Malignant Adrenal Neoplasm

A malignant adrenal neoplasm is a cancer that starts in one of the two adrenal glands that sit on top of the kidneys. The adrenal gland has two main parts: the cortex (outer layer) and the medulla (inner core). Cancers can arise from either part. When the tumor comes from the cortex, it is usually called adrenocortical carcinoma (ACC). When it comes from the medulla, it can be a malignant pheochromocytoma (or a paraganglioma if similar cells occur outside the adrenal). Some adrenal cancers make extra hormones. This can cause clear body changes, such as weight gain from too much cortisol, hair growth or deep voice from extra androgens, or high blood pressure and pounding heartbeat from excess adrenaline-like chemicals. Other tumors make no hormones and are found because they grow large or spread. Diagnosis relies on a mix of careful history, physical exam, hormone tests, and imaging like CT or MRI. Treatment usually involves surgery when possible, plus medicines or other therapies depending on the tumor type and stage. Early detection and correct classification (cortical vs medullary, functional vs non-functional) are key to guide care.

A malignant adrenal neoplasm is a cancer that starts in one of the two adrenal glands that sit above your kidneys. These glands make many hormones that control blood pressure, salt balance, stress response, and sex hormones. “Malignant” means the tumor can grow into nearby tissues and spread to other parts of the body. The two main primary adrenal cancers are adrenocortical carcinoma (ACC), which starts in the outer cortex that makes steroid hormones, and malignant pheochromocytoma/paraganglioma (PPGL), which starts in catecholamine-producing cells of the medulla or nearby nerves. Adrenal glands can also host cancers that spread from elsewhere (metastases). Treatment usually depends on tumor type, size, stage, hormones produced, and whether surgery can remove it completely. Surgery is the key treatment when possible; medicines, radiation, and clinical trials are used when needed. National Cancer Institute+1PMC

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Another names

Malignant adrenal neoplasm is also called adrenal cancer. When arising in the cortex: adrenocortical carcinoma (ACC), adrenal cortical carcinoma, or cortical cancer. When arising in the medulla: malignant pheochromocytoma (adrenal) or metastatic/extra-adrenal paraganglioma (related tumors outside the adrenal). Some reports also use adrenal malignancy, primary adrenal carcinoma, or adrenal cortical cancer. In children, adrenal medullary cancer may include neuroblastoma (a different pediatric tumor family). When the adrenal mass is cancer spread from another organ, it may be called adrenal metastasis rather than primary adrenal cancer.

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Types

By tissue of origin

1. Adrenocortical carcinoma (ACC): Cancer from the adrenal cortex. May secrete cortisol, androgens (e.g., DHEA-S, testosterone), estrogen, or aldosterone; or be non-functional.

2. Malignant pheochromocytoma: Cancer from adrenal medulla chromaffin cells, usually producing catecholamines (adrenaline, noradrenaline); related extra-adrenal tumors are malignant paragangliomas.

3. Adrenal metastasis (secondary adrenal cancer): Cancer that started elsewhere (e.g., lung, kidney, melanoma, colon, breast) and spread to the adrenal. This is common but is not a primary adrenal neoplasm.

4. Rare primaries: Primary adrenal lymphoma or sarcoma (uncommon but malignant).

By hormone function

• Functional tumors: Overproduce hormones (cortisol, androgens, estrogens, aldosterone, catecholamines) causing specific syndromes.

• Non-functional tumors: Do not overproduce hormones; often present as a large mass or due to spread.

By laterality

• Unilateral: One adrenal involved (most common).

• Bilateral: Both adrenals involved (seen in some genetic syndromes or in metastases).

By stage (concept)

• Localized to adrenal only

• Locally advanced into nearby tissues or vessels

• Node-positive

• Metastatic to distant organs

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Causes

1. Li-Fraumeni syndrome (TP53 mutation): A strong hereditary cancer syndrome; germline TP53 defects raise risk of ACC, especially in children.

2. Beckwith–Wiedemann syndrome (11p15 imprinting defects): Overgrowth syndrome that increases risk for adrenal cortical tumors, including carcinoma.

3. Lynch syndrome (MMR gene mutations): DNA mismatch-repair defects; rare cases include ACC as part of the syndrome’s tumor spectrum.

4. Multiple Endocrine Neoplasia type 2 (RET): Strongly linked to pheochromocytoma; some become malignant.

5. Von Hippel–Lindau disease (VHL): Predisposes to pheochromocytoma/paraganglioma; a subset is malignant.

6. Neurofibromatosis type 1 (NF1): Raises risk for pheochromocytoma; malignant transformation can occur.

7. Succinate dehydrogenase (SDHB/SDHD/SDHC/SDHA) mutations: Familial pheochromocytoma/paraganglioma syndromes; SDHB, in particular, carries a higher risk of malignancy and metastasis.

