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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 2  |  Page : 94-100

Study of the thyroid functions in patients with chronic kidney disease at Alexandria University Children’s Hospital


1 Department of Pediatrics, Pediatric Endocrinology Unit, Alexandria, Egypt
2 Department of Pediatrics, Pediatric Nephrology Unit, Faculty of Medicine, Alexandria University, Alexandria, Egypt
3 Department of Pediatrics, Pediatric Endocrinology Unit, Egypt

Date of Submission28-Apr-2020
Date of Acceptance11-May-2020
Date of Web Publication5-Oct-2020

Correspondence Address:
MD Shaymaa E.A.M Ahmed
Department of Pediatric Endocrinology and Diabetology, Alexandria University, Alexandria, 21526
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJOP.AJOP_24_20

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  Abstract 


Introduction The relationship between kidney and thyroid has been found since many years. Thyroid hormones directly affect the kidney through influencing the renal growth and development, glomerular filtration rate (GFR), renal transport systems, sodium and water homeostasis, and any impairment in thyroid functions can lead to or aggravate kidney disorders. On the contrary, the kidney plays an important role in thyroid hormone metabolism, degradation, and excretion so any disturbance in the hypothalamic–pituitary–thyroid axis has been correlated with reduced kidney functions. The earliest and the most common thyroid function abnormality in patients with chronic kidney disease (CKD) is a low triiodothyronine (T3) level (especially total T3 than free T3). This is called ‘low T3 syndrome.’ Moreover, CKD has an increased incidence of primary hypothyroidism and subclinical hypothyroidism. Detailed knowledge of all these interactions is extremely important for both the nephrologists and endocrinologists to plan the optimal management of the patient.
Aim The purpose of the work was to study the thyroid functions in children with CKD (including patients on dialysis) attending Alexandria University Children’s Hospital.
Patients and methods The study was a cross-sectional prospective study. The age of the studied cases ranged from 2 to 15 years. Overall, 52 male and 33 female patients were subjected to detailed history taking and full clinical examination. All patients were evaluated for serum creatinine, blood urea, serum thyroid-stimulating hormone, free triiodothyronine (FT3), and free thyroxine (FT4).
Results A total of 55 (64.7%) cases had normal thyroid functions, 18 (21.2%) cases had low T3 syndrome, 10 (11.8%) cases had subclinical hypothyroidism, and two (2.4%) had hypothyroidism. No significant correlation between eGFR and thyroid-stimulating hormone levels was found, but there was a significant positive correlation between levels of free T3 and eGFR.
Conclusion The low T3 syndrome is a relatively common thyroid disorder among children with CKD followed by subclinical hypothyroidism (11.8%). We recommend regular monitoring of thyroid functions in children with CKD for early detection of any disturbance to reduce the morbidity and mortality of CKD.

Keywords: chronic kidney disease, low T3 syndrome, nonthyroidal illness, thyroid disease


How to cite this article:
Garbadi SF, Thabet MA, Ahmed SE. Study of the thyroid functions in patients with chronic kidney disease at Alexandria University Children’s Hospital. Alex J Pediatr 2020;33:94-100

How to cite this URL:
Garbadi SF, Thabet MA, Ahmed SE. Study of the thyroid functions in patients with chronic kidney disease at Alexandria University Children’s Hospital. Alex J Pediatr [serial online] 2020 [cited 2020 Oct 20];33:94-100. Available from: http://www.ajp.eg.net/text.asp?2020/33/2/94/297245




  Introduction Top


There is a unique relationship between the kidney and thyroid gland. Thyroid hormones directly affect the kidney through influencing the renal growth and development, glomerular filtration rate (GFR), renal transport systems, and sodium and water homeostasis and any impairment in thyroid functions can lead to or aggravate kidney disorders. On the contrary, the kidney plays an important role in thyroid hormone metabolism, degradation, and excretion, so any disturbance in the hypothalamic–pituitary–thyroid axis has been correlated with reduced kidney functions [1].

The etiology of thyroid dysfunction in patients with chronic kidney disease (CKD) is multi-factorial and complex. CKD affects the hypothalamus-pituitary-thyroid axis and the peripheral circulation and metabolism of thyroid hormone release and excretion. The response of thyroid-stimulating hormone (TSH) to thyrotropin-releasing hormone is delayed because of the decreased clearance and the increase of half-life of TSH [2] (as shown in [Figure 1]).
Figure 1 Effects of chronic kidney disease on thyroid hormones profile [2].

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The earliest and the most common thyroid function abnormality in patients with CKD is low T3 level (especially total T3 than free T3). This is called ‘low T3 syndrome.’ Moreover, CKD has an increased incidence of primary hypothyroidism and subclinical hypothyroidism [3].

