Adrenal Gland Cancer: Types, Symptoms, and What Adrenal Tumors Mean

When 61-year-old Linda underwent CT imaging for persistent back pain, radiologists discovered an unexpected 9cm mass on her left adrenal gland. “I’d never heard of adrenal glands before,” Linda recalled. “The doctor explained they’re tiny organs above my kidneys that make hormones. Mine was producing excess cortisol—that’s why I’d gained 40 pounds in a year, developed diabetes, and bruised easily. I thought it was just aging.” Biopsy confirmed adrenocortical carcinoma, stage II. In adults, incidental radiologic finding led to diagnosis in 79% at median age of 61 years. ENSAT stage I, II, III and IV was 19%, 40%, 19% and 21%, respectively. Adrenocortical carcinoma represents one of the most aggressive malignancies, with an estimated incidence of 0.5 to 2 cases per million population annually. This cancer ranks as the second most common malignancy in endocrinology after anaplastic thyroid cancer. The tumor arises from the adrenal cortex and accounts for approximately 0.02% to 0.2% of all cancer-related deaths. A bimodal age distribution is observed, with peaks in children younger than 5 years and in adults in their fourth to fifth decades, along with a female predominance reflected in a 2.5:1 to 3:1 ratio. Understanding adrenal cancer types—and why most cases represent accidental discoveries during imaging for unrelated conditions—reveals critical insights about hormone-producing tumors hiding within these walnut-sized glands. nihNCBI

Adrenal Anatomy: Two Glands, Two Tissue Types

The adrenal glands—small triangular organs perched atop each kidney—comprise two distinct functional regions producing different hormones. Adrenal cortex (outer layer): produces steroid hormones including cortisol (regulates metabolism, stress response, blood pressure), aldosterone (controls sodium/potassium balance, blood pressure), and androgens/estrogens (sex hormones influencing body hair, muscle mass, secondary sexual characteristics). Cortex organized in three zones: zona glomerulosa (aldosterone), zona fasciculata (cortisol), zona reticularis (androgens). Adrenal medulla (inner core): produces catecholamines including epinephrine/adrenaline (stress hormone—fight-or-flight response), norepinephrine/noradrenaline (blood pressure regulation, alertness), and dopamine (neurotransmitter precursor). Medulla composed of chromaffin cells derived from neural crest tissue. This anatomical division explains why adrenal cancers present with dramatically different symptoms depending on tissue of origin—cortical tumors cause hormonal syndromes from steroid excess; medullary tumors cause adrenaline surges with palpitations, sweating, hypertension.

Adrenocortical Carcinoma: The Steroid-Producing Cancer

Adrenocortical carcinomas are rare tumors with an estimated annual incidence of 0.7–2 cases per year and a worldwide prevalence of 4–12 cases per million/year. However, a much higher incidence of these tumors (>15 times) has been demonstrated in south and southeastern Brazil. Most adrenocortical carcinomas cause hypersecretion of steroids including glucocorticoids and androgens. Adrenocortical carcinoma patients have a very poor prognosis with a 5-year overall survival below 30% in most series. Adrenocortical carcinoma is an aggressive cancer originating in the cortex (steroid hormone-producing tissue) of the adrenal gland. Adrenocortical carcinoma is remarkable for the many hormonal syndromes that can occur in patients with steroid hormone-producing (“functional”) tumors, including Cushing’s syndrome, Conn syndrome, virilization, and feminization. Adrenocortical carcinoma has often invaded nearby tissues or metastasized to distant organs at the time of diagnosis, and the overall 5-year survival rate is about 50%. The Brazil cluster: southern/southeastern Brazil shows >15-fold higher pediatric adrenocortical carcinoma incidence—linked to germline TP53 mutations (Li-Fraumeni syndrome variant) endemic in that population. Functional hormone production occurs in approximately 40% to 60% of cases and produces distinct endocrine syndromes, while the remaining cases involve nonfunctional tumors detected incidentally or through mass-effect symptoms. The hormonally active variants of adrenocortical carcinoma constitute approximately 60% of cases. These hormonally silent tumors account for approximately 40% of patients with adrenocortical carcinoma. Nonfunctional variants of adrenocortical carcinoma tend to be more common in older patients and appear to progress more rapidly than functional tumors do. Functional tumor presentations: Cushing’s syndrome (cortisol excess, 30-40% of cases): rapid weight gain (especially face, neck, trunk—”moon face,” “buffalo hump”), purple stretch marks (striae), easy bruising, muscle weakness, diabetes, hypertension, depression, and osteoporosis. Virilization (androgen excess, 20-30%—more common in women): hirsutism (male-pattern hair growth), deepening voice, clitoral enlargement, male-pattern baldness, acne, irregular/absent menstruation, and increased muscle mass. Mixed Cushing’s and virilization: combined glucocorticoid and androgen overproduction—most suggestive of malignancy. Feminization (estrogen excess, <10%—more common in men): gynecomastia (breast development), testicular atrophy, decreased libido, erectile dysfunction. Conn syndrome (aldosterone excess, <5%): hypertension resistant to treatment, unprovoked hypokalemia (low potassium), and muscle weakness. nih + 3

