What is the treatment for an adult patient with growth hormone deficiency, specifically using sermorelin (growth hormone-releasing hormone (GHRH) analogue)?

Sermorelin for Adult Growth Hormone Deficiency

Sermorelin is not recommended as standard treatment for adult growth hormone deficiency; recombinant human growth hormone (rhGH) replacement therapy is the established treatment of choice. 1, 2

Why Sermorelin Is Not Standard Care in Adults

Direct growth hormone replacement with rhGH is the evidence-based standard for treating adult GHD, not growth hormone-releasing hormone (GHRH) analogues like sermorelin. 1, 3, 4 The major clinical guidelines from the Endocrine Society and American Association of Clinical Endocrinologists exclusively recommend rhGH replacement therapy for adults with confirmed GHD, with no mention of sermorelin as a therapeutic option. 1, 2

Limited Evidence Base for Sermorelin in Adults

• Sermorelin has primarily been studied and used diagnostically as a provocative test for GH deficiency, not therapeutically. 5
• The therapeutic data for sermorelin exists almost exclusively in prepubertal children with idiopathic GHD, not adults. 5
• Even in children, sermorelin at 30 mcg/kg/day subcutaneously produced inferior height velocity gains compared to direct rhGH replacement at equivalent dosing. 5

Mechanism Limitations in Adults

• Sermorelin works by stimulating the pituitary to release endogenous GH, which requires a functioning pituitary gland with adequate somatotroph reserve. 5
• Most adult GHD results from pituitary damage (surgery, tumors, radiation), where the pituitary cannot respond adequately to GHRH stimulation. 1, 3
• Post-radiotherapy GHD affects 36% at 99 months and becomes nearly universal by 5 years, representing severe pituitary damage that would not respond to sermorelin. 1

Established Treatment: Recombinant Human Growth Hormone

Adults with confirmed GHD should receive rhGH replacement therapy starting at no more than 0.04 mg/kg/week (approximately 0.006 mg/kg/day) given as daily subcutaneous injections. 1, 2

Dosing Algorithm

• Starting dose: Begin with low-dose rhGH at 0.2-0.3 mg/day (or 0.04 mg/kg/week) for most adults. 1, 2
• Dose adjustments: Titrate at 4- to 8-week intervals based on clinical response and serum IGF-1 levels. 1, 2
• Age considerations: Older adults (>60 years) require lower doses due to increased sensitivity to GH. 2
• Gender considerations: Women, especially those on oral estrogen, may require higher doses than men. 2
• Weight-based adjustments: Regularly adjust dosing based on body weight changes. 1

Administration Details

• Timing: Evening subcutaneous injections to mimic physiological circadian rhythm. 6
• Injection sites: Rotate daily to avoid lipoatrophy. 6
• Formulations: Both reference products and biosimilars are appropriate. 6

Diagnostic Confirmation Required Before Treatment

Dynamic GH stimulation testing is mandatory to confirm adult GHD before initiating any treatment. 1, 2

Gold Standard Testing

• Insulin tolerance test (ITT): Remains the gold standard with GH peak <5 mcg/L indicating severe GHD. 1, 3, 2
• Alternative tests: GHRH-arginine test or glucagon stimulation test when ITT is contraindicated. 1, 2
• IGF-1 alone is insufficient: Low IGF-1 is insensitive for diagnosing adult GHD and cannot be used as the sole criterion. 1, 2

Clinical Context for Testing

• Test adults with pituitary disease, pituitary surgery, or cranial radiation who have ≥3 other pituitary hormone deficiencies. 2
• Dynamic testing is required even with low IGF-1 levels. 1, 2

Treatment Benefits and Monitoring

Expected Outcomes with rhGH Replacement

• Body composition: Decreased body weight, waist circumference, and visceral adiposity. 1
• Lipid profile: Improved total and LDL cholesterol. 1
• Bone health: Enhanced bone mineral density. 1
• Quality of life: Improved psychological well-being and QoL scores. 1, 4

Monitoring Protocol

• Clinical visits: Every 3-6 months initially, then annually once stable. 7, 1
• IGF-1 levels: Target mid-normal range for age and sex. 2
• Metabolic parameters: Monitor glucose, lipids, thyroid function (TSH, free T4). 7, 2
• Adverse effects: Screen for fluid retention, glucose intolerance, and intracranial hypertension. 6, 7

Safety Considerations and Contraindications

Absolute Contraindications to rhGH

• Active malignancy. 7, 2
• Critical acute illness. 7
• Known hypersensitivity to GH or excipients. 7
• Proliferative or severe non-proliferative diabetic retinopathy. 2

Relative Contraindications and Precautions

• Glucose metabolism: GH can worsen insulin resistance; monitor closely in patients with diabetes or prediabetes. 8, 2
• Tumor surveillance: Lifelong monitoring for pituitary tumor recurrence, though rhGH does not increase recurrence risk. 4, 2
• Intracranial hypertension: Perform baseline fundoscopy; evaluate immediately if persistent headache or vomiting develops. 6, 7

Common Pitfalls to Avoid

• Over-replacement: Using excessive doses increases side effects (edema, arthralgias, carpal tunnel syndrome) without additional benefit. 2
• Inadequate monitoring: Failure to adjust doses based on IGF-1 levels and clinical response. 1, 2
• Ignoring contraindications: Starting therapy without confirming absence of active malignancy or severe retinopathy. 2

Why Not Sermorelin? Key Distinctions

Sermorelin's role is limited to diagnostic testing in children, not therapeutic use in adults. 5 The medication requires intact pituitary function, which is absent in most adult GHD cases. 1, 3 Even in its approved pediatric population, sermorelin produces inferior growth outcomes compared to direct rhGH replacement. 5 No major endocrine society guidelines recommend sermorelin for adult GHD treatment. 1, 2