Circulating levels of T3 are low in progressive CKD owing to reduced deiodinase activity, which reduces the peripheral conversion of thyroxine T4 to T3. Inorganic iodide accumulates in advanced CKD owing to reduced GFR, leading to impaired thyroid hormone synthesis. Multiple uremic toxins, in combination with malnutrition and chronic metabolic acidosis and heparin used in hemodialysis as an anticoagulant, inhibit protein binding of T4. Hepatitis C infection, chronic inflammation, and drugs such as amiodarone, steroids, or β-blockers, all those factors have been implicated [4],[5].

Different treatments such as renal replacement therapy including dialysis and kidney transplantation are also associated with changes in circulating thyroid hormones levels, which, in turn, may have prognostic implications [6].

Many significant studies approved that thyroid hormone replacement therapy has noticeable positive effects on kidney functions, especially GFR, and prevents worsening of renal disease, which in turn decreases the morbidity and mortality of CKD and improves outcomes [7],[8].


  Aim Top


The aim of the work was to study the thyroid functions in children with CKD (including patients on dialysis) attending Alexandria University Children’s Hospital.


  Patients and methods Top


This was a cross-sectional prospective study. A total of 85 pediatric patients aged 2–15 years were enrolled in this study. Patients with known thyroid disease or those with a history of autoimmune disease were excluded.

All patients were subjected to detailed history taking, including age, sex, age at diagnosis, the cause of CKD, the duration of renal replacement treatment, and symptoms suggesting thyroid disease. Clinical examination was done including anthropometric measurements, Tanner staging of puberty [9], and palpation of the thyroid gland for goiter. Laboratory investigations were done, including serum creatinine, blood urea, creatinine clearance, and thyroid function tests (TSH, free T3, and free T4).

Ethical approval

Informed consent was taken from all the patients’ guardians. Ethical approval was obtained from Medical Ethics Committee of Faculty of Medicine, Alexandria University, on April 16, 2019.


  Results Top


A total of 52 (61.2%) patients were males and 33 (38.8%) patients were females. The mean age of the cases was 7.65±3.81 years. Overall, 33 (38.8%) cases had short stature (>-2 SD) and 20 (23.5%) cases were underweight (BMI below <5th percentile). Approximately 50% of patients on dialysis had renal replacement therapy duration more than 24 months ([Table 1]).
Table 1 Comparison between studied groups according to clinicodemographic data

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The causes of CKD included congenital anomalies of the kidney and urinary tract (CAKUT) in 38 (44.7%) cases, obstructive uropathy in 24 (28.2%) cases, and glomerulonephritis in nine (10.6%) cases ([Table 2]). The studied cases were distributed according to stages of eGFR ([Table 3]).
Table 2 Distribution of the studied cases according to cause of CKD (n=85)

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Table 3 Distribution of the studied cases according to stages of eGFR (n=85)

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A total of 55 (64.7%) cases had normal thyroid functions tests, 18 (21.2%) cases had low T3 syndrome, 10 (11.8%) cases had subclinical hypothyroidism, and two (2.4%) cases had hypothyroidism ([Table 4]).
Table 4 Distribution of studied groups according to thyroid function test disturbance (n=85)

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There was no statistical significant difference between patients on peritoneal dialysis, patients on hemodialysis, and patients in nephrology outpatient clinic regarding the thyroid function tests ([Table 5]).
Table 5 Relation between the studied groups and thyroid function tests

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No significant correlation between eGFR and TSH levels was found. However, there was a significant positive correlation between the levels of free T3 and eGFR ([Table 6] and [Figure 2] and [Figure 3]).
Table 6 Correlation between eGFR with TSH and FT3 (n=85)

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Figure 2 Correlation between estimated glomerular filtration rate and thyroid-stimulating hormone (n=85).

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Figure 3 Correlation between estimated glomerular filtration rate and FT3 (n=85).

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  Discussion Top


In the present study, the commonest etiology of CKD was CAKUT (44.7%) followed by obstructive uropathy (28.2%). Similar results were reported by Safouh et al. [12] who found that the top cause of pediatric CKD was CAKUT (31.5%). They reported obstructive uropathy in 11.2%, primary glomerulonephritis in 15.3%, reflux/urinary tract infection in 14.6%, familial/metabolic diseases in 6.8%, and unknown causes accounted for 20.6% of the cases. Similarly with a French study done by Deleau et al. [13], CAKUT accounted for 68.5% of CKD children, followed by 30.7% of nephropathies.

In the current study, 33 (38.8%) cases were short stature (>-2 SD) and 20 (23.5%) cases had BMI less than 5th percentile. Similarly, Smith [14] studied 5000 children and showed that one-third had height below the third percentile. In accordance, an American prospective cohort study done by Rodig [15] found that 31% of children with an eGFR less than 25 ml/min/1.73 m2 had a height SDS of below −1.88.