8. MAX and TMEM127 mutations: Additional hereditary drivers for pheochromocytoma/paraganglioma with malignant potential.

9. Somatic TP53 mutations (non-germline): Common in ACC; lead to genomic instability and tumor progression.

10. IGF2 overexpression (11p15 dysregulation): A hallmark in many ACCs; promotes growth signaling.

11. CTNNB1 (β-catenin) pathway activation: Wnt/β-catenin signaling alterations contribute to cortical tumorigenesis.

12. MEN1 and PRKAR1A pathway changes: Less common; disrupt endocrine growth controls; PRKAR1A relates to Carney complex-like biology.

13. Chronic ACTH-driven cortical hyperplasia (rare pathway): Long-standing stimulation may, in rare cases, promote neoplastic change.

14. Prior childhood radiation (general carcinogenic exposure): Not a classic specific cause for adrenal cancer but radiation is a broad carcinogen.

15. Environmental carcinogens (general): Limited direct evidence for adrenal cancer; general carcinogen exposure may contribute to mutations.

16. Long-standing uncontrolled catecholamine excess (medullary cells): Proliferative signaling may support tumor progression in susceptible genotypes.

17. Immunosuppression (general cancer risk): Reduced immune surveillance could allow malignant clones to expand.

18. Adrenal cortical stem/progenitor cell dysregulation: Abnormal renewal/differentiation pathways can seed malignant clones.

19. Family history of adrenal tumors: Indicates potential shared genetic risk, even if the exact gene is unknown.

20. Primary cancers that commonly metastasize to adrenal (secondary cause of adrenal malignancy): Lung, renal cell carcinoma, melanoma, colorectal, and breast cancers frequently seed the adrenals.

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Symptoms

1. Abdominal or flank pain/fullness: From a growing mass stretching tissues or pressing on nearby organs.

2. Palpable abdominal mass or early satiety: Big tumors can be felt or reduce stomach space, causing quick fullness.

3. Unintentional weight loss and fatigue: General signs of advanced cancer or high hormone turnover.

4. Cushing’s features (cortisol excess): Easy bruising, thin skin, round “moon” face, central weight gain, muscle weakness, mood changes, poor wound healing, and high blood sugar.

5. Virilization in females (androgen excess): New facial/body hair, acne, deepened voice, menstrual changes, clitoral enlargement.

6. Feminization in males (estrogen excess): Breast enlargement, decreased libido, erectile dysfunction.

7. Hypertension (aldosterone or catecholamine excess): Persistently high blood pressure, sometimes severe or resistant to drugs.

8. Low potassium symptoms (aldosterone excess): Muscle cramps, weakness, palpitations, constipation.

9. Pheochromocytoma “triad”: Episodes of severe headache, palpitations, and sweating; often with tremor, pallor, and anxiety.

10. Panic-like spells: Sudden fear or doom feeling during catecholamine surges.

11. Orthostatic symptoms: Dizziness when standing due to blood pressure swings.

12. Flushing or pallor spells: Brief color changes during hormone surges.

13. Back pain: Tumor pressure or spread to bone.

14. Symptoms from metastases: Cough or shortness of breath (lung), bone pain, neurologic symptoms if brain/spine involved.

15. General cancer symptoms: Persistent fever without infection, night sweats, appetite loss.

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Diagnostic tests

Below, each test is named with its main category in parentheses, followed by a plain-English explanation of what it is, why it is done, and what it shows. Together, these tests help decide if the adrenal tumor is primary or metastatic, cortical or medullary, functional or non-functional, and whether it has spread.

1. Comprehensive physical examination (Physical exam)
   A head-to-toe exam looks for visible hormone effects (Cushing’s features, virilization, gynecomastia), blood pressure pattern, abdominal tenderness or a mass, skin changes (bruises, striae), and signs of metastasis (bone tenderness, neurologic deficits). It provides the first clues about whether a tumor is making hormones and how advanced disease might be.

2. Manual abdominal palpation and percussion (Manual test)
   The clinician gently presses and taps the abdomen to feel for a mass and assess organ size and tenderness. A large adrenal mass can sometimes be appreciated, especially if it displaces the kidney or liver. Although not definitive, this bedside test can raise suspicion and guide urgent imaging.

3. Seated and standing blood pressure and heart rate (Manual test)
   Blood pressure and pulse are measured in sitting and then standing positions. Large jumps, severe hypertension, or orthostatic changes suggest hormone activity (catecholamines or aldosterone) or volume shifts. It is simple, safe, and helps decide which lab tests to prioritize.

4. Low-dose dexamethasone suppression test (Lab)
   You take a small dose of dexamethasone at night, and your morning cortisol is measured. Normal adrenal glands “turn down” cortisol after dexamethasone. A cortisol-secreting ACC will not suppress well. This screens for autonomous cortisol production (Cushing’s syndrome).

5. 24-hour urinary free cortisol (Lab)
   All urine in 24 hours is collected to measure cortisol output. Repeated high values support cortisol-secreting tumors. It helps confirm hypercortisolism suspected from symptoms or screening tests.

6. Serum DHEA-S, testosterone, and estradiol (Lab)
   These tests evaluate androgen or estrogen excess. ACC often overproduces DHEA-S or testosterone (virilization) or, less commonly, estrogen (feminization). Marked hormonal elevations suggest a functional cortical malignancy.

