Adrenocortical Carcinoma: An Overview of Pathogenesis and Clinical Management

January 13, 2024by Dr. Shehrezad Czar0

Adrenocortical carcinoma (ACC) is a rare and aggressive cancer originating in the adrenal cortex, a part of the adrenal gland responsible for producing several important hormones. This comprehensive overview covers the pathogenesis, clinical presentation, diagnosis, and management of ACC, providing valuable insights for both medical professionals and those seeking to understand this complex disease.


Adrenocortical carcinoma is a malignancy of the adrenal cortex, the outer layer of the adrenal glands, which are located above the kidneys. The adrenal cortex produces essential hormones like cortisol, aldosterone, and androgens. The pathogenesis of ACC involves genetic and molecular factors that lead to uncontrolled cell growth in the adrenal cortex.

Genetic Factors

Several genetic alterations have been linked to the development of ACC. These include mutations in the TP53 gene, overexpression of the insulin-like growth factor 2 (IGF2), and alterations in the Wnt/β-catenin signaling pathway. Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, and familial adenomatous polyposis are genetic syndromes associated with a higher risk of developing ACC.

Molecular Pathways

The dysregulation of cellular pathways is pivotal in ACC pathogenesis. The Wnt/β-catenin pathway, crucial for cell proliferation and differentiation, is often abnormally activated in ACC. Overexpression of growth factors like IGF2 also promotes tumor growth and proliferation. Additionally, alterations in the p53 and RB1 tumor suppressor genes can lead to unchecked cell division and tumor formation.

Clinical Presentation

Adrenocortical carcinoma can present with a variety of symptoms, often related to hormone excess or tumor mass effect.

Hormonal Excess

  • Cushing’s Syndrome: Caused by overproduction of cortisol, leading to weight gain, hypertension, diabetes, and distinctive physical changes.
  • Hyperaldosteronism: Excess aldosterone production can result in hypertension and hypokalemia.
  • Virilization or Feminization: Overproduction of androgens or estrogens can lead to changes in secondary sexual characteristics.

Mass Effect

Large tumors may cause abdominal pain, fullness, or a palpable mass. Weight loss and anorexia can also occur.


Diagnosing ACC involves a combination of clinical evaluation, laboratory tests, and imaging studies.

Laboratory Tests

Hormonal assays to detect excess production of cortisol, aldosterone, androgens, or estrogens are crucial. Elevated levels of dehydroepiandrosterone sulfate (DHEA-S) can be a marker of ACC.


CT scans and MRI are primary tools for visualizing the adrenal tumor. They help in assessing the size, extent, and potential metastasis of the cancer.


A biopsy, though not always required, can be performed to confirm the diagnosis histologically.

Clinical Management

The management of ACC is complex and often involves a multidisciplinary approach.


Complete surgical resection of the tumor is the primary treatment for localized ACC. Minimizing tumor manipulation to avoid cancer cell spread is crucial.


Mitotane, a drug specifically targeting adrenal cortex cells, is commonly used. Combination chemotherapy regimens are also employed, especially in advanced or metastatic cases.

Radiation Therapy

Used as an adjunct to surgery or for palliative care in advanced ACC to control symptoms.

Hormonal Therapy

In cases of hormone-secreting tumors, medications to control hormone levels and alleviate symptoms may be necessary.

Prognosis and Follow-up

The prognosis of ACC depends on the stage at diagnosis, with early-stage tumors having a better outcome. Regular follow-up is essential for detecting recurrence, which is common in ACC.


Adrenocortical carcinoma is a rare but severe malignancy with complex pathogenesis involving genetic and molecular factors. Its management requires a comprehensive approach including surgery, chemotherapy, and hormonal therapy. Early diagnosis and tailored treatment are key to improving outcomes for patients with ACC.

Also Read: Hormonal Imbalances and Amenorrhea

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