Synergistic cortisol suppression by ketoconazole-osilodrostat combination therapy

Area of Science:

• Endocrinology
• Pharmacology

Background:

• Cushing's syndrome is a complex endocrine disorder characterized by excessive cortisol production.
• Adrenocorticotrophic hormone-independent Cushing's syndrome, often linked to adrenal hyperplasia, presents unique treatment challenges.

Purpose of the Study:

• To report a case of successful management of adrenocorticotrophic hormone-independent Cushing's syndrome.
• To evaluate the efficacy and safety of a combination therapy for refractory hypercortisolism.

Main Methods:

• A patient with primary bilateral macronodular adrenocortical hyperplasia and uncontrolled hypercortisolism was treated.
• Monotherapy with ketoconazole and osilodrostat failed due to side effects and lack of efficacy.
• A synergistic combination of ketoconazole and osilodrostat was administered.

Main Results:

• The combination therapy of ketoconazole and osilodrostat was well-tolerated and effectively controlled hypercortisolism.
• This synergistic approach demonstrated improved efficacy compared to monotherapy.

Conclusions:

• Ketoconazole-osilodrostat combination therapy is a safe and efficient strategy for Cushing's syndrome.
• This approach may be particularly valuable for patients with delayed or unsuccessful surgery, especially during the COVID-19 pandemic.
• The combination therapy offers a potentially cost-effective alternative to newer drugs.