7. Aldosterone-renin ratio (ARR) and serum electrolytes (Lab)
   A high aldosterone/renin ratio with low potassium suggests primary aldosteronism. While aldosterone-producing carcinoma is rare, ARR helps identify functional tumors and explains difficult hypertension or hypokalemia.

8. Plasma free metanephrines or 24-hour urinary fractionated metanephrines (Lab)
   These are the preferred biochemical tests for pheochromocytoma. Markedly elevated metanephrines indicate catecholamine overproduction. This is crucial because biopsy or surgery without alpha-blockade in pheo can be dangerous.

9. Chromogranin A (Lab/pathological marker)
   A blood marker often elevated in neuroendocrine tumors, including pheochromocytoma/paraganglioma. While not specific, it supports neuroendocrine activity and helps monitor disease over time.

10. Comprehensive metabolic panel and fasting glucose/HbA1c (Lab)
    Assesses liver and kidney function, electrolytes, and glucose control—important for surgical planning, for recognizing cortisol-induced diabetes, and for monitoring treatment effects.

11. High-resolution CT scan of the adrenals with contrast (Imaging)
    CT defines size, shape, density (Hounsfield units), and washout characteristics. Very large size, irregular margins, necrosis, and high unenhanced density favor malignancy. CT also surveys chest/abdomen/pelvis for spread (nodes, liver, lung).

12. MRI of the adrenals with chemical-shift imaging (Imaging)
    MRI distinguishes lipid-rich benign adenomas from suspicious masses and better evaluates venous invasion and soft tissue planes. Chemical-shift techniques are helpful when CT density is indeterminate. MRI is preferred in patients who should avoid radiation or iodinated contrast.

13. 18F-FDG PET/CT (Imaging)
    Cancer cells often use more glucose and light up on FDG PET. PET/CT helps separate aggressive lesions from benign ones and maps distant metastases. It is valuable in staging ACC and in evaluating indeterminate adrenal masses, especially in patients with another known cancer.

14. MIBG scintigraphy or PET for catecholamine tumors (Imaging)
    For pheochromocytoma/paraganglioma, iodine-123 MIBG scintigraphy or specialized PET tracers (e.g., 18F-FDOPA, 68Ga-DOTATATE) help confirm neuroendocrine origin and detect metastases. Choice of tracer depends on availability and genetics (e.g., SDHB tumors often image better with certain PET tracers).

15. Adrenal-focused PET with specific tracers (Imaging)
    Where available, tracers like 11C-metomidate PET bind enzymes in the adrenal cortex and help identify cortical origin, distinguish ACC from other lesions, and guide therapy planning.

16. Image-guided adrenal biopsy (Pathological)
    A needle biopsy (usually CT-guided) samples the mass for microscopic diagnosis. Important: this is avoided if pheochromocytoma is suspected (biochemical testing must be done first) because of the risk of dangerous catecholamine release. Biopsy is most helpful when imaging suggests metastasis from another known primary cancer.

17. Histopathology with Weiss or modified Weiss criteria (Pathological)
    When tumor tissue is obtained (typically after surgery), a pathologist uses structured scoring systems (e.g., Weiss criteria) and examines features such as mitotic rate, necrosis, invasion, and cellular patterns to distinguish carcinoma from adenoma and to grade aggressiveness.

18. Immunohistochemistry and proliferation index (Pathological)
    Stains like SF-1, inhibin, Melan-A, calretinin support adrenal cortical origin; neuroendocrine markers (chromogranin, synaptophysin) support pheochromocytoma. Ki-67 (MIB-1) proliferation index provides prognostic information (higher values indicate more aggressive behavior).

19. Electrocardiogram (ECG) and Holter monitoring (Electrodiagnostic)
    Catecholamine excess can cause tachycardia, arrhythmias, and ischemic-like changes. ECG documents rhythm problems; Holter records episodes over 24–48 hours. This is especially useful in malignant pheochromocytoma and in pre-operative assessment.

20. Ambulatory blood pressure monitoring (Electrodiagnostic)
    A wearable cuff records blood pressure day and night. It documents severe peaks or variability typical of catecholamine surges or resistant hypertension from aldosterone or cortisol excess, and it helps adjust therapy safely.

Non-pharmacological treatments

A) Physiotherapy & physical rehabilitation

1. Post-adrenalectomy recovery program
   Description: A gentle, staged program after surgery helps you regain mobility, breathing depth, and core strength. It starts with bed exercises, sitting, and standing on day 1–2 (as allowed), then short hallway walks, breathing exercises with an incentive spirometer, and light core activation to support the incision. As pain improves, you add posture drills, shoulder/upper-back mobility (to counter protective hunching), and progressive walking goals. In weeks 2–6, you re-build hip and trunk strength, balance, and stamina while protecting the wound.
   Purpose: Speed safe return to daily life, reduce lung complications, and prevent deconditioning.
   Mechanism: Early movement improves blood flow, lung expansion, and muscle activation; it reduces stiffness and clots.
   Benefits: Less pain and fatigue, quicker bowel recovery, better sleep and mood, and fewer complications.

