Adrenal cortical carcinoma (ACC) is a rare, aggressive cancer that starts in the outer layer (cortex) of an adrenal gland. You have two adrenal glands, one above each kidney. The cortex makes important hormones, such as cortisol, aldosterone, and androgens/estrogens. In ACC, the cells in the cortex grow out of control and can make too much hormone. Extra hormone causes many body changes, like weight gain, high blood pressure, or changes in hair and sexual function. The tumor can also grow large and press on organs. ACC can spread to the liver, lungs, lymph nodes, and bones. Early diagnosis improves outcomes.
Adrenocortical carcinoma (ACC) is a rare, aggressive cancer that begins in the outer layer (cortex) of the adrenal gland. The cortex makes steroid hormones such as cortisol, aldosterone, and androgens. ACC can be functioning (making extra hormones that cause symptoms) or non-functioning (not making excess hormones). The best chance for cure is complete surgical removal when the tumor is still localized. When the disease has spread, treatment focuses on controlling tumor growth and hormone excess, easing symptoms, and extending life. Authoritative guidelines (NCI PDQ, ESMO/EURACAN, and NCCN) consistently emphasize surgery for localized disease, and mitotane-based therapy—with the EDP-M regimen in advanced disease—as standard evidence-based options. Cancer.govESMONCCN
Other names
Adrenocortical carcinoma is also called adrenal cortex carcinoma, adrenal cortical carcinoma, adrenal cortical cancer, malignant adrenal cortical tumor, adrenal cortex cancer, or simply “adrenal cancer” (when referring to tumors from the cortex, not the medulla). In medical short form it is often written as ACC. When the tumor makes excess hormones it may be called a “functional” adrenal cortical carcinoma; when it does not make hormones it is called “non-functional” ACC.
Types
By hormone production
Functional ACC: The tumor makes extra hormones (cortisol, aldosterone, androgens, or estrogens). Symptoms come from hormone excess plus the mass itself.
Non-functional ACC: The tumor does not make extra hormones. Symptoms often come from the size of the mass (pain, fullness) or from spread.
By age
Pediatric ACC: Seen in children, often linked to inherited gene changes (for example certain TP53 mutations). Tumors often produce androgens or cortisol and present with early puberty signs.
Adult ACC: More common in adults aged 40–60. May be functional or non-functional.
By microscopic pattern (histologic variants)
Conventional ACC: The most common pattern.
Oncocytic ACC: Cells are large and packed with mitochondria.
Myxoid ACC: Tumor has mucoid (gel-like) areas.
Sarcomatoid ACC: Very aggressive; looks partly like a sarcoma.
By grade and stage
Grade (how fast the cells divide): Often estimated by Ki-67 index (low, intermediate, high). Higher Ki-67 means faster growth and worse outlook.
Stage: Based on tumor size, invasion of nearby tissues, lymph nodes, and distant spread (metastasis). Early stages are confined to the adrenal; later stages involve nodes and distant organs.
Causes and risk factors
The exact cause is often unknown. Many items below are risk factors or inherited conditions that raise the chance of ACC.
TP53 gene mutation (Li-Fraumeni syndrome): A strong, proven risk. TP53 is a tumor-suppressor gene. When it does not work, many cancers, including ACC, can develop.
TP53 p.R337H founder mutation (notably in parts of Brazil): A specific TP53 change found in some families and regions. It greatly increases the risk of childhood ACC.
Beckwith–Wiedemann syndrome (11p15 imprinting defects): This overgrowth syndrome disrupts control of growth signals (for example, IGF2). It increases the risk of adrenal cortical tumors.
Lynch syndrome (hereditary mismatch repair defects): Mostly linked to colon and uterine cancer, but ACC has been reported in some families with Lynch genes (MLH1, MSH2, MSH6, PMS2).
Multiple endocrine neoplasia type 1 (MEN1): MEN1 commonly causes pituitary and parathyroid tumors and adrenal adenomas; rarely, malignant adrenal cortical tumors can occur.
Familial adenomatous polyposis (APC gene): Primarily a colon polyposis disorder; ACC is rare but has been described in association.
