A Rare Case of Adrenal Cysts Associated With Bilateral Incidentalomas and Diffuse Hyperplasia of the Zona Glomerulosa

Characterization of adrenocortical disorders is challenging because of varying origins, laterality, the presence or absence of hormone production, and unclarity about the benign or malignant nature of the lesion. Histopathological examination in conjunction with immunohistochemistry is generally considered mandatory in this characterization. We report a rare case of bilateral adrenocortical adenomas associated with unilateral adrenal endothelial cysts in a 65-year-old woman whose condition was not diagnosed before surgery. Detailed histological examination of the resected adrenal glands revealed hyperplasia in the zona glomerulosa. Despite hyperplasia, the patient had normal serum aldosterone levels and renin activity without clinical evidence of hypertension. The patient was treated with a sodium-glucose cotransporter protein 2 (SGLT2) inhibitor. This may have stimulated the renin-angiotensin-aldosterone system. To the best of our knowledge, this is the first case in which both relatively large bilateral adrenocortical adenomas and unilateral adrenal endothelial cysts were detected. This case also highlights the complexity and difficulty of preoperative diagnosis. Furthermore, this case reports the first detailed histopathological examination of adrenal lesions with SGLT2 treatment and the possibility of SGLT2 inhibitor treatment resulting in histological hyperplasia in the zona glomerulosa; however, it is difficult to prove a causative relationship between SGLT2 inhibitors and hyperplasia of the zona glomerulosa based on the data of this case. It can be confirmed only under limited conditions; therefore, further studies on adrenal gland histology employing SGLT2 inhibition are warranted.

Automated summary

This case describes a rare occurrence of bilateral adrenocortical adenomas and unilateral adrenal endothelial cysts in a 65-year-old woman that were not diagnosed before surgery. The histological examination revealed hyperplasia in the zona glomerulosa, despite normal serum aldosterone levels and renin activity in the patient. Treatment with a sodium-glucose cotransporter protein 2 (SGLT2) inhibitor may have stimulated the renin-angiotensin-aldosterone system, suggesting a potential relationship between SGLT2 inhibitors and hyperplasia of the zona glomerulosa. Further studies on adrenal gland histology employing SGLT2 inhibition are needed to confirm this potential association.