High-dose glucocorticoid treatment vs. glucocorticoid replacement in immune checkpoint inhibitor associated hypophysitis (CORTICI): an open, randomised controlled trial
Objective One of the most severe endocrine side effects of immune checkpoint inhibitors (ICI) is hypophysitis leading to adrenal insufficiency. Recovery is rare, although it has been reported after high-dose glucocorticoid treatment. This is the first randomised study to evaluate whether hormonal re...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
|
| Series: | Annals of Medicine |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/07853890.2025.2453829 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832586399405047808 |
|---|---|
| author | Verena Theiler-Schwetz Christian Trummer Lisa Schmitt Angelika Terbuch Barbara Obermayer-Pietsch Erika Richtig Stefan Pilz |
| author_facet | Verena Theiler-Schwetz Christian Trummer Lisa Schmitt Angelika Terbuch Barbara Obermayer-Pietsch Erika Richtig Stefan Pilz |
| author_sort | Verena Theiler-Schwetz |
| collection | DOAJ |
| description | Objective One of the most severe endocrine side effects of immune checkpoint inhibitors (ICI) is hypophysitis leading to adrenal insufficiency. Recovery is rare, although it has been reported after high-dose glucocorticoid treatment. This is the first randomised study to evaluate whether hormonal recovery differs in patients treated with high-dose glucocorticoids versus glucocorticoid replacement therapy.Design/Methods In this single-centre, open, randomised controlled study, patients with ICI associated hypophysitis were randomised 1:1 to high-dose glucocorticoid treatment (1 mg/kg of prednisolone for two weeks, followed by tapering until week 7 and a switch to hydrocortisone 20 mg total daily dose in week 8) or glucocorticoid replacement therapy (hydrocortisone 20 mg total daily dose) over 8 weeks. The primary outcome was the frequency of hormonal axes recovery.Results Between 17th April 2019 and 16th September 2022, 18 out of the 20 randomised patients finished the trial; eight completed high-dose, 10 glucocorticoid replacement. Nine patients presented with hyponatraemia, two had typical changes on MRI, 12 had isolated adrenal insufficiency, and six had an additional hormone deficiency. None of the patients in neither group experienced a recovery in adrenal function. One patient in each group showed amelioration of hypogonadism. There was a significant, unfavourable treatment effect of high-dose treatment on HbA1c (mean treatment effect 5.16, 95% confidence interval 0.31 to 10.02, p = 0.039).Conclusions High-dose glucocorticoid treatment was not effective in restoring adrenal function and leads to adverse effects on glucose metabolism. We therefore do not recommend its use for the treatment of ICI associated hypophysitis, except for compressive symptoms. |
| format | Article |
| id | doaj-art-35e6b632ce96419fa52c755569447795 |
| institution | Kabale University |
| issn | 0785-3890 1365-2060 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Annals of Medicine |
| spelling | doaj-art-35e6b632ce96419fa52c7555694477952025-01-25T16:08:29ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602025-12-0157110.1080/07853890.2025.2453829High-dose glucocorticoid treatment vs. glucocorticoid replacement in immune checkpoint inhibitor associated hypophysitis (CORTICI): an open, randomised controlled trialVerena Theiler-Schwetz0Christian Trummer1Lisa Schmitt2Angelika Terbuch3Barbara Obermayer-Pietsch4Erika Richtig5Stefan Pilz6Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaDivision of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaDepartment of Dermatology and Venereology, Graz, AustriaDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaObjective One of the most severe endocrine side effects of immune checkpoint inhibitors (ICI) is hypophysitis leading to adrenal insufficiency. Recovery is rare, although it has been reported after high-dose glucocorticoid treatment. This is the first randomised study to evaluate whether hormonal recovery differs in patients treated with high-dose glucocorticoids versus glucocorticoid replacement therapy.Design/Methods In this single-centre, open, randomised controlled study, patients with ICI associated hypophysitis were randomised 1:1 to high-dose glucocorticoid