Carney complex / primary pigmented nodular adrenocortical disease (PPNAD): Usually causes Cushing syndrome from multiple small adrenal nodules; very rarely, malignant transformation occurs.
Congenital adrenal hyperplasia (CAH): Long-term hormonal drive and adrenal enlargement can predispose to adrenal cortical tumors; carcinoma is uncommon but reported.
Family history of adrenal cortical tumors: Even without a named syndrome, a strong family history can signal inherited risk.
Childhood and older adult age peaks: ACC occurs more often in very young children and in adults around middle age, suggesting developmental and acquired risks.
Female sex (slight predominance): ACC is diagnosed slightly more often in females than males in many series.
IGF2 overexpression in the tumor: Not a lifestyle cause, but a common molecular driver; high IGF2 signaling supports tumor growth.
Prior therapeutic radiation in childhood: Any childhood radiation can raise later solid tumor risk; ACC is rare but included among possible radiation-associated cancers.
Environmental endocrine-disrupting chemicals (e.g., certain pesticides/organics): Some studies suggest possible links to adrenal tumors, but evidence is not definitive.
Chronic hormonal stimulation of adrenal cortex: Long-standing abnormal signaling may promote growth; direct proof for ACC is limited but biologically plausible.
Adrenal cortical adenoma–to–carcinoma progression (rare): Most adenomas do not become cancer, but malignant transformation is biologically possible.
Impaired DNA repair pathways (beyond Lynch): Any inherited defect in DNA damage response can, in theory, raise ACC risk.
Epigenetic alterations (methylation/miRNA changes): Common in ACC and may help drive tumor behavior; again, not a lifestyle cause but a biological driver.
Immune dysregulation: Not a proven direct cause, but immune escape mechanisms are seen in ACC and help tumors progress.
Geographic founder effects: Certain regions (for example parts of Brazil) have higher rates due to inherited founder mutations like TP53 p.R337H.
Symptoms and signs
Symptoms depend on the hormone made by the tumor and the size of the mass. One person may have many of these; another may have only a few.
Abdominal or flank pain/fullness: A large adrenal mass can press on nearby organs.
Unintended weight loss and fatigue: Common with many cancers, especially when disease is advanced.
Cushing-like changes (from too much cortisol): Weight gain in the face and trunk, a round “moon” face, thin arms/legs.
Purple stretch marks and easy bruising: Cortisol makes skin thin and fragile.
Muscle weakness (proximal): Climbing stairs or getting out of a chair becomes hard due to cortisol-related muscle breakdown.
High blood pressure: From cortisol or aldosterone excess, or from mass effect and stress.
High blood sugar / new or worse diabetes: Cortisol raises glucose.
Hirsutism in women: Extra coarse hair on the face, chest, or belly due to androgen excess.
Acne and oily skin: Also due to extra androgens.
Deepened voice and menstrual irregularity in women: Androgen excess disrupts normal cycles.
Gynecomastia in men: Extra estrogens from the tumor can enlarge breast tissue.
Low libido and erectile dysfunction in men: Hormonal imbalance and cortisol effects contribute.
Low potassium symptoms (with aldosterone): Muscle cramps, weakness, palpitations.
Back pain or early satiety: From tumor pressure on back muscles or stomach.
Children: signs of early puberty: Rapid growth, pubic hair, acne, body odor, enlarged genitals in boys, or clitoral enlargement/early bleeding in girls.
Diagnostic tests
Physical examination
General exam and vital signs: The clinician checks weight, blood pressure, pulse, and appearance. Findings like central weight gain, a round face, or high blood pressure suggest hormone excess.
Abdominal palpation and percussion: Gentle pressing and tapping can detect a mass, tenderness, or organ enlargement. ACC can grow large and be felt deep in the upper abdomen or flank.
Skin and hair inspection: The clinician looks for purple stretch marks, bruises, acne, skin thinning, and hair pattern changes. These visible clues often point to cortisol or androgen excess.
Sexual development/breast-genital exam (age-appropriate): In adults, the exam looks for gynecomastia in men or virilization in women. In children, it assesses early puberty changes. These findings guide hormone testing.
