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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2018  |  Volume : 29  |  Issue : 4  |  Page : 846-851
Prevalence of subclinical hypothyroidism in patients with chronic kidney disease on maintenance hemodialysis


1 Department of Nephrology, Jinnah Postgraduate Medical Center, Karachi, Pakistan
2 Department of Nephrology, The Kidney Center Postgraduate Training Institute, Karachi, Pakistan

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Date of Submission19-Jul-2017
Date of Decision05-Sep-2017
Date of Acceptance07-Sep-2017
Date of Web Publication28-Aug-2018
 

   Abstract 

The prevalence of subclinical hypothyroidism (SHT) has been reported to be much higher in patients with chronic kidney disease (CKD) than in the general population. SHT has been identified as a strong predictor of mortality and a risk factor for cardiovascular disease in CKD. The study aimed to provide local data on the prevalence of SHT in CKD patients on maintenance hemodialysis (MHD). A total of 72 patients with CKD on MHD were enrolled. Nonprobability consecutive sampling was performed on patients of either gender aged 14-50 years who met the inclusion and exclusion criteria. Thyroid-stimulating hormone and free thyroxine four levels were obtained and interpreted for the presence of SHT. SHT was present in 22 patients (30.6%). When stratified according to age, 22.7% of patients were younger than 30 years, 20.8% between 30 and 40 years and 46.2% were above 40 years. The percentage of patients above 40 years with SHT was much higher, but not statistically significant (P = 0.096). When stratified according to gender, 21.6% were male, and 46.2% were female (P = 0.03). When stratified according to duration on hemodialysis (HD), 4.5% of patients on HD for two years or less had SHT; 25.9% on HD for three to five years and, 60.9% on HD for more than five years had SHT (P <0.01). The study shows a considerably high prevalence of SHT in CKD patients on HD. Routine screening of thyroid functions in these patients, especially in females and those on HD for >5 years, may help in reducing the morbidity and mortality associated with SHT through early detection and timely intervention.

How to cite this article:
Naseem F, Mannan A, Dhrolia MF, Imtiaz S, Qureshi R, Ahmed A. Prevalence of subclinical hypothyroidism in patients with chronic kidney disease on maintenance hemodialysis. Saudi J Kidney Dis Transpl 2018;29:846-51

How to cite this URL:
Naseem F, Mannan A, Dhrolia MF, Imtiaz S, Qureshi R, Ahmed A. Prevalence of subclinical hypothyroidism in patients with chronic kidney disease on maintenance hemodialysis. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2019 Nov 13];29:846-51. Available from: http://www.sjkdt.org/text.asp?2018/29/4/846/239646

   Introduction Top


Chronic kidney disease (CKD) is a major public health problem worldwide. Studies show that about 13.5% of the adult Australian[1] and 11% of the US population[2] are affected by this disorder. In developing countries like Pakistan, although lack of registries prevent an accurate assessment of the incidence or prevalence of end-stage renal disease (ESRD), a population-based study assessed the age-adjusted incidence at 232 cases per million population per year in India (a population very similar to Pakistan).[3]

Among patients with CKD, cardiovascular disease (CVD) is the principal cause of morbidity and mortality.[4],[5] Among the factors that contribute to cardiovascular risk in CKD, thyroid dysfunction is important and is often overlooked. Derangement of thyroid function is a common finding in patients with CKD.

The distinction between CKD and hypo-thyroidism can be difficult clinically since there is considerable overlap between the symptoms of these two conditions. The situation becomes even more confusing in cases of subclinical hypothyroidism (SHT) because these patients may not have any symptoms related to hypothyroidism at all. The diagnosis of SHT is made when the serum thyroid-stimulating hormone (TSH) level is high (range: 4.2–10 μШ/mL), but the corresponding serum-free thyroxine (FT4) level is within normal limits (range: 0.93–1.7 ng/dL). Of the patients with SHT, approximately 2%–5% per year will progress to overt hypothyroidism.[6]

SHT is recognized as a risk factor for atherosclerotic CVD, hyperlipidemia, low-grade inflammation, and hypercoagulability.[7],[8],[9] As ESRD and SHT are independent risk factors for mortality due to CVD, it is possible that patients suffering from both disease entities may have a higher CVD risk.

Studies have shown that SHT has a prevalence of 4%-10% in the general population[10],[11] and in CKD patients this increases to 18%.[11] The prevalence of SHT increases with the decline of glomerular filtration rate (GFR), and in chronic renal failure, the prevalence has been found to be 24.8%.[10],[12] The overall rate of decline in the estimated GFR was significantly greater in those not treated with thyroid hormones compared to those who were treated with thyroid hormones.[13]

The prevalence of SHT in native Africans is one-third that in Caucasians,[14] and a similar low prevalence is seen in some populations with iodine deficiency.[15],[16]

Studies have been conducted on this topic internationally, but there is insufficient data available from Pakistan related to SHT in patients on maintenance hemodialysis (MHD). This is important because SHT has been identified as a strong predictor of mortality in patients on chronic HD.

