Adrenal Cancer Treatment: Surgery, Mitotane, and Managing Hormones

If you or someone you love has just been told they have adrenal cancer, the first thing to know is that for adrenocortical carcinoma (ACC), the cancer that starts in the outer layer of the adrenal gland, surgery is the cornerstone of treatment. It is the only treatment that can cure this cancer. Everything else in this guide supports, follows, or substitutes for surgery when surgery is not possible. So the most important early decision is not which drug to take. It is who operates, and where.

The second thing to know is that complete removal of the tumor, with no cancer left behind and no cancer cells at the cut edges, is called an R0 resection. Getting an R0 resection is the single strongest factor affecting outcome that you can actually influence. It depends heavily on the skill and experience of the surgeon and the volume of adrenal cancer cases the hospital handles. Adrenal cancer is rare, so many excellent general surgeons have operated on only one or two of these tumors in their whole career.

Adrenal cancer is not treated by one doctor. Good care comes from a team, and one member of that team is easy to overlook: an endocrinologist, a doctor who specializes in hormones. Your team should also include:

• Surgeon experienced in adrenal tumors

• Medical oncologist

• Radiologist

• Pathologist who has seen adrenal tumors before

• Radiation oncologist

• Often a genetic counselor

• Endocrinologist

Because adrenal cancer is so uncommon, no single set of universal guidelines covers every situation, which is another reason experience matters.

Hormone excess has to be treated alongside the cancer, not after it. Many adrenal cortex tumors make extra hormones, and those hormones cause real harm on their own. Too much cortisol raises the risk of serious infections, weakens muscle and bone, causes blood clots, and can trigger mood and thinking changes. Too much aldosterone drives blood pressure up and potassium down. Controlling these hormones is part of cancer treatment, not a side project. Most adrenal cancer symptoms come from hormones rather than from the size of the tumor itself.

Two other points will help you read the rest of this guide.

• First, treatment for children with ACC is genuinely different from treatment for adults, and children should be treated at a children's cancer center on a pediatric protocol. There is a section below just for parents.

• Second, a mass on your adrenal gland is not automatically cancer. The great majority of adrenal masses found by accident on a scan, called incidentalomas, turn out to be benign and need only a careful workup. And cancer that started somewhere else and spread to an adrenal gland, called an adrenal metastasis, is not adrenal cancer at all. It is treated as the original cancer, using that cancer's treatments.

Everything below describes what is generally done. It is not advice about your own case. Bring your questions to your own care team, who know your scans, your pathology, and your hormone results.

Types of Treatment for Adrenal Cancer

Treatment for adrenocortical carcinoma falls into a handful of categories, and most people receive more than one. Surgery removes the tumor. Mitotane is a drug that acts specifically on adrenal cortex tissue and is the only medicine approved anywhere specifically for ACC. Chemotherapy uses cell-killing drugs, usually in combination with mitotane, for cancer that has spread. Radiation therapy uses focused high-energy beams, sometimes after surgery and often to relieve symptoms. A separate group of medicines does not attack the cancer at all but blocks the hormones it makes.

Which of these you are offered depends mostly on the stage of the adrenal cancer, whether the tumor can be removed completely, whether it makes hormones, how fast it is growing, and your overall health. Roughly half or more of people with ACC already have locally advanced or spread disease when they are diagnosed, which shapes the plan from the start.

For a tumor that is confined to the adrenal gland or the area around it, the plan is usually surgery first, followed by a decision about whether to add mitotane, and sometimes radiation to the area where the tumor was. For a tumor that has already spread, surgery may still play a role in selected situations, but drug treatment carries most of the weight, along with treatments aimed directly at hormone control and comfort.

Local treatments are a middle category worth knowing about. Ablation, which destroys small tumors with heat or cold through a needle, and chemoembolization, which delivers drug directly into the blood supply of liver tumors, can control a small number of spots without a major operation. These are not cures, but they can buy meaningful time and reduce hormone output.

Two categories often get more attention online than they deserve for this disease. Immunotherapy and targeted therapy are exciting fields, and both are being actively studied in ACC. Neither is standard first-line treatment for adrenocortical carcinoma today. They are in clinical trials, and that is a reasonable option worth asking about early rather than at the end.

Finally, supportive and palliative care (providing relief from the symptoms, pain, and stress of a serious illness) is a treatment category in its own right, not a last resort. It can start on the day you are diagnosed and run alongside surgery and chemotherapy.

Surgery

Surgery to remove an adrenal gland is called an adrenalectomy. It can be done two ways. In an open adrenalectomy, the surgeon makes a single larger incision, usually in the abdomen or the flank, and works directly on the tumor. In a laparoscopic or robotic adrenalectomy, the surgeon works through several small incisions using a camera and long instruments. Minimally invasive surgery is wonderful for benign adrenal tumors and for small noncancerous masses, and recovery is faster.

For a tumor that is suspected or known to be adrenocortical carcinoma, open surgery is generally preferred, and this matters more than it might sound. ACC tumors are often large, soft, and fragile. Working through small ports raises the risk of nicking or rupturing the tumor capsule, which spills cancer cells into the abdomen and can turn a curable situation into an incurable one. It also raises the risk of leaving microscopic cancer at the edge. The larger the tumor and the more suspicious the imaging, the stronger the case for an open operation. Standard practice includes removing the gland in one piece, avoiding any tumor spillage, and converting to an open operation if a minimally invasive attempt turns out to be difficult.