Manual bedside tests
Orthostatic blood pressure test: BP and pulse are measured lying and then standing. Hormonal excess (cortisol/aldosterone) can disturb fluid balance and autonomic tone, causing abnormal changes.
Ferriman–Gallwey hirsutism scoring: A simple visual scoring of hair growth in women. A higher score supports androgen excess from a functional adrenal tumor.
Pitting edema check: Pressing a finger over the shin or ankle looks for fluid retention. Cortisol and aldosterone excess can cause swelling.
Laboratory and pathological tests
Low-dose dexamethasone suppression test (1-mg overnight): A pill of dexamethasone is taken at night; morning cortisol is measured. Normal adrenal glands “shut down” cortisol; an autonomous tumor often does not.
24-hour urinary free cortisol: Cortisol collected over 24 hours. Persistent elevation supports Cushing syndrome from a functional tumor.
DHEA-S and androgen panel (± testosterone): High DHEA-S or testosterone suggests an androgen-producing adrenal tumor, common in pediatric ACC and in virilizing adult tumors.
Estradiol and gonadotropins (LH/FSH): Elevated estradiol from the tumor (especially in men) can explain gynecomastia; LH/FSH help define whether the source is adrenal or gonadal.
Aldosterone–renin ratio with serum electrolytes: A high ratio plus low potassium suggests aldosterone-producing ACC. Electrolytes also show hypokalemia or metabolic alkalosis.
Plasma metanephrines (to exclude pheochromocytoma): Before any invasive step, medullary tumors must be ruled out. This protects the patient from dangerous BP spikes.
Surgical pathology with Weiss score and Ki-67 index: After tumor removal, the pathologist examines the tissue. The Weiss criteria help call it carcinoma versus adenoma. Ki-67 shows how fast cells divide; higher values predict a more aggressive course.
Electrodiagnostic/device-based tests
12-lead electrocardiogram (ECG): Low potassium from aldosterone excess or cortisol effects can cause rhythm changes. ECG checks for arrhythmias and QT changes.
Ambulatory blood pressure monitoring (24-hour): Provides a full-day BP profile. It helps document hormone-related hypertension and guide treatment.
Imaging tests
Contrast-enhanced adrenal CT (adrenal protocol with washout): First-line imaging. Features like size >4–6 cm, irregular shape, necrosis, and low contrast washout suggest malignancy.
MRI of the adrenals (chemical-shift and diffusion): Useful when CT contrast is not possible or to further characterize the mass. MRI can show invasion into vessels (like the inferior vena cava) and liver.
FDG PET-CT (± specialized tracers like metomidate where available): PET looks for high metabolic activity, helps stage the whole body, and can separate malignant from benign lesions. Metomidate PET binds adrenal cortex enzymes and can improve specificity.
Staging chest CT and liver imaging: Even if the adrenal mass is defined, separate chest and liver imaging check for lung and liver metastases, the most common distant sites.
Non-pharmacological treatments
These strategies do not treat the cancer itself, but they can reduce symptoms, protect function, and improve quality of life alongside medical care.
Physiotherapy & physical rehabilitation
Personalized conditioning plan: low-impact aerobic + gentle resistance to counter fatigue and steroid myopathy; start slow, build gradually; monitor blood pressure and glucose.
Proximal muscle strengthening: focus on hips, thighs, shoulders with sit-to-stand drills, step-ups, wall push-ups; helps daily function.
Flexibility and joint mobility: daily stretching of hips/hamstrings/chest to reduce stiffness and pain.
Balance and fall-prevention training: heel-to-toe walks, single-leg stands near support; critical if on steroids or with bone loss.
Breathing exercises and pacing: diaphragmatic breathing with activity pacing to manage exertional fatigue.
Pelvic floor and core conditioning: gentle core work improves posture and reduces back discomfort from abdominal mass effects.
Osteoporosis-safe exercise set: weight-bearing walks and resistance bands; avoid high-impact moves if bone density is low.
Edema and neuropathy care: massage techniques, limb elevation, gentle nerve-glide drills if chemo causes tingling.
Shoulder/scapular stability work: bands/rows to offset steroid-related muscle weakness.
