The Clinical Analysis Of Antithyroid Drugs-Related Creatine Kinase Elevation

Objective: To observe the changes of serum creatine kinase(CK)in hyperthyroidism patients during the treatment anti-thyroid drugs(ATDs)including methimazole(MMI)and propylthiouracil(PTU)and to study affecting factors and clinical manifestations of elevated creatine kinase,and provide theoretical basis for clinical safe medication.Methods: The objects of this study were 60 cases with hyperthyroidism who came from the First Affiliated Hospital of Guangxi Medical University from March 2016 to February 2017.40 patients took MMI and 20 patients underwent PTU.The patients were divided into three groups,the mild group(n=20),the medium group(n=13)and the severe group(n=27)according to free triiodithyronine(FT3)and free thyroxine(FT4)levels before treatment.Moreover,the patients were divided into three groups,CK normal group(n=43),CK mild grade group(n=9)and CK severe grade group(n=8)according to whether serum CK levels increased after ATDs treatment.Towards initial dose,the mild group was administered orally for MMI(15mg/d)or PTU(150mg/d)and the medium group was administered orally for MMI(20mg/d)or PTU(200mg/d),and severe group was administered orally for MMI(30mg/d)or PTU(300mg/d)respectively.Parameters of thyroid function(T3,T4,FT3,FT4,TSH)and serum CK were tested regularly.The initial dose will be reduced gradually to a suitable one of maintenance therapy(MMI 5mg~15mg/d,PTU 50mg~150mg/d).An individual out of the patients enrolled was followed up for more than three months.ATDs-related serum CK elevation was defined as at least parameters of CK above reached or exceeded 1.5 times upper limit of normal(≥1.5ULN).Results:(1)The incidence of elevated serum CK was 20.0%(4/20)in the mild group and 38.5%(5/13)in the medium group and 29.6%(8/27)in the severe group.There was no significant difference among the three groups(p>0.05).(2)The levels of serum CK began to elevate in 93.5th(58.0,128.0)days in the mild group,the same to CK peak time;the levels of serum CK began to increase in 70.0th(35.0,97.0)days in the medium group,and CK peak time was 97.0th(35.0,189.0)days;the levels of serum CK began to elevate in 56.5th(28.0,196.0)days in the severe group,and CK peak time was 61.0th(28.0,196.0)days.There was no significant difference among the three groups(p>0.05).(3)Serum CK levels started to increase when it was 418(295,843)U/L in the mild group,the same to CK peak values;serum CK levels started to elevate when it was 622(341,899)U/L in the medium group,and the peak value of serum CK was 899(446,9275)U/L;serum CK began to elevate when it was 351(274,1907)U/L in the severe group,and the peak value of serum CK was 356(274,1907)U/L.There was no significant difference among the three groups(p>0.05).(4)The mild group patients didn’t developed myalgia,however,there were 2 cases(15.4%)in the medium group and 4 cases(14.8%)in the severe group with muscle pain and increased serum CK.Myalgia often occurredin the proximal muscles.(5)There was no significant difference in FT3,FT4 levels among CK normal group,CK mild group and CK severe group before ATDs treatment(p>0.05),and there was no significant difference in FT3,FT4 levels or descending rate between CK mild grade group and CK severe grade group after treatment(p>0.05).(6)Serum CK levels started to increase in the patients with muscle symptoms was 516(351,1907)U/L and in the patients without muscle symptoms was 341(274,899)U/L,but there was no significant difference between the two groups(p>0.05);serum CK peak value in the patients along with muscle symptoms was 1324(411,9275)U/L and in the patients without muscle symptoms was 396(274,899)U/L,however,the former is higher,and there was statistically significant between the two groups(p<0.01).(7)There were no significant linear correlation between serum CK levels and FT3 or FT4 level,FT3 or FT4 decrease rate,FT3 or FT4 descending absolute value(p>0.05).Conclusion:(1)28.3%(17/60)in hyperthyroidism patients after ATDs treatment may develop elevated levels of serum creatine kinase(CK)in different degrees,and 70.6%(12/17)of them occur within 3 months.(2)When serum CK levels reach or exceed 3ULN especially accompanied by muscle symptoms after ATDs treatment,clinicians should be aware of ATDs-related muscle diseaseand myalgia and serum CK levels must be monitored closely to prevent acute renal failure caused by rhabdomyolysis syndrome;when the increase of serum CK levels is no more than 3ULN or normal with muscular symptoms,lupus-like syndrome should be identified.(3)ATDs-related serum CK elevation may not be related to the following factors: the type of anti-thyroid drugs,hyperthyroidism severity before treatment,and the decrease levels of thyroid hormones in the blood circulation after ATDs treatment.