Pheochromocytoma: The Adrenaline Storm

Pheochromocytoma or paraganglioma is a metabolically active tumor originating from the chromaffin cells of the adrenal medulla. The incidence of pheochromocytoma/paraganglioma is 0.2 to 0.9 cases per 100,000 individuals per year. Pheochromocytomas are present in approximately 4-7% of patients with adrenal incidentalomas. Classically, pheochromocytoma/paraganglioma manifests as paroxysmal attacks of the following 4 symptoms: headaches, diaphoresis, palpitations, and severe hypertensive episodes. The classic triad of clinical features consists of episodic headaches, palpitations, and diaphoresis. Most pheochromocytomas were sporadic (82.8%), all were adrenal gland tumors, and 89.7% were unilateral. The classic presentation: paroxysmal (episodic) attacks—sudden onset, lasting minutes to hours, unpredictable triggers (physical activity, abdominal pressure, certain foods/medications, stress). Attack symptoms: severe pounding headache, profuse sweating (drenching), rapid forceful heartbeat (palpitations), severe hypertension (systolic >200 mmHg during episodes), pallor (pale skin from vasoconstriction), tremor, anxiety/sense of impending doom, chest/abdominal pain, and nausea. Between attacks: many patients normotensive or only mildly hypertensive; some have sustained hypertension. About 25% of patients have the disease as part of a hereditary syndrome. The inherited familial syndromes associated with pheochromocytoma include multiple endocrine syndrome type 2 (MEN 2), von Hippel-Lindau syndrome and neurofibromatosis type 1. Pheochromocytoma has malignant potential as well. Malignancy is defined as the presence of metastases in non-chromaffin tissue. The prevalence of malignancy varies between 10% and 17%. Distinguishing benign from malignant pheochromocytoma: no reliable histologic criteria—diagnosis of malignancy requires metastases to non-chromaffin tissue (lymph nodes, liver, lung, bone). About 10-17% malignant. Hereditary pheochromocytomas (25% of cases): MEN 2A/2B (medullary thyroid cancer, parathyroid tumors), Von Hippel-Lindau syndrome (renal cysts, renal cell carcinoma, hemangioblastomas), neurofibromatosis type 1 (café-au-lait spots, neurofibromas), and succinate dehydrogenase (SDH) gene mutations (familial paraganglioma/pheochromocytoma syndrome). nih + 2

Neuroblastoma: The Childhood Adrenal Cancer

Neuroblastomas form in nerve cells, so they can affect many different parts of your body. However, about one-third form in the inner part of your adrenal gland (the medulla). The medulla makes epinephrine and norepinephrine. These chemicals help control your sympathetic nervous system, which regulates things like sweating, heart rate and blood pressure. Adrenal neuroblastomas usually affect infants and children under the age of 10. Neuroblastoma basics: most common extracranial solid tumor in children, median age diagnosis 18 months, 40% occur in adrenal glands. Symptoms vary by location and metastases: abdominal mass (most common—parents notice firm swelling), bone pain (if skeletal metastases), periorbital ecchymosis (“raccoon eyes” from orbital metastases), opsoclonus-myoclonus syndrome (“dancing eyes, dancing feet”), and hypertension (catecholamine secretion). Prognosis highly variable: infants with localized disease—excellent (>90% cure); children >18 months with metastatic disease—poor (<40% long-term survival). Unique feature: spontaneous regression occurs in some infant neuroblastomas (stage 4S)—tumor disappears without treatment. Cleveland Clinic

