Thyroid profile in patients of liver cirrhosis and correlation with severity and etiology of liver disease :Smriti Singh, Sharad Kumar Maurya, Anubha Varma, Journal of Internal Medicine of India

ORIGINAL ARTICLE
Year : 2021 | Volume : 15 | Issue : 1 | Page : 8--12

Thyroid profile in patients of liver cirrhosis and correlation with severity and etiology of liver disease

Smriti Singh, Sharad Kumar Maurya, Anubha Varma
Department of Medicine, MLN Medical College, Prayagraj, Uttar Pradesh, India

Correspondence Address:
Dr. Smriti Singh
23 B Park Road, Prayagraj - 211 001, Uttar Pradesh
India

Abstract

INTRODUCTION: Thyroid disease has been observed to be associated with liver injuries or deranged liver function. This study was conducted to study thyroid dysfunction in patients of liver cirrhosis and any association between severity of liver cirrhosis and thyroid profile. MATERIALS AND METHODS: In this case-control study, liver cirrhosis patients aged >18 years with evidence of hepatocellular dysfunction with portal hypertension compared with apparently healthy age-gender matched. Data were collected on a semistructural questionnaire with general physical and systemic examinations, including thyroid examination. The etiology of disease was ascertained on the basis of clinical examination and investigation. RESULTS: The study included 72 case (70.8% male and 29.2% female) and equal number of control participants. Controls as compared to cases had free triiodothyronine (fT3) (2.45 ± 0.40 vs. 1.60 ± 0.50 pg/ml) and free tetraiodothyronine (fT4) (1.26 ± 0.21 vs. 1.15 ± 0.48 ng/ml). Thyroid-stimulating hormone (TSH) value of cases were 3.61 ± 0.95 μIU/ml and controls were 3.01 ± 0.66 μIU/ml. CONCLUSIONS: Liver disease cases as compared to controls had significantly lower fT3 levels and significantly higher TSH levels. Mortality rate of liver disease cases with thyroid dysfunction was also found to be significantly higher.

How to cite this article:
Singh S, Maurya SK, Varma A. Thyroid profile in patients of liver cirrhosis and correlation with severity and etiology of liver disease.J Intern Med India 2021;15:8-12

How to cite this URL:
Singh S, Maurya SK, Varma A. Thyroid profile in patients of liver cirrhosis and correlation with severity and etiology of liver disease. J Intern Med India [serial online] 2021 [cited 2023 Jun 1 ];15:8-12
Available from: http://www.upjimi.com/text.asp?2021/15/1/8/343033

Full Text

Introduction

Liver plays an important role in the metabolism of thyroid hormones, as it is the most important organ in the peripheral conversion of tetraiodothyronine (T4) to triiodothyronine (T3) by type I iodinase resulting in 5' deiodination of T4.[1] Moreover, it is involved in the conjugation and circulation of thyroid hormones by the synthesis of thyroid-binding proteins.[1],[2] On the contrary, thyroid hormones have multiple effects on liver function, including stimulation of enzymes regulating lipogenesis and lipolysis as well as oxidative processes.[3],[4] Some of the lipogenic enzymes that are regulated are malic enzyme, glucose-6-phosphate dehydrogenase, and fatty acid synthase. Thus, the nature of relationship between the thyroid and liver is a mutual one with each one affecting the function of other. Evidence of an association between chronic diseases of the liver and thyroid alterations has often been reported.[5] However, most of the time, this association is traced among liver cirrhosis patients and other conditions are ignored. Recent studies have traced a reverse relationship between thyroid dysfunction and liver disease too.[6],[7] Given this bidirectional relationship, it is of interest to understand and evaluate the relationship between liver disease and thyroid functions under all possible conditions. Hence, the present study was planned with an aim to study thyroid dysfunction in cirrhosis of the liver and to correlate it with severity and etiology of liver disease.

Aims and objective

Evaluation of thyroid function in patients of cirrhosis of the liverTo find out the correlation of thyroid function with clinical profile and biochemical parameters of severity of liver cell dysfunction in patients of liver cirrhosisTo correlate etiology of liver cell dysfunction and derangements of thyroid profile.

Materials and Methods

This case-control study was conducted in the Department of Medicine, SRN Hospital affiliated to MLN Medical College, Prayagraj. A total of 72 liver cirrhosis patients (case) and equal number (72) of healthy controls were included in this study,

Inclusion criteria

Case

All patients with cirrhosis of liver aged >18 years with evidence of hepatocellular dysfunction and portal hypertension as evident clinically and by portal vein diameter >13 mm on ultrasonography (USG) and presence of esophageal varices on endoscopy or evidence of cirrhosis of the liver on fibro scan

Control

Apparently, healthy age-and sex-matched individuals of age >18.

Exclusion criteria

Known cases of thyroid disorder without liver cirrhosis, patient with a history of organ failure, cancer, radio or chemotherapy, individual with active infection, nephrotic syndrome, pregnancy, and history of drugs intake (amiodarone, NSAIDs, etc.).

