Cushing’s syndrome: a combined treatment with etomidate and osilodrostat in severe life-threatening hypercortisolemia

Abstract

Endogenous Cushing’s syndrome (CS) is associated with increased morbidity and mortality. Early diagnosis and initiation of therapy are essential, but effective treatment remains a challenge. In a long-term follow-up, biochemical control of hypercortisolemia, especially when severe, is difficult to achieve. Life-threatening hypercortisolemia is difficult to control due to the limitations of pharmacotherapy, including its side effects, and may require etomidate infusion in the intensive care unit (ICU) to rapidly lower cortisol levels. The effectiveness of hypercortisolemia management can be increased by a dual blockade of cortisol production. We report the efficacy, safety, and tolerability of combined therapy with two steroidogenesis inhibitors, etomidate, and osilodrostat, in a 32-year-old woman diagnosed with severe ACTH-dependent hypercortisolemia, subsequently maintaining a stable level of cortisol with osilodrostat monotherapy. This approach enabled achievement of relatively rapid control of the hypercortisolemia while using an etomidate infusion and concomitant increasing doses of oral osilodrostat applying a “titrations strategy.” Our experience shows that it is worth taking advantage of the synergistic anticortisolic action of etomidate with osilodrostat.

Response to Osilodrostat Therapy in Adrenal Cushing’s Syndrome

“…Such an improvement of the potassium level during osilodrostat dose escalation was previously demonstrated in a patient with CD. 11 Interestingly, in our Patient 2, no potassium supplementation was required during the whole time of osilodrostat therapy, although the doses were increased intensively up to the finally effective dose, which was the same (45 mg/day) as for Patient 1. In Patient 2, no actual response to doses lower than 20 mg/day was observed.…”

“…6 Even in rare cases of CD in whom initial short-term etomidate therapy was given at the beginning of osilodrostat therapy, due to highly severe life-threatening symptoms of hypercortisolism, the final effective dose of osilodrostat was much lower than that in our patients with CPA (25 mg/day vs 45 mg/day) and no increase of cortisol level was observed. 11 It should be underlined that many cases of adrenal insufficiency during osilodrostat therapy in patients with CD have been reported, [3][4][5][6]12,13 and -therefore -low initial dose with slow gradual dose escalation is recommended in patients with CD. 1,6,13 In the cases presented here, CPA led to severe hypercortisolism, the complications of which constituted contraindications for surgery.…”

Etomidate-induced hypokalemia in electronic cigarette users: two case reports and literature review

“…Thus, greater awareness of the risks of unregulated use of products containing etomidate is needed. For conditions involving cortisol excess though, the good therapeutic effects of etomidate warrant further investigation of its clinical value ( 17 ).…”

Cushing’s Disease: Long-Term Effectiveness and Safety of Osilodrostat in a Polish Group of Patients with Persistent Hypercortisolemia in the Experience of a Single Center

“…Moreover, ketoconazole and levoketoconazole are unavailable in Poland at the moment. In specific scenarios (especially of severe hypercortisolemia), osilodrostat in combination with other anticortisolic agents can be considered; however, data on such an approach are limited [37,38].…”