2. Cancer-safe aerobic training
   Description: Moderate walking or cycling most days (build toward ~150 minutes/week) at a pace that raises breathing but still allows talking. Add short bouts at first (5–10 minutes) and join them together. On low-energy days, do shorter, easier sessions.
   Purpose: Reduce cancer-related fatigue and improve fitness during or after treatment.
   Mechanism: Aerobic activity improves mitochondrial function, circulation, and inflammatory balance.
   Benefits: Better energy, mood, sleep, and physical function; lower treatment side effects. ScienceDirectPMCASCO Journals

3. Progressive resistance training
   Description: 2–3 non-consecutive days per week using bodyweight, bands, or light weights (sit-to-stand, wall push-ups, rows, step-ups). Begin with 1 set of 8–12 reps and build to 2–3 sets. Focus on legs, hips, back, chest, arms, and core.
   Purpose: Reverse muscle loss from stress hormones, chemotherapy, and inactivity.
   Mechanism: Muscle loading triggers protein synthesis and improves insulin sensitivity.
   Benefits: More strength, independence, bone protection, and glucose control.

4. Breathing training & incentive spirometry
   Description: Diaphragmatic breathing, pursed-lip breathing, and spirometer use 5–10 times/hour while awake in early post-op days.
   Purpose: Prevent pneumonia and atelectasis after abdominal surgery.
   Mechanism: Deep breaths reopen small airways and improve oxygen delivery.
   Benefits: Easier breathing, less cough pain, faster mobilization.

5. Incision-protective core activation
   Description: Gentle pelvic tilts, abdominal bracing, and log-rolling for bed mobility, progressing to dead-bug variations and bird-dog as healing allows.
   Purpose: Support the surgical site and reduce strain.
   Mechanism: Trains deep stabilizers (transversus abdominis, multifidus).
   Benefits: Safer movement, less pain, better posture.

6. Balance and gait therapy
   Description: Heel-to-toe walking, single-leg stands near support, and dynamic balance tasks.
   Purpose: Reduce fall risk from fatigue or low blood pressure swings (common in hormone-active tumors).
   Mechanism: Enhances vestibular and proprioceptive control.
   Benefits: Safer walking and confidence.

7. Lymph-edema and swelling control
   Description: Elevation, ankle pumps, compression (if advised), and manual lymphatic techniques.
   Purpose: Manage lower-limb or wound-area swelling after extensive surgery.
   Mechanism: Promotes fluid return via muscle pump and lymph flow.
   Benefits: Comfort, mobility, wound healing.

8. Pelvic floor and abdominal wall care
   Description: Gentle pelvic floor activation and coordinated breathing reduce pressure on the incision and help with bowel/bladder function.
   Purpose: Protect repair, reduce hernia risk, improve continence.
   Mechanism: Pressurization control via diaphragm-pelvic floor synergy.
   Benefits: Safer lifting and coughing.

9. Neuropathy-friendly mobility
   Description: If chemotherapy causes numbness/tingling, use ankle circles, calf stretches, and gentle nerve glides; choose low-impact cardio.
   Purpose: Maintain mobility and reduce discomfort.
   Mechanism: Improves nerve gliding and microcirculation.
   Benefits: Better function and balance.

10. Cancer-related fatigue pacing
    Description: Plan the day using “prioritize, plan, pace.” Alternate activity and rest, and keep a fatigue diary.
    Purpose: Do more with less exhaustion.
    Mechanism: Energy conservation and graded exposure.
    Benefits: More control and less crash-and-burn.

11. Postural therapy
    Description: Thoracic extension over a towel roll, scapular setting, chin tucks, and hip flexor stretches.
    Purpose: Counter protective hunching and abdominal guarding.
    Mechanism: Restores length-tension balance.
    Benefits: Less back/neck pain and easier breathing.

12. Safe flexibility program
    Description: Daily gentle stretches for calves, hamstrings, hip flexors, and trunk.
    Purpose: Maintain range of motion after hospital stay.
    Mechanism: Reduces adhesions and stiffness.
    Benefits: Smoother movement and comfort.

13. Bone-aware loading
    Description: If you have bone metastases, your physio modifies exercises to limit stress on affected bones. Avoid high-impact or heavy twisting.
    Purpose: Keep you active while avoiding fracture risk.
    Mechanism: Risk-stratified loading choices.
    Benefits: Safe activity with confidence. PMC

14. Return-to-work conditioning
    Description: Task-specific practice (lifting simulations, desk ergonomics, micro-breaks) and graded hours.
    Purpose: Smooth transition back to roles.
    Mechanism: Functional capacity building.
    Benefits: Fewer flares, better tolerance.

15. Home-based tele-rehab
    Description: Video-guided sessions, wearables for step goals, and messaging with your physio.
    Purpose: Keep momentum if travel is hard.
    Mechanism: Coaching, adherence cues.
    Benefits: Access, convenience, continuity.

B) Mind–body therapies

16. Mindfulness-based stress reduction (MBSR)
    Description: Short daily sessions of breathing awareness, body scan, and gentle yoga.
    Purpose: Reduce anxiety, pain perception, and fatigue.
    Mechanism: Lowers sympathetic arousal and HPA-axis overdrive.
    Benefits: Calmer mood, better sleep, more coping capacity.