Removing the adrenal gland alone is often not enough. Because these tumors grow outward into whatever is next to them, surgeons frequently need to remove neighboring tissue in one connected block, an approach called en bloc resection. That can mean taking the kidney on the same side, part of the liver, part of the diaphragm, the spleen, or part of the pancreas. Nearby lymph nodes, which are small glands that help fight infection and are a common first stop for spreading cancer, are usually removed as well. Retrospective studies have linked systematic lymph node removal with lower recurrence rates and better survival. Sometimes the tumor grows into the inferior vena cava, the large vein returning blood to the heart, and removing it safely requires a vascular or liver surgeon in the room and occasionally bypass. These are exactly the situations where the experience of the center changes what is possible.

The report you get afterward will use the letters R0, R1, and R2, and they are worth understanding in plain language. R0 means the surgeon removed all visible tumor and the pathologist found no cancer cells at the outer edges of what was removed. R1 means all visible tumor was removed, but cancer cells reached the microscopic edge, so some may remain. R2 means visible tumor was left behind. R0 is the goal. If your report says R2 and it is technically possible, a repeat operation is often recommended, because leaving tumor behind carries a poor outlook. Expected mortality from adrenal cancer surgery is under 5%, but that figure varies a great deal with surgical expertise and how sick the patient is. You can read more about staging in HealthTree's Adrenal Cancer Stage Guide.

Recovery from an open adrenalectomy usually means a hospital stay of several days, sometimes longer if the kidney, liver, or a blood vessel was involved. Expect fatigue and incision soreness for weeks, and lifting restrictions for about six weeks. If your tumor was making cortisol, your remaining adrenal gland may be sluggish or asleep for months, so you will very likely go home on steroid pills and a plan to taper slowly. If both glands were removed, hormone replacement is lifelong. That is covered in detail further down.

Surgery is not only for the first operation. When ACC comes back in one place, or has spread to only a few spots, removing those spots can be worthwhile. Metastasectomy, meaning surgical removal of metastases, is most often done for tumors in the liver or lungs, and works best when the disease is limited to one or two organs, is slow-growing, is fully removable, and the person is well enough for the operation. Some centers also use surgery to reduce tumor bulk when severe hormone excess simply cannot be controlled with medicine.

Which brings us to the practical message worth repeating. Ask about a high-volume adrenal center before your first operation, not after. If a first attempt spills tumor, leaves a positive margin, or is done without lymph node removal, the second chance at complete removal is much harder and sometimes gone entirely.

Mitotane

Mitotane, sold under the brand name Lysodren, is unusual. It is the only drug approved specifically for adrenocortical carcinoma by both the United States Food and Drug Administration and the European Medicines Agency. It works by poisoning adrenal cortex cells. It selectively destroys the inner layers of the adrenal cortex and blocks several enzymes the gland needs to make steroid hormones, and it also speeds up how fast the body clears cortisol. So it does two jobs at once. It attacks adrenal cancer cells, and it lowers hormone output.

Mitotane is taken by mouth as tablets, usually several times a day with food that contains some fat, which helps absorption. Doses are much higher than most people expect for a pill, often several tablets at each dose, and they are built up gradually. Your team will adjust your dose based on blood tests rather than on a fixed schedule, taking into account your age, sex, body size, and kidney function.

The blood test that guides everything is the mitotane plasma level. Mitotane is fat-soluble, so it collects in body fat and clears from the body slowly. That combination makes blood level monitoring necessary rather than optional. Levels between roughly 14 and 20 mg/L have been associated with better outcomes, and levels much above that range bring more toxicity without more benefit. Here is the part that frustrates people most: reaching that range commonly takes many weeks to several months of steady dosing and repeated blood draws. It is normal to feel like nothing is happening for a long stretch. It is also normal for the dose to go up and down several times before it settles.

Mitotane causes adrenal insufficiency by design. That is not a side effect to be avoided. It is how the drug works. Because it destroys cortisol-producing tissue and also makes the body clear cortisol faster, everyone on mitotane needs glucocorticoid replacement, usually hydrocortisone, and usually at doses higher than someone with ordinary adrenal insufficiency would need. Some people also need fludrocortisone to replace aldosterone. Replacement is mandatory, not discretionary, and it also reduces the stomach side effects of the drug. If you are on mitotane and you have not been given a steroid plan, a sick day plan, and an emergency injection, ask about all three.

Side effects are common and mostly dose-related. Nausea, loss of appetite, vomiting, and diarrhea are the usual early ones. Fatigue is very common. The nervous system effects are the ones patients tell us they were least prepared for: slowed thinking, word-finding trouble, difficulty concentrating, drowsiness, unsteadiness on the feet, and sometimes slurred speech or double vision. These neurologic effects usually mean the level is too high and usually improve when the dose comes down, or the drug is paused. Mitotane can also raise cholesterol and liver enzymes, lower thyroid hormone, and lengthen bleeding times, so those get checked too.

