SUN-488 - Cushing'S Syndrome Secondary to A Rare Functional Adrenal Oncocytic Neoplasm

Oncocytic adrenocortical neoplasms (OANs) are rare adrenal tumors, typically benign and nonfunctioning. Functional OANs causing cortisol excess are uncommon and may lack classic Cushingoid features, leading to delayed recognition.

A 77-year-old physically active man with type 2 diabetes mellitus at age 70, despite lifelong normal BMI and stable lifestyle presented with progressive fatigue, cognitive fog, proximal muscle weakness, and declining exercise tolerance despite daily activity. Diabetes remained well controlled (HbA1c low 6%) on metformin monotherapy. Additional history included hypertension, osteopenia, extensive spontaneous ecchymoses, skin thinning, and low libido, without cushingoid appearance. Given unexplained myopathy, skin fragility, osteopenia, and late-onset diabetes, evaluation for hypercortisolism was pursued. Testing revealed elevated AM cortisol (18.5 µg/dL), suppressed ACTH ( < 5 pg/mL), low-normal DHEAS (41 µg/dL), inadequate suppression on 1-mg dexamethasone test (cortisol 25.9 µg/dL with appropriate dexamethasone level), two elevated midnight salivary cortisols (0.20, 0.17 µg/dL), and elevated 24-h urine free cortisol (48.9 µg), consistent with ACTH-independent hypercortisolism. Imaging showed a
2.5×2.4×2.3 cm left adrenal mass. He underwent left adrenalectomy. Pathology revealed a benign oncocytic adrenocortical neoplasm, supported by immunohistochemistry (SF-1+, synaptophysin+, MART-1+) and absence of Lin–Weiss–Bisceglia criteria. Postoperatively, physiologic glucocorticoid replacement was initiated due to contralateral adrenal suppression.

OAN remains exceptionally rare with approximately 200 cases reported. Approximately one-third of OANs are hormonally active, most commonly presenting with cortisol excess, virilizing syndromes, or with features mimicking pheochromocytoma. Although most are benign, approximately 22% have shown malignant behavior. The standard Weiss criteria, commonly used to evaluate adrenocortical malignancy, tend to overestimate malignancy when applied to OAN. Consequently, the Lin-Weiss-Bisceglia criteria was proposed specifically for OAN, a system that has since demonstrated utility in stratifying recurrence risk and survival.

Functional OANs should be considered in the differential diagnosis of ACTH-independent hypercortisolism even in the absence of classic Cushing’s syndrome features. Heightened clinical suspicion and appropriate histopathologic classification are key to timely diagnosis and optimal management.

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