What is the treatment for paraneoplastic Adrenocorticotropic hormone (ACTH) secretion?

From the Guidelines

The treatment for paraneoplastic Adrenocorticotropic hormone (ACTH) secretion primarily involves addressing the underlying malignancy while managing the resulting hypercortisolism, with the most effective approach being surgical removal of the ACTH-producing tumor when possible, or medical therapy with steroidogenesis inhibitors such as ketoconazole, metyrapone, or mitotane, as recommended by the most recent and highest quality study 1.

Key Considerations

• The definitive treatment is surgical removal of the ACTH-producing tumor when possible, as this addresses the root cause of the syndrome.
• When surgery isn't feasible, medical therapy becomes essential, with steroidogenesis inhibitors being the mainstay of medical management.
• Ketoconazole (400-1200 mg/day in divided doses), metyrapone (250-1000 mg every 6 hours), or mitotane (2-6 g/day in divided doses) are the most commonly used options, blocking different steps in cortisol production and effectively reducing hypercortisolism.
• Etomidate (0.1-0.3 mg/kg/hr) can be used intravenously for severe, life-threatening cases requiring rapid cortisol reduction.
• Glucocorticoid receptor antagonists like mifepristone (300-1200 mg/day) may also be considered.

Management and Monitoring

• Supportive care includes managing complications such as hypertension, hyperglycemia, and electrolyte imbalances.
• Patients typically require close monitoring of cortisol levels, electrolytes, and blood glucose.
• The prognosis depends largely on the underlying malignancy, with successful tumor treatment often leading to resolution of the paraneoplastic syndrome, as noted in the study 1.

Treatment Options

• Laparoscopic bilateral adrenalectomy can rapidly decrease circulating cortisol levels to allow patients with rapidly progressive SCLC and ectopic CS to begin chemotherapy in a timely manner, as mentioned in the study 1.
• Medical management of hypercortisolism is achieved with adrenostatic agents, including ketoconazole and mitotane, as recommended in the study 1.
• The study 1 also suggests that ketoconazole, given at a daily dose of 600–800 mg, is the most popular and effective treatment for Cushing syndrome in patients with pulmonary carcinoids.

From the Research

Treatment Options for Paraneoplastic Adrenocorticotropic Hormone (ACTH) Secretion

• The treatment of paraneoplastic Cushing syndrome due to ectopic ACTH secretion involves a multistep approach, including tumor management, somatostatin analogs, steroidogenesis inhibitors, and bilateral adrenalectomy 2.
• Steroidogenesis inhibitors, such as ketoconazole, mitotane, metyrapone, and aminoglutethimide, are commonly used to reduce cortisol levels in patients with ectopic ACTH secretion 3, 4.
• Ketoconazole has been shown to be effective in managing paraneoplastic Cushing's syndrome secondary to ectopic ACTH production, with improvements in clinical and biochemical abnormalities 4.
• Immediate-acting steroidogenesis inhibitors are required for the treatment of hypercortisolism, and catecholamine excess should also be appropriately managed before surgical removal of the tumor 5.
• A multidisciplinary approach is necessary for the treatment of ectopic ACTH secretion, involving a combination of medical therapy, surgery, and radiation therapy 2, 5, 6.

Medical Therapy

• Medical therapy may have either a primary or adjunctive role in the treatment of paraneoplastic Cushing syndrome, especially in patients who cannot undergo surgery or have recurrent disease 3.
• Neuromodulatory compounds, such as bromocriptine and cyproheptidine, are not very effective in treating Cushing's disease, while glucocorticoid antagonists may be used in some cases 3.
• Steroidogenesis inhibitors are the agents of choice for medical therapy, with ketoconazole being the best tolerated and most effective agent in many cases 3, 4.

Surgical Intervention

• Surgical removal of the tumor is the optimal treatment for paraneoplastic Cushing syndrome, especially in cases where the tumor is localized and resectable 2, 5.
• Bilateral adrenalectomy may be considered in some cases, especially in patients with severe hypercortisolism who are not responsive to medical therapy 2.