SERUM CREATINE KINASE ACTIVITY IN THYROID DYSFUNCTION

The serum activity of creatine kinase was determined in 52 patients with hypothyroidism (19 males and 33 females), 110 patients with hyperthyroidism (27 males and 83 females) and 187 control subjects (47 males and 140 females). The creatine kinase activity in patients with hypothyroidism was on the average significantly higher than controls (p<0.005). In hyperthyroid patients, although the serum activity of creatine kinase was significantly lower as compared with controls, however, it is within the normal range. Hypothyroidism should be put into consideration in patients presented with symptoms suggestive of cardiovascular abnormality without other evidence of myocardial damage and have raised creatine kinase activity.


Introduction
reatine kinase (CK) is a cytoplasmic and mitochondrial enzyme with wide tissue distribution 1 .Its physiological role is associated with adenosine triphosphate (ATP) generation that is required for contractile or transport systems 2 .creatine kinase catalyzes the reversible phosphorylation of creatine, a reaction in which ATP is the donor of the phosphate group 3 .Creatine kinase activity is greatest in striated muscle, brain and heart tissue which contain some 2500, 550 and 470 u/g protein, respectively.Other tissues, such as kidney and the diaphragm, contain significantly less activity (< 30 u/g protein), while the liver and erythrocytes are essentially devoid of activity 4 .Despite the wide tissue distribution of creatine kinase, it consider as muscle specific enzyme with clinical utility in the detection of acute or chronic disorder of muscle 5 .Abnormalities of thyroid function can cause a wide array of muscle disorders.These conditions are related to the important role of thyroid hormones in regulating the metabolism of carbohydrates and lipids as well as the rate of protein synthesis and enzymes production.Thyroid hormones also stimulate calorigenesis in muscle, increase muscle demand for vitamins, and enhance muscle sensitivity to circulating catecholamines 6 .The purpose of the present study was to evaluate the changes in the serum activity of creatine kinase among patients with hypothyroidism and hyperthyroidism.

Patients
The study was carried out in 162 patients with thyroid diseases.Fifty two patients (19 males and 33 females; 2-61 years of age) with hypothyroidism and in 110 patients (27 males and 83 females; 4-65 years of age) with hyperthyroidism.They were patients referred from different hospitals and clinics in Basrah for the suspicion of thyroid dysfunction.The diagnosis was based on clinical grounds and serum levels of T4 and T3.

Controls
The group consist of 187 individuals (47 males and 140 females, 7-63 years of age).All were seen consecutively in the same diagnostic laboratory for the suspicion of thyroid dysfunction and they were in fact euthyroid depending on the results of thyroid hormones assay.

Methods
Serum concentration of T4 and T3 were measured by enzyme immuno assay (EIA) using bioleisa kits (COD.3000-1147 and 3000-1146 respectively) from biokit, S.A. Span; as well as by radio immunoassay (RIA) using Gamma-Coat TM RIA kits (Ref CA-1541 and CA 1535 respectively) from DiaSorin, USA.Serum activity of creatine kinase was measured by enzymatic colorimertic method using kit (Cat.No. CK 1673) from Randox Laboratories Ltd., U.K. All procedures were followed according to the instruction of the manufecturer.Quality control sera from were included in each assay batch for all the above analytes.The data were statistically analyzed using student t-test for the difference between two means.P<0.05 was considered to be statistically significant.

Results
The mean values and the standard error of the mean for T4, T3 and serum activity of creatine kinase in the hypothyroid and hyperthyroid male patients compared to normal control males are summarized in table 1.The mean values of serum creatine kinase activity in male patients with hypothyroidism were significantly increased in comparison with controls (p<0.005).
Although the mean values of creatine kinase activity in hyperthyroid male patients are within the normal range, however, it is significantly lower as compared to controls (P<0.005).Table 2 summarized the results obtained in female patients with hypothyroidism, hyperthyroidism and control subjects.Similarly the serum activity of creatine kinase was significantly higher among hypothyroid females as compared with control females (P<0.005).Also the serum creatine kinase activity in hyperthyroid females is within the normal range, but ut us significantly lower as compared to control females (p<0.005).

Discussion
The results of the presented study revealed that hypothyroid patients have significantly higher serum creatine kinase activity as compared with controls (P<0.005).This finding also have been reported by other authors [7][8][9][10][11][12] .The source of the raised serum creatine kinase activity appears to be skeletal rather than cardiac muscle [13][14][15] .Myopathy was frequent complication of hypothyroidism and hypothyroid patients have frequent muscle complaints 5 .Proximal muscle weakness, prefentially affecting the legs, muscle pains or cramps and delayed tendon jerk relaxation represented the commonest feature of hypothyroid myopathy 16 .Beyer et al. 12 stated that even in subclinical hypothyroidism there is some degree of dysfunction in skeletal metabolism.Burnett et al. 17 suggested that the clinical diagnosis of hypothyroidism should be considered in with unexplained persistent elevations of serum creatine kinase.Gianpietro et al. 18 have proved that the creatine kinase activity is one of the best indicators of the hypothyroid myopathy.Since it is sensitive for the early detection of muscle involvement due to the metabolis disorders and is closely correlate to the metabolic conditions of patients.
Various explanations have been suggested as possible mechanisms for elevation of creatine kinase activity in hypothyroidism.Some stated that the cause has not been established 17 , while other suggested that the increased membrane permeability in relation to variations in high energy phosphate levels 19 , increased muscle bulk 10 , and diminished clearance 9 are the most likely explanations.
Although hyperthyroid patients had significantly lower creatine kinase activity values as compared to control subjects (P<0.005), the creatine kinase levels were within the normal range.The presented finding were in accordance with other studies regarding serum creatine kinase activities hyperthyroidism 9,20,21 .
Thyrotoxic patients commonly have proximal muscle weakness and atrophy on examination, but rarely complain of the deficit, however, on rare occasion generalized thyroitoxic myopathy could occur 6 .There is an inverse relationship of serum creatine kinase activity with thyroid status 22,23 .In hyperthyroidism, the serum creatine kinase activity tends to be at the end of the reference interval 22,24 .The lower level of creatine kinase activity in hyperthyroidism had been attributed to muscle wasting 24 rather than to be due to a direct inhibitory effect of the thyroid hormones on the enzyme 25 .
From the study, it is evident that hypothyroidism can cause significant increases in creatine kinase activity.Since hypothyroid patients may present with symptoms suggestive of cardiovascular disease 14 .The diagnosis of hypothyroidism should bear in mind in any patient with persistent elevation of creatine kinase activity associated with cardiovascular symptoms but without demonstrable myocardial damage.

Acknowledgement
The cooperation of the specialists in referring their patients for hormonal investigation is highly appreciated with a special indebt to Dr. Hashim S. Al-Khayat, consultant surgeon, chairman of surgery department, Basrah General Hospital.Our thanks to Al-Sadder Medical Laboratory, Baghdad and its director Dr. Abbas A. Aziz for allowing access to the hormonal analysis by radio immunoassay (RIA)