European Journal of Cardiovascular Medicine

Thyroid dysfunction has been demonstrated to alter the functioning of all organ systems in the body, including the heart, muscles, and brain. Thyroid hormone levels exert an influence on renal function. The thyroid hormone exerts its influence on the kidney by inducing systemic or local hemodynamic alterations and directly impacting its function [1]. Thyroid dysfunction can also result in notable alterations in kidney blood flow, glomerular filtration rate (GFR), tubular secretory and absorptive capacity, electrolyte pumps, and kidney structure. Both hypothyroidism and hyperthyroidism patients exhibit significant alterations in renal function [2]. Previous studies have found a connection between different forms of glomerulopathies and both hyper- and hypofunction of the thyroid gland [3]. Nevertheless, there is a lack of clinical trials investigating the relationship between thyroid dysfunction and renal function, and our understanding of how thyroid disease impacts renal function in people is limited. Furthermore, the impact of thyroid hormones on the kidneys in humans can be cleverly disguised, as alterations in the measured parameters of kidney function often fall within the expected range.
The objective of this study was to assess renal function by measuring serum levels of urea, creatinine, estimated glomerular filtration rate (eGFR), and uric acid. Additionally, the study aimed to determine if there is any link between these renal function markers and thyroid hormones (FT3, FT4, TSH).

Case-control research was undertaken at Index Medical College and Hospital, Indore, to investigate the relationship between Renal Function Tests and Thyroid Hormones in patients with thyroid problems. A total of 319 cases were evaluated, including 100 controls, 294 patients with hypothyroidism, and 25 patients with hyperthyroidism. The participants were divided into three age categories: 21-30, 31-40, and 41-45. The control group was selected to match the age of the participants.

Selection Criteria:

This study comprises a cohort of 419 patients aged between 20 and 60 years. The duration of the study was 3 years, and the subjects were divided into 3 groups.

Group I: Primary hypothyroidism.

Group II: Primary hyperthyroidism.

Group III: Control group.

Population study:

The people attending outpatient at the Medicine Department.

Inclusion criteria:

Patients with primary Hypothyroidism and primary Hyperthyroidism are in the age group 20-60 years.

Exclusion criteria:

1. Pregnancy
2. Lactating mothers
3. Secondary thyroid dysfunction
4. Alcohol and smoking
5. History of Renal or Hepatic disease
6. History of various endocrine disorders
7. History of medications that can affect UA or thyroid hormone levels.

Ethical Consideration:

The current study was carried out after the approval of the Institutional Ethics Committee (IEC) to use human subjects.

Sample collection:

The sample was taken together with a comprehensive medical history. The clinical examination encompasses the assessment of Body Mass Index (BMI) in kilograms per square meter, as well as the consideration of age and gender distribution. The laboratory study involves measuring thyroid hormone levels, namely free T3, Free T4, and TSH, using the ELISA method. Urea, creatinine, and uric acid levels were measured using the EM-360 fully automated system. The fasting blood sample was obtained, then subjected to centrifugation, and the resulting serum was stored in the refrigerator for future utilization.

Statistical Analysis:

The biochemical parameters were compared between the patients and controls using a student t-test. The results were expressed as standard deviation. The statistical software package SPSS Version 21 was utilized to compute Karl Pearson's correlation coefficient in order to establish the relationship between the parameters across the cases. A significance level of p<0.05 was regarded statistically significant, while a significance level of p<0.01 was considered extremely significant.

The results of our study showed a significant increase in the average levels of serum urea (36.26±3.69) and uric acid (6.55± 0.34) in patients with hypothyroidism. This increase was statistically significant with a p-value of less than 0.001. Similarly, we observed a significant increase in serum urea (29.98±2.17) and uric acid (6.59± 0.34) levels in patients with hyperthyroidism, with a p-value of less than 0.001. On the other hand, hyperthyroid patients showed a decrease in serum creatinine levels (0.70± 0.04) compared to the control group, resulting in an increase in estimated glomerular filtration rate (eGFR) (121.55± 5.79). In contrast, the hypothyroid group exhibited a significant increase in creatinine levels (1.04± 0.05) (p value < 0.001), leading to a decrease in eGFR (102.05± 5.38) compared to the control group (Table 2).