treatment (1 mg/kg of prednisolone for two weeks, followed by tapering until week 7 and a switch to hydrocortisone 20 mg total daily dose in week 8) or glucocorticoid replacement therapy (hydrocortisone 20 mg total daily dose) over 8 weeks. The primary outcome was the frequency of hormonal axes recovery.Results Between 17th April 2019 and 16th September 2022, 18 out of the 20 randomised patients finished the trial; eight completed high-dose, 10 glucocorticoid replacement. Nine patients presented with hyponatraemia, two had typical changes on MRI, 12 had isolated adrenal insufficiency, and six had an additional hormone deficiency. None of the patients in neither group experienced a recovery in adrenal function. One patient in each group showed amelioration of hypogonadism. There was a significant, unfavourable treatment effect of high-dose treatment on HbA1c (mean treatment effect 5.16, 95% confidence interval 0.31 to 10.02, p = 0.039).Conclusions High-dose glucocorticoid treatment was not effective in restoring adrenal function and leads to adverse effects on glucose metabolism. We therefore do not recommend its use for the treatment of ICI associated hypophysitis, except for compressive symptoms.https://www.tandfonline.com/doi/10.1080/07853890.2025.2453829Immune checkpoint inhibitor associated hypophysitisendocrine adverse eventshypopituitarismadrenal insufficiency |
| spellingShingle | Verena Theiler-Schwetz Christian Trummer Lisa Schmitt Angelika Terbuch Barbara Obermayer-Pietsch Erika Richtig Stefan Pilz High-dose glucocorticoid treatment vs. glucocorticoid replacement in immune checkpoint inhibitor associated hypophysitis (CORTICI): an open, randomised controlled trial Annals of Medicine Immune checkpoint inhibitor associated hypophysitis endocrine adverse events hypopituitarism adrenal insufficiency |
| title | High-dose glucocorticoid treatment vs. glucocorticoid replacement in immune checkpoint inhibitor associated hypophysitis (CORTICI): an open, randomised controlled trial |
| title_full | High-dose glucocorticoid treatment vs. glucocorticoid replacement in immune checkpoint inhibitor associated hypophysitis (CORTICI): an open, randomised controlled trial |
| title_fullStr | High-dose glucocorticoid treatment vs. glucocorticoid replacement in immune checkpoint inhibitor associated hypophysitis (CORTICI): an open, randomised controlled trial |
| title_full_unstemmed | High-dose glucocorticoid treatment vs. glucocorticoid replacement in immune checkpoint inhibitor associated hypophysitis (CORTICI): an open, randomised controlled trial |
| title_short | High-dose glucocorticoid treatment vs. glucocorticoid replacement in immune checkpoint inhibitor associated hypophysitis (CORTICI): an open, randomised controlled trial |
| title_sort | high dose glucocorticoid treatment vs glucocorticoid replacement in immune checkpoint inhibitor associated hypophysitis cortici an open randomised controlled trial |
| topic | Immune checkpoint inhibitor associated hypophysitis endocrine adverse events hypopituitarism adrenal insufficiency |
| url | https://www.tandfonline.com/doi/10.1080/07853890.2025.2453829 |
| work_keys_str_mv | AT verenatheilerschwetz highdoseglucocorticoidtreatmentvsglucocorticoidreplacementinimmunecheckpointinhibitorassociatedhypophysitiscorticianopenrandomisedcontrolledtrial AT christiantrummer highdoseglucocorticoidtreatmentvsglucocorticoidreplacementinimmunecheckpointinhibitorassociatedhypophysitiscorticianopenrandomisedcontrolledtrial AT lisaschmitt highdoseglucocorticoidtreatmentvsglucocorticoidreplacementinimmunecheckpointinhibitorassociatedhypophysitiscorticianopenrandomisedcontrolledtrial AT angelikaterbuch highdoseglucocorticoidtreatmentvsglucocorticoidreplacementinimmunecheckpointinhibitorassociatedhypophysitiscorticianopenrandomisedcontrolledtrial AT barbaraobermayerpietsch highdoseglucocorticoidtreatmentvsglucocorticoidreplacementinimmunecheckpointinhibitorassociatedhypophysitiscorticianopenrandomisedcontrolledtrial AT erikarichtig highdoseglucocorticoidtreatmentvsglucocorticoidreplacementinimmunecheckpointinhibitorassociatedhypophysitiscorticianopenrandomisedcontrolledtrial AT stefanpilz highdoseglucocorticoidtreatmentvsglucocorticoidreplacementinimmunecheckpointinhibitorassociatedhypophysitiscorticianopenrandomisedcontrolledtrial |