To date, very limited studies have examined the relationship between subclinical hypothyroidism and biochemical markers that indicate renal function [
9,
12-
14]. All of these studies have been conducted in adults. By searching in MEDLINE, we could not find any study about this subject in pediatric patients and the recent study seems to be the first study to examine the relationship between subclinical hypothyroidism and biochemical markers of kidney function in children. In this case-control study, we recruited 56 children with subclinical hypothyroidism in the case group and 51 healthy children in the control group and finally we concluded that serum creatinine was significantly higher in the case group than the control group. The results showed that, although the amount of uric acid in the subclinical hypothyroid children group was slightly higher than healthy children, this difference was not statistically significant. In line with our study, Tayal et al. [
9], in a case-control study that includes 98 patients in the subclinical hypothyroidism group, 89 in the overt hypothyroidism group and 187 in the control group, stated that serum creatinine level was significantly higher in subjects with subclinical and overt hypothyroidism than in control group (
P<0.01). In line with the results of our study, they did not show a significant increase in serum uric acid in patients with subclinical hypothyroidism in comparison to the control group. In a similar study, Kaur et al. [
12] examined the relationship between overt and subclinical hypothyroidism and renal function. In their research, 100 subjects in the control group, 50 in the overt hypothyroidism group and 50 in the subclinical hypothyroid group were studied. All participants in the study were between 20–70 years of age. At the end, they also concluded that subclinical hypothyroidism significantly increased serum creatinine (
P<0.001), while they did not show significant increases in serum uric acid. Verhelst et al. [
13] in a study that was designed to find out the relationship between serum creatinine and other Guanidino compounds in patients with thyroid dysfunction, concluded that in patients with subclinical hypothyroidism, serum creatinine levels increased. In their study, uric acid serum was not measured. Liang et al. [
14], in a study that was conducted on 356 subclinical hypothyroid patients in the case group and 331 in the control group, concluded that serum uric acid in subclinical hypothyroid patients significantly increased. In their study, serum creatinine was not studied. Regarding serum uric acid levels in subclinical hypothyroid patients, the results of our study were in line with most studies and contrary to the results of Liang study. For this purpose, one of the important tasks of thyroid hormones (T3 and T4) is to regulate various metabolic pathways in the body. One of these metabolic pathways that can be affected by thyroid hormones, is purine metabolism pathway. This metabolic pathway is one of the most effective cycles in the production of uric acid. Increasing or decreasing T3 and T4 leads to changes in the purine metabolism cycle and ultimately alteration in production of uric acid [
4,
15,
16]. Whereas in subclinical hypothyroidism, the blood levels of T3 and T4 hormones are maintained within the normal range, and it is therefore entirely reasonable that the level of uric acid remains in the natural range. In addition, several authors in their research on hypothyroidism have investigated the serum levels of uric acid in patients with overt and sub-clinical hypothyroidism simultaneously [
9,
10,
12]. Tayal et al. [
9] concluded that although subclinical hypothyroidism does not change serum levels of uric acid, but in patients with clinical hypothyroidism, the serum levels of uric acid clearly increase. In their study, TSH levels were reported in the clinical hypothyroid group as 41.46±1.01 and TSH levels in subclinical hypothyroid patients was 11.9±0.50. Kaur et al. [
12] obtained similar results with Tayal regarding serum uric acid levels in patients with overt and subclinical hypothyroidism. In their study, TSH levels in the clinical and subclinical hypothyroid patients were 46.06±58.06 and 7.12±1.32, respectively. Arora et al. [
10], demonstrated that in patients with overt hypothyroidism, serum uric acid levels were significantly higher than in the control group. The level of patient’s TSH in this study was 36.44±15.48. So it seems that serum uric acid increases at high levels of TSH. However, in patients with subclinical hypothyroidism, the mean TSH was 8.94±4.80 in the present study.
In justifying the findings of recent research on serum creatinine levels, it can be stated that increasing serum creatinine levels in patients with subclinical hypothyroidism is quite reasonable. Various studies have demonstrated that increased levels of TSH, both in hypothyroidism and in subclinical hypothyroidism, are associated with a decrease in GFR. Following a reduction in GFR, renal plasma flow decreases and consequently serum creatinine increases.18-20]. In this study, we could not find any relationship between renal function factors and thyroid parameters. Although few studies have investigated this issue, but studies by Tayal et al. [
9] and Kaur et al. [
12] confirm our results. They also failed to achieve a relationship between the parameters of renal function and thyroid tests in adult patients with subclinical hypothyroidism. Due to the high similarity in the function of thyroid hormones in children and adults in many cases, these findings can be generalized to children.
At the end, it should be noted that since subclinical hypothyroidism is a relatively common condition in children [
21], all of its aspects, especially its association with renal function, physicians should be trained on it. This is especially important when it has been shown that abnormal kidney function in patients with hypothyroidism is reversible [
9,
22]. In addition, a study by Elgadi et al. [
23] has shown that in the long term, in children with hypothyroidism treated with levothyroxine, decline in renal function will return 1–5 years after the onset of treatment. Considering the results of this study and the above mentioned issues, it seems that monitoring of renal function in children with subclinical hypothyroidism should be considered. Moreover, in the presence of creatinine changes, subclinical hypothyroidism can be considered as one of the causes that increases this factor. It is suggested that future studies with a larger sample size be done to confirm the results of recent research on children with subclinical hypothyroidism.