Study period

The study period was from January 2019 to March 2020.

Ethical aspects

The protocol for the study was approved by the ethical and research committee. Data were collected only after the patient informed and written consent.

Diagnostic tool

The diagnosis of cirrhosis was based on the case history, clinical examination, biochemical, endoscopic and ultrasound findings, and elastography. The functional severity of the liver injury was determined on the basis of the Child‒Pugh‒Turcotte (CPT) grading system and Model for End-Stage and Liver-Stage Disease (MELD). The etiology of cirrhosis was determined on the basis of case history and biochemical tests. Thyroid function test was done by electrochemiluminescence immunoassay. Normal range of thyroid parameters were fT3 = 1.71–3.71 pg/ml, fT4 = 0.70–1.48 ng/ml, and thyroid-stimulating hormone (TSH) = 0.5–4.94 μIU/ml.

Statistical analysis

The statistical analysis was done using the SPSS (Statistical Package for the Social Sciences) version 21.0 statistical analysis Software. The values were represented in number (%) and mean ± standard deviation.

Results

A total of 72 liver cirrhosis cases (51 males and 21 females) and 72 apparently healthy controls (51 males and 21 females) were included in the final analysis. The mean age was 49.22 ± 7.22 years for cases and 49.14 ± 6.27 years for controls. Controls as compared to cases had higher free T3 (fT3) (2.45 ± 0.40 vs. 1.60 ± 0.50 pg/ml) and free T4 (fT4) (1.26 ± 0.21 vs. 1.15 ± 0.48 ng/ml), although the difference was significant only for free T3. On the contrary, TSH values of cases were found to be significantly higher as compared to that of controls (3.61 ± 0.95 vs. 3.01 ± 0.66 μIU/ml) [Table 1]. Low T3 syndrome and hypothyroidism were common thyroid disorders (25.0% and 18.1%), normal thyroidal illness syndrome with low T4 and high T4 were observed among 16.7% and 13.9% cases, whereas out of 72 controls, 65 (90.3%) did not have any abnormality in thyroid functions. Only 7 (9.7%) cases were diagnosed as normal thyroidal illness syndrome with high T4 abnormality. The difference in thyroid dysfunctions between cases and controls was found to be significant statistically [Table 2].{Table 1}{Table 2}

A subsequent decline with severity of liver disease according to CPT score was observed in fT3 and fT4 levels, while a subsequent increment in TSH with severity of liver disease was observed. However, the association of severity of liver disease was found to be significant only for fT3 levels while a significant increment in proportion of cases with thyroid dysfunction was observed with increase in severity of the disease, i.e., Category A (16.7%), Category B (69.4%), and Category C (90.0%) [Table 3]. A subsequent significant decline with increase in mortality risk (MELD) was observed in fT3 levels, and this association was found to be significant statistically. Association of mortality risk with fT4 levels and TSH levels were not found to be significant. Although an increment in proportion of cases with thyroid dysfunction with increase in mortality risk was observed, i.e., very low risk followed by mild risk, moderate risk, and very high risk (42.9%, 73.8%, 77.8%, and 100.0%), this association was not found to be significant statistically [Table 4]. On comparing the fT3, fT4, and TSH levels of cases with different etiology (alcoholic liver disease 51.38%, hepatitis B 25%, hepatitis C 9.73%, nonalcoholic fatty liver disease [NAFLD] 12.5%, and Wilson's disease 1.39%), all the thyroid function parameters were found to be comparable for different etiologies and difference in proportion of cases with thyroid dysfunction in different etiology group were also found to be statistically insignificant.{Table 3}{Table 4}

Discussion

In the present study, observed mean fT3, fT4, and TSH levels as 1.60 ± 0.50 pg/ml, 1.15 ± 0.48 ng/ml, and 3.61 ± 0.95 μIU/ml, respectively, in cases as compared to 2.45 ± 0.40 pg/ml, 1.26 ± 0.21 ng/ml, and 3.01 ± 0.66 μIU/ml, respectively, in controls. However, only differences in fT3 and TSH levels were found to be significant. Similarly, Vincken et al.[8] reported that the mean fT3 and fT4 was significantly lower in cases (2.80 ± 0.59 ng/L and 11.80 ± 1.92 ng/L) as compared to controls (3.30 ± 0.45 ng/L, 13.00 ± 1.57 ng/L). Moreover, the mean TSH was not significantly different between cases (1.60 ± 0.74 mIU/L) and controls (1.77 ± 1.23 mIU/L). In another study, Punekar et al.[9] observed mean fT3, fT4, and TSH levels as 1.95 ± 0.57, 1.27 ± 0.54, and 4.09 ± 1.70, respectively, in cases as compared to 3.13 ± 0.59, 1.86 ± 0.36, and 3.15 ± 1.20, respectively, in controls, thus showing mean fT3 and fT4 values of cases to be significantly lower while that of TSH to be significantly higher in cases as compared to that in controls.

