What are the diagnostic criteria and treatment options for acromegaly?

Diagnosis and Treatment of Acromegaly

The diagnosis of acromegaly requires elevated IGF-1 levels and failure to suppress growth hormone (GH) below 1 μg/L during an oral glucose tolerance test (OGTT), with treatment aimed at normalizing these biochemical parameters to reduce morbidity and mortality. 1

Diagnostic Criteria

Biochemical Diagnosis

• Initial Screening: Measure serum IGF-1 levels (minimal diurnal variation makes single measurement sufficient) 1
• Confirmatory Test: Oral glucose tolerance test (OGTT) - gold standard 1
  • Administer 75g oral glucose
  • Measure GH at baseline and at intervals over 2 hours
  • Normal response: GH suppression to <1 μg/L
  • Failure to suppress confirms acromegaly

Important Considerations

• Use assay-specific and method-specific normal GH cut-offs 1
• Random GH <0.4 μg/L and normal age/gender-matched IGF-1 exclude acromegaly 2
• Laboratory variability can affect results; stress, exercise, and certain medications can falsely elevate GH 1
• Liver or kidney disease can affect IGF-1 levels 1

Comprehensive Evaluation

Imaging

• MRI of the pituitary to identify adenoma and assess size, invasiveness, and compression effects 1

Comorbidity Screening

• Cardiovascular assessment (echocardiography) 1
• Glucose tolerance test for diabetes 1
• Sleep study for sleep apnea 1
• Colonoscopy (due to increased risk of polyps) starting at age 40 1

Treatment Approach

First-Line Treatment

• Transsphenoidal surgery - preferred initial approach for most patients, especially those with microadenomas or macroadenomas causing compression symptoms 1

Medical Therapy

Used when surgery is not feasible, has failed, or as adjunctive therapy:

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

   • Octreotide LAR or Lanreotide 3
   • Initial normalization achieved in approximately 25% of treatment-naive patients 4
   • Goal: Reduce GH <1 μg/L and normalize IGF-1 3
   • Dosing algorithm:
     • Starting dose: 90 mg every 4 weeks for 3 months 3
     • After 3 months, adjust 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

2. Dopamine Agonist (Cabergoline)

   • Best response in patients with mildly elevated GH and IGF-1 <2× ULN 4
   • Less effective if pre-treatment IGF-1 >2.5× ULN 4

3. GH Receptor Antagonist (Pegvisomant)

   • Indicated for patients with inadequate response to surgery/radiation 5
   • Normalizes IGF-1 in most patients at appropriate dose 4
   • Requires monitoring of liver function and tumor size 4

4. Combination Therapy

   • SRL + pegvisomant for partial or non-responders to SRL monotherapy 4
   • SRL + cabergoline may be more effective than monotherapy in resistant cases 1

Radiation Therapy

• Usually considered third-line treatment 6
• Increasingly administered using stereotactic techniques 6

Monitoring and Follow-up

• Regular measurement of GH and IGF-1 levels 1
• MRI to evaluate tumor size 1
• Treatment goals:
  • Fasting morning GH <1 μg/L
  • IGF-1 within normal age- and sex-adjusted range 1
  • Relief of symptoms and signs
  • Control of tumor mass 4

Special Considerations

• Genetic testing recommended in young patients (<30 years), those with family history of pituitary adenomas or endocrine tumors 1
• Discordant results between GH and IGF-1 may occur in approximately 15% of patients 2
• Patients with controlled disease on SRLs may be considered for extended dosing intervals 3

Early diagnosis and adequate treatment are essential to mitigate excess mortality associated with acromegaly, with the goal of normalizing biochemical parameters to improve quality of life and reduce comorbidities 6.