Adrenal Tumors

The adrenal glands are a pair of small, triangular endocrine organs situated directly above each kidney. Despite their modest size, they produce a wide range of hormones that are essential for sustaining life — including cortisol (which regulates stress responses and metabolism), aldosterone (which controls blood pressure and electrolyte balance), and catecholamines such as epinephrine and norepinephrine (which govern the body's fight-or-flight response). Each adrenal gland is composed of two functionally distinct regions: the outer cortex, which produces steroid hormones, and the inner medulla, which produces catecholamines.

Adrenal tumors are abnormal growths that arise within one or both adrenal glands. They are among the most commonly encountered endocrine tumors in clinical practice, largely because cross-sectional imaging performed for unrelated reasons frequently detects unsuspected adrenal masses. The majority of adrenal tumors are benign (noncancerous) and do not produce hormones; however, a clinically significant subset causes excessive hormone secretion that produces characteristic and sometimes severe systemic effects. A smaller proportion are malignant and require more aggressive evaluation and treatment.

Accurate characterization of any adrenal tumor is essential for determining the appropriate management strategy.

Adrenocortical carcinoma (ACC)

• Adrenocortical carcinoma is the most common primary malignancy of the adrenal gland. It arises from cells in the outer cortex and is rare, with an incidence of approximately one to two cases per million people per year. ACC may produce excess steroid hormones — most commonly cortisol, androgens, or a combination — resulting in recognizable clinical syndromes. Alternatively, it may be non-functioning, in which case it typically grows silently until it reaches a size that causes local symptoms or is detected on imaging. ACC tends to be aggressive, with a high rate of recurrence and a propensity to spread to the liver, lungs, and lymph nodes.

Pheochromocytoma

• Pheochromocytoma is a tumor that arises from chromaffin cells in the adrenal medulla. It autonomously secretes catecholamines — primarily epinephrine and norepinephrine — producing episodic or sustained cardiovascular effects that can be dramatic and potentially life-threatening. The majority of pheochromocytomas are benign, but approximately 10–15% are malignant. A particularly important clinical feature is the strong hereditary component.

Neuroblastoma

• Neuroblastoma is a malignant tumor arising from primitive neural crest cells in the adrenal medulla. It is predominantly a disease of early childhood — the most common extracranial solid tumor in children under five. It rarely presents in adults. Neuroblastoma can behave unpredictably, from spontaneous regression in infants to rapid dissemination in older children.

Benign functional adenomas

• While not malignant, hormonally active adrenal adenomas warrant mention because they produce the same clinical syndromes as their cancerous counterparts and often present similarly. A cortisol-secreting adenoma causes Cushing's syndrome; an aldosterone-secreting adenoma (aldosteronoma) causes primary aldosteronism (Conn's syndrome); and rarely, an adenoma may secrete androgens.

Symptoms of cortisol excess (Cushing's syndrome):

• Gradual, unexplained weight gain, especially in the abdomen and face (moon face) with sparing of the limbs
• Purple or red stretch marks (striae) on the abdomen, thighs, or arms
• Easy bruising and thinning of the skin
• Proximal muscle weakness, causing difficulty rising from a chair or climbing stairs
• Hypertension and elevated blood glucose
• Osteoporosis and an increased risk of fractures
• Depressed mood, cognitive changes, and sleep disturbances
• In women: menstrual irregularities, hirsutism (excess facial or body hair), and acne

Symptoms of aldosterone excess (primary aldosteronism):

• Persistently elevated blood pressure, often poorly controlled despite multiple antihypertensive medications
• Low blood potassium (hypokalemia): manifesting as muscle cramps, weakness, and fatigue
• Increased urinary frequency, particularly at night (nocturia)
• Headache

Symptoms of catecholamine excess (pheochromocytoma):

• Episodic or sustained severe hypertension
• Paroxysmal attacks of intense headache, palpitations, sweating, and pallor
• Anxiety
• Tremor and chest pain
• Nausea, vomiting, and abdominal pain

Symptoms related to tumor mass effect:

• Abdominal or flank pain
• A palpable abdominal mass in cases of large tumors

Symptoms of androgen or estrogen excess:

• In women: deepening of the voice, hirsutism, clitoral enlargement, and menstrual irregularities
• In men: gynecomastia (breast tissue enlargement) or other signs of feminization (rare)

The specific cause of most adrenal tumors remains unknown. However, the following factors are recognized as contributors:

Genetic syndromes

• Approximately 15% of adrenal tumors — including both benign and malignant types — occur in the context of inherited conditions

Sporadic DNA mutations

• The majority of adrenal tumors arise from somatic mutations in genes regulating cell growth; no identifiable hereditary cause is found in most adult cases.

Environmental and lifestyle factors

• Cigarette smoking and exposure to certain chemicals, including asbestos and radon, have been associated with an elevated risk of adrenal cancer.

Prior radiation

• Previous radiation therapy to the abdomen increases the risk of subsequent adrenal malignancy.

Age and sex

• Adrenocortical carcinoma occurs most frequently in women in their forties and fifties. Neuroblastoma is predominantly a disease of early childhood.

There is no established method to prevent the development of most adrenal tumors, as the underlying genetic and molecular events are not fully understood. However, the following measures may reduce risk or facilitate early detection:

• Individuals with a confirmed or suspected hereditary syndrome associated with adrenal tumors should undergo regular surveillance imaging and biochemical screening as directed by a specialist.
• Genetic counseling and testing are recommended for all patients diagnosed with pheochromocytoma or ACC, given the high rate of hereditary association.
• Avoiding tobacco use and known carcinogenic exposures may lower the risk of adrenal malignancy.