Dear Editor,
We read with interest Sharma et al.’s[1] article on a prospective and comparative diagnostic accuracy study on serum levels of creatine-kinase (CK), creatine-kinase with subunit M and subunit B (CK-MB), and beta-human chorionic gonadotropin (HCG) in 105 pregnant females in the first trimester, 35 with tubal ectopic pregnancy (EP): 35 with abortive intrauterine pregnancy (AP), and 35 with normal intrauterine pregnancy (NP). CK and CK-MB levels were higher in females with EP than in women with NP, but there was no difference between females with EP and AP.[1] CK was a better predictor of EP than CK-MB.[1] The study is impressive, but several points require discussion.
The major limitation of the study is that alternative causes of increased CK were not sufficiently ruled out. The most common causes of elevated CK are physical activity, sport, myocardial infarction, cerebral disease, seizures, sepsis, shock, trauma, intramuscular injection, primary or secondary muscle disease, hyperthermia, burns, medications, poisoning, and pregnancy itself.[2] Therefore, we should know how many of the included patients suffered from one of these diseases or conditions and how many regularly took medications such as statins, fibrates, amiodarone, angiotensin II (ATII)-blockers, chloroquine, colchicine, propofol, clozapine, D-penicillamine, interferon-beta, antiretroviral drugs (e.g., zidovudine), daptomycin, procainamide, brigatinib, alectinib, steroids, immune-checkpoint inhibitors (pembrolizumab, sintilimab, bevacizumab, gefitinib, cabozantinib, baricitinib), or vincristine.
A second limitation of the study is that the group size in each of the three groups was small. Each group (EP, AP, and NP) included only 35 females. These numbers are not representative and may lead to statistical errors.
A third limitation of the study is that differential causes of elevated CK-MB levels were not sufficiently ruled out. The most common causes of increased CK-MB are myocardial damage, asthma, renal failure, pulmonary embolism, myopathy, malignancy, and hypothyroidism.[3] Therefore, it is imperative that the individual history and current medication of each of the included females be presented and alternative causes for elevated CK-MB be adequately ruled out. A troponin and proBNP determination should have been carried out in all included patients in order to exclude myocardial damage or heart failure as a cause of the CK-MB deviation.
To sum up, this excellent study has limitations that should be addressed before final conclusions are drawn. Clarifying the weaknesses would strengthen the conclusions and improve the study. Because the CK value depends on so many influencing factors, it can only be used as a biomarker of tubal EP if all of these different causes of an elevated CK or CK-MB value have been completely ruled out. Unless alternative causes of elevated CK and CK-MB are ruled out, a tubal EP should not be diagnosed in the presence of elevated CK and CK-MB levels.
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Conflicts of interest
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References
- 1.Sharma N, Kharkongor D, Basu R, Sundaram SP, Singh SA, Shullai WK, et al. Role of creatine phosphokinase as a diagnostic marker in tubal ectopic pregnancy. J Family Med Prim Care. 2023;12:2774–9. doi: 10.4103/jfmpc.jfmpc_2483_22. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Finsterer J, Scorza FA, Scorza CA. Significance of asymptomatic hyper creatine-kinase Emia. J Clin Neuromuscul Dis. 2019;21:90–102. doi: 10.1097/CND.0000000000000269. [DOI] [PubMed] [Google Scholar]
- 3.Ghosh A, Datta P, Dhingra M. Higher levels of creatine kinase MB (CK-MB) than total creatine kinase (CK): A biochemistry reporting error or an indicator of other pathologies? Cureus. 2023;15:e50792. doi: 10.7759/cureus.50792. [DOI] [PMC free article] [PubMed] [Google Scholar]