What is the initial workup and treatment for a patient suspected of having acromegaly?

Initial Workup and Treatment for Acromegaly

The initial workup for suspected acromegaly should include measurement of serum IGF-1 levels and GH levels with oral glucose tolerance test (OGTT), followed by pituitary MRI imaging if biochemical tests are positive, with first-line treatment being surgical resection of the pituitary adenoma by an experienced neurosurgeon. 1, 2

Diagnostic Workup

Biochemical Testing

1. IGF-1 measurement:

   • First-line screening test
   • Must be interpreted using age- and sex-adjusted normal ranges
   • Elevated levels strongly suggest acromegaly 2

2. GH suppression test (OGTT):

   • Administer 75g oral glucose
   • Measure GH levels at baseline and at intervals over 2 hours
   • Normal response: GH suppression to <1 μg/L
   • Failure to suppress confirms acromegaly 1, 3

3. Important considerations:

   • Discordant results between IGF-1 and GH can occur in ~15% of cases 4
   • Normal IGF-1 with elevated GH may occur in poorly controlled diabetes 5
   • Use assay-specific and method-specific normal GH cut-offs 1

Imaging

• Pituitary MRI with contrast: Essential to locate and characterize the adenoma
• Evaluate for:
  • Tumor size and location
  • Invasion of surrounding structures (cavernous sinus, optic chiasm)
  • Mass effect on adjacent structures 2

Additional Assessments

• Visual field testing: If tumor is near optic chiasm
• Pituitary function tests: To assess for hypopituitarism
• Screening for comorbidities:
  • Cardiovascular: Hypertension, cardiomyopathy, arrhythmias
  • Metabolic: Glucose intolerance, diabetes
  • Respiratory: Sleep apnea
  • Gastrointestinal: Colonoscopy (starting at age 40)
  • Musculoskeletal: Joint pain, arthropathy 2

Treatment Approach

First-Line Treatment

• Transsphenoidal surgery by an experienced pituitary neurosurgeon
  • Offers the best chance of complete remission
  • Even if complete remission is unlikely, debulking can reduce GH burden and improve response to medical therapy 1
  • Success rate is approximately 50% in experienced centers 1

Post-Surgical Assessment

• Measure GH and IGF-1 levels at 3 and 6 months post-operatively 1
• Treatment goals:
  • Fasting morning GH <1 μg/L
  • IGF-1 within normal age- and sex-adjusted range 1

Medical Therapy

• First-line medical therapy (if surgery fails or is contraindicated):

  • Somatostatin receptor ligands (SRLs): octreotide or lanreotide 1, 6
  • Starting dose for lanreotide: 90 mg subcutaneously every 4 weeks 6
  • After 3 months, adjust dose based on GH/IGF-1 levels 6

• Second-line options:

  • For partial responders to SRLs: Add pegvisomant (GH receptor antagonist) 1
  • For non-responders to SRLs: Switch to pegvisomant 1
  • For mild disease (IGF-1 <2× upper limit of normal): Consider cabergoline (dopamine agonist) 1

• Combination therapy:

  • SRL + cabergoline
  • SRL + pegvisomant
  • Consider for patients with inadequate response to monotherapy 1, 2

Radiotherapy

• Consider for patients with:
  • Persistent disease after surgery
  • Incomplete response to medical therapy
  • Uncontrolled tumor growth 1
• Effects may take up to 10 years to fully manifest
• Medical therapy often required while awaiting radiotherapy effects 1

Monitoring

• Regular assessment of GH and IGF-1 levels
• Periodic MRI to evaluate tumor size
• Screening for comorbidities:
  • Cardiovascular assessment
  • Glucose tolerance/HbA1c
  • Colonoscopy (every 3-5 years)
  • Sleep studies if symptomatic 2

Pitfalls and Caveats

• Discordant biochemical results: When GH and IGF-1 results don't match, consider:

  • Assay variability or limitations
  • Concomitant conditions (diabetes, malnutrition, liver disease)
  • Medications affecting GH/IGF-1 (estrogens, opioids)
  • Base treatment decisions primarily on IGF-1 levels 4

• Hepatic impairment: Reduce initial lanreotide dose to 60 mg in patients with moderate to severe hepatic impairment 6

• Glucose metabolism: SRLs may worsen glucose tolerance, while pegvisomant typically improves it 2

• Long-term management: Even after successful treatment, lifelong monitoring is required due to risk of recurrence 2