Hyperuricemia and gout in thyroid endocrine disorders N. Giordano, C. Santacroce, G. Mattii, S. Geraci, A. Amendola, C. Gennari Institute of Internal Medicine, University of Siena, Siena, Italy Abstract Objective A significant correlation between thyroid function and purine nucleotide metabolism has been established in hypothyroidism. On the contrary, the relationship between hyperthyroidism and purine metabolism is more controversial. The present study evaluates the prevalence of hyperuricemia and gout in patients affected by primary hypothyroidism and hyperthyroidism. Methods We studied 28 patients with primary hypothyroidism and 18 patients with primary hyperthyroidism, all hospitalized because of endocrine dysfunction. All underwent a series of clinical, biochemical and instrumental evaluations; in particular, thyroid-stimulatin hormone (TSH), free thyroxine (fT4), blood urea, serum creatinine, creatinine clearance, serum and urinary uric acid levels were measured. Results In comparison to the prevalence reported in the general population, a significant increase of both hyperuricemia and gout was found in the hypothyroid patients, and of hyperuricemia in the hyperthyroid patients. In hyperthyroidism the hyperuricemia is due to the increased urate production, while in hypothyroidism the hyperuricemia is secondary to a decreased renal plasma flow and impaired glomerular filtration. Conclusions Our findings confirm the data in the literature concerning the high prevalence of hyperuricemia and gout in hypothyroidism. It shows that hyperthyroidism can cause a significant increase in serum uric acid, as well, although lower than the hyperuricemia due to thyroid hormone deficiency. Key words Hyperuricemia, gout, hypothyroidism, hyperthyroidism, pathogenesis. Clinical and Experimental Rheumatology 2001; 19: 661-665. Hyperuricemia and gout in thyroid endocrine disorders / N. Giordano et al. Nicola Giordano, MD, Assistant Introduction ed secretion of thy roid horm o n e, i n Professor; Clorinda Santacroce, MD, The association between hypothyroid- particular the manifestations of cardio- Assistant Professor; Giancarlo Mattii, ism and hyperuricemia was first sug- vascular, central nervous and cutane- MD, Assistant Professor; Simone Geraci, gested in 1955 by Kuzell and colleag- ous system invo l vement. More ove r, MD, Assistant Professor; Alessandra ues (1), who examined 520 pat i e n t s they satisfied the biochemical criteria Amendola, MD, Assistant Professor; suffering from gout and found hypo- for the diagnosis of primary hypothy- Carlo Gennari, MD, Full Professor. thyroidism in 20% of the males and in roidism (21), in particular, low serum Please address correspondence and 30% of the females. Subsequent stud- l evels of fT4 and increase titres of reprint requests to: Dr. Nicola Giordano, ies (2-10) confirmed this association, TSH. Patients with secondary (pitui- MD, Institute of Internal Medicine, University of Siena, Viale Bracci no. 1, furthermore suggesting that hypothy- t a ry and hypothalamic) hy p o t hy ro i d- 53100 Siena, Italy. roid hyperuricemia could be due to a ism, transient hypothyroidism,or a his- E-mail: [email protected] decrease in both the renal plasma flow t o ry of renal disease we re ex cl u d e d Received on December 12, 2000; and urate excretion (11-14). from the case study. In the 12 months accepted in revised form on May 22, 2001. On the contra ry, the association be- preceding their admission, 7 (25.5%) t ween hy p e rt hy roidism and hy p e r- of the 28 patients (5 women and 2 © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2001. uricemia has always been more contro- men) manifested relapsing monoarthri- versial. In 1989 Ford et al. (15),in con- t i s , wh i ch was diagnosed as acute t rast with previous rep o rts (16, 1 7 ) , gouty attacks by their doctors. These 7 demonstrated that hyperthyroidism can p atients we re tre ated with a non- cause hy p e ru ricemia through the in- s t e roidal antiinfl a m m at o ry, but they c rease of purine nu cleotide turn ove r had stopped any drug that might have and the decrease of renal urate excre- interfered with uric acid metabolism at tion. Other studies (18,19) confirmed least 2 months before their admission their findings and also suggested that to hospital. They were all on a normal hyperthyroid hyperuricemia might be purine diet. c o rrected by antithy roid drugs such The fo l l owing lab o rat o ry tests we re methimazole. However, in 1999 Raber c a rried out: cy t o m e t ric full bl o o d et al. (20) did not find any significant count, total cholesterol, triglycerides, s t atistical diffe rence in serum urat e p l a s m atic