17. Cognitive behavioral therapy (CBT)
    Description: Brief, structured sessions to challenge unhelpful thoughts and build coping actions.
    Purpose: Manage fear of recurrence, insomnia, and treatment stress.
    Mechanism: Thought–behavior change rewires stress responses.
    Benefits: Less distress, better adherence to care.

18. Guided imagery & relaxation audio
    Description: 10–15 minutes of audio once or twice daily.
    Purpose: Ease nausea and pain.
    Mechanism: Conditioned relaxation reduces autonomic symptoms.
    Benefits: Comfort, sense of control.

19. Acceptance & commitment therapy (ACT)
    Description: Skills to notice difficult thoughts, then act on personal values despite them.
    Purpose: Improve quality of life during uncertain treatment paths.
    Mechanism: Psychological flexibility.
    Benefits: Meaning-focused living.

20. Sleep hygiene coaching
    Description: Fixed wake time, light exposure in the morning, caffeine limits, wind-down routine, and exercise earlier in the day.
    Purpose: Improve insomnia common in cancer care.
    Mechanism: Stabilizes circadian rhythm.
    Benefits: Better energy and mood.

21. Group support or peer navigators
    Description: Meetings or calls with others who faced adrenal cancer or endocrine tumors.
    Purpose: Reduce isolation and share practical tips.
    Mechanism: Social learning and validation.
    Benefits: Hope, problem-solving, resource access.

C) Educational & genetic counseling therapies

22. Treatment education sessions
    Description: Simple explanations of your exact tumor type (ACC vs PPGL vs metastasis), the role of surgery, and why medicines like mitotane or targeted options might be used.
    Purpose: Help you make informed choices.
    Mechanism: Closes knowledge gaps; improves adherence.
    Benefits: Less anxiety, better self-care. National Cancer Institute

23. Hormone self-monitoring training
    Description: Learn signs of cortisol deficiency (fatigue, dizziness), mineralocorticoid imbalance (salt craving, blood pressure swings), and catecholamine surges (headache, palpitations).
    Purpose: Early detection of problems.
    Mechanism: Symptom tracking and BP logs.
    Benefits: Faster help, fewer crises.

24. Genetic counseling and testing (when indicated)
    Description: Some adrenal tumors associate with inherited syndromes (e.g., Li-Fraumeni, Lynch, MEN2/PPGL). Sessions explain benefits and limits of testing and guide family screening.
    Purpose: Clarify risk and surveillance.
    Mechanism: Germline risk assessment.
    Benefits: Tailored follow-up for you and relatives. PMC

25. Clinical-trial navigation
    Description: Help finding trials for ACC or PPGL (new drugs, PRRT, improved surgery/radiation).
    Purpose: Access cutting-edge options in rare cancers.
    Mechanism: Registry search and referral.
    Benefits: More choices and expert care teams.

Important safety notes: Exercise is usually safe and helpful for people living with or after cancer; most guidelines aim for ~150 minutes/week of moderate activity plus twice-weekly strength work, adapted to your situation. Use extra caution if you have bone metastases, anemia, infection, or very low platelets; get a tailored plan from your team. Nutrition care should be routine and proactive. ScienceDirectPMCPubMed

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Drug treatments

Doses below are typical reference ranges for clinicians; your oncology/endocrine team will individualize and monitor them. Some drugs are used together.

1. Mitotane (adrenolytic)
   Class: Adrenolytic steroidogenesis inhibitor.
   Typical dose/time: Oral; gradually escalated to a therapeutic blood level (often several grams/day, divided). Requires close monitoring and steroid replacement.
   Purpose: Core systemic drug for ACC; used alone, adjuvantly, or with chemotherapy.
   Mechanism: Selectively damages adrenal cortical cells and suppresses steroid production.
   Key side effects: Nausea, fatigue, neurologic symptoms, high lipid levels; adrenal insufficiency managed with replacement steroids. National Cancer Institutehemonc.org

2. EDP-M regimen (Etoposide, Doxorubicin, Cisplatin + Mitotane)
   Class: Cytotoxic combination + adrenolytic.
   Typical dose/time: Cycles every 3–4 weeks in specialized centers; mitotane continued to maintain target levels.
   Purpose: First-line regimen for many advanced ACC cases.
   Mechanism: Multi-agent DNA damage and topoisomerase inhibition plus adrenolysis.
   Side effects: Low blood counts, nausea, hair loss, neuropathy, kidney/heart monitoring required. National Cancer Institute

3. Streptozocin + Mitotane
   Class: Alkylating agent + adrenolytic.
   Typical dose/time: Cycles; used when EDP-M is unsuitable.
   Purpose: Alternative systemic therapy for ACC.
   Mechanism: DNA alkylation.
   Side effects: Nausea, kidney/pancreas effects; regular labs. National Cancer Institute

