Growth Potential Assessment

• Bone age radiograph (wrist) is mandatory to determine remaining growth potential 3, 4
• Height must be documented serially on growth charts with calculated growth velocity 3
• Mid-parental target height calculation determines if current trajectory will reach genetic potential 3

Nutritional Optimization Required First

• Ensure adequate caloric and protein intake before initiating GH therapy 3
• Supplement identified deficiencies (vitamin D, iron, zinc) which independently impair growth 3
• Comprehensive nutritional evaluation including albumin, prealbumin, vitamin D, B12, folate, iron studies, and zinc 3

Dosing and Administration Protocol

Standard Regimen

• Daily subcutaneous injections at 0.045-0.05 mg/kg/day administered at night to mimic physiological circadian rhythm 5
• Injection site must be rotated daily to prevent lipoatrophy 5
• Both reference products and biosimilars are acceptable 5

Monitoring Schedule

• Clinical consultations every 3-6 months to assess: 5
  • Height and growth velocity 5
  • Pubertal development (Tanner staging) 5, 3
  • Skeletal maturation (annual wrist radiography) 5, 3
  • Thyroid function (TSH, free T3) 5
  • Blood glucose, calcium, phosphate, bicarbonate 5

Response Evaluation

• If growth velocity in the first year is less than 2 cm/year above baseline, evaluate: 5
  • Patient adherence to therapy 5
  • Serum IGF-1 levels 5
  • Dose adjustment based on weight 5
  • Nutritional and metabolic factors 5

Absolute Contraindications

Do not initiate GH therapy in: 5, 1

• Closed epiphyses 5, 1
• Active malignancy 5, 1
• Critical acute illness 5, 1
• Severe secondary hyperparathyroidism (PTH > 500 pg/ml) 5
• Known hypersensitivity to somatropin or excipients 5, 1

Critical Safety Monitoring

Serious Adverse Events Requiring Immediate Evaluation

• Intracranial hypertension (requires baseline fundoscopy before starting therapy) 5
• Persistent headache or vomiting mandates immediate ophthalmologic evaluation 5
• Femoral head epiphysiolysis (perform radiographs if hip/knee pain or limping occurs) 5
• Glucose intolerance, especially in obese patients 5

Mandatory Discontinuation Criteria

Stop GH therapy when: 5, 4

• Epiphyseal closure occurs 5, 4
• Persistent severe secondary hyperparathyroidism (PTH > 500 pg/ml) 5
• Intracranial hypertension develops 5
• Femoral head epiphysiolysis occurs 5
• Height velocity drops below 2 cm/year 4
• Inadequate response despite optimal nutritional and metabolic control 5

Age-Specific Considerations

Pubertal Patients

• At age 13, pubertal stage (Tanner staging) is essential as growth potential diminishes with advancing puberty 4
• Bone age assessment becomes even more critical to determine remaining growth window 4
• Consider higher dosing (up to 0.7 mg/kg/week) in pubertal patients with GHD 1

Early Treatment Advantage

• Early recognition and treatment initiation is essential for optimal height outcome 6, 7
• Greater height deficit at treatment start lowers probability of reaching target height 7
• Treatment of neonatal hypopituitarism has resulted in excellent growth responses 7

Common Clinical Pitfalls

• Failing to distinguish normal variants (constitutional delay, familial short stature) from pathologic causes leads to unnecessary treatment 3
• Missing Turner syndrome in girls—always obtain karyotype in short girls even without obvious features 3
• Overlooking nutritional deficiencies that are readily treatable causes of growth impairment 3
• Delaying evaluation when growth velocity declines—progressive deceleration suggests pathology requiring prompt investigation 3
• Poor compliance is the most common cause of suboptimal response 5, 7