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Dexamethasone Suppression Testing in a Contemporary Cohort with Adrenal Incidentalomas in Two U.S. Integrated Healthcare Systems.

ABSTRACT: Autonomous cortisol secretion (ACS) from an adrenal adenoma can increase the risk for comorbidities and mortality. The dexamethasone suppression test (DST) is the standard method to diagnose ACS. A multi-site, retrospective cohort of adults with diagnosed adrenal tumors was used to understand patient characteristics associated with DST completion and ACS. Time to DST completion was defined using the lab value and result date; follow-up time was from the adrenal adenoma diagnosis to the time of completion or censoring. ACS was defined by a DST > 1.8 µg/dL (50 nmol/L). The Cox proportional hazards regression model assessed associations between DST completion and patient characteristics. In patients completing a DST, a logistic regression model evaluated relationships between elevated ACS and covariates. We included 24,259 adults, with a mean age of 63.1 years, 48.1% obese, and 28.7% with a Charlson comorbidity index ≥ 4. Approximately 7% (n = 1768) completed a DST with a completion rate of 2.36 (95% CI 2.35, 2.37) per 100 person-years. Fully adjusted models reported that male sex and an increased Charlson comorbidity index were associated with a lower likelihood of DST completion. Current or former smoking status and an increased Charlson comorbidity index had higher odds of a DST > 1.8 μg/dL. In conclusion, clinical policies are needed to improve DST completion and the management of adrenal adenomas.

SUBMITTER: Crawford M

PROVIDER: S-EPMC10740617 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Dexamethasone Suppression Testing in a Contemporary Cohort with Adrenal Incidentalomas in Two U.S. Integrated Healthcare Systems.

Crawford Mackenzie M McDonald Bennett B Chen Wansu W Chowdhry Hina H Contreras Richard R Reyes Iris Anne C IAC Dhakal Eleena E Villanueva Tish T Barzilay Joshua I JI Vaughn Candace F CF Czerwiec Frank S FS Katz David A DA Adams Annette L AL Gander Jennifer C JC

Biomedicines 20231128 12

Autonomous cortisol secretion (ACS) from an adrenal adenoma can increase the risk for comorbidities and mortality. The dexamethasone suppression test (DST) is the standard method to diagnose ACS. A multi-site, retrospective cohort of adults with diagnosed adrenal tumors was used to understand patient characteristics associated with DST completion and ACS. Time to DST completion was defined using the lab value and result date; follow-up time was from the adrenal adenoma diagnosis to the time of c ...[more]

PMID: 38137386

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Project description:ObjectiveTo determine all-cause mortality risk in patients with and without adrenal incidentaloma.MethodsRetrospective cohort study of patients with CT abdomen performed within 24 h of emergency room presentation at an academic medical center from January 1, 2005, to December 31, 2009, without history of adrenal disease, adrenal lab testing, or cancer. Incidentaloma cohort identified by database query of imaging reports followed by manual review and matched to no-nodule controls at 3:1 on age ± 1 year and exam date ± 3 months. Mortality ascertained by in-hospital deaths and National Death Index query. Survival analysis performed with Kaplan-Meier curves and Cox proportional hazards models.ResultsAmong 42,575 adults with abdominal CT exams, 969 adrenal incidentaloma patients and 2907 no-nodule controls were identified. All 3876 individuals entered survival analysis with 31,182 person-years at risk (median follow-up 8.9 years [IQR, 6.9-10.7]). All-cause mortality was significantly higher among those with adrenal incidentalomas (353/969, 36.4%) compared with those without (919/2907, 31.6%; mortality difference 7.6 per 1000 person-years; multivariable-adjusted hazard ratio [aHR] 1.14; 95% CI, 1.003-1.29). Exploratory analyses, limited by missing covariates, found that adrenal incidentalomas were associated with significantly increased incidence of malignancy (aHR 1.61; 95% CI, 1.22-2.12), diabetes (aHR 1.43; 95% CI, 1.18-1.71), heart failure (aHR 1.32; 95% CI, 1.07-1.63), peripheral vascular disease (aHR 1.28; 95% CI, 1.95-1.56), renal disease (aHR 1.21; 95% CI, 1.01-1.44), and chronic pulmonary disease (aHR 1.22; 95% CI, 1.01-1.46) compared with controls.ConclusionsAdrenal incidentalomas are associated with increased mortality and may represent a clinically valuable biomarker.Key points• Adrenal incidentalomas are associated with increased mortality. • Adrenal incidentaloma size is not predictive of mortality. • On exploratory analyses, adrenal incidentalomas are associated with chronic illnesses.

