How is acromegaly diagnosed?

Diagnosis of Acromegaly

The diagnosis of acromegaly requires measuring serum IGF-I levels as the initial screening test, followed by an oral glucose tolerance test (OGTT) with GH measurement, where failure to suppress GH to <1 μg/L during OGTT confirms the diagnosis. 1

Initial Screening

• Measure serum IGF-I levels as the first-line screening test when acromegaly is clinically suspected 1
• IGF-I levels must be interpreted using age-specific, sex-specific, and (in adolescents) Tanner stage-specific reference ranges 1
• An elevated IGF-I level warrants confirmatory testing with OGTT 1

Confirmatory Testing

The oral glucose tolerance test (OGTT) with GH measurement is the gold standard diagnostic test for acromegaly 1:

• Administer 75g oral glucose load and measure GH levels at baseline and during the test 2, 3
• Normal individuals suppress GH to <1 μg/L during OGTT using modern sensitive assays 1
• Failure to suppress GH to <1 μg/L confirms acromegaly 1
• With ultrasensitive assays, the suppression cutoff may be as low as 0.4 μg/L 1

Critical Interpretation Points

• Both GH and IGF-I must be evaluated together at baseline and during follow-up 1
• IGF-I correlates linearly with GH only up to 4 μg/L, then plateaus around 10 μg/L 1
• Discordant results between GH and IGF-I require careful clinical correlation 4

Clinical Recognition

Suspect acromegaly in patients presenting with:

• Acral enlargement: broadened hands and feet, widened thickened fingers 2, 5
• Facial changes: widened nose, prominent cheekbones, forehead bulges, thick lips, prognathism, jaw malocclusion, tooth separation 2, 5
• Soft tissue thickening: frontal bossing, coarsened facial features 2, 5
• Systemic manifestations: joint pain, headache, excessive sweating, visual field defects 4, 5
• Cardiovascular complications: hypertension, left ventricular hypertrophy 6
• Metabolic dysfunction: diabetes mellitus, insulin resistance 4, 5
• Respiratory issues: sleep apnea 6

Special Considerations in Children and Adolescents

In children and young people (CYP), test for GH excess when there is 4:

• Height >2 standard deviation scores (SDS) above age-adjusted and sex-adjusted norms, OR
• Height >2 SDS above mid-parental target height, OR
• Persistently elevated growth velocity (>2 SDS) with acromegalic features 4
• Delayed or arrested puberty with tall stature 4
• Family history of pituitary adenoma 4

Factors Affecting Test Interpretation

Conditions That Lower IGF-I (False Negatives)

• Severe hypothyroidism 1
• Malnutrition or severe infection 1
• Hepatic and/or renal insufficiency 1

Conditions That May Elevate IGF-I (False Positives)

• Hepatic and/or renal insufficiency can paradoxically cause false elevations 1

Imaging Studies

• Contrast-enhanced pituitary MRI is essential after biochemical confirmation to identify and characterize the pituitary adenoma 4, 3
• MRI assesses tumor volume, extension, and relationship to surrounding structures 2

Assessment of Comorbidities

Once acromegaly is diagnosed, evaluate for:

• Cardiovascular complications: echocardiography for left ventricular hypertrophy and valvular disease 6, 2
• Sleep apnea: polysomnography or sleep study 6
• Metabolic complications: glucose tolerance testing for diabetes mellitus 6
• Colonoscopy: starting at age 40 due to increased colorectal neoplasia risk 1, 6
• Visual field testing: if tumor shows mass effect 2
• Musculoskeletal evaluation: for arthropathy 6

Common Pitfalls to Avoid

• Do NOT use GH suppression during OGTT for monitoring patients on medical therapy – results are inconsistent and unreliable in this setting 4, 1
• Do not rely on random GH levels alone, as GH secretion is pulsatile 4
• Ensure proper assay selection and interpretation using method-specific reference ranges 4
• Remember that acromegaly is often diagnosed 5-10 years after onset due to insidious progression 2, 5
• Less than 15% of patients actively seek care for appearance changes; most present with systemic complications 5