{"id":1596,"date":"2018-11-11T19:50:38","date_gmt":"2018-11-11T18:50:38","guid":{"rendered":"http:\/\/www.newslab.sk\/2018\/11\/11\/drahomira-springer-tomas-zima\/"},"modified":"2018-11-11T20:15:36","modified_gmt":"2018-11-11T19:15:36","slug":"drahomira-springer-tomas-zima","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/drahomira-springer-tomas-zima\/","title":{"rendered":"Thyroid in Pregnancy"},"content":{"rendered":"

*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.<\/span><\/strong><\/p>\n

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T\u011bhotenstv\u00ed je komplexn\u00ed fyziologick\u00fd proces, p\u0159i kter\u00e9m prob\u00edh\u00e1 \u0159ada hormon\u00e1ln\u00edch a metabolick\u00fdch zm\u011bn. T\u011bmito zm\u011bnami i z\u00e1t\u011b\u017e\u00ed, kter\u00e1 je na \u0161t\u00edtnou \u017el\u00e1zu b\u011bhem t\u011bhotenstv\u00ed kladena, m\u016f\u017ee b\u00fdt iniciov\u00e1na porucha jej\u00ed funkce(1). Zvy\u0161uje se pot\u0159eba tyreoid\u00e1ln\u00edch hormon\u016f, co\u017e je d\u016fsledkem transplacent\u00e1rn\u00edho p\u0159enosu hormon\u016f \u0161t\u00edtn\u00e9 \u017el\u00e1zy matky k plodu. Hormony \u0161t\u00edtn\u00e9 \u017el\u00e1zy jsou d\u016fle\u017eit\u00fdm faktorem diferenciace bun\u011bk b\u011bhem nitrod\u011blo\u017en\u00edho v\u00fdvoje a p\u016fsob\u00ed zvl\u00e1\u0161t\u011b na v\u00fdvoj mozku(2). \u0160t\u00edtn\u00e1 \u017el\u00e1za zdrav\u00e9 t\u011bhotn\u00e9 \u017eeny s dostate\u010dn\u00fdm p\u0159\u00edsunem j\u00f3du se na tyto po\u017eadavky adaptuje a je schopna se s nimi vyrovnat(3). Do 14. t\u00fddne je plod zcela z\u00e1visl\u00fd na mat\u010din\u011b produkci tyroxinu, pozd\u011bji jen \u010d\u00e1ste\u010dn\u011b.<\/p>\n

V t\u011bhotenstv\u00ed indukuj\u00ed estrogeny vzestup koncentrac\u00ed globulinu v\u00e1zaj\u00edc\u00edho tyroxin (TBG); v d\u016fsledku toho stoup\u00e1 i koncentrace celkov\u00e9ho T3 a T4. Zv\u011bt\u0161uje se distribu\u010dn\u00ed prostor hormon\u016f \u0161t\u00edtn\u00e9 \u017el\u00e1zy d\u00edky zvy\u0161uj\u00edc\u00edmu se objemu plazmy, metabolick\u00fd obrat tyroxinu je zrychlen, pot\u0159eba hormon\u016f \u0161t\u00edtn\u00e9 \u017el\u00e1zy stoup\u00e1 a\u017e o 50 %. V prvn\u00edm trimestru gravidity doch\u00e1z\u00ed k vysok\u00e9mu n\u00e1r\u016fstu hladiny choriov\u00e9ho gonadotropinu (hCG), kter\u00fd je ve vysok\u00e9 koncentraci stimul\u00e1torem tvorby tyreoid\u00e1ln\u00edch hormon\u016f prost\u0159ednictv\u00edm receptor\u016f pro TSH(4)\u00a0a vede tak fyziologicky ke zvy\u0161ov\u00e1n\u00ed produkce mate\u0159sk\u00e9ho T4 a T3 v dob\u011b kritick\u00e9ho v\u00fdvoje mozkov\u00e9 k\u016fry (11. \u2013 14. t\u00fdden).<\/p>\n

Na produkci tyreoid\u00e1ln\u00edch hormon\u016f m\u00e1 krom\u011b v\u00fd\u0161e zm\u00edn\u011bn\u00fdch fyziologick\u00fdch podm\u00ednek vliv tak\u00e9 dostate\u010dn\u00e9 z\u00e1soben\u00ed organizmu j\u00f3dem.<\/p>\n

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Pot\u0159eba j\u00f3du v t\u011bhotenstv\u00ed<\/h3>\n

Bu\u0148ka tyreoidey aktivn\u011b vychyt\u00e1v\u00e1 pot\u0159ebn\u00fd j\u00f3d v podob\u011b jodidov\u00e9ho iontu z krve. Sv\u011btov\u00e1 zdravotnick\u00e1 organizace (WHO) stanovila doporu\u010den\u00fd denn\u00ed p\u0159\u00edjem j\u00f3du pro net\u011bhotn\u00e9 a nekoj\u00edc\u00ed \u017eeny star\u0161\u00ed 14 let na 150 mg j\u00f3du denn\u011b(5). P\u0159i p\u0159\u00edjmu men\u0161\u00edm ne\u017e 50 mg\/den nen\u00ed tyreoidea schopna udr\u017eet p\u0159im\u011b\u0159enou hormon\u00e1ln\u00ed sekreci, zv\u011bt\u0161uje se a vznik\u00e1 struma, n\u011bkdy i hypotyre\u00f3za. Z\u00e1sobn\u00ed mno\u017estv\u00ed j\u00f3du je ve \u0161t\u00edtn\u00e9 \u017el\u00e1ze zna\u010dn\u00e9 a je ochranou p\u0159ed obdob\u00edm eventu\u00e1ln\u00edho deficitu. V t\u011bhotenstv\u00ed stoup\u00e1 pot\u0159eba j\u00f3du vzhledem k vy\u0161\u0161\u00ed produkci tyroxinu, v pozd\u011bj\u0161\u00edm st\u00e1diu t\u011bhotenstv\u00ed se pokr\u00fdv\u00e1\u00a0 i pot\u0159eba plodu pro jeho vlastn\u00ed produkci tyreoid\u00e1ln\u00edch hormon\u016f. Zvy\u0161uje se i ren\u00e1ln\u00ed clearence j\u00f3du. Pro t\u011bhotn\u00e9 \u017eeny se tedy doporu\u010den\u00e1 d\u00e1vka zvy\u0161uje na 250 mg j\u00f3du denn\u011b(6). Plat\u00ed to v zem\u00edch, kde je dlouhodob\u011b prov\u00e1d\u011bna jodizace soli, mezi kter\u00e9 pat\u0159\u00ed i \u010cesk\u00e1 republika a Slovensko, kde je \u00faprava kuchy\u0148sk\u00e9 soli prov\u00e1d\u011bna od pades\u00e1t\u00fdch let minul\u00e9ho stolet\u00ed, tak\u017ee populaci na\u0161ich t\u011bhotn\u00fdch lze pova\u017eovat za \u017eeny s dobr\u00fdm j\u00f3dov\u00fdm z\u00e1soben\u00edm(7).<\/p>\n

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V\u00fdznam hormon\u016f \u0161t\u00edtn\u00e9 \u017el\u00e1zy pro plod<\/h3>\n

