Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is a rare form of cancer that develops in the adrenal cortex — the outer layer of the adrenal glands, which sit atop each kidney. These glands produce essential hormones like cortisol, aldosterone, and androgens that help regulate metabolism, immune response, blood pressure, and sexual development.

ACC is considered an orphan disease due to its rarity, affecting approximately 1-2 people per million globally each year. Although uncommon, ACC is highly aggressive and poses significant challenges in diagnosis and management. Because many adrenal tumours are benign, differentiating malignant ACC from other non-cancerous growths is vital. Early detection plays a critical role in improving survival outcomes.

Adrenocortical carcinoma is a malignant tumour that arises from the cortex of the adrenal glands. These glands are part of the endocrine system and help maintain hormonal balance in the body. Tumours can be either functional (secreting hormones) or non-functional.

Functional tumours can cause excessive hormone production, leading to conditions like Cushing’s syndrome (excess cortisol), Conn’s syndrome (excess aldosterone), or virilisation (excess androgens). Non-functional tumours may not produce hormones and are often detected late due to lack of obvious symptoms.

Adrenocortical carcinoma can grow rapidly and metastasise to other organs, including the lungs, liver, and lymph nodes. Due to its aggressive nature, ACC requires timely and specialised treatment.

Adrenocortical carcinoma is an ultra-rare disease, affecting about 1–2 individuals per million population annually. It accounts for less than 0.02% of all cancers. The tumour occurs at any age but typically affects children under 5 and adults aged 40–60 years. Women are slightly more affected than men.

In India, data on the prevalence of ACC is limited due to underreporting and lack of comprehensive cancer registries. However, based on global incidence rates, similar prevalence can be assumed. Awareness and improved diagnostic capabilities are gradually aiding in better recognition of the disease.

ACC can be classified into:

1. Functional ACC: Produces excess adrenal hormones.
   
   • Cushing’s syndrome: Due to high cortisol.
   • Virilisation/Feminisation: Excess androgen or oestrogen production.
   • Primary aldosteronism: Overproduction of aldosterone.
2. Non-functional ACC: Does not produce hormones; symptoms are often related to tumour size and spread.

Based on histological appearance:

• Low-grade ACC: Less aggressive with better prognosis.
• High-grade ACC: Highly aggressive, poor prognosis.

Although the exact cause of ACC is not fully known, a combination of genetic and environmental factors is believed to contribute. These include:

• Inherited genetic mutations: Mutations in genes like TP53, IGF2, MEN1 are commonly found in ACC cases.
• Syndromes associated with ACC:
  
  • Li-Fraumeni syndrome
  • Beckwith-Wiedemann syndrome
  • Multiple Endocrine Neoplasia type 1 (MEN1)
• Family history of adrenal or endocrine cancers
• Exposure to carcinogens: Though not definitively proven, some occupational and environmental exposures may increase risk.

Symptoms depend on the tumour type:

Hormone-Related Symptoms (Functional Tumours):

• Weight gain and central obesity (Cushing’s syndrome)
• Facial puffiness (moon face)
• High blood pressure
• Muscle weakness
• Menstrual irregularities in women
• Increased facial/body hair in women (hirsutism)
• Breast enlargement in men (gynecomastia)
• Mood swings, irritability, and depression
• Hypokalaemia (low potassium levels)

Mass Effect Symptoms (Non-Functional Tumours):

• Abdominal pain or discomfort
• Fullness or bloating
• Back pain
• Nausea and vomiting
• Palpable mass in the abdomen

Symptoms can be vague, making diagnosis difficult without thorough testing.

Diagnosing ACC involves multiple stages:

1. Medical history and physical exam: Assessment of symptoms and risk factors.
2. Hormonal assays: Measurement of cortisol, aldosterone, and androgen levels in blood and urine.
3. Imaging studies:
   
   • CT scan: To visualise tumour size and spread.
   • MRI: Offers detailed views, especially for liver or vascular involvement.
   • PET scan: Assesses metastasis and tumour activity.
4. Biopsy: Usually avoided unless metastasis is suspected, to prevent cancer spread.
5. Histopathological grading: Determines tumour aggressiveness.

Early and accurate diagnosis improves the chances of successful treatment.

Treatment is based on the tumour's size, spread, and hormone-secreting status:

• Surgery: The mainstay of treatment. Adrenalectomy (removal of adrenal gland) is the preferred method. Lymph node dissection may be done if cancer has spread.
• Chemotherapy:
  
  • Mitotane: A drug specifically for adrenal cancers.
  • Other agents include cisplatin, doxorubicin, and etoposide.
• Radiation therapy: Postoperative radiation helps prevent recurrence, especially in high-grade or incomplete resections.
• Hormonal therapy: To manage hormone excess or deficiency after surgery.
• Targeted therapy and immunotherapy: Still under research. Some trials show promise for refractory ACC cases.

Management requires a multidisciplinary team involving oncologists, endocrinologists, and surgeons.

While conventional treatment remains critical, alternative and supportive therapies can complement care:

• Nutritional therapy: Helps maintain strength and combat fatigue.
• Mind-body practices: Yoga, meditation, and breathing exercises reduce stress.
• Psychological support: Support groups and therapy help patients cope emotionally.
• Ayurvedic remedies: Used by some patients in India; always consult a physician before using.
   

Factors that increase the risk of ACC include:

• Inherited genetic conditions (Li-Fraumeni, Beckwith-Wiedemann)
• Family history of endocrine tumours
• Female gender
• Age under 5 or between 40–60
• Genetic mutations in tumour suppressor genes (e.g., TP53)

Complications arise due to the cancer or treatment side effects:

• Adrenal insufficiency post-adrenalectomy
• Cushingoid features from excess cortisol
• Severe hypertension and electrolyte imbalance
• Metastases to liver, lungs, bones, or brain
• Chemotherapy side effects: Hair loss, nausea, immunosuppression

Managing complications requires continuous follow-up.

• Adhere strictly to prescribed treatment and medications.
• Maintain a journal to track symptoms and medication side effects.
• Attend regular follow-up appointments and lab tests.
• Communicate openly with your healthcare team.
• Seek emotional support through therapy or peer groups.
• Practise self-care: balanced diet, adequate sleep, and light exercise.

• "All adrenal tumours are dangerous": Most are benign adenomas.
• "Hormonal symptoms mean hormonal imbalance, not cancer": They could signal functional ACC.
• "ACC only affects elderly people": It can affect young children too.
• "There’s no treatment for ACC": Multiple treatment options are available.

See a doctor if you experience:

• Unexplained weight changes
• High blood pressure not controlled by medication
• Abdominal fullness or pain
• Hormonal symptoms like hirsutism or irregular periods
• A family history of adrenal or endocrine cancers
   

• What is the stage and grade of my tumour?
• Is my tumour functional or non-functional?
• What treatment plan is best for me?
• What side effects should I expect?
• Will I need hormone replacement therapy?
• How will my condition be monitored long-term?
   

• Educate yourself about the condition to offer better help.
• Accompany them to medical appointments if possible.
• Offer practical help with chores, meals, or childcare.
• Encourage them to talk about their feelings.
• Respect their privacy but check in regularly.

Adrenocortical carcinoma is a rare yet severe form of cancer that demands early detection, specialised care, and ongoing support. Though treatment is complex, advancements in medical research are offering hope. Patients and families should prioritise emotional well-being, stay informed, and engage actively with their healthcare team.