Endocrine Abstracts

JOINT2940

Introduction: Desmopressin stimulation testing (DST) is increasingly used in the differential diagnosis between central and ectopic ACTH-dependent hypercortisolism since CRH became unavailable. Herein, we report two patients with Cushing’s disease (CD) and negative DST (10 μg IV) (defined as <50% and <20% increase of ACTH and cortisol levels, respectively) but with positive petrosal sinus ACTH response to desmopressin administration.

Case Presentation: Case 1: A 47-year-old Greek woman, with 1-year history of dyslipidaemia and hypertension, was investigated for Cushingoid phenotype (central obesity, moon face, facial plethora, hirsutism, buffalo hump and supraclavicular fat pads). Hormonal work-up revealed ACTH-dependent hypercortisolism [late night serum cortisol 308 nmol/l (NR <208), 1-mg overnight dexamethasone suppression 286 nmol/l (NR <50), 24h urine free cortisol 724 nmol (NR 11.8-485.6), ACTH 51 pg/ml]. DST led to 45% and 14% rise in peripheral ACTH and cortisol levels, respectively. Pituitary MRI revealed a 3 mm lesion. Due to its size, inferior petrosal sinus sampling (IPSS) was performed. Central-to-peripheral ACTH gradient, before and after IV desmopressin, was indicative of CD. Desmopressin administration led to 593% increase of petrosal sinus ACTH levels compared to 27.4% increase of peripheral ACTH levels. Transsphenoidal adenomectomy resulted in Cushing’s remission. Case 2: A 22-year-old Greek woman was investigated for hypercortisolism due to 1-year history of fatigue, muscle weakness, substantial weight gain, hirsutism, easy bruising, round face and abdominal striae. Hormonal evaluation was indicative of ACTH-dependent hypercortisolism [1-mg overnight dexamethasone suppression 13.1 μg/dl (NR <1.8), 24h urine free cortisol 317 μg (NR 20.9-292.3), ACTH 47 pg/ml]. DST was negative (8.97% and 16.90% increase in peripheral ACTH and cortisol levels, respectively). Pituitary MRI revealed a 4 mm central microadenoma. IPSS with IV desmopressin identified pituitary origin of ACTH excess. Desmopressin administration led to 400% and 46% increase of petrosal sinus and peripheral ACTH levels, respectively. The patient is currently awaiting transsphenoidal surgery.

Discussion: To our knowledge, only four other patients unresponsive to DST but with positive central ACTH response in IPSS after desmopressin administration, as in our cases, have been described. The discrepancy between central and peripheral ACTH levels after desmopressin administration may be attributed to different sampling intervals between DST and IPSS or cyclic hypercortisolism. Short and transient increase in ACTH secretion after desmopressin, detected in the petrosal sinus but not significantly affecting ACTH peripheral levels may also contribute. Our cases highlight that desmopressin administration during IPSS is useful even in patients with negative desmopressin stimulation testing.