4. Pembrolizumab (immune checkpoint inhibitor)
   Class: Anti-PD-1 antibody.
   Typical dose/time: IV every 3–6 weeks.
   Purpose: Option for selected refractory ACC; activity is modest but meaningful in some patients.
   Mechanism: Reactivates anti-tumor T-cells.
   Side effects: Immune-related effects (thyroid, liver, colon, skin); steroid management protocols apply. National Cancer Institute

5. Adrenal steroid replacement (Hydrocortisone/Fludrocortisone)
   Class: Glucocorticoid and mineralocorticoid replacement.
   Typical dose/time: Daily physiologic dosing; stress-dose during illness/surgery.
   Purpose: Treats adrenal insufficiency caused by mitotane, surgery, or disease.
   Mechanism: Replaces hormones you can’t make.
   Side effects: Dose-dependent weight gain, BP/ glucose changes; careful titration by clinicians. National Cancer Institute

6. Alpha-blockers (Phenoxybenzamine or Doxazosin) for malignant PPGL
   Class: Alpha-adrenergic antagonists.
   Typical dose/time: Daily titration before and sometimes after surgery or radionuclide therapy.
   Purpose: Control dangerous high blood pressure and spells.
   Mechanism: Blocks catecholamine effects on vessels.
   Side effects: Low BP, dizziness, nasal stuffiness; add beta-blocker only after alpha blockade if needed for heart rate. PMC

7. I-131 MIBG therapy (for MIBG-avid PPGL)
   Class: Targeted radionuclide therapy.
   Typical dose/time: One or more therapeutic infusions in specialized centers.
   Purpose: Shrink or control metastatic PPGL that takes up MIBG.
   Mechanism: Delivers radiation inside tumor cells via norepinephrine transporter.
   Side effects: Fatigue, low counts; radiation safety steps. The Lancet

8. Lutetium-177 DOTATATE (PRRT) for somatostatin-receptor–positive PPGL
   Class: Peptide receptor radionuclide therapy.
   Typical dose/time: IV every 8 weeks × 4 cycles in centers with PRRT.
   Purpose: Disease control in metastatic PPGL with receptor uptake.
   Mechanism: Delivers targeted radiation via somatostatin receptors.
   Side effects: Nausea, low counts, renal/ liver monitoring. PMC

9. Sunitinib
   Class: Multi-target VEGFR tyrosine kinase inhibitor.
   Typical dose/time: Oral in cycles (e.g., 4 weeks on, 2 weeks off) for advanced PPGL in selected cases.
   Purpose: Slow tumor growth and reduce hormone output.
   Mechanism: Blocks angiogenesis and tumor signaling.
   Side effects: Fatigue, hypertension, hand–foot syndrome; labs and BP monitoring needed. EJCancer+1ScienceDirect

10. Temozolomide (especially in SDHB-mutated PPGL)
    Class: Alkylating oral chemotherapy.
    Typical dose/time: 5 days every 28 days or metronomic schedules.
    Purpose: Disease control in selected PPGL.
    Mechanism: DNA methylation causing tumor cell death; may work better with SDHB loss.
    Side effects: Low counts, nausea; needs antiemetics. PMC

11. CVD regimen (Cyclophosphamide, Vincristine, Dacarbazine) for PPGL
    Class: Cytotoxic combination.
    Typical dose/time: Cycles every 3–4 weeks.
    Purpose: Shrink symptomatic or progressive disease.
    Mechanism: Multiple DNA-damaging pathways.
    Side effects: Low counts, neuropathy, nausea; careful monitoring. PMC

12. Radiation therapy (external beam or stereotactic)
    Class: Local therapy.
    Typical dose/time: Several sessions focused on painful or risky sites.
    Purpose: Pain relief, local control, prevention of fracture or cord compression.
    Mechanism: Damages DNA in targeted tumor regions.
    Side effects: Skin irritation, fatigue; site-specific risks. National Cancer Institute

13. Bisphosphonates or Denosumab (bone protection)
    Class: Anti-resorptive agents.
    Typical dose/time: IV/oral bisphosphonates every 3–12 weeks or SC denosumab monthly.
    Purpose: Reduce skeletal events from bone metastases.
    Mechanism: Inhibit osteoclast activity.
    Side effects: Low calcium, jaw osteonecrosis (rare); dental check first.

14. Antiemetics (Ondansetron, Aprepitant, Olanzapine as needed)
    Class: 5-HT3 antagonists, NK1 antagonists, multi-receptor agents.
    Typical dose/time: Per chemo cycle and 2–4 days after.
    Purpose: Prevent nausea/vomiting from chemo or mitotane.
    Mechanism: Blocks emetogenic pathways.
    Side effects: Constipation, sleepiness; QT monitoring for some.

15. Pain control ladder (Acetaminophen → NSAIDs → opioids when required)
    Class: Analgesics.
    Typical dose/time: Stepwise, using the lowest effective dose; bowel regimen with opioids.
    Purpose: Maintain function and sleep while treating cancer pain.
    Mechanism: Central and peripheral pain pathway modulation.
    Side effects: Constipation, sedation (opioids); kidney/ulcer risk (NSAIDs).

