Revisiting Adrenal Incidentalomas: Who Really Needs Surgery?
Abstract
Adrenal incidentalomas are adrenal masses discovered on imaging performed for reasons unrelated to suspected adrenal disease. Their management has shifted from size-driven decision-making toward a more selective strategy based on imaging phenotype, hormone secretion, malignancy risk, age, comorbidities, and patient preference. Most adrenal incidentalomas are benign, nonfunctioning adrenocortical adenomas and do not require adrenalectomy.
The initial evaluation should answer three practical questions. Does the lesion have benign imaging features? Is there clinically significant hormone excess? Does the patient have a context that raises the likelihood of malignancy, such as young age, pregnancy, prior extra-adrenal cancer, heterogeneous imaging, high unenhanced CT attenuation, invasion, or significant growth?
Current guidance supports no further imaging for a homogeneous adrenal mass with unenhanced CT attenuation of 10 Hounsfield units or less. Mild autonomous cortisol secretion should replace older terms such as subclinical Cushing syndrome or subclinical hypercortisolism. Surgery is standard for unilateral adrenal tumors with clinically significant hormone excess, including pheochromocytoma, overt adrenal Cushing syndrome, and lateralizing primary aldosteronism in appropriate surgical candidates. In MACS, surgery is individualized and should be considered when relevant cortisol-associated comorbidities are present. Nonfunctioning lesions with obvious benign imaging features should not be resected solely because they were discovered incidentally.
The modern question is not whether the mass exceeds an arbitrary cutoff. The more important question is whether the lesion is hormonally active, radiologically suspicious, clinically consequential, or likely to harm the patient if observed.
Introduction
Adrenal incidentalomas are increasingly detected because computed tomography and magnetic resonance imaging are used frequently for abdominal, thoracic, vascular, oncologic, and emergency evaluations. Most are benign adrenal adenomas. A smaller subset represents pheochromocytoma, aldosterone-producing adenoma, cortisol-producing adenoma, adrenocortical carcinoma, metastasis, myelolipoma, cyst, hemorrhage, infiltrative disease, or bilateral adrenal hyperplasia.
The evaluation should be efficient and risk-based. Over-investigation exposes patients to unnecessary radiation, repeated testing, anxiety, cost, and referral burden. Under-investigation can miss pheochromocytoma, primary aldosteronism, cortisol excess, adrenocortical carcinoma, or metastatic disease. A structured approach helps clinicians identify the minority who need surgery while avoiding intervention for benign lesions that pose little clinical threat.
Initial Imaging: Benign or Indeterminate?
The first imaging task is to determine whether the lesion is homogeneous and lipid-rich. If noncontrast CT has not been performed, it is often the most useful initial adrenal imaging test. A homogeneous adrenal lesion with unenhanced attenuation of 10 HU or less is highly consistent with a benign lipid-rich adenoma. In this setting, no further imaging is usually required.
Lesions with HU between 11 and 20, lipid-poor lesions, heterogeneous lesions, or lesions with irregular borders require additional characterization. Options include adrenal-protocol CT, MRI with chemical-shift imaging, FDG-PET/CT in selected oncologic settings, or interval imaging. Washout CT and chemical-shift MRI can support a benign diagnosis, but they should be interpreted in context and with attention to local radiology expertise.
A lesion 4 cm or larger that is heterogeneous or has unenhanced HU greater than 20 should be treated as higher risk and discussed in a multidisciplinary adrenal team. In many such cases, surgery is appropriate, but staging and operative planning matter because suspected adrenocortical carcinoma should not be approached like a routine benign adrenalectomy.
Hormonal Evaluation
Hormonal assessment should begin with a history and examination for symptoms and signs of catecholamine, cortisol, aldosterone, androgen, or estrogen excess. Biochemical testing then depends on the clinical and imaging context.
