Background: Patients with Cushing's Syndrome (CS) and Conn's Syndrome with bilateral adrenal masses pose a dilemma. Uptake of 18F-FDG by hyperfunctioning adrenal glands has not been previously reported and may help lateralize. The aim was to determine if 18F-FDG PET/CT scan could identify hyperfunctioning adrenal masses and determine a biological basis for uptake.
Methods: Patients with nonfunctional adenomas (n = 9), CS (n = 11), and Conn's syndrome (n = 4) underwent an 18F-FDG PET/CT scan with a volume of interest circumscribing each mass to obtain a maximal standardized uptake value (SUVmax). Thirty-two adrenal masses were analyzed. Genome-wide expression data from an independent cohort were analyzed in nonfunctioning adenomas (n = 20), Conn's syndrome (n = 29), and CS (n = 24) focusing on GLUT genes. For genes differentially expressed, immunohistochemistry was performed on tissue samples.
Results: Cortisol-secreting masses (n = 16) had a higher average SUVmax of 5.9 compared to nonfunctioning masses (n = 11, average SUVmax 4.2) and aldosterone-hypersecreting masses (n = 5, average SUVmax 3.2) (p = 0.007). SUVmax cut-off of 5.33 had 50.0% sensitivity and 81.8% specificity in localizing a cortisol-secreting mass. GLUT3 expression was 2.19-fold higher in patients with CS compared to patients with nonfunctioning adenomas (p = 0.003) and 2.16-fold higher in patients with CS compared to Conn's syndrome (p = 0.006). GLUT3 immunohistochemistry showed 2.2-fold higher staining in CS tumor samples compared to nonfunctioning adenomas.
Conclusions: Differential 18F-FDG PET/CT uptake was observed in patients with nonfunctioning, aldosterone-hypersecreting, and cortisol-secreting masses. GLUT3 overexpression in cortisol-secreting tumor likely accounts for the differential uptake. Future larger cohort studies will need to be conducted to determine if 18F-FDG PET/CT uptake can lateralize cortisol-secreting adrenal masses in patients with bilateral adrenal masses.