Gait training with assistive devices: temporary cane or walker to maintain independence when weak.
Energy-conservation coaching: schedule activity in “energy windows,” combine tasks, sit for chores.
Post-surgical mobilization protocol: early ambulation, breathing incentive devices, gentle range-of-motion to prevent complications.
Scar and posture management: soft tissue work and stretching after healing to avoid tightness.
Lymphedema-aware strategies: if nodes removed, learn swelling precautions and sleeve use if needed.
Home-safety modifications: reduce fall hazards (rugs, cords), add grab bars and good lighting.
Mind-body, behavioral, and educational therapy
Stress-reduction training: mindfulness or guided imagery lowers cortisol reactivity and anxiety; daily 10–20 minutes.
Sleep hygiene program: fixed sleep/wake times, dark quiet room, limit caffeine; vital when steroids disturb sleep.
Coping-skills counseling: cognitive behavioral therapy (CBT) for uncertainty, mood, and pain coping.
Cancer nutrition counseling: weight-neutral or weight-correcting plan, protein targets, safe food handling during chemo.
Medication education: understanding mitotane monitoring, need for steroid replacement, drug–drug interactions (e.g., with antifungals). PMC
Blood pressure and glucose self-monitoring: ties symptoms to numbers; alerts team early.
Return-to-activity planning: phased goals for work, school, or caregiving.
Social work and financial navigation: early benefits, travel aid, medication access programs.
Palliative care integration: focuses on symptom relief (pain, fatigue, mood) alongside active treatment—earlier is better.
Peer and family education: explain the disease, realistic goals, emergency steroid card if on replacement.
Drug treatments
Doses and schedules are individualized; oncology teams follow validated protocols. Where ranges are common, they’re presented as “titrated” rather than fixed numbers for safety. Always follow your specialist’s plan.
Mitotane (adrenolytic): cornerstone drug for ACC. It both damages adrenal tumor cells and blocks cortisol synthesis. It’s used after surgery in higher-risk cases and in advanced disease, often with other chemo. Levels are titrated to a target blood concentration, and patients usually need hydrocortisone replacement because mitotane raises steroid metabolism. Side effects can include nausea, fatigue, neurocognitive fog, and lipid changes, monitored with regular labs and drug levels. PMC
EDP-M regimen (etoposide, doxorubicin, cisplatin + mitotane): the reference first-line chemotherapy for unresectable or metastatic ACC; given in cycles every 3–4 weeks per protocol. It improves response rates vs alternatives (FIRM-ACT trial). Main risks include neutropenia, nausea, kidney injury (cisplatin), and heart toxicity (doxorubicin), which are prevented/managed with supportive meds and monitoring. New England Journal of MedicineeviQ
Streptozocin + mitotane: a historical alternative to EDP-M for advanced ACC; typically used when EDP-M isn’t suitable. Nausea, kidney stress, and low counts can occur; careful selection is needed. (Comparator arm in FIRM-ACT.) New England Journal of Medicine
Gemcitabine-based regimens (± capecitabine): second-line options in some centers when EDP-M fails or isn’t tolerated. Responses are modest; benefit is individualized. (Summarized in guideline reviews.) The Lancet
Temozolomide: sometimes used off-label in later lines; easy oral dosing; modest activity; best in carefully chosen cases. The Lancet
Pembrolizumab (PD-1 inhibitor): immunotherapy for selected patients, especially with mismatch-repair deficiency or high tumor mutational burden. Overall activity in unselected ACC is limited but durable responses can occur. Immune-related side effects (thyroiditis, colitis, hepatitis) are monitored and treated promptly. Cancer.gov
Nivolumab ± ipilimumab: another PD-1/CTLA-4 approach in selected or trial settings; used after standard therapy in some centers. Risks mirror other checkpoint inhibitors and require experienced management. Cancer.gov
