Endocrine Abstracts

Background: Adrenocortical oncocytoma is a veryrare adrenal tumor type, usually nonfunctioning and benign. Neurofibromatosistype 1 (NF1) is an autosomal dominant disease caused by mutations of the NF1 gene encoding neurofibromin, a tumor supressor gene that acts by activating a RAS GTP-ase which negatively regulates RAS activity. NF 1 is usually associated with pheocromocytoma, rarely with adrenal carcinoma, and no association with adrenal oncocytoma has been reported.

Aim: To report a case of a functioning adrenal oncocytoma in a young patient diagnosed with NF1.

Case report: A 22 years-old-female, with a family history of possible NF1 (father with cafe-au-lait spots) presented in July 2019, following the CT diagnosis of a 9.2 × 9.6 × 7.3 cm right adrenal tumor after a pregnancy loss at week 21. The tumor was apparently encapsulated and homogeneous, without evidence of local invasion or lymphadenopathy. Physical examinationrevealed signs of Cushing’s syndrome, hirsutism, acne and multiple cafe-au-lait spots, axillary freckles and Lisch nodules on ophtalmological examination. Hormonal assessment revealed: 0800 h cortisolemia = 16.84 mg/dl, unsupressed on LDDST (15.27 mg/dl), ACTH = 1.91 pg/ml, DHEA-S = 1151 ug/dl (18-391), testosterone = 2.06 ng/ml (<0.75), while aldosterone/renin ratio and serum metanephrines were normal. A right open adrenalectomy was performed for the suspicion of adrenocortical carcinoma and the patient was started on prednisone replacement for adrenal insufficiency. On microscopical examination, tumor cells were large, polygonal, with eosinophilic granulated cytoplasm, suggestive of oncocytoma. The mitotic activity was low, without evidence of capsular and vascular invasion and large areas of necrosis were present. Immunohistochemical analysis showed positivity for calretinin and inhibin, confirming an adrenocortical origin. Cytokeratin staining was negative, vimentin was positive. Ki-67 index was 10 %. The Lin-Weiss-Bisceglia score was low (2 minor criteria: large size and tumor necrosis), supporting a diagnosis of functioning adrenocortical oncocytoma of uncertain malignant potential. Postoperatively, on glucocorticoid replacement (due to contralateral adrenal suppression), we observed an improvement of signs of hypercortisolism and androgen excess, paralleling the normalisation of androgens and restauration of cortisol diurnal rhythm and normalisation of ACTH. No signs of local recurrence were observed on the 3 months follow-up CT scan.

Conclusion: Functioning adrenocortical oncocytoma has rarely been described and its association with NF1 is novel. Careful monitoring is required for adrenal tumor relapse and for other NF1-associated tumors.