This study was aimed to provide local data on the prevalence of SHT in chronic renal failure patients on MHD. This assessment in our part of the world was deemed important so that effective strategies can be made, and protocols can be developed for screening and detection of SHT in HD patients for early detection and follow-up. This will ultimately lead to reduction in morbidity and mortality as intervention can be initiated early once SHT is detected.[17]


   Materials and Methods Top


A total of 72 patients, of both genders aged 14 years or above with CKD on maintenance dialysis, who were registered at the nephrology department, Jinnah postgraduate medical center (JPMC), Karachi were included in this study. This was a cross-sectional study and samples were collected on the nonprobability consecutive sampling technique. The study was conducted from 13 December 2013 onward for six months. Patients were explained about the study.

The confounding factors were controlled by excluding patients with known hypothyroi-dism, patients on medication that affect thyroid function, for example, lithium, high dose corticosteroids, interferon therapy, etc., and pregnant women.

Demographic data, age, gender, and duration on MHD were noted on a prescribed form. Serum TSH and FT4 levels were tested using immunometric assay at the Atomic energy department of JPMC. SHT was defined as serum TSH level >4.7 μIU/mL with the corresponding serum-free thyroxine (FT4) level within normal limits (range: 0.7–1.72 ng/dL).


   Statistical Analysis Top


Data were analyzed using the Statistical Package for Social Sciences (SPSS) version 20.0 for Windows (SPSS Inc., Chicago, IL, USA). Frequency and percentage was calculated for gender and SHT. Mean ± standard deviation was computed for quantitative variables. Age and duration on HD were divided into groups for stratification. Stratification was done by age, gender, and duration on HD for SHT. Chi-square was applied poststratification. Value of P ≤0.05 was taken as statistically significant.


   Results Top


A total of 72 patients with CKD on MHD were included in the study. Samples were collected on the nonprobability consecutive sampling technique. Of the 72, 46 were males, and 26 were females; the mean age of the patients was 36.3 ± 9.48 years. The mean age of males was 33.8 ± 9.85, and the mean age of females was 40.6 ± 7.10 years.

SHT was present in 22 patients (30.6%) overall. The overall patient characteristics are shown in [Table 1].
Table 1: Demographic characteristics of the study patients.

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When stratified according to age groups, it was observed that 22.7% of patients younger than 30 years and 20.8% of patients aged between 30 and 40 years had SHT. In patients above 40 years, the percentage of patients with SHT was much higher at 46.2%. This was however not statistically significant with a value of P = 0.096 [Table 2].
Table 2: Subclinical hypothyroidism stratified according to age groups (n = 72).

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When stratified according to gender, 21.6% of males, and 46.2% of females had SHT, which was statistically significant (P-value 0.03) [Figure 1].
Figure 1: Subclinical hypothyroidism stratified according to gender in the study patients.

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When the prevalence was stratified according to duration on HD, it was observed that in the group with two years or less of HD, 4.5% had SHT, 25.9% of patients on HD between three and five years had SHT and in the group on HD for longer than five years, 60.9% had SHT. This was statistically significant with value of P <0.01 [Table 3].
Table 3: Subclinical hypothyroidism stratified according to time since the start of hemodialysis (n=72).

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   Discussion Top


SHT is defined as an elevation in serum TSH concentration (normal range 5–10 μШ/mL) in conjunction with a normal serum-free T4 concentration. With the decline in GFR, the prevalence of SHT increases consistently. One study showed that approximately 18% of the patients with CKD not requiring dialysis have subclinical primary hypothyroidism.[10] This finding is independently associated with a progressively lower estimated GFR. The prevalence of subclinical primary hypothyroidism increased from 7% to 17.9% in individuals in whom GFR had decreased from ≥90 mL/min to 60 mL/min.[10] Studies also showed that unresolved SHT was independently associated with rapid decline of renal function and had a greater risk of progression to ESRD.[18]

The results from our study show that SHT is a relatively common disorder in the population of patients undergoing MHD. The overall prevalence of SHT has been found to be close to reports from earlier studies from the region. Shantha et al[12] in their study from India had described the prevalence to be 24.8%, whereas in this study, the overall prevalence was found to be 30.5%. Studies from other regions also found a high prevalence of SHT in ESRD patients. In a study by Lim,[19] the prevalence of goiter in ESRD was 0%–58%, and of SHT, it was 0%–9.5%. Kang et al[5] in their study reported that SHT was common (27.5%) among ESRD patients who were receiving continuous ambulatory peritoneal dialysis and that it may be associated with cardiac dysfunction.

