- This is an adrenal vein sampling procedure, but we are testing for excess cortisol production (Cushing's disease) and not excess aldosterone (primary hyperaldosteronism) - This is to help lateralize which adrenal gland is producing too much cortisol to aid in a possible surgical cure - In order to normalize the excess cortisol on each side, we need to use the aldosterone as a reference (similarly to how we use the cortisol as a reference to normalize the excess aldosterone) - Sample both adrenal veins, the IVC and a peripheral vein - For each adrenal side, IVC and peripheral vein, test for: - Cortisol, aldosterone, adrenaline, noradrenaline, and DHEAS One last VERY important thing. This patient SHOULD NOT get the typical Cortrosyn drip the morning of the procedure, this will make the samples incorrect and we will have to reschedule if he does get it. ###### Procedure Day (From Brad Poore email) So, for DHEAS, Cortisol, and Aldosterone, 1 mL of serum (**without a separator gel**), is required per site. However, I would recommend 2 mL serum (**so roughly 4 mL whole blood**). Both tests can be on the same tube. Epinephrine and norepinephrine require **2.5 mL** of plasma/site in a lithium or sodium heparin tube (**Green Top**). This is a very heat labile test, so post collection, this tube needs to be put on ice and sent to the lab immediately.  This means: - 1 full red top tube per site - 1 full sodium heparin (dark green top), per site - In addition, the dark green should be put into ice for transport to the lab [https://testdirectory.questdiagnostics.com/test/test-detail/314/catecholamines-fractionated-plasma?p=r&q=epinephrine&cc=MASTER](https://testdirectory.questdiagnostics.com/test/test-detail/314/catecholamines-fractionated-plasma?p=r&q=epinephrine&cc=MASTER) For ordering, I believe you should be able to order these the same way as before. However, you could put the comment: "**AVS Sample. Include DHEAS and Catecholamines**" just in case. ### Published Studies #### Adrenal venous sampling in patients with ACTH-independent hypercortisolism https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838037/ AVS is performed on the 2nd day of 48-h dexamethasone suppression (0.5 mg every sixth hour) Draw blood from the right adrenal vein, left adrenal vein, IVC, and peripheral vein Serum cortisol, aldosterone, DHEAS, plasma adrenaline, and noradrenaline are measured Selectivity index: Aldosterone (adrenal vein)/aldosterone (peripheral vein) >2 Lateralization index: Use aldosterone to normalize Then check each concentration (aldosterone, adrenaline, noradrenaline, and DHEAS) and compare side-to-side Since no consensus exists on how to optimally define laterality during AVS in patients with CS, each patient was evaluated individually. However, in general, a patient was considered to have a unilateral dominant cortisol production when the side-to-side lateralization ratio was >2, when using aldosterone as a reference hormone, especially in conjunction with a concordant side-to-side lateralization ratio >2 using the other three hormones as reference. When the concentration of the aldosterone, adrenaline, or noradrenaline was unmeasurably low, the lower limit of detection was used for calculation of selectivity and lateralization. #### Adrenal Vein Cortisol to Metanephrine Ratio for Localizing ACTH-Independent Cortisol-Producing Adenoma: A Case Report Open Access Rishi Raj , Philip A Kern , Neelima Ghanta , Edilfavia M Uy , Kamyar Asadipooya Journal of the Endocrine Society, Volume 5, Issue 4, April 2021, bvab009, https://doi.org/10.1210/jendso/bvab009 When AVS is used for evaluation of SCS patients, the measurements should be performed after an overnight fast and with low-dose (1-2 mg) or high-dose (8 mg) dexamethasone the day before the procedure to suppress ACTH and minimize the effect of stress on cortisol level. In addition, the correct catheter position is important, which is based on the adrenal vein (AV) to peripheral vein (PV) metanephrine ratio. An AV:PV metanephrine ratio greater than 12 indicates correct adrenal vein position and successful catheterization [17, 21]. There are 2 usual approaches to lateralize a cortisol-secreting adenoma. The AV:PV cortisol gradient is one method, with a ratio less than 3.3 not clinically significant, between 4.1 and 6.4 associated with adrenal hyperplasia, and greater than 6.5 consistent with cortisol-producing adenoma [17, 18]. The second approach involves a higher to lower cortisol gradient between the 2 adrenal veins. It has been reported that a gradient greater than 2.3 proves lateralization and less than 2 is associated with bilateral cortisol production [17, 21]. However, this is a very narrow window of cortisol ratios on which to base a surgical decision of which adrenal to remove, and it also does not account for a gradient between 2 and 2.3. We present a case to justify the role of cortisol to metanephrine ratio as an alternative approach in the situation where the current criteria cannot lateralize a cortisol-producing adenoma. #### The Clinical Conundrum of Corticotropin-independent Autonomous Cortisol Secretion in Patients with Bilateral Adrenal Masses https://link.springer.com/article/10.1007/s00268-007-9332-8 A cortisol AV:PV gradient >6.5 was consistent with a cortisol-secreting adenoma Mean (± SD) maximal diameter of the adrenal masses on computed tomography was 3.3 ± 1.3 cm (range: 1.2–6.0 cm). Successful catheterization was confirmed with AV:PV epinephrine gradients. A cortisol AV:PV gradient >6.5 was consistent with a cortisol-secreting adenoma in 11 adrenal glands; 5 patients had clinically important bilateral autonomous cortisol hypersecretion, 3 had bilateral cortisol-secreting adenomas, and 2 had ACTH-independent macronodular adrenal hyperplasia. Adrenal venous sampling-guided adrenalectomy was completed in all 10 patients—2 patients had total bilateral adrenalectomy and 2 others had subtotal bilateral adrenalectomy. During a mean follow-up of 36.1 months (range: 0.7–123 months), CS or clinically important cortisol secretory autonomy did not recur. #### Adrenal venous sampling in a patient with adrenal Cushing syndrome https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536821/ The patient did not have any postoperative complication and received replacement therapy with hydrocortisone 50 mg every 8 h during the first 48 h and subsequently received prednisolone 10 mg and 0.1 mg of fludrocortisone replacement with resolution of the hypokalemia.