Bilateral adrenal uptake of 123I MIBG scintigraphy with mild catecholamine elevation, the diagnostic dilemma, and its characteristics

Cases in which bilateral adrenal I-123-Metaiodobenzylguanidine (I-123-MIBG) scintigraphy accumulation is sometimes shown, with mildly elevated catecholamine (CA) or metanephrine (MN) levels (within 3 times the upper reference limit) are diagnostic dilemmas. We experienced 3 cases of adrenal incidentalomas with this dilemma in the differential diagnosis. The clinical diagnosis was subclinical Cushing's syndrome in 2 cases, and primary aldosteronism in 1. Despite suspected CA excess in clinical symptoms and imaging findings, the pathological findings of all these tumors were revealed to be cytochrome P450 family 11 subfamily B member 1 (CYP11B1) positive adrenocortical adenomas. Interestingly, adrenal medullary hyperplasia (AMH) was detected in the adrenal parenchyma of all those backgrounds. To clarify the clinical features of such cases, a cross-sectional study was conducted at the Kobe University Hospital from 2014 to 2020. One-hundred sixty-four patients who had undergone I-123-MIBG scintigraphy were recruited. Among them, 10 patients (6.1%) met the above criteria, including the presented 3 cases. Plasma adrenaline, noradrenaline, urinary metanephrine, and normetanephrine had values of 0.05 +/- 0.05 ng/mL, 0.63 +/- 0.32 ng/mL, 0.22 +/- 0.05 mg/day, and 0.35 +/- 0.16 mg/day, respectively. Nine cases were complicated with hypertension, and symptoms related to CA excess were observed. Half of them (5 cases) including presented 3 cases had unilateral adrenal tumors. These suggest that in cases of bilateral adrenal uptake on I-123-MIBG, AMH needs to be considered. Adrenocortical adenomas may be associated with AMH and further larger investigation is needed for this pathology.