Vliv t\u011b\u017ek\u00e9ho jodov\u00e9ho deficitu nebo vrozen\u00e9 hypotyre\u00f3zy na plod a novorozence je dlouhodob\u011b zn\u00e1m, stejn\u011b jako vliv t\u011b\u017ek\u00e9 mate\u0159sk\u00e9 hypotyre\u00f3zy. Z mnoha sou\u010dasn\u00fdch studi\u00ed ale plyne dal\u0161\u00ed z\u00e1va\u017en\u00fd z\u00e1v\u011br, a to, \u017ee i m\u00edrn\u00e1 mate\u0159sk\u00e1 hypotyre\u00f3za m\u016f\u017ee ovlivnit v\u00fdvoj fet\u00e1ln\u00edho mozku(8,9,10). Dostate\u010dn\u00e1 produkce tyreoid\u00e1ln\u00edch hormon\u016f je tak mimo\u0159\u00e1dn\u011b v\u00fdznamn\u00e1 zvl\u00e1\u0161t\u011b na po\u010d\u00e1tku t\u011bhotenstv\u00ed, proto\u017ee hormony \u0161t\u00edtn\u00e9 \u017el\u00e1zy jsou d\u016fle\u017eit\u00fdm faktorem diferenciace bun\u011bk b\u011bhem nitrod\u011blo\u017en\u00edho v\u00fdvoje. Tyroxin je z\u00e1sadn\u011b d\u016fle\u017eit\u00fd v mnoha aspektech v\u00fdvoje mozku v\u010detn\u011b neurogeneze, migrace neuron\u016f, formace axon\u016f a dendrit\u016f, myelinizace, synaptogeneze a regulace neurotransmiter\u016f. K cel\u00e9mu v\u00fdvoji doch\u00e1z\u00ed b\u011bhem n\u011bkolika m\u011bs\u00edc\u016f, ale kritick\u00fdm obdob\u00edm je druh\u00fd trimestr t\u011bhotenstv\u00ed(11). Plod p\u0159itom za\u010d\u00edn\u00e1 produkovat vlastn\u00ed hormony \u0161t\u00edtn\u00e9 \u017el\u00e1zy a\u017e od 20. t\u00fddne t\u011bhotenstv\u00ed.<\/p>\n

Nepoznan\u00e1 porucha funkce \u0161t\u00edtn\u00e9 \u017el\u00e1zy spojen\u00e1 s hypotyroxin\u00e9mi\u00ed matky, kter\u00e1 nemus\u00ed ohrozit pr\u016fb\u011bh gravidity, m\u016f\u017ee m\u00edt negativn\u00ed vliv na psychomotorick\u00fd v\u00fdvoj d\u00edt\u011bte. V\u010dasn\u00e1 a spr\u00e1vn\u00e1 diagn\u00f3za a l\u00e9\u010dba jsou spolehlivou prevenc\u00ed n\u00e1sledk\u016f(12).<\/p>\n

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Poruchy funkce \u0161t\u00edtn\u00e9 \u017el\u00e1zy v t\u011bhotenstv\u00ed<\/h3>\n

Podle mnoha rozs\u00e1hl\u00fdch studi\u00ed jsou poruchy funkce \u0161t\u00edtn\u00e9 \u017el\u00e1zy v t\u011bhotenstv\u00ed spojen\u00e9 s v\u00e1\u017en\u00fdmi mate\u0159sk\u00fdmi, fet\u00e1ln\u00edmi a novorozeneck\u00fdmi komplikacemi: spont\u00e1nn\u00ed potraty, p\u0159ed\u010dasn\u00e9 porody, preeklampsie, gesta\u010dn\u00ed diabetes, c\u00edsa\u0159sk\u00e9 \u0159ezy, del\u0161\u00ed pobyt na jednotce intenzivn\u00ed p\u00e9\u010de, abrupce placenty nebo poporodn\u00ed krv\u00e1cen\u00ed. \u017deny s TSH vy\u0161\u0161\u00edm ne\u017e 6 mU\/l ve druh\u00e9m trimestru maj\u00ed \u010dty\u0159ikr\u00e1t vy\u0161\u0161\u00ed riziko \u00famrt\u00ed plodu ne\u017e \u017eeny s TSH pod t\u00edmto limitem(2).<\/p>\n

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Hypotyre\u00f3za<\/h3>\n

U zdrav\u00fdch t\u011bhotn\u00fdch \u017een jejich \u0161t\u00edtn\u00e1 \u017el\u00e1za zvl\u00e1d\u00e1 zv\u00fd\u0161en\u00e9 n\u00e1roky b\u011bhem t\u011bhotenstv\u00ed, ale u \u017een, jejich\u017e \u0161t\u00edtn\u00e1 \u017el\u00e1za m\u00e1 n\u011bjak\u00e1 omezen\u00ed, zp\u016fsoben\u00e1 autoimunitn\u00edm onemocn\u011bn\u00edm nebo nedostatkem j\u00f3du, m\u016f\u017ee doj\u00edt k rozvoji hypotyre\u00f3zy(1,13). Jej\u00ed klinick\u00e9 p\u0159\u00edznaky jsou stejn\u00e9 jako u net\u011bhotn\u00fdch, ale n\u011bkdy je t\u011b\u017ek\u00e9 je odli\u0161it od nespecifick\u00fdch pot\u00ed\u017e\u00ed prov\u00e1zej\u00edc\u00edch b\u011b\u017en\u00e9 t\u011bhotenstv\u00ed. U v\u011bt\u0161iny \u017een je hypotyre\u00f3za objevena a\u017e po stanoven\u00ed zv\u00fd\u0161en\u00e9 koncentrace TSH p\u0159i laboratorn\u00edm vy\u0161et\u0159en\u00ed.<\/p>\n

T\u011bhotensk\u00e1 hypotyre\u00f3za je \u010dasto autoimunitn\u00edho p\u016fvodu, proto se p\u0159i diagnostice vych\u00e1z\u00ed nejen z koncentrac\u00ed TSH a FT4, ale stanovuje se tak\u00e9 pozitivita protil\u00e1tek proti tyreoid\u00e1ln\u00ed peroxid\u00e1ze (TPOAb), n\u011bkdy i protil\u00e1tek proti tyreoglobulinu (TAbg). Manifestn\u00ed hypotyre\u00f3za, kter\u00e1 je typick\u00e1 zv\u00fd\u0161enou hladinou TSH a sn\u00ed\u017eenou hladinou tyroxinu, nen\u00ed u t\u011bhotn\u00fdch obvykl\u00e1 (0,3-0,5 %), subklinick\u00e1 forma, kdy je s\u00e9rov\u00e1 hladina TSH zv\u00fd\u0161en\u00e1, ale FT4 je v referen\u010dn\u00edm intervalu, se vyskytuje u minim\u00e1ln\u011b 2,5 % t\u011bhotenstv\u00ed(14,15).<\/p>\n

U \u017een m\u016f\u017ee b\u00fdt hypotyre\u00f3za spojena s neplodnost\u00ed a porodn\u00edmi komplikacemi. Nedostatek tyreoid\u00e1ln\u00edch hormon\u016f m\u016f\u017ee v\u00e9st k nevratn\u00e9mu po\u0161kozen\u00ed plodu; nedostate\u010dn\u00e9 diferenciaci nervov\u00fdch bun\u011bk, m\u016f\u017ee b\u00fdt ovlivn\u011bn v\u00fdvoj nervov\u00e9ho syst\u00e9mu i psychomotorick\u00fdch funkc\u00ed. Hypotyre\u00f3za matky m\u016f\u017ee v\u00e9st k narozen\u00ed d\u011bt\u00ed se signifikantn\u011b ni\u017e\u0161\u00edm IQ(9,16) a hypotyroxinemie m\u016f\u017ee zap\u0159\u00ed\u010dinit sn\u00ed\u017eenou schopnost vyjad\u0159ov\u00e1n\u00ed i neverb\u00e1ln\u00ed komunikace(17,18).<\/p>\n

