Adrenal Incidentaloma Interpreter
Adrenal Incidentaloma Interpreter
An adrenal mass turned up on a scan done for something else. Three questions decide everything that follows: does it look benign, is it making a hormone, and does it ever need re-imaging. The third answer has changed — the 2023 European Society of Endocrinology and ENSAT guideline recommends against routine follow-up imaging and against repeat hormonal testing for a lesion that is clearly benign on imaging and hormonally silent, and it dropped the 4 cm size limit from the benign imaging definition at the same time.
Benign? Functioning? Re-image?
Imaging + function → what happens nextA 2.2 cm right adrenal nodule found on a CT for renal colic. Unenhanced attenuation 4 HU, homogeneous, no prior imaging. The 1 mg overnight dexamethasone suppression test gives an 08:00 cortisol of 28 nmol/L, and the patient is normotensive with a normal potassium.
The 2023 thresholds, and what each one decides
Relevant malignancy risk — 4 cm or more AND (heterogeneous OR unenhanced attenuation above 20 HU). Recommendation 2.5.
Immediate additional imaging — homogeneous, 11 to 20 HU, under 4 cm, no hormone excess. Recommendation 2.4.
Everything else — multidisciplinary discussion. Recommendation 2.6.
Significant growth — more than 20% of maximum diameter AND at least 5 mm. Recommendation 5.2.
Autonomous cortisol secretion excluded — post-dexamethasone cortisol 50 nmol/L (1.8 µg/dL) or less. Recommendation 3.3.
MACS — anything above that, with no clinical Cushing’s syndrome, and with no further stratification. Recommendation 3.4.
- 10 HU
- the attenuation threshold, and it is a threshold about FAT rather than about cancer. An adrenocortical adenoma is lipid-rich, and intracytoplasmic lipid lowers unenhanced CT attenuation. A lesion at or below 10 HU on an unenhanced series contains enough lipid to be an adenoma and essentially nothing else. About 30% of adenomas are lipid-poor and sit above the line, which is why being above it is not a diagnosis of anything
- unenhanced
- load-bearing, and the commonest error on this page. Attenuation must come from the non-contrast series. Contrast raises the density of an ordinary adenoma well above 10 HU, so a portal-venous measurement misclassifies benign lesions as indeterminate. If the only scan was contrast-enhanced, the honest answer is that this criterion has not been assessed
- 4 cm
- the size at which the guideline attaches a relevant malignancy risk to a lesion that also looks indeterminate. Note what 2023 did with it: it kept 4 cm in recommendation 2.5, where it is combined with an imaging feature, and removed it from the benign definition in recommendation 2.3, where it used to stand alone. Size alone no longer sends a homogeneous lipid-rich lesion for surveillance
- more than 20% AND at least 5 mm
- the growth definition, and it needs both halves. Twenty per cent of a 15 mm lesion is 3 mm, which is within the measurement variability of two radiologists on two scanners, so the absolute 5 mm term is what stops surveillance turning into surgery for noise. The conjunction is in the recommendation and is often dropped when it is quoted
- 50 nmol/L, and not 138
- recommendation 3.3 excludes autonomous cortisol secretion at a post-dexamethasone cortisol of 50 nmol/L (1.8 µg/dL) or less, and recommendation 3.4 calls anything above that mild autonomous cortisol secretion with no further stratification. The 138 nmol/L (5 µg/dL) line that separated "possible" from "definite" autonomous secretion belongs to the 2016 guideline and was deliberately removed
- 80 to 85%
- the proportion of adrenal incidentalomas that are non-functioning adrenocortical adenomas or macronodular bilateral hyperplasia, from the guideline’s Table 2. It is the base rate that makes the rest of the page reasonable: most of these findings are nothing, which is precisely why the tests used to prove it have to have good specificity
Worked example
A 2.2 cm right adrenal nodule found on a CT for renal colic. Unenhanced attenuation 4 HU, homogeneous, no prior imaging. The 1 mg overnight dexamethasone suppression test gives an 08:00 cortisol of 28 nmol/L, and the patient is normotensive with a normal potassium.