Most patients should undergo a 1-mg overnight dexamethasone suppression test to assess for autonomous cortisol secretion. In frail patients with limited life expectancy, testing may reasonably be omitted when results would not change management. A post-dexamethasone cortisol of 1.8 µg/dL or less generally excludes autonomous cortisol secretion. A value above 1.8 µg/dL in the absence of overt Cushing features is consistent with mild autonomous cortisol secretion, provided ACTH independence is confirmed, and test confounders are considered.
Pheochromocytoma should be excluded using plasma-free metanephrines or fractionated urinary metanephrines when the lesion is not typical for a benign adenoma, when imaging is indeterminate, or when biopsy or surgery is being considered. A homogeneous lesion with HU 10 or less has a very low likelihood of pheochromocytoma, so routine metanephrine testing is less compelling in that specific setting under current European guidance.
Primary aldosteronism should be assessed with aldosterone, renin, and the aldosterone-renin ratio in patients with hypertension or unexplained hypokalemia. Newer guidance also supports broader PA screening among patients with hypertension. Hypokalemia should be corrected before testing because low potassium can falsely suppress aldosterone. Medication effects should be considered, but testing should not be delayed indefinitely when primary aldosteronism is clinically plausible.
If adrenocortical carcinoma is suspected based on imaging or clinical features, sex steroids and steroid precursors should be measured when available, ideally using multisteroid profiling by tandem mass spectrometry.
Mild Autonomous Cortisol Secretion
MACS is one of the most important areas where older incidentaloma articles need revision. The term describes biochemical autonomy of cortisol without the classic clinical features of Cushing syndrome. It should not be treated as overt Cushing syndrome, and it should not be dismissed as clinically irrelevant.
Patients with MACS should be assessed for potentially cortisol-related comorbidities, particularly hypertension, type 2 diabetes, obesity, dyslipidemia, osteoporosis, vertebral fracture, frailty, and cardiovascular disease. The decision to offer adrenalectomy should consider the degree and persistence of cortisol nonsuppression, ACTH independence, unilateral disease, age, operative risk, severity of comorbidities, and patient preference.
Surgery may improve selected cardiometabolic outcomes, but the evidence is not uniform enough to justify routine adrenalectomy for every patient with MACS. The decision should be made in an expert multidisciplinary setting.
Who Really Needs Surgery?
Surgery is clearly appropriate for several groups. Patients with pheochromocytoma generally require adrenalectomy after appropriate preoperative preparation. Patients with unilateral primary aldosteronism who are surgical candidates and desire surgery should be considered for adrenalectomy after lateralization, usually by adrenal vein sampling, unless criteria for imaging-directed surgery are met. Patients with overt adrenal Cushing syndrome require surgery unless contraindicated. Patients with adrenal masses suspicious for adrenocortical carcinoma should be referred to an experienced adrenal surgeon and managed in a multidisciplinary center.
Surgery should also be considered for indeterminate or suspicious adrenal lesions, particularly if the mass is heterogeneous, has HU greater than 20, shows local invasion, grows significantly during surveillance, or occurs in a younger patient or pregnant patient. The surgical approach depends on suspicion of malignancy. A minimally invasive approach is appropriate for many benign hormone-secreting tumors. Open adrenalectomy is preferred when there is suspected malignancy with local invasion or when oncologic resection could be compromised by minimally invasive surgery.
Surgery is usually not indicated for an asymptomatic, nonfunctioning unilateral adrenal mass with obvious benign imaging features. This is the group most vulnerable to overtreatment.
