Adrenocortical carcinoma (ACC)
What is Adrenocortical carcinoma?
Adrenocortical carcinoma (ACC) is a rare and aggressive cancer that develops in the outer layer (cortex) of the adrenal glands, which sit above the kidneys. This malignancy affects approximately 1-2 people per million annually worldwide, making it one of the rarest endocrine cancers. ACC can occur at any age but shows two peak incidence periods: in children under 5 years and adults between 40-50 years. The tumor often produces excess hormones, leading to distinctive symptoms, though some cases may be non-functioning and detected only when the mass becomes large enough to cause physical symptoms.
Key statistics
| Annual incidence | 1-2 cases per million people |
| Age distribution | Bimodal: children |
| 5-year survival rate | 35-50% (varies by stage at diagnosis) |
| Gender ratio | Slightly more common in women (1.5:1 ratio) |
Symptoms
Hormone-related symptoms: Cushing’s syndrome, virilization, feminization, hypertension, muscle weakness
Physical symptoms: Abdominal pain, palpable mass, rapid weight gain or loss, purple stretch marks
The symptoms of ACC depend largely on whether the tumor produces hormones and which hormones are involved. Functioning tumors, which occur in 60-70% of cases, cause distinctive hormonal syndromes. Cushing’s syndrome is the most common presentation, characterized by rapid weight gain, purple stretch marks, muscle weakness, high blood pressure, and mood changes. Virilization occurs when the tumor produces excess male hormones, causing deepening voice, excessive body hair, and male-pattern baldness in women. Less commonly, feminization can occur in men due to excess estrogen production.
Non-functioning tumors may remain silent until they grow large enough to cause abdominal pain, a palpable mass, or pressure on surrounding organs. Some patients experience rapid progression of symptoms over weeks to months, which often prompts earlier medical attention. Constitutional symptoms like fatigue, weight loss, and fever may also occur, particularly in advanced cases.
Causes and risk factors
Most cases of ACC are sporadic with no clear environmental cause, but genetic factors play a significant role. Approximately 10-15% of cases are associated with hereditary cancer syndromes, most notably Li-Fraumeni syndrome caused by mutations in the TP53 gene. Other genetic syndromes linked to ACC include Beckwith-Wiedemann syndrome, multiple endocrine neoplasia type 1 (MEN1), and familial adenomatous polyposis.
Known risk factors include previous radiation exposure, particularly in childhood, and certain genetic conditions. A family history of cancer, especially at young ages, may indicate an inherited predisposition. Environmental factors have not been clearly established, though some studies suggest potential links to tobacco use and certain chemical exposures, but evidence remains limited.
Prevention
There are no established methods for preventing ACC, as most cases occur sporadically without identifiable environmental triggers. However, genetic counseling and testing are crucial for families with hereditary cancer syndromes, particularly Li-Fraumeni syndrome. Individuals with known genetic predispositions may benefit from enhanced surveillance protocols, though specific screening recommendations for ACC are not well-established due to its rarity.
For families affected by ACC, genetic testing can help identify at-risk relatives and inform family planning decisions. Prenatal genetic testing is available for known familial mutations. While routine screening for the general population is not recommended, awareness of symptoms is important for early detection.
Complications
Without treatment, ACC typically progresses rapidly with local invasion and distant metastases, most commonly to the liver, lungs, and lymph nodes. The aggressive nature of this cancer means that delays in diagnosis and treatment significantly impact outcomes. Hormonal complications can be life-threatening, including severe Cushing’s syndrome leading to diabetes, osteoporosis, and increased infection risk.
Advanced disease may cause organ dysfunction due to tumor mass effect or metastases. Adrenal insufficiency can develop if both adrenal glands are affected. Treatment complications may include side effects from chemotherapy and hormone replacement needs after surgery.
Diagnosis
Diagnosis requires a combination of clinical assessment, biochemical testing, and imaging studies. Initial evaluation includes comprehensive hormone testing, measuring cortisol, aldosterone, androgens, and their precursors in blood and urine. The dexamethasone suppression test helps confirm autonomous hormone production.
Imaging studies begin with CT or MRI of the abdomen to characterize the adrenal mass, assess local invasion, and detect metastases. Chest imaging is essential to evaluate for pulmonary metastases. FDG-PET scanning may help distinguish malignant from benign lesions and identify distant disease.
Biopsy is generally avoided due to the risk of tumor seeding, except in cases where metastatic disease is present and tissue diagnosis would change management. The Weiss criteria, based on histological features, help pathologists distinguish ACC from benign adrenal adenomas when tissue is available.
Treatment
Complete surgical resection remains the primary treatment for localized ACC and offers the best chance for cure. This typically involves adrenalectomy with removal of surrounding tissue and lymph nodes when indicated. In cases of local invasion, en bloc resection of involved organs may be necessary.
Mitotane is the primary medical therapy for ACC, functioning both as adjuvant treatment after surgery and for advanced disease. This medication selectively targets adrenal tissue but requires careful monitoring due to significant side effects and drug interactions.
Chemotherapy combinations, typically including etoposide, doxorubicin, and cisplatin (EDP) with or without mitotane, are used for advanced or metastatic disease. Radiation therapy may be employed for local control or palliation of metastatic sites. Hormone replacement therapy is often necessary after bilateral adrenalectomy or in cases of adrenal insufficiency.
Prognosis
The prognosis for ACC varies significantly based on the stage at diagnosis and completeness of surgical resection. For localized disease that can be completely resected, 5-year survival rates range from 60-80%. However, for advanced or metastatic disease, 5-year survival drops to 10-20%.
