FRI248 A Case of Cyclic Cushing’s Disease With No Peripheral ACTH Response But A Marked Inferior Petrosal Sinus ACTH Response After Desmopressin Administration
Authors: Guay-Gagnon Martin , Cheng Ran , Younes Nada , La Fontaine Alexandre , Larose Stéphanie , Thérasse Éric , Beauregard Catherine , Lacroix André 
Published: October 2023

Disclosure: M. Guay-Gagnon: None. R. Cheng: None. N. Younes: None. A. La Fontaine: None. S. Larose: None. É. Thérasse: None. C. Beauregard: None. A. Lacroix: None.

Background: Desmopressin is commonly used for the diagnosis of Cushing’s disease (CD) especially when CRH is unavailable. We report a case of CD with no peripheral ACTH response but with an unexpectedly marked ACTH and prolactin (PRL) response in inferior petrosal sinus sampling (IPSS) performed with desmopressin. Following failure of pituitary surgery, cabergoline was introduced, which rapidly induced central adrenal insufficiency (AI). Case Report: A 32-y.o. man was referred to our center for Cushing’s syndrome (CS). Over the last years he had developed diabetes, hypertension, hypokalemia, osteoporosis, obesity, and an overt Cushingoid appearance. Morning cortisol was variable with values up to 8065 nmol/L (292 μg/dL) with elevated ACTH of 63 pmol/L (285 pg/mL). The 1 mg dexamethasone suppression test (DST), 24-hour urinary free cortisol (up to 422 x ULN) and bedtime salivary cortisol (up to 74 x ULN) were elevated. The 4 mg IV DST showed partial cortisol suppression, but a very elevated value of 3750 nmol/L (136 μg/dL) the following morning. Desmopressin (10 mcg IV) stimulation test showed no response: ACTH went from 3.8 pmol/L (17.3 pg/mL) to 3.9 pmol/L, and cortisol, from 688 nmol/L (25 μg/dL) to 622 nmol/L. Pituitary MRI, thoracic CT and DOTATATE PET/CT identified no lesion; abdominal CT showed bilateral adrenal hyperplasia. IPSS with desmopressin stimulation identified a pituitary origin with central/peripheral (C/P) ACTH ratios that rose from 7.1 to 34.2 on the left. PRL increased by 83% in left IPSS after desmopressin, while peripheral ACTH and PRL remained stable. During pituitary exploration, the surgeon suspected a tumor on the left, but pathology showed normal pituitary tissue. Hypercortisolism persisted with partial DI requiring oral desmopressin, and cabergoline 0.5 mg twice weekly was initiated. Two weeks later, he was admitted with nausea, vomiting, lethargy, hypotension, hyponatremia, hyperkalemia and a negative septic evaluation. Morning cortisol was 233 nmol/L (8.4 μg/dL), abnormally low in this context. His condition resolved with IV hydrocortisone and fluid resuscitation. ACTH was not measured initially but was 2 x ULN a few weeks later and 4 mg IV DST showed an early cortisol and ACTH rebound. In view of recurrent hypercortisolism, the patient underwent bilateral adrenalectomy resulting in rapid clinical remission. Under hydrocortisone replacement, his most recent ACTH was 21 pmol/L. Conclusions: This is the first report of a petrosal sinus ACTH response to desmopressin without any peripheral response, suggesting a central source of ACTH. Thus, the use of desmopressin during IPSS should still be attempted in patients with no prior peripheral response. It is unclear whether the acute AI episode was due to a combination of nadir of cyclic CD or partial apoplexy and response to cabergoline of a residual corticotroph tumor with desmopressin induced prolactin co-secretion.

Presentation: Friday, June 16, 2023