Glossary

Short term for Adrenocortical Carcinoma, meaning Adrenal Cancer.

Adrenocortical carcinoma (ACC) is a rare tumor that affects only 0.72 persons per one million. Although it mainly occurs in adults, children can be affected, too. The median age at diagnosis is 46 years. Historically, only about 30% of these malignancies are confined to the adrenal gland at the time of diagnosis. However, recently, more ACCs have been diagnosed at early stages, most likely due to the widespread use of high-quality imaging techniques.

In approximately 60% of patients, symptoms related to excessive hormone secretion are the main reasons for seeking medical attention. Biochemical hormone testing reveals that up to 80% of tumors are functioning. The second most common symptoms at time of initial presentation are unspecific abdominal symptoms, such as abdominal pain or fullness. A small percentage of ACCs is discovered incidentally by imaging studies conducted for reasons other than potential adrenal disease.

Source: https://www.cancer.gov/types/adrenocortical/hp/adrenocortical-treatment-pdq

Adrenocorticotropic hormone (ACTH) is a hormone that stimulates the production of cortisol. Cortisol is a steroid hormone made by the adrenal glands that is important for regulating glucose, protein, and lipid metabolism, suppressing the immune system’s response, and helping to maintain blood pressure.

ACTH is produced by the pituitary gland. Located below the brain in the center of the head, the pituitary gland is part of the endocrine system, a network of glands that work together to produce hormones that act on organs, tissues, and other glands to regulate systems throughout the body.

An increased ACTH result can mean that a person has Cushing syndrom, Addison disease, overactive, tumor-forming endocrine glands (multiple endocrine neoplasia), or ectopic ACTH-producing tumors.

A decreased ACTH result can be due to an adrenal tumor, steroid medication, or hypopituitarism.

Source: https://labtestsonline.org/tests/adrenocorticotropic-hormone-acth#:~:text=Adrenocorticotropic%20hormone%20(ACTH)%20is%20a,helping%20to%20maintain%20blood%20pressure

This is a rare disorder of the adrenal glands. It occurs when the body doesn’t produce enough of certain hormones (often cortisol and aldosterone). It occurs in ACC patients having their adrenal gland(s) removed and undergoing treatment like Mitotane (that suppresses the function of adrenal glands). As a result, treatment to supplement the missing hormones that the body can no longer produce is required as long as needed. Patients suffering from adrenal insufficiency must be aware and look out for the signs of adrenal crisis.

An adrenal crisis is the result of an extreme physical or emotional stress that does not get the necessary steroid coverage to meet that stress. It is a potentially life-threatening medical emergency that requires management in a hospital or emergency department . Or it might require an emergency injection of hydrocortisone (called Solu-cortef). Check with your medical team.

Learn to recognize the signs of a potential adrenal crisis (see below) so you can avoid it.

• Hyperpigmentation of exposed and non-exposed parts of the body
• Extreme weakness
• Salt craving
• Unintentional weight loss
• Loss of appetite
• Chronic diarrhea
• Nausea/vomiting

Source: https://www.nadf.us/emergency-handout.html

You should also learn what kind of physical or emotional stress can induce a crisis. Some are straightforward suach as surgery, a severe flu, or dental work but some can vary from person to person (emotional shock, heat wave…)

Everyone has 2 adrenal glands. They are small, about the size of a walnut, and shaped like a pyramid. They sit on top of each kidney. They are sometimes called "supra-renal glands" which is Latin for "above the kidney".

What do the adrenal glands do? The adrenal glands may be small, but they play an important role in the way you think and feel. The adrenal glands are organs that make and secrete hormones. The hormones produced by these small powerhouses affect the way every tissue, organ and gland in your body works. Each adrenal gland is made up of 2 parts: an inner area called the medulla, and an outer area called the cortex. The adrenal glands play an important role in how your body responds to stress.

Source: https://www.rogelcancercenter.org/files/adrenal-patient-handbook.pdf

Drawing from: http://surrenales.aphp.fr/

An adrenalectomy is surgery to remove one or both adrenal glands. Most adrenal tumors are noncancerous (benign). You may need surgery (adrenalectomy) to remove an adrenal gland if the tumor is producing excess hormones or is large in size (more than 2 inches or 4 to 5 centimeters). If you have a cancerous tumor, you also may need an adrenalectomy. You may also need an adrenalectomy to remove cancer that has spread from another location, such as the kidney or lung.