Project description:BackgroundAutonomous cortisol secretion (ACS), resulting from cortisol-producing adenomas (CPA), causes endogenous steroid-induced osteoporosis (SIOP). However, the risk of endogenous SIOP cannot be explained by cortisol excess alone, and how other steroid metabolites affect bone status is unclear.MethodsACS was diagnosed as serum cortisol ≥1.8 μg/dL after the 1-mg dexamethasone suppression test (DST-cortisol). Using liquid chromatography tandem mass spectrometry, 21 plasma steroid metabolites were measured in 73 patients with ACS and 85 patients with non-functioning adrenal tumors (NFAT). Expression of steroidogenic enzymes and relevant steroid metabolites were analyzed in some of CPA tissues.FindingsDiscriminant and principal component analyses distinguished steroid profiles between the ACS and NFAT groups in premenopausal women. Premenopausal women with ACS exhibited higher levels of a mineralocorticoid metabolite, 11-deoxycorticosterone (11-DOC), and lower levels of androgen metabolites, dehydroepiandrosterone-sulfate, and androsterone-glucuronide. In premenopausal women with ACS, DST-cortisol negatively correlated with trabecular bone score (TBS). Additionally, 11-DOC negatively correlated with lumbar spine-bone mineral density, whereas androsterone-glucuronide positively correlated with TBS. The CPA tissues showed increased 11-DOC levels with increased expression of CYP21A2, essential for 11-DOC synthesis. Adrenal non-tumor tissues were atrophied with reduced expression of CYB5A, required for androgen synthesis.InterpretationThis study demonstrates that unbalanced production of adrenal steroid metabolites, derived from both adrenal tumor and non-tumor tissues, contributes to the pathogenesis of endogenous SIOP in premenopausal women with ACS.FundingJSPS KAKENHI, Secom Science and Technology Foundation, Takeda Science Foundation, Japan Foundation for Applied Enzymology, AMED-CREST, JSTA-STEP, JST-Moonshot, and Ono Medical Research Foundation.

Project description:Objective: Germline ARMC5 mutations are considered to be the main genetic cause of primary macronodular adrenal hyperplasia (PMAH). PMAH is associated with high variability of cortisol secretion caused from subclinical hypercortisolism to overt Cushing's syndrome (CS), in general due to bilateral adrenal nodules and rarely could also be due to non-synchronic unilateral adrenal nodules. The frequency of adrenal incidentalomas (AI) associated with PMAH is unknown. This study evaluated germline allelic variants of ARMC5 in patients with bilateral and unilateral AI and in patients with overt CS associated with bilateral adrenal nodules. Methods: We performed a retrospective multicenter study involving 123 patients with AI (64 bilateral; 59 unilateral). We also analyzed 20 patients with ACTH pituitary independent overt CS associated with bilateral adrenal nodules. All patients underwent germline genotyping analysis of ARMC5; abdominal CT and were classified as normal, possible or autonomous cortisol secretion, according to the low doses of dexamethasone suppression test. Results: We identified only one pathogenic allelic variant among the patients with bilateral AI. We did not identify any pathogenic allelic variants of ARMC5 in patients with unilateral AI. Thirteen out of 20 patients (65%) with overt CS and bilateral adrenal nodules were carriers of pathogenic germline ARMC5 allelic variants, all previously described. The germline ARMC5 mutation was observed in only one patient with bilateral AI; it was associated with autonomous cortisol secretion and showed to be a familial form. Conclusion: The rarity of germline ARMC5 mutations in AI points to other molecular mechanisms involved in this common adrenal disorder and should be investigated. In contrast, patients with overt Cushing's syndrome and bilateral adrenal nodules had the presence of ARMC5 mutations that were with high prevalence and similar to the literature. Therefore, we recommend the genetic analysis of ARMC5 for patients with established Cushing's syndrome and bilateral adrenal nodules rather than patients with unilateral AI.

Dataset Information

Dexamethasone Suppression Testing in a Contemporary Cohort with Adrenal Incidentalomas in Two U.S. Integrated Healthcare Systems.

Publications

Dexamethasone Suppression Testing in a Contemporary Cohort with Adrenal Incidentalomas in Two U.S. Integrated Healthcare Systems.

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