8169 Bilateral Inferior Petrosal Sinus Sampling Using Metyrapone as a Reliable Alternative to Differentiate Between Cushing Disease and Ectopic ACTH Syndrome- A Single Center Experience
Authors: Azmath Misbah , Faisal Sobia , Caetano Celina , Vedere Tarunya , Aftab Hassaan , Tendler Beatriz , Malchoff Carl 
Published: October 2024

Disclosure: M. Azmath: None. S. Faisal: None. C. Caetano: None. T. Vedere: None. H. Aftab: None. B. Tendler: None. C. Malchoff: None.

Introduction: Bilateral IPSS is a crucial test in accurately diagnosing Cushing disease (CD) and differentiating it from ectopic ACTH syndrome (EAS). [1] CRH stimulated IPSS is the gold standard technique but cannot be performed due to current shortage of CRH. Metyrapone is a safe and reliable alternative to CRH that can stimulate corticotrophs to secrete ACTH and hence used for IPSS. [2] We would like to share a single center experience using a novel low dose metyrapone protocol for IPSS that successfully helped differentiate CD and EAS. Methods: This was a retrospective analysis of patients presenting with Cushing syndrome. Initial diagnosis was confirmed based on standard testing including 24-hour urinary free cortisol (UFC), late night saliva concentrations (LNSC) and MRI. Metyrapone 500 mg every 4 hours for 3 doses was administered orally starting midnight prior to IPSS performed in the morning. ACTH levels drawn during initial evaluation for Cushing syndrome was compared to ACTH values post metyrapone from the peripheral vein sample to calculate a gradient. Ultimately, pituitary CD or EAS was confirmed based on cure following surgery and /or positive ACTH of tumor staining on pathology and/or concordant results with CRH stimulated IPSS. Results: There were 9 patients, out of which 5 had pituitary CD, and 4 had EAS. Pre ACTH levels for patients ranged between 14.5 and1164 pg/ml (normal reference range 6-50). Following metyrapone, ACTH level rose to 40-4705 pg/ml (normal reference range 6-50). The increase in ACTH levels ranged from 81-547% pre and post metyrapone. An average of 5-6 ACTH samples were drawn during IPSS. Catheterization was successful in all patients and was confirmed by IR. The mean central to peripheral (C/P) ACTH ratio for patients with confirmed CD was 20.53 in comparison with a ratio of 1.34 in patients with EAS. IPSS was confirmed to be diagnostic for pituitary CD if the peak ratio after metyrapone administration was more than 3. No adverse effects were observed during or after the procedure and no hospitalization was required pre-procedure. Discussion: We present single center experience with a novel low dose metyrapone protocol for IPSS. Our protocol was successful in increasing ACTH/cortisol secretion by tumorous cells as evidenced by increase in ACTH levels post metyrapone. It is an easy oral protocol which proved to be safe without the risk for adrenal insufficiency that can occur with higher doses. It also mitigates the small thromboembolic risk that can occur with DDAVP administration. A clear distinction in C/P ACTH ratios was observed in patients with CD versus EAS as early as the 3rd sample. In conclusion, our low dose metyrapone protocol was safe and reliable in accurately differentiating between CD and EAS in small sample of patients at our institution.

Presentation: 6/1/2024