Approach to adrenal glands mass or tumer
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adrenal incidentaloma AND management
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2023 European Society Endocrinology guideline adrenal incidentaloma imaging hormonal evaluation
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https://academic.oup.com/ejendo/article/189/1/G1/7198474
Approach to an adrenal mass or tumor
An adrenal mass is evaluated along two questions:
- Is it producing hormones?
- Is it benign, malignant, or metastatic?
Most incidentally discovered adrenal masses are benign adenomas, but every patient needs a focused hormonal and imaging assessment. Harrison’s Principles of Internal Medicine, 22e, p. 3063.
1. First assess for urgent features
Refer urgently to endocrinology, endocrine surgery, or oncology if there is:
- Suspected pheochromocytoma: episodic headache, sweating, palpitations, marked/labile hypertension
- Overt cortisol excess: proximal muscle weakness, easy bruising, new diabetes, severe hypertension, hypokalemia
- Virilization or feminization: rapid hirsutism, deep voice, acne, gynecomastia
- Large, irregular, heterogeneous or invasive mass
- Known extra-adrenal cancer, particularly lung, breast, melanoma, renal, or GI cancer
- Acute abdominal/flank pain with suspected adrenal hemorrhage
- Bilateral large masses with illness suggesting adrenal insufficiency
Important: Never biopsy an adrenal lesion until pheochromocytoma has been excluded biochemically. Biopsy can precipitate a dangerous catecholamine crisis.
2. Clinical assessment
History
Ask about:
- Hypertension, hypokalemia
- Episodic headache, palpitations, diaphoresis
- Weight gain, bruising, weakness, diabetes, osteoporosis, mood changes
- Hirsutism, acne, menstrual irregularity, virilization
- Previous or current malignancy
- Familial endocrine tumor syndromes: MEN2, VHL, NF1, SDHx-related disease
- Prior trauma, sepsis, anticoagulation, or severe illness suggesting hemorrhage
Examination
Look for:
- Blood pressure, including episodic/labile hypertension
- Cushingoid phenotype and proximal myopathy
- Signs of androgen or estrogen excess
- Abdominal mass or metastatic disease
- Features of inherited syndromes
3. Hormonal work-up
For most adrenal incidentalomas, initial biochemical testing should include:
| Clinical question | Recommended test |
|---|---|
| Autonomous cortisol secretion | 1-mg overnight dexamethasone suppression test |
| Pheochromocytoma | Plasma free metanephrines or 24-hour urinary fractionated metanephrines |
| Primary aldosteronism | Aldosterone-renin ratio if hypertension and/or unexplained hypokalemia |
| Adrenocortical carcinoma suspected | Androgens and steroid precursors, such as DHEAS, testosterone, androstenedione, 17-hydroxyprogesterone, estradiol in appropriate patients |
Interpretation highlights
- After 1-mg dexamethasone, a cortisol level >1.8 micrograms/dL (50 nmol/L) suggests mild autonomous cortisol secretion (MACS) in a patient without overt Cushing syndrome.
- Screen for aldosteronism in any patient with hypertension, especially if hypokalemia is present.
- Under the 2023 ESE guidance, metanephrine testing may be omitted only when imaging is unequivocally typical of a lipid-rich adenoma, namely a homogeneous lesion with noncontrast CT attenuation of 10 HU or less. See the ESE adrenal incidentaloma guideline.
4. Imaging assessment
Preferred first test
Dedicated noncontrast adrenal CT.
Assess:
- Size
- Homogeneity
- Unenhanced attenuation in Hounsfield units (HU)
- Borders, calcification, necrosis, hemorrhage, local invasion
- Growth on prior imaging
- Laterality
Key CT patterns
| Imaging finding | Likely implication / next step |
|---|---|
| Homogeneous, ≤10 HU on noncontrast CT | Lipid-rich adenoma. Usually benign, no further imaging needed if asymptomatic and nonfunctioning. |
| Homogeneous 11-20 HU and <4 cm | Indeterminate. Obtain immediate second-line characterization such as washout CT, MRI chemical-shift imaging, or sometimes FDG-PET/CT, or repeat imaging in about 12 months. |
| ≥4 cm, heterogeneous, or >20 HU | Meaningful malignancy risk. Discuss in multidisciplinary team; surgery is commonly appropriate. |
| Macroscopic fat | Usually myelolipoma. |
| Fluid-density, thin-walled lesion | Adrenal cyst. |
| Very high density after acute illness/trauma or anticoagulation | Consider adrenal hemorrhage; repeat imaging after resolution to exclude an underlying lesion. |
| Bilateral lesions | Consider metastases, lymphoma, bilateral adenomas, congenital adrenal hyperplasia, infiltrative disease, or bilateral hemorrhage. |
MRI with chemical-shift imaging helps identify intracellular lipid in adenomas. CT/radiologic assessment must establish both hormonal activity and the probability of benign versus malignant disease. Grainger & Allison’s Diagnostic Radiology, p. 935.
5. When to operate
Adrenalectomy is generally indicated for:
-
Functioning tumors
- Pheochromocytoma
- Primary aldosteronism with a unilateral surgically correctable source
- Overt cortisol-producing adenoma
- Selected MACS with clinically important cortisol-related comorbidities, such as difficult hypertension, diabetes, osteoporosis, or young age
-
Suspected malignancy
- Large or enlarging lesion
- Heterogeneous lesion, irregular margins, necrosis, invasion
- High unenhanced CT attenuation, especially >20 HU
- Suspicion for adrenocortical carcinoma
-
Selected symptomatic benign lesions
- Large or symptomatic myelolipoma
- Symptomatic cyst
- Hemorrhage or mass effect
Operative precautions
- Suspected pheochromocytoma: alpha-adrenergic blockade and volume optimization before surgery.
- Cortisol-secreting mass or MACS: perioperative glucocorticoid cover and postoperative assessment for adrenal insufficiency.
- Suspected adrenocortical carcinoma should be managed in a high-volume specialist center, usually with open oncologic resection rather than routine laparoscopic surgery.
6. When not to biopsy
Adrenal biopsy is not a routine test to distinguish adenoma from adrenocortical carcinoma.
Consider it only if all are true:
- There is a known extra-adrenal malignancy,
- Pheochromocytoma has been excluded,
- Imaging cannot establish the diagnosis, and
- The result will change treatment, for example, confirming metastasis before systemic therapy.
7. Follow-up
- Homogeneous lesion ≤10 HU: generally no imaging follow-up is needed.
- Indeterminate lesion not removed: individualized additional imaging or repeat imaging, commonly at 6-12 months.
- Repeat hormonal tests are not routinely needed if initial testing is normal, unless new endocrine features or worsening hypertension/diabetes appear.
- For MACS, monitor blood pressure, glycemia, lipids, weight, fractures/osteoporosis, and cardiovascular risk.
Practical one-line algorithm
Adrenal mass on imaging → assess symptoms and cancer history → noncontrast CT characterization + dexamethasone suppression test + aldosterone-renin ratio if hypertensive/hypokalemic + metanephrines unless clearly lipid-rich adenoma → classify benign/nonfunctioning versus functional versus indeterminate/suspicious → observe, further characterize, or refer for adrenalectomy.
The 2023 ESE recommendations emphasize multidisciplinary review for indeterminate imaging, hormone excess, significant growth, or possible surgery.
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