Table 1. Surgery Versus Observation in Adrenal Incidentalomas
| Clinical scenario | Usual management direction | Key considerations |
| Homogeneous adrenal mass, HU ≤10, no hormone excess | Observation: no further imaging usually required | Benign lipid-rich adenoma phenotype |
| HU 11 to 20, homogeneous, <4 cm, no hormone excess | Additional imaging now or interval imaging | Aim to avoid prolonged surveillance when benignity can be established |
| ≥4 cm and heterogeneous or HU >20 | Multidisciplinary review; surgery is often appropriate | Stage before surgery; consider ACC |
| Pheochromocytoma | Adrenalectomy after preoperative alpha blockade | Avoid biopsy; prepare for hemodynamic instability |
| Lateralizing primary aldosteronism | Adrenalectomy if the patient is a surgical candidate and desires surgery | AVS is usually needed, except for selected younger patients |
| MACS with relevant comorbidities | Individualized discussion of surgery | Consider age, frailty, comorbidity severity, ACTH independence, and patient preference |
| Overt adrenal Cushing syndrome | Surgery unless contraindicated | Perioperative and postoperative glucocorticoid replacement required |
| Known extra-adrenal malignancy with an indeterminate adrenal lesion | Oncology-directed workup | Exclude pheochromocytoma before biopsy |
| Bilateral adrenal masses | Assess each lesion and hormonal pattern | Avoid bilateral adrenalectomy unless clearly necessary |
| Frail patient with limited life expectancy | Proportionate evaluation | Avoid testing that will not change management |
Table 2. Biochemical Testing and Common Caveats
| Clinical question | Preferred test | Key caveats |
| Autonomous cortisol secretion | 1 mg overnight DST | Frailty and limited life expectancy may change the value of testing; oral estrogen, CYP3A4 inducers, acute illness, alcohol use disorder, and poor sleep may affect interpretation |
| Pheochromocytoma | Plasma-free metanephrines or urinary fractionated metanephrines | Most importantly, when imaging is not clearly benign, false positives can occur with medications, stimulants, withdrawal states, severe illness, and improper sampling |
| Primary aldosteronism | Aldosterone, renin, ARR, potassium | Correct hypokalemia; account for medication effects; PA can occur with normal potassium |
| Suspected ACC | Sex steroids and steroid precursors, preferably multisteroid profiling when available | Use when imaging or clinical phenotype suggests malignancy |
| Bilateral destructive or infiltrative disease | Morning cortisol, ACTH, and adrenal insufficiency testing as appropriate | Consider adrenal insufficiency with bilateral metastases, hemorrhage, infection, or infiltrative disease |
Medication and Perioperative Safety
Pheochromocytoma requires careful preparation. Alpha-adrenergic blockade is started before surgery, commonly with phenoxybenzamine or a selective alpha-1 blocker such as doxazosin. Beta blockers should not be started before adequate alpha blockade because unopposed alpha-adrenergic stimulation can worsen hypertension. Patients often require salt and fluid repletion before surgery, and postoperative monitoring should include blood pressure, heart rate, and glucose because hypotension and hypoglycemia may occur after tumor removal.
Primary aldosteronism requires attention to potassium, renal function, and antihypertensive therapy. Mineralocorticoid receptor antagonists such as spironolactone or eplerenone are appropriate for bilateral disease, nonsurgical patients, or patients awaiting definitive evaluation. Monitoring should include potassium and kidney function. Spironolactone may cause gynecomastia, breast tenderness, menstrual irregularity, sexual adverse effects, and hyperkalemia. Eplerenone is more selective but can still cause hyperkalemia, has important CYP3A-mediated interactions, and may require twice-daily dosing.
Patients undergoing adrenalectomy for cortisol excess need perioperative glucocorticoid coverage because the contralateral adrenal gland may be suppressed. Hydrocortisone replacement is typically tapered over time, but recovery of the hypothalamic-pituitary-adrenal axis can take months. Patients should receive education on adrenal insufficiency symptoms, stress dosing, and emergency steroid precautions, as appropriate.
Medications and physiology can confound the dexamethasone suppression test. Enzyme-inducing drugs such as phenytoin, carbamazepine, phenobarbital, rifampin, and some antiretrovirals can lower dexamethasone exposure and produce false-positive results. Oral estrogen therapy can increase cortisol-binding globulin and raise total cortisol. Depression, alcohol use disorder, acute illness, and poor sleep may also complicate interpretation.