electro ly t e s , s e rum cre at i- c o n c e n t ration between hy p e rt hy ro i d nine and blood urea, creatinine clear- patients and euthyroid ones. ance, serum uric acid, 24-hour urinary Here we report our experience regard- uric acid, thyroid-stimulation hormone ing the possible relationship between (TSH), and free thyroxine (fT4) (TSH uric acid metabolism and thyroid dis- and fT3 were dosed by an automated orders, presenting data obtained from chemiluminescence immu n o a s s ay ) . patients suffering from either primary The fo l l owing eva l u ations we re also hypothyroidism or hyperthyroidism. performed: blood pressure, electrocar- di o gram (ECG), ech o c a rd i o gram , che s t Patients and methods X - ray, renal and uri n a ry tract sono- Th i rty-eight patients affected by pri- grams and thyroid sonogram. The bio- mary hypothyroidism, 20 (71.4%) wo- chemical para m e t e rs (with the ex- men and 8 (28.5%) men, aged between c eption of thy roid hormones) we re 34 and 81 years (average age, 65 ± 9.5 m e a s u red seve ral times during each years), were examined. Eighteen pri- patient’s hospitalization and 2 months mary hyperthyroid patients were stud- after the beginning of the substitute ied as well, 14 (77.7%) women and 4 hormone therapy with L-thyroxin (L- (22.2%) men, aged between 28 and 79 T4) (doses ra n ging between 75 and years (average age, 55 ± 8.3 years). All 100 g/day), while fT4 and TSH were the patients were admitted to the Insti- measured at 0, 30 and 60 days from the tute of Internal Medicine of the Uni- beginning of L-thyroxin therapy. Thy- versity of Siena during the period 1998 roid sonogram, chest X-ray, echocar- – 2000 due to signs and symptoms of diogram and renal sonogram were car- thyroid dysfunction. ried out only once, at the moment of admission. ECG and blood pre s s u re Hypothyroid patients (group A) eva l u ations we re ve ri fied fre q u e n t ly, The hypothyroid patients presented the and in particular at 30 and 60 day s classic signs and symptoms of decreas- after beginning the hormone substitu- 662 Hyperuricemia and gout in thyroid endocrine disorders / N. Giordano et al. tion therapy, in order to monitor the ef- of hospitalization. Both patients pre- normalization of TSH, fT4 and serum ficacy and tolerability of the treatment. sented increased values of uric acid in and urinary uric acid levels, as well as the serum and of urate crystals in the of creatinine and creatinine clearance Hyperthyroid patients (group B) joint fluid. In these 2 patients a diagno- values. A statistically significant corre- The 18 hyperthyroid patients presented sis of gout was made and they were lation was found between serum TSH the classic signs and symptoms of treated with colchicine (average dose: and fT4 on the one hand, and creati- increased secretion of thyroid hormone 3 mg/day, for 4 days). They had pre- nine clearance on the other (p < 0.05, (Basedow’s disease), in particular dif- sented the same articular disease at Pearson’s correlation coefficient) in the fuse goiter and manifestations of car- home before their admission. Table I group of hypothyroid patients. d i ovascular and nervous system in- shows the demographic and laboratory Table III shows the demographic and vo l vement. More ove r, t h ey sat i s fi e d data of the hypothyroid patients. laboratory data on the 20 hyperthyroid the biochemical criteria for the diagno- Table II describes the biochemical par- patients. The results first of all demon- sis of primitive hyperthyroidism (21): ameters in the 7 hyperuricemic hypo- strate that 5 (27.7%) of the hyperthy- elevated serum levels of fT4 and low thyroid patients under basal conditions roid patients presented stable hy p e r- l evels of TSH. Patients with other and 2 months after L-thyroxin treat- uricemia (demonstrated by at least 3 causes of thyrotoxicosis and patients ment. Among the hypothyroid patients, co n s e c u t i ve tests); these 5 patients wer e with a history of renal insuffi c i e n cy 9 (32.1%) presented stable hyperuri- a ffected by asymptomatic hy p e ru ri- we re ex cluded from this case study. cemia, a decrease in uric acid excretion cemia, and 3 (60%) of them were fe- None of the patients enrolled in the (in 3 consecutive tests), increased crea- males. Of the 13 (72.2%) normourice- study presented signs or symptoms of tinine, and decreased creatinine clear- mic hyperthyroid patients, 11 (84.6%) gout, either previously or at the mo- ance (Table I). Six (66.6%) of these 9 were females. Between the two groups ment of hospitalization. All were on a patients were female, and 3 (33.3%) of hyperthyroid patients, no significant normal purine diet.