Many causes are contributed to longitudinal growth delay in CKD such as disturbed growth hormone metabolism and insulin-like growth factor-I, electrolyte disturbances, poor nutrition, metabolic acidosis, uremia, anemia, and chronic infections and inflammations, recurrent hospital admissions, bone and mineral disturbances, and hormonal changes such as vitamin D deficiency and hyperparathyroidism.

Weight affection was considered a common comorbidity in children with CKD owing to many contributing factors such as poor appetite, severe anorexia, anemia, and malnutrition. In the present study, 29.4% cases were underweight. Similarly, an Indian study done by Gupta et al. [16] observed that 60% of all cases had moderate to severe malnutrition. Their mean weight and height (HtSD) were −2.77±2.07 and −2.30±1.38, respectively.

In accordance, Ku et al. [17] studied 854 participants with ESRD, and they concluded that BMI z scores remained stable until eGFR decreased to less than 35 ml/min/1.73 m2. They demonstrated significant weight loss (defined as decline in BMI z score >0.2 per year) after eGFR decreased to less than 35 ml/min/1.73 m2.

In the present study, TSH level was elevated in 12 (14.1%) cases. TSH levels are variably elevated in CKD. It is released in response to thyrotropin-releasing hormone in patients with CKD, indicating pituitary disturbances in uremia. In accordance, Toda et al. [18] revealed 645 (4%) cases had high TSH level. Similarly, Kaptein et al. [19] reported that TSH was elevated in 10.5% of cases, 9.1% of cases had TSH level between 5 and 10 mUl/l, and 1% of cases had TSH elevation above 10 mUl/l. In addition, van Hoek [20] concluded that there was a correlation between CKD and elevated TSH levels.

In this study, we recorded 18 (21.2%) cases with low FT3 level, which was the most prevalent thyroid hormonal disturbance. Decreased T3 levels in CKD may be owing to the iodothyronine deiodinase enzyme affection (helps inT3 synthesis from T4) by chronic metabolic acidosis and chronic protein malnutrition. Such factors influence the proteins binding to T3. Low T3 levels in CKD may also be owing to the decreased peripheral (extra thyroidal) conversion from T4 to T3 due to decreased clearance of the inflammatory cytokines such as tumor necrosis factor-α and interleukin-1. These cytokines inhibit conversion of T4 to T3. Similarly, Pan et al. [21] found 626 (69.1%) cases with low T3 level. Moreover, Kamal et al. [22] had 42% of their cases with low T3 syndrome. In addition, an Italian study done by Enia et al. [23] on 41 continuous ambulatory peritoneal dialysis patients reported lower FT3 levels than healthy subjects.

There was a significant positive correlation between eGFR and free T3 levels in the current study. Similar results were obtained by Song et al. [24], who observed that low T3 levels was associated with decreased GFR and directly proportional with severity of CKD.

A total of 10 (11.8%) cases had subclinical hypothyroidism, which came second in order to low T3 syndrome in the present study. Similar to our results, Chonchol et al. [25] reported that 9.5% had subclinical hypothyroidism and Chaker et al. [26] observed that subclinical hypothyroidism was found in 9.2% of their cases. In an American study done by Lo et al. [27], 56% of their cases were considered subclinical hypothyroidism. In accordance, Kamal et al. [22] reported that 46% their cases had subclinical hypothyroidism.

In this study, only two (2.4%) cases had hypothyroidism; with only one of them being symptomatic. No significant correlation between high TSH levels and low eGFR was found. In contrast, Rhee et al. [28] studied patients with stage 3–5 CKD and observed that 10 ml/min lower estimated GFR increased the risk of hypothyroidism by 18% and was associated with an increase in 0.11 mU/l in TSH levels.

No cases of hyperthyroidism had been reported in the current study. Similar to our results, Singh et al. [29] observed that CKD was associated with a higher prevalence of primary hypothyroidism, both overt and subclinical, but not with hyperthyroidism. On the contrary, Chaker et al. [26] recorded 10 (0.2%) cases with hyperthyroidism. Missing to record any case of hyperthyroidism in current study does not exclude the occurrence of hyperthyroidism in patients with CKD.


  Conclusion Top


From the present study we concluded the following:
  1. CKD acts as a nonthyroidal illness pathology, which influences the thyroidal hormone concentration, action, and metabolism.
  2. Low T3 syndrome (21.2%) is a relatively common thyroid disorder among children with CKD, then followed by subclinical hypothyroidism (11.8%).


So, we recommend regular monitoring of thyroid functions in patients with CKD for early detection for any disturbance. Moreover, further researches are needed to confirm these findings in large number groups in cooperation with other centers for better understanding the mechanisms that relate thyroid hormones with CKD.

Acknowledgements

The research was supported by Alexandria Faculty of Medicine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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