Adrenocortical Carcinoma


What is Adrenocortical Carcinoma?

Adrenocortical Carcinoma (ACC) is a malignant, or cancerous, tumor that starts in the adrenal glands. ACC may produce any hormone that is made by the cortex adrenal glands. These include glucocorticoids (cortisol), androgens (progesterone), and mineralcorticoids (aldosterone).

How rare is ACC? 

ACC is a rare condition. It represents only 0.3% of all adrenal tumors, and only 3% are cancerous. In endocrinology, ACC is the most common malignant adrenal tumor. It represents 4% of all adrenal tumors treated by endocrinologists. 

Who is predisposed to developing ACC?

ACC presents in bimodal pattern, in the very young in the first decade of life and again in adults.   In adults, ACC is slightly more predominant in female patients (60-65%), with a median age of diagnosis at age 50. Certain genetic syndromes or conditions predispose to ACC, including Li-Fraumeni syndrome, Lynch Syndrome and Beckwith-Wiedemann syndrome.

In children almost 80% occurs in the setting of genetic syndromes – most notably Li-Fraumeni syndrome.

How is ACC diagnosed? 

A few cases of ACC are diagnosed incidentally, or by chance. In 40% of cases, doctors may find the tumor when imaging is performed for reasons that are unrelated to the adrenal mass. A third of patients may have overt hormone excess, that result in hirsutism (excessive growth of male pattern hair that appear on the face, back, chest, abdomen, and thighs in women), hypertension, acne in women, and/or features of cortisol excess -  Cushing Syndrome

There are many tests that can be done to facilitate the diagnosis of ACC:

  1. Most important is the radiologic assessment with an imaging procedure - usually a CT scan or MRI
  2. Hormonal testing in blood or urine can support diagnosis
  3. Physical exam can support diagnosis
  4. While we usually do not biopsy adrenal masses - microscopic assessment following surgical removal remains the gold standard.

What are the symptoms of ACC? 

The symptoms of ACC will vary, based on the size of the tumor and hormonal secretion. Many patients may be asymptomatic or have no symptoms. Some patients may have mild symptoms at the time of diagnosis. 

If the adrenal mass is large, it may cause pain or abdominal discomfort. When presenting with symptoms of hormone excess, symptoms may include those of Cushing Syndrome in both men and women. Common symptoms of Cushing Syndrome are weight gain, thin bones, and high blood pressure. When there is too much androgen production, men are usually asymptomatic, but women may develop features of androgen excess. This may include acne, hirsutism, amenorrhea, and alopecia, a condition that occurs when the immune system attacks the hair follicles and leads to hair loss. When aldosterone secreting, patients may have low potassium and hypertension that is resistant to multiple medications.

Adrenal nodules are common, up to 7% of the population. Nodule is another word for lump, bump, lesion or tumor. These terms do not equate with cancer. ACC is extremely rare and sometimes “looks” similar to other non-cancerous conditions on imaging.  Moreover, ACC commonly presents with hormone excess, most notably Cushing Syndrome. Cushing Syndrome is a hormonal condition that also occurs in benign conditions such as adrenal adenoma or hyperplasia.  

What are the stages of ACC? 

The most common staging system used in ACC is ENSAT staging, which includes four stages. Tumor sizes are often measured in centimeters 

1 cm tumor

Size of a pea

 2 cm tumor

Size of a peanut

 3 cm tumor

Size of a grape

 4 cm tumor

Size of a walnut

 5 cm tumor

Size of a lime

 6 cm tumor

Size of an egg

 7 cm tumor

Size of a peach

 10 cm tumor

Size of a grapefruit

Stage 1: A tumor less than 5 cm without any affected lymph nodes or spreading to other parts of the body (metastases). 

Stage 2: A tumor larger than 5 cm without any affected lymph nodes or spreading to other parts of the body. 

Stage 3: ACC with some tumor infiltration in surrounding tissue or invasion in adjacent tissue, but without affected lymph nodes or spreading to other parts of the body.

Stage 4: Metastatic ACC or spread outside of the adrenal glands. 

What treatment options are available? 

  • Surgery
  • Mitotane therapy/Lysodren 
  • Local therapies: Radiation, radiofrequency ablation
  • Chemotherapy (cytotoxic therapy)

Surgery is the only therapy sometimes in patients with Stage 1 and 2 cases. This is known as an open adrenalectomy, which is done by an experienced adrenal surgeon.

Lysodren, also known as mitotane therapy, is a prescription medication used to treat ACC. It is the only approved treatment by the FDA for advanced stages of ACC.

Other than mitotane, the combination of etopiside, doxorubicin and cisplatin is the most frequently used cytrotoxic chemotherapy regimen for advanced ACC.ACC Infographic Image

New treatment options 

Several other therapeutic approaches/medication combinations based on the emerging genetics of the disease are currently being tested. However, the progress in treatment of ACC, like most rare diseases is slow.

Are there potential side effects to treatment or medication options?

There are side effects to Lysodren and chemotherapy. Common side effects of Lysodren are:

  • Anorexia
  • Diarrhea
  • Nausea and vomiting
  • Rash

What types of providers should patients have on their health care team?

ACC is a rare cancer and should always be treated only in centers with high levels of expertise. Usually, patients need a multidisciplinary team of providers: endocrinologist, adrenal surgeon, radiation oncologist, endocrine pathologist, cancer geneticist and a medical oncologist with experience in treating ACC.

Given the initial surgery is the only way to assure the best prognosis. Referral to a center needs to happen before surgery (and not after).

Questions to ask your healthcare provider: 

  • What type of surgery do I need? What type of provider should conduct the surgery?
  • Where can I receive expert care for ACC?
  • What are the indications for mitotane? What are the side effects? 
  • How can I improve my prognosis? 
  • What type of hormones does my ACC secrete? Do I need treatment for it? 
  • Do I have a genetic predisposition for ACC?
The development of this resource was made from the generous support of our sponsor HRA Pharma Rare diseases
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