Article: Evaluation of ketoconazole as a treatment for Cushing's disease in a retrospective cohort.
2022 Volume 13, Page(s) 1017331
Abstract: Objective: The first-line treatment for Cushing's disease is transsphenoidal surgery, after which the rates of remission are 60 to 80%, with long-term recurrence of 20 to 30%, even in those with real initial remission. Drug therapies are indicated for ... ...
| Abstract | Objective: The first-line treatment for Cushing's disease is transsphenoidal surgery, after which the rates of remission are 60 to 80%, with long-term recurrence of 20 to 30%, even in those with real initial remission. Drug therapies are indicated for patients without initial remission or with surgical contraindications or recurrence, and ketoconazole is one of the main available therapies. The objective of this study was to evaluate the safety profile of and the treatment response to ketoconazole in Cushing's disease patients followed up at the endocrinology outpatient clinic of a Brazilian university hospital. Patients and methods: This was a retrospective cohort of Cushing's disease patients with active hypercortisolism who used ketoconazole at any stage of follow-up. Patients who were followed up for less than 7 days, who did not adhere to treatment, or who were lost to follow-up were excluded. Results: Of the 172 Cushing's disease patients who were followed up between 2004 and 2020, 38 received ketoconazole. However, complete data was only available for 33 of these patients. Of these, 26 (78%) underwent transsphenoidal surgery prior to using ketoconazole, five of whom (15%) had also undergone radiotherapy; seven used ketoconazole as a primary treatment. Ketoconazole use ranged from 14 days to 14.5 years. A total of 22 patients had a complete response (66%), three patients had a partial response (9%), and eight patients had no response to treatment (24%), including those who underwent radiotherapy while using ketoconazole. Patients whose hypercortisolism was controlled or partially controlled with ketoconazole had lower baseline 24-h urinary free cortisol levels than the uncontrolled group [times above the upper limit of normal: 0.62 (SD, 0.41) Conclusion: Ketoconazole effectively controlled hypercortisolism in 66% of Cushing's disease patients, being a relatively safe drug for those without remission after transsphenoidal surgery or whose symptoms must be controlled until a new definitive therapy is carried out. Hypokalemia is a frequent metabolic effect not yet described in other series, which should be monitored during treatment. |
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| MeSH term(s) | Humans ; Pituitary ACTH Hypersecretion/complications ; Pituitary ACTH Hypersecretion/drug therapy ; Pituitary ACTH Hypersecretion/surgery ; Ketoconazole/therapeutic use ; Retrospective Studies ; Hydrocortisone ; Cabergoline ; Hypokalemia/drug therapy ; Cushing Syndrome/drug therapy |
| Chemical Substances | Ketoconazole (R9400W927I) ; Hydrocortisone (WI4X0X7BPJ) ; Cabergoline (LL60K9J05T) |
| Language | English |
| Publishing date | 2022-10-07 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2592084-4 |
| ISSN | 1664-2392 |
| ISSN | 1664-2392 |
| DOI | 10.3389/fendo.2022.1017331 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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