Acknowledgement of Adrenocortical Carcinoma has not been added yet.

Adrenocortical carcinoma is a rare disease only diagnosed in about 1 in 1 million people every year. It is more commonly diagnosed in women than in men. About 50% of cases of adrenocortical carcinoma are caused by inherited genetic mutations that increase a person’s risk of developing cancer.

Name	Abbreviation
	ACC

The exact cause of adrenocortical carcinoma is unknown. There are many genetic mutations that affect protein tumor suppressors and proteins that control cell growth. When these no longer function properly, cells start to grow without proper control. This out-of-control growth causes cancerous tumors to develop, and when these occur in the adrenal cortex, it causes adrenocortical carcinoma. 

Certain heritable diseases may increase an individual’s risk of developing adrenocortical carcinoma. This does not necessarily guarantee that an individual with these diseases will get this type of cancer, but it can increase the chances. These genetic conditions may not be due to inherited mutations, and can also occur spontaneously in individuals whose parents do not have the mutation: 

1. Li-Fraumeni syndrome - Mutations occur in the p53 gene that acts as a tumor suppressor, and loss of function leads to uncontrolled cell growth. This disease has an autosomal dominant inheritance pattern and increases the likelihood of developing cancer by 70% in males and by 90% in females.

2. Beckwith-Wiedemann syndrome - A genetic alteration on the 11p15 chromosome location causes an overgrowth of cells or tumor predisposition that may result in early childhood development of adrenocortical carcinoma (ACC).

3. Carney complex - An inactivating mutation of the PRKAR1A gene leads to a lack of functional signals in the cell that tell it to stop dividing when something is wrong. If left unchecked, the cell will grow and divide out of control and form a cancerous tumor. 

4. Lynch syndrome - An inherited disorder that increases one’s likelihood of developing cancer, most commonly colorectal cancer. 

5. Multiple endocrine neoplasia (MEN1) - A rare disorder that causes tumor development in the endocrine glands, which increase hormone levels released to other parts of the body. This can cause an overproduction of adrenal hormones and lead to similar disease phenotypes as ACC. 

6. Neurofibromatosis Type 1 (NF1) - A rare disease caused by mutations in the NF1 gene that prevents proper formation of the neurofibromin protein, which is a tumor suppressor. Without this tumor suppressor, tumors such as neurofibromas can form in the body. 

7. Von Hippel-Lindau (VHL) syndrome - A rare disease caused by mutations in the VHL gene which encodes the VHL protein. The VHL protein regulates cell division and survival, and without it the cells can grow and divide without regulation. 

8. Familial adenomatous polyposis (FAP) - A rare disease caused by mutations in the APC gene that can lead to the development of precancerous polyps.

The presence of a cancerous tumor in the adrenal cortex may cause physical symptoms and symptoms associated with higher levels of adrenal hormones. The physical symptoms may include a lump in the abdomen, pain in the abdomen or back, or feeling full. Individuals with nonfunctional adrenocortical carcinoma (ACC) may not experience many symptoms and may have to rely on detecting the physical presence of a tumor for diagnosis. Individuals with functional adrenocortical carcinoma (ACC) release a high amount of adrenal hormones, and depending on the hormone type this can cause a variety of symptoms to emerge:

1. High cortisol:

• weight gain in face, neck, and midsection

• hair growth on face, upper back, or arms

• appearance of round, red, full face

• lump of fat on the back of neck

• deepened voice

• muscle weakness

• high blood sugar, high blood pressure

2. High aldosterone:

• High blood pressure

• Muscle weakness or cramping

• Frequent urination

• Thirst

3. High testosterone:

• Hair growth on face, upper back, or arms

• Appearance of acne

• Balding or loss of hair

• Deepened voice

• In biological females, this can lead to a lack of menstrual periods

4. High estrogen:

• In biological females, this can lead to irregular periods, vaginal bleeding, and weight gain.

• In biological males, this can lead to growth of breast tissue, lowered libido, and possible impotence.

Virilization is the most common symptom of ACC, most obvious in women, producing excess facial and body hair, acne, enlargement of the clitoris, deepening of the voice and cessation of menstruation. In men, estrogen excess is noted, leading to breast enlargement, decreased libido and impotence. Cushing’s Syndrome occurs in approximately one third of cases, signs of which include moon-like faces, centripetal fat distribution and plethora.

Depending on the type of adrenocortical carcinoma, functioning or nonfunctioning, an individual may not experience symptoms that prompt a physical examination. Physical signs of growth such as the appearance of a lump or abdominal pain may prompt an individual to seek medical examination. Diagnostic tests can include a combination of physical exams, tests for hormonal levels, and imaging and scans.

