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Cited by 263Adrenal and Paraganglionic TumorsPituitary Gland Disorders and TreatmentsAdrenal Hormones and Disorders

Natural History of Adrenal Incidentalomas With and Without Mild Autonomous Cortisol Excess: A Systematic Review and Meta-analysis

Elhassan, Yasir S., Alahdab, Fares, Prete, Alessandro, Delivanis, Danae A., Khanna, Aakanksha, Prokop, Larry, Murad, Mohammad H., O'Reilly, Michael W. +2 more·2019·Annals of Internal Medicine
DOI 10.7326/m18-3630
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Abstract

Background: Adrenal incidentalomas are mostly benign nonfunctioning adrenal tumors (NFATs) or adenomas causing mild autonomous cortisol excess (MACE), but their natural history is unclear. Purpose: To summarize the follow-up data of adults with NFAT or MACE to determine the proportions of tumor growth, malignant transformation, and incident changes in hormone function; the prevalence of incident cardiometabolic comorbid conditions; and mortality. Data Sources: MEDLINE, Embase, Cochrane, and Scopus (January 1990 to February 2019) and bibliographies of identified articles, without language restriction. Study Selection: Studies that included 20 or more conservatively managed patients with NFAT or MACE and reported outcomes at baseline and after at least 12 months of follow-up. Data Extraction: Pairs of reviewers extracted outcomes and assessed methodological quality. Data Synthesis: Thirty-two studies reported outcomes of 4121 patients with NFAT or MACE, 61.5% of whom were women; the mean age was 60.2 years, and mean follow-up was 50.2 months. Mean tumor growth was 2 mm over 52.8 months. Clinically significant tumor enlargement (≥10 mm) occurred in 2.5% of patients, and none developed adrenal cancer. Clinically overt hormone excess was unlikely to develop (<0.1%) in patients with NFAT or MACE. Only 4.3% of patients with NFAT developed MACE, and preexisting MACE was unlikely to resolve (<0.1%). Hypertension, obesity, dyslipidemia, and type 2 diabetes were highly prevalent (60.0%, 42.0%, 33.7%, and 18.1% of patients, respectively) and were more likely to develop and worsen in MACE than NFAT. New cardiovascular events were more prevalent in MACE (15.5%) than NFAT (6.4%). Mortality was 11.2% and was similar between NFAT and MACE. Limitation: Evidence was scarce, and definitions of MACE and comorbid conditions were heterogeneous. Conclusion: During follow-up, NFAT and MACE do not show clinically relevant changes in size or hormonal function, but they may carry an increased risk for cardiometabolic comorbid conditions. Primary Funding Source: None.

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  • Although overt physical features may be absent, the subtle hypercortisolism seen in MACS has been associated with adverse cardiovascular and metabolic outcomes, including hypertension, diabetes, dyslipidemia, weight gain, osteoporosis, increased frailty, and increased mortality.

    “Although overt physical features may be absent, the subtle hypercortisolism seen in MACS has been associated with adverse cardiovascular and metabolic outcomes, including hypertension, diabetes, dyslipidemia, weight gain, osteoporosis, increased frailty, and increased mortality (33, 34, 97-101).”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [97]

  • Pre-existing MACE was unlikely to resolve (<0.1%).

    “and pre-existing MACE was unlikely to resolve (<0.1%).”

    From Adrenal incidentaloma (2020) · cites this paper as [269]

  • Reported mortality (11.2%) was similar between NFATs and MACE.

    “However, reported mortality (11.2%) was similar between NFATs and MACE.”

    From Adrenal incidentaloma (2020) · cites this paper as [269]

  • Only 4.3% of patients with NFATs developed MACE.

    “Only 4.3% of patients with NFATs developed MACE, and pre-existing MACE was unlikely to resolve (<0.1%).”

    From Adrenal incidentaloma (2020) · cites this paper as [269]

  • New cardiovascular events were more prevalent in MACE (15.5%) than NFATs (6.4%) during follow-up.

    “new cardiovascular events were more prevalent in MACE (15.5%) than NFATs (6.4%) during follow-up.”

    From Adrenal incidentaloma (2020) · cites this paper as [269]

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Authors
Elhassan, Y. S., Alahdab, F., Prete, A., Delivanis, D. A., Khanna, A., Prokop, L., Murad, M. H., O'Reilly, M. W., Arlt, W., & Bancos, I.
Affiliations
  • University of Birmingham (GB)
  • Mayo Clinic (US)
  • University of Birmingham Institute of Metabolism and Systems Research and Birmingham Health Partners Centre for Endocrinology, Diabetes and Metabolism, Birmingham, United Kingdom (Y.S.E., A.P., M.W.O., W.A.)
ORCID
Venue
Annals of Internal Medicine
Publisher
American College of Physicians
Published
2019-07-16
Volume
171
Issue
2
Pages
107-116
ISSN
  • 0003-4819 (ISSN-L)
  • 1539-3704
DOI
10.7326/m18-3630
OpenAlex
W2954206106
Cited by
263
References
58
Citations by year
2026: 38 · 2025: 49 · 2024: 33 · 2023: 35 · 2022: 42 · 2021: 37 · 2020: 24 · 2019: 4
FWCI
5.51
Type
journal article
Language
en
Open access
closed
Licence
www.acpjournals.org/journal/aim/text-and-data-mining (tdm)
Locations
  • Annals of Internal Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
adrenal incidentaloma, non-functioning adrenal tumor, adrenal adenoma, tumor growth, malignant transformation, cortisol excess, cardiometabolic comorbidities, cardiovascular events, mortality, conservative treatment
MeSH terms
Adrenal Gland Neoplasms, Humans, Hydrocortisone, Risk Factors, Biomarkers, Tumor, Comorbidity

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