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Dietary “molecular” supplements

Evidence favors nutrition counseling, adequate protein–calorie intake, and exercise as first-line care. No supplement cures adrenal cancer. Always check for drug–supplement interactions (e.g., with TKIs, chemo, or blood thinners). ESPN+1

1. Medical nutrition therapy (protein-energy formula as needed)
   Dose: Individualized; often 1.2–1.5 g protein/kg/day total intake.
   Function/Mechanism: Supplies building blocks to counter muscle loss and support healing.
   Notes: Priority intervention when appetite is low; can include oral nutrition supplements. ESPN

2. Vitamin D (if deficient)
   Dose: As per blood levels (often 800–2000 IU/day; higher short-term repletion under supervision).
   Function: Bone and muscle health; may improve fall risk when deficient.
   Mechanism: Regulates calcium–phosphate and muscle function.

3. Omega-3 fatty acids (EPA/DHA)
   Dose: Common clinical targets ~1–2 g/day EPA+DHA from food/supplement if tolerated.
   Function: May help weight maintenance and inflammation balance in cancer-related cachexia.
   Mechanism: Eicosanoid modulation.

4. Oral creatine (for deconditioning)
   Dose: 3–5 g/day (renal safety review first).
   Function: Supports short-burst strength alongside resistance training.
   Mechanism: Increases muscle phosphocreatine stores.

5. Probiotics (strain-specific)
   Dose: Per product; avoid in severe immunosuppression.
   Function: May reduce antibiotic-associated diarrhea and support gut comfort.
   Mechanism: Microbiome modulation.

6. Soluble fiber (oats/psyllium)
   Dose: 5–10 g/day added gradually with fluids.
   Function: Helps bowel regularity with opioids or antiemetics.
   Mechanism: Water-holding gel formation.

7. Ginger extract
   Dose: ~0.5–1.0 g/day divided (capsules or tea), if compatible with meds.
   Function: Nausea relief in some patients.
   Mechanism: 5-HT3 and gastric motility effects.

8. Magnesium (if low)
   Dose: Correct deficiency (often 200–400 mg elemental/day, divided).
   Function: Muscle cramp relief; counters cisplatin-related wasting.
   Mechanism: Cofactor in neuromuscular function.

9. B-complex (for documented deficiency)
   Dose: Per lab-guided needs.
   Function: Supports nerve health and energy pathways.
   Mechanism: Coenzymes in cellular metabolism.

10. Protein-rich convenience foods
    Dose: Practical swaps: Greek yogurt, eggs, lentils, nut butters; aim to include protein at each meal/snack.
    Function: Real-world way to hit protein targets when appetite is limited.
    Mechanism: Amino acids for repair. ESPN

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Immunity booster / regenerative / stem-cell” items

1. Seasonal influenza and COVID-19 vaccination (as advised) — Supports protection from serious infection during cancer care.

2. G-CSF (filgrastim/pegfilgrastim; prescription) — Clinician uses this to prevent or treat chemo-related low white cells; reduces infection risk.

3. Rehabilitation + protein nutrition — The most evidence-based “immune support”: move your body and meet protein needs.

4. Checkpoint immunotherapy (e.g., pembrolizumab) in selected ACC — Not a supplement; a hospital-delivered immune treatment for some. National Cancer Institute

5. No approved stem-cell drugs for adrenal cancers — Stem-cell “shots” or “regenerative infusions” marketed to patients are unproven and potentially unsafe; avoid outside clinical trials.

6. Clinical trials — Safest path to novel immune or gene-targeted options under expert monitoring.

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Surgeries

1. Open adrenalectomy (en bloc resection)
   Procedure: Surgeon removes the adrenal tumor with a margin of healthy tissue through an open incision; may remove nearby tissues/organs if invaded.
   Why done: It is the main curative option for localized ACC and many adrenal tumors. Complete removal gives the best chance of long-term control. National Cancer Institute

2. Adrenalectomy with lymph node dissection (selected cases)
   Procedure: Removes enlarged or suspicious regional nodes during tumor removal.
   Why done: Staging and local control when nodes are involved. National Cancer Institute

3. IVC thrombectomy (when tumor extends into the vena cava)
   Procedure: Multidisciplinary operation to remove tumor thrombus from the large vein; sometimes uses bypass.
   Why done: Prevents life-threatening vascular blockage and allows complete resection.

4. Metastasectomy (selected lung/liver lesions)
   Procedure: Surgical removal or ablation of limited metastases.
   Why done: May relieve symptoms and, in very selected cases, prolong control when systemic disease is otherwise stable.

5. Palliative/debulking surgery
   Procedure: Intent is not cure but to reduce bulk or hormone excess when other measures fail.
   Why done: Symptom control and quality of life. National Cancer Institute

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Prevention

1. Know your family history; seek genetic counseling if relatives had ACC, PPGL, or related syndromes. PMC

2. Do not ignore progressive hypertension, headaches, palpitations, or weight changes—early evaluation matters.

3. Maintain a healthy weight, move daily, and avoid tobacco.

4. Limit alcohol and avoid performance drugs that affect blood pressure.

5. Manage sleep and stress to support blood pressure and glucose control.

6. Keep up with vaccines to reduce infection risk during treatment.

7. Use a medication list so providers can check interactions with cancer drugs.

8. Protect bones with calcium/vitamin D if indicated, plus resistance exercise.

9. Avoid unproven “cancer cures” or stem-cell offers.

10. Join survivorship follow-up for scans, labs, and hormone checks on the schedule your team sets.

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When to see doctors urgently

• Severe or worsening headache, palpitations, heavy sweating, chest pain, or very high blood pressure (possible PPGL crisis).