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Hypertyre\u00f3za<\/h3>\n

Hypertyre\u00f3za (tyreotoxik\u00f3za) je definov\u00e1na jako klinick\u00fd syndrom hypermetabolismu a hyperaktivity d\u016fsledkem vysok\u00fdch hladin FT4 a\/nebo FT3. Sou\u010dasn\u011b je TSH sn\u00ed\u017eeno pod referen\u010dn\u00ed interval. Gravesova-Basedowova choroba (GB) je nej\u010dast\u011bj\u0161\u00ed p\u0159\u00ed\u010dinou autoimunitn\u00ed hypertyre\u00f3zy v t\u011bhotenstv\u00ed a objevuje se u 0,1 \u2013 1 % t\u011bhotn\u00fdch \u017een(13). V prvn\u00ed polovin\u011b t\u011bhotenstv\u00ed se nej\u010dast\u011bji vyskytuje (1 \u2013 3 %) p\u0159echodn\u00e1 tyreotoxik\u00f3za, syndrom gesta\u010dn\u00ed hypertyre\u00f3zy. Je definov\u00e1na hrani\u010dn\u00edmi nebo lehce zv\u00fd\u0161en\u00fdmi hodnotami FT4 a t\u00e9m\u011b\u0159 nem\u011b\u0159iteln\u00fdm TSH, negativn\u00edmi protil\u00e1tkami a v\u00fdsledkem sonografie. Jde o vliv vysok\u00fdch hladin hCG, kter\u00fd p\u016fsob\u00ed na TSH receptorech, \u0159e\u0161\u00ed se obvykle samovoln\u011b s poklesem hCG(4). Pokud je u t\u011bhotn\u00e9 diagnostikov\u00e1na subklinick\u00e1 hypertyre\u00f3za, nen\u00ed spojena se zhor\u0161en\u00fdm v\u00fdsledkem t\u011bhotenstv\u00ed(18,19) \u00a0a nen\u00ed nezbytn\u00e9 ji tedy ani l\u00e9\u010dit. Tyreotoxik\u00f3za GB typu je autoimunitn\u00edho p\u016fvodu, vyskytuje se u 0,2 % t\u011bhotn\u00fdch \u017een. Nedostate\u010dn\u011b kontrolovan\u00e1 GB toxik\u00f3za v t\u011bhotenstv\u00ed m\u016f\u017ee b\u00fdt komplikov\u00e1na preeklampsi\u00ed, potratem, p\u0159ed\u010dasn\u00fdm porodem, abrupc\u00ed placenty, malformacemi a n\u00edzkou porodn\u00ed v\u00e1hou plodu. Tyreotoxik\u00f3za GB typu m\u00e1 tendenci v pr\u016fb\u011bhu t\u011bhotenstv\u00ed se zm\u00edr\u0148ovat. Pokud je diagn\u00f3za stanovena spr\u00e1vn\u011b a v\u010das zah\u00e1jena l\u00e9\u010dba, je progn\u00f3za pro matku i plod velmi dobr\u00e1(20).<\/p>\n

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Autoimunitn\u00ed onemocn\u011bn\u00ed<\/h3>\n

U mlad\u00fdch \u017een bez klinick\u00fdch p\u0159\u00edznak\u016f poruchy funkce \u0161t\u00edtn\u00e9 \u017el\u00e1zy se \u010dasto vyskytuj\u00ed pozitivn\u00ed anti-TPO protil\u00e1tky. \u017deny s autoimunitn\u00ed chorobou \u0161t\u00edtn\u00e9 \u017el\u00e1zy, zn\u00e1mou je\u0161t\u011b p\u0159ed ot\u011bhotn\u011bn\u00edm, by m\u011bly b\u00fdt sledov\u00e1ny pomoc\u00ed TSH cel\u00e9 t\u011bhotenstv\u00ed. Poporodn\u00ed tyreoiditida je syndrom p\u0159echodn\u00e9 nebo trval\u00e9 poruchy funkce \u0161t\u00edtn\u00e9 \u017el\u00e1zy, kter\u00fd se objev\u00ed v prvn\u00edm roce po porodu a je zp\u016fsoben autoimunitn\u00edm z\u00e1n\u011btem \u0161t\u00edtn\u00e9 \u017el\u00e1zy. Incidence poporodn\u00edch tyreoiditid se uv\u00e1d\u00ed 5 \u2013 9 % v\u0161ech \u017een a hlavn\u00edm rizikov\u00fdm faktorem je p\u0159\u00edtomnost latentn\u00ed autoimunitn\u00ed tyreoiditidy(20). Poporodn\u00ed tyreoiditida se obvykle nevyskytne u \u017een bez zv\u00fd\u0161en\u00fdch protil\u00e1tek proti \u0161t\u00edtn\u00e9 \u017el\u00e1ze; jej\u00ed v\u00fdskyt byl pozorov\u00e1n u \u017een s pozitivn\u00edmi protil\u00e1tkami a projev\u00ed se u 50 % z nich. Poporodn\u00ed tyreoiditida pak p\u0159ejde v trvalou hypotyre\u00f3zu v 25 \u2013 30 % p\u0159\u00edpad\u016f(21,22,23).<\/p>\n

Malignity \u0161t\u00edtn\u00e9 \u017el\u00e1zy se vyskytuj\u00ed v t\u011bhotenstv\u00ed jen v\u00fdjime\u010dn\u011b.<\/p>\n

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Stanovovan\u00e9 parametry funkce \u0161t\u00edtn\u00e9 \u017el\u00e1zy v t\u011bhotenstv\u00ed<\/h3>\n

Diagnostika poruch funkce \u0161t\u00edtn\u00e9 \u017el\u00e1zy se prov\u00e1d\u00ed nej\u010dast\u011bji pomoc\u00ed dvou laboratorn\u00edch marker\u016f TSH a FT4. Stanoven\u00ed TSH je z\u00e1kladn\u00ed vy\u0161et\u0159ovac\u00ed metodou pro posouzen\u00ed funk\u010dn\u00ed poruchy \u0161t\u00edtn\u00e9 \u017el\u00e1zy. Stanoven\u00ed FT4 umo\u017e\u0148uje zjistit mno\u017estv\u00ed biologicky dostupn\u00e9ho tyroxinu pro t\u011bhotnou \u017eenu i jej\u00ed plod a nen\u00ed ovlivn\u011bno koncentraci vazebn\u00fdch protein\u016f (24). Hladina FT4 je ovlivn\u011bna dostate\u010dn\u00fdm mno\u017estv\u00edm j\u00f3du a tak\u00e9 d\u00e9lkou t\u011bhotenstv\u00ed. Anti-TPO protil\u00e1tky jsou markerem autoimunitn\u00edho procesu prob\u00edhaj\u00edc\u00edho ve \u0161t\u00edtn\u00e9 \u017el\u00e1ze a jejich stanoven\u00ed je diagnosticky i prognosticky velmi v\u00fdznamn\u00e9. P\u0159\u00edtomnost anti-TPO protil\u00e1tek v t\u011bhotenstv\u00ed tak\u00e9 nazna\u010duje nebezpe\u010d\u00ed v\u00fdskytu poporodn\u00ed tyreoiditidy, proto je vhodn\u00e9 toto vy\u0161et\u0159en\u00ed prov\u00e9st sou\u010dasn\u011b se stanoven\u00edm TSH a FT4(25).<\/p>\n

