From the Guidelines
The initial treatment approach for Cushing's syndrome should be tailored to its underlying cause, with transsphenoidal surgery being the first-line treatment for ACTH-dependent Cushing's disease caused by a pituitary adenoma, as recommended by the most recent guideline 1. When considering the treatment of Cushing's syndrome, it is crucial to identify the underlying cause, as this will guide the most effective treatment strategy.
- For ACTH-dependent Cushing's disease caused by a pituitary adenoma, transsphenoidal surgery is the first-line treatment, as it allows for the selective removal of the adenoma while preserving normal pituitary tissue 1.
- For adrenal tumors producing excess cortisol, surgical removal of the affected adrenal gland (adrenalectomy) is recommended, as it can provide a definitive cure for the condition 1.
- When ectopic ACTH production from tumors like small cell lung cancer is responsible, treatment should target the primary tumor, with the goal of reducing ACTH production and alleviating symptoms of Cushing's syndrome 1. If surgery is not immediately possible or during preparation for surgery, medical therapy may be used to control hypercortisolism, including steroidogenesis inhibitors like ketoconazole (400-1200 mg/day) or metyrapone (500-6000 mg/day), which can help reduce cortisol levels and alleviate symptoms 1. However, these medications require careful monitoring for side effects and efficacy, and their use should be confined to normalizing cortisol levels in preparation for surgery or while awaiting a biochemical response to radiotherapy 1. In severe cases that are unresponsive to other treatments, bilateral adrenalectomy may be considered as a last resort, although it necessitates lifelong glucocorticoid and mineralocorticoid replacement 1. Overall, prompt treatment is essential to prevent the significant morbidity associated with chronic hypercortisolism, including diabetes, hypertension, osteoporosis, and increased cardiovascular risk 1.
From the FDA Drug Label
The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by inhibiting the 11-beta-hydroxylation reaction in the adrenal cortex.
The initial treatment approach for a patient with Cushing's syndrome may involve the use of metyrapone, an adrenal steroid synthesis inhibitor, to reduce cortisol production.
- Key points:
- Metyrapone inhibits the 11-beta-hydroxylation reaction in the adrenal cortex.
- This leads to a reduction in cortisol and corticosterone production.
- Metyrapone may be used as part of the diagnostic and treatment approach for Cushing's syndrome. 2
From the Research
Initial Treatment Approach for Cushing's Syndrome
The initial treatment approach for a patient with Cushing's syndrome typically involves a multidisciplinary approach, including endocrinologists, neurosurgeons, oncologists, and radiotherapists 3. The primary goal is to remove the tumor causing the excessive cortisol secretion.
Medical Therapy
When surgery is not curative or possible, medical therapy is used to control hypercortisolemia and associated symptoms. Several drugs are available to reduce cortisol levels, including:
- Adrenal-blocking agents, such as ketoconazole, metyrapone, mitotane, and etomidate, which inhibit adrenal steroidogenesis 4, 5, 6
- Centrally acting agents, such as dopamine agonists, somatostatin receptor agonists, and retinoic acid, which suppress ACTH secretion 3, 4, 7
- Glucocorticoid receptor antagonists, such as mifepristone, which block the peripheral action of cortisol 4, 7
Treatment Considerations
The choice of medical therapy depends on the underlying cause of Cushing's syndrome, the severity of symptoms, and the patient's overall health. Combination therapy may be used to achieve biochemical control, and careful dose titration and patient monitoring are necessary to ensure safety and effectiveness 5, 6.
Available Medications
Several medications are currently available for the medical treatment of Cushing's syndrome, including: