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Table of Content - Volume 11 Issue 2 - August 2019


A biochemical evaluation of serum enzymes CK, LDH and AST in patients of hypothyroidism

 

Onjal Taywade1, Neelam Patil2*

 

1Assistant Professor, Department of Biochemistry, MGMMC, Indore, Madhya Pradesh, INDIA.

2Associate Professor, Department of Biochemistry, TNMC, Mumbai, Maharashtra, INDIA.

Email: dronjal@gmail.com

 

Abstract               Background: The onset of hypothyroidism is insidious and patients commonly presents with generalized symptoms involving skeletal muscle dysfunction such as weakness, fatigue, tiredness and myalgia which indicates the involvement of the skeletal muscle system. Objectives: The aim of this study was to determine the activities of serum creatine kinase (CK), lactated eydrogenase (LDH) and aspartate transaminase (AST) in established cases of hypothyroidism and to estimate the usefulness of these enzymes to detect myopathy associated with hypothyroidism. Materials and Methods: In this retrospective study, serum CK, LDH and AST activities were estimated in newly diagnosed patients of hypothyroidism attending the thyroid clinic at the medicine OPD of the Sasoon General Hospital, Pune. Results: Elevation of CK activity was found in all 50 patients with hypothyroidism. The mean CK activity in hypothyroid patients was 233.58±120.90(U/l) as compared with controls 126.33±43.76. The mean LDH activity in patients with hypothyroidism was 476.21±175.83(U/l) against controls294.73±84.04. While the mean AST level in hypothyroid patients was 57.97±19.33(U/l), it was within normal limits in controls i.e.21.28±8.31. Significant positive correlation of CPK was observed with LDH(r=0.617, p< 0.0001) and AST(r=619, P<0.0001). Conclusion: Elevated serumenzymes levels of CK, LDH and AST can be used for screening of myopathy in hypothyroid patients. The estimation of these enzymes can also help to predict and monitor the outcome of hormone replacement therapy.

Key Words: Hypothyroidism, creatine kinase, lactate dehydrogenase, aspartate transaminase.

 

 

INTRODUCTION

Hypothyroidism is clinico-biochemical syndrome that results from decreased thyroid hormone synthesis and action. It is a common disorder that occurs in mild to severe forms in 4 to 15% of the population, women being affected more often than males and frequency of hypothyroidism increasing with age.1,2,3 The onset of hypothyroidism is insidious and the patient commonly presents with generalized symptoms involving skeletal muscle dysfunction such as weakness, fatigue, tiredness and myalgia which indicates the involvement of the skeletal muscle system.1,2Creatine kinase (CK/CPK) activity is greatest in the striated skeletal muscles and heart tissue. Though the serum CK activity is subject to a number of physiological variations, it is greatly elevated in all types of muscular dystrophy as well as various inflammatory conditions of the skeletal muscles including muscle damage. Apart from creatine kinase, lactose dehydrogenase(LDH) and aspartate transaminase(AST) has also been observed to be elevated in skeletal muscle injury1,2.

Hence, this study was done with the aim to estimate the serum enzyme activity of CK, LDH and AST in newly diagnosed patients of hypothyroidism and to estimate the usefulness of these enzymes as a screening method to detect myopathy associated with hypothyroidism.

 

 