If both adrenal glands are removed, you’ll need to take hormone medications. If only one gland is removed, the remaining gland will take over if you don’t need any kind of treatment.

Source: https://www.mayoclinic.org/tests-procedures/adrenalectomy/about/pac-20385243

Adrenaline is a hormone released from the adrenal glands that prepares your nervous system to fight or flee, and your body makes it in response to a stressor or threat. It’s an amazing thing to have coursing through your system when facing danger—people have been known to lift cars off children and run faster than they ever had due to adrenaline. It increases the flow of blood to muscles, releasing sugar into your bloodstream, along with a cascade of other effects that make your body alert and more able to fight off an attacker or outrun a flood.

Source: https://www.endocrineweb.com/adrenaline

This affects the body’s ability to regulate blood pressure. It sends the signal to organs, like the kidney and colon, that can increase the amount of sodium the body sends into the bloodstream or the amount of potassium released in the urine. The hormone also causes the bloodstream to reabsorb water with the sodium to increase blood volume. All of these actions are integral to increasing and lowering blood vessels. Indirectly, the hormone also helps maintain the blood’s pH and electrolyte levels.

Source: https://www.hormone.org/your-health-and-hormones/glands-and-hormones-a-to-z/hormones/aldosterone

BWS arises from epigenetic changes or genetic mutations in genes that regulate growth, particularly on chromosome 11p15. This region contains genes such as IGF2 and H19, which play a crucial role in cell proliferation.
ACC occurs in association with BWS but is significantly rarer than other tumors. Children with BWS have an increased risk of developing tumors, including ACC, particularly in early childhood. Therefore, close monitoring is recommended during the first 8 years of life.

The removal of cells or tissues for examination by a pathologist. The pathologist may study the tissue under a microscope or perform other tests on the cells or tissue. In case of ACC, the mass must be studied only after removal to avoid the risk of spreading potentially tumorous cells in the body.

Source: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/biopsy

An X-ray image made using a form of tomography in which a computer controls the motion of the X-ray source and detectors, processes the data, and produces the image.

It’s your body’s main stress hormone. It works with certain parts of your brain to control your mood, motivation, and fear. Your adrenal glands make cortisol. It’s best known for helping fuel your body’s “fight-or-flight” instinct in a crisis, but cortisol plays an important role in a number of things your body does. For example, it:

– Manages how your body uses carbohydrates, fats, and proteins.
– Keeps inflammation down.
– Regulates your blood pressure
– Increases your blood sugar (glucose)
– Controls your sleep/wake cycle.
– Boosts energy so you can handle stress and restores balance afterwards.

Your hypothalamus and pituitary gland — both located in your brain — can sense if your blood contains the right level of cortisol. If the level is too low, your brain adjusts the amount of hormones it makes. Your adrenal glands pick up on these signals. Then, they fine-tune the amount of cortisol they release.
Cortisol receptors — which are in most cells in your body — receive and use the hormone in different ways. Your needs will differ from day to day. For instance, when your body is on high alert, cortisol can alter or shut down functions that get in the way. These might include your digestive or reproductive systems, your immune system, or even your growth processes.

Source : https://www.webmd.com/a-to-z-guides/what-is-cortisol

– High cortisol : see Cushing syndrome
– Low cortisol: see Adrenal insufficiency

Cushing syndrome occurs when your body has too much of the hormone cortisol over time: your body might produce too much cortisol. This can result also from taking oral corticosteroid medication. Too much cortisol can cause some of the hallmark signs of Cushing syndrome — a fatty hump between your shoulders, a rounded face, and pink or purple stretch marks on your skin. Treatments for Cushing syndrome can return your body’s cortisol levels to normal and improve your symptoms. The earlier treatment begins, the better your chances for recovery.

Source: https://www.mayoclinic.org/diseases-conditions/cushing-syndrome/symptoms-causes/syc-20351310

This blood test is often done for women who seem to have too many male hormones. It can also be done when a woman has a low sex drive and when a boy starts puberty too early.

