Confirmation of Acromegaly Diagnosis
Acromegaly is definitively confirmed through biochemical testing that includes elevated insulin-like growth factor I (IGF-I) levels and failure to suppress growth hormone (GH) during an oral glucose tolerance test (OGTT). 1, 2
Biochemical Diagnostic Criteria
- Elevated serum IGF-I levels (age and gender-matched) serve as the initial screening test for acromegaly 2
- Confirmation requires demonstration of lack of GH suppression during an oral glucose tolerance test (OGTT) 2
- Using modern sensitive assays, GH should suppress to <1 μg/L during OGTT in normal individuals; failure to suppress confirms acromegaly 1, 2
- Random GH <0.4 μg/L and normal IGF-I levels exclude the diagnosis of acromegaly 2
Interpretation of Biochemical Results
- Discordant results between GH and IGF-I can occur in approximately 15% of cases 2
- GH and IGF-I should be considered together when making the diagnosis 3
- Providers must be aware of conditions that can alter GH and IGF-I levels and each assay's performance characteristics 3
- The clinical significance of slightly elevated IGF-I levels remains to be established 1
Imaging Studies
- Once biochemically confirmed, magnetic resonance imaging (MRI) of the pituitary is indicated to identify the underlying pituitary adenoma 4
- In very rare cases, acromegaly may be due to ectopic secretion of growth hormone-releasing hormone (GHRH) 5
Common Pitfalls in Diagnosis
- Acromegaly is often diagnosed 4-10 years after onset due to insidious progression 5
- Early or mild cases present diagnostic challenges as clinical recognition and biochemical confirmation can be difficult 3
- GH assays have evolved to become more sensitive, requiring updated cut-off values 1, 6
- Conditions that alter GH and IGF-I levels must be considered when interpreting results 3
- Results of GH suppression during OGTT are not useful in follow-up of medically treated patients due to inconsistent results 1
Clinical Importance of Accurate Diagnosis
- Elevated GH and IGF-I levels are predictors of mortality in acromegaly 1
- Normalizing GH and IGF-I levels results in mortality rates similar to the general population 1
- Heart failure is the most common cause of death in untreated acromegaly 7
- Early diagnosis and adequate treatment are essential to mitigate excess mortality 4
The diagnostic approach to acromegaly has evolved with improvements in assay methods, allowing for diagnosis in patients with milder forms of the disease. The combination of elevated IGF-I levels and failure to suppress GH during OGTT remains the gold standard for diagnosis.