Subtyping of Primary Aldosteronism in the AVIS-2 Study: Assessment of Selectivity and Lateralization.

CONTEXT: Adrenal venous sampling (AVS) is the key test for subtyping primary aldosteronism (PA), but its interpretation varies widely across referral centers and this can adversely affect the management of PA patients. OBJECTIVES: To investigate in a real-life study the rate of bilateral success and identification of unilateral aldosteronism and their impact on blood pressure outcomes in PA subtyped by AVS. DESIGN AND SETTINGS: In a retrospective analysis of the largest international registry of individual AVS data (AVIS-2 study), we investigated how different cut-off values of the selectivity index (SI) and lateralization index (LI) affected rate of bilateral success, identification of unilateral aldosteronism, and blood pressure outcomes. RESULTS: AVIS-2 recruited 1625 individual AVS studies performed between 2000 and 2015 in 19 tertiary referral centers. Under unstimulated conditions, the rate of biochemically confirmed bilateral AVS success progressively decreased with increasing SI cut-offs; furthermore, with currently used LI cut-offs, the rate of identified unilateral PA leading to adrenalectomy was as low as <25%. A within-patient pairwise comparison of 402 AVS performed both under unstimulated and cosyntropin-stimulated conditions showed that cosyntropin increased the confirmed rate of bilateral selectivity for SI cut-offs ≥ 2.0, but reduced lateralization rates (P < 0.001). Post-adrenalectomy outcomes were not improved by use of cosyntropin or more restrictive diagnostic criteria. CONCLUSION: Commonly used SI and LI cut-offs are associated with disappointingly low rates of biochemically defined AVS success and identified unilateral PA. Evidence-based protocols entailing less restrictive interpretative cut-offs might optimize the clinical use of this costly and invasive test. (J Clin Endocrinol Metab XX: 0-0, 2020).

Laparoscopic simultaneous bilateral adrenalectomy: assessment of feasibility and potential indications.

OBJECTIVE: To report a single-center experience with laparoscopic simultaneous bilateral adrenalectomy (LSBA) and to evaluate its safety, surgical outcomes, and potential indications of the procedure. METHODS: A total of 21 patients underwent LSBA between 2000 and 2010 at our institution. Four patients had bilateral Cushing's syndrome (CS), two had bilateral pheochromocytoma, and one had a bilateral metastatic tumor. Eleven patients had unilateral or bilateral aldosterone-producing adenoma (APA), associated with CS or subclinical CS. Three patients had unilateral APA with contralateral non-functioning adenoma. Partial adrenalectomy was performed first by using with four ports. After the excision of one gland, the contralateral gland was removed after repositioning of the patient. RESULTS: LSBA was completed in all 21 patients without major complications. Mean operative time was 329.7 min and the estimated blood loss was 94.1 mL. Mean tumor size was 21.8 mm. Of the 16 patients receiving an adrenal-sparing procedure, nine of 11 discontinued glucocorticoid replacement after 2 years. The remaining five patients receiving bilateral total adrenalectomy required 0.5-0.75 mg of dexamethasone permanently. No open conversions, no deaths or no adrenal insufficiencies were encountered. CONCLUSIONS: LSBA represents a safe and viable treatment option for selected patients with bilateral adrenal disease.

Development of sensitive derivatization method for aldosterone in liquid chromatography-electrospray ionization tandem mass spectrometry of corticosteroids.

A highly sensitive quantification method of aldosterone by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) was investigated in a positive mode using recently developed picolinyl derivatization. Aldosterone was smoothly and quantitatively converted to the ethyl ether-picolinyl derivative by treatment with HCl-ethanol followed by the esterification with picolinic acid in the presence of 2-methyl-6-nitrobenzoic anhydride and 4-dimethylaminopyridine. The positive ion-ESI mass spectrum of the ethyl ether-picolinyl derivative was characterized by an appearance of protonated molecule ([M+H](+)) as a base peak. The ethyl ether-picolinyl derivatization gave a successful result in a separation of aldosterone from corticosterone, dehydrocorticosterone and cortexolone, and also provided an approximately 10-fold higher ESI response in the positive-LC-ESI-MS/MS (selected reaction monitoring; SRM) when compared to that of underivatized molecule (negative mode). The limit of quantification of aldosterone by SRM using ethyl ether-picolinyl derivatization (m/z 494-->m/z 448) was 1 pg/0.2 ml serum with accuracy and precision of 92.6% and 5.6%, respectively.