Adrenal cancers are rare malignancies that originate in the adrenal glands, located above each kidney. These cancers can be classified into two major types, depending on whether they arise from the outer adrenal cortex or the inner adrenal medulla, which have distinct functions.
WHAT IS ADRENAL CANCER
Adrenal Cortex Cancer (Adrenocortical Carcinoma)
This cancer originates in the adrenal cortex, the outer layer of the adrenal gland that produces steroid hormones such as cortisol, aldosterone, and sex hormones (androgens and oestrogens).
Subtypes:
- Functional tumours: Produce excess hormones, leading to symptoms related to hormonal imbalances (e.g., Cushing’s syndrome, Conn’s syndrome, or virilization/feminisation).
- Non-functional tumours: Do not produce hormones and are often detected incidentally or due to mass effects (e.g., pain, abdominal discomfort).
Key Features:
- Rare, aggressive, and often diagnosed at advanced stages.
- Most common in children under 5 and adults in their 40s to 50s.
- Can cause symptoms related to hormone overproduction or due to the tumour’s growth.
Adrenal Medulla Tumours
The adrenal medulla is the inner part of the adrenal gland responsible for producing catecholamines (epinephrine and norepinephrine), which regulate stress responses.
Types of Tumours in the Adrenal Medulla:
a) Pheochromocytoma:
- A rare tumour arising from the chromaffin cells of the adrenal medulla.
- Most pheochromocytomas are benign, but about 10% can be malignant (spread to other parts of the body).
- Symptoms: High blood pressure, palpitations, sweating, headaches, and episodes of anxiety due to excess catecholamine production.
- Malignant pheochromocytomas can spread to the bones, liver, or lungs.
b) Neuroblastoma:
- A cancer primarily found in children, originating from immature nerve cells (neuroblasts) in the adrenal medulla or nearby sympathetic nervous tissue.
- It is the most common extracranial solid tumour in children and often diagnosed before age 5.
- Symptoms: Abdominal swelling, pain, weight loss, and, sometimes, paraneoplastic syndromes like diarrhoea or hypertension.
- Neuroblastomas are typically aggressive and can spread to bones, liver, or lymph nodes.
Metastatic Tumours to the Adrenal Gland
These are cancers that spread (metastasise) to the adrenal glands from other primary sites, such as the lungs, breast, kidney, or melanoma. While not true adrenal cancers, metastatic tumours in the adrenal glands are relatively common because of the gland’s rich blood supply.
Key Features:
- Usually non-functional (do not produce hormones).
- Detected during imaging for other cancers or as part of a metastatic workup.
Adrenal Incidentalomas
Although not cancer per se, adrenal incidentalomas are tumours discovered incidentally during imaging for other reasons. While most of these are benign (e.g., adrenal adenomas), a small percentage can be malignant, including adrenal cortical carcinoma or pheochromocytoma.
Differences Between Functional and Non-Functional Tumours
| Type | Functional Tumours | Non-Functional Tumours |
|---|---|---|
| Hormonal activity | Excess hormone production (e.g., cortisol, aldosterone). | No hormone production. |
| Symptoms | Hormone-related symptoms (e.g., Cushing’s, Conn’s). | Symptoms from mass effect or incidental detection. |
| Examples | Cushing’s syndrome, Conn’s syndrome, feminisation. | Adrenal adenomas or non-functional carcinoma. |
Diagnosis of Adrenal Gland Cancers
To differentiate between these types of adrenal gland cancers, doctors use:
Hormonal Testing
Blood and urine tests to measure hormone levels (e.g., cortisol, aldosterone, catecholamines).
Imaging
CT scan or MRI for tumour localisation and evaluation.
Biopsy
Rarely performed for adrenal cancer but may be done for metastatic tumours.
Genetic Testing
Recommended for patients with pheochromocytomas or family history of cancer syndromes.
Treatment
The treatment of adrenal gland cancers varies based on the type of cancer, whether it is functional or non-functional, and the stage of the disease. Below is a detailed overview of treatments for the different types of adrenal gland cancers:
Adrenal Cortex Cancer (Adrenocortical Carcinoma)
This is an aggressive cancer that originates in the adrenal cortex. Treatments are often aimed at removing the tumour and managing hormone overproduction.
Treatment Options:
Surgery (Adrenalectomy):
- The primary treatment for localised adrenocortical carcinoma.
- Open adrenalectomy is preferred for large or invasive tumours.
- If the tumour has invaded nearby organs, those may also need to be removed.
Medications for Hormone Overproduction:
- If the tumour is functional (producing excess hormones), drugs like ketoconazole, mitotane, or metyrapone may be used to block hormone production before or after surgery.