• Dizziness, fainting, severe fatigue, vomiting, or low blood pressure during mitotane therapy or after adrenal surgery (possible adrenal crisis).

• New severe back pain, weakness, or numbness (possible bone/nerve compression).

• Fever ≥38°C, shaking chills, bleeding, or mouth sores during chemotherapy (possible neutropenia).

• Fast weight gain with leg swelling or sudden shortness of breath.

• Any new red-flag symptom your team warned about.

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What to eat and what to avoid

1. Eat protein at every meal (eggs, fish, poultry, tofu, lentils, yogurt).

2. Choose energy-dense snacks when appetite is low (smoothies, nut butters, trail mix).

3. Hydrate well, especially during chemo and hot weather.

4. Salt intake may need adjustment if you’re on fludrocortisone or have mineralocorticoid changes—follow your team’s plan.

5. Fiber balance: enough to stay regular, but reduce very high-fiber roughage on days of nausea or bowel irritation.

6. If PPGL with catecholamine surges, avoid large caffeine doses and energy drinks that spike BP.

7. Limit alcohol; avoid unpasteurized products when counts are low.

8. Food safety first (wash produce, cook meats properly) during immunosuppression.

9. Use nutrition supplements selectively—focus on meeting protein-calorie goals first. ESPN

10. See an oncology dietitian early for a personalized plan. ESPN

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Frequently Asked Questions (FAQs)

1. Is malignant adrenal neoplasm the same as ACC?
   Not always. ACC is one type (from the cortex). Malignant pheochromocytoma/paraganglioma is another. Adrenal metastases are cancers from other organs that spread to the adrenal. Treatment paths differ. National Cancer InstitutePMC

2. What is the main treatment for ACC?
   Complete surgical removal when feasible. Mitotane and combinations like EDP-M are used for advanced or recurrent disease, and clinical trials are encouraged. National Cancer Institute

3. Can laparoscopic surgery be used?
   Open surgery is preferred for suspected ACC due to risks of tumor spill; minimally invasive approaches may be considered only in very selected small tumors at expert centers. (Discuss with your surgeon.)

4. Do all PPGLs need alpha-blockade?
   Before surgery or MIBG/PRRT, most patients require alpha-blockade to prevent dangerous blood-pressure spikes; beta-blockers are added only after alpha control if needed. PMC

5. What is mitotane and why do I need steroid replacement?
   Mitotane damages adrenal cells and often lowers your cortisol and aldosterone, so doctors prescribe hydrocortisone and sometimes fludrocortisone to prevent adrenal crisis. National Cancer Institute

6. Is immunotherapy used in adrenal cancer?
   Some patients with advanced ACC may receive checkpoint inhibitors like pembrolizumab, often in trials or after other treatments. Responses vary. National Cancer Institute

7. What about targeted therapy for PPGL?
   If the tumor expresses certain targets or receptors, options may include sunitinib, PRRT, or I-131 MIBG therapy in specialist centers. EJCancerThe Lancet

8. Will I need hormones after surgery?
   If one adrenal is removed and the other is healthy, many people do not need long-term replacement. After mitotane or bilateral adrenal removal, hormone replacement is usually lifelong and carefully adjusted. National Cancer Institute

9. How often are scans and labs done?
   Follow-up is individualized but typically frequent in the first 2–3 years, then spaced out if stable. Hormone tests and imaging check for recurrence or spread. National Cancer Institute

10. Can exercise make me worse?
    When tailored, exercise is safe and helpful for most people with cancer. Your team will adapt it if you have anemia, low platelets, infection, or bone risk. PMC

11. Are there diets that cure adrenal cancer?
    No. Evidence supports meeting calorie–protein needs, staying active, and working with a dietitian. Supplements are supportive only. ESPN

12. Should I take “immune boosters” or stem-cell infusions?
    Avoid over-the-counter immune “boosters” that may interact with treatment and avoid stem-cell products outside clinical trials; there is no approved stem-cell drug for these cancers.

13. Can malignant adrenal tumors be part of an inherited syndrome?
    Yes, some are. Genetic counseling/testing may be advised for you and family members. PMC

14. What if surgery is not possible?
    Your team may offer systemic therapy (mitotane-based, chemo, immunotherapy), radiation, radionuclide therapy for PPGL, and symptom-focused care. Clinical trials are important in rare adrenal cancers. National Cancer InstitutePMC

15. What is the outlook?
    Prognosis depends on tumor type, stage, complete resection, and response to therapy. Close follow-up and care at an experienced center improve decision-making and access to trials. National Cancer Institute

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 09, 2025.

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