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PubMed This is a summary of 22 peer-reviewed journal articles Updated
Surgery

Navigating Treatment: Surgery, Medications, and Specialized Therapies

At a Glance

Adrenal gland cancer treatment depends on tumor type, spread, and whether surgery can remove it safely. Localized disease is often treated with surgery; advanced ACC may need mitotane or chemotherapy, while advanced PPGL may qualify for receptor-guided radionuclide therapy.

Treating adrenal gland cancer requires a coordinated plan between surgeons, oncologists, and endocrinologists. Because these tumors are rare and complex, the best results are often achieved at “high-volume” medical centers where teams specialize in these specific diseases [1].

Surgery: The First Line of Defense

For both Adrenocortical Carcinoma (ACC) and Pheochromocytoma (PPGL), surgery is the primary goal if the tumor is localized and resectable. However, the preparation and technique differ significantly.

Surgical Standard for ACC

The preferred approach for suspected ACC is an open en-bloc resection [1].

  • En-bloc means the surgeon removes the tumor in one piece, along with any nearby tissue or organs (like parts of the kidney or liver) that are involved, to ensure clear margins [2].
  • The Goal: Achieving an R0 resection (no visible or microscopic cancer left behind) is a vital factor for long-term survival [3][2].
  • Minimal Invasion: While minimally invasive surgery (laparoscopic or robotic) may be considered by highly experienced surgeons for small tumors without signs of invasion, open surgery is standard to prevent the tumor capsule from breaking, which could spill cancer cells into the abdomen [4][5].

Essential Preparation for PPGL Surgery

If you have a catecholamine-secreting PPGL, your body is essentially flooded with adrenaline. Surgery can cause a massive release of these hormones, leading to a dangerous hypertensive crisis [6].

  • Alpha-Blockade: You must take an alpha-blocker (such as phenoxybenzamine or doxazosin) for weeks before surgery [7]. This relaxes your blood vessels and prevents dangerous pressure spikes during the operation [8].
  • Salt and Fluid: You will likely be directed to increase your fluid and salt intake during this time to prevent your blood pressure from dropping too low after the tumor is removed [9].
  • Beta-Blockers: These are only used if you have a racing heart, and they must never be started before adequate alpha-blockade is established, as this can cause a severe spike in blood pressure [10].

Mitotane: A Unique Medication for ACC

Mitotane is a specialized medication used exclusively for ACC. It works by suppressing steroid production and inducing toxicity in adrenal cells [11]. It is used for advanced disease and sometimes as an “adjuvant” therapy (after surgery) to reduce the risk of recurrence.

Managing the Drug Levels

Mitotane builds up in your body slowly. Clinicians often aim for a therapeutic target range of 14–20 mg/L [12].

  • Levels are individualized; a level below 14 is not automatically useless, and levels above 20 do not guarantee severe toxicity, but higher levels are generally associated with more side effects [13].

The Necessity of Steroid Replacement and Monitoring

Because mitotane suppresses adrenal function and speeds up how fast your body breaks down cortisol, glucocorticoid replacement (like hydrocortisone) is generally required during treatment [14].

  • Mitotane is a strong “enzyme inducer,” meaning it interacts with many other medications, including blood thinners, sedatives, and hormonal contraceptives (reducing their effectiveness). You must review all your medications with your oncology team [14].
  • Your team will closely monitor your thyroid function, liver tests, and cholesterol levels, as mitotane frequently affects these systems.

Systemic Care for Advanced Disease

If the cancer has spread or cannot be removed by surgery, other systemic treatments are discussed by your multidisciplinary team.

Options for Advanced ACC

The standard chemotherapy combination for aggressive or advanced ACC is EDP-M [15]:

  • Etoposide, Doxorubicin, CisPlatin, plus Mitotane.
    This combination aims to control the tumor but carries significant side effects, such as low blood counts and nausea [16][17]. Other individualized options may include localized radiation, clinical trials, or different systemic therapies.

