Oncology · Endocrine Malignancies
The facts most likely to be tested
Adrenocortical carcinoma is a rare, highly aggressive malignancy that frequently presents with hormonal hypersecretion or mass effect symptoms.
Patients often present with virilization (due to androgen excess) or Cushing syndrome (due to cortisol excess), which are more common in malignant tumors than benign adenomas.
The presence of a large (>4-6 cm), heterogeneous, or irregularly shaped adrenal mass on CT imaging is highly suspicious for malignancy.
Mitotane is the primary adrenolytic agent used as adjuvant therapy following surgical resection to reduce recurrence risk.
Adrenocortical carcinoma is associated with genetic syndromes including Li-Fraumeni syndrome (TP53 mutation) and Beckwith-Wiedemann syndrome.
Surgical resection (adrenalectomy) remains the definitive treatment and the only potential for cure in localized disease.
Elevated serum DHEA-S levels are a hallmark laboratory finding that strongly suggests an adrenocortical origin of the malignancy.
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A 34-year-old woman presents with a 4-month history of rapidly progressive hirsutism, deepening of the voice, and amenorrhea. Physical examination reveals clitoromegaly and a palpable right-sided abdominal mass. Laboratory studies demonstrate markedly elevated serum DHEA-S and normal aldosterone levels. A CT scan of the abdomen reveals a 7 cm heterogeneous, irregular mass arising from the right adrenal gland.
What is the most likely diagnosis?
Adrenocortical carcinoma
The patient's presentation of rapid virilization, a large adrenal mass, and significantly elevated DHEA-S is classic for adrenocortical carcinoma, which is distinguished from benign adenomas by its size and hormonal profile.
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High yield triage
Etiology / Epidemiology
Rare, aggressive malignancy often associated with Li-Fraumeni syndrome or Beckwith-Wiedemann syndrome.
Clinical Manifestations
Presents with virilization or Cushing syndrome due to autonomous hormone hypersecretion.
Diagnosis
CT abdomen/pelvis is the gold standard; elevated DHEA-S is highly suggestive of malignancy.
Treatment
Surgical resection is the only curative option; Mitotane is the primary adjuvant therapy.
Prognosis
Poor prognosis with a 5-year survival rate < 35%; high risk of metastatic recurrence.
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Epidemiology & Etiology
Adrenocortical carcinoma (ACC) is a rare malignancy with a bimodal age distribution, peaking in childhood and the fourth to fifth decades. It is strongly linked to genetic predispositions, specifically TP53 mutations in Li-Fraumeni syndrome. Sporadic cases are more common in adults, often presenting as large, invasive masses.
Pertinent Anatomy
The tumor arises from the adrenal cortex, typically involving the zona fasciculata or reticularis. Due to the proximity of the inferior vena cava, large tumors frequently exhibit venous tumor thrombus, complicating surgical management.
Pathophysiology
ACC results from the malignant transformation of adrenocortical cells, leading to the loss of normal feedback inhibition of the HPA axis. The tumor autonomously secretes excess cortisol, androgens, or mineralocorticoids. This unregulated production leads to rapid onset of paraneoplastic syndromes and systemic metabolic derangements.
Clinical Manifestations
Approximately 60% of patients present with hormone excess, manifesting as virilization (hirsutism, clitoromegaly) or Cushing syndrome (central obesity, striae, hypertension). Non-functioning tumors present with abdominal pain, palpable mass, or weight loss. Rapid progression of symptoms is a red flag for malignancy compared to benign adenomas.
Diagnosis
Initial evaluation includes a hormonal workup, specifically checking DHEA-S levels, which are typically markedly elevated in ACC. CT abdomen/pelvis with contrast is the gold standard for imaging, revealing large (>4 cm), heterogeneous masses with irregular borders. Biopsy is contraindicated due to the risk of tumor seeding and inability to distinguish adenoma from carcinoma on histology.
Treatment
Complete surgical resection (adrenalectomy) is the only potentially curative treatment. For patients with residual disease or high-risk features, Mitotane is the standard adjuvant therapy. Mitotane requires careful monitoring for adrenal insufficiency and neurotoxicity. Chemotherapy (e.g., etoposide, doxorubicin, cisplatin) is reserved for metastatic disease.
Prognosis
The prognosis is generally poor, with a 5-year survival rate < 35% for all stages. Patients require lifelong surveillance for local recurrence and distant metastasis, typically to the lungs or liver, using serial imaging.
Differential Diagnosis
Adrenal Adenoma: usually < 4 cm and homogeneous on imaging
Pheochromocytoma: presents with episodic hypertension and elevated metanephrines
Adrenal Metastasis: history of primary malignancy elsewhere (e.g., lung, breast)
Cushing Disease: pituitary-dependent, usually bilateral adrenal hyperplasia
Congenital Adrenal Hyperplasia: presents in infancy with salt-wasting or ambiguous genitalia