What is the initial evaluation and treatment approach for a patient with acromegaly?

Initial Evaluation and Treatment Approach for Acromegaly

The initial evaluation of acromegaly requires biochemical confirmation through elevated IGF-I levels and failure to suppress GH during an oral glucose tolerance test, followed by pituitary MRI to identify the adenoma, with transsphenoidal surgery as the first-line treatment for most patients. 1, 2

Diagnostic Evaluation

Biochemical Confirmation

• Measure serum IGF-I levels as the initial screening test for suspected acromegaly 1
• Perform oral glucose tolerance test (OGTT) with GH measurement as the gold standard diagnostic test - failure to suppress GH to <1 μg/L confirms acromegaly 1, 3
• Using modern sensitive assays, normal individuals should suppress GH to <1 μg/L during OGTT 1
• Random GH <0.4 μg/L and normal age/gender-matched IGF-I can exclude acromegaly 3

Imaging

• Pituitary MRI is essential to identify the underlying pituitary adenoma and assess its size, invasiveness, and relationship to surrounding structures 2
• Evaluate for potential mass effect on optic chiasm and other adjacent structures 2

Comorbidity Assessment

• Evaluate for cardiovascular complications, including left ventricular hypertrophy and heart failure, as these are the most common causes of death in untreated acromegaly 4, 5
• Screen for metabolic complications including diabetes mellitus 6
• Assess for sleep apnea, which is common in acromegaly 6
• Evaluate for musculoskeletal complications, particularly arthropathy 6
• Colonoscopic screening is recommended starting at age 40 due to increased risk of colorectal neoplasia 6, 5

Treatment Approach

First-Line Treatment

• Transsphenoidal surgery is the recommended first-line treatment when an experienced surgeon is available and the tumor is resectable, especially for small well-circumscribed adenomas 6
• Surgery aims to remove the tumor while preserving normal pituitary function 2

Medical Therapy

• Medical therapy is indicated for patients with persistent disease after surgery or as primary therapy when surgery is not appropriate 6
• Somatostatin receptor ligands (SRLs) are the primary medical treatment option if surgery is not appropriate 6, 2

Somatostatin Receptor Ligands (SRLs)

• The recommended starting dosage of lanreotide is 90 mg given subcutaneously at 4-week intervals for 3 months 7

• After 3 months, adjust dosage based on GH and IGF-I levels 7:

  • If GH >1 to ≤2.5 ng/mL, normal IGF-I, and controlled symptoms: maintain 90 mg every 4 weeks
  • If GH >2.5 ng/mL, elevated IGF-I, or uncontrolled symptoms: increase to 120 mg every 4 weeks
  • If GH ≤1 ng/mL, normal IGF-I, and controlled symptoms: reduce to 60 mg every 4 weeks

• SRLs normalize IGF-I levels in approximately 25% of treatment-naive patients 6

• Long-term (>3 years) results on efficacy and safety of SRLs are reassuring 6

Alternative Medical Options

• For patients with inadequate response to SRLs:
  • Dopamine agonist (cabergoline) - best response occurs with mildly elevated GH and IGF-I <2× upper limit of normal 6, 8
  • GH receptor antagonist (pegvisomant) - highly effective in normalizing IGF-I levels in most patients 6, 8
  • Combination therapy may be considered for resistant cases 8

Radiation Therapy

• Radiation therapy is typically a third-line option after surgery and medical therapy 2
• Caution is needed with conventional radiation therapy due to reports of increased mortality and morbidity 6
• Stereotactic radiation techniques may have improved safety profiles 6, 2

Treatment Goals and Monitoring

• The primary goal is to reduce GH and IGF-I levels to normal, which reduces mortality to rates similar to the general population 6, 1
• Aim for GH <1 μg/L and age/sex-normalized IGF-I levels 6
• Monitor GH and IGF-I levels regularly to assess treatment efficacy 6
• Evaluate improvement in clinical symptoms and comorbidities 6
• For patients on SRLs, monitor for potential side effects including glucose metabolism alterations 6

Common Pitfalls and Caveats

• Delayed diagnosis is common due to the insidious nature of the disease, leading to established complications at diagnosis 9
• Discordance between GH and IGF-I levels can occur in approximately 15% of patients, requiring careful interpretation 3
• Pre-surgical SRL treatment might improve outcomes for macroadenomas, but prospective data are limited 6
• When evaluating post-surgical outcomes in patients who received pre-surgical SRL treatment, consider the drug carry-over effect 6
• SRLs may have negative effects on glucose metabolism, requiring monitoring of blood glucose and HbA1c levels 6