Bilateral sampling of the internal jugular vein to distinguish between mechanisms of adrenocorticotropic hormone-dependent Cushing syndrome

Abstract

Background: Bilateral sampling of the petrosal sinuses to distinguish Cushing disease from the ectopic adrenocorticotropic hormone (ACTH) syndrome is accurate but technically demanding and risky. Bilateral sampling of the internal jugular vein is simpler and safer.

Objective: To compare bilateral internal jugular vein sampling with bilateral inferior petrosal sinus sampling for distinguishing patients with Cushing disease from those with the ectopic ACTH syndrome.

Setting: Tertiary referral hospital.

Patients: 20 patients with surgically proven Cushing disease and 1 patient with proven ectopic ACTH syndrome.

Intervention: All patients underwent petrosal sinus sampling and jugular vein sampling before and after administration of corticotropin-releasing hormone (CRH) on separate days.

Measurements: Ratios of central ACTH to peripheral ACTH in petrosal sinus samples and jugular vein samples were calculated before and after administration of CRH.

Results: Ratios of central to peripheral ACTH were diagnostic for Cushing disease (> 2 before administration of CRH and > 3 after administration of CRH) in jugular vein samples from 16 of 20 patients with surgically proven Cushing disease (sensitivity, 80% [95% CI, 56% to 96%]). Ten of these 16 patients (63%) had diagnostic results only after CRH was administered. The average ratio of central to peripheral ACTH in jugular vein samples was 2.7 before CRH and 7.7 after CRH. Ratios of central to peripheral ACTH were diagnostic in petrosal sinus samples from 19 of 20 patients with surgically proven Cushing disease (sensitivity, 95% [CI, 75% to 99%]). Samples from all 19 patients had diagnostic ratios before and after administration of CRH. The average ratio of central to peripheral ACTH in petrosal sinus samples was 17.7 before CRH and 90.0 after CRH. In the patient with the ectopic ACTH syndrome, ratios of central to peripheral ACTH were negative in jugular vein samples and petrosal sinus samples before and after CRH (< 2 and < 3, respectively).

Conclusions: Jugular vein sampling correctly identified ACTH-secreting pituitary adenomas in 80% of patients with proven Cushing disease. Administration of CRH was essential for diagnostic results in 63% of the patients. Jugular vein sampling is less invasive than petrosal sinus sampling. Negative results on jugular vein sampling should be confirmed by petrosal sinus sampling.