Hormonal syndromes should be confirmed with laboratory testing. Radiological studies of the abdomen, such as CT scans and magnetic resonance imaging are useful for identifying the site of the tumor, differentiating it from other diseases, and determining the extent of invasion of the tumor into surrounding tissues.

Most diagnostic tests for adrenocortical carcinoma are imaging scans designed to detect tumors and other cancers. Some are physical examinations and hormone level tests designed to detect abnormalities in the adrenal glands. Below is a list of the most common diagnostic tests for ACC:

• Physical examination: An individual may be checked for lumps, asked about their medical history and medications, and/or family history of certain genetic conditions that may predispose them to cancer development and/or adrenocortical carcinoma.

• Urine test: Measuring an individual’s cortisol levels will assess whether they have risen or lowered abnormally as a sign of a malfunctioning adrenal gland.

• Dexamethasone suppression test: An individual will be administered dexamethasone and then their blood/urine tested for resulting cortisol levels. These will be compared to healthy standards to determine if their cortisol levels are abnormal.

• CT/CAT scan: This is an imaging technique that collects different images at different angles of the body to show the organs and tissues clearly to reveal any lumps. 

• MRI: The use of radio waves to scan the body and detect abnormal masses. 

• Adrenal angiography/venography: To determine the health and function of the adrenal glands, an individual will be injected with a contrast dye near the adrenal glands to track the flow of blood into (angiography) and away from (venography) the adrenal glands. The dye levels are measured via x-rays and compared to healthy standards of blood flow. 

• PET scan: An individual will be injected with a small amount of glucose which will migrate to areas of the body that are growing and burning energy at the fastest rate, therefore revealing tumors when scanned. 

• MIBG scan: The radioactive material MIBG will be injected and detected to determine a diagnosis of adrenocortical carcinoma vs. pheochromocytoma (two different adrenal gland cancers that have different forms of treatment). 

• Biopsy: A small amount of the tissue or tumor in question can be removed during surgery to examine for signs of cancer.

Treatments for adrenocortical carcinoma depend on the aggressiveness and severity of the cancer. The three main procedures to target and remove cancerous cells are the following:

1. Surgery - removal of the cancerous tumor.

2. Chemotherapy - the use of drugs to kill cells or stop them from dividing and forming tumors; often used in combination with surgery when cancer has spread to other parts of the body.

3. Radiation - the use of x-rays administered either from the outside or inside the body to target the cancer tumor for destruction.

Other more experimental treatments may be prescribed on an individual, case-by-case basis when the other treatments fail to remove the tumor or cannot be performed for other reasons:

1. Immunotherapy - targeting cancer cells with the body’s own immune cells so that it recognizes them as a foreign antigen for destruction.

2. Targeted therapy - repairing the gene mutation associated with the tumor suppressor gene using targeted gene therapy.

Because adrenocortical carcinoma is a type of cancer, an individual’s prognosis depends on the stage the cancer has progressed to by the time it is discovered. The stage of the cancer is usually determined by the size of the tumor and whether the cancerous cells have spread and started growing in other parts of the body (metastatic). Other factors can influence a person’s prognosis and treatment options for adrenocortical carcinoma, including whether the tumor is localized to the adrenal cortex and can be removed, the patient’s overall health, and the appearance or aggressiveness of the cancer cells. Individuals who are younger or whose tumors are still small have a better prognosis. If the adrenocortical carcinoma (ACC) is characterized by a larger tumor and/or has spread, the five year survival rate for the individual with ACC is between 36%-46%.

Tips or Suggestions of Adrenocortical Carcinoma has not been added yet.

1. https://www.cancer.gov/types/adrenocortical/patient/adrenocortical-treatment-pdq#:~:text=Adrenocortical%20carcinoma%20is%20a%20rare,include%20pain%20in%20the%20abdomen.

2. https://my.clevelandclinic.org/health/articles/6152-adrenocortical-carcinoma

3. https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-endocrine-tumor/adrenocortical-carcinoma

4. https://www.hopkinsmedicine.org/health/conditions-and-diseases/adrenocortical-carcinoma

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490795/

6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900890/#:~:text=Li%2DFraumeni%20Syndrome%20(LFS),is%20commonly%20associated%20with%20LFS.

7. https://pubmed.ncbi.nlm.nih.gov/31588532/#:~:text=The%20majority%20of%20childhood%20ACC,embryonal%20tumors%20and%20childhood%20ACC.

8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739861/ 

9. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/multiple-endocrine-neoplasia-type-2-syndrome

10. https://medlineplus.gov/genetics/condition/neurofibromatosis-type-1/#causes

11. https://medlineplus.gov/genetics/condition/von-hippel-lindau-syndrome/#causes

12. https://rarediseases.org/rare-diseases/familial-adenomatous-polyposis/#:~:text=Familial%20adenomatous%20polyposis%20(FAP)%20is,at%20a%20relatively%20young%20age.