Adrenocortical Carcinoma (ACC): Types, Symptoms and Treatment

Table of Contents

What is Adrenocortical Carcinoma (ACC)?

Adrenocortical carcinoma (ACC) is malignant cancer in the adrenal cortex, the outer layer of our adrenal glands. The adrenal glands are located just above the kidneys.
Adrenocortical carcinoma is a rare type of cancer occurring in one in a million people. However, the seriousness of this cancer demands adequate prevention, diagnosis and timely treatment.
There are basically two types of adrenocortical carcinoma;
- Functioning Adrenocortical Carcinoma
- Non- functioning Adrenocortical Carcinoma

What are the Differences Between Benign and Malignant Adrenocortical Tumors?

There are multiple differences between benign and malignant adrenocortical tumors.
The differences mainly lie on the basis of nature, spread to other organs, growth behaviour, invasion of the tissues, symptoms, hormone production, diagnosis, treatment approach etc.
In benign adrenocortical tumor, there is a non-cancerous growth of the adrenal cortex which does not spread outside the adrenal gland. It does not have any symptoms and remains in the inactive form and generally diagnosed by chance only.
On the other hand, in malignant adrenocortical tumor, there is a cancerous growth of the adrenal cortex which can grow fast and spread to the nearby tissues. Its symptoms are generally noticeable and are diagnosed easily often due to large size/symptoms.

Basis	Benign Adrenocortical Tumor (Adenoma)	Malignant Adrenocortical Tumor (Carcinoma)
Nature	Non-cancerous growth of the adrenal cortex	Cancerous growth of the adrenal cortex
Spread to other organs	Does not spread outside the adrenal gland	Can spread to nearby tissues and distant organs
Growth behaviour	Usually grows slowly	Often grows fast and aggressively
Invasion of nearby tissue	Remains confined to the adrenal gland	Can invade surrounding organs
Symptoms	Often causes no symptoms	More likely to cause noticeable symptoms
Hormone production	May produce hormones or may be inactive	Often produces excess hormones
Effect of hormone excess	Hormonal symptoms may occur but are usually mild	Hormonal symptoms are often severe
Diagnosis/Detection	Commonly found by chance during scans	Often found due to symptoms or large size
Treatment approach	Observation or surgery if needed	Surgery and additional cancer treatment
Outcome	Very good outcome after treatment	Outcome depends on stage and spread

Epidemiology of ACC

How Rare Is Adrenocortical Carcinoma?

Adrenocortical carcinoma is an uncommon type of cancer. Among children, it makes up about one percent of all cancer cases.
In adults, it is even rarer, accounting for only a very small fraction, approximately 0.02% to 0.2% of all cancer diagnoses.

Who are mainly affected by Adrenocortical carcinoma?

Adrenocortical carcinoma (ACC) tends to occur mainly at two stages of life. It is more commonly seen in very young children, especially those under five years of age, and in adults between their forties and fifties.
This cancer affects females more often than males, indicating a higher occurrence among women.

What causes Adrenocortical Carcinoma?

Genetic Syndromes Linked to Adrenocortical Carcinoma (ACC)

Adrenocortical carcinoma (ACC) is very rare, but certain inherited genetic syndromes can increase the risk of developing this cancer.
Around 10–15% of ACC cases are associated with hereditary genetic conditions.
Li-Fraumeni syndrome is the strongest genetic risk factor for ACC.
- It is caused by mutations in the TP53 gene, which normally controls cell division and prevents tumour formation.
- When TP53 is altered, cells can grow without control, raising the risk of many cancers, including ACC.
- This syndrome is especially important in children, making it the most common inherited cause of paediatric ACC.
Beckwith-Wiedemann syndrome is linked to abnormal gene regulation on chromosome 11p15.5, which affects growth control.
- Children with this condition have a higher risk of embryonal tumors, including ACC.
Familial adenomatous polyposis (FAP) results from mutations in the APC gene.
- These mutations activate the Wnt/β-catenin signaling pathway, leading to excessive cell growth and an increased risk of ACC.
Carney complex is a rare inherited disorder involving multiple endocrine abnormalities.
- It has been occasionally associated with ACC, although this link is uncommon.

What are the Sign and Symptoms of ACC?

Major signs and symptoms of ACC are:

Weight gain
Muscle weakness
Round face (moon face), easy bruising
Fatigue
High blood pressure
Muscle cramps
Low potassium levels
Facial hair growth in women
Voice deepening
Breast development in men
Early puberty
High blood pressure
Increased risk of infections
Osteoporosis
Electrolyte imbalance

Hormone-Related Symptoms of Adrenocortical Carcinoma (ACC)

Many adrenocortical carcinomas produce excess hormones, leading to noticeable symptoms.

