Adrenocortical carcinoma is a rare but severe cancer that manifests in the outer layer of the adrenal glands, known as the adrenal cortex. These small, triangular glands, located above each kidney, play a key role in regulating crucial bodily functions by producing hormones such as cortisol, aldosterone, and androgens.
When adrenocortical carcinoma develops, it can lead to significant hormonal imbalances, resulting in a wide range of symptoms that affect metabolism, blood pressure, and physical appearance.
This article provides a comprehensive overview of adrenocortical carcinoma, including its symptoms, causes, stages, and available treatment options.
Symptoms of Adrenocortical Carcinomas
The following are the symptoms of adrenocortical carcinoma:
Unexplained Weight Changes
Individuals with adrenocortical carcinoma may experience sudden and significant weight gain, especially in areas like the abdomen and face, or unexpected weight loss without making any effort, depending on the tumour’s impact on metabolism.
Muscle Weakness and Skin Changes
Hormonal imbalances caused by the tumour can lead to generalised muscle weakness, making daily activities more challenging. Additionally, patients may notice the development of pink or purple stretch marks, particularly on the abdomen, due to elevated cortisol levels.
Hormonal Imbalances in Women
In women, excess production of male hormones (androgens) may lead to physical changes, including excess facial or body hair, hair thinning on the scalp, and irregular menstrual cycles.
Hormonal Imbalances in Men
For men, overproduction of female hormones (estrogens) may result in breast enlargement (gynecomastia) and shrinking of the testicles, symptoms that can signal underlying hormonal disruption.
Gastrointestinal Disturbances
Adrenocortical carcinoma can cause nausea, vomiting, and abdominal bloating. These symptoms may arise from the tumour pressing on nearby organs or disrupting normal digestive processes.
Pain and Discomfort
Patients with adrenocortical carcinoma often report persistent back pain or abdominal discomfort, which may indicate tumour growth or pressure on surrounding structures.
Fever and Appetite Loss
Fever often comes with a generalised feeling of disease. It may also lead to fatigue and unintended weight loss, as may a decreased appetite.
Causes and Risk Factors of Adrenocortical Carcinoma
The exact cause of adrenocortical carcinoma remains unclear, but certain genetic and environmental factors increase the likelihood of developing the disease.
Genetic Factors
Certain inherited syndromes significantly increase the risk of adrenocortical carcinoma. For instance, Li-Fraumeni syndrome, caused by mutations in the TP53 tumour suppressor gene, predisposes individuals to a range of cancers, including those of the adrenal cortex. Similarly, Beckwith-Wiedemann syndrome, a genetic disorder often diagnosed in childhood, is related to a heightened risk of adrenal and other tumours.
Another condition, Lynch syndrome, primarily known for its link to colorectal and other cancers, also raises the likelihood of adrenocortical carcinoma. In some cases, familial clustering of adrenal cancers or hormone-related disorders may indicate a genetic predisposition, even in the absence of a categorical syndrome.
Environmental Factors
Although less well-established, environmental factors may contribute to the development of adrenocortical carcinoma. Chronic exposure to carcinogenic substances, such as industrial chemicals, is suspected to play a role in some cases. Additionally, prolonged hormonal imbalances, particularly from long-term use of synthetic hormones, influence the adrenal glands’ function and potentially trigger cancerous changes.
Sporadic Cases
Despite these known risk factors, most instances of adrenocortical carcinoma occur sporadically without a clear genetic or environmental cause. In these cases, mutations in tumour suppressor genes, such as TP53, are frequently identified as key contributors. These sporadic mutations often arise unpredictably, complicating efforts to identify high-risk individuals.
Stages of Adrenocortical Carcinomas
Adrenocortical carcinoma is categorised into four stages based on the extent of the disease:
- Stage I: The tumour is small (less than 5 cm) and limited to the adrenal gland.
- Stage II: The tumour is bigger than 5 cm but still localised to the adrenal gland.
- Stage III: The cancer has metastasised to adjacent tissues or lymph nodes.
- Stage IV: The disease has metastasised to distant organs, such as the liver or lungs.
Treatment Options for Adrenocortical Carcinomas
Here are the various treatment options for adrenocortical carcinoma:
Surgery
The standard treatment for localised adrenocortical carcinoma is surgical excision of the afflicted adrenal gland. The goal of the adrenalectomy procedure is to remove the tumour and all surrounding tissues in order to reduce the likelihood of recurrence. In advanced cases, surgery may also involve removing nearby organs or lymph nodes affected by cancer. Post-surgical follow-up is essential to monitor for any potential recurrence or complications.
Chemotherapy and Radiation Therapy
For advanced-stage or inoperable adrenocortical carcinoma, chemotherapy is often used to slow tumour progression. Drugs like mitotane target cancer cells and inhibit adrenal hormone production. Radiation therapy, though less commonly employed, can help eliminate residual tumour cells after surgery or provide palliative relief for symptoms like pain. Chemotherapy is frequently combined with other treatment modalities to manage more aggressive disease stages.
Hormonal Therapy
In cases of functional tumours, hormonal therapy is used to manage symptoms of hormone overproduction. Medications like mitotane not only control excessive hormone levels but also reduce tumour growth, making it a dual-purpose treatment. Hormonal therapy can help stabilise metabolic and physical symptoms, improving patient comfort and quality of life.
Targeted and Immunotherapy
Emerging treatments like targeted therapy focus on disrupting specific pathways that fuel tumour growth, while immunotherapy enhances the immune response of the body against cancer cells. These therapies are primarily available through clinical trials and hold promise for improving outcomes in aggressive or metastatic cases. Targeted therapies may offer more personalised treatment approaches, tailoring care based on genetic mutations found in individual tumours.
Palliative Care
For patients with advanced adrenocortical carcinoma, palliative care aims to improve life’s quality by addressing symptoms such as pain, fatigue, and hormonal imbalances. This approach is often combined with other treatments to provide comprehensive support. Palliative care also focuses on managing emotional and psychological stress, helping patients and families navigate the challenges of advanced cancer.
Conclusion
In conclusion, adrenocortical carcinoma is a rare but serious condition that demands prompt diagnosis and specialised treatment. Early diagnosis through awareness of symptoms and risk factors is critical for improving outcomes. While treatment often involves a combination of surgery, medications, and emerging therapies, ongoing research continues to expand the possibilities for managing this condition effectively. With advancements in targeted therapies and immunotherapy, there is hope for more potent treatments and better survival rates in the future.