Metanephrine testing is sensitive but vulnerable to false positives. Sympathomimetics, stimulants, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, withdrawal states, severe illness, and improper sampling conditions can elevate results. Plasma metanephrines should be collected under appropriate conditions, ideally with the patient supine and at rest, when feasible.
Table 3. Drug and Perioperative Safety Issues
| Situation | Medication issue | Practical monitoring |
| Pheochromocytoma preparation | Alpha blockade with phenoxybenzamine or doxazosin | Monitor orthostasis, tachycardia, blood pressure, and volume status |
| Pheochromocytoma with tachycardia | Beta blocker only after adequate alpha blockade | Avoid an unopposed alpha effect |
| Primary aldosteronism, medical therapy | Spironolactone or eplerenone | Monitor potassium, creatinine, eGFR, blood pressure, and drug interactions |
| Eplerenone use | Strong CYP3A inhibitors can raise exposure | Avoid strong CYP3A inhibitors; monitor potassium closely |
| Cortisol-producing tumor surgery | Perioperative glucocorticoid replacement | Monitor for adrenal insufficiency and taper over months as the axis recovers |
| DST interpretation | CYP3A4 inducers, oral estrogen, illness, and alcohol use disorder | Confirm ACTH independence and repeat or interpret cautiously when confounded |
| Metanephrine testing | Stimulants, SNRIs, TCAs, sympathomimetics, withdrawal states | Optimize sampling conditions and review medications before labeling positive |
Biopsy: Rarely the First Answer
Adrenal biopsy has a limited role. It should not be used to distinguish adenoma from adrenocortical carcinoma in routine incidentaloma workup. A biopsy may be considered when there is a history of extra-adrenal malignancy, and the result would change management. Pheochromocytoma must be excluded before biopsy because biopsy of an unrecognized pheochromocytoma can precipitate severe catecholamine release.
Follow-up When Surgery Is Not Performed
Follow-up should be targeted rather than automatic. If a lesion is clearly benign on imaging and the initial hormonal evaluation is normal, repeated imaging and annual biochemical testing are often unnecessary. Patients should instead receive routine clinical care and reassessment if new hypertension, worsening diabetes, unexplained hypokalemia, symptoms of catecholamine excess, new Cushingoid features, or other relevant changes develop.
For indeterminate masses that are not resected, repeat noncontrast CT or MRI at 6 to 12 months is reasonable. Significant growth should prompt renewed multidisciplinary review. A commonly used threshold is more than 20% growth in maximum diameter, plus at least 5 mm.
Patients with MACS who do not undergo surgery should have annual reassessment of comorbidities potentially attributable to cortisol, including blood pressure, glycemic status, bone health, weight, and cardiovascular risk. Endocrinology reassessment is appropriate if comorbidities worsen or new endocrine features appear.
Special Populations
Bilateral adrenal masses should not be managed as a single lesion. Each adrenal lesion should be characterized individually, and the hormonal pattern should guide management. Bilateral adenomas or bilateral macronodular hyperplasia with MACS require individualized treatment. Bilateral infiltrative disease, metastases, lymphoma, hemorrhage, or infection should prompt consideration of adrenal insufficiency.
Pregnant patients and adults younger than 40 deserve urgent evaluation because the pretest probability of clinically significant hormone excess or malignancy is higher than in older adults with typical adenomas. MRI is preferred when dedicated imaging is needed in pregnancy or in younger patients, where radiation should be minimized.
Patients with a known extra-adrenal malignancy require a different diagnostic frame. A benign-appearing adrenal lesion on noncontrast CT may not need further adrenal-specific follow-up, but an indeterminate lesion may require FDG-PET/CT, interval imaging, or biopsy if the result would alter cancer staging or treatment. Pheochromocytoma should be excluded before biopsy.
Practical Bottom Line
The patients who really need surgery are those with clinically significant unilateral hormone excess, suspected adrenocortical carcinoma, lesions with concerning imaging features, significant growth, selected young or pregnant patients with indeterminate lesions, and selected patients with MACS plus relevant comorbidities after multidisciplinary review.