In the present study, only 26.4% of cases as compared to 90.3% of controls were euthyroid, thus showing that thyroid disorders were highly prevalent in patients with liver cirrhosis. Among cases, low T3 syndrome was the most common thyroid dysfunction (25%), followed by hypothyroidism (18.1%), normal thyroidal illness syndrome with low T4 (16.7%), and normal thyroidal illness syndrome with high T4 (13.9%), respectively, whereas among controls all the 9.7% of cases had normal thyroidal illness syndrome with high T4. Compared to the present study, Punekar et al.[9] in their study had only 23% euthyroid cases. The most common thyroid dysfunction pattern was low T3 syndrome (41%) followed by hypothyroidism (20%), normal thyroidal illness syndrome with low T4 (15%), and hyperthyroidism (1%), respectively. Kumar et al.[10] found hypothyroidism in 20% and sick euthyroid syndrome in 10% of cirrhosis cases. Joeimon et al.[11] in their study also found hypothyroidism (21.6%) to be thyroid disorder and did not come across any case of hyperthyroidism. Assem et al.[12] in their study among NAFLD, cases found hypothyroidism in 36.7% and hyperthyroidism in 5% of cases.

As far as severity is concerned, in the present study, we used two criteria to grade the severity, one of them was clinical staging (Child‒Pugh Scoring [CPS]) and other was prognostic score (MELD). In the present study, according to CPS, half (50%) patients were in Class B followed by Class C (41.7%) and Class A (8.3%), respectively. According to the MELD score, majority had score 10–19 (58.3%) followed by score 20–29 (25%), <9 (9.7%), and 30–39 (6.9%), respectively. On the assessment of association between thyroid function hormones and severity scores, a significant decreasing trend of fT3 was observed with increasing CPS class and MELD score, the prevalence of thyroid dysfunction also showed an incremental trend with increasing CPS class and MELD score, thus implying that thyroid function, especially fT3 levels are affected by severity of liver cirrhosis. These results are in agreement with the findings of the previous studies[11],[13],[14] that have shown an incremental trend of thyroid dysfunction with increasing severity of liver disease. Patira et al.[13] in their study found that all the three thyroid function hormones (fT3, fT4, and TSH) show a significant association with CPS classes. Verma et al.[14] in their study reported both fT3 and fT4 levels to be significantly associated with MELD scores. They also showed a significant association between Child‒Pugh class and fT3 levels. However, they did not find a significant association of TSH levels with either Child‒Pugh class or MELD score and fT4 with Child‒Pugh class. In the present study too, we found that for mean thyroid functions, only fT3 levels showed a significant association with CPS class and MELD scores. In fact, almost all the previous studies have shown a significant inverse association of fT3 levels with increasing severity of liver disease as observed in the present study.

In the present study, we did not find a significant difference in thyroid function hormone levels with respect to etiology. No significant association between thyroid statuses (euthyroid vs. thyroid dysfunction) could also be seen for different etiologies. Prevalence of thyroid dysfunction for different etiologies could be seen in 66.7% to 100% of cases. Joeimon et al.[11] in their study, while focusing only on hypothyroidism, found prevalence of thyroid dysfunction in patients with alcoholic and viral infection etiology to be 25% and 19%, respectively. Kumar et al.[10] too did not find a significant difference in thyroid function profile when comparing between alcoholic and postviral etiologies. Verma et al.[14] also did not find a statistically significant difference in fT4 levels and TSH levels with respect to the etiology of cirrhosis of the liver. As such, it seems that instead of etiology, the severity of liver cirrhosis is more instrumental in bringing about changes in thyroid function profile.

The findings of the present study are in agreement with the previous literature and show that thyroid dysfunction is quite prevalent in liver cirrhosis patients irrespective of etiology but in correlation with increasing severity of disease. Further, studies to corroborate the findings of the present study are recommended.

Conclusions

In this study, the mean fT3 was significantly lower and TSH was significantly higher in liver disease cases as compared to controls. Among cases of liver disease as compared to controls, abnormal fT3, fT4, and TSH levels were observed in significantly higher proportion. Thyroid dysfunction was observed in significantly higher among cases. A trend of significant decline in fT3 levels with increase in severity was observed. Thyroid dysfunction was also observed in higher proportion of higher category of cases, and this association was significant. Duration of hospital stay of liver disease cases was not found to be associated with thyroid dysfunction. The fT3 levels of expired cases were significantly lower and TSH levels significantly higher. Mortality rate of liver disease cases with thyroid dysfunction was also found to be significantly higher. The above findings indicate that thyroid dysfunction was more common in patients of liver disease as compared to healthy counterparts and the risk of thyroid dysfunction increases with severity of the disease and is associated with poor outcomes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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