What is the treatment for acromegaly?

Treatment of Acromegaly

The primary treatment for acromegaly is transsphenoidal surgery by an experienced pituitary neurosurgeon, followed by medical therapy with somatostatin receptor ligands (SRLs) if surgery fails or is contraindicated. 1

Treatment Algorithm

First-Line Treatment

• Surgical Approach
  • Transsphenoidal surgery offers the best chance of complete remission
  • Success rate approximately 50% in experienced centers 1
  • Goal: Complete tumor removal and normalization of GH and IGF-1 levels

Second-Line Treatment (If Surgery Fails or Is Contraindicated)

• Medical Therapy Options:

1. First-line medical therapy: Somatostatin Receptor Ligands (SRLs)

   • Octreotide LAR or Lanreotide Injection 2, 3
   • Lanreotide starting dose: 90 mg subcutaneously every 4 weeks for 3 months 3
   • After 3 months, adjust dosage based on response:
     • GH >1 to ≤2.5 ng/mL, normal IGF-1, controlled symptoms: maintain 90 mg
     • GH >2.5 ng/mL, elevated IGF-1, uncontrolled symptoms: increase to 120 mg
     • GH ≤1 ng/mL, normal IGF-1, controlled symptoms: reduce to 60 mg 3
   • SRLs normalize biochemical parameters in approximately 25% of unselected treatment-naive patients 2

2. Second-line options for partial or non-responders to SRLs:

   • Add pegvisomant (GH receptor antagonist) for partial SRL responders 1, 4

     • Pegvisomant blocks GH action at peripheral receptors
     • Normalizes IGF-1 levels in most patients 2
     • Goal: Normalize serum IGF-1 levels 4

   • Switch to pegvisomant for SRL non-responders 1

   • Add cabergoline (dopamine agonist) 2, 1

     • Best response occurs in patients with mildly elevated GH levels and IGF-1 levels <2 times upper limit of normal
     • Less effective if pre-treatment IGF-1 levels are >2.5× upper limit of normal 2

3. Combination therapy options:

   • SRL + cabergoline
   • SRL + pegvisomant 2, 1
   • These combinations may be more effective than monotherapy in resistant cases

Third-Line Treatment

• Radiotherapy
  • Consider for patients with persistent disease after surgery and inadequate response to medical therapy
  • Effects may take up to 10 years to fully manifest 1
  • Medical therapy is often required until radiation effects are evident 2

Monitoring Treatment Response

• Measure GH and IGF-1 levels at 3 and 6 months post-treatment
• Treatment goals:
  • Fasting morning GH <1 μg/L
  • IGF-1 within normal age- and sex-adjusted range 1
• Regular MRI to evaluate tumor size
• Screen for and manage comorbidities (cardiovascular, metabolic, respiratory, gastrointestinal, musculoskeletal)

Important Considerations

• Patients with well-controlled acromegaly on SRLs may be considered for decreased dosing or extended intervals between injections 2
• Long-term safety profiles of SRLs, dopamine agonists, and pegvisomant are generally reassuring 2
• Pegvisomant requires ongoing vigilance to monitor liver function and tumor size 2
• Multidisciplinary management is essential to address the various complications of acromegaly 1

Pitfalls to Avoid

• Delaying treatment can lead to increased morbidity and mortality from cardiovascular, cerebrovascular, and metabolic complications
• Inadequate biochemical monitoring may miss disease progression
• Focusing solely on biochemical parameters without addressing clinical symptoms and comorbidities
• Failure to adjust medication dosages based on treatment response
• Not considering combination therapy in patients with partial response to monotherapy

By following this treatment algorithm and closely monitoring biochemical parameters and clinical symptoms, most patients with acromegaly can achieve disease control, leading to improved quality of life and normalized life expectancy.