Compared to the general population, the prevalence of SHT in ESRD patients is much higher. Studies have shown that SHT has a prevalence of 4%–10% in the general population.[10],[11] A study by Vanderpump et al[20] showed a prevalence of 3% in men and 8% in women of SHT in the general population.

Of patients with SHT, approximately 2%–5% will progress to overt hypothyroidism each year.[21] The rate of progression to overt hypo-thyroidism is proportional to the baseline serum TSH concentration and is higher in individuals with anti-thyroid antibodies. In individuals not taking thyroid hormone, the serum TSH returns to normal after one year of follow-up in approximately 5% but remains elevated in the remainder.[6] Some researchers reported that hypothyroidism could be corrected with restriction of dietary iodine in uremic patients on dialysis which decreases the need for hormone replacement therapy.[22]

In one clinical trial, the overall rate of decline in the estimated GFR was significantly greater in those not treated with thyroid hormones compared to those who were treated with thyroid hormones.[17]

SHT is recognized as a risk factor for atherosclerotic CVD, hyperlipidemia, low-grade inflammation, and hypercoagulability.[7],[8],[9] As ESRD and SHT are independent risk factors for CVD mortality, it is possible that patients suffering from both disease entities may have a higher CVD risk.

Some interesting results were obtained in our study when the outcome was stratified according to age, gender, and duration on MHD.

Older patients were noted to have higher rates of SHT compared with the other two younger age groups. These results were however not statistically significant. Data regarding the relation of age with the prevalence of SHT in ESRD are not available; however, a study from India showed that in the general population, 74% of cases with SHT belonged to 35–54 years age-group and the prevalence increased with age (in postmenopausal females, prevalence was found to be 20%). The prevalence of thyroid autoimmunity also increases after the age of 35 years.[23] This result may reflect the increased frequency of SHT in ESRD patients when compared with the general population.

In our study, we also found that more females have SHT compared to males (46.2% vs. 21.7%, respectively, P = 0.03). These values were statistically significant. Here again, in the general population, the prevalence of SHT was more in females (81.8%) than in males (18.2%).[24] Similarly, a study by Deshmukh et al found that SHT was present in the ratio of 1:3.7 in males and females.[23] Both of the above studies were performed in population of our region.

When stratified according to time since the commencement of MHD, it was observed that as the duration on HD increases, the prevalence of SHT also increases and these results were found to be statistically significant (P <0.01). This finding may suggest that the prevalence of SHT not only increases with the deterioration of GFR in early CKD[10] but also continues to increase with increasing duration of CKD or MHD.

The lower prevalence of SHT in Caucasians indicates that the prevalence of SHT can vary from population to population and also among races. Studies have been conducted on this topic internationally, but there is insufficient data available from the population of Pakistan in this regard, especially related to SHT in patients on MHD. Our study will fulfill this deficit of information from our population and provide local data on this subject. The assessment of the magnitude of this problem in our part of the world is important so that effective strategies can be made, and protocols can be developed for screening and detection of SHT in HD patients for early detection and follow-up. This will ultimately lead to a reduction in morbidity and mortality as intervention can be initiated early.


   Limitations of Study Top


The total number of patients included in this study was 72, and studies involving a larger number of patients and in collaboration with many hospitals will yield more significant results. Furthermore, single measurements of laboratory values create doubts regarding the precision of the outcome.


   Ethical issues Top


Principles laid down by the Helsinki declaration were observed. All participants were duly informed and made their free choice to join the study. No formal written informed consent was taken from the patients. However, they were all informed verbally that their non-identifiable data will be used in a research study.


   Conclusion Top


In conclusion, our study showed an overall prevalence of 30.56% of SHT among patients with ESRD on MHD in our population, which is more or less similar to other studies from the population of our region and also from other parts of the world. Screening and detection of SHT in HD patients are therefore recommended in our population for early detection of SHT, especially in female patients and in patients who have been on HD for more than five years.

Conflict of interest: None declared.

