Chronic kidney disease (CKD) are determined by permanent kidney damage and progressive loss of kidney function. The stages of CKD are classified based on glomerular filtration rate (GFR). Stage 5 is called the end stage renal disease (ESRD), in which the patient´s life becomes dependent on renal replacement therapy (dialysis or transplant).  The onset of CKD can be asymptomatic, or with symptoms gradually appearing with decreasing glomerular filtration rate (GFR).  The symptoms of CKD include anorexia, nausea, vomiting, weight loss, fatigue, drowsiness, irritability, seizures, encephalopathy, and coma. Water - electrolyte imbalance, metabolic acidosis, hypertension, anemia, hyperphosphatemia and bone disorders, and uremic syndrome are other associated disorders (1-3).
The thyroid gland is one of the important endocrine glands has a profound effect on increasing the body metabolism by secreting the two main hormones thyroxine (T4) and triiodothyronine (T3). The anterior pituitary gland regulates thyroid function by secreting Thyroid Stimulating Hormone (TSH). Hypothyroidism refers to cases in which the function of the thyroid gland is reduced. Symptoms of hypothyroidism include fatigue and weakness, impaired concentration and memory loss, constipation, weight gain, decreased appetite, decreased libido, and dry rough skin. Assessment of serum thyroid stimulating hormone (TSH) levels is essential for the diagnosis of primary hypothyroidism. In fact, normal serum TSH levels rule out primary hypothyroidism. Measurement of serum thyroxine (T4) levels is necessary to confirm the presence of clinical hypothyroidism if serum TSH levels are elevated. If the T4 levels were normal, the disorder would be called subclinical hypothyroidism (4,5).
In patients with kidney disease, thyroid dysfunction occurs as a result of impaired blood flow, impaired metabolism of proximal hormones and carrier proteins. In addition, CKD affects the hypothalamic-pituitary-thyroid axis. The combination of the above factors can increase the risk of primary and subclinical hypothyroidism. (6,7)
The clinical signs and symptoms of hypothyroidism overlap with CKD. These two diseases cannot be differentiated only on the basis of clinical symptoms ,therefore, the diagnosis of hypothyroidism may be delayed (7-9).
Due to the great importance of the thyroid gland in the metabolism of human body and its role in increasing cardiovascular disease and quality of life, the goal of our study was to evaluate the rate of hypothyroidism in patients with CKD who need hemodialysis, emphasizing that paying more attention to the early diagnosis of hypothyroidism in CKD can help to improve the quality of life and reduce the rate of disability in patients. This article is the result of a research study on the prevalence of hypothyroidism in chronic kidney disease conducted for the first time in our region that can help to increase the epidemiological information on the disease and be a basis for increasing knowledge in the diagnosis and treatment of these disorders.

 

According to the inclusion and exclusion criteria, a total of 108 patients were included in the study, 58 (53.7%) male and 50 (46.3%) female. 97 people (89.8%) were urban and 11 (10.2%) were rural residents. The mean age of the patients was 61.09 ± 13.45years. 26 people (24.08%) were under 50 years and 82 (75.92%) were over 50 years.104 particip (96.3%) were married and 4 (3.7%) were single. In our study, the etiology of CKD based on the information contained in the patients' records was as follows: 52 patients (48.14%)with hypertension, 14 patients (12.96%) with diabetes, 4 patients (3.7%) with glomerulonephritis, 7 patients (6.48%) with polycystic kidney disease, 7 patients (6.48%) with urological problems, 10 patients (9.25%) with both diabetes and hypertension and 14 patients (12.96%) unspecified (table1).
The normal values of T4, T3, TSH based on the values mentioned in the kit used for adults are as follows:
TSH: 0.4 – 4.5 µIU/mL              T3: 0.7-1.9 ng/dL             T4: 5-µg/dl
In our study, the mean values of patients' hormone levels were as follows:
TSH:1.64±1.78 µIU/mL              T3:0.88 ± 0.2ng/dl    T4:7.7±1.6 µg/dl
Serum TSH levels in 8 patients (7.4%) were higher than normal; serumT4 levels in 4 patients (3.7%) were lower than normal; and serum T3 levels in 11 patients (10.2%) were lower than normal. In our study, hypothyroidism was diagnosed as TSH> 4.5 µIU/mL with T4 <5 µg /dl, and subclinical hypothyroidism was diagnosed as high TSH and normal T4. Thus, 8 patients (7.4%) had thyroid dysfunction, of whom 4 patients (3.7%) had hypothyroidism and 4 patients (3.7%) had subclinical hypothyroidism (table1).