Drug interactions can be an issue and worth flagging to every prescriber you see, including dentists and urgent care. Mitotane speeds up liver enzymes that break down many other medicines, so it can weaken the effect of hormonal contraceptives, some blood pressure drugs, certain seizure medicines, and others. It interacts with warfarin. Vitamin K supplementation is sometimes recommended. Mitotane can harm a developing pregnancy and stays in body fat long after the last dose, so reliable non-hormonal or backup contraception is advised during treatment and for a long time afterward. Ask your pharmacist to review your full list.

Mitotane is used in two very different settings. As adjuvant therapy, it is given after surgery has removed all visible cancer, to lower the chance of recurrence, usually started within about three months of the operation. As therapy for advanced disease, it is used either alone or, more often, together with chemotherapy. Adjuvant mitotane is generally suggested for people at high risk of recurrence, for example, ENSAT stage III disease, an R1 resection, or a Ki-67 proliferation index above 10%. For people at low risk of recurrence, current guidance makes no recommendation either for or against it. The ADIUVO trial tested adjuvant mitotane against observation in a population that was mostly low risk, defined by R0 resection, no metastases, and Ki-67 under 10%, and did not find a significant difference between the two approaches. That is genuinely a discussion to have with your own team rather than a settled answer.

Chemotherapy

For adrenocortical carcinoma that has spread or cannot be removed, the standard first-line systemic regimen is EDP plus mitotane. EDP stands for three chemotherapy drugs given together: etoposide, doxorubicin, and cisplatin. They are given on top of ongoing mitotane, which is continued by mouth throughout. This combination became standard on the strength of the FIRM-ACT trial, the largest randomized treatment trial ever run in this disease, which compared EDP plus mitotane against streptozocin plus mitotane and found better response rates and longer progression-free survival with EDP plus mitotane.

Even with the best available regimen, responses in ACC are limited, and across collected studies the objective response rate with mitotane-based treatment has been at best around 24%. Chemotherapy for advanced ACC is given to shrink or slow the cancer and to relieve symptoms, not with the expectation of cure. Knowing that up front helps people weigh how much treatment they want and when.

A cycle of EDP plus mitotane typically runs about four weeks. Doxorubicin is given on one day, then etoposide and cisplatin on several consecutive days, usually in an infusion center, with fluids before and after cisplatin to protect the kidneys. Mitotane tablets continue daily the whole time. Blood counts are checked between cycles. Most people receive several cycles, with scans in between to see whether it is working, and treatment continues as long as it helps and side effects stay manageable.

Side effects come mostly from the chemotherapy rather than the mitotane. You can expect

• Nausea (usually controlled with anti-nausea medicines)

• Hair loss

• Mouth sores

• Low blood counts (raises the risk of infection and bleeding)

• Kidney damage (usually caused by Cisplatin)

• Ringing in the ears or hearing loss

• Numbness and tingling in the hands and feet

• Fatigue

• Fertility issues can be affected

• Doxorubicin has a lifetime dose limit because of possible heart effects, so you may have a heart function scan before starting.

If the cancer progresses on first-line treatment, there are further options, though the evidence behind them is thinner. Streptozocin plus mitotane is the usual comparator regimen and a recognized next choice. Other combinations, including gemcitabine-based regimens and drugs used in the metastatic setting, are chosen case by case. At this point, a clinical trial often becomes one of the better available options rather than a fallback, so it is fair to ask about joining a clinical trial for adrenal cancer at each decision point, not just the last one.

Radiation Therapy

Radiation therapy uses precisely aimed high-energy beams to damage cancer cells. It is delivered from a machine outside the body over a series of short daily appointments, usually Monday through Friday for several weeks in the curative setting, or in a much shorter course when the goal is comfort. Planning involves a scan and small skin marks so the beams hit the same place every time.

After surgery, radiation to the tumor bed, meaning the area where the tumor used to sit, is sometimes offered to lower the chance of the cancer coming back in that spot. The evidence here is mixed and comes from small retrospective studies. Some have shown fewer local recurrences with radiation after surgery, and others have not, and no survival benefit has been demonstrated. Because of that, routine radiation after every ACC operation is not recommended. It is considered selectively, most often when the risk of local recurrence looks high, for example after an R1 resection, with a large tumor, or when the tumor capsule was broken.

Radiation has a clearer role in two other situations. When ACC recurs in one local spot, and there is no distant disease, radiation after a repeat operation may help. And for advanced disease, palliative radiation aimed at specific troublesome sites can control symptoms and slow local growth.

Palliative radiation is often the fastest way to relieve certain problems. Bone metastases that hurt frequently respond within days to a couple of weeks, and radiation can also reduce the risk of a bone breaking. Brain metastases are usually treated with focused stereotactic radiosurgery or, when there are many, with whole-brain radiation. Radiation can also shrink a mass that is pressing on the spinal cord, blocking a vessel, or causing bleeding. Short courses, sometimes a single treatment, are common for pain.

Side effects depend entirely on what is being treated. Radiation to the abdomen can cause nausea, loose stools, and skin redness that looks like sunburn. Radiation to bone often causes a temporary flare of pain before it improves. Radiation to the brain causes fatigue and hair loss in the treated area. Fatigue is the one nearly everyone gets, and it typically builds through treatment and fades over several weeks afterward. Radiation does not make you radioactive, and you are safe to be around family and children.