Radionuclide Therapy for PPGL

For advanced PPGL, doctors may use specialized targeted radiation, provided you have the appropriate receptor imaging and organ function [18].

  • 131I-Iobenguane (Therapeutic MIBG): Used if a diagnostic MIBG scan shows your tumor takes up the drug. It delivers radiation directly to the tumor cells [19][20].
  • 177Lu-DOTATATE (PRRT): Used if the tumor expresses specific “somatostatin receptors” on a DOTATATE scan. These therapies can often provide meaningful disease control, though they are not guaranteed to work for everyone [21][22].

Common questions in this guide

Is open surgery usually recommended for adrenocortical carcinoma?
For suspected adrenocortical carcinoma, an open en-bloc resection is usually preferred when the tumor is localized and removable. The surgeon removes the tumor in one piece and may remove nearby involved tissue or organs to help achieve clear margins. Minimally invasive surgery may be considered only for selected small tumors without invasion by highly experienced surgeons.
Why do I need an alpha-blocker before pheochromocytoma surgery?
Some pheochromocytoma or paraganglioma tumors release hormones that can cause dangerous blood-pressure surges during surgery. An alpha-blocker such as phenoxybenzamine or doxazosin is usually started weeks beforehand to relax blood vessels and reduce this risk. If a beta-blocker is needed for a racing heart, it is generally added only after adequate alpha-blockade.
How is mitotane used to treat adrenal cancer?
Mitotane is a medication used for adrenocortical carcinoma, including advanced disease and sometimes treatment after surgery to lower recurrence risk. It suppresses adrenal steroid production and can build up slowly, so clinicians monitor blood levels and organ function. A commonly used target blood level is 14–20 mg/L, but the goal is individualized.
Will I need hydrocortisone while taking mitotane?
Usually, yes. Mitotane can reduce adrenal function and make the body break down cortisol faster, so glucocorticoid replacement such as hydrocortisone is generally needed. Ask your care team for a sick-day plan that explains how to adjust the dose during infection or injury.
What chemotherapy is used for advanced adrenocortical carcinoma?
EDP-M is a standard chemotherapy combination used for aggressive or advanced adrenocortical carcinoma. It includes etoposide, doxorubicin, cisplatin, and mitotane. It can cause important side effects such as low blood counts and nausea, so the oncology team monitors you closely.
How do doctors choose radionuclide therapy for advanced PPGL?
Eligibility depends on specialized imaging and organ function. Tumors that take up a diagnostic MIBG scan may be treated with 131I-iobenguane, while tumors showing somatostatin receptors on a DOTATATE scan may be treated with 177Lu-DOTATATE, also called PRRT. These treatments can control disease in some people but are not effective for everyone.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Is my surgeon experienced in high-volume adrenal centers, and do they plan an 'en-bloc' resection to ensure the tumor is removed intact?
  2. 2.If I have a catecholamine-secreting PPGL, which alpha-blocker will I be taking, and what should my target blood pressure and heart rate be before surgery?
  3. 3.When we start mitotane, how often will we check my blood levels and organ function to ensure we manage toxicity while aiming for a therapeutic range?
  4. 4.What is my 'sick day rule' plan for increasing my hydrocortisone dose if I get an infection or have an accident while on mitotane?
  5. 5.For my advanced PPGL, which imaging test (MIBG or DOTATATE) will determine which radionuclide therapy I am eligible for?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (22)
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    American Association of Clinical Endocrinology Disease State Clinical Review on the Evaluation and Management of Adrenocortical Carcinoma in an Adult: a Practical Approach.

    Kiseljak-Vassiliades K, Bancos I, Hamrahian A, et al.

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    American Association of Endocrine Surgeons Guidelines for Adrenalectomy: Executive Summary.

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This page explains treatment and preparation for adrenal gland cancer, ACC, and PPGL for informational purposes only; it does not constitute medical advice. Discuss your treatment plan with your oncology, surgical, and endocrinology team.

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