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.

Using serum urate levels to determine the period free of gouty symptoms after withdrawal of long-term urate-lowering therapy: a prospective study.

OBJECTIVE: Withdrawal of urate-lowering therapy (ULT) is associated with recurrence of acute gouty arthritis and tophi, but no data are available about factors associated with recurrence of gouty symptoms. Therefore, life-long therapy prescription is usually advised, but the prospect of life-long therapy may contribute to very low compliance rates. Our objective was to ascertain the outcome of ULT withdrawal after long-term, documented control of serum urate levels. METHODS: We conducted a prospective, long-term, followup study of patients treated with ULT during a 5-year period. Both diagnosis and recurrence of gout were determined based on monosodium urate crystal identification in synovial fluid or material aspirated from tophi. RESULTS: Low average serum urate levels while receiving ULT and during the followup period after ULT withdrawal were statistically associated with the longest period in which patients were free of gouty symptoms, suggesting that depletion and formation of the body's urate pool is dependent on both time and serum urate levels. Patients whose average serum urate levels were <5.05 mg/dl while receiving ULT and <8.75 mg/dl after ULT withdrawal had the longest (>4 years) time to recurrence. CONCLUSION: Proper and long-term reduction of serum urate level is associated with long-term periods in which patients are free of gouty symptoms, probably due to the reduction of the urate pool. These results suggest that 5-year intermittent, instead of life-long, ULT could be offered to patients with good serum urate control during ULT.