An adrenal cortical adenoma is a benign (non-cancerous) tumour that develops from cells in the outer part of the adrenal gland, the adrenal cortex. The adrenal cortex normally produces hormones that help control blood pressure, salt and water balance, metabolism, and the body’s response to stress.
Some adrenal cortical adenomas make excess hormones and cause symptoms. Others do not produce hormones and are incidentally identified during imaging performed for another reason.
This article explains the pathology report for adrenal cortical adenoma, including how it is diagnosed, what features pathologists look for, and how these findings relate to prognosis and treatment.
What are the symptoms of an adrenal cortical adenoma?
The symptoms associated with an adrenal cortical adenoma depend on whether the tumour is producing hormones.
Aldosterone-producing adenoma
Some adenomas produce excess aldosterone, a hormone that regulates salt and water balance. Excess aldosterone can cause high blood pressure and may lead to low potassium, although many patients have normal potassium levels. This condition is called primary aldosteronism (Conn syndrome) and is the most common cause of secondary (treatable) hypertension.
People may experience headaches, palpitations, weakness, increased thirst, and frequent urination. Diagnosis requires blood tests, usually starting with the aldosterone-to-renin ratio, followed by confirmatory testing. Because excess aldosterone can come from one adrenal gland or both, additional tests (including adrenal venous sampling in some cases) may be needed to determine whether surgery is appropriate.
Cortisol-producing adenoma
Some adenomas produce too much cortisol, a hormone involved in metabolism and the stress response. Cortisol excess can cause weight gain (especially around the abdomen), a rounded face, muscle weakness, easy bruising, stretch marks, high blood pressure, high blood sugar, osteoporosis, and increased susceptibility to infection. In children, poor growth can be an important clue.
Some tumours produce only small amounts of excess cortisol (sometimes called mild autonomous cortisol secretion), which can be harder to detect and may appear similar to nonfunctioning adenomas without special endocrine testing.
Sex steroid–producing adenoma
Very rarely, adrenal cortical adenomas produce sex hormones (androgens or estrogens), causing virilization or feminization. Because this is unusual, adrenal cortical carcinoma must be carefully excluded in these cases.
Nonfunctioning adenoma
Many adrenal cortical adenomas do not produce hormones and cause no symptoms. These are often found incidentally on CT or MRI scans. Imaging features such as size, lipid content, and contrast washout help doctors decide whether surgery is needed.
Who gets an adrenal cortical adenoma?
Adrenal cortical adenomas are very common. About 5% of the general population have at least one adrenal cortical nodule, often discovered incidentally with modern imaging. They are the most common adrenal cortical tumour.
What causes an adrenal cortical adenoma?
Most adrenal cortical adenomas occur sporadically, meaning there is no single known cause. Both genetic and environmental factors likely contribute. Tobacco use has been associated with an increased risk of adrenal cortical tumours.
A small subset of adrenal cortical tumours occurs in the context of inherited genetic conditions, especially when tumours are multiple, bilateral, or appear at a young age.
How is the diagnosis made?
The diagnosis is made by combining clinical information, imaging findings, and microscopic examination of the tumour. Pathologists also evaluate the surrounding adrenal gland for features that support hormone production.
Microscopic (pathologic) features
Under the microscope, adrenal cortical adenomas are well-circumscribed tumours made of cells that resemble normal adrenal cortex. They commonly contain a mixture of lipid-rich clear cells (similar to the zona fasciculata) and more compact cells (similar to the zona reticularis). The cells are usually arranged in nests or cords, and the tumour’s supporting framework is typically preserved.
Most adenomas show minimal cell division and lack features of malignancy, such as tumour necrosis, high mitotic activity, atypical mitoses, vascular invasion, or infiltrative growth. These features are important because they help distinguish adenoma from adrenal cortical carcinoma.
Some adenomas show prominent oncocytic change, meaning the cells have abundant dense pink cytoplasm. Oncocytic tumours can be functioning or nonfunctioning. Other changes, such as pigment (black adenoma), fat-like change, or myxoid change, may be seen. Myxoid change is less common and can make interpretation more difficult in some cases.
