Incidentally discovered nonfunctioning adrenal tumors (NFAT) or adenomas causing mild autonomous cortisol excess (MACE) are unlikely to grow significantly or affect hormonal function, but they may be associated with an increased risk for cardiometabolic conditions, a review found.
The systematic review and meta-analysis included 32 studies analyzing more than 4,000 patients with NFAT or MACE and outcomes of tumor growth, malignant transformation, changes in hormone function, incident cardiometabolic comorbid conditions, and mortality. All 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. Results were published by Annals of Internal Medicine on June 25.
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 developed in very few patients (<0.1%) with NFAT or MACE. Only 4.3% of patients with NFAT developed MACE, and pre-existing 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 those with MACE than in those with NFAT. New cardiovascular events were more prevalent in patients with MACE (15.5%) than in those with NFAT (6.4%). The mortality rate was 11.2% overall and was similar between patients with NFAT and those with MACE.
The researchers reported that MACE was associated with increased risk for tumor growth but that risk for new-onset overt Cushing syndrome, primary aldosteronism, or pheochromocytoma was virtually absent.
An accompanying editorial said that the meta-analysis strongly supports guidelines from the European Society of Endocrinology and European Network for the Study of Adrenal Tumors (ESE/ENSAT), which recommend against further follow-up imaging for masses smaller than 4 cm with clear benign features on imaging. “This meta-analysis should end controversy about the need for routine follow-up imaging,” the editorial said.