 <\/p>\n

Jodurie<\/h3>\n

Vhodn\u00fdm biomarkerem\u00a0 pro stanoven\u00ed saturace j\u00f3dem v populaci je stanoven\u00ed koncentrace jodidov\u00e9ho aniontu v mo\u010di (jodurie), kter\u00e9 m\u016f\u017ee eventu\u00e1ln\u011b slou\u017eit i k vylou\u010den\u00ed intoxikace j\u00f3dem jako p\u0159\u00ed\u010diny hypertyre\u00f3zy. Neju\u017e\u00edvan\u011bj\u0161\u00ed laboratorn\u00ed metodou pro stanoven\u00ed jodurie je Sandellova-Kolthoffova metoda zalo\u017een\u00e1 na fotometrick\u00e9m stanoven\u00ed Ce3+ iont\u016f, kter\u00e9 vznikaj\u00ed v redox syst\u00e9mu Ce4+\/As3+ katalytick\u00fdm p\u016fsoben\u00edm jodidov\u00fdch aniont\u016f. Fotometrick\u00e9mu stanoven\u00ed p\u0159edch\u00e1z\u00ed mineralizace vzorku v kysel\u00e9m prost\u0159ed\u00ed. Metoda je \u010dasov\u011b n\u00e1ro\u010dn\u00e1, nep\u0159\u00edli\u0161 vhodn\u00e1 do sou\u010dasn\u00fdch klinick\u00fdch laborato\u0159\u00ed. Stanoven\u00ed jodurie nen\u00ed b\u011b\u017enou metodou a suplementace j\u00f3dem je tak vy\u0161et\u0159ov\u00e1na jen v\u00fdjime\u010dn\u011b(26).<\/p>\n

Stanoven\u00ed hormon\u016f \u0161t\u00edtn\u00e9 \u017el\u00e1zy a TSH<\/h3>\n

K vy\u0161et\u0159ov\u00e1n\u00ed koncentrac\u00ed tyreoid\u00e1ln\u00edch hormon\u016f se b\u011b\u017en\u011b pou\u017e\u00edvaj\u00ed imunoanalytick\u00e1 stanoven\u00ed. Rozd\u00edln\u00e1 kvalita pou\u017e\u00edvan\u00fdch protil\u00e1tek, nastaven\u00ed metody na automatick\u00e9m analyz\u00e1toru a odli\u0161n\u00e9 v\u00fdrobn\u00ed postupy mohou v\u00e9st k tomu, \u017ee analytick\u00e9 soupravy jednotliv\u00fdch v\u00fdrobc\u016f in vitro diagnostiky (IVD) poskytuj\u00ed \u010dasto nesrovnateln\u00e9 v\u00fdsledky. Imunoanal\u00fdza m\u016f\u017ee b\u00fdt tak\u00e9 ovlivn\u011bna zk\u0159\u00ed\u017een\u00fdmi reakcemi s podobn\u00fdmi slou\u010deninami nebo metabolity.<\/p>\n

Naproti tomu kapalinov\u00e1 chromatografie s tandemovou hmotnostn\u00ed spektrometri\u00ed (LC\/MS\/MS) nab\u00edz\u00ed v\u00fdrazn\u00e9 zlep\u0161en\u00ed specificity a senzitivity stanoven\u00ed tyreoid\u00e1ln\u00edch hormon\u016f v porovn\u00e1n\u00ed s konven\u010dn\u00edmi imunoanalytick\u00fdmi metodami a pravd\u011bpodobn\u011b se v bl\u00edzk\u00e9 dob\u011b stane diagnostick\u00fdm standardem(27). P\u0159i stanoven\u00ed FT4 referen\u010dn\u00edm postupem je pro odd\u011blen\u00ed voln\u00e9 formy tyroxinu od v\u00e1zan\u00e9 pou\u017e\u00edv\u00e1na rovnov\u00e1\u017en\u00e1 dial\u00fdza. Pou\u017e\u00edvan\u011bj\u0161\u00ed, rychlej\u0161\u00ed a spolehliv\u011bj\u0161\u00ed metodou, kter\u00e1 byla zvolena i jako referen\u010dn\u00ed metoda pro stanoven\u00ed tyroxinu se uk\u00e1zala metoda LC\/MS\/MS s izotopovou diluc\u00ed (ID). V sou\u010dasn\u00e9 dob\u011b testujeme postup stanoven\u00ed syst\u00e9mem LC\/MS\/MS bez zvl\u00e1\u0161tn\u00ed extrakce pouze po odstran\u011bn\u00ed vazebn\u00fdch protein\u016f. Imunoanal\u00fdza a tandemov\u00e1 hmotnostn\u00ed spektrometrie poskytuj\u00ed v\u00fdsledky, kter\u00e9 nen\u00ed mo\u017en\u00e9 zam\u011b\u0148ovat. Tyto rozd\u00edly jsou nejv\u011bt\u0161\u00ed ve vy\u0161\u0161\u00edch koncentrac\u00edch. Ze srovn\u00e1n\u00ed IA a MS\/MS metod plyne, \u017ee imunoanal\u00fdza nem\u00e1 dostate\u010dnou specificitu a tak\u00e9 b\u00fdv\u00e1 \u010dasto ovlivn\u011bna n\u011bkter\u00fdmi interferuj\u00edc\u00edmi l\u00e1tkami \u2013 od zm\u011bn\u011bn\u00fdch vazebn\u00fdch protein\u016f po nespecifick\u00e9 heterofiln\u00ed protil\u00e1tky typick\u00e9 pro t\u011bhotenstv\u00ed. Nev\u00fdhodou pou\u017eit\u00ed MS\/MS je po\u017eadavek zku\u0161en\u00e9\u00a0\u00a0 a vy\u0161kolen\u00e9 obsluhy. Nav\u00edc rychlost odezvy nen\u00ed p\u0159\u00edli\u0161 vysok\u00e1 a doba zdr\u017een\u00ed vzorku v laborato\u0159i je tak\u00e9 mnohem del\u0161\u00ed ne\u017e u imunoanal\u00fdzy(28).<\/p>\n

 <\/p>\n

Stanoven\u00ed referen\u010dn\u00edch interval\u016f pro parametry funkce \u0161t\u00edtn\u00e9 \u017el\u00e1zy v t\u011bhotenstv\u00ed<\/h3>\n

Fyziologick\u00e9 zm\u011bny \u0161t\u00edtn\u00e9 \u017el\u00e1zy v t\u011bhotenstv\u00ed a p\u016fsoben\u00ed vysok\u00fdch hladin hCG jsou p\u0159\u00ed\u010dinou nezbytnosti stanoven\u00ed referen\u010dn\u00edch interval\u016f v t\u011bhotenstv\u00ed. Z\u00e1sadn\u00ed je spr\u00e1vn\u011b a v\u010das identifikovat v t\u011bhotenstv\u00ed \u017eeny, kter\u00e9 by m\u011bly potenci\u00e1ln\u011b u\u017eitek z nasazen\u00ed l\u00e9\u010dby. Referen\u010dn\u00ed hodnoty TSH v gravidit\u011b se li\u0161\u00ed v z\u00e1vislosti na laboratorn\u00edch metod\u00e1ch a existuj\u00ed rozd\u00edly mezi r\u016fzn\u00fdmi populacemi. Na z\u00e1klad\u011b v\u00fdsledk\u016f mnoha sv\u011btov\u00fdch pracovi\u0161\u0165 je t\u0159eba konstatovat, \u017ee nen\u00ed mo\u017en\u00e9 pou\u017e\u00edvat jedin\u00e9 obecn\u011b platn\u00e9 referen\u010dn\u00ed intervaly pro tyreoid\u00e1ln\u00ed parametry v t\u011bhotenstv\u00ed(29).<\/p>\n