MATERIALS AND METHODS

The present study comprised of 50 cases of hypothyroidism diagnosed for the first time in medicine or endocrinology OPD of the Sasoon General Hospital, Pune. The diagnosis of hypothyroidism is based on the presence of typical signs and symptoms, goiter and low circulating concentrations of thyroid hormones with high TSH concentrations(>10 uIU/ml).5,6 We excluded the myopathy patients with causes other than hypothyroidism, patients with hepatosplenomgaly, known liver or cardiac disorders and patients on long term medications. The control group consisted of 50 normal healthy adult precisely matched for the age and sex. A consent form was duly signed by the participants of both groups after getting the clearance from the institutional ethics committee. Three ml venous blood was collected in plain tube without applying tourniquet under aseptic precautions. The blood was allowed to clot in incubator at 37oC and serum was separated. The samples from both the groups were analyzed immediately for CK, LDH and AST on Transasia semi auto analyzer (Chem-5) by UV kinetic methods. Haemolysed, lipemic or fibrin clotted samples were discarded. Estimation of serum CK was done by kit from Radox laboratories for CK-NAC activated. CK reversibly catalyzes the transfer of a phosphate group from creatine phosphate to ADP to give creatine and ATP as products. The ATP formed is used to produce glucose-6-phosphate and ADP from glucose. This reaction is catalyzed by hexokinase. The glucose-6-phosphate is oxidized by the action of the enzyme G-6-PDH with simultaneous reduction of the coenzyme NADP to give NADPH and 6-phosphogluconate. The rate of increase of absorbance at 340nm due to the formation of NADPH is directly proportional to the activity of CK in the sample.7Estimation of LDH was done by the Randox laboratories kit based on the principle that LDH reduces pyruvate to lactate by transferring hydrogen from NADH and H⁺.8 Estimation of AST was done by the Randox laboratories kit, AST/SGOT reagent set UV kinetic method. AST/SGOT catalyzes the transfer of an amino group between L-Aspartate and 2-Oxaloglutarate. The Oxaloglutarate form is then reacted with NADH⁺ and H⁺ in presence of enzyme malate dehydrogenase to form NAD. The enzyme activity was determined by measuring the rate of oxidation of NADH at 340nm.9 Descriptive statistics and Chi square tests (χ2), correlations (Spearman rank) were carried out using Statistical Package for Social Sciences (SPSS, Chicago, Illinois, USA). p value <0.05 was considered as significant.

OBSERVATION AND RESULTS

The enzymes CK, LDH and AST levels were found to be significantly higher in patients of hypothyroidism as compared with controls. Statistically significant positive correlation of CK was observed with LDH(r=0.617, p< 0.05) and AST(r=0.619, p<0.05).

 

Table 1:

 

Cases

Healthy Controls

p-value

Age

34.10±5.8

34.8±6.4

0.647

Sex(Female)

43

42

0.718

CK(U/L)

233.58±120.90

126.33±43.76

<0.01*

LDH (U/L)

476.21±175.83

294.73±84.04

<0.01*

AST(U/L)

57.97±19.33

21.28±8.31

<0.01*

* p-value Statistically significant.

 