 
   References Top

1.
Chadban SJ, Briganti EM, Kerr PG, et al. Prevalence of kidney damage in Australian adults: The AusDiab kidney study. J Am Soc Nephrol 2003 ;14:S131-8.  Back to cited text no. 1
    
2.
Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 2003;41: 1-2.  Back to cited text no. 2
    
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Modi GK, Jha V. The incidence of end-stage renal disease in India: A population-based study. Kidney Int 2006;70:2131-3.  Back to cited text no. 3
    
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Edwards NC, Steeds RP, Ferro CJ, Townend JN. The treatment of coronary artery disease in patients with chronic kidney disease. QJM 2006; 99:723-36.  Back to cited text no. 4
    
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Kang EW, Nam JY, Yoo TH, et al. Clinical implications of subclinical hypothyroidism in continuous ambulatory peritoneal dialysis patients. Am J Nephrol 2008;28:908-13.  Back to cited text no. 5
    
6.
Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorders in the community: A twenty-year follow-up of the whickham survey. Clin Endocrinol (Oxf) 1995; 43:55-68.  Back to cited text no. 6
    
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Baskin HJ, Cobin RH, Duick DS, et al. American association of clinical endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypo-thyroidsm. Endocr Pract 2002;8:457-69.  Back to cited text no. 7
    
8.
Dillmann WH. Mechanism of action of thyroid hormones. Med Clin North Am 1985;69:849-61.  Back to cited text no. 8
    
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Serter R, Demirbas B, Korukluoglu B, et al. The effect of L-thyroxine replacement therapy on lipid based cardiovascular risk in subclinical thypothyroidism. J Endocrinol Invest 2004;27: 97-903.  Back to cited text no. 9
    
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Chonchol M, Lippi G, Salvagno G, et al. Prevalence of subclinical hypothyroidism in patients with chronic kidney disease. Clin J Am Soc Nephrol 2008;3:1296-300.  Back to cited text no. 10
    
11.
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The colorado thyroid disease prevalence study. Arch Intern Med ' 2000;160:526-34.  Back to cited text no. 11
    
12.
Shantha GP, Kumar AA, Bhise V, et al. Prevalence of subclinical hypothyroidism in patients with end-stage renal disease and the role of serum albumin: A cross-sectional study from South India. Cardiorenal Med 2011;1: 255-60.  Back to cited text no. 12
    
13.
Mohamedali M, Reddy Maddika S, Vyas A, Iyer V, Cheriyath P. Thyroid disorders and chronic kidney disease. Int J Nephrol 2014; 2014:520281.  Back to cited text no. 13
    
14.
Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002;87:489-99.  Back to cited text no. 14
    
15.
Robuschi G, Safran M, Braverman LE, Gnudi A, Roti E. Hypothyroidism in the elderly. Endocr Rev 1987;8:142-53.  Back to cited text no. 15
    
16.
Kung AW, Janus ED. Thyroid dysfunction in ambulatory elderly Chinese subjects in an area of borderline iodine intake. Thyroid 1996;6: 111-4.  Back to cited text no. 16
    
17.
Shin DH, Lee MJ, Kim SJ, et al. Preservation of renal function by thyroid hormone replacement therapy in chronic kidney disease patients with subclinical hypothyroidism. J Clin Endocrinol Metab 2012;97: 2732-40.  Back to cited text no. 17
    
18.
Kim EO, Lee IS, Choi YA, et al. Unresolved subclinical hypothyroidism is independently associated with progression of chronic kidney disease. Int J Med Sci 2014;11:52-9.  Back to cited text no. 18
    
19.
Lim VS, Fang VS, Katz AI, Refetoff S. Thyroid dysfunction in chronic renal failure. A study of the pituitary-thyroid axis and peripheral turnover kinetics of thyroxine and triiodothyronine. J Clin Invest 1977;60:522-34.  Back to cited text no. 19
    
20.
Vanderpump MP, Tunbridge WM. Epidemiology and prevention of clinical and subclinical hypothyroidism. Thyroid 2002;12:839-47.  Back to cited text no. 20
    
21.
Khandelwal D, Tandon N. Overt and subclinical hypothyroidism: Who to treat and how. Drugs 2012;72:17-33.  Back to cited text no. 21
    
22.
Sanai T, Inoue T, Okamura K, et al. Reversible primary hypothyroidism in Japanese patients undergoing maintenance hemodialysis. Clin Nephrol 2008;69:107-13.  Back to cited text no. 22
    
23.
Deshmukh V, Behl A, Iyer V, et al. Prevalence, clinical and biochemical profile of subclinical hypothyroidism in normal population in Mumbai. Indian J Endocrinol Metab 2013;17:454-9.  Back to cited text no. 23
    
24.
Bashir H, Farooq R, Bhat MH, Majid S. Increased prevalence of subclinical hypothyroidism in females in mountainous valley of Kashmir. Indian J Endocrinol Metab 2013;17: 76-80.  Back to cited text no. 24
    

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Correspondence Address:
Dr. Murtaza F Dhrolia
Department of Nephrology, The Kidney Centre Postgraduate Training Institute, Karachi 75530
Pakistan
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DOI: 10.4103/1319-2442.239646

PMID: 30152421

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