3-Dimensional Volumetric Modeling of Adrenal Gland Size in Primary Bilateral Macronodular Adrenocortical Hyperplasia

Presentation Number: OR04-4
Date of Presentation: April 1st, 2017

Fady Hannah-Shmouni*1, Georgios Papadakis2, Amit Tirosh3, Annabel Sophie Berthon4, Fabio R Faucz3, Elena Belyavskaya5, Charalampos Lyssikatos1, Andrew Paul Demidowich1, Maya Beth Lodish3 and Constantine A Stratakis1
1Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 2National Institutes of Health, 3National Institutes of Health, Bethesda, MD, 4National Institutes of Health (NIH), Bethesda, MD, 5Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)., Bethesda, MD


Background: Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) causes ACTH-independent Cushing syndrome. PBMAH typically manifests with subclinical hypercortisolemia and bilateral macronodules (≥1cm) with hyperplasia and/or internodular atrophy. Inactivating mutations in the Armadillo repeat containing 5 (ARMC5) gene, a putative tumor suppressor, causes the majority of cases. Accurate radiologic characterization of adrenal size in PBMAH and its putative correlation to disease have not been previously performed.

Methods: Forty-five patients with PBMAH were evaluated at the National Institutes of Health (NIH) under an IRB-approved protocol. Clinical, biochemical and radiographic characteristics were assessed. Biochemical diagnosis of hypercortisolemia was confirmed with loss of diurnal variation of cortisol and/or elevated 24-h urinary free cortisol (UFC) and 17-hydroxysteroids (17OHS). Criteria for radiographic diagnosis included bilateral macronodules with hyperplasia. CT scans were used to create 3-dimensional volumetric models by contouring each adrenal gland, in each slice, using Vitrea Core Fx v6.3 software (Vital Images, Minnetonka, Minnesota).

Results: Forty-five patients with PBMAH (32 females, 52.3±11.9 years) were evaluated. Their midnight cortisol concentration, UFC and 17OHS were 8.3±4.9 μg/dL, 54.6±61.9 μg/24h and 9.3±4.7 μg/24h, respectively. Their mean adrenal volumes were; right 18.5cc±10.18, left 26.6cc±19.3, and total 45.1cc±24.4. In our mixed cohort, total adrenal volume positively correlated with 17OHS (r=0.4, p=0.01, n=41). The other biochemical parameters did not significantly correlate with adrenal volume. However, in the African American cohort (n=10), total adrenal volume positively correlated with midnight cortisol concentration (r=0.8, p=0.03, n=8), UFC (r=0.8, p=0.004, n=9) and 17OHS (r=0.9, p=0.004, n=8).

Conclusion: 3-dimensional volumetric modeling, in combination with clinical and biochemical measures, may be used as a marker of severity in patients with PBMAH. This appears to be particularly useful in African American patients with PBMAH, which may reflect their previously described increased prevalence of ARMC5-variant carrier state.


Nothing to Disclose: FH, GP, AT, ASB, FRF, EB, CL, APD, MBL, CAS