Adrenal Metastases

Adrenal metastases are secondary tumours in one or both adrenal glands. They are common in advanced cancer and often found on staging imaging, usually without symptoms, though bilateral disease can cause adrenal insufficiency.

The key tasks are to confirm metastatic disease, exclude phaeochromocytoma and adrenal cortical carcinoma, and decide between treatment of oligometastatic disease and systemic therapy.

The adrenal is a common metastatic site, found in 9% to 27% of patients with cancer at autopsy. The commonest primaries are lung (35%), breast (about 15%), melanoma, renal cell carcinoma, colorectal, gastric and oesophageal cancers, and lymphoma. In a patient with a known cancer, about 30% to 70% of adrenal masses are malignant. Median age follows the primary tumour, and bilateral involvement occurs in 30% to 50%.

Pathophysiology

The adrenal's rich sinusoidal blood supply favours haematogenous spread. Adrenal insufficiency occurs when about 90% of both adrenal cortices are destroyed (bilateral metastases, usually lymphoma, lung or renal cancer), and bleeding into metastases can cause adrenal crisis.

Prognosis

Median survival is about 8 to 14 months overall. Solitary metastases after complete resection with controlled primary disease have a 5-year survival of 25% to 45%. Disease free interval from the primary of over 6 to 12 months predicts better outcomes.

• Usually asymptomatic, found on staging imaging.
• Flank or abdominal pain, from enlargement or haemorrhage.
• Adrenal insufficiency (bilateral disease): fatigue, weight loss, anorexia, nausea, abdominal pain, hypotension, hyponatraemia, hyperkalaemia, hyperpigmentation (primary insufficiency).
• Features of the primary cancer, and rarely hormone excess.

Red flags.

• Hypotension, vomiting, confusion or hypoglycaemia (adrenal crisis).
• Sudden severe flank pain with falling haemoglobin (haemorrhage).

• CT of the adrenal: unenhanced attenuation over 10 Hounsfield units, heterogeneous enhancement and delayed washout (absolute washout under 60%), often over 3 cm. MRI with chemical shift imaging, and FDG-PET-CT (high sensitivity for malignancy).
• Biochemical workup before biopsy or surgery: plasma free metanephrines (to exclude phaeochromocytoma), morning cortisol or short corticotropin stimulation test, overnight dexamethasone suppression test, aldosterone and renin, DHEA sulphate.
• Percutaneous biopsy only when the result would change management and phaeochromocytoma has been excluded.
• Staging of the primary tumour and other metastatic sites.

Differential diagnosis.

• Adrenal adenoma (the commonest incidental mass), phaeochromocytoma
• Adrenocortical carcinoma and adrenal lymphoma
• Adrenal haemorrhage, myelolipoma and tuberculosis
• Granulomatous disease and infection (histoplasmosis)

Management depends on the primary tumour, extent of disease, adrenal function and fitness.

Systemic therapy. For widespread disease, treatment follows the primary tumour (chemotherapy, targeted drugs, hormone therapy, immunotherapy) and responses are assessed on imaging.

Local therapy for oligometastatic disease (solitary or limited, with controlled primary).

• Stereotactic body radiotherapy (for example 30 to 50 Gy in 3 to 5 fractions, or 24 Gy in 2 fractions), with local control of 70% to 90%.
• Adrenalectomy (laparoscopic for tumours under 6 cm without invasion, open for larger or invasive disease), with 5-year survival of 25% to 45% in selected patients.
• Thermal ablation (radiofrequency, microwave) or arterial embolisation for tumours under 4 cm in patients not fit for surgery.
• Pre-procedure alpha blockade if any biochemical suspicion of catecholamine excess.

Adrenal insufficiency (after bilateral disease or bilateral adrenalectomy).

• Glucocorticoid replacement: hydrocortisone 15 to 25 mg orally daily in 2 to 3 divided doses (for example 10 mg on waking, 5 mg at midday and 5 mg in the late afternoon), doubling or tripling the dose for fever or illness and giving 100 mg IM or IV for vomiting or collapse; maximum 30 mg daily in routine replacement; monitoring: symptoms, blood pressure, weight, sodium, potassium; adjustment: add fludrocortisone for mineralocorticoid deficiency, give a steroid emergency card and sick day rules, give stress dose cover for surgery, increase the dose with enzyme inducers such as rifampicin
• Mineralocorticoid replacement: fludrocortisone 0.05 to 0.2 mg orally once daily, titrated to blood pressure, potassium and plasma renin; maximum 0.3 mg daily; monitoring: seated and standing blood pressure, potassium, oedema, renin; adjustment: reduce for hypertension, hypokalaemia or oedema, increase with salt loss

Adrenal crisis. Hydrocortisone 100 mg IV immediately, followed by IV fluids (0.9% saline 1 L over 1 hour) and hydrocortisone 200 mg IV over 24 hours, with treatment of precipitants and early endocrine review.

Monitoring. Imaging every 3 months after local therapy for 2 years and then every 6 months. Adrenal function (morning cortisol, electrolytes) every 3 to 6 months in bilateral disease or after stereotactic therapy.

Referral and escalation.

• Referral to an endocrine and oncology multidisciplinary team for any adrenal mass in a patient with cancer.
• Emergency admission for suspected adrenal crisis or haemorrhage.

Special groups.

• Bilateral metastases: adrenal sparing options and lifelong replacement if both glands are lost.
• Patients on enzyme inducers or checkpoint inhibitors: monitor for adrenal insufficiency and adjust steroids.
• Pregnancy: individualised planning with endocrine and obstetric input.