Table No – 1. Comparison of FT3, FT4 and TSH among the study and control group.

*Highly significant at the 0.01 level.

Table No- 2: Comparison of Kidney parameters among the study and control group.

Table No- 3. Correlation between TSH with different parameters among Hyperthyroid group.

*Correlation is significant at the 0.05 level.

Table No 4. Correlation between FT3 with different parameters among Hyperthyroid.

*Correlation is significant at the 0.05 level.

Table No- 5.  Correlation between FT4 with different parameters among Hyperthyroid.

*Correlation is significant at the 0.05 level.

Table No-6. Correlation between TSH with different parameters among Hypothyroid.

*Correlation is significant at the 0.05 level.

Table No- 7. Correlation between FT3 with different parameters among Hypothyroid.

*Correlation is significant at the 0.05 level.

Table No- 8. Correlation between FT4 with different parameters among Hypothyroid.

*Correlation is significant at the 0.05 level.

The serum creatinine levels exhibited a notable positive association with TSH in both the hyperthyroid and hypothyroid groups (r= 0.465 and r= 0.524, respectively), as indicated in Table 3 and Table 6. However, there was no significant negative connection observed between serum creatinine and FT3 or FT4 in either group. The eGFR exhibited a noteworthy inverse association with TSH in both the hyperthyroid and hypothyroid groups (r = -0.677, r = -0.586) (Table 3, Table 6), while it displayed an insignificant positive connection with FT3 and FT4 in both groups. The study found a strong positive relationship between TSH levels and serum creatinine levels, as well as a strong negative relationship between TSH levels and estimated glomerular filtration rate (eGFR) in all individuals with thyroid dysfunction. There was no significant association observed between serum urea and thyroid hormones in both the hyperthyroid and hypothyroid groups. Among patients with hyperthyroidism, there was a statistically significant negative connection between serum uric acid (SUA) and TSH (r = -0.705) (Table 3). Additionally, there was a substantial positive correlation between FT3 (r = 0.501) (Table 4) and FT4 (r = 0.522) (Table 5). We observed no significant connection between serum uric acid (SUA) levels and thyroid function tests in patients with hypothyroidism.

