A CT scan finds an adrenal nodule nobody asked for. The report says it is 2.4 centimeters, well-defined, and probably benign. Everyone exhales. Then the question nobody can answer from the image alone: is this thing actually making hormones? The size of the nodule — 1 centimeter or 3 — has no fixed relationship to whether it secretes. The scan measures density, borders, and dimensions. Hormones go straight into the blood and leave no mark on the image. To judge function, you test the blood.
The European Society of Endocrinology's 2023 guideline on adrenal incidentalomas is blunt: every incidentally discovered adrenal nodule gets two hormone checks — an overnight 1-milligram dexamethasone suppression test, plus metanephrines in blood or urine. If the person has high blood pressure or low potassium, add the aldosterone-to-renin ratio.
Functional nodules are not rare. A Chongqing screening center ran adrenal CT on 25,356 routine physical-exam adults: 351 had adrenal tumors, a prevalence of 1.4 percent — 0.2 percent in the 18-to-25 group, rising to 3.2 percent above age 65. Of the 212 adenomas that completed endocrine workup, 69.3 percent secreted nothing, 18.9 percent showed autonomous cortisol secretion, 11.8 percent were primary aldosteronism, and not one was a pheochromocytoma. Roughly 3 of every 10 people who got the blood tests came back functionally abnormal.
| Function of the adenoma (n=212) | Share | ≈ people |
|---|---|---|
| Nonfunctioning | 69.3% | 147 |
| Autonomous cortisol secretion | 18.9% | 40 |
| Primary aldosteronism | 11.8% | 25 |
| Pheochromocytoma | 0% | 0 |
| Source: 212 adenomas with completed endocrine workup, Chongqing screening population (Jing Y, et al. Ann Intern Med 2022). | ||
Why the image can't answer the question: hormones leave no footprint. The real question is whether a cluster of cells has broken out of the normal command chain and started secreting on its own. Only the hormones — or their metabolites — in the blood tell you that.
Cortisol: the overnight 1-mg dexamethasone suppression test
Dexamethasone is a potent artificial glucocorticoid. Take 1 milligram at night, and a normal pituitary assumes the body has enough steroid, suppresses ACTH, and the morning blood cortisol should be low. The guideline cut-off is serum cortisol ≤50 nmol/L (1.8 µg/dL).
If it will not suppress, the nodule is secreting on its own and ignoring the pituitary. The guideline calls cortisol that won't drop below the line — without Cushing's appearance — mild autonomous cortisol secretion, and flags these people for higher risk of hypertension and type 2 diabetes. Find it, and treat those diseases properly.
Catecholamines: metanephrines in blood or urine
Pheochromocytomas are rare in screening populations — zero in that Chongqing set of 212. The guideline still orders the test for everyone, because the cost of a miss is high: these tumors release bursts of catecholamines, and anesthesia, surgery, or certain drugs can trigger a dangerous spike in blood pressure. Being caught unaware is what you don't want. The test measures metanephrines, the catecholamine metabolites — stable in blood, so a quiet moment during the blood draw does not hide them.
Aldosterone: add it when blood pressure is high or potassium is low
Aldosterone tells the kidney to hold sodium and dump potassium. Too much of it drives blood pressure up and potassium down, which is why the guideline targets the screening at people with hypertension and hypokalemia, using the aldosterone-to-renin ratio. In the Chongqing data, primary aldosteronism made up a large share of functioning adenomas — anyone with poorly controlled blood pressure should not shrug this off.
