Comparison of Serum Cortisol Profiles By LC/MS-MS and Ria to Identify Subclinical Hypercortisolism Among Adrenal Incidentalomas

Presentation Number: SUN 382
Date of Presentation: April 2nd, 2017

Martha Katherine Huayllas*1, Lilian F. Hayashi2, Kelly C. Oliveira2, Ravinder J. Singh3, Brian Netzel4 and Claudio E. Kater2
1Universidade Federal de São Paulo - UNIFESP, São Paulo, Brazil, 2Federal University of São Paulo, São Paulo, SP, Brazil, 3Mayo Clinic, 4Mayo Clinic, Rochester, MN

Abstract

Introduction: SCH occurs in 5-30% of AI and is critical to detect since associated metabolic abnormalities increase mortality. Definition is subjective and relies on serum cortisol (Fs) response to 1mg dexamethasone (Dx) suppression test (DST). Cortisol resistance to DST is based on arbitrary cutoffs ranging from 1.8 to 5.0 mg/dL. False-positive results may be due to impaired absorption or accelerated Dx disposal and be influenced by the method by which Fs is measured. Aim: 1) compare Fs determined by LC/MS-MS and RIA over the range of values spanning from responses to DST (pDST) and to ACTH (pACTH) in patients with AI and control subjects (CS); 2) recognize SCH among NFA. Patients and methods: 73 AI patients: 52 unilateral (UAI, 34F, 22-87y) and 21 bilateral (BAI, 14F, 44-77y), and 33 CS (22F, 36-74y) underwent ACTH stimulation (Synacthen 0.25mg IV bolus) followed a week later by 1mgDST. Basal, pDST, and 60min-pACTH Fs levels were determined by a specific in-house RIA at Steroids Laboratory (Brasil) and by LC-MS/MS at Mayo Endocrine Research Labs (Rochester, MN, USA). Serum Dx was measured in all by an in-house RIA: DST was validated if serum Dx >140ng/dL. We define SCH if pDST Fs level is >2.5 mg/dL plus an elevated 23h saliva F and suppressed ACTH or DHEAS. Results: Average Fs values measured by RIA were 15% higher than by LC/MS-MS, especially at the upper range, but 32% of all 315 pairs of values were higher by LC/MS-MS. Correlation between both methods for basal, pDST and pACTH Fs values was r=0.941 (p<0.0001; y= 0.663x + 1.98). Basal, pDST, and pACTH values were higher in BAI than in UAI, as compared to CS. Percent changes from basal of pDST and pACTH Fs were greatest in BAI. We identified 10/48 (21%) UAI and 9/20 (45%) BAI whose Fs values were >2.5 mg/dL (consistent with SCH). ACTH <10 pg/mL and DHEAS <40 mg/dL were seen in 36% and 48% of UAI and in 50% and 50% of BAI, respectively, but also in 25% and 42% of CS. These numbers were significantly more consistent in the SCH subgroups for both UAI (70% and 50%) and BAI (78% and 67%). pDST saliva cortisol was elevated in 42% and 62% of UAI and BAI, respectively, but only in 7% of CS. Discussion: Although steroid quantification is being upgraded to LC/MS-MS, we found a robust correlation between Fs values measured by RIA and LC/MS-MS, that was even stronger across the zone of interest (normal to lower range). Basal, pDST and pACTH Fs values were significantly higher than CS in UAI and highest in BAI. SCH was recognized in 21% and 45% of UAI and BAI patients, 82% and 89% of whom satisfying 2 additional criteria for autonomous cortisol production. Conclusion: Concurrent LC/MS-MS- and RIA-determined Fs in patients with UAI, BAI and in CS resulted in similar figures across a wide spectrum of values ranging from low (pDST) to high values (pACTH), yielding an excellent correlation close to 1. At least for RIA Fs results do not affect decision-making concerning test cutoffs and SCH classification.

 

Nothing to Disclose: MKH, LFH, KCO, RJS, BN, CEK