Vinsamlegast notið þetta auðkenni þegar þið vitnið til verksins eða tengið í það: https://hdl.handle.net/1946/20451
Inngangur: Þreyta er algeng kvörtun flogaveikra einstaklinga og hefur mikil áhrif á lífsgæði. Orsök þreytunnar er óljós. Ein kenning er sú að þreytan geti tengst flogalyfjameðferðinni. Rannsóknir þar að lútandi hafa sérstaklega beinst að elstu flogalyfjunum, svo sem fenemal (kom á markað árið 1912) þar sem slæving er einnig oftast áberandi. Þróun flogalyfjameðferðar hefur því beinst að því að finna afbrigði af fenemal með samsvarandi flogastillandi áhrifum og minni slævingu. Það leiddi til uppgötvunar fenýtóíns árið 1938. Grunur hefur verið um að flogalyf hafi einnig áhrif á skjaldkirtilshormónaöxul og þær fáu rannsóknir sem gerðar hafa verið benda til þess að flogalyf geti valdið miðlægum skjaldvakabresti (MSB, central hypothyroidism) en þá er magn skjaldkirtilshórmónsins fT4 lágt án þess að heiladingulshormónið TSH (thyroid stimulating hormone) hækki. Algengasta einkenni MSB er þreyta.
Markmið rannsóknarinnar er að kanna hvort einstaklingar á flogalyfjum séu oftar með skjaldvakabrest en almennt gerist og að athuga hvort einhverjir þættir valdi aukinni áhættu á MSB.
Aðferðir: Rannsóknarhópurinn samanstóð af fullorðnum flogaveikum einstaklingum eldri en 18 ára sem voru í eftirliti á göngudeild taugadeildar Landspítala (LSH) á tímabilinu 01.01.1998 - 31.12.2011. Einstaklingar voru útilokaðir ef þeir höfðu þekktan skjaldkirtilssjúkdóm eða ef lengd flogalyfjameðferðar var styttri en 3 mánuðir. Skráð voru lyf einstaklinga og niðurstöður úr blóðmælingum á TSH og fríu týroxíni (fT4). Ef blóðgildi TSH og fT4 lá ekki fyrir voru einstaklingar boðaðir í blóðprufur. MSB var skilgreindur sem blóðgildi fT4 undir viðmiðunarmörkum og blóðgildi TSH innan viðmiðunarmarka.Við tölfræðiútreikninga voru notuð Mann-Whitney próf, fundinn var Kendall´s tau-b stikalaus fylgnistuðull og gerð tvíundargreining (logistic regression).
Niðurstöður: Rannsóknarhópurinn var 165 einstaklingar (73 karlar og 92 konur). Meðalaldur var 45,6 (±15,5) ár. Meðaltalsgildi TSH var 2,2 (±1.3) mIU/L, bil <0,01–7,98 (viðmiðunargildi 0,30–4,20 mIU/L). Meðaltalsgildi fT4 í rannsóknarhópnum var 14,2 (±2,9) pmol/L, bil 8,1-24,4 (viðmiðunargildi 12-22 pmol/L) samanborið við meðaltalið 16,9 (±6,1) pmol/L í 13248 mælingum á rannsóknarstofu LSH á eins árs tímabili og var munurinn marktækur (p<0,001). Munur á fT4 gildum karlmanna í rannsóknarhópnum samanborið við mælingar karlmanna á rannsóknarstofu LSH var marktækur (p<0.001) og munurinn var einnig marktækur fyrir konur (p<0.001). Þrjátíu og fimm einstaklingar (21%) voru með MSB. Notuð var tvíundargreining til að meta hugsanlega áhættuþætti MSB. Greiningin sýndi marktæk tengsl milli MSB og notkunar á annaðhvort karbamazepín eða oxkarbazepín, sérstaklega hjá konum (áhættuhlutfall (odds ratio) 15,0 með 95% öryggisbil 4,6 til 49,5).
Ályktun: MSB er algengari meðal einstaklinga sem taka karbamazepín eða oxkarbazepín, sérstaklega meðal kvenna. MSB tengdist ekki öðrum flogalyfjum. FT4 gildi var lægra hjá þeim sem tóku flogalyf samanborið við allar fT4 mælingar sem framkvæmdar voru á rannsóknarstofu LSH árið 2011.
Introduction: A high number of patients with epilepsy complain of fatigue. The cause of the fatigue is unknown. Fatigue is commonly reported as an adverse effect of treatment with antiepileptic drugs (AEDs). The fatigue is most commonly connected to the old AEDs, such as fenemal (phenobarbital), which also has a lot of sedative side effects. After the development of fenemal in 1912 the aim was to find a less sedative AED and that led to production of a new drug, phenytoin, in 1938. It is also suspected that AED can affect the thyrotropic axis and may cause central hypothyroidism (CH) according to the few studies that have been published. CH is a hypothyroid condition where the free thyroxine (fT4) level is low but the thyroid stimulating hormone (TSH) level is normal. Fatigue is the most common symptom of central hypothyroidism (CH).
The aim of this study was to retrospectively find if patients on antiepileptic treatment did more often have CH than expected and to evaluate potential risk factors for CH.
Methods: Adult epileptic patients (over 18 years of age) who attended the outpatient neurology clinic at Landspitali University Hospital (LUH), the only University Hospital in Iceland, from 1st of January 1998 to 31st of December 2011 were included in the study. Patients with previous history of thyroid disease or patient who had used AEDs for less than 3 months were excluded. Information on medical treatment, medical history, serum fT4 and TSH levels was collected from medical records. CH was defined as fT4 levels below the reference range and normal TSH levels. The patients were invited for a blood test if either TSH or fT4 had not already been obtained. Data was analyzed using logistic regression and Mann-Whitney test. Kendall´s tau-b coefficient was found for possible correlataion.
Results: Our study group contained 165 individuals, 92 women and 73 men. The mean age at inclusion was 45.6 (±15.5) years. The mean serum TSH level was 2.2 (±1.3) mIU/L, range <0.01–7.98 (reference value 0.30–4.20 mIU/L). The mean serum level of fT4 in our group was 14.2 (±2.9) pmol/L, range 8.1-24.4 (reference value 12-22 pmol/L) compared with 16.9 (±6.1) pmol/L in a sample of 13248 measurements at LUH, comprising all measurements in a single hospital (LUH) done during one year, and the difference was significant (p<0.001). The difference in fT4 level between men in our group and the LUH group as well as women in our group compared to the LUH group was significant (p<0.001 and p<0.001 respectively). Thirty-five patients (21%) had CH and CH was defined as an outcome measure. Logistic regression was used to evaluate potential risk factors for this outcome. Regression modeling showed statistically significant associations with the use of either carbamazepine (CBZ) or oxcarbazepine (OCBZ), especially for women; odds ratio 15.0 (95% confidence interval 4.6 to 49.5)
Conclusion: CH is observed more often in individuals taking CBZ or OCBZ, especially women. CH was not associated with other AEDs in our study. The fT4 level was lower among those using AEDs, compared with all individuals who had their fT4 level measured in a single University Hospital clinical laboratory during one year.
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