The natural progression and outcomes of adrenal incidentaloma: a systematic review and meta-analysis

Minerva Endocrinol. 2017 Mar;42(1):77-87. doi: 10.23736/S0391-1977.16.02394-4. Epub 2015 Dec 23.


Introduction: 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.

Evidence acquisition: 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.

Evidence synthesis: 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.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adrenal Gland Neoplasms / drug therapy*
  • Adrenal Gland Neoplasms / pathology*
  • Disease Progression
  • Humans
  • Treatment Outcome

Supplementary concepts

  • Adrenal incidentaloma