Podle doporu\u010den\u00ed IFCC by m\u011bly b\u00fdt referen\u010dn\u00ed intervaly zalo\u017eeny na stanoven\u00ed 2,5 a 97,5 percentilu v populaci s dostate\u010dn\u00fdm j\u00f3dov\u00fdm z\u00e1soben\u00edm(2). Stanoven\u00ed neparametrick\u00e9ho cut-off by m\u011blo b\u00fdt provedeno v dostate\u010dn\u011b velk\u00e9, neselektovan\u00e9 populaci zdrav\u00fdch kontroln\u00edch osob. U TSH a n\u011bkdy i u FT4 existuje vysok\u00e1 interindividu\u00e1ln\u00ed variabilita a \u0161ikm\u00e9 rozlo\u017een\u00ed jejich hladin ve skupin\u011b t\u011bhotn\u00fdch. Pokud se jedn\u00e1 o stanoven\u00ed referen\u010dn\u00edch interval\u016f pro TSH a FT4, je pot\u0159eba vybrat t\u011bhotn\u00e9 \u017eeny, u kter\u00fdch jsou vylou\u010deny faktory stimuluj\u00edc\u00ed nebo inhibuj\u00edc\u00ed funkci \u0161t\u00edtn\u00e9 \u017el\u00e1zy. Preferov\u00e1na je populace anti-TPO negativn\u00edch \u017een bez osobn\u00ed \u010di rodinn\u00e9 historie poruch \u0161t\u00edtn\u00e9 \u017el\u00e1zy a dal\u0161\u00edch faktor\u016f, jako je u\u017e\u00edv\u00e1n\u00ed n\u011bkter\u00fdch l\u00e9k\u016f nebo v\u00edce\u010detn\u00e9 t\u011bhotenstv\u00ed.<\/p>\n

R\u016fzn\u00ed auto\u0159i publikuj\u00ed pom\u011brn\u011b \u0161irokou \u0161k\u00e1lu referen\u010dn\u00edch interval\u016f pro TSH a FT4 b\u011bhem \u010dasn\u00e9ho t\u011bhotenstv\u00ed vypo\u010d\u00edtan\u00fdch dle mezin\u00e1rodn\u00edch doporu\u010den\u00ed z dostate\u010dn\u011b velk\u00fdch skupin anti-TPO negativn\u00edch \u017een(31,32,33). Horn\u00ed hranice pro TSH je uv\u00e1d\u011bna od 2,15 do 4,68 mU\/l.<\/p>\n

Klinicky je v\u00fdznamn\u00fd fakt, \u017ee p\u0159i pou\u017eit\u00ed nevhodn\u00fdch limit\u016f by doch\u00e1zelo ke zbyte\u010dn\u00e9 l\u00e9\u010db\u011b eutyreoidn\u00edch \u017een, p\u0159\u00edpadn\u011b nedostate\u010dn\u00e9 l\u00e9\u010db\u011b p\u0159i pou\u017eit\u00ed referen\u010dn\u00edch interval\u016f pro b\u011b\u017enou populaci. I kdy\u017e n\u011bkter\u00e9 d\u0159\u00edv\u011bj\u0161\u00ed studie ukazovaly, \u017ee mezi v\u00fdsledky z\u00edskan\u00fdmi rozd\u00edln\u00fdmi komer\u010dn\u00edmi soupravami nejsou velk\u00e9 rozd\u00edly, p\u0159i porovn\u00e1n\u00ed referen\u010dn\u00edch interval\u016f pro t\u011bhotnou populaci jsou rozd\u00edly pom\u011brn\u011b zna\u010dn\u00e9, jak je mo\u017en\u00e9 vid\u011bt i v tabulce 1 <\/em><\/strong>shrnuj\u00edc\u00ed referen\u010dn\u00ed intervaly stanoven\u00e9 r\u016fzn\u00fdmi pracovi\u0161ti v Evrop\u011b, Asii i USA a zahrnuj\u00edc\u00ed i rozd\u00edly mezi rasov\u011b odli\u0161n\u00fdmi populacemi(34).<\/p>\n

Sv\u011btov\u00e1 doporu\u010den\u00ed Endocrine Society(5), American Thyroid Association (ATA)(13) a European Thyroid Association (ETA)(21) uv\u00e1d\u00ed, \u017ee trimestr specifick\u00e9 referen\u010dn\u00ed intervaly by m\u011bly b\u00fdt stanoveny v ka\u017ed\u00e9m diagnostick\u00e9m centru. Pokud to nen\u00ed mo\u017en\u00e9, lze pou\u017e\u00edt postup uveden\u00fd v tabulce 2<\/em><\/strong>.<\/p>\n

 <\/p>\n

Screening poruch \u0161t\u00edtn\u00e9 \u017el\u00e1zy<\/h3>\n

V\u0161eobecn\u00fd screening tyreopati\u00ed v t\u011bhotenstv\u00ed je dlouhodob\u011b kontroverzn\u00edm t\u00e9matem. Hlavn\u00ed rozpory jsou v rozsahu screeningu (v\u0161eobecn\u00fd nebo c\u00edlen\u00fd na rizikov\u00e9 skupiny)(45,46,72). V pr\u016fb\u011bhu pokra\u010duj\u00edc\u00edch diskus\u00ed se odborn\u00edci p\u0159ikl\u00e1n\u011bj\u00ed k v\u0161eobecn\u00e9mu screeningu st\u00e1le \u010dast\u011bji(47). Pro vy\u0161et\u0159en\u00ed funkce \u0161t\u00edtn\u00e9 \u017el\u00e1zy jsou navrhov\u00e1ny t\u0159i\u00a0 s\u00e9rov\u00e9 markery TSH, anti-TPO protil\u00e1tky a FT4, p\u0159i\u010dem\u017e ka\u017ed\u00fd z nich p\u0159in\u00e1\u0161\u00ed jin\u00e9 informace. Screening tyreopati\u00ed by m\u011bl b\u00fdt proveden u v\u0161ech \u017een nejpozd\u011bji v prvn\u00edm trimestru gravidity. Za p\u0159edpokladu suplementace v\u0161ech t\u011bhotn\u00fdch \u017een j\u00f3dem (100 mg denn\u011b) a s p\u0159ihl\u00e9dnut\u00edm k ekonomick\u00fdm aspekt\u016fm se pro t\u011bhotensk\u00fd screening jev\u00ed jako nejv\u00fdhodn\u011bj\u0161\u00ed minim\u00e1ln\u00ed kombinace TSH a anti-TPO protil\u00e1tek(26). <\/em>O\u0161et\u0159uj\u00edc\u00ed gynekolog by m\u011bl u v\u0161ech t\u011bhotn\u00fdch \u017een zhodnotit rizikov\u00e9 faktory, uveden\u00e9 d\u00e1le, a p\u0159i pozitivit\u011b kter\u00e9hokoliv z nich prov\u00e9st vy\u0161et\u0159en\u00ed TSH a anti-TPO.<\/p>\n

Rizikov\u00e9 faktory tyreopatie v t\u011bhotenstv\u00ed:<\/p>\n

    \n
  • Tyreopatie v osobn\u00ed nebo rodinn\u00e9 anamn\u00e9ze<\/li>\n
  • V\u011bk nad 30 let<\/li>\n
  • P\u0159\u00edznaky tyreoid\u00e1ln\u00ed dysfunkce nebo struma<\/li>\n
  • Pozitivn\u00ed anti-TPO<\/li>\n
  • DM typu nebo jin\u00e9 autoimunitn\u00ed onemocn\u011bn\u00ed<\/li>\n
  • Potrat, infertilita nebo p\u0159ed\u010dasn\u00fd porod v anamn\u00e9ze<\/li>\n
  • Oz\u00e1\u0159en\u00ed hlavy a\/nebo krku v anamn\u00e9ze<\/li>\n
  • Z\u00e1va\u017en\u00e1 obezita s BMI \u2265 40 kg\/m2<\/li>\n
  • U\u017e\u00edv\u00e1n\u00ed amiodaronu, lithia, aplikace cytokin\u016f, ned\u00e1vn\u00e1 aplikace jodov\u00e9ho rtg. kontrastu<\/li>\n
  • \u017dena \u017eije v oblasti se st\u0159edn\u00edm \u010di t\u011b\u017ek\u00fdm jodov\u00fdm deficitem<\/li>\n<\/ul>\n