Chemotherapy:
- Used for advanced or metastatic cases.
- The drug mitotane is often combined with other chemotherapeutic agents such as:
– Etoposide, doxorubicin, and cisplatin (EDP regimen). - Mitotane specifically targets adrenal cortical cells and helps control hormone production.
Radiotherapy:
- Rarely used but may be helpful in managing residual disease or pain from metastases.
Targeted Therapy and Immunotherapy:
- Emerging treatments, but no standard targeted therapies are currently available for adrenocortical carcinoma.
- Clinical trials may be an option for patients with advanced disease.
Palliative Care:
- Symptom management for advanced cancer, focusing on improving the quality of life.
Adrenal Medulla Tumours
Most pheochromocytomas are benign, but treatment is required to prevent complications from excess catecholamines (e.g., high blood pressure).
Treatment Options:
Surgery:
- Adrenalectomy is the primary treatment for pheochromocytoma.
- Pre-surgical preparation with medications is critical to manage the effects of excess catecholamines:
– Alpha-blockers (e.g., phenoxybenzamine) are given first to control blood pressure.
– Beta-blockers (e.g., propranolol) may be added later to manage heart rate.
Medications for Inoperable Tumours:
- If the tumour cannot be removed or if it has metastasised, drugs such as metyrosine may be used to reduce catecholamine production.
Radiation and Chemotherapy:
- For malignant pheochromocytomas, treatments like radioisotope therapy (using MIBG radiopharmaceuticals) and chemotherapy (e.g., cyclophosphamide, vincristine, and dacarbazine) may be used.
Targeted Therapy:
- Drugs like sunitinib (a tyrosine kinase inhibitor) have shown promise in treating advanced cases.
Neuroblastoma (Adrenal Medulla Cancer in Children)
Neuroblastoma is a rare but aggressive cancer that typically affects children under 5 years old.
Treatment Options:
Surgery:
- The first-line treatment for localised neuroblastoma is complete surgical removal of the tumour.
Chemotherapy:
- Used for advanced or high-risk neuroblastomas.
- Common drugs include cyclophosphamide, doxorubicin, vincristine, etoposide, and cisplatin.
Radiation Therapy:
- Applied to shrink tumours that cannot be fully removed surgically or to treat metastases.
Immunotherapy:
- Advanced neuroblastoma may be treated with monoclonal antibodies like dinutuximab, which targets neuroblastoma cells.
Stem Cell Transplantation:
- High-dose chemotherapy followed by an autologous stem cell transplant is used for high-risk neuroblastoma.
Clinical Trials:
- Experimental therapies, including novel immunotherapies and targeted agents, are often available for children with refractory neuroblastoma.
Metastatic Tumours to the Adrenal Gland
When adrenal tumours are secondary (i.e., metastases from other cancers like lung, kidney, or melanoma), treatment focuses on the primary cancer and any symptoms caused by the adrenal tumour.
Treatment Options:
Surgery:
- Adrenalectomy may be performed if the metastatic tumour is isolated and can be removed surgically.
Systemic Therapy:
- Chemotherapy, targeted therapy, or immunotherapy tailored to the primary cancer (e.g., lung or kidney cancer).
Palliative Care:
- Radiation therapy or medications to relieve pain or control hormone-related symptoms.
5. Adrenal Incidentalomas
For incidentalomas (tumours discovered incidentally during imaging), the treatment depends on their size, function, and whether they appear suspicious for malignancy:
- Tumours >4-6 cm or those with suspicious features on imaging may require surgical removal.
- Smaller, non-functional tumours are often monitored with periodic imaging and hormonal evaluations.
Comparative Summary of Treatments
| Cancer Type | Primary Treatment | Additional Options |
|---|---|---|
| Adrenocortical Carcinoma | Surgery (adrenalectomy) | Chemotherapy (mitotane, EDP), radiation, clinical trials, hormone-blocking drugs. |
| Pheochromocytoma | Surgery (adrenalectomy) | Pre-surgical medications (alpha/beta-blockers), MIBG radiotherapy for malignant cases. |
| Neuroblastoma | Surgery, chemotherapy | Immunotherapy, radiation, stem cell transplant, clinical trials. |
| Metastatic Tumours | Treat primary cancer | Surgery (if isolated), systemic therapy based on the primary tumour type. |
| Adrenal Incidentalomas | Observation or surgery | Depends on size, function, and malignancy potential. |
Prognosis
- Localised cancers: Early detection and surgical removal often result in better outcomes.
- Advanced cancers: Prognosis depends on the type of cancer and response to systemic therapies.
- Neuroblastoma: High-risk cases remain challenging but newer therapies (e.g., immunotherapy) are improving survival rates.