Medicines That Control Hormone Excess

A separate group of drugs exists purely to control the hormones an adrenal tumor makes. These drugs do not shrink the cancer and are not chemotherapy. They exist because uncontrolled hormone excess can hurt you faster than the tumor will, and because feeling human again matters. Treatment with these medicines is usually supervised by an endocrinologist, since they can affect several hormone systems at once and may make it necessary to replace other hormones.

For too much cortisol, the drugs used include metyrapone, ketoconazole, osilodrostat, mifepristone, and, in urgent hospital situations, etomidate. Metyrapone, ketoconazole, and osilodrostat all work by blocking enzymes the adrenal gland uses to build cortisol, and they are adjusted using blood or urine cortisol measurements. Ketoconazole requires liver monitoring and interacts with many drugs. Mifepristone works differently: it blocks the cortisol receptor rather than lowering cortisol, which helps symptoms and blood sugar but means cortisol blood levels no longer tell you whether the dose is right, so it is dosed by how the person is doing clinically.

Etomidate deserves its own note. It is an anesthetic drug that happens to be a powerful, fast blocker of cortisol production. Given as a controlled infusion in an intensive care or high dependency setting, it can bring dangerously high cortisol down within hours. It is reserved for severe, life-threatening hypercortisolism when swallowing pills is not fast enough or not possible.

For too much aldosterone, spironolactone and eplerenone are the mainstays. Both block the aldosterone receptor, which lowers blood pressure and lets potassium come back up. Amiloride is another option. Spironolactone can cause breast tenderness or enlargement and menstrual irregularity, so eplerenone is sometimes chosen instead. Potassium and kidney function are watched closely, especially at the start. Blood pressure medicines are often needed alongside.

Excess androgens or estrogens can also be blocked when they cause distressing symptoms. Drugs used include bicalutamide, finasteride, and spironolactone for testosterone effects, and tamoxifen for estrogen effects. Removing or treating the tumor is the definitive answer, but these can help in the meantime.

Severe cortisol excess is dangerous in its own right. Here are some of the side effects:

• Suppresses the immune system, increasing the likelihood of serious infections, including unusual ones that can be the cause of death in people with hormone-producing ACC.

• It decreases muscle, especially in the thighs and shoulders

• Thins bone so that fractures happen from minor strain

• It thickens the blood and sharply raises the risk of clots in the legs and lungs

• It drives blood sugar and blood pressure up.

• It can cause psychiatric symptoms that patients rarely get warned about, including insomnia, agitation, depression, anxiety, and sometimes frank psychosis.

Bringing cortisol down treats all of that. It also often makes a person well enough to tolerate surgery or chemotherapy that would otherwise be too risky.

Ablation and Other Local Treatments

• Ablation means destroying a tumor in place rather than cutting it out. A radiologist advances a thin needle through the skin into the tumor using CT or ultrasound guidance, usually with sedation, and then delivers energy through the needle tip. Radiofrequency ablation and microwave ablation use heat. Cryoablation uses extreme cold to freeze the tissue. Most people go home the same day or after one night.

• Chemoembolization is a different local technique used for tumors in the liver. A catheter is threaded through an artery in the groin or wrist up into the specific vessels feeding the liver tumors. Chemotherapy is delivered directly into those vessels, and tiny particles are then injected to block the blood supply, trapping the drug where it is needed and starving the tumor. Radioembolization, which uses radioactive beads instead, is used similarly at some centers.

These treatments are considered in specific situations rather than routinely. They are most useful when there are only a few metastases, when those spots are small and reachable, when the disease is otherwise stable, or when the goal is to knock down a hormone-producing deposit that is making someone unwell. They are also an option when a person is not well enough for a major operation, or when surgery has already been used, and a new small spot appears.

Ablation is not a substitute for proper surgery on the primary adrenal tumor. For a tumor still in the adrenal gland that could be removed by an experienced surgeon, an operation gives a chance at cure that ablation does not. Ablation of the primary tumor is generally reserved for people who cannot have surgery.

Risks are usually modest but real, and include pain, bleeding, injury to nearby structures, and a collapsed lung when treating tumors near the diaphragm or in the lung. One risk is specific to adrenal tissue: heating or freezing a hormone-producing adrenal tumor can dump hormones into the bloodstream and cause a spike in blood pressure, so these procedures need a team that knows adrenal disease and is prepared for it.

Immunotherapy

Immunotherapy uses drugs that release the brakes on your own immune system so it can recognize cancer. Checkpoint inhibitors such as pembrolizumab, nivolumab, and avelumab have been tested in adrenocortical carcinoma. Some people did respond, and a few responses lasted, but overall response rates in these studies were modest. Immunotherapy is not standard first-line treatment for ACC. If tumor testing shows features such as high microsatellite instability, mismatch repair deficiency, or a high tumor mutational burden, immunotherapy may be an option under approvals that apply to other cancer types rather than to ACC specifically. This is called off-label treatment. This is uncommon in ACC, but it is a reason to ask whether your tumor has been tested and can be treated with an immunotherapy approved for treating other cancer types. Three common immunotherapies are:

• Pembrolizumab (Keytruda): This anti-PD-1 antibody is the most frequently studied immunotherapy in adrenal cancer. Clinical trials (such as those led by MD Anderson Cancer Center) have shown that it can provide durable, long-term tumor control in a subset of advanced ACC patients. It is sometimes paired off-label with mitotane to boost its efficacy.

