A diagnosis of Adrenocortical Carcinoma (ACC), a rare and aggressive cancer originating in the adrenal glands, is challenging and often requires complex, specialized care. ACC is unique because the tumor can cause symptoms both by its physical size and by overproducing hormones like cortisol, which leads to physical changes such as rapid weight gain, high blood pressure, and severe muscle weakness. Dealing with these dramatic hormonal shifts on top of a cancer diagnosis can be incredibly taxing on a patient’s daily routine and quality of life. 

Treatment is essential to control the tumor’s growth and, equally important, to manage the dangerous effects of hormone excess, which can cause metabolic crises. Because ACC is aggressive, a multidisciplinary approach combining surgery with specialized medications is vital. The choice of drugs depends critically on whether the disease is localized, has spread, or whether the hormones are severely elevated (National Cancer Institute, 2024). 

Overview of treatment options for Adrenocortical Carcinoma 

The primary treatment for localized ACC is surgical removal of the tumor. However, given the high risk of recurrence, systemic therapy (medication) plays a major role, used both after surgery (adjuvant therapy) and as the main treatment for advanced or metastatic disease. 

The main goals of medication are twofold: to directly target and destroy the adrenal cancer cells, and to counteract the excess hormones produced by the tumor. The drugs used are highly specialized. Unlike many common cancers, the medical management of ACC is highly specialized and often centered around one unique drug, Mitotane, which directly attacks the adrenal tissue. Medications are often used to reduce symptoms even before or during chemotherapy. 

Medications used for Adrenocortical Carcinoma 

1. Adrenolytic Agents (Mitotane): Mitotane is the cornerstone of ACC medical therapy. It is often prescribed after surgery to prevent recurrence (adjuvant treatment) or as the primary systemic treatment for advanced tumors. Its success relies on maintaining high levels in the bloodstream over many months. Clinical experience suggests that Mitotane prolongs disease-free survival when used adjuvantly in patients with high risk of recurrence. 

2. Cytotoxic Chemotherapy: For rapidly growing or metastatic ACC, chemotherapy is typically used, often in combination with Mitotane. A common regimen includes the drugs etoposide, doxorubicin, and cisplatin (known as the EDP regimen). These combinations aim to shrink the tumor and slow disease progression when surgical options are exhausted. 

3. Hormone Blockers and Steroid Replacement: Since many ACC tumors overproduce cortisol, medications are used to suppress this excess production and control symptoms like high blood pressure and muscle wasting. Steroid synthesis inhibitors, such as ketoconazole or metyrapone, block the enzymes the adrenal gland uses to make cortisol. Conversely, because Mitotane destroys healthy adrenal tissue, patients treated with it often require lifelong hormone replacement therapy (e.g., hydrocortisone) to prevent adrenal insufficiency (Endocrine Society, 2020). 

How these medications work 

Mitotane is unique in that it is an adrenolytic agent, meaning it specifically causes the necrosis (death) of the cells in the adrenal cortex, including the cancerous cells. It disrupts the machinery of the adrenal gland, causing the tumor tissue to slowly atrophy. 

Chemotherapy drugs are cytotoxic; they interfere with the process of cell division (DNA replication) in all rapidly dividing cells, including cancer cells. The combination of drugs is designed to hit the cancer from multiple angles, maximizing cell death. 

Hormone blockers provide relief by directly interfering with the body’s synthesis pathway. For example, ketoconazole inhibits key enzymes necessary to produce cortisol, while other drugs may block the cortisol receptors on target tissues, preventing the excess hormone from causing damage. 

Side effects and safety considerations 

Mitotane requires close management due to severe side effects like GI issues (nausea, vomiting, diarrhea) and neurological symptoms (dizziness, fatigue). Because Mitotane destroys the adrenal gland, steroid replacement therapy must begin immediately to prevent a life-threatening adrenal crisis.  

Chemotherapy risks include bone marrow suppression, high fatigue, and temporary hair loss. Patients on these therapies need frequent blood monitoring for Mitotane levels and to ensure balanced steroid replacement. Hormone replacement therapy must never be stopped abruptly; immediate medical care is needed for severe vomiting, fever, or signs of adrenal crisis (extreme weakness, dizziness, collapse) (Mayo Clinic, 2023). 

Since everyone’s experience with the condition and its treatments can vary, working closely with a qualified healthcare provider helps ensure safe and effective care. 

References 

1. American Cancer Society. https://www.cancer.org 

2. Endocrine Society. https://www.endocrine.org 

3. Mayo Clinic. https://www.mayoclinic.org 

4. National Cancer Institute. https://www.cancer.gov