Homogeneous, and unenhanced attenuation 4 HU is at or below 10 → recommendation 2.3 is met, so no further imaging, and since 2023 that holds independent of size
Post-dexamethasone cortisol 28 nmol/L is at or below 50 → recommendation 3.3 excludes autonomous cortisol secretion
Normotensive and normokalaemic, so recommendation 3.10 does not ask for an aldosterone-to-renin ratio; the lesion is typical for a benign adenoma, so recommendation 3.9 does not ask for metanephrines
Recommendation 5.1 then recommends against follow-up imaging, and 5.3 against repeating the hormonal work-up
So the correct action is to tell the patient the nodule is benign and inactive, and to discharge them. The older habit of an annual CT for three to five years is what this guideline set out to stop
What would reopen it: new or worsening hypertension, new type 2 diabetes, hypokalaemia, a fragility fracture, or spells of headache, palpitation and sweating — recommendation 5.3's "new clinical signs of endocrine activity"
What changed between the 2016 and the 2023 guideline
| 2016 | 2023 | |
|---|---|---|
| Benign on imaging | Homogeneous, under 4 cm, and 10 HU or less | Homogeneous and 10 HU or less — independent of size |
| Follow-up imaging of a benign, non-functioning lesion | Not suggested, but widely practised anyway | Recommended against (R.5.1) |
| Repeat hormonal work-up after a normal screen | Suggested against | Recommended against unless new signs appear or comorbidities worsen (R.5.3) |
| Post-dexamethasone cortisol above 50 nmol/L | Split into "possible autonomous cortisol secretion" 51–138 and "autonomous cortisol secretion" above 138 | A single category, MACS, with no stratification (R.3.4) |
| Indeterminate lesion under 4 cm at 11–20 HU | Three options offered, including interval imaging | Immediate additional imaging suggested, to avoid follow-up imaging (R.2.4) |
| Significant growth | Variously defined; one national guideline used more than 1 cm | More than 20% of maximum diameter and at least 5 mm (R.5.2) |
The four imaging categories, and what each one triggers
| Unenhanced attenuation | Under 4 cm | 4 cm or above |
|---|---|---|
| 10 HU or less, homogeneous | Benign — no further imaging (R.2.3) | Benign — no further imaging (R.2.3); size still worth an MDT discussion |
| 11–20 HU, homogeneous | Immediate additional imaging (R.2.4) | Individualised, MDT (R.2.6) |
| Above 20 HU, homogeneous | Individualised, MDT (R.2.6) | Relevant malignancy risk (R.2.5) |
| Heterogeneous, any attenuation | Individualised, MDT (R.2.6) | Relevant malignancy risk (R.2.5) |
Why the guideline stopped scanning these patients
An adrenal incidentaloma is a mass of 1 cm or more found on imaging performed for an unrelated reason. It is common — the prevalence rises steeply with age and with the volume of cross-sectional imaging performed — and between 80 and 85 per cent of them are non-functioning adrenocortical adenomas or macronodular hyperplasia. The clinical problem has never really been the adenomas. It has been what gets done to the people who have them.
The older convention was an annual CT for three to five years, and a repeat hormonal screen each year alongside it. The 2023 European Society of Endocrinology guideline, produced with the European Network for the Study of Adrenal Tumors, recommends against both for a lesion with clear benign imaging features and a normal initial hormonal work-up. The reasoning is in the numbers: the rate at which a lesion meeting the benign imaging definition later turns out to be malignant is close to zero, the rate at which a hormonally silent lesion later becomes functioning is very low, and the costs of surveillance — radiation, contrast, incidental findings elsewhere, appointments, and the sustained anxiety of being followed up for a possible cancer — are neither zero nor evenly distributed.
The guideline also removed the size criterion from the benign imaging definition. Under the 2016 version a lesion had to be homogeneous, under 4 cm and at most 10 Hounsfield units to qualify; under the 2023 version the size term is gone, and a homogeneous lipid-rich lesion needs no further imaging whatever its diameter. Size still appears in recommendation 2.5, where it is combined with heterogeneity or with attenuation above 20 HU to define a relevant malignancy risk, and it still belongs in a multidisciplinary discussion. What it no longer does is send a benign-looking lesion into surveillance on its own.
Two things did not get easier. The Hounsfield measurement has to come from an unenhanced series, and a great deal of abdominal imaging is contrast-enhanced only, in which case the criterion simply has not been assessed and pretending otherwise misclassifies ordinary adenomas as indeterminate. And the functional screen has not been relaxed at all: recommendation 3.2 asks for a 1 mg overnight dexamethasone suppression test in every patient, because mild autonomous cortisol secretion is invisible clinically and carries measurable cardiovascular, metabolic and skeletal risk. The 1 mg overnight dexamethasone suppression test interpreter reads that test, though note that its 138 nmol/L cut-off is the 2016 stratification and the 2023 guideline replaced it with a single threshold at 50 nmol/L. The plasma metanephrines interpreter reads the metanephrines, the aldosterone-to-renin ratio calculator the aldosterone screen, and the ACTH-dependent or ACTH-independent interpreter is the next step when hypercortisolism is confirmed.
Frequently asked questions
Does an adrenal incidentaloma need a repeat scan?
Not if it is clearly benign on imaging. The 2023 ESE/ENSAT guideline’s recommendation 5.1 states: "We recommend against further imaging during follow-up in patients with an adrenal lesion with clear benign features on imaging studies." Clear benign features means homogeneous with unenhanced CT attenuation of 10 Hounsfield units or less — and, since 2023, independent of size. An indeterminate lesion is different: recommendation 5.2 suggests one repeat non-contrast CT or MRI at 6 to 12 months, with surgery suggested if it grows by more than 20 per cent of its maximum diameter and by at least 5 mm. That is a single repeat scan, not a surveillance programme.
What Hounsfield unit value rules out a malignant adrenal mass?