• Nivolumab (Opdivo): Another anti-PD-1 checkpoint inhibitor that has been evaluated in phase II clinical trials for advanced rare tumors, showing modest single-agent activity in some adrenal cancer patients.

• Ipilimumab (Yervoy): This is an anti-CTLA-4 antibody. While rarely used on its own for ACC, it is used off-label in combination with Nivolumab (dual checkpoint blockade). Data from rare-cancer trials (like the CA209-538 study) show that combining these two drugs can trigger a significant response, particularly in specific genetic subsets of ACC.

Immunotherapy does not work for every adrenal cancer patient especially if due to high cortisol levels. However, an oncologist is much more likely to prescribe off-label immunotherapy if a patient's genetic tumor profiling reveals certain biomarkers:

1. MSI-H / dMMR (Microsatellite Instability-High / Mismatch Repair Deficient): Tumors with these features cannot properly repair their DNA, making them highly visible to the immune system. Pembrolizumab has a tissue-agnostic FDA approval for any solid tumor that is MSI-H, meaning its use here may technically be "on-label" if the tumor meets this genetic requirement.

2. High TMB (Tumor Mutational Burden): Tumors with a high number of genetic mutations present more targets for the immune system to recognize, making dual immunotherapy (Nivolumab + Ipilimumab) highly effective in documented case studies.

There is also a specific interaction worth knowing. Mitotane speeds up the metabolism of many drugs, and this can affect how some targeted and immune agents behave. Some trials therefore require mitotane to be stopped or its level documented before enrollment. This is a practical detail that can affect your eligibility, so mention your mitotane level when a trial is discussed.

Targeted Therapy

Targeted therapy means drugs aimed at a specific molecular pathway. In ACC, this remains investigational despite a lot of laboratory promise. Early trials targeted the epidermal growth factor receptor with gefitinib and with erlotinib plus gemcitabine. Drugs that block blood vessel growth, such as sunitinib, showed modest activity in phase 2 testing. Combinations aimed at the insulin-like growth factor pathway together with mTOR inhibition produced periods of stable disease in some heavily pretreated patients but few tumor shrinkages. The pattern across all of this is that single agents have not been enough, and trials of newer agents are ongoing.

That is not a reason to dismiss them. It is a reason to pursue them properly, through a clinical trial at a center that runs them, where you get the drug plus careful monitoring plus the chance to help answer the question for the next patient. Because ACC is rare, trials often need to accept patients from far away, and travel support sometimes exists. Ask about trials at diagnosis, at the start of each new treatment, and at every progression, and be a little wary of any clinic offering an unproven therapy for cash outside a registered trial.

What Is Still Investigational or Emerging Off-Label Combinations

Oncologists are also exploring combining immunotherapies with targeted "tyrosine kinase inhibitors" (TKIs) off-label to break down the tumor's defense mechanisms. For example, regimens combining Pembrolizumab with Lenvatinib or evaluated clinical pairings like Cemiplimab (Libtayo) with Cabozantinib are being used to treat aggressive, refractory cases.

To help you understand if you could qualify for one of these treatments, you would need to:

• Undergo genetic tumor profiling (e.g., looking for MSI status or TMB)?

• Know if the tumor is hormone-producing (such as causing Cushing's syndrome or excess cortisol)?

• Have already tried mitotane or standard chemotherapy?

Treatment for Pheochromocytoma and Paraganglioma

Pheochromocytoma is a different adrenal cancer and works differently. It arises from the adrenal medulla, the inner core of the gland, rather than from the cortex. Paraganglioma is the same kind of tumor arising outside the adrenal gland along nerve pathways. Together, they are called PPGL. These tumors make catecholamines, the fight-or-flight hormones adrenaline and noradrenaline, so their symptoms, their tests, their genetics, their staging, their treatment, and their outlook all differ from ACC. Nothing in the ACC sections above should be assumed to apply here.

The most important difference is what has to happen before surgery. Anyone with a hormone-producing pheochromocytoma or paraganglioma needs medical preparation with alpha blockade for a period beforehand, typically one to two weeks or more. Drugs such as phenoxybenzamine or doxazosin block the receptors that catecholamines act on. Alongside this, people are usually asked to increase salt and fluid intake to refill blood volume, and a beta blocker may be added afterward to control heart rate. This sequence is not optional, and the order matters. Handling the tumor during surgery, or even placing a needle in it, can release a surge of catecholamines. Without alpha blockade, that surge can cause a hypertensive crisis, meaning blood pressure high enough to cause stroke, heart failure, dangerous heart rhythms, or death on the operating table. Giving a beta blocker first, before alpha blockade, can make the crisis worse. If you have a pheochromocytoma and surgery is being scheduled without hormone testing and a preparation plan, that is a reasonable moment to ask for an endocrinologist and a second opinion.

Surgery is the main treatment and is often curative for tumors that have not spread. Unlike ACC, a minimally invasive laparoscopic adrenalectomy is frequently appropriate for pheochromocytoma, and for smaller tumors surgeons sometimes spare part of the adrenal cortex, which is especially valuable in people with hereditary syndromes who may need surgery on both sides. Blood pressure is managed minute to minute during the operation, and it can drop sharply once the tumor's blood supply is tied off, so careful monitoring continues afterward. Paragangliomas in the head and neck sit near critical nerves and vessels and are sometimes watched rather than removed, or treated with radiation.

