Adrenocortical carcinoma (Adrenal cortical carcinoma) is a malignant tumor originating from the shell of the adrenal glands (also known as “cortex”) – triangular shaped glands located above the kidneys. The cortex of the adrenal gland produces important hormones that help the body regulate water balance, blood pressure, stress reactions, and more, and even has an effect on sex hormones. The cancerous tumor may be a functional tumor, meaning that it produces more hormone than usual, or non-functional – without any effect on hormone production. Often these tumors produce in excess the hormones cortisol, aldosterone, testosterone and estrogen. Adenocortical carcinoma is a very rare disease, and may develop in adults and children. Its incidence is 1-2 per million, with women being more likely to get it.
What causes the disease?
The reasons for the development of adenocortical carcinoma are not fully known, and in most cases the disease develops spontaneously. However, people with certain genetic syndromes have a higher risk of developing it. In fact, studies show that in 50% of cases, it is a cancer that “runs” in families. Accordingly, it has been shown that mutations in genes associated with specific syndromes play a significant role in the onset of cancer. For example, families with family members with Li-Fraumann syndrome, caused by a mutation in the TP53 gene, have an increased risk of developing the disease. Also, among people who have had this cancer, the loss or reduced activity of various genes may occur, such as genes that are important for the growth and development of the fetus in the womb.
What are the signs and symptoms of the disease?
The symptoms of adenocortical carcinoma are often caused by excess production of hormones or as a result of the tumor pressing on organs. Symptoms usually include pain in the stomach or back, and a feeling of fullness in the stomach. A non-functioning tumor may not cause signs or symptoms in the early stages – indeed, in about half of the patients, the symptoms do not appear until the tumor is large enough and pressing on nearby organs.
In a functioning tumor, excess production of cortisol and aldosterone may cause high blood pressure, high blood sugar, weight gain in the face, neck and chest and abdomen, irregular menstruation, light bruises on the skin, depression, urinary frequency and muscle cramps. A tumor that produces excess estrogen in women will cause irregular periods and weight gain, while in men it will lead to enlarged or more sensitive breasts and damage to the sexual drive and fertility. A tumor that produces excess testosterone in women may cause increased hair growth in the facial area, acne, as well as changes in the voice and making it deeper. Men with a tumor that produces too much testosterone usually have no signs or symptoms. Children may present with excessive growth of hair in the pubic area, face and armpits, enlarged genitalia and early development of sex signs.
Who is at risk of the disease?
People with certain inherited genetic conditions have a higher risk of developing adrenal gland cancer. Genetic conditions that increase the risk of cancer include, but are not limited to: Beckwith-Wiedmann syndrome, Li-Fraumann syndrome, Kerney syndrome, familial adenomatous polyposis, Lynch syndrome, multiglandular syndrome, neurofibromatosis type 1, and von Hippel-Lindau disease. It is important to note in this context that the patients with adenocortical carcinoma may have one of these syndromes, so genetic counseling and genetic tests are important for them and their family members. Also, studies show that smoking is a risk factor for the development of this cancer.
What is the treatment for the disease?
Treatment usually includes surgery to remove the tumor. The goal of the surgery is to remove the entire tumor, and for this the surgeon must remove the entire damaged adrenal gland. If the doctor finds evidence that cancer has spread to nearby structures, such as the liver or kidney, some or all of these organs may also be removed during surgery. A relatively old drug used to treat advanced adrenal cortex cancer shows promising results in delaying the recurrence of the disease after surgery. It is given after surgery, mainly to patients with a high risk of cancer recurrence. Radiation therapy is sometimes used after surgery to remove the tumor to kill any cells that may have remained. In addition, the radiation may help reduce pain and other symptoms, in cases of generalized cancer. Also, chemotherapy may be a therapeutic option to slow down the progression of cancer, in cases of a tumor that cannot be removed by surgery or a tumor that returns after another primary treatment.
