Most adults with Cushing’s disease achieve remission with ketoconazole after surgery
Click Here to Manage Email Alerts
Key takeaways:
- Ketoconazole led to normal urinary free cortisol levels for 63% of adults with Cushing’s disease.
- Remission was not observed in 20% of adults receiving ketoconazole.
Most adults with Cushing’s disease who received ketoconazole after transsphenoidal surgery had a reduction in cortisol to normal levels, according to findings published in Frontiers in Endocrinology.
“Ketoconazole effectively controlled hypercortisolism in approximately 63% of Cushing’s disease patients when used according to its principal indication, ie, in patients without remission after transsphenoidal surgery,” Mauro Antonio Czepielewski, MD, PhD, professor of endocrinology at Federal University of Rio Grande do Sul in Brazil, and colleagues wrote. “No association was found between hypercortisolism biochemical control and total medication dose, treatment duration or initial serum cortisol levels.”
Researchers conducted a systematic review and meta-analysis of observational, case-control and clinical trials conducted with adults diagnosed with Cushing’s disease who underwent transsphenoidal surgery as first-line therapy, either did not achieve remission or had recurrence during follow-up and were prescribed ketoconazole as a second-line therapy. A search was conducted in the MEDLINE, Embase and SciELO databases in June 2021. The primary outcome was the percentage of adults with complete, partial or no biochemical control of hypercortisolism with ketoconazole therapy.
There were 10 articles included in the study with 270 adults. Biochemical control was defined as the normalization of 24-hour urinary free cortisol in all but one study. The mean treatment duration with ketoconazole was 31.4 months.
Of the study population, 63% achieved normal 24-hour urinary free cortisol levels. The remission rate varied greatly between studies and ranged from 39% to 89%. The researchers cited clinical differences between the study groups as one of the reasons behind the variability. Overall, 20% of study participants did not reach normal urinary free cortisol levels.
Five studies assessed a reduction of more than 50% in cortisol levels despite incomplete normalization. Of the participants in those studies, 21.7% had a decrease in cortisol of more than 50%. Five studies also examined how many adults underwent radiotherapy during ketoconazole treatment. Of those participants, 21% received radiotherapy either alongside or after ketoconazole therapy.
“These findings indicate that based on the current literature available, ketoconazole is an efficacious and safe drug for treating active Cushing’s disease after pituitary surgery,” the researchers wrote.
Most studies did not provide data on adverse events from ketoconazole. Of the two reporting adverse events, elevated transaminase levels, diarrhea, abdominal pain, skin rash, gynecomastia and adrenal insufficiency were most common. No deaths were reported in any study.
“Our analyses have several limitations since nine of the 10 primary studies that were included in the meta-analysis were retrospective and uncontrolled in design,” the researchers wrote. “We could find no randomized clinical trials, and we know that only randomized controlled trials with an intention-to-treat analysis can provide accurate estimates of drug efficacy. New therapeutic options are under investigation in clinical trials and will likely bring more robust data about hypercortisolism control in Cushing’s disease.”
Collapse
Read more about
Click Here to Manage Email Alerts