Are there safety concerns with using Spironolactone (spironolactone) in patients with Cushing's disease?

From the Guidelines

Spironolactone should be used with caution in patients with Cushing's disease due to potential safety concerns, particularly the risk of hyperkalemia and effects on glucose metabolism, as noted in the 2018 American Heart Association scientific statement on resistant hypertension 1. When considering the use of spironolactone in patients with Cushing's disease, it is crucial to weigh the benefits against the potential risks. Key concerns include:

• Electrolyte imbalances: Cushing's disease can cause potassium retention, and spironolactone, as a potassium-sparing diuretic, can further increase potassium levels, potentially leading to hyperkalemia.
• Effects on glucose metabolism: Both Cushing's disease and spironolactone can affect glucose levels, potentially worsening diabetes control.
• Interference with diagnostic testing: Spironolactone may affect cortisol and aldosterone levels, potentially interfering with diagnostic tests for Cushing's disease. Given these concerns, the primary treatment for Cushing's disease should focus on addressing the underlying cause, typically a pituitary adenoma, through surgery, radiation, or medications that directly target cortisol production, as outlined in recent guidelines 1. If spironolactone is necessary for managing symptoms like hypertension or edema in Cushing's patients, it should be used at the lowest effective dose, usually starting at 25-50 mg daily, with close medical supervision and frequent laboratory monitoring, including regular checks of serum potassium, sodium, and renal function, to mitigate potential risks 1.

From the FDA Drug Label

The following clinically significant adverse reactions are described elsewhere in the labeling: Hyperkalemia [see Warnings and Precautions ( 5.1)] Metabolism: Hyperkalemia, electrolyte disturbances [see Warnings and Precautions ( 5.1,5. 3)]

There are safety concerns with spironolactone, particularly related to hyperkalemia and electrolyte disturbances.

• Hyperkalemia is a significant concern, as it can be life-threatening.
• Patients with Cushing's disease may be at increased risk for electrolyte imbalances due to the disease itself. No direct information is available regarding the safety of spironolactone in patients with Cushing's disease. However, given the potential for hyperkalemia and electrolyte disturbances, caution should be exercised when using spironolactone in these patients 2.

From the Research

Cushing Disease and Spironolactone Safety Concerns

• The use of spironolactone in patients with Cushing disease is mentioned in a study 3 as a treatment for hypokalemia, a potential side effect of mifepristone, which is used to control hypercortisolism.
• Spironolactone is a potassium-sparing diuretic that can help mitigate the risk of hypokalemia associated with thiazide diuretics 4.
• In the context of Cushing disease, spironolactone may be used to manage hypokalemia, but its safety and efficacy in this specific population are not extensively studied.
• The primary treatment for Cushing disease is surgery, and pharmacological treatment is typically reserved for cases where surgery is not possible or has failed 5.
• Mifepristone, a glucocorticoid receptor antagonist, is approved for the treatment of hyperglycemia secondary to endogenous hypercortisolism in patients with Cushing syndrome who have failed surgery or are not candidates for surgery 3.
• The safety concerns associated with spironolactone in patients with Cushing disease are largely related to its potential to exacerbate hyperkalemia, although this is not a primary concern in the context of Cushing disease treatment.
• Other safety concerns associated with spironolactone, such as antiprogesterone effects and hypothyroidism, are not directly relevant to the treatment of Cushing disease 3.

Potential Interactions and Side Effects

• The use of spironolactone in combination with other medications, such as mifepristone, may increase the risk of adverse events, including hypokalemia and other electrolyte imbalances 3.
• Patients with Cushing disease who are treated with spironolactone should be closely monitored for signs of hypokalemia, hyperkalemia, and other potential side effects.
• The optimal dosage and duration of spironolactone treatment in patients with Cushing disease are not well established and may require individualized adjustment based on patient response and tolerance.