     <\/p>\n

    Doporu\u010den\u00ed Americk\u00e9 tyreoidologick\u00e9 spole\u010dnosti (ATA) navrhuj\u00ed c\u00edlen\u00fd screening pouze u rizikov\u00fdch skupin \u017een(13). U \u017een s nov\u011b zachycenou hypotyre\u00f3zou, \u017een ji\u017e d\u0159\u00edve l\u00e9\u010den\u00fdch pro hypotyre\u00f3zu, eutyroidn\u00edch \u017een s pozitivn\u00edmi TPOAb l\u00e9\u010den\u00fdch euthyroxinemickou l\u00e9\u010dbou nebo eutyroidn\u00edch \u017een s pozitivn\u00edmi TPOAb nel\u00e9\u010den\u00fdch se prov\u00e1d\u00ed kontroly TSH v 5. \u2013 6., 10., 14., 20., n\u011bkdy 30. t\u00fddnu gravidity a pak po \u0161estined\u011bl\u00ed a podle toho se upravuje nebo i zahajuje l\u00e9\u010dba levotyroxinem. Tyto kontroly obvykle prov\u00e1d\u00ed endokrinolog. U \u017een s hypertyre\u00f3zou krom\u011b TSH se monitoruje FT4 ve stejn\u00fdch intervalech jako u hypotyre\u00f3zy. Zv\u00fd\u0161enou p\u00e9\u010di v pr\u016fb\u011bhu 1. roku po porodu vy\u017eaduj\u00ed \u017eeny s pozitivn\u00edmi TPOAb kv\u016fli mo\u017enosti v\u00fdvoje poporodn\u00ed tyreoiditidy. T\u011bhotn\u00e9 \u017eeny s eutyreoidn\u00edmi hladinami TSH i FT4 maj\u00ed v p\u0159\u00edpad\u011b\u00a0pozitivity anti-TPO protil\u00e1tek asi 50% pravd\u011bpodobnost, \u017ee se u nich rozvine poporodn\u00ed tyreoiditida, kter\u00e1 p\u0159ejde v trvalou hypotyre\u00f3zu v 25 \u2013 30 % p\u0159\u00edpad\u016f.<\/p>\n

     <\/p>\n

    Zku\u0161enosti z \u010cesk\u00e9 republiky<\/h3>\n

    V \u010cesk\u00e9 republice se u\u017e v roce 2006 objevilo \u00fasil\u00ed o zaveden\u00ed v\u0161eobecn\u00e9ho vy\u0161et\u0159ov\u00e1n\u00ed \u0161t\u00edtn\u00e9 \u017el\u00e1zy v t\u011bhotenstv\u00ed. Od t\u00e9 doby se uskute\u010dnilo mnoho studi\u00ed, p\u0159i\u010dem\u017e v\u0161echny dosp\u011bly k z\u00e1v\u011bru, \u017ee mezi t\u011bhotn\u00fdmi \u017eenami jsou tyreopatie, zvl\u00e1\u0161t\u011b autoimunitn\u00ed, velmi roz\u0161\u00ed\u0159en\u00e9(44,48,49,50).<\/p>\n

    V letech 2009 \u2013 2010 jsme prov\u00e1d\u011bli pilotn\u00ed studii podporovanou V\u0161eobecnou zdravotn\u00ed poji\u0161\u0165ovnou ve 13 \u010desk\u00fdch regionech s dobr\u00fdm laboratorn\u00edm i endokrinologick\u00fdm z\u00e1zem\u00edm. C\u00edlem projektu bylo zjistit prevalence tyreopati\u00ed a tyreoid\u00e1ln\u00edch autoimunit u t\u011bhotn\u00fdch \u017een a stanovit optim\u00e1ln\u00ed kombinaci a v\u00fdt\u011b\u017enost diagnostick\u00fdch test\u016f. Odb\u011br krve byl spojen s vy\u0161et\u0159ov\u00e1n\u00edm provotrimestr\u00e1ln\u00edho testu pro stanoven\u00ed rizika v\u00fdvoje plodu s Downov\u00fdm syndromem (9. \u2013 13. t\u00fd- den t\u011bhotenstv\u00ed). V\u0161echny t\u0159i testy TSH, FT4 a anti-TPO byly vy\u0161et\u0159eny celkem u 2 937 \u017een. V\u00fdsledky uk\u00e1zaly, \u017ee 18 % asymptomatick\u00fdch \u017een m\u011blo alespo\u0148 jeden patologick\u00fd n\u00e1lez ve vy\u0161et\u0159ovan\u00fdch parametrech. Hypertyre\u00f3za byla prok\u00e1z\u00e1na u 0,5 % \u017een, dal\u0161\u00ed sn\u00ed\u017een\u00e9 hladiny byly zp\u016fsobeny vysokou hladinou hCG. Hypotyre\u00f3za dan\u00e1 zv\u00fd\u0161enou hladinou TSH a\/nebo sn\u00ed\u017eenou hladinou FT4 se projevila u 7,8 % \u017een. V\u00fdznamn\u00e1 hypotyroxin\u00e9mie byla nalezena ve 3,7 % p\u0159\u00edpad\u016f. TPOAb pozitivitu m\u011blo 8,9 % v\u0161ech \u017een. V roce 2012 jsme tyto v\u00fdsledky potvrdili \u0161ir\u0161\u00ed studi\u00ed, kter\u00e1 zahrnula 5 223 t\u011bhotn\u00fdch \u017een(44,51). Projekt vedl k z\u00e1v\u011br\u016fm, \u017ee prov\u00e1d\u011bn\u00ed v\u0161eobecn\u00e9ho screenigu by m\u011blo b\u00fdt v na\u0161\u00ed republice velmi v\u00fdznam\u011b doporu\u010deno. Nav\u00edc se potvrdilo, \u017ee je mo\u017en\u00e9 vytvo\u0159it v republice s\u00ed\u0165 endokrinolog\u016f, kte\u0159\u00ed jsou ochotni p\u0159ijmout t\u011bhotnou do sv\u00e9 ordinace b\u011bhem jednoho t\u00fddne.<\/p>\n

     <\/p>\n

    Stanoven\u00ed marker\u016f funkce \u0161t\u00edtn\u00e9 \u017el\u00e1zy r\u016fzn\u00fdmi\u00a0analytick\u00fdmi syst\u00e9my<\/strong><\/h3>\n

    O\u0161et\u0159uj\u00edc\u00ed l\u00e9ka\u0159 by m\u011bl m\u00edt p\u0159ehled o tom, jak\u00fd imunoanalytick\u00fd system vyu\u017e\u00edv\u00e1 jeho laborato\u0159 a zda m\u00e1 stanoven\u00e9 specifick\u00e9 referen\u010dn\u00ed intervaly pro t\u011bhotenstv\u00ed alespo\u0148 pro TSH. V roce 2014 jsme stanovili referen\u010dn\u00ed intervaly pro TSH a FT4 v prvn\u00edm trimestru t\u011bhotenstv\u00ed. Kontrolovali jsme hladinu anti-TPO protil\u00e1tek, zda je mo\u017en\u00e9 pou\u017e\u00edvat cut-off doporu\u010den\u00fd v\u00fdrobcem reagenci\u00ed(52). Vy\u0161et\u0159ovan\u00e1 skupina zahrnovala 216 t\u011bhotn\u00fdch \u017een v 9. \u2013 13. t\u00fddnu t\u011bhotenstv\u00ed, kter\u00e9 potvrdily, \u017ee nemaj\u00ed v osobn\u00ed ani rodinn\u00e9 anamn\u00e9ze tyreopatii. Stanovili jsme hladinu TSH, FT4, a TPOAb v s\u00e9ru sou\u010dasn\u011b na sedmi odli\u0161n\u00fdch imunoanalyz\u00e1torech, kter\u00e9 reprezentuj\u00ed celosv\u011btov\u011b neju\u017e\u00edvan\u011bj\u0161\u00ed syst\u00e9my. Pro TSH a FT4 jsme stanovili 95% referen\u010dn\u00ed interval (2,5 \u2013 97,5 percentilu) za pou\u017eit\u00ed parametrick\u00e9ho p\u0159\u00edstupu; pro TPOAb jsme stanovili limit pozitivity jednoduchou neparametrickou metodou (95. percentil v\u0161ech hodnot). Standardizace stanoven\u00ed TPOAb je nemo\u017en\u00e1, proto by bylo vhodn\u011bj\u0161\u00ed vyjad\u0159ovat v\u00fdsledek stanoven\u00ed t\u011bchto protil\u00e1tek jako TPOAb-pozitivn\u00ed nebo TPOAb-negativn\u00ed. Spole\u010dnou hodnotu nen\u00ed mo\u017en\u00e9 stanovit.<\/p>\n