DHEA stands for dehydroepiandrosterone. This is a hormone found in the adrenal glands, above the kidneys. DHEA helps to make other hormones, like testosterone in men and estrogen in women. Your natural DHEA levels are highest when you’re a young adult. They get lower as you age. In your adrenal glands and liver, DHEA changes to DHEA-S (DHEA-sulfate).

The DHEA-S test is done to check whether your adrenal glands are working well. It measures the amount of DHEA-S in your bloodstream.
In women, high DHEA-S levels can cause symptoms like:

– No menstrual periods
– A lot of body and facial hair
– Lots of acne
– Hair loss
– Fertility problems
– Other traits usually found in men, including a deep voice, lack of breasts, male pattern baldness, and a large Adam’s apple
– More muscle

Too much DHEA may not be as noticeable in men. High levels of DHEA-S in children can cause boys and girls to get pubic or underarm hair early.

Source: https://www.webmd.com/healthy-aging/aging-dhea-test#1

Standard chemotherapy protocol dedicated to advanced ACC. It stands for etoposide, doxorubicin, cisplatin. Often associated with Mitotane, this regimen is known to be the most effective chemotherapy at the moment.

see FLUDROCORTISONE

A corticosteroid, which is used to help control the amount of sodium and fluids in your body. It is used to treat Addison’s disease and syndromes where excessive amounts of sodium are lost in the urine. It works by decreasing the amount of sodium that is lost (excreted) in your urine.

Source: https://medlineplus.gov › druginfo › meds

Refer to the drawing below to see where the adrenal glands, pituitary gland and thyroid gland are located.

Source: https://www.mountsinai.org/health-library/diseases-conditions/adrenocortical-carcinoma?_ga=2.107125313.255792733.1627598727-1373815667.1627598727

Hormones are your body’s chemical messengers. They travel in your bloodstream to tissues or organs. They work slowly, over time, and affect many different processes, including:

– Growth and development
– Metabolism – how your body gets energy from the foods you eat
– Sexual function
– Reproduction
– Mood

Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, thymus, thyroid, adrenal glands, and pancreas. In addition, men produce hormones in their testes and women produce them in their ovaries.

Hormones are powerful. It takes only a tiny amount to cause big changes in cells or even your whole body. That is why too much or too little of a certain hormone can be serious. Laboratory tests can measure the hormone levels in your blood, urine, or saliva. Your health care provider may perform these tests if you have symptoms of a hormone disorder. Home pregnancy tests are similar – they test for pregnancy hormones in your urine.

Source: https://medlineplus.gov/hormones.html

see HYDROCORTISONE

Hydrocortisone, a corticosteroid, is similar to a natural hormone produced by your adrenal glands. It is often used to replace this chemical when your body does not make enough of it.

Source: https://medlineplus.gov/druginfo/meds/a682206.html

Known as one of the most powerful tools to predict the risk of recurrence and therefore patients’ survival. It is to be included in standard work-up of ACC patients. There are three levels of Ki67, expressed in percentages. The greater the number is, the worse the prognosis.

– grade 1 tumors with Ki67 <10%
– grade 2 with Ki67 10–19%
– grade 3 tumors with Ki67 ≥20%

Source : Adrenocortical carcinoma: differentiating the good from the poor prognosis tumors

Laparoscopy refers to using multiple small incisions to perform surgery with tools. Laparotomy is a single large incision that allows the surgeon to access the tumor directly and remove it by hand. You might hear surgery ‘en bloc’ in medical articles. It leaves a L-shaped scar on the abdominal region.

In case of ACC suspicion, recommendation is to perform a laparotomy if the mass is over 6cm. However, this point is still under debate and your medical team's recommendation may differ according to your case.

LFS is closely associated with mutations in the TP53 gene, which plays a central role in controlling cell division and cell death. When TP53 is mutated, the body's ability to repair cell damage is significantly impaired, leading to a greatly increased susceptibility to many types of cancer.
In LFS, ACC tends to occur during childhood. About 6–13% of children with LFS develop ACC, often between the ages of 1 and 4.

Lynch syndrome is typically characterized by mutations in mismatch repair genes, such as MLH1, MSH2, MSH6, and PMS2. These genes are responsible for repairing DNA damage that occurs during cell division.
Lynch syndrome is primarily associated with an increased risk of colorectal and endometrial cancers. There are relatively few cases of ACC in patients with Lynch syndrome.

