What is the full form of CK

Detail - Swiss Medical Forum

Case description

The 56-year-old patient seeks medical advice because she has been suffering from progressive asthenia associated with muscle pain for a year. No relevant events have occurred in the past and the patient said there was no fever, sweating or weight loss. She denies any heart or breathing problems and has no cardiovascular risk factors. The patient undergoes regular gynecological examinations, the last time being two months ago. She doesn't use drugs or medication.

Clinically, there is a good general condition with the following vital parameters: heart rate 67 / min, arterial blood pressure 124/76 mm Hg, oxygen saturation in room air 98%, body temperature 36.9 ° C. The cardiopulmonary findings are normal and the physical examination does not provide any further indications, especially with regard to neurological, osteoarticular or cutaneous aspects.

The laboratory tests show that the blood count is in the normal range, as are the coagulation tests, electrolytes, kidney function, lactate dehydrogenase (LDH) value, liver values ​​and thyroid function. An inflammation syndrome was also not found. It should be mentioned that the attending physician has determined the concentration of creatine kinase (CK): This has been increased and has fluctuated between 255 and 340 U / l (reference range: 26–192) with a CK-MB value between 44 and for six months 62 U / l (reference range: 7–25) and a CK-MB / CK ratio of around 18% (normal: <6%), with no comparison value available. The repeatedly measured concentration of the highly sensitive troponin T is in the normal range. The levels of myositis-specific autoantibodies and aldolase are also normal. The electrocardiogram (EKG) does not indicate ischemia and the echocardiography reveals a preserved left ventricular ejection fraction (LVEF).

In summary, the patient suffers from asthenia and muscle pain, the laboratory tests show an increased total CK value with an increase in the CK-MB / CK ratio.

Question: Why should the interpretation of these laboratory results give rise to?


a) A stress test

b) A muscle biopsy

c) CK electrophoresis

d) An oncological work-up (computed tomography of the chest, abdominal or pelvic area, gynecological work-up and colonoscopy)

Answer:


The correct answer is c.

discussion

The patient showed no cardiovascular risk factors and no anginal symptoms; the ECG did not indicate ischemia. The troponin level is normal and the CK concentration shows no increasing tendency. The transthoracic echocardiography shows a preserved LVEF, no kinetic disturbance is recognizable. These factors are sufficient to reasonably rule out ischemic cardiopathy; an exercise test is not indicated.

The fluctuations in CK levels can indicate inflammatory myositis. However, according to the criteria proposed by Troyanov and Targoff [1], this diagnosis is very unlikely, since there is no muscle weakness, the muscle enzyme serum concentrations (aldolase, alanine aminotransferase [ALAT], aspartate aminotransferase [ASAT] and LDH) and myositis-specific autoantibodies are normal and there are no rashes or papules.

A muscle biopsy would be indicated if electromyography should reveal specific myopathic changes.

Since there is no evidence of ischemic cardiopathy or inflammatory myopathy and no suspicion of rhabdomyolysis, the presence of macro-CK should be considered. These are complex, high molecular weight macroenzymes characterized by lower plasma clearance and longer half-life compared to normal isoenzymes. This leads to an artifact increase in the serum activity of the CK and in particular the CK-MB.

The CK is a cytoplasmic enzyme that occurs in various tissues in a dimeric form. The two subunits are referred to as CK-M and CK-B. These subunits form three isoenzymes: CK-BB, CK-MB and CK-MM. There is also a mitochondrial isoform. The CK-MM is the predominant form in the skeletal muscles, the CK-BB occurs in the brain and smooth muscles. The CK-MB is found in high concentrations in the myocardium and to a lesser extent in the skeletal muscles. In healthy individuals, the CK-MM isoform essentially makes up all of the CK in serum (96-100%). A myocardial lesion, for example in the context of an acute infarction, leads to an increase in the concentration of the circulating isoform CK-MB. Because macro-CK interferes with the CK-MB measurement, it can be the cause of falsely elevated CK-MB values ​​and can lead to an erroneous diagnosis of myocardial infarction. The result is often unnecessary, expensive and invasive cardiological examinations.

A distinction is made between two types of macro-CK: They arise either through the binding of a CK isoenzyme (usually isoform BB, more rarely MB or MM) to an immunoglobulin, usually IgG, sometimes IgA or IgM (macro-CK type 1), or through Polymerization of the mitochondrial isoenzyme (macro-CK type 2).

