Chronic kidney disease (CKD) encloses a range of different pathophysiological procedures connected with the abnormal kidney function and a continuous decrease in glomerular filtration rate (GFR <60 mL/min per 1.73 m2) for 3 or more months, irrespective of the etiology or by signs of kidney damage like proteinuria involving hematuria, abnormal imaging, micro-albuminuria, or biopsy findings¹.

Kidney is involved in the metabolism and eradication of the thyroid hormone, consequently the decline in the kidney function is assisted by changes in the synthesis, secretion, metabolism and elimination of the thyroid hormones leading to thyroid dysfunction. However, thyroid hormone is required for the growth and development of the kidney and also for the maintenance of water and electrolyte homeostasis².

Patients with chronic renal failure often have signs and symptoms suggestive of thyroid dysfunction. These findings include dry skin, shallow complexion, low temperature, cold intolerance, decreased basal metabolic rate, lethargy, fatigue, edema and hyporeflexia ³.

Various studies of thyroid functions in uremic patients have been carried out which have shown conflicting results. Hyperthyroidism, hypothyroidism and euthyroid state have all been reported by various workers. Serum triiodothyronine (T3) levels were consistently found to be low without any regard for the treatment of CRF. Serum total and free thyroxine (T4) concentrations have been reported as low, normal, or high ⁴. Serum thyroid-stimulating hormone (TSH) levels were found to be normal in most patients of CRF even in those whose CRF is complicated by low T3 concentration. A reduction in total T3, but not in free T3 concentrations were associated with an increased all-cause and cardiovascular mortality in

euthyroid CKD patients ⁵.

 Total and free T3 behave as survival markers in patients with CKD both in HD and in PD ⁶. The prevalence of hypothyroidism in end-stage renal disease (ESRD) has been estimated between 0 and 9%. There is also an increased prevalence of goiter in patients with ESRD. Though there are multiple factors which predicts the overall mortality and severity of t h e renal disease, one among the important factor is thyroid dysfunction. So it is prudent for the internist and treating physician to be aware of thyroid dysfunction so that early intervention can be instituted to improve the outcome ⁷.

Multiple procedures can account for these syndromes: alteration of peripheral hormone metabolism, possible reduction in tissue thyroid content, lowering circulating thyroid hormone concentration, disturbed binding to carrier proteins, and a raised iodine stores in thyroid glands^8,9.  Triiodothyronine (T3), the most metabolically active thyroid hormone, for example, can decrease in CKD patients even with a normal level of TSH. This is referred as ‘Low T3 Syndrome¹⁰.

Thyroid dysfunction may depict in one of the following form such as: thyroid hormone deficiency or in excess (hypothyroidism or hyperthyroidism); thyroid enlargement (diffuse or nodular); asymptomatic or symptomatic (the subclinical state or overt)¹¹. 

The glomerular filtration rate (GFR) decreases in hypothyroidism by reduced cardiac output, intrarenal vasoconstriction, raised peripheral vascular resistance, decreased renal response to vasodilators, and a decreased expression of renal Vasodilators^12,13.

 Furthermore, pathologic alteration in the glomerular structure in hypothyroidism, like thickening of the glomerular basement membrane and the mesangial matrix

expansion, might also lead to a decline in GFR¹⁴.  The influence of the hyperthyroidism on the kidney are generally opposite to the effects of  Hypothyroidism¹⁵.  Amid the pre-renal factors, thyroid hormones raise the cardiac output by a positive chronotropic and inotropic effects also a decrease in systemic vascular resistance. It raises the endothelial production of nitric oxide (NO) and leads to vasodilation.

Ethical clearance was obtained from Institute’s ethical clearance committee. Informed consent was taken from both cases and controls after explaining the procedure. 50 patients were included in this study. Patients who fulfill the criteria for CRF and who were on conservative management were taken for the study. A thyroid profile was done in all patients who fulfill the criteria. Inclusion Criteria for Chronic Renal Failure: • Symptoms of uremia for 3 months or more. • Elevated blood urea, serum creatinine, and decreased creatinine clearance. • Ultrasound evidence of chronic renal failure: Bilateral contracted kidneys – size less than 8 cm in male and female. • Poor corticomedullary differentiation. • Supportive laboratory evidence of CRF like anemia, low specific gravity, changes in serum electrolytes, etc. • Radiological evidence of renal osteodystrophy. Exclusion criteria: • Patients underwent peritoneal dialysis or hemodialysis. • Nephrotic range of proteinuria. • Low serum protein especially albumin. After selecting the patients, fulfilling the above criteria, about 5 ml of blood sample was collected in a non-heparinized serum bottle and sent for thyroid profile. Components of thyroid profile in this study • Serum triiodothyronine(T3)- 0.60-1.58 ng/ml • Serum thyroxine(T4)-4.82-15.65 μg/dl. • Serum thyroid stimulating hormone (TSH)- 0.25-5.5μI U/ml. Statistical analysis :Data was expressed in terms of mean ± SD. Chi- square test was applied to estimate the difference between the two groups of population. Unpaired ‘t’-test was used to study the changes in biochemical parameters in thyroid cases. Pearson correlation was performed to establish the relationship between study variables. p value <0.05 was considered statistically significant.

The present study was aimed to evaluate thyroid function abnormalities in chronic kidney disease. A total of 50 patients with CKD were included in the study at Department of General Medicine. In this study, the mean age of study was 54.26±16.92 years. 54% patients were male, and 46% patients were female. 28% of patients were diabetic and 54% of patients were hypertensive. 54% of patients were smoker and 36% of patients were alcoholic

The mean of serum T3 was 2.32±7.93. Total 30% patients had low, 57% patients had normal, and 13% patients had high T3 levels.