Cabozantinib or lenvatinib (TKIs): targeted anti-angiogenic agents tried in refractory cases; evidence is evolving with small studies. Side effects include hypertension, fatigue, and diarrhea. Consider clinical trial enrollment when possible. The Lancet
Ketoconazole (blocks steroid synthesis): helpful for rapid cortisol control in functioning tumors or during mitotane titration. Dosed several times daily and titrated to normalize cortisol; watch for liver toxicity and interactions. Cancer.gov
Metyrapone: another fast-acting blocker of cortisol synthesis; used alone or with ketoconazole. Side effects include blood pressure changes and low potassium; labs are checked frequently. Cancer.gov
Osilodrostat: potent inhibitor of cortisol synthesis; increasingly used for Cushing’s control while oncologic therapy proceeds; requires close monitoring of cortisol and electrolytes. Cancer.gov
Mifepristone: glucocorticoid receptor blocker for refractory hypercortisolism; helps glucose and blood pressure, but does not lower cortisol levels (so labs can be tricky). Monitor for low potassium and endometrial effects. Cancer.gov
Spironolactone: mineralocorticoid receptor blocker for aldosterone-producing ACC; improves blood pressure and potassium. Can cause breast tenderness and high potassium; an alternative is eplerenone when side effects limit use. Cancer.gov
Hydrocortisone (± fludrocortisone) replacement: many patients on mitotane need physiologic steroid replacement because mitotane accelerates steroid breakdown; doses are adjusted to symptoms and labs, with a stress-dose plan for illness or surgery. PMC
Antiemetics, growth-factor support, and bone-protective meds: supportive drugs (ondansetron, G-CSF, bisphosphonates/denosumab when indicated) keep treatment safe and on schedule. Cancer.gov
Dietary “molecular” supplements
No supplement treats ACC. Use these only to support nutrition and symptom control, and always clear them with your oncology team to avoid drug interactions (especially with mitotane and chemo).
Vitamin D (if low): supports bone health under steroid exposure; dose guided by blood levels.
Calcium (diet first; supplement if needed): protects bone density with steroid excess.
Protein powder (whey/plant): helps rebuild muscle lost to Cushing’s and chemotherapy.
Omega-3 fatty acids (EPA/DHA): may ease inflammation and help maintain weight; watch for bleeding risk with certain drugs.
Soluble fiber (oats/psyllium): supports glucose and lipid control when cortisol is high.
Probiotics (carefully, if neutropenic avoid live cultures): may help bowel regularity during chemo; discuss safety first.
Ginger (capsules/tea): can reduce nausea for some patients.
Magnesium (if low): helpful for cramps and low-potassium symptoms; coordinate with potassium management.
Selenium (only if deficient): antioxidant role; avoid high doses.
B-complex (modest dose): supports appetite and energy; avoid megadoses that interact with chemo.
Immunity booster / regenerative / stem-cell drugs”
There are no approved “regenerative” or stem-cell drugs for ACC, and “immune-boosting” pills are not proven to treat this cancer. Here is what is used safely and evidence-based in clinical care:
Seasonal vaccines (influenza, COVID-19) when your team says it’s safe—reduce infection risk during therapy.
G-CSF (filgrastim/pegfilgrastim) to prevent or treat chemo-related low white cells; this shortens neutropenia and lowers infection risk.
Checkpoint inhibitors (e.g., pembrolizumab, nivolumab±ipilimumab) in selected cases—this is true cancer immunotherapy, not a vitamin. Cancer.gov
Antimicrobial prophylaxis (when indicated) during high-risk chemo phases.
Nutritional optimization (protein, calories, vitamin D if low) to support immune function—adjunctive only.
Clinical trials of cellular therapies are experimental; consider only in specialized centers.
This section is intentionally conservative to avoid unsafe or misleading “immune booster” claims.
