How do carcinoid tumors cause Cushing's syndrome?

How Carcinoid Tumors Cause Cushing's Syndrome

Carcinoid tumors cause Cushing's syndrome primarily through ectopic production of adrenocorticotropic hormone (ACTH), leading to excessive cortisol secretion and subsequent hypercortisolemia.

Mechanism of Cushing's Syndrome in Carcinoid Tumors

• Bronchial and thymic carcinoids are most commonly associated with ectopic ACTH production, which is a cause of Cushing's syndrome 1
• Approximately 2% of patients with pulmonary and thymic carcinoids present with Cushing's syndrome caused by this ectopic ACTH production 1
• The excessive ACTH stimulates the adrenal glands to produce cortisol in amounts that exceed normal physiologic requirements 1

Types of Carcinoid Tumors Associated with Cushing's Syndrome

• Bronchopulmonary (lung) carcinoids are the most frequent source of ectopic ACTH production 1, 2
• Other carcinoid locations that can produce ACTH include:
  • Thymic carcinoids 1
  • Pancreatic carcinoids 1
  • Duodenal carcinoids (rare) 3
  • Other gastrointestinal tract carcinoids 1

Clinical Presentation and Diagnosis

• Patients with carcinoid-induced Cushing's syndrome typically present with:

  • Hypertension, sometimes severe or in crisis 4, 5
  • Hyperglycemia or diabetes 5
  • Hypokalemia and metabolic alkalosis 1, 6
  • Muscle weakness and atrophy 1
  • Characteristic cushingoid features (moon facies, striae) may develop if the syndrome persists 5

• Diagnostic approach includes:

  • Measurement of 24-hour urinary cortisol (elevated levels indicate Cushing's syndrome) 1
  • Elevated serum ACTH levels suggest an ectopic source rather than primary adrenal pathology 1
  • Imaging studies (CT, MRI) to locate the carcinoid tumor 1
  • Somatostatin receptor scintigraphy may help identify carcinoid tumors 1

Treatment Approaches

• Primary treatment is surgical removal of the ectopic ACTH-producing carcinoid tumor when possible 1
• If the primary tumor is unresectable, options include:
  • Bilateral laparoscopic adrenalectomy to control hypercortisolism 1
  • Medical management with adrenostatic agents such as ketoconazole (400-1200 mg/day) or mitotane 1
  • Octreotide may be considered if the tumor is Octreoscan-positive, though it may be less effective for controlling ectopic ACTH secretion 1

Prognosis and Outcomes

• Despite delays in surgical therapy, pulmonary resection for ACTH-secreting carcinoids often results in a favorable prognosis 2
• Complete resolution of Cushing's syndrome can be achieved after successful removal of the tumor 2
• Anatomic resection with complete mediastinal lymphadenectomy decreases local recurrence 2
• Patients require close follow-up as recurrence of both the carcinoid tumor and Cushing's syndrome can occur 2

Important Considerations

• Carcinoid crisis may occur in previously asymptomatic patients following bronchoscopic biopsy or surgical manipulation 1
• Postoperative corticosteroid supplementation is required after adrenalectomy until recovery of the hypothalamus-pituitary-adrenal (HPA) axis 1
• Early recognition of the signs and symptoms of excess ACTH is crucial for prompt and appropriate treatment 4