Evaluation of thyroid function in patients of chronic kidney disease

 

V Ratnakumari¹, P Kiranmai^2*

 

^1,2Associate Professor, Department of Biochemistry, Osmania Medical College, Koti, Hyderabad, Telangana, INDIA.

Email: drkiranmai_23@yahoo.co.in

 

Abstract               Background: Chronic Kidney Disease (CKD) is abnormal kidney function with low GFR (<60 ml/min/1.73m2) for 3 or more months. Prevalence of CKD in India is 17.2% and over 2 million people world wide receive dialysis treatment. Kidney plays an important role in the metabolism and excretion of thyroid hormones. CKD is known to affect the pituitary thyroid axis and the peripheral metabolism of thyroid hormones. Euthyroid state, hypothyroidism and hyperthyroidism have all been reported in previous studies. Considering the variation of thyroid function tests in patients with CKD in previous studies, the present study is undertaken to evaluate thyroid function and to establish a correlation if any between thyroid dysfunction and severity of CKD. Materials and Methods: 50 patients of established CKD in the age group of 30-60 yrs without thyroid disease were included in study group and 50 age matched healthy subjects formed the control group. Thyroid function is evaluated in both groups by measuring Total serum T4, serumT3 and serum Thyroid stimulating Hormone (TSH). Serum creatinine and blood urea are measured in both the study and control groups. Statistical analysis was done by student t test by comparing mean serum values. Results: In study group mean serum creatinine and mean blood urea level are higher than the mean blood urea level in control group, which is statistically significant (p<0.001). Mean value of serum T3 level was significantly less in study group (0.692±0.37) when compared to control group (1.19±0.82) (p <0.001). Mean value of serum T4 level was significantly low in study group (5.4±2.6) as compared to control group (7.86±1.94) (p<0.0001) Mean serum TSH level was significantly higher in study group (4.76±2.99) when compared to the control group (3.12±1.77) (p<0.001)).Patients with high TSH levels above normal range (0.34 to 5.6 µIU/L ) were 17. The prevalence of subclinical hypothyroidism is calculated as 34 % in study group. In control group only two subjects were having more TSH levels than normal range. So prevalence of subclinical hypothyroidism is 4 %. Conclusions: Mean serum T3and T4 levels are low and mean serum TSH levels are high in study group compared to control group suggesting association of subclinical hypothyroidism in cases of CKD.

Key Words: Chronic Kidney Disease (CKD), Serum T3, Serum T4, Serum TSH.

 

 

 

INTRODUCTION

Chronic Kidney Disease (CKD) is a public health problem affecting 5-10% of the world population¹. Global burden of disease study in 2010 ranked CKD at 18^th place in the list of causes of total number of deaths worldwide². CKD is abnormal kidney function with low GFR (<60 ml/min/1.73m2) for 3 or more months^3,4,5. Prevalence of CKD in India is 17.2% and over 2 million people world wide receive dialysis treatment⁶. Thyroid hormones T3 (Tri idoThyronine ) and T4 (Tetra iod Thyroxine) are the main regulating hormones of body metabolism. They have a significant role in the growth and development of the kidney for the maintenance of Acid base and electrolyte homeostasis^7,8. Whereas kidney plays an important role in the metabolism and excretion of thyroid hormones. CKD is known to affect the pituitary thyroid axis and the peripheral metabolism of thyroid hormones⁹. Previous studies of thyroid function in CKD patients have shown conflicting results. Euthyroid state, hypothyroidism and hyperthyroidism have all been reported by various workers^{10,11,12,13,14}. The incidence of goiter in CKD patients is also reported in literature^15,16,17. A study has reported reversion of thyroid function to normal after successful renal transplantation¹³. Development of immunemediated glomerular injury has been linked to thyroid disorders^18,19,20. Considering the variation of thyroid function tests in patients with CKD in previous studies, the present study is undertaken to evaluate thyroid function and to establish a correlation if any between thyroid dysfunction and severity of CKD.

 

MATERIALS AND METHODS

The study was conducted in the department of Biochemistry Osmania General Hospital. Fifty (50) patients of Chronic Kidney Disease (CKD) admitted in the department of Medicine in the age group of 30-60 yrs formed the study group. Diagnosis of chronic kidney disease was established based on the clinical presentation with kidney disease of > 3 months duration. and biochemical tests like Serum creatinine and Blood urea.