The Incidentaloma Phenomenon: Accidental Discovery

In one review including 44 studies, benign adrenocortical adenomas accounted for 41% of nodules, metastases from extra-adrenal malignancies 19%, adrenocortical carcinomas 10%, myelolipomas 9%, and pheochromocytomas 8%, with other lesions such as adrenal cysts comprising the remainder. A prospective, multicenter, cross-sectional observational study including 1005 Korean patients with newly diagnosed adrenal incidentalomas found the vast majority were non-functional adrenocortical adenomas (83.3%); the remainder included cortisol-secreting tumors (4.4%), pheochromocytomas (6.0%), and aldosterone-secreting tumors (6.1%). An adrenal incidentaloma is conventionally defined as an asymptomatic adrenal lesion ≥1 cm discovered unexpectedly on imaging performed for indications unrelated to suspected adrenal disease. Modern imaging explosion: widespread use of abdominal CT/MRI for trauma, abdominal pain, cancer staging reveals adrenal masses in 3-7% of scans. Most incidentalomas benign: 80-85% benign non-functioning adenomas, 4-5% pheochromocytomas (potentially life-threatening if unrecognized), 1-2% primary aldosteronism, 1-4% adrenocortical carcinoma, and remainder metastases (lung, kidney, melanoma, breast cancer spreading to adrenals). In adults, incidental radiologic finding led to diagnosis in 79% at median age of 61 years. Contemporary adrenocortical carcinoma predominantly presents as an incidental imaging finding, characterised by >20 Hounsfield Units on nonenhanced CT but variable tumour size (20–196 mm). Malignancy cannot be ruled out by small tumour size only. The workup dilemma: every incidentally discovered adrenal mass requires evaluation for (1) hormonal function and (2) malignant potential. Hormonal testing: screen ALL incidentalomas for pheochromocytoma (plasma/urine metanephrines—failure to diagnose before surgery can cause fatal hypertensive crisis), autonomous cortisol secretion (1mg dexamethasone suppression test), and primary aldosteronism if hypertensive (aldosterone/renin ratio). Imaging features predicting cancer: size >4cm (malignancy risk increases with size—>6cm very concerning), irregular margins, heterogeneous appearance, high Hounsfield units on non-contrast CT (>10-20 HU suggests lipid-poor lesion—adenomas typically lipid-rich <10 HU), rapid growth on serial imaging, and vascular invasion. nih + 2

Survival and Treatment: Size and Stage Determine Outcomes

The 5-year survival rate for adrenocortical carcinoma is approximately 35%, whereas the 10-year survival rate of malignant pheochromocytoma reaches 40%. Overall 5-year survival was 67%, and 96% vs. 26% for ENSAT stage I–II vs. III–IV. ENSAT stage and Ki67 predicted survival, type of surgery did not. Mitotane associated with better survival. Adrenocortical carcinoma staging (ENSAT system): Stage I: tumor ≤5cm, confined to adrenal. Stage II: tumor >5cm, confined to adrenal. Stage III: tumor any size with lymph node involvement OR invasion into surrounding tissues/organs. Stage IV: distant metastases (lung, liver, bone). The survival divide: stages I-II (96% five-year survival if completely resected)—excellent outcomes; stages III-IV (26% five-year survival)—poor despite treatment. Treatment cornerstone: complete surgical resection (R0 resection—no microscopic residual) only potentially curative approach. Open surgery preferred over laparoscopic for suspected cancer (risk of tumor spillage/peritoneal seeding). Adjuvant mitotane therapy: oral chemotherapy drug specifically targeting adrenal cortex tissue, used after surgery to kill residual microscopic disease and reduce recurrence. For adrenocortical carcinoma, adjunctive treatment with oral mitotane leads to well-documented improvement of survival. Rare malignant pheochromocytomas with distant metastases are preferably treated by ¹³¹I-MIBG. Chemotherapy is reserved for unresectable tumors without sufficient response to mitotane or ¹³¹I-MIBG, respectively. Malignant pheochromocytoma treatment: surgery when feasible, ¹³¹I-MIBG (radioactive iodine that concentrates in chromaffin tissue)—targets metastases throughout body, external beam radiation for bone metastases (pain control), and chemotherapy (CVD regimen: cyclophosphamide, vincristine, dacarbazine) for progressive disease. PubMed + 2