The interaction between thyroid and kidney function is well-established, with thyroid illness having a significant impact on renal function, particularly by altering glomerular filtration rate (GFR) [6,7]. Various renal function tests are commonly utilised in routine clinical practice, with blood creatinine and eGFR being the most frequently utilised indicators. The aim of our study was to investigate the potential influence of thyroid dysfunction on the laboratory markers of renal function. The latest research indicates that there are significant discrepancies in kidney function that are directly linked to the seriousness of thyroid disease. Regardless of whether renal function is measured by creatinine levels or eGFR, the alterations observed are identical. In our study, we observed a significant decrease in serum creatinine levels in hyperthyroid individuals, which led to an increase in glomerular filtration rate (GFR). Conversely, we found that creatinine levels fell in hypothyroid patients, resulting in an increase in GFR. The TSH levels exhibited a notable positive association with serum creatinine levels and a substantial negative association with eGFR in all patients with thyroid impairment. The results presented here are consistent with the findings of prior research studies [2,7,8]. The notable elevation in serum creatinine was associated with a rise in TSH levels. Prior research indicates a reversible increase in serum creatinine levels among individuals with hypothyroidism [3,8]. Verhelst et al. demonstrated that those diagnosed with hyperthyroidism exhibited decreased levels of serum creatinine, whereas those with hypothyroidism displayed somewhat elevated numbers[9]. Moreover, a majority of persons with hypothyroidism undergo a reversible decline in glomerular filtration rate (GFR), usually amounting to approximately 40%. The decrease in glomerular filtration rate (GFR) in hypothyroid patients is caused by several factors, including lower cardiac output, higher peripheral vascular resistance, constriction of blood vessels in the kidneys, reduced kidney response to substances that dilate blood vessels, and decreased production of renal vasodilators such as vascular endothelial growth factor and insulin-like growth factor-1. These factors likely contribute to the decrease in blood flow to the kidneys in individuals with hypothyroidism. Hypothyroidism can cause pathological changes in the glomerular structure, including thickening of the glomerular basement membrane and expansion of the mesangial matrix. These changes might result in decreased blood flow to the kidneys. The decrease in glomerular filtration rate (GFR) is caused by a decrease in sensitivity to adrenergic stimulation, a reduction in the production of renin, lower levels of angiotensin II, and an overall decrease in the activity of the renin-angiotensin system [2]. Hypothyroidism leads to impaired growth of the renal parenchyma, resulting in a reduced glomerular surface area for filtration, which imposes structural constraints. Furthermore, there is a reduction in the uptake of electrolytes such as sodium, chloride, and water by the proximal tubules. The expression of the chloride channel in the basolateral region of the kidney is likewise reduced. Consequently, the reduced reabsorption of chloride causes an elevation in the amount of chloride reaching the distal part of the kidney, triggering the activation of tubuloglomerular feedback through the macula densa. This, in turn, reduces the activity of the renin-angiotensin system (RAS). Consequently, the glomerular filtration rate (GFR) falls (1,2). Effective treatment typically leads to the normalisation of renal function by regulating thyroid hormones [2,3]. Hyperthyroidism, which is marked by an overproduction of thyroid hormones, has a significant effect on the activities of the heart and kidneys [2]. It enhances heart function by increasing heart rate and contractility, resulting in an enhanced cardiac output. Hyperthyroidism leads to the stimulation of the renin-angiotensin system, resulting in an increase in both blood volume and renal blood flow. In addition, excessive synthesis of thyroid hormone reduces the resistance in the arterioles of the kidney, leading to an increase in glomerular pressure and filtration rate [2]. Tubuloglomerular feedback is initiated, resulting in a decrease in chloride load and a subsequent increase in filtration. Lower levels of serum creatinine in hyperthyroid patients indicate enhanced glomerular filtration rate (GFR) and decreased muscle mass. By treating hyperthyroidism, the adverse consequences are reversed, leading to the restoration of cardiac and renal function, as well as the normalisation of creatine levels [10].Hyperthyroid patients experience an elevation in glomerular filtration rate (GFR) and a reduction in total muscle mass, leading to decreased levels of serum creatinine. These lower levels of serum creatinine act as an inverse indication of GFR [10]. These findings indicate that the influence of thyroid hormone levels on glomerular filtration rate (GFR) can explain the differences in blood creatinine levels seen in various thyroid diseases. While these variations may appear insignificant, they might have substantial consequences for individual patients. Hypothyroidism can cause alterations in glomerular filtration rate (GFR), which might have an impact on individuals who are taking drugs with limited therapeutic ranges, such digoxin or metformin. This can potentially result in hazardous effects. Our research has revealed an important implication: it is essential to do thyroid hormone screening in patients who have unexplained increases in serum creatinine levels in order to identify any underlying hypothyroidism. Uric acid (UA) is an antioxidant that is largely synthesised by the liver. It plays a crucial role in safeguarding cell membranes and DNA from harm caused by free radicals [17]. It acts as a significant antioxidant in relation to several biochemical factors and is impacted by thyroid function [18]. Thyroid disease can interfere with the metabolism of UA, which may result in an elevation of its levels [19]. The association between thyroid dysfunction and UA metabolism has produced conflicting results [20]. Although certain studies have found a limited connection between thyroid stimulating hormone (TSH) levels and serum uric acid (SUA) levels [21,22], earlier research has observed a significant occurrence of increased UA levels in both hypothyroidism [23] and hyperthyroidism [23,24]. The elevation of UA levels in thyroid diseases may be attributed to an enhanced rate of purine metabolism in primary hyperthyroidism and decreased renal perfusion and glomerular filtration rate (GFR) in primary hypothyroid patients [25,26].

