Understanding Adrenocortical Carcinoma: Symptoms and Treatments

Adrenocortical carcinoma (ACC) is a rare but aggressive cancer originating in the cortex of the adrenal gland. This malignancy presents significant challenges in terms of diagnosis, treatment, and prognosis.

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Causes and Risk Factors

The precise etiology of adrenocortical carcinoma remains unclear, although several genetic and environmental factors have been implicated. Mutations in the TP53 gene, which is responsible for cell cycle regulation, have been associated with ACC. Additionally, hereditary syndromes such as Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, and multiple endocrine neoplasia type 1 (MEN1) are recognized risk factors.

Environmental influences, although less clearly defined, may also contribute to ACC development. Epidemiological studies suggest a potential link between prolonged exposure to certain industrial chemicals and an increased risk of adrenal tumours.

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Symptoms of Adrenocortical Carcinoma

Adrenocortical carcinoma can produce a variety of symptoms, often dependent on whether the tumour is functional or nonfunctional. Functional tumours secrete excess hormones, leading to distinct clinical manifestations.

Hormonal Symptoms

Functional ACCs may lead to overproduction of hormones such as cortisol, aldosterone, and androgens. This hormonal imbalance can result in conditions like Cushing's syndrome, characterized by obesity, hypertension, and glucose intolerance. Additionally, excess androgens can cause virilization, presenting with hirsutism, acne, and amenorrhea in females.

Local and Systemic Symptoms

Nonfunctional tumours or large masses may exert pressure on surrounding tissues, causing abdominal pain or a palpable mass. Systemic symptoms such as unexplained weight loss, fatigue, and fever may also occur.

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Diagnosis of Adrenocortical Carcinoma

Early and accurate diagnosis of ACC is crucial for effective management. Several diagnostic modalities are employed:

Imaging Studies

Computed tomography (CT) and magnetic resonance imaging (MRI) are pivotal in assessing tumour size, location, and potential metastasis. These imaging techniques help differentiate ACC from benign adrenal lesions.

Biochemical Evaluation

Hormonal assays are essential for evaluating functional tumours. Elevated levels of cortisol, aldosterone, or androgens can confirm excessive hormone production.

Histopathological Analysis

A definitive diagnosis requires histological examination, typically obtained through surgical resection or biopsy. Pathological evaluation distinguishes ACC from other adrenal tumours, such as adenomas.

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Staging of Adrenocortical Carcinoma

The staging of adrenocortical carcinoma follows the TNM (Tumor, Node, Metastasis) classification, which assesses the extent of the primary tumour, lymph node involvement, and distant metastasis.

Accurate staging is critical for determining the most appropriate treatment approach and assessing prognosis.

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Treatment Options for Adrenocortical Carcinoma

The management of adrenocortical carcinoma involves a multidisciplinary approach, often combining surgery, medical therapy, and occasionally radiotherapy.

Surgical Resection

Complete surgical resection remains the cornerstone of curative treatment for localized ACC. An adrenalectomy, potentially with en bloc resection of surrounding tissues, is performed to achieve clear margins and minimize recurrence risk.

Adjuvant and Neoadjuvant Therapy

In cases where complete resection is challenging or when there is a high risk of recurrence, adjuvant therapy with mitotane, an adrenolytic agent, may be prescribed. Neoadjuvant therapy, administered prior to surgery, can reduce tumour size and facilitate resection.

Chemotherapy and Radiotherapy

For advanced-stage or metastatic ACC, systemic chemotherapy regimens incorporating agents such as etoposide, doxorubicin, and cisplatin may be utilized. Radiotherapy is typically reserved for palliative care or in cases of local recurrence.

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Prognosis of Adrenocortical Carcinoma

The prognosis of adrenocortical carcinoma varies significantly based on factors such as tumour stage, resectability, and response to treatment.

Prognostic indicators also include the Ki-67 proliferation index, mitotic rate, and histopathological features.