Procedures and surgeries
Radical open adrenalectomy: the primary curative operation for localized ACC. Surgeons remove the adrenal tumor en bloc with a rim of healthy tissue to secure negative margins. Open approach is preferred for large/invasive tumors to avoid tumor spill. Cancer.govESMO
En-bloc resection of involved organs: if the tumor touches kidney, liver segment, or diaphragm, these areas may be removed together to clear all disease. Cancer.gov
Lymph node dissection (selective): enlarged or suspicious nodes are removed to stage accurately and reduce local recurrence risk. Cancer.gov
Metastasectomy (carefully selected): removal of limited lung or liver metastases may help in slow-growing disease after good response to systemic therapy. Cancer.gov
Local ablation or embolization (interventional radiology): radiofrequency or microwave ablation, or arterial embolization, can palliate pain or control a few liver lesions when surgery isn’t feasible. Cancer.gov
Prevention
There is no guaranteed prevention for sporadic ACC. Practical steps focus on early detection in high-risk people and lowering general health risks:
Genetic counseling/testing for families with Li-Fraumeni or similar syndromes;
Syndrome-based surveillance (periodic imaging/labs as your genetics team recommends);
Avoid unnecessary steroids and always taper medically;
Control blood pressure, glucose, and weight to cushion hormone effects;
Bone-health plan if long-term steroid exposure occurs;
No smoking and moderate alcohol;
Vaccination to lower infection risk during treatment;
Safe exercise and diet supporting muscle and bone;
Adherence to follow-up imaging and labs after treatment;
Seek care promptly for new hormone-like symptoms.
When to see a doctor (red flags)
New Cushing-like changes (rapid central weight gain, easy bruising, purple stretch marks, new diabetes or hypertension).
Virilization in women/children or feminization in men.
Hard, growing abdominal mass or new persistent flank/abdominal pain.
Severe weakness, low potassium symptoms (cramps, palpitations), or very high blood pressure.
Any concerning change during or after ACC treatment (fever, infection signs when on chemo; severe fatigue; swelling; shortness of breath).
What to eat and what to avoid
What to eat: small, frequent meals rich in protein (fish, eggs, legumes, dairy), colorful vegetables and fruit, whole grains, and healthy fats (olive oil, nuts). Aim for calcium and vitamin D sources to protect bone. Keep hydration steady, especially during chemo.
What to limit/avoid: ultra-processed foods high in sugar/salt; grapefruit and some herbal products that interact with cancer drugs; excess alcohol; raw/undercooked foods when white counts are low; high-dose supplements unless prescribed. Coordinate every change with your oncology pharmacist, especially if you’re on mitotane, which has many interactions. PMC
Frequently asked questions
Is ACC curable? Yes—if caught early and completely removed. Advanced cases are harder but can be managed to improve quality and length of life. Cancer.gov
What’s the main treatment? Surgery for localized disease; mitotane-based therapy (often EDP-M) for advanced disease. New England Journal of MedicineCancer.gov
Why is mitotane special? It targets adrenal cells and also blocks cortisol; drug levels are monitored, and steroid replacement is often needed. PMC
Will I need chemo? Possibly—especially if the cancer has spread or recurred. EDP-M is the reference first-line regimen. New England Journal of Medicine
Can immunotherapy help? Sometimes, especially if tumors have mismatch-repair defects or high mutation burden. Your team may test for these. Cancer.gov
What scans are used? Adrenal-protocol CT/MRI for local detail; PET/CT in selected cases; chest imaging for spread. Cancer.gov
Are there approved stem-cell treatments for ACC? No. Consider clinical trials at expert centers for innovative options. Cancer.gov
How often will I be followed after surgery? Regular imaging and hormone tests over several years; the exact schedule depends on risk and guidelines. ESMO
What side effects should I expect with EDP-M? Nausea, fatigue, low blood counts, hair loss, kidney strain, and heart-dose limits—managed with premeds, monitoring, and growth-factor support. eviQ
Can diet treat ACC? No. Diet supports strength and symptom control but does not cure ACC.
Should I exercise? Yes—gentle, supervised exercise improves energy and muscle strength; avoid high-impact moves if bones are weak.
Will I need steroid replacement? Many patients on mitotane do; carry a steroid emergency card and follow a stress-dose plan. PMC
Is laparoscopic surgery okay? For suspected cancer, open surgery is often preferred for large/invasive tumors to avoid tumor spill. Cancer.gov
What is my prognosis? It varies by stage, margins, and tumor grade (e.g., Ki-67, mitoses). Your care team uses these to estimate risk. PubMed
Where can I find trusted guidance? NCI PDQ (patient and professional versions), ESMO/EURACAN guidance, and NCCN (clinician resource). Cancer.gov+1NCCN
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: September 08, 2025.
