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Jugular Vein Sampling in Cushing Disease

IN RESPONSE: As noted by Dr. Thaler, there is a discrepancy between the lower boundaries of the ranges of the central-to-peripheral ACTH ratios described in the Results section and the ranges of the data shown in the figure. The reason for this discrepancy is that the figure presents all the data, whereas the ranges presented in the Results section refer just to those cases with positive sampling results (that is, ratios >2 before and >3 after CRH administration). Previously in the text we had commented that 16 of 20 patients (80%) with surgically proven Cushing disease had positive findings on jugular vein sampling. Our intention in highlighting and contrasting the ranges for these positive results was to point out that the positive jugular vein samples were lower and more tightly clustered than the positive petrosal vein samples both before and after CRH administration; petrosal ratios ranged from 110.5 to 407.1 before and after CRH but jugular values ranged from only 3.7 to 14.9. We should also clarify that the average ratios of central to peripheral ACTH reported with these ranges in the text and in the abstract pertain just to these positive sampling results. Dr. Thaler also correctly points out that the 95% CI for the sensitivity for jugular vein samples presented in the Discussion section is incorrect; the correct CI (56% to 96%) is given in the abstract and the Results section. Dr. Thaler raises an interesting point about the diagnostic cut-points used in our study of jugular venous sampling. We considered lower cut-points given the inevitable increased dilution of ACTH levels in the jugular vein as opposed to the petrosal sinus, but we chose to apply the cut-points established by our group for petrosal sinus sampling [1]. As our experience grows, it should be possible to establish lower specific cut-points for jugular vein sampling in patients with Cushing disease. This might increase the sensitivity of jugular vein sampling. However, our problem is the paucity of sampling results from patients with proven ectopic ACTH syndrome, the control group on which the specificity of jugular venous sampling for Cushing disease must depend. We now are acquiring the sampling results in a larger group of patients with proven ectopic ACTH syndrome before reanalyzing the data for cut-points for the jugular vein ACTH samples.