Testing for Acromegaly
Initial Screening Test
Measure serum IGF-1 levels as the initial screening test for any patient with suspected acromegaly. 1, 2
- IGF-1 must be interpreted using age-, sex-, and Tanner stage-specific reference ranges (in adolescents) 1
- Elevated IGF-1 alone is sufficient to establish the diagnosis of acromegaly in the majority of clinically suspected cases, particularly when IGF-1 is markedly elevated (>2 times upper limit of normal) 3
- In confirmed acromegaly cases, IGF-1 is elevated in essentially all patients prior to therapy, with median standard deviation scores of +9.52 3
Confirmatory Diagnostic Test
Perform an oral glucose tolerance test (OGTT) with GH measurement as the gold standard confirmatory test. 4, 1, 5
- Administer 75g oral glucose load and measure GH levels during the test 1
- Using modern sensitive assays, failure to suppress GH to <1 μg/L during OGTT confirms acromegaly 1, 5
- With ultrasensitive assays, the cutoff for GH suppression may be as low as 0.4 μg/L 1
- In healthy adults, GH should suppress to <1 μg/L during OGTT 1
When OGTT is Most Useful
The OGTT provides critical corroborative evidence in specific scenarios:
- When IGF-1 elevation is modest (<2 times upper limit of normal) with absent or equivocal clinical features 3
- When clinical suspicion remains high despite borderline IGF-1 results 3
- In patients with IGF-1 elevation but atypical presentations 3
Critical Pitfalls to Avoid
Do NOT use OGTT with GH suppression for monitoring medically treated patients—results are inconsistent and unreliable in this setting. 1, 5
Factors That Falsely Alter IGF-1 Levels
Be aware that IGF-1 may be falsely normal or low despite active acromegaly in:
- Severe hypothyroidism 1
- Malnutrition or severe infection 1
- Poorly controlled diabetes mellitus (IGF-1 can remain normal despite markedly elevated GH) 6
Conversely, IGF-1 may be falsely elevated in:
Biochemical Discordance
Normal IGF-1 levels do NOT exclude acromegaly, especially in patients with poorly controlled diabetes mellitus. 6
- In one case report, a patient with acromegaly and severe diabetes (HbA1c 17.7%) had markedly elevated GH (32.4 ng/mL) but normal IGF-1 (110 ng/mL) 6
- After diabetes control improved post-treatment, IGF-1 rose to 219-233 ng/mL while GH normalized 6
- IGF-1 correlates linearly with GH only up to 4 μg/L, then plateaus around 10 μg/L 1
Monitoring During Follow-Up
Monitor both GH and IGF-1 levels at baseline and during all follow-up visits. 1
- Target goals: GH <1 μg/L and age/sex-normalized IGF-1 levels 1
- Elevated GH and IGF-1 are predictors of mortality 4, 1, 5
- Normalizing both markers reduces mortality to rates similar to the general population 4, 1, 5
Additional Diagnostic Workup
Once biochemical diagnosis is confirmed, obtain:
- Brain MRI to visualize the pituitary adenoma 6
- Cardiovascular evaluation (echocardiogram for left ventricular hypertrophy and valvular disease, as heart failure is the most common cause of death) 4, 1
- Metabolic screening for diabetes mellitus 1
- Sleep study to assess for sleep apnea 1
- Colonoscopy starting at age 40 due to increased colorectal neoplasia risk 4, 1