Levels of serum creatine phosphokinase in thyroid disorders

 

Priyanka Vaitla¹, Sarada Munagavalasa^2*, N Vani³

 

¹Resident specialist, Department of Biochemistry,³Professor and HOD, Osmania Medical College, Hyderabad, Telangana, INDIA.

²Assistant Professor, Modern Government Maternity Hospital, Hyderabad, Telangana, INDIA.

Email: saradamunagavalasa1@gmail.com

Keywords: Hypothyroid patients, Hyperthyroid patients, serum creatine phosphokinase

 

 

INTRODUCTION

Dysfunction and anatomical abnormalities of the thyroid are among the most common diseases of the endocrine glands¹. Thyroid gland secretes thyroxine (T4) and triidothyronine (T3) which play a critical role in cell differentiation during development and help to maintain thermogenic and metabolic homeostasis in adults. Production of these hormones is regulated by TSH and thyrotropin releasing hormones. In hypothyroidism there will be low T3 and T4 associated with high circulating TSH levels and in Hyperthyroidism there will be excess circulating free T3 and T4 with supressed TSH levels. Out of these TSH has been accepted as the initial screening test. However, the abnormal TSH level necessitates the use of other indicators of thyroid status including total and FT3 and T4. None of these parameters have proven to be ideal as their measured levels tend to vary in conditions like pregnancy, use of oral contraceptives, protein wasting diseases, liver disease, certain drugs and heparin, etc.² The inherent limitations of these parameters necessitate the establishment of alternate markers and enzymes like transaminases, lactate dehydrogenase (LDH) and creatine kinase (CK). Among these, CK has shown promising results as a diagnostic tool for thyroid disease. These disorders are common in women than in men at all ages³. In recent years studies have been conducted to establish a relationship between creatine phosphokinase and thyroid disorders^{4, 5}. A majority of patients with hypothyroidism have been shown to have increased serum CPK. Few studies have concluded that serum enzyme activities which are derived from muscle such as CPK, AST, ALT, amylase, alkaline phosphatase and LDH are elevated in thyroid dysfunction. They also mentioned the presence of hypercholesterolemia and hypertriglyceridemia in hypothyroidism^{6, 7}. Mere elevation of CPK, serum cholesterol and triglycerides in hypothyroidism are rarely useful diagnostically. However obtaining serum TSH levels and thereby making a diagnosis of hypothyroidism may explain elevation of CPK, cholesterol and triglycerides.

Hence, the present study was carried out to establish relationship of serum CPK levels with T3, T4 and TSH in Hypothyroid and Hyperthyroid patients which can lead to usage of CPK as an alternate marker in diagnosis of thyroid disorders.

 

MATERIALS AND METHODS

A case control study was conducted in the Department of Biochemistry, Osmania General Hospital, Hyderabad. The study was conducted over a period of one year. 150  thyroid dysfunction patients and controls were included in the study. The cases and samples were collected from  Department of Endocrinology, Osmania General Hospital. Investigations were performed at the Department of Biochemistry, Osmania Medical College/Osmania General Hospital, Hyderabad.

Inclusion criteria

Group 1 included healthy controls who were matched for age and sex.

Group 2 included those individuals with diagnosed with Hypothyroidism

Group 3 included those individuals with diagnosed with Hyperthyroidism

Exclusion criteria

Excluded other causes which alter the CK levels

1. Myalgia of other causes
2. Polymyositis
3. Myositis
4. Any neurogenic diseases like Myasthenia gravis, multiple sclerosis, polymyelitis, parkinsonism

Data collection

Proforma including age, sex, medical history, onset and duration of thyroid disorder was filled. Physical examination was done measuring height, weight, waist circumference was recorded.

Fasting venous blood sample was collected from all the subjects.

Laboratory parameters including T3, T4, TSH and CPK levels were estimated in the samples.

The data was analyzed using GraphPad Prism software version 6.0. Descriptive results are expressed as mean and SD of various parameters in different groups. to assess the significance of the differences observed in the mean values of different parameters observed in different groups studied, the data is subjected to ANOVA test. The significance of difference of mean values of different groups and within the groups is represented by p values and p value ˂0.05 is considered as significant.

 

OBSERVATION AND RESULTS

Serum CPK was significantly higher in cases with low T3 and T4 compared to controls (p<0.001). In group 2, Serum CPK values were found to be elevated in hypothyroid patients compared to healthy individuals with a p<0.001. In group 3, CPK was negatively correlated with T3 and T4 but was not statistically significant with a p value < 0.05 Table 3. Results show that serum CPK levels increased significantly in hypothyroid patients. There was also a correlation observed between CPK and thyroid hormones in hyperthyroid patients but it was not significant.

 

Table 1: Showing mean, SD, SEM and P value of Hypothyroid group

 

Table 2: Showing mean, SD, SEM and P value of Hyperthyroid group

 

Table 3: Showing comparison of levels of serum creatine phosphokinase in controls, hypothyroid patients and hyperthyroid patients.

DISCUSSION

The study was done to evaluate the role of CPK in individuals with thyroid disorders.  The results of this study confirm that elevated serum CPK levels is frequently found in hypothyroidism and decreased in hyperthyroidism. According to our study, the CPK levels also correlated with the degrees of hypothyroidism and hyperthyroidism, as evident by the magnitude of the TSH. These findings are in accordance with those of other studies, which report a 43% to 97% elevation of serum CK activity in hypothyroidism: Beyer et al, 43%⁸, Giampietro et al, 90%⁹ and Soufir et al,¹⁰ 97%. This is in contrast to the findings of Hartl et al, who found an elevation of CK activity in only 2 of its patients¹¹.

