Context The normal cortisol response 30 or 60 min after cosyntropin (ACTH[1-24]) is considered ≥18 μg/dL (500 nmol/L). This threshold is based on older serum cortisol assays. Specific monoclonal antibody immunoassays or LC-MS/MS may have lower thresholds for a normal response. Objective To calculate serum cortisol cutoff values for ACTH stimulation testing with newer specific cortisol assays. Design Retrospective analysis of ACTH stimulation tests performed in ambulatory and hospitalized patients suspected of adrenal insufficiency (AI). Serum samples were assayed for cortisol in parallel using Elecsys I and Elecsys II immunoassays, and when volume was available, by Access immunoassay and LC-MS/MS. Results 110 patients were evaluated. Using 18 μg/dL as the cortisol cutoff after ACTH stimulation, 14.5%, 29%, 22.4%, and 32% of patients had a biochemical diagnosis of AI using the Elecsys I, Elecsys II, Access, and LC-MS/MS assays, respectively. Deming regressions of serum cortisol were used to calculate new cortisol cutoffs based on the Elecsys I cutoff of 18 μg/dL. For 30 min values, new cutoffs were 14.6 μg/dL for Elecsys II, 14.8 μg/dL for Access, and 14.5 μg/dL for LC-MS/MS. Baseline cortisol <2 μg/dL was predictive of subnormal stimulated cortisol values. Conclusions To reduce false positive ACTH stimulation testing, we recommend a new serum cortisol cutoff of 14-15 μg/dL depending on the assay used (instead of the historical value of 18 μg/dL with older polyclonal antibody assays). Clinicians should be aware of the new cutoffs for the assays available to them when evaluating patients for AI.

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ObjectiveDemonstrate the safety and efficacy of a standardized intravenous etomidate infusion protocol in normalizing cortisol levels in patients with severe and life-threatening hypercortisolism.MethodsA retrospective case series of seven patients representing nine episodes of severe hypercortisolism at two large academic medical centers was conducted. Patients were included in this series if they received an etomidate infusion for the treatment of severe and life-threatening hypercortisolism. The etomidate infusion was administered via a newly developed protocol designed to safely reduce cortisol levels until more long-term medical or definitive surgical therapy could be instituted.ResultsSeven patients representing nine episodes received etomidate treatment. In eight of nine episodes of therapy, rapid control of hypercortisolemia was achieved, generally defined as a serum cortisol level of 10 to 20 µg/dL. Patients with a median baseline cortisol of 105 µg/dL (range, 32 to 245 µg/dL) achieved a median nadir serum cortisol of 15.8 µg/dL (range, 6.9 to 27 µg/dL) after a median of 38 hours (range, 26 to 134 hours).ConclusionsA standardized continuous intravenous etomidate infusion protocol is a safe and effective means of achieving a serum cortisol level of 10 to 20 µg/dL in patients with severe hypercortisolemia.

Context Late-night salivary cortisol (LNSC) measured by enzyme immunoassay (EIA-F) is a first-line screening test for Cushing’s syndrome (CS) with a reported sensitivity and specificity of >90%. However, liquid chromatography-tandem mass spectrometry, validated to measure salivary cortisol (LCMS-F) and cortisone (LCMS-E), has been proposed to be superior diagnostically. Objective, Setting, and Main Outcome Measures Prospectively evaluate the diagnostic performance of EIA-F, LCMS-F, and LCMS-E in 1453 consecutive late-night saliva samples from 705 patients with suspected CS. Design Patients grouped by the presence or absence of at least one elevated salivary steroid result and then subdivided by diagnosis. Results We identified 283 patients with at least one elevated salivary result; 45 had an established diagnosis of neoplastic hypercortisolism (CS) for which EIA-F had a very high sensitivity (97.5%). LCMS-F and LCMS-E had lower sensitivity but higher specificity than EIA-F. EIA-F had poor sensitivity (31.3%) for ACTH-independent CS (5 patients with at least one and 11 without any elevated salivary result). In patients with Cushing’s disease (CD), most non-elevated LCMS-F results were in patients with persistent/recurrent CD; their EIA-F levels were lower than in patients with newly diagnosed CD. Conclusions Since the majority of patients with ≥1 elevated late-night salivary cortisol or cortisone result did not have CS, a single elevated level has poor specificity and positive predictive value. LNSC measured by EIA is a sensitive test for ACTH-dependent Cushing’s syndrome but not for ACTH-independent CS. We suggest that neither LCMS-F nor LCMS-E improves the sensitivity of late-night EIA-F for CS.

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The peak cortisol response 30 or 60 minutes after cosyntropin [ACTH (1-24)] is regarded to be ≥18 μg/dL (500 nmol/L). This threshold is based on older immunoassays using polyclonal antibodies to detect cortisol. The use of more specific monoclonal antibody immunoassays or LC-MS/MS has been reported to provide a lower cutoff for a normal response. We compared the polyclonal antibody cortisol assay, Elecsys Cortisol I (Roche Diagnostic), whose peak cortisol response to ACTH 250 μg is ≥18 μg/dL (500 nmol/L), to two monoclonal antibody cortisol assays, Elecsys Cortisol II (Roche Diagnostic) and Access Cortisol (Beckman-Coulter), and LC-MS/MS in 55 patients undergoing testing for possible adrenal insufficiency. Using the Elecsys Cortisol I assay as the gold standard, all but 11 patients had a normal response at 30 or 60 minutes. Those patients were felt to have secondary adrenal insufficiency due to exogenous glucocorticoid therapy, endogenous glucocorticoid exposure, pituitary surgery, critical illness, or opioid use. ROC curves were used to determine thresholds for the other assays. A cortisol threshold of 14.5 μg/dL (400 nmol/L) would result in sensitivities and specificities of 100% and 94% for the Elecsys Cortisol II assay, 100% and 100% for the Access Cortisol assay, and 100% and 88% for LC-MS/MS. In conclusion, we recommend a new peak cortisol threshold of 14.5 μg/dL (400 nmol/L) after ACTH stimulation testing using one of these more highly specific cortisol assays. It will be important for clinicians to be aware of this new cutoff when evaluating patients for adrenal insufficiency.

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