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J Family Med Prim Care
J Family Med Prim Care
JFMPC
J Family Med Prim Care
Journal of Family Medicine and Primary Care
2249-4863
2278-7135
Wolters Kluwer - Medknow India

JFMPC-13-3453
10.4103/jfmpc.jfmpc_148_24
Letter to Editor
Before creatine-kinase is proposed as a biomarker for tubal ectopic pregnancy, all alternative causes must be off the table
Finsterer Josef
Department of Neurology, Neurology and Neurophysiology Center, Vienna, Austria
Address for correspondence: Prof. Josef Finsterer, Postfach 20, 1180 Vienna, Austria. E-mail: fifigs1@yahoo.de
8 2024
26 7 2024
13 8 34533454
30 1 2024
15 2 2024
07 3 2024
Copyright: © 2024 Journal of Family Medicine and Primary Care
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
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pmcDear 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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.
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1 Sharma N Kharkongor D Basu R Sundaram SP Singh SA Shullai WK Role of creatine phosphokinase as a diagnostic marker in tubal ectopic pregnancy J Family Med Prim Care 2023 12 2774 9 38186834
2 Finsterer J Scorza FA Scorza CA Significance of asymptomatic hyper creatine-kinase Emia J Clin Neuromuscul Dis 2019 21 90 102 31743252
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 38239552
