Growth Hormone Therapies

Growth hormone therapies include recombinant somatropin (daily), long-acting weekly growth hormone preparations, growth hormone releasing hormone analogues (tesamorelin), recombinant IGF-1 (mecasermin) and the growth hormone receptor antagonist pegvisomant. They treat growth failure, adult growth hormone deficiency, selected syndromes, HIV lipodystrophy and, for pegvisomant, acromegaly.

Mechanism. Growth hormone acts on the growth hormone receptor through JAK2 and STAT5 signalling and raises hepatic IGF-1, which drives linear growth. It also promotes lipolysis, protein synthesis and glucose counter-regulation. Pegvisomant blocks receptor dimerisation.

Pharmacokinetics. Somatropin is given subcutaneously, half-life 3 to 4 hours, with effects lasting longer through IGF-1. Weekly preparations give sustained exposure. Doses are titrated to growth and IGF-1.

Weekly preparations. Lonapegsomatropin about 0.24 mg/kg, somapacitan about 0.16 mg/kg and somatrogon about 0.66 mg/kg weekly in children with growth hormone deficiency.

Others. Tesamorelin 2 mg daily for HIV-associated abdominal lipodystrophy. Mecasermin 0.04 to 0.08 mg/kg twice daily for severe primary IGF-1 deficiency. Pegvisomant for acromegaly: 40 mg subcutaneous loading, then 10 mg daily, titrated by 5 mg increments to a maximum of 30 mg daily by IGF-1.

• Children: start after biochemical confirmation (peak stimulated growth hormone under 7 to 10 micrograms/L, depending on the test and laboratory) and low IGF-1; give at bedtime; stop at near-final height.
• Adults: treat severe deficiency with symptoms or low quality of life, starting low in older adults and with higher doses in women on oral oestrogen.
• Targets: height velocity in children; IGF-1 in the age-adjusted mid to upper normal range in adults.
• Syndromes: Prader-Willi syndrome, with caution for sleep apnoea and obesity; Turner syndrome; chronic kidney disease.
• Transition: re-test growth hormone status at the end of growth.

Special groups. Pregnancy: stop when pregnancy is confirmed, because placental growth hormone takes over. Breastfeeding: avoid or specialist advice. Children: monitor glucose, scoliosis and thyroid status. Older adults: start at 0.1 to 0.2 mg daily. Kidney and liver impairment: dose by response. Regional: cost and the cold chain (2 to 8 degrees C) limit access.

Adverse effects. Headache, idiopathic intracranial hypertension, slipped capital femoral epiphysis, scoliosis progression, fluid retention, arthralgia, carpal tunnel syndrome, insulin resistance and hyperglycaemia, unmasking of central hypothyroidism, and injection site lipoatrophy.

Contraindications. Active malignancy, active proliferative diabetic retinopathy, closed epiphyses (for growth indications), acute critical illness, and severe obesity or untreated sleep apnoea in Prader-Willi syndrome.

Interactions. Oral oestrogen raises dose needs. Glucocorticoids oppose growth, so keep replacement doses low. Growth hormone increases cortisol clearance and can unmask adrenal insufficiency; it also raises T4 to T3 conversion.

Monitoring. Height and weight every 3 to 6 months, IGF-1 yearly or after dose changes, fasting glucose or HbA1c yearly, thyroid function, bone age yearly, and fundoscopy with headache.

Referral and escalation. All patients are managed by a paediatric or adult endocrinologist. Urgent review for severe headache with visual symptoms, limp or hip pain, or suspected tumour recurrence.