Exclusion Criteria: Patients with family history of thyroid disease, patients on medications like beta blockers and Corticosteroids were excluded from the study. Fifty (50) age matched healthy subjects without kidney and thyroid disease formed the control group. They were selected from the working staff of Osmania General Hospital. After taking due consent 12 hrs fasting venous sample of 5ml was collected from patients and subjects in both study and control groups. Thyroid function is evaluated in both groups by measuring Total serum T4, serumT3 and serum TSH by Chemiluminiscence Immunodiagnostic method on Seimens Advia Centaur. (Normal ranges Serum T3-0.87 to 1.78ng/ml, Serum T4- 6.09 to 12.23µgm/dl and serum TSH- 0.34 to 5.60 µIU/ml) Serum creatinine and blood urea are measured in both the study and control groups by creatininase and urease methods respectively (Enzymatic Kinetic photometric methods- Beckman coulter Autoanalyser AU 5800).

Statistical Analysis: The results are analysed on SSPS statistical software. The estimates are expressed as Mean±SD and the comparison is done by using student t test. Statistical significance is indicated by p value < 0.05.

 

RESULTS

50 patients admitted in the department of Medicine with established diagnosis of CKD based on clinical and biochemical evaluation in the age group of 30-60 yrs formed the study group. (n=50). 28 were males and 22 were females. The control group included 50 healthy age matched subjects 34 males and 16 females. Serum creatinine, blood urea, serum T4, T3 and TSH are measured in both study and control groups. In study group mean serum creatinine is 6.68±3.48, this is higher than mean of control group0.73±0.24.which is statistically significant (p<0.001). Mean blood urea level in study group 136.22±48.36 is higher than the mean blood urea level in control group 22.45±8.56, Which is statistically significant (p<0.001) Table-1.Fig-1

 

Table 1:

 

Figure 1: Comparison of serum creatinine and blood urea levels in study and control groups

Mean value of serum T3 level was significantly less in study group (0.692±0.37) when compared to control group (1.19±0.82) (p <0.001) Table-2. Fig-2. Mean value of serum T4 level was significantly low in study group (5.4±2.6) as compared to control group (7.86±1.94) (p<0.0001) Mean serum TSH level was significantly higher in study group (4.76±2.99) when compared to the control group (3.12±1.77) (p<0.001)) Table-2. Fig-2.

 

Table 2: Comparison of Serum T3,T4 and TSH mean values in study and control groups

 

Figure 2: Comparison of Mean serum T3, T4 and TSH levels in study and control groups

 

DISCUSSION
Study is conducted in 50 patients with established CKD. Control group is constituted by 50 healthy age matched subjects without kidney disease and thyroid dysfunction. In the study group serum creatinine and blood urea values are more than normal values further confirming the CKD diagnosis. The Mean serum creatinine and mean blood urea levels in study group are significantly more than the mean values in control group. Mean Serm T3 and T4 levels in study group are less than that of control group which is statistically significant. This is comparable to previous studies15,17,21,22. The probable explanation for low levels of both Serum T3 and T4 could be defective release in response to TSH or due to possible loss of thyroid hormones in the urine23 Mean Serum TSH level is higher in study group when compared to control group with statistical significance. Our study showed that there is subclinical hypothyroidism in CKD patients with prevalence of34 %. Similar report was given in previous studies 24,25 where prevalence of subclinical hypothyroidism was 24.8%. There are several hypothesis to explain the link between CKD and primary thyroid dysfunction like altered iodine metabolism, decreased sensitivity to hormones and autoimmune thyroiditis but remains unclear26. Our study showed a higher prevalence of subclinical hypothyroidism in patients of CKD and primary thyroid dysfunction with low serum T3 and T4 levels and high serum TSH levels in study group when compared to the control group. This suggests that CKD patients must be regularly screened for thyroid dysfunction and treated early to prevent complications related to thyroid hormone dysfunction.

CONCLUSIONS
Mean serum T3and T4 levels are low and mean serum TSH levels are high in study group compared to control group suggesting association of subclinical hypothyroidism in cases of CKD. Screening of all patients with CKD for thyroid dysfunction by doing thyroid profile tests is suggested for early diagnosis of subclinical hypothyroidism in CKD patients.

REFERENCES
1. Eknoyan G, Lameire N, Barsoum R. The burden of kidney disease: improving global outcomes. Kidney Int. 2004; 66:1310-4.
2. Jha V, Garcia G, Iseki K. Chronic kidney disease: global dimension and perspectives. Lancet. 2013; 382:260-72.
3. Harrison’s principles of Internal Medicine. 18th edition, chapter 280, Chronic Kidney Disease.pp-1289-94.
4. Balaji Rajagopalan et al. Renal function markers and thyroid hormone status in undialyzed chronic kidney disease, Al Ameen J Med Science 2013; 6(1):70-4.
5. Mohamed A Sobh et al. Nephrology for medical students, Urology and Nephrology Centre, University of Mansaura, Mansaura, Egypt. 45-9.
6. Couser WG, Remuzzi G, Mendis S, Tonelli M. The contribution of chronic kidney disease to the global burden of major non-communicable diseases. Kidney Int. 2011; 80(12):1258-70. 