The patients who usually do not need surgery are those with asymptomatic, nonfunctioning, homogeneous adrenal lesions with HU 10 or less. These patients are often harmed more by repeated imaging, repeated testing, and anxiety than by the adrenal lesion itself.
Adrenal incidentaloma management has become more selective and more precise. The older reflex of treating size as the primary surgical trigger is being replaced by a more clinically relevant framework: imaging phenotype, hormone secretion, malignancy risk, patient age, frailty, comorbidities, and patient preference.
Surgery remains essential for pheochromocytoma, unilateral primary aldosteronism in appropriate surgical candidates, overt adrenal Cushing syndrome, and suspected adrenal malignancy. Surgery may also help selected patients with MACS and relevant comorbidities, but that decision requires individualized review. Most benign, nonfunctioning adenomas do not require surgery.
The best incidentaloma care avoids both errors: missing dangerous endocrine or malignant disease, and overtreating benign lesions that can safely be left alone.
References
Yip L, Duh Q, Wachtel H, et al. American Association of Endocrine Surgeons Guidelines for Adrenalectomy: Executive Summary. JAMA Surg. 2022;157(10):870–877. doi:10.1001/jamasurg.2022.3544
Adler GK, Stowasser M, Correa RR, Khan N, Kline G, McGowan MJ, Mulatero P, Murad MH, Touyz RM, Vaidya A, Williams TA, Yang J, Young WF, Zennaro MC, Brito JP. Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2025 Aug 7;110(9):2453-2495. doi: 10.1210/clinem/dgaf284. Erratum in: J Clin Endocrinol Metab. 2025 Oct 16;110(11):e3933-e3934. doi: 10.1210/clinem/dgaf472. PMID: 40658480.
Bovio, S., Cataldi, A., Reimondo, G., Sperone, P., Novello, S., Berruti, A., et al. (2006). Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. Journal of Endocrinological Investigation, 29(4), 298-302.
Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J, Pelsma I, Marina L, Lorenz K, Bancos I, Arlt W, Dekkers OM. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2023 Jul 20;189(1):G1-G42. doi: 10.1093/ejendo/lvad066. PMID: 37318239.
Funder, J. W., Carey, R. M., Mantero, F., Murad, M. H., Reincke, M., Shibata, H., et al. (2016). The management of primary aldosteronism: Case detection, diagnosis, and treatment. Journal of Clinical Endocrinology & Metabolism, 101(5), 1889-1916.
Grumbach, M. M., Biller, B. M. K., Braunstein, G. D., Campbell, K. K., Carney, J. A., Godley, P. A., et al. (2003). Management of the clinically inapparent adrenal mass. Annals of Internal Medicine, 138(5), 424-429.
Johnson, P. T., Horton, K. M., & Fishman, E. K. (2009). Adrenal mass imaging with multidetector CT: Pathologic conditions, pearls, and pitfalls. Radiographics, 29(5), 1333-1351.
Lenders, J. W. M., Duh, Q. Y., Eisenhofer, G., Gimenez-Roqueplo, A. P., Grebe, S. K. G., Murad, M. H., et al. (2014). Pheochromocytoma and paraganglioma: An Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism, 99(6), 1915-1942.
Nieman, L. K., Biller, B. M. K., Findling, J. W., Murad, M. H., Newell-Price, J., Savage, M. O., & Tabarin, A. (2015). Treatment of Cushing’s syndrome: An Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism, 100(8), 2807-2831.
Park SS, Kim JH. Recent Updates on the Management of Adrenal Incidentalomas. Endocrinol Metab (Seoul). 2023 Aug;38(4):373-380. doi: 10.3803/EnM.2023.1779. Epub 2023 Aug 16. PMID: 37583083; PMCID: PMC10475962.
U.S. National Library of Medicine. DailyMed prescribing information for phenoxybenzamine, spironolactone, and eplerenone. Accessed: June 2026.
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