For PPGL that has spread, there are treatment options.

• MIBG therapy uses a molecule that catecholamine-producing cells take up, attached to radioactive iodine, so the radiation is delivered from inside the tumor cells.

• Radioligand therapy works on the same principle using a different target, somatostatin receptors, with lutetium Lu 177 dotatate, and is used for some PPGL at experienced centers.

Both require a scan first to confirm the tumor actually takes up the tracer, because only tumors that do will respond. Which of these is available to you depends on your country, your center, and your tumor's imaging, so ask specifically.

Chemotherapy for advanced PPGL usually means CVD, a combination of cyclophosphamide, vincristine, and dacarbazine. It can shrink tumors and reduce hormone output, and it is often chosen when disease is growing quickly. Targeted drugs including tyrosine kinase inhibitors have shown activity, and agents aimed at the hypoxia pathway are of particular interest because so many PPGLs carry mutations in that pathway. Availability of these differs by country and by center, and much of this work is still happening in trials, so ask your oncologist what is standard where you are treated rather than assuming.

Two more differences matter. Genetics are central in PPGL: a large share of these tumors are hereditary, with mutations in SDHx genes, VHL, RET, and NF1 among others, and genetic testing is recommended for essentially everyone with a PPGL, partly because the specific gene predicts how the tumor is likely to behave and whether relatives need screening. And the outlook is generally better than for ACC. Many PPGLs are cured by surgery, and even metastatic PPGL often grows slowly and can be managed for many years, though SDHB-related disease tends to be more aggressive. People with PPGL also need long-term follow-up with blood or urine metanephrine testing, sometimes for life, because these tumors can return years later.

Treatment for Children with Adrenal Cancer

Adrenocortical carcinoma does occur in children, most often in the first few years of life, and it is not simply adult ACC in a smaller body. Children's tumors more often make androgens, so the first sign is frequently early or unusual sexual development, rapid growth, body hair, or acne in a very young child. Deciding whether a childhood adrenal cortical tumor is benign or malignant is harder than in adults, because the features pathologists rely on behave differently in children.

Surgery is the primary treatment, just as in adults, and the same principle applies with even more force: complete removal in one piece by an experienced surgeon, without rupturing the tumor, offers the best chance of cure. Many children with a completely removed, localized tumor do well with surgery alone and no further treatment. Because these tumors can be fragile and are sometimes large relative to a small child, the operation belongs in the hands of a pediatric surgeon at a center that handles rare pediatric tumors.

Chemotherapy is approached differently in children. Mitotane is used, but dosing in children is its own challenge and requires blood level monitoring by a team familiar with it. Chemotherapy for higher-risk or advanced pediatric ACC often uses cisplatin-based combinations, and children have been enrolled in international pediatric collaborations to build better evidence. Children also tolerate some drugs differently from adults, and long-term effects on growth, puberty, hearing, kidneys, and fertility must be planned for from the start.

Every child with ACC should be treated at a children's cancer center, ideally on a pediatric protocol or clinical trial. This is not simply about having a nicer waiting room. Pediatric protocols pool the small number of cases so that treatment intensity is matched to risk, and they build in surveillance for late effects that a general oncology practice may not track for decades.

Genetic testing is recommended for every child diagnosed with adrenocortical carcinoma, without exception. A large proportion of pediatric ACC is linked to germline TP53 changes and Li-Fraumeni syndrome, and other syndromes, including Beckwith-Wiedemann, are associated as well. This has consequences beyond the child. It affects future cancer surveillance for that child, testing decisions for parents and siblings, and reproductive planning. A genetic counselor should be part of the team from early on. You can read more about the inherited syndromes involved in our guide to risk factors for adrenal cancer.

Side Effects and Life After Adrenal Cancer Treatment

One of the most important things to understand after adrenal surgery is hormone replacement. If one adrenal gland was removed and the tumor was making cortisol, the other gland has usually been idling for months or years and cannot immediately take over. You will go home on hydrocortisone or a similar steroid and taper down slowly under an endocrinologist's guidance, and that taper can take six months to a year or longer. If both adrenal glands were removed, you have permanent adrenal insufficiency and will need glucocorticoid replacement, usually hydrocortisone, and mineralocorticoid replacement, usually fludrocortisone, for the rest of your life. This is manageable, but it is not optional, and it is not something to adjust on your own. People on mitotane typically need higher glucocorticoid doses than usual, because mitotane makes the body clear cortisol faster.

Stress dosing is the part that saves lives, so it is worth learning properly. A healthy adrenal gland pumps out extra cortisol when the body is under stress from illness, injury, or surgery. Yours cannot. So when you are sick, you must temporarily increase your steroid dose, commonly doubling or tripling it for the duration of a fever or infection, and you need a bigger increase for major stress such as an operation. If you are vomiting or have severe diarrhea and cannot keep tablets down, oral dosing will not work, and you need an injection. Every person with adrenal insufficiency should have an emergency hydrocortisone injection kit at home, should be trained to use it, and should have a family member or friend trained too. Carry a medical alert card and wear a bracelet or necklace that says you have adrenal insufficiency and are steroid dependent. Emergency responders cannot guess this, and the card can be the difference in an unconscious patient.