The CPK levels were found to be decreased in hyperthyroid cases compared to controls. This of decreased CPK levels in patients with hyperthyroidism compared with controls is in accordance with other studies^{12, 13}. Hekimsoy et al in a study conducted in 2005, found that skeletal muscle in overt hypothyroidism is affected more compared to subclinical hypothyroidism. They also found that there was a positive correlation between CK and TSH (r = 0.432;p = 0.04), a negative correlation between FT3 and CK (r = –0.556, p = 0.002)¹⁴. Giampietro et al in 1984, suggested that myoglobin and CK are the best indicators of hypothyroid myopathy, since they are sensitive for the early detection of muscle involvement due to metabolic disorder and are closely correlated to the metabolic condition of patients.⁹ Different mechanisms have been proposed to cause elevated CPK activity in hypothyroidism, although these mechanisms may have varying influence at different stages of the disease¹⁵. Hypothyroidism leads to a hypo-metabolic state which can cause a reduction in glycolysis and oxidative phosphorylations and thus reducing adenosine triphosphate (ATP) concentrations beyond a critical limit. Increased cell permeability and the leakage of CK from cells can also be caused due to alteration in sarcolemmal membranes.^{16, 17}. Another possibility is that because of hypothyroidism there occurs a reduced turnover of CK allowing serum activities to rise generating a marked release of CK through the altered sarcolemnalmembranes¹⁸. Some authors suggest direct role of T3 at the regulation of gene expression. It has been shown to induce or repress production of different proteins by increasing or decreasing transcription.^{19, 20}

The lower levels of CK activity in hyperthyroidism may be due to the hypermetabolic state which inturn may increase enzyme degradation, which may have contributed to these low CK activity.

 

CONCLUSION

It is clear from the results of the present study that increased serum CPK levels are associated with Hypothyroidism. Though we recommend further studies in this regard, we suggest that serum CPK can be used as an alternate  and supportive marker for the diagnosis of Hpothyroidism.

 

REFERENCES

• William’s Textbook of Endocrinology- International edition – 10^th edition.
• Whitley RJ. Thyroid functions. In: Teitz Fundamentals of Clinical Chemistry. 5^th edition, Burtis CA,Ashwood ER (Eds.) WB Saunders 2001:p.842.
• Davidson’s principles and practice of medicine – 18^th edition.
• Wan Nazaimoon, W.M., Siano, F.S, Sheriff, I.H., Faridah, I., Khalid IA(2001): serum creatine kinase an adjunct unit biochemical index of subclinical thyrotoxicosis. Ann. ClinBiochem (Pt-I), 57-8.
• Finsterer J, Stellberger C, Grossege C, Koroiss A (1999): Hypothyroid myopathy with unusually high serum creatine kinase. Hormone Res, 52(4), 205-208.
• Gomberg – Maitland M, Frishmanlott. Thyroid hormone and cardiovascular disease Am Heart J 135:187-196, 2000.
• Deschanpheleive M, Luyckx FH, Scheen AJ, Thyroid disorders and dyslipidemias. Rev Med Liege. 54; 746-750, 1999
• Beyer IW, Karmali R, DeMeester-Mirkine N, Cogan E, Fuss MJ. Serum creatine kinase levels in overtand subclinical hypothyroidism. Thyroid 1998;8:1029-31
• Giampietro O, Clerico A, Buzzigoli G, Del Chicca MG, Boni C, Carpi A. Detection of hypothyroidmyopathy by measurements of various serum muscle markers - Myoglobin, creatine kinase, lactatedehydrogenase and their isoenzymes. Horm Res 1984;19:232-42.
• Soufir JC, Zbranca TE, Bernheim R, Perlemuter L, Hazard J. Assay of serum creatine phosphokinase inprimary hypothyroidism: Comparison with other thyroid gland function tests in 32 cases: Values ofisoenzyme study. NouvPresse Med 1975;4:3055-9.
• Hartl E, Finstere J, Grossegger C, Kroiss A, Stöllberger C. Relationship between thyroid function andskeletal muscle involvement in subclinical and overt hypothyroidism. Endocrinologist 2001;11:217-21.
• Aquaron R, Boeuf G, Codacciona JL. Serum creatinine in thyroid disorders. Ann Endocrinol1971;32:142-56.
• Doran GB. Serum enzyme disturbances in thyrotoxicosis and myxoedema. JR Soc Med 1978;71:189-94.
• Hekimsoy Z, Oktem IK. Serum creatine kinase levels in overt and subclinical hypothyroidism. EndocrRes 2005;31(3):171-5.
• Monforte R, Fernández-Sola J, Casademont J, Vernet M, Grau JM, Urbano- Marquez A. Miopatiahipotiroidea: Estudioprospectivoclínico e histológico de 19 pacientes. Med Clin (Bare) 1990;95:126-9.
• Robinson JM, Wilkinson JH. Effect of energy-rich compounds on release of intracellular enzymes fromhuman leukocytes and rat lymphocytes.ClinChem 1974;20:1331-6.
• Robinson JM, Wilkinson JH, Johnson KP. Factors affecting the release of haemoglobin and enzymesfrom human erythrocytes. Ann ClinBiochem 1974;12:58-65.
• O’Malley BP, Davies TJ, Rosenthal FD. Effects of rest, exercise and warming on serum creatine kinaselevels in primary hypothyroidism.ClinSci 1981;60:595-7.
• Tsai MJ, O’Malley BW. Molecular mechanisms of action of steroid/thyroid receptor superfamilymembers.Annu Rev Biochem 1994;63:451-86.
• Liu YY, Brent GA. Thyroid hormone-dependent gene expression in differentiated embryonic stem cellsand embryonal carcinoma cells: identification of novel thyroid hormone target genes by deoxyribonucleicacid microarray analysis. Endocrinology 2005;146(2):776-83.