Table 1 Mean age of cases

Distribution of CKD Stages: The distribution of patients across different CKD stages is shown in Table 2.

Table 2: Distribution of Patients According to CKD Stages

Definition of Chronic Kidney Disease Chronic kidney disease is defined as abnormalities in kidney function, present for more than three months with implications for health. Chronic kidney disease stages were defined according to Kidney Disease Improving Global Outcomes (KDIGO) and classify using estimated GFR.eGFR calculated using CKD – EPI Equation (Chronic Kidney Disease Epidemiology Collaboration). Definition and classification of categories of thyroid dysfunction: Thyroid dysfunction was considered if a patient’s thyroid hormones fall outside the reference range. The categories of thyroid dysfunction were classified based on the reference intervals for the hormones and pattern of derangement in the thyroid hormones profile .The abnormal thyroid function tests result was classified into any of the following: Subclinical hypothyroidism: TSH elevation between ˃4.7 mIU/L in patients with normalserum TT3 or FT3 and TT4 or FT4. Primary subclinical hypothyroidism: TSH ˃4.7 mIU/L and suppressed serum TT3 or FT3 and TT4 orFT4T4. Primary overt hypothyroidism: TSH (>20 µIU/dl) with low serum FT4 and low FT3 Subclinical hyperthyroidism: suppressed TSH (<0.27) mIU/L and normal TT3 or FT3 andTT4or FT4 serum concentration. Overt hyperthyroidism: Suppressed TSH (<0.27) mIU/L and elevated serum TT3 or FT3 and TT4 or FT4 concentration. Non-thyroidal illness or low T3 syndrome: Low TT3 or FT3 in the presence of normal TSH, TT4 and FT4 levels. Euthyroid hyperthyroxinemic: Isolated elevation of FT4 or TT4 in the presence of TSH, FT3 and TT3 within reference limits. In our study, the mean age of study was 54.26±16.92 years. In a study by Khatiwada et al, the mean age of study population was 44.1 ± 16.4 years. In a study by Sadara and Visawa, the mean age of the patients was 34.30 ± 7.37 years. In a study by BR et al, the mean age was 53.93±9.91 years. In our study, 54% patients were male, and 46% patients were female. In a study by Khatiwada et al, 17the study population comprised 360 CKD patients with 53.8% males and 46.1% females. In a study by Enia et al, 12 patients were male and 2 patients were female in group I, in group II 7 patients each was male and female while group III 7 patients each was male and female. In a study by Rafeeq et al, 80% were male and 20% female. In our study, 54% of patients were hypertensive, 28% of patients had diabetic, 54% of patients had smoker, 36% of patients had alcoholic. In a study by Enia et al, in I tertile <5.9 pg/ml, 64% patients were smoker, 14% patients were diabetics and 71% hypertensive, in II tertile 6.0–10.9 pg/ml, 54% were smoker, 15% were diabetics and 61% hypertensive and III tertile >10.9 pg/ml, 50% patients were smoker, 21% patients were diabetics and 71% hypertensive.. Thyroid Hormone In our study, the mean of T3 was 2.32±7.93.30% patients had low, 57% patients normal, and >30%patients had low T3 levels. The mean of serum T4 was 6.64±2.74.21% of patients had low while 79% patients had normal T4 levels. The meaning of TSH was 5.27±6.67.1% of patients had low, 82% patients had normal, and 17% patients had high TSH levels. In a study by Manickam, the prevalence of low T4 among the males was 18.9% and among the females was 30.8%. The difference among the sexes was not statistically significant i.e., P>0.05. The prevalence of TSH in clinical hypothyroidism range among males was 2.7%. And among the females was 7.7%. The prevalence of the sexes was not statistically significant (P>0.05). In a study by Rafeeq et al, T3 level varied from 0.2 to 2 ng/ml. The mean value of T3 was 0.67ng/ml. Excluding the patients with primary hypothyroidism, the mean value is 0.71 ng/ml. This value was in low normal limit. Serum T4 level in the study varies from 0.5 to 9.5 µg/dl. Mean value of serum T4 among 50 patients 5.62 µg/dl .Excluding hypothyroid patients, the mean value is 5.99 µg/dl. This value is within the low normal level of T4. Values of TSH vary from 0.6 to 27µIU/ml with mean value in 6.53 µIU/ml. Excluding hypothyroidism mean value is 4.75 μIU/ml. In a study by Okaka et al, T3 levels had a negative correlation with age. This agrees with the findings in previous studies, for T3 levels. It is thought that age-dependent decline in T3 levels is due to the decreased deiodination of T4 to form T3 that occurs with advancing age. In addition, the prevalence of anti-thyroperoxidase and antithyroglobulin antibodies increases with age,

The present study was aimed to evaluate thyroid function abnormalities in chronic kidney disease. A total of 100 patients with CKD were included .Total 30% patients had low, 57% patients had normal, and 13% patients had high T3 levels. 21% patients had low while 79% patients had normal T4 levels. 1% patients had <0.25, 82% patients had 0.25-5.50, and 17% patients had >5.50 TSH levels. It was observed that the patients with severe renal disease had a significantly lower T3 levels (P<0.0001). Although, we could not found significant association between T4, TSH and severity of renal disease but small sample size and single centre study was our limitation.

Future study:Further studies on these parameters on large scale is required to establish diagnosic and prognostic role of these parameters in Diabetes mellitus.

Acknowledgement : I would like to thank my teachers, my family  for their  constant guidance and support throughout the study.

Source of support : Nil

Conflict of interest : None declared

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