Ten or less on an unenhanced CT, in a homogeneous lesion. The threshold works because adrenocortical adenomas are lipid-rich and intracytoplasmic lipid lowers attenuation, so a lesion at or below 10 HU contains enough fat to be an adenoma and essentially nothing else. Two limits are worth knowing. Roughly a third of adenomas are lipid-poor and sit above the line, so being above 10 HU is common and is not a diagnosis of anything. And the value must come from the non-contrast series: after contrast, an ordinary adenoma reads well above 10 HU, and using that number is the commonest way a benign lesion gets classified as indeterminate.
Is a 4 cm adrenal mass automatically suspicious?
No, and this is what changed in 2023. Under the 2016 guideline a lesion had to be under 4 cm to meet the benign imaging definition; under the 2023 guideline recommendation 2.3 requires only that it be homogeneous with attenuation of 10 HU or less, independent of size. Size matters in recommendation 2.5, which attaches a relevant malignancy risk to a lesion of 4 cm or more that is also heterogeneous or above 20 HU. A large, homogeneous, lipid-rich lesion — a myelolipoma, for instance — is not that. It still merits a multidisciplinary discussion, because the decision about whether to operate takes in more than attenuation, but it does not need surveillance imaging.
Which hormone tests does an adrenal incidentaloma need?
A 1 mg overnight dexamethasone suppression test in everybody (recommendation 3.2). Plasma free metanephrines or urinary fractionated metanephrines in patients whose lesion has features not typical for a benign adenoma (recommendation 3.9). An aldosterone-to-renin ratio in patients who are hypertensive or hypokalaemic (recommendation 3.10). If all three are normal, recommendation 5.3 advises against repeating them unless new clinical signs of endocrine activity appear or comorbidities such as hypertension or type 2 diabetes worsen. What is not recommended as routine screening is a full adrenocortical panel: DHEA sulfate, androstenedione and 11-deoxycortisol have their place when adrenocortical carcinoma is suspected, not as a screen for every nodule.
What is MACS, and is it the same as subclinical Cushing’s syndrome?
MACS is mild autonomous cortisol secretion: a post-dexamethasone serum cortisol above 50 nmol/L (1.8 µg/dL) in a patient with no clinical signs of Cushing’s syndrome. It replaced the older terms "subclinical Cushing’s syndrome" and "autonomous cortisol secretion", and recommendation 3.4 is explicit that it should be recorded without further stratification by how high the cortisol is. That is a deliberate break with the 2016 scheme, which split the range at 138 nmol/L (5 µg/dL) into possible and definite autonomous secretion. MACS is not a cosmetic label: it is associated with hypertension, type 2 diabetes, vertebral fracture and increased mortality, and the management is to look for and treat those, with adrenalectomy discussed individually in younger patients whose comorbidities are not controlled.
Can an adrenal mass be biopsied to settle the question?
Rarely, and never before a phaeochromocytoma has been excluded biochemically — biopsy of an unrecognised phaeochromocytoma can precipitate a hypertensive crisis. Beyond that, adrenal biopsy cannot reliably distinguish an adrenocortical adenoma from an adrenocortical carcinoma, which is usually the question being asked, so a benign biopsy result often settles nothing. Its main legitimate use is in a patient with a known extra-adrenal malignancy where the question is whether the adrenal lesion is a metastasis and the answer would change treatment. Imaging characterisation, hormonal assessment and, where indicated, surgery are the routes the guideline describes.
Related calculators
References
- 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;189(1):G1–G42. doi:10.1093/ejendo/lvad066. R.2.3: "if the noncontrast CT is consistent with a benign adrenal mass (homogenous appearance and HUs ≤ 10) no further imaging is required". R.2.5: "If the adrenal mass is ≥4 cm and heterogeneous or has unenhanced HU > 20, there is a relevant risk that this lesion is malignant". R.5.1: "We recommend against further imaging during follow-up in patients with an adrenal lesion with clear benign features on imaging studies".
- Fassnacht M, Arlt W, Bancos I, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016;175(2):G1–G34. doi:10.1530/EJE-16-0467. The superseded version, cited here because its 4 cm benign criterion and its 51–138 nmol/L "possible autonomous cortisol secretion" band are still in wide circulation.
- Nieman LK, Biller BMK, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing’s syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2008;93(5):1526–1540. doi:10.1210/jc.2008-0125. The source for confirming hypercortisolism where the screen is abnormal; note that it is a screening document and does not address the differential diagnosis.
- Lenders JWM, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SKG, Murad MH, Naruse M, Pacak K, Young WF. Pheochromocytoma and paraganglioma: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(6):1915–1942. doi:10.1210/jc.2014-1498. Cited for the contraindication to biopsy before biochemical exclusion of phaeochromocytoma.
Medical Disclaimer: The tools and content provided here are for educational and reference purposes only. They are not intended to substitute for professional medical advice, diagnosis, or treatment. Clinical decisions should always be based on the comprehensive assessment of a qualified healthcare professional.