Endocrine Abstracts

Objective: Most patients with ACTH-dependent Cushing’s syndrome have Cushing’s disease, i.e. a pituitary corticotroph adenoma, but the presence of another tumor secreting ACTH (although the prevalence of ectopic ACTH syndrome is lower) needs to be considered in the differential diagnosis. Distinguishing between these two etiologies can be difficult despite biochemical and radiological examinations. Previous research showed that inferior petrosal/cavernous sinus sampling (IPSS/CSS) has the highest diagnostic accuracy in this differential diagnosis. The aim of this study was to determine the accuracy of IPSS/CSS in predicting the source of ACTH-dependent Cushing syndrome in a tertiary center in Switzerland.

Methods: Retrospective, single center study of 21 patients (seven male, 14 female; age 40.4±16.8y) with ACTH-dependent Cushing’s syndrome who underwent a selective bilateral inferior petrosal sinus (n=6) or superselective bilateral cavernous sinus (n=15) sampling at the University Hospital Zurich between 2000 and 2017 and provided written informed consent. ACTH levels were measured before and within 20 min after corticotropin-releasing hormone (CRH) administration, and the ratios of central-to-peripheral plus interpetrosal ACTH levels were calculated. A central-to-peripheral ratio ≥2 before and ≥3 after CRH is diagnostic of an orthotopic source of ACTH. A ratio ≥1.4 between the two sinuses predicted the tumor lateralization.

Results: IPSS/CSS confirmed orthotopic (pituitary) source of ACTH in 19 patients with Cushing’s disease and correctly identified 2 patients with ectopic disease. A central-to-peripheral plasma ACTH ratio was diagnostic for Cushing’s disease in 19 patients before CRH and in 19 patients after CRH-administration. Interpetrosal ratios for ACTH lateralization were found in 17 (pre-CRH) and 17 (post-CRH) patients. The IPSS/CSS pre- and post-CRH ACTH ratio was negative (close to 1) in both patients with ectopic Cushing’s syndrome. There was no adverse event in the context of the catheterization procedure. Perioperative MRI (n=18) showed 1 macroadenoma, 12 microadenomas and no visible lesion in five patients. In patients with visible pituitary lesions, IPSS/CSS predicted correctly the localization to the left, right or paramedian side in seven cases. Judged by surgery, the IPSS/CSS predicted correctly the lateralization of the pituitary tumor in 14 of 19 patients. Pituitary surgery was successful in 14 patients; five had persistent cortisol excess.

Conclusion: Our results confirm previous reports that IPSS/CSS is an effective intervention to locate the source of ACTH production. IPSS/CSS was safe and useful in planning the surgical therapy in patients with Cushing disease.