Nelson Syndrome

Nelson syndrome is a specific clinical condition that develops as a direct complication of bilateral adrenalectomy.
Bilateral adrenalectomy, which can often be accomplished laparoscopically, is a surgical intervention sometimes required when a patient with Cushing syndrome possesses an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma that does not respond to conventional treatment.
The procedure may also be indicated if ACTH is being excessively secreted by an ectopic metastatic tumor.
The syndrome is explicitly defined by the subsequent increased secretion of ACTH originating from an unresected pituitary adenoma.
The complete removal of the adrenal glands eliminates the endogenous production of cortisol, which permanently removes the physiological negative feedback loop on the pituitary gland, thereby allowing the preexisting residual pituitary adenoma to autonomously hypersecrete ACTH.

Nelson syndrome is a highly significant risk associated with the surgical management of refractory hypercortisolism, occurring in approximately 25% of adult patients who undergo bilateral adrenalectomy for Cushing syndrome.

The hallmark clinical manifestation and the primary physical evidence of Nelson syndrome is the development of marked cutaneous hyperpigmentation.
This profound hyperpigmentation is driven directly by the massively elevated circulating levels of ACTH secreted by the expanding pituitary adenoma.

Because bilateral adrenalectomy carries the substantial risk of precipitating Nelson syndrome, pharmacological alternatives that inhibit adrenocortical function are frequently considered to manage the underlying Cushing syndrome.
Food and Drug Administration (FDA)-approved agents include mitotane, which exerts a direct toxic effect on adrenocortical cells, and osilodrostat, which acts as a potent cortisol synthesis inhibitor.
Levoketoconazole, a stereoisomer of ketoconazole that inhibits several key steroidogenic enzymes, represents another medical alternative utilized to control hypercortisolism without necessitating the removal of the adrenal glands.