title: The natural progression and outcomes of adrenal incidentaloma: a systematic review and meta-analysis.
abstract: BACKGROUND
  Long-term outcome of patients with adrenal incidentaloma (AI) is unknown. The aim of this study was to systematically summarize the follow-up and outcome of clinically silent AI who do not undergo surgery.
  
  
  METHODS
  All major databases and medical literature in English-language, published from 1998 to May 2015, were systematically searched for publications on AI. Primary endpoint was hormonal hyper function; secondary endpoints were time from diagnosis to study endpoint and the outcome of adrenalectomy. Meta-analysis was performed using both qualitative and quantitative approach.
  
  
  RESULTS
  A total of 11 publications were included. Total sample size was 1298 patients. Mean follow-up duration was 44.2 months. There were 82 patients confirmed to have subclinical Cushing's syndrome at diagnosis, with 1.79% new cases at the end of follow up (95% CI, 0.002 to 0.045). Incidence of Cushing's syndrome was 0.7% (95% CI, 0.001 to 0.013) and pheochromocytoma 0.4% (95% CI, 0.001 to 0.008). The mean tumor size was 2.52cm, with mean increment of 0.03cm to 2.9cm at the end of follow up. About 3% of patients ended up with surgery (95% CI, 0.01 to 0.05) but none were due to primary adrenal malignancy. Time of greatest risk of developing Cushing's syndrome and pheochromocytoma was between months 36 and 42 (hazard rate 14%), and between months 48 and 54 (hazard rate 7%) respectively.
  
  
  CONCLUSIONS
  Malignant change in non-functioning AI is rare. The risk of developing overt disease over the follow-up period is low. A less stringent imaging and functional work-up interval can be considered.
authors.affiliation: Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Sarawak, Malaysia - hh_loh@yahoo.com.my.
authors.forename: Huai H
authors.initials: HH
authors.lastname: Loh
authors.affiliation: Department of Psychiatry, University of Malaya Medical Center, Kuala Lumpur, Malaysia.
authors.forename: Anne
authors.initials: A
authors.lastname: Yee
authors.affiliation: Clinical Academic Unit (Family Medicine), Newcastle University Medicine, Iskandar Puteri, Malaysia.
authors.forename: Huai S
authors.initials: HS
authors.lastname: Loh
authors.affiliation: Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center, Bangi Selangor, Malaysia.
authors.forename: Norlela
authors.initials: N
authors.lastname: Sukor
authors.affiliation: Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center, Bangi Selangor, Malaysia.
authors.forename: Nor A
authors.initials: NA
authors.lastname: Kamaruddin
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D016896:Treatment Outcome