What are the treatment options for acromegaly?

Treatment Options for Acromegaly

Surgery performed by an experienced neurosurgeon is the first-line treatment for acromegaly, offering the prospect of complete remission and should be recommended as the initial approach for most patients. 1

Treatment Algorithm

First-Line Treatment

• Transsphenoidal surgery is the preferred initial treatment for most patients 1
  • Even when complete remission is unlikely, tumor debulking can reduce GH burden and facilitate subsequent medical therapy 1
  • Surgical success rates are approximately 50% in experienced centers 1

Second-Line Treatment (Post-Surgery or Primary Medical Therapy)

When surgery is inappropriate, unsuccessful, or contraindicated, medical therapy becomes essential:

Somatostatin Receptor Ligands (SRLs)

• First-generation SRLs (octreotide and lanreotide) are the drugs of choice for patients with persistent disease after surgery 1
  • Achieve biochemical normalization in approximately 25% of unselected treatment-naive patients 1
  • Long-term (>3 years) safety and efficacy profiles are reassuring 1
  • FDA-approved for "long-term treatment of acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option" 2
  • Both lanreotide and octreotide have similar efficacy but differ in administration methods 1

Dopamine Agonists

• Cabergoline can be used:
  • As monotherapy in patients with mild GH excess 1
  • In combination with SRLs when GH hypersecretion is inadequately controlled 1
  • Best response occurs in patients with mildly elevated GH and IGF-I levels <2 times the upper limit of normal 1
  • Long-term safety profile is reassuring regarding cardiac valve effects 1

GH Receptor Antagonist

• Pegvisomant has well-established efficacy in normalizing IGF-I levels 1, 3
  • FDA-approved for "treatment of acromegaly in patients who have had an inadequate response to surgery or radiation therapy, or for whom these therapies are not appropriate" 3
  • At appropriate doses, normalizes IGF-I levels in most patients 1
  • Long-term safety data are reassuring with few serious adverse events 1
  • Requires ongoing monitoring of liver function and tumor size 1

Third-Line Treatment

• Radiotherapy for patients with:
  • Uncontrolled tumor growth 1
  • Incomplete surgical and medical response 1
  • May take up to 10 years to be fully effective in suppressing GH 1
  • Medical therapy is typically required while awaiting full radiotherapy effect 1

Treatment Decision Algorithm for Medical Therapy

When Disease is Well-Controlled on SRLs

• Consider reducing SRL dose or increasing dose interval 1
• If response is lost, consider switching to pegvisomant 1

When Partial Response to SRLs

• Increase SRL dose 1
• If still inadequate, consider adding pegvisomant 1

When No Response to SRLs

• Consider combination of SRL + pegvisomant 1
• If no response, consider SRL withdrawal and closely monitor IGF-I levels 1

Treatment Goals and Monitoring

• Normalize growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels 1, 4
• Reduce tumor size and preserve vision 1
• Prevent long-term morbidity and mortality 1, 4
• Regular monitoring of IGF-1 levels and repeat biochemical and radiological assessments 1

Important Considerations

• Mortality reduction: Medical treatment of acromegaly with normalization of GH and IGF-I levels decreases mortality rates 1
• Comorbidity management: Treatment improves left ventricular hypertrophy, hypertension, and obstructive sleep apnea 1
• Limitations: Medical treatment might not improve arthropathy, and effects on soft-tissue tumors remain unknown 1
• Caution with radiation: Conventional radiation therapy requires careful consideration due to potential increased mortality and morbidity 1

Special Populations

• Genetic causes: In patients with genetic causes of acromegaly (McCune-Albright syndrome, Carney complex, X-linked acrogigantism), the whole pituitary gland may be affected, requiring different surgical approaches 1
• Children and adolescents: GH receptor antagonists like pegvisomant can effectively suppress growth velocity in children with gigantism 1