Adrenal crisis is a genuine medical emergency, like a heart attack, and treatment cannot wait. Warning signs include severe weakness, dizziness or fainting, low blood pressure, intense nausea and vomiting, abdominal or flank pain, muscle and joint pain, fever, confusion, and drowsiness sliding toward unresponsiveness. It is often triggered by an infection, a stomach bug, an injury, a missed dose, or surgery without extra steroid cover. The response is to inject hydrocortisone immediately, call emergency services, and say clearly, "This person has adrenal insufficiency and may be in adrenal crisis." Do not wait to see whether it passes. Steroid given unnecessarily to someone who was not in crisis does very little harm. Steroid withheld from someone who was in crisis can be fatal.

Fatigue is the side effect people underestimate most. It can come from the cancer, from surgery, from chemotherapy, from radiation, from mitotane, from steroid replacement that is not quite right, from low thyroid hormone, from anemia, or from all of these at once. Some of those causes are fixable, so persistent exhaustion deserves a workup rather than acceptance. Gentle graded activity, protecting sleep, and pacing genuinely help. So does asking your endocrinologist to review the timing and dose of your steroid replacement, since taking too little, or taking it too late in the day, are both common and correctable causes of feeling wiped out.

Many people on mitotane describe a mental fog: slower thinking, trouble finding words, losing the thread mid-sentence, difficulty with numbers or driving directions, and physical unsteadiness. It can affect work performance and confidence. These effects are usually dose-related and usually improve when the level comes down, so report them promptly rather than pushing through. Ask for a level check. Write things down, use lists and phone reminders, and tell close colleagues or family what is going on so they are not left guessing. If your work involves driving, machinery, or high-stakes decisions, discuss that with your team.

If you had months or years of cortisol excess before diagnosis, your body will need time to recover, and the timeline is longer than most people expect. Muscle strength in the thighs and shoulders comes back slowly and needs active rebuilding, ideally with physical therapy rather than on your own. Bone density improves gradually and often needs vitamin D, calcium, a bone density scan, and sometimes bone-strengthening medicine. Skin thinning, easy bruising, and stretch marks fade but do not fully disappear. Blood sugar and blood pressure often improve. Expect the recovery to unfold over one to two years, not weeks, and expect to feel worse before better as your cortisol level drops toward normal, since the body has adapted to high levels and going down feels like withdrawal.

Fertility and sexual function matter and are often skipped in the rush of treatment. Cisplatin and other chemotherapy drugs can damage fertility in both women and men, sometimes permanently, and mitotane can affect hormone levels and is unsafe in pregnancy. If having children in the future is something you might want, ask about fertility preservation, such as sperm banking or egg or embryo freezing, before treatment starts, because the window closes quickly. Hormone excess and its correction also affect sex drive, erectile function, vaginal dryness, and menstrual cycles. These are treatable problems. Bring them up, and if your oncologist seems uncomfortable, ask for a referral to a specialist in sexual health or reproductive endocrinology.

Body image changes are real in both directions. Hormone-driven changes such as facial rounding, weight redistribution, increased body hair, acne, hair loss on the scalp, voice deepening in women, or breast growth in men often improve after the tumor is treated, but they improve unevenly and slowly. Some changes, particularly voice deepening, may not fully reverse. Meanwhile, you may be dealing with a long scar, surgical numbness, steroid-related weight change, and hair loss from chemotherapy. It is completely normal to grieve the way you looked and to feel like a stranger in the mirror. Mental health support helps here, and so does connecting with other people who have been through it. Anxiety, depression, and fear of recurrence are common after adrenal cancer, and hormone shifts amplify all of them. Ask for a referral to a psycho oncology counselor, and know that our guide to adrenal cancer support lists places to find other patients and families.

Supportive and Palliative Care for Adrenal Cancer

Palliative care is specialized medical care focused on relieving symptoms and improving quality of life for people with serious illness. That is the whole definition. It is delivered by a team that usually includes doctors, nurses, social workers, chaplains, pharmacists, dietitians, and mental health professionals, and it works alongside your cancer treatment rather than replacing it. Palliative care can and should start at diagnosis, while you are pursuing surgery, mitotane, and chemotherapy with the goal of cure or long-term control.

Palliative care is not hospice. This confusion causes real harm, because people decline a referral that would have made them feel better. Hospice is one specific kind of palliative care, provided when cancer treatment aimed at the cancer itself is no longer being pursued, and life expectancy is expected to be short. Palliative care is the much broader category and has no requirement about prognosis or stopping treatment. You can receive palliative care for years while on active chemotherapy. Accepting a palliative care referral says nothing about how your doctors expect things to go.

Pain control is a core part of it. Adrenal cancer pain can come from a large tumor pressing on the flank or belly, from bone metastases, from surgery, or from chemotherapy-related nerve damage. Options run from ordinary pain relievers through opioids, nerve-targeted medicines, radiation to a painful spot, nerve blocks, and physical therapy. Untreated pain does not make anyone stronger. It worsens sleep, appetite, mood, and function, and it is almost always improvable.