Functional vs. Nonfunctional: Why Hormones Matter

Although in some cases, they are found incidentally, nonfunctional adrenocortical carcinomas typically present with any of the following: abdominal pain, palpable mass, weight loss. Patients with adrenal carcinoma report weight loss. Virilization is reported in women (for androgen-secreting tumors), and feminization in men (for estrogen-secreting tumors). Cushing syndrome (reflecting cortisol-secreting adenomas) includes weight gain, weakness, depression, and bruising. Nonfunctional (hormonally silent) adrenal cortical adenomas are not premalignant, and surgical excision is not indicated. Functional tumors (60% of adrenocortical carcinoma): hormone production creates symptoms prompting earlier medical evaluation, smaller tumor size at diagnosis (hormone effects apparent before mass effects), and potentially better prognosis (earlier detection allows surgery before metastases). Nonfunctional tumors (40% of adrenocortical carcinoma): no hormonal symptoms—growth silent until large enough to cause mass effect, larger size at diagnosis (often >10cm), more likely stage III-IV at presentation, worse prognosis, and symptoms only from tumor bulk (abdominal/flank pain, early satiety, weight loss from cancer itself). The clinical implication: even small adrenal masses with hormonal syndromes warrant aggressive evaluation; large hormonally-silent masses carry high malignancy suspicion. MedscapeMedscape

Frequently Asked Questions

Q1: I have a 3cm adrenal mass found on CT for kidney stones. My doctor says it’s likely benign. How worried should I be?

Most 3cm incidentalomas are benign adenomas, but evaluation is essential before reassurance. Your doctor should order: biochemical testing screening for pheochromocytoma (plasma metanephrines—mandatory before any intervention), autonomous cortisol secretion (overnight dexamethasone suppression test), and aldosterone excess if you’re hypertensive. Imaging characteristics matter: benign adenomas show low Hounsfield units (<10 HU) on non-contrast CT (lipid-rich), homogeneous appearance, smooth margins, and stable size on follow-up imaging 6-12 months later. Your 3cm size falls in intermediate risk zone—malignancy risk about 5-10%. Size >4cm raises cancer concern significantly. If imaging features benign AND hormones normal: observation with repeat imaging acceptable. If atypical imaging features OR any hormonal activity OR size increase: surgical removal recommended. Never assume “probably benign” without proper workup—undiagnosed pheochromocytoma can cause fatal complications.

Q2: I was diagnosed with Cushing’s syndrome from an adrenal adenoma. Does this mean I have cancer?

Not necessarily. Adrenal Cushing’s syndrome (ACTH-independent) can result from benign cortisol-producing adenoma (most common) OR adrenocortical carcinoma (less common but must be excluded). Distinguishing factors: Benign adenoma: slow symptom onset over months-years, stable size, homogeneous appearance on imaging, low Hounsfield units, size typically 2-5cm, only cortisol excess (no virilization/feminization). Adrenocortical carcinoma: rapid symptom onset (weeks-months), large size (>6cm), heterogeneous/irregular appearance, high Hounsfield units (>20), mixed hormone production (cortisol PLUS androgens/estrogens), invasion into surrounding structures. Your endocrinologist will determine malignancy risk based on imaging, hormone profile, tumor markers (if done), and clinical trajectory. Surgical removal curative for benign adenoma—Cushing’s symptoms resolve completely after recovery from adrenal insufficiency period (requires temporary steroid replacement). If cancer suspected, oncologic resection with possible adjuvant mitotane needed.

Q3: My brother died from pheochromocytoma at age 35. Should I and my children be tested?