    V tabulce 3 <\/em><\/strong>je p\u0159ehled v\u00fdsledk\u016f pro v\u0161ech sedm analytick\u00fdch syst\u00e9m\u016f.<\/p>\n

     <\/p>\n

    Z\u00e1v\u011bry<\/h3>\n

    Poruchy \u0161t\u00edtn\u00e9 \u017el\u00e1zy v t\u011bhotenstv\u00ed jsou \u010dast\u00e9 a p\u0159edstavuj\u00ed hlavn\u00ed epidemiologick\u00e9 riziko t\u00fdkaj\u00edc\u00ed se sou\u010dasn\u00e9ho a budouc\u00edho t\u011bhotenstv\u00ed, stejn\u011b jako v\u00fdvoje d\u011bt\u00ed. T\u011bhotn\u00e9 \u017eeny se sn\u00ed\u017eenou funk\u010dn\u00ed rezervou kv\u016fli jodov\u00e9 insuficienci nebo autoimunit\u011b \u0161t\u00edtn\u00e9 \u017el\u00e1zy nemohou pot\u0159ebn\u011b zv\u00fd\u0161it produkci hormon\u016f \u0161t\u00edtn\u00e9 \u017el\u00e1zy a vyvine se u nich subklinick\u00e1 nebo zjevn\u00e1 hypotyre\u00f3za.<\/p>\n

    Spojen\u00ed mezi zjevnou hypotyre\u00f3zou, gynekologick\u00fdmi komplikacemi a poruchami neuropsychologick\u00e9ho v\u00fdvoje d\u011bt\u00ed bylo jasn\u011b stanoveno, proto je l\u00e9\u010dba levotyroxinem v\u0161eobecn\u011b doporu\u010dena. Manifestn\u00ed hypotyre\u00f3za postihuje minim\u00e1ln\u011b 0,4 % t\u011bhotn\u00fdch \u017een. P\u0159i p\u0159epo\u010dtu na populaci 10 milion\u016f obyvatel se 100 000 porody ro\u010dn\u011b, lze konstatovat, \u017ee 400 novorozenc\u016f ro\u010dn\u011b je ohro\u017eeno v\u00e1\u017en\u00fdmi neuropsycho- logick\u00fdmi komplikacemi.<\/p>\n

    Screening tyroid\u00e1ln\u00edch dysfunc\u00ed by m\u011bl b\u00fdt v \u010dasn\u00e9 f\u00e1zi t\u011bhotenstv\u00ed prov\u00e1d\u011bn minim\u00e1ln\u011b u rizikov\u00e9 populace, i kdy\u017e mnoh\u00e9 autority se p\u0159ikl\u00e1n\u011bj\u00ed ke screeningu v\u0161eobecn\u00e9mu. Stanoven\u00ed TSH a anti-TPO protil\u00e1tek nen\u00ed n\u00e1ro\u010dn\u00e9 a l\u00e9\u010dba levotyroxinem nen\u00ed drah\u00e1. V\u00fdznamn\u00e9 je u\u017e\u00edv\u00e1n\u00ed specifick\u00fdch referen\u010dn\u00edch interval\u016f pro TSH v t\u011bhotenstv\u00ed.<\/p>\n

    Na l\u00e9\u010dbu subklinick\u00e9 formy tyreopati\u00ed v t\u011bhotenstv\u00ed se n\u00e1zory odborn\u00edk\u016f rozch\u00e1zej\u00ed. N\u011bkter\u00e9 celosv\u011btov\u011b u\u017e\u00edvan\u00e9 imunoanalytick\u00e9 syst\u00e9my poskytuj\u00ed odli\u0161n\u00e9 v\u00fdsledky a t\u00edm i referen\u010dn\u00ed intervaly jsou vz\u00e1jemn\u011b nesrovnateln\u00e9. Nen\u00ed mo\u017en\u00e9 pou\u017e\u00edvat jednotnou rozhodovac\u00ed horn\u00ed mez pro TSH.<\/p>\n

    Na z\u00e1klad\u011b mnoha studi\u00ed je z\u0159ejm\u00e9, \u017ee t\u011bhotn\u00e9 anti-TPO pozitivn\u00ed \u017eeny by m\u011bly b\u00fdt sledov\u00e1ny v pr\u016fb\u011bhu t\u011bhotenstv\u00ed kv\u016fli riziku rozvoje hypotyre\u00f3zy, proto je doporu\u010deno vy\u0161et- \u0159ovat krom\u011b TSH tak\u00e9 anti-TPO protil\u00e1tky, a\u0165 u\u017e jde o screening univerz\u00e1ln\u00ed nebo c\u00edlen\u00fd na rizikovou skupinu \u017een. Riziko rozvoje poporodn\u00ed tyreoiditidy u anti-TPO pozitivn\u00edch \u017een je podlo\u017eeno dostate\u010dn\u00fdm mno\u017estv\u00edm studi\u00ed. Naproti tomu riziko neplodnosti, potratu, p\u0159ed\u010dasn\u00e9ho porodu a vrozen\u00fdch vad u plodu si zasluhuje je\u0161t\u011b podrobn\u011bj\u0161\u00ed potvrzen\u00ed.<\/p>\n

    V \u010cesk\u00e9 republice byla prok\u00e1z\u00e1na proveditelnost v\u0161eobecn\u00e9ho screening poruch funkce \u0161t\u00edtn\u00e9 \u017el\u00e1zy s mo\u017enost\u00ed n\u00e1sledn\u00e9 endokrinologick\u00e9 p\u00e9\u010de. V\u0161eobecn\u00fd screening autoimunitn\u00ed tyreoiditidy je doporu\u010den \u010ceskou endokrinologickou spole\u010dnost\u00ed \u010cLS JEP i \u010ceskou spole\u010dnost\u00ed klinick\u00e9 biochemie \u010cLS JEP a je prov\u00e1d\u011bn v n\u011bkter\u00fdch velk\u00fdch zdravotnick\u00fdch centrech.<\/p>\n