In cortisol-producing adenomas, the surrounding adrenal cortex often becomes thin (atrophic) because the normal gland is suppressed by excess cortisol. This finding supports autonomous cortisol secretion in the correct clinical setting.
In aldosterone-producing disease, evaluation can be more complex because hormone-producing tissue can be small, multifocal, or present in both glands. In these situations, special stains may be used to identify the exact source of aldosterone production.
Immunohistochemistry
Immunohistochemistry is a laboratory test that uses special stains to detect proteins inside tumour cells. These stains help confirm that the tumour arises from the adrenal cortex and exclude other tumours, such as pheochromocytoma or metastatic cancer.
A marker called SF1 is the most reliable stain for confirming adrenal cortical origin. Other markers such as melan-A, inhibin, calretinin, and synaptophysin may also be used as part of a panel, but they are less specific.
Molecular testing
Molecular testing looks for genetic changes in tumour cells or in inherited DNA. Routine molecular testing is not required for most adrenal cortical adenomas.
Genetic testing may be considered when clinical features suggest an inherited condition, such as young age, multiple tumours, bilateral disease, or a relevant family history.
What is the Weiss score?
The Weiss score is a tool pathologists use to help determine whether an adrenal tumour is a benign adrenal cortical adenoma or a malignant adrenal cortical carcinoma. This decision is important because adenomas and carcinomas behave and are treated very differently.
The Weiss score is based on how the tumour looks under the microscope. Pathologists carefully examine the tissue and look for 9 specific microscopic features associated with more aggressive behaviour. Each feature counts as one point.
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A total score of 0–2 supports a diagnosis of adrenal cortical adenoma, meaning the tumour is unlikely to behave like cancer.
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A total score of 3 or higher supports a diagnosis of adrenal cortical carcinoma, meaning the tumour has features associated with cancer and a higher risk of spread.
The nine features used in the Weiss score
Pathologists look for the following features when examining the tumour:
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High nuclear grade – The tumour cell nuclei look large, dark, and irregular compared with normal adrenal cells.
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Increased mitotic activity – More than 5 dividing tumour cells (mitoses) seen in a defined area, indicating rapid growth.
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Atypical mitotic figures – Abnormal patterns of cell division, which are more often seen in cancer.
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Necrosis – Areas where tumour cells have died, suggesting the tumour is growing faster than its blood supply.
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Diffuse architecture – Tumour cells growing in large, solid sheets rather than in smaller, organized clusters.
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Low proportion of clear cells – Clear, lipid-rich cells make up less than 25% of the tumour, which is more typical of carcinoma than adenoma.
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Capsular invasion – Tumour cells growing into or through the capsule that surrounds the adrenal gland.
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Vascular invasion – Tumour cells found inside blood vessels.
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Lymphatic invasion – Tumour cells found inside lymphatic vessels.
Why the Weiss score matters
The Weiss score helps ensure that adrenal tumours are classified as accurately as possible. While no single feature alone determines whether a tumour is cancerous, the overall pattern seen across these features provides essential information about how the tumour is likely to behave. This information helps guide follow-up, treatment decisions, and long-term monitoring.
What is the prognosis for a person with an adrenal cortical adenoma?
Adrenal cortical adenomas are benign tumours with an excellent prognosis.
For hormone-producing tumours, prognosis depends mainly on the effects of hormone excess. Uncontrolled cortisol excess can cause serious health problems, and aldosterone excess increases cardiovascular risk. Identifying and treating the underlying hormone imbalance is therefore essential.
For aldosterone-producing tumours, CYP11B2 staining and careful pathological assessment can help predict whether aldosterone excess is likely to improve after surgery, especially in complex cases.
Questions to ask your doctor
- Is my adrenal cortical adenoma producing hormones?
- Do I have primary aldosteronism or cortisol excess, and what tests confirm this?
- Was the tumour completely removed, and is there any concern for carcinoma?
- Do I need follow-up imaging or repeat hormone testing?
- Should I be evaluated for an inherited condition based on my results?
