What are the characteristics and clinical effects of adrenal carcinoma?

Characteristics of Adrenal Carcinoma

Adrenal carcinoma typically produces excessive hormones rather than causing symptoms through mass effect, and commonly produces androgens, making option C (A & B) the correct answer. 1

Hormonal Production in Adrenal Carcinoma

Excessive Hormone Production

• Adrenal carcinomas are functionally active in the majority of cases, with hormone production being a key characteristic rather than just mass effect 1
• Even seemingly hormonally inactive lesions often show evidence of steroid hormone secretion when carefully analyzed 2
• Standardized diagnostic work-up should include endocrine assessment for excess hormone production as a critical component 1

Androgen Production

• Adrenal carcinomas commonly produce androgens, leading to virilization in female patients 2
• The mechanism of excess adrenal androgen production in carcinomas is primarily due to diminished activity of 3β-hydroxysteroid dehydrogenase (3β-HSD) 3
• This contrasts with adrenal adenomas, which typically have lower 17,20-lyase activity, resulting in reduced androgen production 3

Aldosterone Production in Adrenal Carcinoma

• Aldosterone-secreting adrenal carcinomas are indeed rare 4
• Most hormonally active adrenocortical carcinomas primarily secrete cortisol 4
• When aldosterone is secreted, it's often in combination with other hormones rather than as the sole hormone product 4

Malignancy and Hormone Secretion

• Hormone secretion alone does not definitively indicate malignancy; both benign and malignant adrenal tumors can produce hormones 1, 5
• The pattern of hormone secretion may provide clues to malignancy, with co-secretion of multiple hormones (cortisol, androgens, and aldosterone) being more suggestive of carcinoma 4
• The definitive diagnosis of malignancy relies on histopathological criteria (Weiss score ≥3) rather than hormone production 1, 5

Diagnostic Approach

• All patients with suspected adrenal carcinoma should undergo:

  • Detailed endocrine work-up to identify hormone excess 5
  • Adrenal-focused imaging (CT/MRI) 1
  • Review by an expert adrenal pathologist using the Weiss score and Ki67 index 5

• Imaging characteristics typically show:

  • Inhomogeneous appearance
  • Necrosis and irregular borders
  • Low fat content compared to benign adenomas 2

Treatment Considerations

• Complete surgical extirpation (R0 resection) is the mainstay of potentially curative approaches 1, 5
• Adjuvant mitotane is recommended for patients at high risk of recurrence (ENSAT stage III, R1 resection, or Ki67 >10%) 5
• For advanced disease, treatment options include mitotane monotherapy or combination therapy with etoposide, doxorubicin, and cisplatin plus mitotane 1, 5

Important Clinical Caveat

The hormonal status should be carefully investigated in all cases of suspected adrenocortical carcinoma, as the pattern of hormone secretion may provide important diagnostic and prognostic information 4. The co-secretion of multiple hormones (cortisol, androgens, and aldosterone) is particularly suggestive of malignancy.