What is the diagnostic approach for acromegaly?

Diagnostic Approach for Acromegaly

The diagnosis of acromegaly requires biochemical confirmation with elevated IGF-1 levels and failure to suppress growth hormone (GH) below 1 μg/L during an oral glucose tolerance test (OGTT), followed by pituitary MRI imaging to identify the source of GH excess. 1

Clinical Suspicion

• Look for characteristic physical features:

  • Enlarged hands and feet with widened, thickened fingers
  • Facial changes: prominent forehead, enlarged nose, thickened lips, prognathism
  • Increased spacing between teeth, jaw malocclusion
  • Progressive changes in appearance (comparing old photographs)
  • Increased ring or shoe size

• Associated symptoms and complications:

  • Joint pain and arthropathy
  • Excessive sweating
  • Sleep apnea
  • Headaches and visual disturbances
  • Hypertension and cardiac dysfunction
  • Impaired glucose tolerance or diabetes

Biochemical Diagnosis

First-line Tests:

1. Serum IGF-1 measurement:

   • Must be interpreted using age- and sex-specific reference ranges
   • Elevated levels strongly suggest acromegaly
   • Single measurement is usually sufficient due to minimal diurnal variation

2. Oral Glucose Tolerance Test (OGTT):

   • Gold standard confirmatory test
   • 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 1
   • Use assay-specific and method-specific normal GH cut-offs

Interpretation:

• According to current guidelines, diagnosis is established when:

  • IGF-1 is elevated above age- and sex-adjusted normal range AND
  • GH fails to suppress to <1 μg/L during OGTT 1, 2

• A random GH <0.4 μg/L and normal IGF-1 exclude acromegaly 2

Imaging Studies

• Pituitary MRI with contrast:

  • Required once biochemical diagnosis is established
  • Identifies pituitary adenoma (source in ~95% of cases)
  • Evaluates tumor size, location, and relationship to surrounding structures

• Additional imaging if pituitary source not identified:

  • Chest and abdominal imaging to look for ectopic GHRH or GH-secreting tumors
  • Common sites: pancreas, lungs, carcinoid tumors 3

Additional Workup

1. Pituitary function assessment:

   • Evaluate for hypopituitarism or hypersecretion of other hormones
   • TSH, free T4, prolactin, ACTH, cortisol, LH, FSH, testosterone/estradiol

2. Comorbidity screening:

   • Cardiovascular assessment (echocardiography)
   • Glucose tolerance test for diabetes
   • Sleep study for sleep apnea
   • Colonoscopy (increased risk of polyps)

Special Considerations

• Genetic testing should be considered in:

  • Young patients (<30 years)
  • Family history of pituitary adenomas or endocrine tumors
  • Multiple endocrine neoplasia syndromes
  • X-linked acrogigantism, McCune-Albright syndrome, or Carney complex 4

• Pitfalls in diagnosis:

  • Laboratory assay variability can affect results
  • Stress, exercise, and certain medications can falsely elevate GH
  • Liver or kidney disease can affect IGF-1 levels
  • Pregnancy and adolescence can cause physiologic elevation of GH/IGF-1

Diagnostic Algorithm

1. Clinical suspicion of acromegaly
2. Measure serum IGF-1 level
3. If IGF-1 is elevated, perform OGTT
4. If GH fails to suppress to <1 μg/L during OGTT, diagnosis is confirmed
5. Obtain pituitary MRI to localize the tumor
6. Screen for associated comorbidities and complications
7. Consider genetic testing in appropriate cases

Early diagnosis is critical as untreated acromegaly significantly increases morbidity and mortality, primarily due to cardiovascular, cerebrovascular, and metabolic complications 5. The average delay in diagnosis is often 4-10 years after disease onset due to the insidious progression of symptoms 5.