Natural History of Adrenal Incidentalomas with and without Mild Autonomous Cortisol Excess A Systematic Review and Meta-analysis

Yasir S. Elhassan, Fares Alahdab, Alessandro Prete, Danae A. Delivanis, Aakanksha Khanna, Larry Prokop, Mohammad H. Murad, Michael W. O'Reilly, Wiebke Arlt, Irina Bancos

Research output: Contribution to journalReview article

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)107-116
Number of pages10
JournalAnnals of internal medicine
Volume171
Issue number2
DOIs
StatePublished - Jul 16 2019

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Natural History
Glandular and Epithelial Neoplasms
Hydrocortisone
Meta-Analysis
Adrenal incidentaloma
Adrenal Gland Neoplasms
Hormones
Neoplasms
Mortality
Information Storage and Retrieval
Bibliography
Dyslipidemias
Growth
MEDLINE
Adenoma
Type 2 Diabetes Mellitus
Language
Obesity
Hypertension

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Elhassan, Y. S., Alahdab, F., Prete, A., Delivanis, D. A., Khanna, A., Prokop, L., ... Bancos, I. (2019). Natural History of Adrenal Incidentalomas with and without Mild Autonomous Cortisol Excess A Systematic Review and Meta-analysis. Annals of internal medicine, 171(2), 107-116. https://doi.org/10.7326/M18-3630

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.; Arlt, Wiebke; Bancos, Irina.

In: Annals of internal medicine, Vol. 171, No. 2, 16.07.2019, p. 107-116.

Research output: Contribution to journalReview article

Elhassan, YS, Alahdab, F, Prete, A, Delivanis, DA, Khanna, A, Prokop, L, Murad, MH, O'Reilly, MW, Arlt, W & Bancos, I 2019, 'Natural History of Adrenal Incidentalomas with and without Mild Autonomous Cortisol Excess A Systematic Review and Meta-analysis', Annals of internal medicine, vol. 171, no. 2, pp. 107-116. https://doi.org/10.7326/M18-3630
Elhassan, Yasir S. ; Alahdab, Fares ; Prete, Alessandro ; Delivanis, Danae A. ; Khanna, Aakanksha ; Prokop, Larry ; Murad, Mohammad H. ; O'Reilly, Michael W. ; Arlt, Wiebke ; Bancos, Irina. / Natural History of Adrenal Incidentalomas with and without Mild Autonomous Cortisol Excess A Systematic Review and Meta-analysis. In: Annals of internal medicine. 2019 ; Vol. 171, No. 2. pp. 107-116.
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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.",
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AU - Prete, Alessandro

AU - Delivanis, Danae A.

AU - Khanna, Aakanksha

AU - Prokop, Larry

AU - Murad, Mohammad H.

AU - O'Reilly, Michael W.

AU - Arlt, Wiebke

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N2 - 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.

AB - 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.

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