DISCUSSION

Hypothyroidism is an important cause of morbidity in middle aged females, especially those with long standing disease.1 Skeletal muscle is one of the major target organs of the thyroid hormones. Thyroid hormones are essential for the development of vertebrate skeletal muscles; hence an intact thyroid gland is required both for the development of muscle mass and the differentiation of biochemical as well as contractile characteristics of skeletal muscles. Involvement of skeletal muscle is amongst the most prevalent clinical consequences of hypothyroidism. Symptoms such as weakness, fatigue, exercise intolerance, exertional myalgias, and cramps are frequent hallmarks of such involvement. All these musclulo-skeletal symptoms are the prodromal signs of hypothyroidism. Hypotonic weakness with or without muscle atrophy is usually seen in severe hypothyroidism. It mainly affects the proximal muscles of the lower as well as the upper extremity.1,2,4The serum activities of various enzymes have been shown to be influenced by thyroid hormones.1,2 Injury to skeletal muscles release intracellular enzymes into blood which in turn can be used as markers of the tissue damage. Various studies have shown that the enzymes such as CK, LDH, AST, ALT, aldolase, glycogen phosphorylase etc are often raised in myositis and this is linked to the inflammatory process that happens in skeletal muscles.1,2,10 The postulated theory for rise in the serum levels of these hormones is the leakage of the enzymes from the cells which involves the muscles, coupled with the decreased rate of enzyme clearance from the circulation.10,12,13 Increased enzyme levels may be found even in absence of muscle symptoms which is probably due to increased sarcolemmal permeability and slowed enzyme clearance. A high index of suspicion would therefore be required for the clinical diagnosis of hypothyroidism and should be considered in patients with unexplained persistent elevations of serum muscle enzymes.11 The majority of hypothyroidism patients in our study had signs and symptoms related to the involvement of musculoskeletal system. We found that all these patients had raised levels of these enzymes i.e. CK, LDH and AST. The findings of this study match with Graig et al who recorded abnormal serum levels of CK in patients of hypothyroidism on the other hand found normal levels in other diseases of thyroid gland and suggested that thyroid hormones influences cell permeability of muscle enzymes.13 Saito et al demonstrated that the elevated serum CK returns to normal following hormone replacement therapy in hypothyroidism.14 Giampietro et al had proposed CK as the best indicators of the hypothyroid myopathy, since it is sensitive for the early detection of muscle involvement due to the metabolic disorder and correlate well with the metabolic conditions of patients.15 Roti et al demonstrated that CK as well as LDH were raised in hypothyroidism and also showed that they were inversely related to the thyroid hormone concentrations.16 Like McGrowder et al we too observed significant elevation in serum CK and LDH activities and suggest that these can be used as parameters for screening hypothyroid patients but not the hyperthyroid patients.17 Petkova M et al showed multiple enzymes such as AST, ALT, CK and LDH are often raised in myositis associated with hypothyroidism and linked this to the inflammatory process that happens in the skeletal muscles.18 Reuters et al suggested that muscle enzymes like CK, LDH and AST should also be taken into account in the decision of beginning hormone replacement therapy.19 Therefore, it can be advised that the serum levels of enzymes CK, LDH and AST should be estimated biochemically and monitored closely to ameliorate the effects of hypothyroidism on the skeletal muscles by monitoring and adjusting the hormone replacement therapy. Hence raised enzyme level can be considered as marker of muscle dysfunction in patients of hypothyroidism. Estimation of these enzymes will also help to confirm that the myopathy associated with hypothyroidism is secondary to the reduced thyroid hormone levels. However this needs further evaluation on larger sample size. The follow up of the above enzyme levels before and during the initial phases of the treatment of hypothyroidism could also provide considerable possibilities of differential diagnosis with ischemic heart disease which is often manifested during that period. The determination of serum CK level, in advance would help in determining the necessity of studies of other enzymes as well.(18) Once the diagnosis of hypothyroidism is confirmed, these enzymes can be suggested to be used to monitor the response to hormone replacement therapy, since the level of all these three enzymes revert to normal as the thyroid hormone levels come to normal range. We suggest for studies on correlation of enzymes of muscle dysfunction with thyroid hormones for better understanding of etio-pathogenesis of hypothyroidism. Thus, it could be suggested that the muscle disorders associated with hypothyroidism need careful study of their chemical composition and pattern in health as well as disease since their pathophysiological correlation might throw valuable light on the natural history of the disease process. To summarize, we express that this study serves to outline the present state of knowledge, the areas in which future advances may be made, and a basis for rationale of monitoring the pathophysiology of hypothyroidism.

 

CONCLUSION   

Though an important cause of morbidity, myopathy in hypothyroidism has remained enigmatic. Therefore, this study was designed to further explore the effects of hypothyroidism on skeletal muscles. It was found that serum CK, LDH and AST levels were significantly increased as compared to the controls indicating release of these enzymes from the muscle tissue in hypothyroidism. Demonstration of elevated levels of serum enzymes like CK, LDH and AST along with the clinical correlation can aid in early suspicion and diagnosis of hypothyroidism. Once the diagnosis of hypothyroidism is confirmed, these enzymes can be used to monitor the response to hormone replacement therapy. However, further studies with larger sample size are required for the confirmation of the findings.

 

REFERENCES

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  8. Lactate Dehydrogenase (LDH) reagent set UV kinetic method manual, Randox Diagnostics.
  9. AST/SGOT reagent set UV kinetic method manual, Randox Diagnostics
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  14. Saito M, Hib L et al, Creatine phosphokinase levels in hypothyroidism, (1963). Lancet, 2, 252.
  15. Giampietro O, Clerico A et al, Detection of hypothyroid myopathy by measurement of various serum muscle markers Mb, CK, LDH and their isoenzymes. Correlations with thyroid hormone levels (free and total) and clinical usefulness. HormRes. 1984;19(4):232-42
  16. Roti E, Bandini P et al, Serum concentrations of mb, ck, ldh and cardiac isoenzymes in euthyroid, hypothyroid and hyperthyroid subjects. RicClin Lab. 1980 Oct-Dec;10(4):609-17.
  17. McGrowderDA, FraserYP, Serum CK and LDH activities in patients with thyroid disorders, N J C P, Oct-Dec 2011, Vol 14, Issue 4              
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  19. Reuters VS, Buescu A et al, Clinical and muscular evaluation in patients with subclinical hypothyroidism Arq Bras EndocrinolMetabol. 2006 Jun; 50(3):523-31.

 

 

 

 
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