See Mitotane

MITOTANE (brand name: Lysodren^®): Mitotane is an antitumoral medicine. It used to treat the symptoms of adrenal cortical carcinoma (cancer of the outer layer of the adrenal gland). Mitotane is used when the cancer is inoperable, metastatic or recurrent malignant tumours of the adrenal glands¹ . Mitotane affects the adrenal glands where some hormones are produced and impacts the way cortisol is processed in other parts of the body.²

It is thought Mitotane works by selectively destroying cancer cell in the adrenal cortex. Mitotane inhibits the production of adrenal hormones.³ It can take several weeks to several months for Mitotane to reach the appropriate blood levels needed to destroy the cancer cells. The effects of Mitotane are reversible, but the drug can stay in the bloodstream for weeks following discontinuation of taking the drug.¹

1 Package leaflet Lysodren EU
2 Lysodren US PI
3 Hinojosa-Amaya JM et al., Drugs. 2019;79(9):935-956

You can also refer to https://www.rogelcancercenter.org/files/adrenal-patient-handbook.pdf, page 21-22 and 23 for more details

A short term often used by doctors in certain countries and that you will find commonly used by ACC groups.

A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

Source: https://www.cancer.gov/types/adrenocortical/patient/adrenocortical-treatment-pdq#_1

Cancer cells show up as bright spots on PET scans because they have a higher metabolic rate than do normal cells. PET scans may be useful in:

– Detecting cancer
– Revealing whether your cancer has spread
– Checking whether a cancer treatment is working
– Finding a cancer recurrence

Source: https://www.mayoclinic.org/tests-procedures/pet-scan/about/pac-20385078

This is a small, bean-shaped gland situated at the base of your brain, somewhat behind your nose and between your ears. Despite its small size, the gland influences nearly every part of your body. The hormones it produces help regulate important functions, such as growth, blood pressure and reproduction.

Source: https://www.mayoclinic.org/diseases-conditions/pituitary-tumors/symptoms-causes/syc-20350548#:~:text=The%20pituitary%20gland%20is%20a,growth%2C%20blood%20pressure%20and%20reproduction.S

Solu-Cortef is indicated for any condition in which rapid and intense corticosteroid effect is required such as primary or secondary adrenocortical insufficiency.

Source: https://www.medicines.org.uk/emc/medicine/7833#gref

Steroids are a man-made version of chemicals, known as hormones, that are made naturally in the human body. Steroids are designed to act like these hormones to reduce inflammation.

They’re also known as corticosteroids, and are different to anabolic steroids used by bodybuilders and athletes. Steroids won’t cure your condition, but they’re very good at reducing inflammation and will ease symptoms such as swelling, pain and stiffness.

Source: https://www.versusarthritis.org/about-arthritis/treatments/drugs/steroids/

The thyroid is a butterfly-shaped gland that sits low on the front of the neck. Your thyroid lies below your Adam’s apple, along the front of the windpipe. The thyroid has two side lobes, connected by a bridge (isthmus) in the middle. When the thyroid is its normal size, you can’t feel it.

Brownish-red in color, the thyroid is rich with blood vessels. Nerves important for voice quality also pass through the thyroid. The thyroid secretes several hormones, collectively called thyroid hormones. The main hormone is thyroxine, also called T4. Thyroid hormones act throughout the body, influencing metabolism, growth and development, and body temperature. During infancy and childhood, adequate thyroid hormone is crucial for brain development.

Source: https://www.webmd.com/women/picture-of-the-thyroid

The Weiss score is the reference method to distinguish between a benign and a malignant adrenocortical tumor. It includes nine criteria. If a Weiss score is above 3 it means that the mass is cancerous and the diagnosis of ACC can be established. Scores of 2 and below define the adrenal adenoma (benign mass), even if sometimes a Weiss score of 2 can be suspicious. It is to be included in standard work-up of ACC patients, but is not used by every medical team or in every country.

Source: https://www.tribvn-hc.com/wp-content/uploads/2016/11/Adrenocortical-Tumors-Improving-the-Practice.pdf