PMON102 Utility of the Desmopressin Stimulation Test to Detect Cyclic Cushing's Disease

BACKGROUND: Arginine-vasopressin stimulates pituitary ACTH secretion after binding to arginine-vasopressin receptor 1B on corticotropes. Desmopressin (DDAVP), which preferentially binds to arginine-vasopressin receptor 2, stimulates the release of ACTH in most patients with pituitary corticotrope adenomas (Cushing's disease, CD), but not in most patients with ectopic ACTH-producing tumors or healthy people. Cyclic CD is characterized by periods of normal or low cortisol and ACTH, interspersed with hypercortisolism. We postulated that the DDAVP stimulation test, with measurement of ACTH and cortisol after a 10 mcg injection of DDAVP, might confirm the presence of an ACTH-producing pituitary adenoma even during periods without hypercortisolemia. CLINICAL CASE: A 27-year-old woman was diagnosed with Cushing's disease one year after developing weight gain, striae, intermittent acne, balding, irregular menses, a dorsal fat pad and facial rounding. Pituitary MRI revealed a right-sided 7 mm microadenoma; inferior petrosal sinus sampling confirmed a pituitary source of ACTH. Transsphenoidal resection was performed 6 months later. Histology showed an ACTH-positive adenoma and cortisol levels fell to 33nmol/L (1.2 ug/dL). Ten months later, due to intermittent symptoms, testing confirmed elevated UFC, with midnight cortisol of 565 nmol/L (20.3 ug/dL). Pituitary MRI showed a new right-sided lesion, interpreted as a residual adenoma or postoperative changes. Repeat surgical resection was recommended. She presented to our institution for a second opinion. On evaluation three weeks after recurrent hypercortisolism was confirmed, ACTH was low-normal (11.9 pg/mL, RR 5.0-46.0) and serum cortisol was undetectable. This rapid decrease was thought to signify apoplexy of the remaining adenoma or cyclic Cushing's disease. An MRI excluded apoplexy. However, surgery seemed inappropriate given hypocortisolism. To evaluate for the possibility of cyclic Cushing's disease due to residual adenoma, we performed a DDAVP stimulation test. This showed significant increases in ACTH and cortisol levels from 0 min to a 30-minute peak (ACTH 31.6 to 73.1 pg/mL, 131% increase, nl <50%; cortisol 2.6 to 8.1 mcg/dL [72 - 225 nmol/L], 212% increase, nl <20%). This led to transsphenoidal resection of a right-sided lesion. Cortisol levels were undetectable on post-operative day 3 and pathology showed an ACTH-producing adenoma. One week postoperatively, a repeat DDAVP stimulation test showed an insignificant rise in ACTH, and undetectable cortisol throughout (ACTH 11.1 to 12.4 pg/mL, 12% increase; cortisol <1.0 mcg/dL, 0% increase), which was deemed to indicate successful resection of the residual adenoma. She continues to lose weight and her clinical features of cortisol excess are involuting. CONCLUSION: This case demonstrates how the DDAVP stimulation test can be used to both confirm the presence of ACTH-producing pituitary adenomas and assess the response to surgical resection. It may be particularly useful in the setting of cyclic Cushing's disease when cortisol and ACTH levels are not persistently elevated. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.