Thyroid issues can impact the process of purine metabolism, leading to elevated amounts of uric acid (UA) in the bloodstream. Prior research has observed a significant occurrence of hyperuricemia in persons with thyroid problems, however the connection between levels of thyroid stimulating hormone (TSH) and levels of uric acid in the blood appears to be restricted. Our study found a strong negative correlation between uric acid and TSH, as well as a significant positive correlation between uric acid and FT3 and FT4 in patients with hyperthyroidism. These investigations by Giordano et al. [11] and Sato et al. [12] propose that FT4 and FT3 may enhance purine nucleotide turnover by affecting the kidneys, particularly in cases of hyperthyroidism. In contrast, prior research conducted on patients with hypothyroidism did not find any notable association between uric acid levels and thyroid function tests. Arora et al. [13] found that there is a negative connection between uric acid and T3 levels in persons with hypothyroidism. Several studies, such as those conducted by See et al. [14], Saini et al. [15], and Raber et al. [16], have demonstrated a weak or inadequate connection between TSH and blood uric acid levels.

Our investigation revealed a statistically significant rise in the mean levels of serum urea, creatinine, and uric acid in patients with hypothyroidism. Additionally, there was a statistically significant increase in the mean levels of serum urea and uric acid in patients with hyperthyroidism. Nevertheless, hyperthyroid patients had a reduction in serum creatinine levels, resulting in an elevation of estimated glomerular filtration rate (eGFR). The study found a strong positive relationship between TSH levels and serum creatinine, as well as a strong negative relationship between TSH levels and eGFR, in all individuals with thyroid dysfunction. Thyroid dysfunction is linked to abnormal kidney function. Therefore, it is important for the clinician to recognise the connection between thyroid disorders and unusual biochemical markers of renal function. This awareness will help them decide whether to perform a thyroid function test for a patient with only slightly elevated biochemical markers of renal function. Furthermore, these data underscore the importance of monitoring uric acid levels in patients with thyroid disease. Additional research is needed to investigate the potential adverse impact of thyroid disease on renal function. It is crucial to closely observe and track the condition of these patients

1. Iglesias P, Bajo MA, Selgas R, Díez JJ: Thyroid dysfunction and kidney disease: an update. Rev Endocr Metab Disord. 2017, 18:131-44. 10.1007/s11154-016-9395-7
2. Dousdampanis P, Trigka K, Vagenakis GA, Fourtounas C: The thyroid and the kidney: a complex interplay in health and disease. Int J Artif Organs. 2014, 37:1-12. 10.5301/ijao.5000300
3. Saini V, Yadav A, Arora MK, Arora S, Singh R, Bhattacharjee J: Correlation of creatinine with TSH levels inovert hypothyroidism - a requirement for monitoring of renal function in hypothyroid patients?. ClinBiochem. 2012, 45:212-4. 10.1016/j.clinbiochem.2011.10.012
4. Rifai N, Horvath AR, Wittwer CT: Tietz Textbook of Clinical Chemistry And Molecular Diagnostics . ElsevierInc., St. Loius, Missouri; 2018.
5. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease study group. Ann Intern Med. 1999, 130:461-70. 10.7326/0003-4819-130-6-199903160-00002
6. Iglesias P, Díez JJ: Thyroid dysfunction and kidney disease . Eur J Endocrinol. 2009, 160:503-15. 10.1530/EJE-08-0837
7. Kimmel M, Braun N, Alscher MD: Influence of thyroid function on different kidney function tests . Kidney Blood Press Res. 2012, 35:9-17.10.1159/000329354
8. den Hollander JG, Wulkan RW, Mantel MJ, Berghout A: Correlation between severity of thyroid dysfunction and renal function. Clin Endocrinol (Oxf). 2005, 62:423-7. 10.1111/j.1365-2265.2005.02236.x
9. Verhelst J, Berwaerts J, Marescau B, et al.: Serum creatine, creatinine, and other guanidino compounds in patients with thyroid dysfunction. Metabolism. 1997, 46:1063-7. 10.1016/S0026-0495(97)90279-1
10. Hataya Y, Igarashi S, Yamashita T, Komatsu Y: Thyroid hormone replacement therapy for primary hypothyroidism leads to significant improvement of renal function in chronic kidney disease patients. Clin Exp Nephrol. 2013, 17:525-31. 10.1007/s10157-012-0727-y 2023