The majority of adrenal masses are found incidentally during imaging for non-adrenal causes. Approximately 5% of adrenal incidentalomas have proved to be pheochromocytomas. The majority of incidentalomas are benign and non-secretory.
A 73 years-old white male with pre-diabetes and morbid obesity has been followed by endocrine service for right adrenal incidentaloma overall several years. A 1.6 cm right adrenal nodule with 31 Hounsfield Unit was found incidentally in 2009 CT abdomen for abdominal pain. It was a lipid poor adenoma with >60% absolute contrast washout in 10 minutes. Biochemically it was non-secretory. The size of nodule was gradually increased over next seven years measuring at 1.9 x 1.6 cm in 2010 and 2.1 x 1.6 cm in 2012 but remained non-secretory. In 2015 CT scan, it was measured at 3.0 x 2.3 cm with absolute washout value of 45% and relative washout value of 34%. The size was overall stable again for next three years measuring at 3.2 x 2.2 cm in 2018 scan. Repeat plasma and urine metanephrine were about 2-folds higher than upper normal reference level in 2015 and 3-folds higher in 2017. Clinically he was asymptomatic except anxiety. He has normocalcemia. He underwent laproscopic right adrenectomy after alpha blockage with doxazosin. Pathology showed 4.5 cm pheochromocytoma with positive chromogranin and synaptophysin. Fulgent paraganglioma-pheochromocytoma comprehensive panel with negative for RET,NF1,FH,SDHB,SDHD,SDHC,SDHAF2,SDHA,MAX,TMEM127 and VHL but noted to have heterozygous VUS of VHL c.205>G(p.Arg69Gly). He has no significant family history or personal history to suggest VHL.
In a patient with lipid poor adrenal incidentaloma, pheochromocytoma should be ruled out biochemically with either plasma or 24hr urine fractionated metanephrine. Both tests have similar specificity and sensitivity. Even with initial negative biochemical assessment, repeat screening should be performed annually based on clinical suspicion and radiology characteristics. Imaging can be performed annually or biannually to assess the stability of nodule. VHL is an autosomal dominant hereditary disease with del/dup mutation in the VHL gene and associated with multisystem tumor such as CNS or retinal hemagioblastomas, RCC, pheochromocytoma, pancreatic NET, endolymphatic sac tumor, epididymal and broad ligament cystadenoma and visceral cysts.
Lipid poor adrenal incidentaloma needs interval biochemical and imaging follow up. The frequency of monitoring can be individualized based on clinical suspicion and radiology findings. Pheochromocytoma can be clinically silent especially if it is small, however, it can be lethal with late or missed diagnosis. This is the first published case report of c.205C>G VHL variant associated with pheochromocytoma.