Increase in thyroid stimulating hormone levels in patients with gout treated with inhibitors of xanthine oxidoreductase.
Increase in thyroid stimulating hormone (TSH) levels over the upper normal limit has been reported in a small percentage of patients treated with febuxostat in clinical trials, but a mechanistic explanation is not yet available. In an observational parallel longitudinal cohort study, we evaluated changes in TSH levels in patients with gout at baseline and during urate-lowering treatment with febuxostat. Patients to be started on allopurinol who had a measurement of TSH in the 6-month period prior to baseline evaluation were used for comparison. TSH levels and change in TSH levels at 12-month follow-up were compared between groups. Patients with abnormal TSH levels or previous thyroid disease or on amiodarone were not included for analysis. Eighty-eight patients treated with febuxostat and 87 with allopurinol were available for comparisons. Patients to be treated with febuxostat had higher urate levels and TSH levels, more severe gout, and poorer renal function, but were similar regarding other characteristics. A similar rise in TSH levels was observed in both groups (0.4 and 0.5 µUI/mL for febuxostat and allopurinol, respectively); at 12-mo, 7/88 (7.9 %) of patients on febuxostat and 4/87 (3.4 %) of patients on allopurinol showed TSH levels over 0.5 µUI/mL. Doses prescribed (corrected for estimated glomerular filtration rate in the case if patients on allopurinol) and baseline TSH levels were determinants of TSH levels at 12-month follow-up. No impact on free T4 (fT4) levels was observed. Febuxostat, but also allopurinol, increased TSH levels in a dose-dependent way, thus suggesting rather a class effect than a drug effect, but with no apparent impact on either clinical or fT4 levels.
Rheumatology Division, Hospital Universitario Cruces and Biocruces Health Research Institute, Pza. Cruces sn, 48903, Baracaldo, Spain. fernando.perezruiz@osakidetza.eus.
Fernando
F
Perez-Ruiz
Rheumatology Division, Hospital Universitario Cruces, Baracaldo, Spain.
Sandra Pamela
SP
Chinchilla
Rheumatology Division, Hospital Universitario Cruces and Biocruces Health Research Institute, Pza. Cruces sn, 48903, Baracaldo, Spain.
Joana
J
Atxotegi
Rheumatology Division, Hospital Universitario Cruces, Baracaldo, Spain.
Irati
I
Urionagüena
Physical Medicine Division, Hospital de Górliz and Biocruces Helath Research Institute, Górliz, Spain.
Ana Maria
AM
Herrero-Beites
Biochemistry Division, Hospital Universitario Cruces, Baracaldo, Spain.
Maria Angeles
MA
Aniel-Quiroga
D000368:Aged; D000493:Allopurinol / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D000069465:Febuxostat / Q000627:therapeutic use*; D005260:Female; D006073:Gout / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013972:Thyrotropin / Q000097:blood*; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D014527:Uric Acid / Q000097:blood; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D015415:Biomarkers; D004791:Enzyme Inhibitors; D006074:Gout Suppressants; D000069465:Febuxostat; D014527:Uric Acid; D000493:Allopurinol; D013972:Thyrotropin; D014968:Xanthine Dehydrogenase
Allopurinol; Febuxostat; Gout; TSH; Xanthine oxidase