# ACTH-dependent Cushing Syndrome with No Peripheral Response But a Marked Petrosal Sinus ACTH Response to Desmopressin

## TL;DR

A 32-year-old man with Cushing syndrome showed a central ACTH response to desmopressin but no peripheral response, highlighting the importance of IPSS in diagnosis.

## Contribution

This case presents a rare scenario where desmopressin IPSS revealed central ACTH secretion without peripheral response or identifiable tumor.

## Key findings

- Desmopressin IPSS showed elevated central-to-peripheral ACTH ratio and prolactin co-secretion.
- No corticotroph tumor was found despite persistent hypercortisolism and normal imaging.
- The patient developed severe adrenal insufficiency after cabergoline treatment.

## Abstract

Desmopressin is increasingly used for the diagnosis of Cushing disease (CD) since corticotropin-releasing hormone became unavailable. We report the case a 32-year-old man who presented with overt Cushing syndrome. Morning blood cortisol, ACTH, 1 mg dexamethasone suppression test, 24-hour urinary free cortisol, and bedtime salivary cortisol were highly variable, reaching markedly elevated values. Intravenous desmopressin administration produced no ACTH or cortisol increase. Pituitary magnetic resonance imaging, thoracic computed tomography, and DOTATATE positron emission tomography scan identified no lesion. Inferior petrosal sinus sampling (IPSS) with desmopressin stimulation resulted in elevated central-to-peripheral ACTH ratio and prolactin co-secretion, while peripheral ACTH remained stable. No corticotroph tumor was identified on pituitary surgery pathology. Hypercortisolism persisted postoperatively. Cabergoline was initiated, after which the patient rapidly developed transient severe adrenal insufficiency (AI). Bilateral adrenalectomy was performed in view of persistent hypercortisolism. This is an unusual case of petrosal sinus ACTH response to desmopressin without any peripheral response, suggesting a central source of ACTH. Thus, desmopressin should still be used during IPSS in patients with no peripheral response. It is unclear whether the AI episode resulted from a combination of nadir of cyclic hypercortisolism, partial apoplexy, and response to cabergoline of an occult corticotroph tumor.