The prevalence of macro-CK type 1 in adults is low and varies between 0.43% and 2.5% depending on the study [2, 3]. An association with certain diseases has been described, in particular with myositis, hypothyroidism, ulcerative colitis and cardiovascular diseases [2]. An occurrence in healthy people has also been described [2].

The prevalence of macro-CK type 2 is estimated at 0.5 to 3.7% [3, 4]. In adults, macro-CK type 2 occurs in people with oncological (often metastatic) diseases and appears to be released during tumor lysis or formed directly by the cancer cell. The most frequently associated cancers are colorectal, lung, hepatocellular, breast, urological and gastric cancer [5]. This macro-CK type is also associated with liver diseases, especially cirrhosis. The macro-CK is likely to be released into the circulation by the hepatocytes during necrosis and cell regeneration. It should be noted that macro-CK type 2 has also been demonstrated in HIV-positive people who are treated with antivirals [2].

The determination of the CK-MB activity by means of immune inhibition is based on monoclonal antibodies against the CK-M monomer, which inhibit the CK-MM activity completely and half the CK-MB activity. The residual activity is consequently due to the activity of the CK-B monomer of the CK-MB. This applies to a method that presupposes that the activity of the isoenzyme CK-BB is almost undetectable in normal serum. This is the reason for the low specificity when other forms than CK-MB are present in the serum sample, be it CK-BB or macro-CK. In both cases, the CK-MB activity is therefore rated too high. The presence of macro-CK can sometimes lead to falsified results with a CK-MB activity that is higher - sometimes far higher - than the total CK activity [5].

Once macro-CK is suspected, the diagnosis must be confirmed using electrophoresis. It is currently the gold standard for the detection of macro-CK and enables the differentiation of the three isoforms as well as the detection of any macro-CK (Fig. 1). This method has the advantage of high specificity and sensitivity [6]. Since the presence of macro-CK is generally only suspected when the total CK value is increased, the overall diagnosis is lacking in sensitivity: the total CK value can occur in up to 80 to 90% of cases in which Macro CK are found to be normal.

CK electrophoresis costs CHF 31.

In our patient, macro-CK type 2 is detected by electrophoresis. A colonoscopy then reveals four sessile polyps, the largest of which is 22 mm in diameter. After its complete removal, the histological examination reveals a well-differentiated adenocarcinoma with a deep invasion of less than 1 mm. The three remaining polyps are villous adenomas that are completely removed.

The asymptomatic increase in CK or CK-MB without an ascertainable cause should therefore always be examined using CK electrophoresis in order to detect any macro-CK.

Oncological examinations are only indicated if macro-CK type 2 has been detected by means of electrophoresis. In this case, a gynecological examination with mammography, a CT scan of the chest, abdominal or pelvic area, and a colonoscopy should be performed.

Main messages

• The presence of macro-CK should be considered if:

- the total CK value has been increased over a long period of time for no identifiable cause;

- the proportion of CK-MB in the total CK concentration is over 50% [3], and even more so if the CK-MB value exceeds the total CK value.

• The detection of macro-CK type 2 should be the reason for oncological examinations.

Thanks
The authors would like to thank Prof. Gérard Waeber, Chief Physician Département de médecine, CHUV, and Dr. Emilio Minas Valvini, Head of Service de médecine internal, Hôpital du Jura Bernois, for reviewing the article.
Disclosure statement
The authors have not declared any financial or personal connections in connection with this post.
Credits

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Correspondence

Correspondence:
Damiano Pongan, graduate doctor
Internal medical service
Center hospitalier universitaire vaudois
Rue du Bugnon 46
CH-1011 Lausanne
damiano.pongan [at] chuv.ch

literature
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5 Chang CC, Liou CB, Su MJ, Lee YC, Liang CT, Ho JL, et al. Creatine kinase (CK) -MB-to-total-CK ratio: a laboratory indicator for primary cancer screening. Asian Pac J Cancer Prev. 2015; 16 (15): 6599-603.
6 Bohner J, Stein W, Steinhart R, Würzburg U, Eggstein M. Macro creatine kineses: results of isoenzyme electrophoresis and differentiation of the immunoglobulin-bound type by radioassay. Clin Chem. 1982; 28: 618-23.
7 Lee KN, Csako G, Bernhardt P, Elin RJ. Relevance of macro creatine kinase type 1 and type 2 isoenzymes to laboratory and clinical data. Clin Chem. 1994; 40: 1278-83.
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