Poster Presentation ESA-SRB 2023 in conjunction with ENSA

Biochemically negative phaeochromocytomas (#317)

Sneha Krishna 1 , Adam Morton 1
  1. Mater Hospital Brisbane, South Brisbane, QLD, Australia

The prevalence of adrenal incidentaloma >1cm in diameter on CT varies from 1.4-7.3%.1 Phaeochromocytomas account for 4-7% of adrenal incidentalomas.2 Plasma free metanephrine measurement by LC-MS/MS is the appropriate biochemical screening test for pheochromocytoma with adrenal incidentalomas, with 99% sensitivity and 89% specificity.3

Case

A 46-year-old woman awaiting urogynaecological surgery was found to have a 21mm right adrenal incidentaloma on CT. She was asymptomatic, normotensive, and had no clinical features of Cushing’s syndrome or hereditary syndromes associated with phaeochromocytoma. The adrenal lesion was 30HU with 20% washout and hyperintense on T2-weighted MRI. Seated fasting plasma metanephrines and 3-methoxytyramine by LC-MS/MS were normal on two occasions (Table 1). 1mg overnight dexamethasone suppression test showed incomplete suppression with cortisol 94nmol/L (REF <50) in the setting of obesity. DOTATATE-PET showed avid uptake in the adrenal nodule. Following alpha-blockade with phenoxybenzamine, a 27mm phaeochromocytoma was removed uneventfully. Histology revealed cellular monotony, large nests, and focal marked nuclear pleomorphism, but no spindling, necrosis, or capsular/vascular invasion. Staining for succinate dehydrogenase A (SDHA), SDHB, fumarate hydratase, and S-(2-succinyl) cysteine was negative. Further genetic tests are pending.

Discussion

Biochemically negative phaeochromocytomas are uncommon, with fewer than 40 cases described. Plasma metanephrines should be performed supine, as there are posture-associated increases. False negative testing can also occur with small tumours, early recurrences, and familial phaeochromocytoma syndromes. In patients presenting with characteristic radiologic features of phaeochromocytomas and negative biochemical testing, functional imaging with PET should be considered.4,5 Genetic mutations were found in 12 of 16 (62.5%) of patients tested - SDHB (5); MEN2A (4); VHL (2), and SDHD (1).3,6,7 Defective catecholamine synthesis due to negligible tyrosine hydroxylase immunoreactivity has been shown in biochemically negative phaeochromocytomas with SDHB gene mutations. Alpha-blockade is imperative to prevent haemodynamic instability.3,4 Follow-up with annual whole-body MRI can be appropriate in absence of guidelines.

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  1. Muangnoo, N., Manosroi, W., Leelathanapipat, N., Meejun, T., Chowchaiyaporn, P., & Teetipsatit, P. (2022). Predictive Factors of Functioning Adrenal Incidentaloma: A 15-Year Retrospective Study. Medicina (Kaunas, Lithuania), 58(5), 597. https://doi.org/10.3390/medicina58050597
  2. Nieman L. K. (2010). Approach to the patient with an adrenal incidentaloma. The Journal of clinical endocrinology and metabolism, 95(9), 4106–4113. https://doi.org/10.1210/jc.2010-0457
  3. Lenders, J. W., Pacak, K., Walther, M. M., Linehan, W. M., Mannelli, M., Friberg, P., Keiser, H. R., Goldstein, D. S., & Eisenhofer, G. (2002). Biochemical diagnosis of pheochromocytoma: which test is best?. JAMA, 287(11), 1427–1434. https://doi.org/10.1001/jama.287.11.1427
  4. Spiro, A., Usman, A., Ajmal, A., Hoang, T. D., & Shakir, M. K. M. (2020). Asymptomatic and Biochemically Silent Pheochromocytoma with Characteristic Findings on Imaging. Case reports in endocrinology, 2020, 8847261. https://doi.org/10.1155/2020/8847261
  5. Fountas, A., Kanti, G., Glycofridi, S., Christou, M. A., Kalantzi, A., Giagourta, I., Markou, A., Ntali, G., Aggeli, C., Saoulidou, E., Dimakopoulou, A., Zografos, G. N., Kounadi, T., Tigas, S., & Papanastasiou, L. (2022). Pre- and peri-operative characteristics, complications and outcomes of patients with biochemically silent pheochromocytomas; a case series. Endocrine, 78(3), 570–579. https://doi.org/10.1007/s12020-022-03182-w
  6. Hirsch, D., Grossman, A., Nadler, V., Alboim, S., & Tsvetov, G. (2019). Pheochromocytoma: Positive predictive values of mildly elevated urinary fractionated metanephrines in a large cohort of community-dwelling patients. Journal of clinical hypertension (Greenwich, Conn.), 21(10), 1527–1533. https://doi.org/10.1111/jch.13657
  7. Wachtel, H., Hutchens, T., Baraban, E., Schwartz, L. E., Montone, K., Baloch, Z., LiVolsi, V., Krumeich, L., Fraker, D. L., Nathanson, K. L., Cohen, D. L., & Fishbein, L. (2020). Predicting Metastatic Potential in Pheochromocytoma and Paraganglioma: A Comparison of PASS and GAPP Scoring Systems. The Journal of clinical endocrinology and metabolism, 105(12), e4661–e4670. https://doi.org/10.1210/clinem/dgaa608