Table1. Characteristics of the study participants

Among those with high serum TSH levels, 7 people (8.5%) were over 50years and one (3.8%) was under 50 years (P:0.67). 4 patients (50%) were male and 4 (50%) were female. All of 8 (100%) abnormal TSH serum levels belonged to urban residents. The mean weight of patients was calculated based on body mass index, which was 26.2 ± 2.3 kg / m² in patients with thyroid disorder and 24.3 ± 3.4 kg / m² (P:0.12) in other patients . In patients with thyroid disorder, the mean systolic blood pressure was 145±25 mm Hg and diastolic blood pressure was 80±10 mm Hg; in other patients mean systolic and diastolic blood pressures were 135 ±15 mm Hg and 85±5 mm Hg, respectively (P<0.09).In this study, although people with severe disorder in fasting blood sugar and lipid profile were excluded, people with hypothyroidism had significantly higher blood sugar and lipid levels (P<0.01) (table2).

…Fisher Exact test
…… Independent t test

Discussion

It is estimated that the average rates of clinical hypothyroidism and subclinical hypothyroidism in the normal population are about 0.3% and 4.3% respectively These rates may vary from about 1% in the East Asia to about 4.6 percent in the United States. Recent studies have reported a higher rate of thyroid dysfunction in people with kidney failure treated with dialysis (8-14). In our study, 7.4% of the patients had high TSH levels and thyroid dysfunction, 3.7% of patients had decreased T4 levels and clinical hypothyroidism, and 3.7% of the patients had subclinical hypothyroidism; these rates of hypothyroidism were higher than the normal population(1) but lower than those reported in the Chandra’s study(2016) in India(11).
There are interactions between thyroid and kidney functions. Hypothyroidism affects the final function of the kidney by affecting renal blood flow and reducing GFR, as well as impairing renal tubular function. On the other hand, renal failure affects thyroid function by several mechanisms. These include decreased levels of circulating thyroid hormones, altered peripheral hormone metabolism, decreased carrier proteins binding, decreased tissue hormonal content, and increased iodine storage in the thyroid. In addition, CKD affects the hypothalamic-pituitary-thyroid axis. The above set of factors can lead to primary and subclinical hypothyroidism. It is suggested that the decrease in thyroid gland activity occur following the accumulation of waste products in patients, because the levels of these hormones increase after hemodialysis compared to previous levels (10,15-18). The results of our study were consistent with various studies showing that thyroid hormone levels were lower in hemodialysis patients than in healthy individuals.
According to the findings of some studies in CKD patients, plasma T3 levels are often reduced, which can be due to a defect in the peripheral conversion of T4 to T3 as a result of uremia (19-21). In the study by Jusufovic, serum T3 and T4 levels were lower than normal and TSH was higher than normal in dialysis patients and low T3 syndrome was reported in 12.5% of the patients (22). In our study, the mean serum level of T3 was 0.88± 0.21 ng/dL, which was lower than normal in 10.2% of the patients. This result is consistent with previous studies.
In a study by Chonchol, 3,080 outpatients were studied and the prevalence of subclinical hypothyroidism was indicated 9.5%, which increased with decreasing GFR and  the rate of subclinical hypothyroidism increased with age but was not related to gender (8). In our study, the rate of hypothyroidism was equal in both sexes (4 men and 4 women) and its prevalence was higher in people over 50 years (P<0.05).
Hypothyroidism causes an increase in inflammatory markers in the vascular intima and ultimately exacerbates atherosclerosis and disorders of the systole and diastole of the heart leading to increased mortality from cardiovascular disease. Various studies have shown that there is an association between the rate of subclinical hypothyroidism in CKD patients and the risk factors for cardiovascular disease (21, 23-25). In our study, patients with hypothyroidism also had higher BMIs, higher blood pressure, higher blood sugar and lipid levels which could increase the risk of cardiovascular disease.

 

Study Limitations

 One of the problems of our study was the small sample size. Obviously, if a study is conducted with a larger sample size, more accurate results will be obtained. We recommend that future studies compare the levels of hormones at the start of dialysis and 3 months later.

 

Conclusion

Based on our study, the rate of clinical and subclinical hypothyroidism in CKD patients who need hemodialysis is higher than the normal population. Since hypothyroidism can affect the quality of life of CKD patients and increase their cardiovascular complications and mortality and morbidity, it is recommended that serum T4 and TSH levels be measured regularly in CKD patients.

 

Acknowledgements

We would like to thank Kurdistan University of Medical Sciences and staff of hemodialysis ward of Tohid hospital in Sanandaj for their cooperation.

 

Conflicts of Interest

Authors declare conflict of interest.