Excess Hormone	Associated Condition	Key Signs and Symptoms
Cortisol	Cushing syndrome	Weight gain, muscle weakness, round face (moon face), easy bruising, fatigue
Androgens / Estrogens	Sex hormone excess	Early puberty, facial hair growth in women, voice deepening, breast development in men
Aldosterone	Hyperaldosteronism	High blood pressure, low potassium levels, muscle cramps

What are the physical changes seen in ACC?

Fat pad on the back of the neck (buffalo hump)
Excess hair growth (hirsutism) or acne, especially in women
Menstrual irregularities in women
Voice deepening or virilization in women
Muscle weakness
Rounded face (moon face)
Central weight gain / abdominal obesity

What are the metabolic changes during ACC?

High blood sugar or development of diabetes
Insulin resistance
Electrolyte imbalance
Low potassium levels (hypokalemia)
Protein breakdown/muscle wasting
Bone thinning or osteoporosis
Increased risk of infections
High blood pressure

How is Adrenocortical Carcinoma (ACC) Diagnosed?

Laboratory and Hormone Tests

Blood tests
Cortisol tests: 24-hour urine, blood, or saliva tests; sometimes a dexamethasone suppression test is done.
Androgen or Estrogen level test

Imaging tests

Computed tomography (CT)
Magnetic resonance imaging (MRI)
Positron emission tomography (PET)

Tumor Staging and Grading

TNM Staging of Adrenocortical Carcinoma

Stage I:

Tumor is 5 cm or smaller.
Found only in the adrenal gland.

Stage II:

Tumor is larger than 5 cm.
Still only in the adrenal gland.

Stage III:

Tumor can be any size.
Has spread either to nearby lymph nodes or to nearby organs (like kidney, liver, pancreas, spleen, diaphragm) or large blood vessels.

Stage IV:

Tumor can be any size.
May involve nearby lymph nodes.
Has spread to distant organs (like lungs, bones, or the lining of the abdomen).

How can Adrenocortical Carcinoma (ACC) be treated?

Surgery as the Primary Treatment

Adrenocortical carcinoma is commonly treated through adrenalectomy, which involves removing the affected adrenal gland. In some cases, the surgery may also include the removal of nearby lymph nodes and surrounding tissues where the cancer may have spread.
Open surgery is considered the standard approach for patients with confirmed or strongly suspected adrenocortical carcinoma (ACC).
For smaller tumors under 6 cm without evidence of local spread, laparoscopic adrenalectomy may be appropriate.

Mitotane Therapy

Mitotane is the main drug used to treat adrenocortical carcinoma (ACC).
It blocks adrenal hormone production and kills adrenal cancer cells.
Often given after surgery to remove any tiny leftover cancer cells and reduce the chance of recurrence.
Used for unresectable, recurrent, or metastatic tumors to shrink or control cancer growth.
Especially helpful in controlling hormone-related symptoms, even if the tumor size doesn’t decrease.
Taken orally 3–4 times daily and requires close monitoring for side effects and dose adjustments.
Plays a key role in both disease control and improving patient quality of life.

Chemotherapy and Radiation: When Are They Used?

Radiation therapy and chemotherapy are used to treat cancer depending on its type, stage, and location.

Radiation therapy uses high-energy rays to kill or control cancer cells and can be delivered externally, using a machine outside the body, or internally, by placing radioactive materials directly near the tumour.
Chemotherapy uses drugs to stop cancer cell growth, either throughout the body (systemic) or in a specific area (regional). Both treatments are selected based on how the cancer is progressing, its spread, and the overall treatment plan, sometimes using a combination of drugs for better effectiveness.

Public Health & Awareness

Why Early Detection/diagnosis is Difficult?

Early detection of adrenocortical carcinoma is difficult because it is a very rare cancer and there is no routine screening. Many people have no symptoms in the early stage. When symptoms appear, they are unclear and similar to common health problems, which can delay diagnosis. Some tumors do not produce hormones, so early warning signs may be missing. As a result, many cases are found by chance during imaging done for other medical reasons.

Why is Specialist Care needed for ACC?

Surgeries performed by surgeons with experience in adrenal and oncologic procedures lead to lower recurrence rates and longer recurrence-free survival (RFS).
High-volume centers (HVCs) and specialized surgeons are associated with improved survival, lower recurrence, and delayed time to recurrence.

What are the survival rates and prognosis of ACC?

About half of the people diagnosed with adrenocortical carcinoma are still alive five years after their diagnosis. However, survival rates can differ widely based on several factors such as the stage of the tumor when diagnosed, whether the tumor produces hormones, age of the patient, and overall health.

Five-Year Survival Rates by Stage

Stage of ACC	Five-Year Survival Rate
Stages I & II	74%
Stage III	54%
Stage IV	38%

Source: Cleveland Clinic

Long-Term Monitoring After Treatment

ACC has a high risk of recurrence even after complete surgical removal, so structured long-term follow-up is essential for early detection of recurrence.
Regular follow-up typically includes hormone testing and cross-sectional imaging (e.g., CT or MRI) to monitor for biochemical changes and tumor regrowth.

References

Public Health Notes

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