Yes, absolutely. Twenty-five percent of pheochromocytomas are hereditary, and your brother’s young age raises genetic syndrome suspicion. You and your children should undergo: genetic counseling and testing for MEN 2 (RET gene), Von Hippel-Lindau (VHL gene), neurofibromatosis type 1 (NF1 gene), and SDH gene mutations (SDHB, SDHC, SDHD—associated with malignant pheochromocytoma and paraganglioma). Biochemical screening: annual plasma metanephrines or 24-hour urine metanephrines/catecholamines starting age 5-10 years (depending on syndrome) continuing lifelong. Imaging surveillance: if gene mutation identified, periodic MRI or CT scanning per syndrome-specific protocols. Why testing matters: hereditary pheochromocytomas often bilateral, occur younger, higher malignancy risk, associated with other tumors (thyroid cancer in MEN 2, renal cancer in VHL). Early detection allows planned surgical removal preventing hypertensive crises, strokes, arrhythmias. Your children especially need evaluation—if they inherit mutation, surveillance prevents catastrophic presentations.

Q4: What’s the difference between adrenal cancer and metastatic cancer to the adrenal glands?

Primary adrenal cancer: originates in adrenal tissue—adrenocortical carcinoma (cortex), pheochromocytoma (medulla), neuroblastoma (childhood). Relatively rare. May produce hormones. Treated as primary malignancy with adrenalectomy, specific chemotherapy regimens. Metastatic cancer to adrenals: spread from other primary site—lung, kidney, melanoma, breast most common. Adrenals highly vascular—frequent metastatic destination. Usually bilateral involvement. Never produce hormones (metastatic cells don’t make adrenal hormones). Treated as metastatic disease from primary cancer—rarely resected. Distinguishing factors: imaging (bilateral suggests metastases; unilateral favors primary), history of prior cancer (known lung/kidney/melanoma makes metastases likely), biopsy if needed (though risky for pheochromocytoma—must exclude biochemically first), and hormone production (suggests primary adrenal origin). Clinical context crucial—69-year-old with history of lung cancer and bilateral adrenal masses almost certainly has metastases, not primary adrenal cancer.

Q5: I’m starting mitotane therapy after adrenocortical carcinoma surgery. What should I expect?

Mitotane is adrenal-toxic chemotherapy specifically targeting adrenal cortex tissue—kills residual cancer cells but also destroys normal adrenal function. Expect: Adrenal insufficiency (intentional effect): you’ll need lifelong steroid replacement (hydrocortisone for cortisol, fludrocortisone for aldosterone). Higher doses during illness/stress/surgery essential preventing adrenal crisis. Gastrointestinal side effects: nausea, diarrhea, vomiting common—especially during dose titration. Anti-nausea medication helps. Neurological effects: ataxia (balance problems), confusion, dizziness—may require dose reduction. Drug interactions: mitotane induces liver enzymes accelerating metabolism of many medications—requires higher doses of steroids, thyroid hormone, warfarin, others. Inform all physicians you’re taking mitotane. Monitoring: frequent blood tests checking mitotane levels (therapeutic range 14-20 mg/L), liver/kidney function, cholesterol (often increases). Duration: typically continued 2-5 years after surgery if tolerated. Benefit: studies show improved disease-free survival and overall survival versus surgery alone. Despite side effects, mitotane remains most effective adjuvant therapy for adrenocortical carcinoma.

Disclaimer

This article adapts publicly available information from reputable cancer research organizations and medical databases. This content is for informational and educational purposes only and does not constitute medical advice. ObserverVoice.com is a news and information platform — not a healthcare provider. Decisions about adrenal tumor evaluation, diagnosis, and treatment should be made in consultation with qualified physicians, endocrinologists, surgeons, and oncologists who can evaluate your individual symptoms, imaging findings, and health status. If you have symptoms concerning for adrenal disease or an incidentally discovered adrenal mass, please consult with your healthcare team promptly.

References

1. StatPearls. Adrenocortical Carcinoma. https://www.ncbi.nlm.nih.gov/books/NBK546580/
2. PMC. Primary malignant tumors of the adrenal glands. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257058/
3. Cleveland Clinic. Adrenal Cancer: Symptoms, Prognosis & Treatment. https://my.clevelandclinic.org/health/diseases/25236-adrenal-cancer
4. PMC. Adrenocortical carcinoma: presentation and outcome of a contemporary patient series. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606857/
5. PMC. Clinical Characteristics and Outcome of Patients With Pheochromocytoma. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274258/

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