Managing hormone symptoms is palliation in its own right for this disease, which is something unique to adrenal cancer. Bringing down high cortisol or high aldosterone can transform how someone feels even when it does nothing to the tumor. Better sleep, less muscle weakness, less swelling, better blood sugar, steadier mood, fewer infections, lower blood pressure, and normal potassium all follow. This is why an endocrinologist should stay involved throughout, including in advanced disease. Endocrine support also covers getting steroid replacement dialed in, checking thyroid function, and keeping the stress dosing plan current.

Nutrition support is practical and often needed. High cortisol changes appetite and where the body stores fat, muscle wasting means protein needs go up, chemotherapy causes nausea and taste changes, and both steroids and the disease can raise blood sugar. Aldosterone excess brings potassium and salt questions. A dietitian who works with cancer patients can help you eat enough protein, manage nausea, and handle these specific issues instead of guessing from the internet. Be cautious about supplements, which can interact with mitotane and other drugs.

Mental health care, social work, and financial navigation round out the team. Social workers help with transportation to a distant high-volume center, lodging, medical leave paperwork, disability applications, insurance appeals, and drug assistance programs. Mitotane and specialty medicines can be expensive, and manufacturer or foundation assistance programs often exist but require someone to find and file them. Ask early for a social worker or financial navigator rather than waiting for a bill you cannot pay. Caregivers need support too, and most palliative care teams will care for them alongside you.

Follow-Up Care After Treatment Ends

Follow-up after adrenal cancer treatment is more intensive than for many cancers, because ACC can come back and because early detection of a single recurrence sometimes allows another attempt at removal. A commonly used schedule, reflected in published reviews, is follow-up every three months for the first two years, then every six months until year five, then once a year after that. Some centers extend intensive imaging longer, and children are typically followed on a pediatric protocol schedule. Your own schedule may differ based on your stage, your margin status, and your Ki-67, so ask for your plan in writing.

Each visit usually combines imaging with hormone tests. Imaging generally means a CT scan of the chest, abdomen, and pelvis, since the lungs, liver, and the area around the original tumor are the most common places for ACC to return. MRI or PET scans are used in particular situations. Hormone markers are followed for any hormone your tumor was making at diagnosis, since a rising level can flag recurrence before it is visible on a scan. That may include cortisol and dexamethasone suppression testing, DHEA sulfate and other androgens, estradiol, aldosterone and renin, and steroid precursors. If you have PPGL rather than ACC, follow-up centers instead on plasma or urine metanephrines, sometimes for life.

If you are taking mitotane, its blood level is checked regularly and indefinitely while you remain on it, usually along with liver enzymes, cholesterol, thyroid function, and blood counts. Levels drift over time as body composition and other medicines change, so this is ongoing rather than a one-time calibration. Report new unsteadiness, confusion, or slurred speech promptly, since these often mean the level has climbed too high.

Watching for adrenal insufficiency continues at every visit whether or not you are on mitotane. Your team should check that your steroid dose still fits, confirm your stress dosing plan, confirm your emergency injection has not expired, and make sure your medical alert card is current. If you had one gland removed, your remaining gland's function may be tested periodically to see whether replacement can be reduced or stopped. Do not stop steroids on your own based on feeling well.

A survivorship care plan is a written summary of exactly what treatment you had, including drug names, total doses, radiation fields, and surgical details, plus your follow-up schedule and what late effects to watch for. It matters because you will see other doctors over the years who need this information. Late effects to keep on the radar include heart function after doxorubicin, hearing and kidney function and nerve damage after cisplatin, bone density after cortisol excess and steroid use, thyroid changes, fertility, and second cancers, which is particularly relevant for anyone with an inherited syndrome such as Li-Fraumeni who needs lifelong cancer surveillance of their own. If genetic testing has not happened yet, follow-up is a good time to revisit it.

Some things should not wait for the next appointment. Call your care team urgently, or seek emergency care, for any of the following: symptoms of possible adrenal crisis such as severe weakness, vomiting, dizziness, confusion, or collapse; fever or signs of infection, especially while on chemotherapy or high-dose steroids; new or worsening flank, belly, back, or bone pain; sudden shortness of breath, chest pain, or a swollen painful leg, which can signal a blood clot; new or rapidly returning hormone symptoms such as fast weight gain, muscle weakness, or blood pressure spikes; new confusion, unsteadiness, or slurred speech while on mitotane; a new headache with vision changes or a seizure; and inability to keep down your steroid tablets for any reason. Keep your team's after-hours number where you can find it, and keep a current medication list with you.

Between visits, the ordinary things still help. Keep moving as much as your energy allows, eat enough protein, keep vaccinations current since immune suppression is a real issue with hormone-producing tumors, avoid tobacco, and keep your dental and primary care up to date. If a scan or a symptom worries you, say so rather than waiting. Every plan described here is a general pattern, and only your own care team can tell you how it applies to your situation.

Sources:

• Adrenocortical Carcinoma Treatment (PDQ) Patient Version, National Cancer Institute

• Adrenocortical Carcinoma Treatment (PDQ) Health Professional Version, National Cancer Institute

• Childhood Adrenocortical Carcinoma, National Cancer Institute

• Childhood Adrenocortical Carcinoma Treatment (PDQ) Health Professional Version, National Cancer Institute