Yee-Ming M Cheung1, Karen Van2, Lan Lan3, Rahul Barmanray4, Sarah Y Qian5, William Y Shi6, Jennifer L A Wong2,7, Peter S Hamblin3,8, Peter G Colman4, Duncan J Topliss5,9, Justin T Denholm10,11, Mathis Grossmann1,12. 1. Department of Endocrinology, Austin Health, Melbourne, Victoria, Australia. 2. Diabetes and Vascular Medicine Unit, Monash Health, Melbourne, Victoria, Australia. 3. Department of Endocrinology and Diabetes, Western Health, Melbourne, Victoria, Australia. 4. Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia. 5. Department of Endocrinology and Diabetes, The Alfred Hospital, Melbourne, Victoria, Australia. 6. Melbourne Medical School, The University of Melbourne, Victoria, Australia. 7. Diabetes and Vascular Medicine Research Program, Monash Centre for Health Research and Implementation, School of Public Health, Monash University, Melbourne, Victoria, Australia. 8. Department of Medicine-Western Precinct, The University of Melbourne, Melbourne, Victoria, Australia. 9. Department of Medicine, Monash University, Melbourne, Victoria, Australia. 10. Victorian Tuberculosis Program, Melbourne Health, Melbourne, Victoria, Australia. 11. Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia. 12. Department of Medicine (Austin Health), The University of Melbourne, Melbourne, Victoria, Australia.
Abstract
BACKGROUND: Reports from resource-poor countries have associated thionamide- and para-aminosalicylate sodium (PAS)-based treatment of multi-drug-resistant tuberculosis (MDR-TB) with the development of hypothyroidism. AIM: To identify predictors and assess the cumulative proportions of hypothyroidism in patients treated for MDR-TB with these agents in Australia. METHODS: Retrospective multicentre study of MDR-TB patients from five academic centres covering tuberculosis (TB) services in Victoria, Australia. Patients were identified using each centre's pharmacy department and cross checked with the Victorian Tuberculosis Program. Hypothyroidism was categorised as subclinical if the thyroid-stimulating hormone was elevated and as overt if free thyroxine (fT4) was additionally reduced on two separate occasions. Our main outcome measured was the cumulative proportion of hypothyroidism (at 5 years from treatment initiation). RESULTS: Of the 29 cases available for analysis, the cumulative proportion of hypothyroidism at 5 years was 37% (95% confidence interval (CI): 0-57.8%). Eight of the nine affected cases developed hypothyroidism within the first 12 months of treatment. Hypothyroidism was marginally (P = 0.06) associated with higher prothionamide/PAS dosing and was reversible with cessation of the anti-tuberculosis medication. CONCLUSIONS: Prothionamide/PAS treatment-associated hypothyroidism is common in MDR-TB patients in Australia, emphasising the importance of regular thyroid function monitoring during this treatment. Thyroid hormone replacement, if initiated, may not need to be continued after MDR-TB treatment is completed.
BACKGROUND: Reports from resource-poor countries have associated thionamide- and para-aminosalicylate sodium (PAS)-based treatment of multi-drug-resistant tuberculosis (MDR-TB) with the development of hypothyroidism. AIM: To identify predictors and assess the cumulative proportions of hypothyroidism in patients treated for MDR-TB with these agents in Australia. METHODS: Retrospective multicentre study of MDR-TB patients from five academic centres covering tuberculosis (TB) services in Victoria, Australia. Patients were identified using each centre's pharmacy department and cross checked with the Victorian Tuberculosis Program. Hypothyroidism was categorised as subclinical if the thyroid-stimulating hormone was elevated and as overt if free thyroxine (fT4) was additionally reduced on two separate occasions. Our main outcome measured was the cumulative proportion of hypothyroidism (at 5 years from treatment initiation). RESULTS: Of the 29 cases available for analysis, the cumulative proportion of hypothyroidism at 5 years was 37% (95% confidence interval (CI): 0-57.8%). Eight of the nine affected cases developed hypothyroidism within the first 12 months of treatment. Hypothyroidism was marginally (P = 0.06) associated with higher prothionamide/PAS dosing and was reversible with cessation of the anti-tuberculosis medication. CONCLUSIONS:Prothionamide/PAS treatment-associated hypothyroidism is common in MDR-TB patients in Australia, emphasising the importance of regular thyroid function monitoring during this treatment. Thyroid hormone replacement, if initiated, may not need to be continued after MDR-TB treatment is completed.