7. Ajay K Singh et al. Epidemiology and risk factors of chronic kidney disease in India – results from the SEEK (Screening and Early Evaluation of Kidney Disease) study, BMC Nephrology 2013.14:114.
8. Gopal Basu et al. Interactions between thyroid disorders and kidney disease, Indian J Endocrinal Metab, 2012. Mar- Apr 16(2):204-13.
9. Laurence E. Carroll et al. The Stages of Chronic Kidney Disease and the Estimated Glomerular Filtration Rate, the Journal of Lancaster General Hospital Vol.1, 2006.–No.2. 

10. Ingbar HS, Woeber AK. The thyroid gland: The textbook of endocrinology. 5th ed. Williams RH (ed). Philadelphia. WB SaundersCompany: 1977;p-174 

11. Schmidt P, Stobaeus N, Prame G. Schittek F. Exophthalmos inchronic renal insufficiency. Scand J UrolNephrol 1971;5;146-53 

12. Kalz IA, Emmanovel DS, Lindheimer MD. Thyroid hormone and the kidney. Nephron 1975;15:223-49 

13. Yashpal et al. Thyroid fuction in uraemia. Ind J Nephrol (New Series) 1991; 1:2, vol.1, No.2,April-June,1991. 

14. Spector DA, Davis PJ, Helderman JH et al. Thyroid function and metabolic state inchronic renal failure. Ann Int Med 1976; 85:724-30.
15. Ramirez G. O’Neil WM, Jubiz W. Bloomer HA. Thyroid dysfunction in uraemia. Evidence with thyroid and hypophyseal abnormalities. Ann Int Med 1976;84:672
16. Silverberg DS, Ulan RA, Fawcett DM, Dossetor JB, Grace M, Beitcher K. Effects of chronic haemodialysis on thyroid fuvction chronic in renal failure. Can Med Assoc J 1974; 109:282-86
17. Lim VS, Fang VS, Refetoff S. Katz Al. T3 hypothyroidism in uraemia. Impaired T4 to T3 conversion. No. 636. Abstracts of 6th International Congress of Nephrology, 1975 

18. Ajay K Singh et al. Epidemiology and risk factors of chronic kidney disease in India – results from the SEEK (Screening and Early Evaluation of Kidney Disease) study, BMC Nephrology 2013.14:114.
19. Shin DH et al. Chronic Renal Disease is a Clinical 
indication for Thyroid Replacement Therapy in 
Subclinical Hypothyroidism. Volume 24, 2012. 

20. Sanjay Kr Singh et al. CDKD: a clinical database of kidney 
diseases, BMC Nephrology, 2012, 13:23. 

21. PaqualiniT.ZantieiferD,BalzarettiH.GranilloE,Patricia FD, Ramierz ZJ, Ruiz S. Gutman R. Ferraris J. Evidence of hypothalamus pitutitaary thyroid abnormalitieas in children with end stage renal disease. J Paed1991;118:873-78 

22. Pagliacci MC, Pelicci G. Grignani F. Giammatince FL, Carobi C, Buoncristiani U, Nicolitti I. Thyroid function tests inpatients undergoing manitenance dialysis. Nephron 1987;46:225-30 

23. Gilles R, den Heijer M, Ross AH, Sweep FC, Hermus AR, Wetzels JF. Thyroid function in patients with proteinuria. Neth J Med. 2008; 66:483- 5. 

24. Shantha GPS, Kumar AA, Bhise V, Khanna R, Sivagnanam K, Subramanian KK. Prevalence of subclinical hypothyroidism in patients with end- stage renal disease and the role of serum albumin. 2011; 1(4):255-60.
25. Khatiwada S, Rajendra KC, Gautam S, Lamsal M, Baral N. Thyroid dysfunction and dyslipidemia in chronic kidney disease patients. BMC Endocrine Disorders. 2015; 15:65.
26. Chonchol M, Lippi G, Salvagno G, Zoppini G, Muggeo M, Targher G. Prevalence of subclinical hypothyroidism in patients with chronic kidney disease. Clin J Am Society Nephrol. 2008; 3(5):1296-300.