The European Network for the Study of Adrenal Tumors (ENSAT) staging system helps predict outcomes, with stage I and II tumors having substantially better prognosis than stages III and IV. Complete surgical resection (R0 resection) is the most important prognostic factor. Age, tumor size, and hormonal activity also influence outcomes.
Quality of life
Living with ACC requires ongoing medical management and lifestyle adaptations. Patients on mitotane therapy need regular monitoring and may experience gastrointestinal side effects, requiring dietary modifications and supportive care. Those requiring hormone replacement must maintain consistent medication schedules and carry emergency supplies.
Physical activity should be tailored to individual capacity, with attention to bone health if Cushing’s syndrome was present. Nutritional support may be needed to address treatment-related side effects or hormonal imbalances. Mental health support is crucial, given the psychological impact of a rare cancer diagnosis and uncertain prognosis.
Regular follow-up care includes imaging studies, hormone level monitoring, and symptom assessment. Patients should be educated about signs of disease recurrence and adrenal crisis, which requires emergency treatment.
Pregnancy and fertility
ACC during pregnancy is extremely rare but presents significant challenges for both mother and fetus. Hormonal changes of pregnancy can complicate diagnosis, and treatment decisions must balance maternal and fetal risks. Surgery may be feasible during the second trimester, while chemotherapy is generally avoided during the first trimester.
Fertility may be impaired by hormonal imbalances caused by functioning tumors or as a result of treatment with chemotherapy. Genetic counseling is essential for patients with hereditary forms of ACC to discuss inheritance risks and reproductive options.
Children
Pediatric ACC has distinct characteristics, with a higher likelihood of being associated with genetic syndromes, particularly in very young children. The clinical presentation often includes virilization and rapid growth, making early recognition possible. Treatment principles are similar to adults, though chemotherapy protocols may differ.
Long-term follow-up is crucial in pediatric survivors to monitor for late effects of treatment, including secondary cancers, growth and development issues, and fertility concerns. Psychosocial support for both children and families is an essential component of care.
When to see a doctor
Urgent medical attention is needed for rapidly developing Cushing’s syndrome symptoms, severe abdominal pain, or a palpable abdominal mass. Signs requiring immediate care include severe muscle weakness, uncontrolled high blood pressure, signs of adrenal crisis (severe fatigue, nausea, low blood pressure), or rapid onset of virilization.
Routine medical evaluation should be sought for gradual onset of unexplained weight gain, new stretch marks, muscle weakness, or changes in body hair distribution. Family members of patients with hereditary cancer syndromes should discuss genetic counseling and testing with their healthcare providers.
Regional context
Limited data exists on ACC prevalence specifically in the Caucasus region (Georgia, Armenia, Azerbaijan) and Eastern Mediterranean countries. The rarity of this condition makes regional epidemiological studies challenging. We invite healthcare professionals and researchers from these regions to contribute their experiences and data to the Global Medical Journal to better understand regional variations in ACC presentation and outcomes.
Research and clinical trials
Current research focuses on identifying new therapeutic targets, improving surgical techniques, and developing more effective chemotherapy combinations. Immunotherapy approaches are being investigated, including checkpoint inhibitors and tumor vaccines. Molecular profiling of tumors aims to identify personalized treatment strategies.
Recent studies have explored the role of IGF-1 receptor inhibitors and other targeted therapies. Research into the genetic basis of sporadic ACC continues to reveal new insights into tumor biology. Patients and families are encouraged to explore clinical trial opportunities through ClinicalTrials.gov and specialized cancer centers.
Frequently asked questions
Is ACC hereditary?
Most cases are sporadic, but 10-15% are associated with genetic syndromes like Li-Fraumeni syndrome. Genetic testing is recommended for young patients or those with family cancer history.
Can ACC be cured?
Complete cure is possible with early detection and complete surgical removal. However, the aggressive nature of ACC means that early diagnosis and treatment are crucial for optimal outcomes.
What are the side effects of mitotane?
Common side effects include nausea, diarrhea, skin rash, and neurological symptoms. Regular monitoring is required, and the medication interacts with many other drugs.
How often should I be monitored after treatment?
Follow-up typically involves imaging every 3-6 months initially, then less frequently over time. Hormone levels and symptoms are monitored regularly throughout survivorship.
Can I have children after ACC treatment?
Fertility may be affected by the tumor itself or treatment. Genetic counseling is important for hereditary cases. Fertility preservation options should be discussed before treatment when possible.
Support and resources
- Orphanet – orpha.net – Rare disease information portal
- National Organization for Rare Disorders (NORD) – rarediseases.org
- EURORDIS – eurordis.org – European rare disease organization
- Adrenal Gland Tumor Support Group – Patient support and information
- ClinicalTrials.gov – clinicaltrials.gov – Clinical trial information
Related conditions
- Li-Fraumeni syndrome
- Cushing’s syndrome
- Pheochromocytoma
- Adrenal adenoma
- Beckwith-Wiedemann syndrome
Sources: Orphanet (orpha.net), OMIM, GeneReviews (NCBI), WHO ICD-11, relevant guidelines. Informational only; not medical advice. CC BY 4.0.
Cite this page
GMJ News Desk. “Adrenocortical carcinoma.” GMJ News — Georgian Medical Journal, 2 June 2026. https://news.gmj.ge/condition/adrenocortical-carcinoma/
Licensed under CC BY 4.0. Free to share with attribution to GMJ News.Sources: Orphanet (orpha.net), OMIM, GeneReviews (NCBI), WHO ICD-11, EULAR/ACR guidelines. Schema.org MedicalCondition structured data included.
Was this article helpful?