Increase in thyroid stimulating hormone levels in patients with gout treated with inhibitors of xanthine oxidoreductase

Abstract

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.

Association between Decreased Thyroid Stimulating Hormone and Hyperuricemia in Type 2 Diabetic Patients with Early-stage Diabetic Kidney Disease

“…However, the majority of previous studies are consistent with our ndings. A previous large-scale cross-sectional study documented a linear association between FT4 and SUA in general subjects [12]. The risk of hyperuricemia was also signi cantly increased in individuals with higher FT4 level [12].…”

“…A previous large-scale cross-sectional study documented a linear association between FT4 and SUA in general subjects [12]. The risk of hyperuricemia was also signi cantly increased in individuals with higher FT4 level [12]. Additionally, a recent study also demonstrated that the decrease of SUA by the treatment of febuxostat or allopurinol exerted effects on the elevation of TSH in patients with gout [13].…”

“…Some studies supported that there was a higher risk of hyperuricemia in patients with hypothyroidism [10] or with subclinical hypothyroidism [11] relative in comparison to the general subjects. On the other hand, a linear relationship between free thyroxine (FT4) and SUA was observed in a large-scale cross-sectional clinical study in individuals without overt thyroid dysfunction [12]. Moreover, a recent study has also demonstrated that the decrease of SUA by the treatment of febuxostat or allopurinol led to the increase of TSH in patients with gout [13].…”

Risk of Thyroid Disorders in Patients with Gout and Hyperuricemia

“…Additionally, several observational studies reported abnormally increased level of serum uric acid among patients with hypothyroidism or hyperthyroidism, suggesting that uric acid may be involved in development or progression of thyroid dysfunction [45][46][47]. Finally, urate-lowering drugs used in patients with gout or hyperuricemia proved to increase TSH level in a dose-dependent way, providing another explanation for the increased risk of hypothyroidism among patients with gout or hyperuricemia [48]. However, the molecular mechanisms underlying the increased risk of thyroid disorders among gout and hyperuricemic patients are still elusive, and need to be explored in future research.…”

Febuxostat for Treatment of Chronic Hyperuricemia in Gout Patients

“…При длительном применении фебуксостата у 5,5% пациентов отмечалось повышение концентрации тирео-тропного гормона (>5,5 мкМЕ/мл), в связи с чем пациен-там с нарушением функции щитовидной железы фебук-состат следует назначать с осторожностью [67].…”