Abstract
Background
Up to 50% of patients with adrenal incidentalomas have mild autonomous cortisol secretion, which may increase their cardiometabolic morbidity, compared with patients with nonfunctional adrenal tumors. Studies evaluating cardiometabolic outcomes of patients with mild autonomous cortisol secretion defined by 1-mg dexamethasone suppression testing (cortisol 1.8–5 μg/dL) have demonstrated mixed results. The aim of this study was to assess the metabolic outcomes of patients with mild autonomous cortisol secretion, defined by the 1-mg dexamethasone suppression testing criterion, compared with patients with nonfunctional adrenal tumors who underwent adrenalectomy.
Methods
We conducted a single-institution retrospective cohort study comparing adult patients who underwent unilateral adrenalectomy from November 30, 2011, to August 19, 2023, for mild autonomous cortisol secretion (1-mg dexamethasone suppression testing cortisol 1.8–5 μg/dL) or nonfunctional adrenal tumors (1-mg dexamethasone suppression testing cortisol <1.8 μg/dL). Preoperative prevalences and postoperative changes in diabetes mellitus, hypertension, dyslipidemia, and elevated body mass index (≥25) were assessed. Patients were followed from the time of surgery until their last outpatient visit. Multivariable logistic regression was pursued for outcomes that varied between cohorts.
Results
A total of 65 patients (53 mild autonomous cortisol secretion and 12 nonfunctional adrenal tumors) were analyzed. Patients with mild autonomous cortisol secretion were older and more likely to have diabetes mellitus than patients with nonfunctional adrenal tumors (odds ratio: 7.81, 95% confidence interval [0.94, 64.96], P = .04). Patients were followed for a median of 28.1 months [11.1, 55.3 months]. Patients with mild autonomous cortisol secretion were more likely to have postoperative weight improvement (odds ratio: 8.31, [0.97, 71.14], P = .03). After adjusting for clinically relevant variables, the 1-mg dexamethasone suppression testing cortisol was predictive of postoperative weight improvement (odds ratio: 1.88, [1.1, 3.65], P = .04).
Conclusion
Weight loss should be considered as a potential benefit of adrenalectomy in patients with mild autonomous cortisol secretion.
Graphical abstract
Introduction
Mild autonomous cortisol secretion (MACS) is the most common hormonal abnormality diagnosed in patients with adrenal incidentalomas, impacting 20%–50% of patients.1 Patients with MACS have biochemical evidence of adrenocorticotropic hormone (ACTH)-independent hypercortisolism but lack clinical stigmata commonly associated with overt hypercortisolism, such as facial plethora, abdominal adiposity, extremity weakness and wasting, and/or violaceous striae.2 Overt hypercortisolism is well recognized to cause cardiovascular, musculoskeletal, and metabolic disorders, which have variable resolution even after diagnosis and treatment.3 There is a growing body of evidence that patients with MACS also have increased cardiometabolic morbidity and mortality compared with patients with nonfunctional adrenal tumors,4 but this evidence is challenging to interpret given wide variability in diagnostic criteria that have historically been used.5, 6, 7
Recent guidelines have suggested that a diagnosis of MACS be applied to all patients with a morning (AM) serum cortisol of >1.8 μg/dL after low-dose (1-mg) dexamethasone suppression testing (DST) who lack overt features of hypercortisolism.8,9 However, prior studies comparing cardiometabolic outcomes between patients with MACS and nonfunctional adrenal tumors as well as between patients who underwent operative and nonoperative management have used a 1-mg DST AM serum cortisol of 1.8–5.0 μg/dL as a definition of mild (“subclinical”) hypercortisolism.10, 11, 12, 13, 14, 15, 16 Given that these studies have demonstrated mixed results,4 the primary aim of this study was to assess the metabolic outcomes of patients with MACS, as defined by a 1-mg DST AM cortisol of 1.8–5.0 μg/dL, compared with patients with nonfunctional adrenal tumors who underwent adrenalectomy.
Section snippets
Methods
This was a single-institution retrospective cohort study of patients aged ≥18 years who underwent initial unilateral adrenalectomy from November 30, 2011, to August 19, 2023. Patients were identified through a prospectively maintained database of all patients who underwent adrenalectomy at the study institution. Patients were excluded if they had a 1-mg DST AM serum cortisol of >5 μg/dL, ACTH-dependent hypercortisolism, primary aldosteronism, pheochromocytoma, primary bilateral macronodular
Results
Of the 460 patients who underwent adrenalectomy during the study period, 53 patients met criteria for MACS and 12 patients for nonfunctional adrenal tumors, yielding a cohort of 65 patients. Patients with MACS were older than those with nonfunctional adrenal tumors (MACS, median 60 years [IQR: 54, 68 years] vs nonfunctional adrenal tumors, 49 years [37, 57 years], P = .02) but were similar by sex, race, ethnicity, BMI, nodule size, laterality, and surgical approach (Table II). Among patients
Discussion
MACS is the most common hormonal abnormality diagnosed in patients with adrenal incidentalomas. Despite lacking clinical stigmata of overt hypercortisolism, patients with MACS appear to have increased cardiometabolic morbidity and mortality similar to patients with overt hypercortisolism. The optimal management of MACS is debated, and prior studies using a 1-mg DST AM serum cortisol of 1.8–5.0 μg/dL as a definition of mild hypercortisolism have demonstrated mixed results. Hence, this study
Funding/Support
This project is funded in part by the Advancing a Healthier Wisconsin Endowment at the Medical College of Wisconsin. This publication was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through grant number UL1TR001436. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The grant supports the creation and maintenance of
CRediT authorship contribution statement
Alexa Lisevick Kumar: Writing – original draft, Visualization, Methodology, Formal analysis, Data curation, Conceptualization. Sophie Dream: Writing – review & editing, Validation, Supervision, Methodology, Investigation. Tahseen Shaik: Resources, Project administration, Investigation, Data curation. Kara Doffek: Resources, Project administration, Investigation, Data curation. Ryan Conrardy: Writing – review & editing, Methodology, Formal analysis. James W. Findling: Writing – review & editing,
Conflict of Interest/Disclosure
Dr Findling reports consulting for Corcept, Diurnal, Crinetics and serving as an investigator for Recordati. The rest of the authors reported no biomedical financial interests or potential conflicts of interest.
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Filed under: adrenal, Clinical trials | Tagged: adrenal incidentaloma, cortisol, dexamethasone suppression test, unilateral adrenalectomy |
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