     <\/p>\n

    LITERATURA<\/strong><\/p>\n

      \n
    1. Abalovich M, Gutierrez S, Alcaraz G, et Overt and subclinical hypothyroidism complicating pregnancy. Thyroid 2002; 12: 63-68.<\/li>\n
    2. Allan WC, Haddow JE, Palomaki GE, et Maternal thyroid deficiency and pregnancy complications: implications for population screening. Journal of medical screening 2000; 7: 127-130.<\/li>\n
    3. Finken MJJ, Van Eijsden M, Loomans EM, et al. Maternal Hypothyroxinemia in Early Pregnancy Predicts Reduced Performance in Reaction Time Tests in 5- to 6-Year-Old The Journal of Clinical Endocrinology 2013; 98(4): 1417-1426.<\/li>\n
    4. Hershman The role of human chorionic gonadotropin as a thyroid stimulator in normal pregnancy. J Clin Endocrinol Metab 2008, 93: 3305-3306.<\/li>\n
    5. De Groot L, Abalovich M, Alexander EK, et Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. <\/em>J Clin Endocrinol Metab 2012; 97: 2543-2565.<\/li>\n
    6. Alvarez-Pendrerol M, Guxens M, Mendez M, et al. Iodine levels and thyroid hormones in healthy pregnant women and birth weight of their off- spring. European Journal of Endocrinology 2009; 160(3): 423-429.<\/li>\n
    7. Zamrazil V, Bilek R, Cerovska J, et The elimination of iodine defi- ciency in the Czech Republic: the steps toward success. Thyroid 2004; 14: 49-56.<\/li>\n
    8. Haddow JE, Palomaki GE, Allan WC, et Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Eng J Med 1999; 341: 549-555.<\/li>\n
    9. Morreale de Escobar G, Obregon MJ, et al. Role of thyroid hormone during early brain development. European journal of endocrinology\/European Federation of Endocrine Societies 2004; 151(Suppl 3): U25-37.<\/li>\n
    10. Henrichs J, Bongers-Schokking JJ, Schenk JJ, et al. Maternal thyroid function during early pregnancy and cognitive functioning in early childhood: the generation R J Clin Endocrinol Metab 2010; 95: 4227-4234.<\/li>\n
    11. Lazarus JH, Bestwick JP, Channon S, et Antenatal Thyroid Screening and Childhood Cognitive Function. N Eng J Med 2012; 366: 493-501.<\/li>\n
    12. Korevaar TI, Muetzel R, Medici M, et Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphol- ogy in childhood: a population-based prospective cohort study. The lancet Diabetes & endocrinology 2016; 4: 35-43.<\/li>\n
    13. Anagnostis P, Lefkou E, Goulis Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease during Pregnancy and the Postpartum Thyroid 2017; 27(9): 1209-1210.<\/li>\n
    14. Negro R, Stagnaro-Green Diagnosis and management of subclinical hypothyroidism in pregnancy. BMJ 2014; 349: g4929-g4929.<\/li>\n
    15. Wilson KL, Casey BM, McIntire DD, et Subclinical Thyroid Disease and the Incidence of Hypertension in Pregnancy. Obstetrics 2012; 119(2, Part 1): 315-320.<\/li>\n
    16. Li Y, Shan Z, Teng W, et Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25-30 months. Clin Endocrinol (Oxf) 2010; 72: 825-829.<\/li>\n
    17. Morreale de Escobar G, Obregon MJ, Escobar del Rey Is neuropsychological development related to maternal hypothyroidi sm or to mater- nal hypothyroxinemia? J Clin Endocrinol Metab 2000; 85(11): 3975-3987.<\/li>\n
    18. Glinoer The Systematic Screening and Management of Hypothyroidism and Hyperthyroidism During Pregnancy. Trends in Endocrinology 1998; 9(10): 403-411.<\/li>\n
    19. Burggraaf J, Lalezari S, Emeis JJ, et al. Endothelial Function in Patients with Hyperthyroidism Before and After Treatment with Propranolol and Thyroid 2001; 11(2): 153-160.<\/li>\n
    20. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and Endocrine Practice 2002; 8(6): 457-469.<\/li>\n
    21. Lazarus J, Brown RS, Daumerie C, et European Thyroid Association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J 2014; 3: 76-94.<\/li>\n
    22. Potlukov\u00e1 E, \u00a0Jiskra \u00a0J, \u00a0Teli\u010dka \u00a0Z, \u00a0a \u00a0kol. \u00a0Pozitivita \u00a0protil\u00e1tek \u00a0proti tyreoid\u00e1ln\u00ed peroxid\u00e1ze u eutyre\u00f3zn\u00edch t\u011bhotn\u00fdch \u017een jako rizikov\u00fd faktor pozd\u011bj\u0161\u00edho rozvoje dystyre\u00f3zy. Diabetologie \u2013 Metabolismus \u2013 En- dokrinologie \u2013 V\u00fd\u017eiva 2011; 14(1): 27-32.<\/li>\n
    23. Potlukov\u00e1 E, Jiskra J, Springer D, a V\u00fdvoj funkce \u0161t\u00edtn\u00e9 \u017el\u00e1zy po porodu u \u017een zachycen\u00fdch v prvotrimestr\u00e1ln\u00edm screeningu tyreopati\u00ed. Di- abetologie \u2013 Metabolismus \u2013 Endokrinologie \u2013 V\u00fd\u017eiva 2011; 14(2): 57-58.<\/li>\n
    24. L\u00edmanov\u00e1 Z, Pikner R, Springer Doporu\u010den\u00ed pro laboratorn\u00ed diagnostiku funk\u010dn\u00edch a autoimunn\u00edch onemocn\u011bn\u00ed \u0161t\u00edtn\u00e9 \u017el\u00e1zy. Klinick\u00e1 biochemie a metabolismus 2011; 19(1): 48-61.<\/li>\n
    25. Walker JA, Illions EH, Huddleston JF, et Racial comparisons of thyroid function and autoimmunity during pregnancy and the postpartum period. Obstet Gynecol 2005; 106: 1365-1371.<\/li>\n
    26. Hor\u00e1\u010dek J, Jiskra J, L\u00edmanov\u00e1 Z, a Doporu\u010den\u00ed pro diagnostiku a l\u00e9\u010dbu onemocn\u011bn\u00ed \u0161t\u00edtn\u00e9 \u017el\u00e1zy v t\u011bhotenstv\u00ed a pro \u017eeny s poruchou fertility. Klinick\u00e1 biochemie a metabolismus 2013; 21(42): 41-64.<\/li>\n
    27. Soldin JS, Soukhova N, Janicic N, et The measurement of free thyroxine by isotope dilution tandem mass spectrometry. Clin Chem Acta 2005; 358: 113-118.<\/li>\n
    28. Anckaert E, Poppe K, Van Uytfanghe K, et FT4 immunoassays may display a pattern during pregnancy similar to the equilibrium dialysis ID\u2013 LC\/tandem MS candidate reference measurement procedure in spite of susceptibility towards binding protein alterations. Clinica Chimica Acta 2010; 411: 1348-1353.<\/li>\n
    29. Stricker R, Echenard M, Eberhart R, et Evaluation of maternal thyroid function during pregnancy: the importance of using gestational age-specific reference intervals. Eur J Endocrinol 2007; 157: 509-514.<\/li>\n
    30. Gilbert RM, Hadlow NC, Walsh JP, et Assessment of thyroid func- tion during pregnancy: first-trimester (weeks 9 \u2013 13) reference intervals derived from Western Australian women. Med J Aust 2008; 189: 250-253.<\/li>\n
    31. Haddow JE, Knight GJ, Palomaki GE, et The reference range and within- person variability of thyroid stimulating hormone during the first and second trimesters of pregnancy. J Med Screen 2004; 11: 170-174.<\/li>\n
    32. Panesar NS, Li LY, Rogers MG. Reference intervals for thyroid hor- mones in pregnant Chinese Annals of Clinical Biochemistry 2001; 38(4): 329-332.<\/li>\n
    33. Soldin OP, Soldin D, Sastoque Gestation-specific thyroxine and thyroid stimulating hormone levels in the United States and worldwide. Ther Drug Monit 2007; 29: 553-559.<\/li>\n
    34. Medici M, Korevaar TI, Visser WE, et Thyroid Function in Pregnancy: What Is Normal? Clin Chem 2015; 61: 704-713.<\/li>\n
    35. Bestwick JP, John R, Maina A, et Thyroid stimulating hormone and free thyroxine in pregnancy: expressing concentrations as multiples of the median (MoMs). Clin Chim Acta 2014; 430: 33-37.<\/li>\n
    36. Bocos-Terraz JP, Izquierdo-Alvarez S, Bancalero-Flores JL, et Thyroid hormones according to gestational age in pregnant Spanish women. BMC Res Notes 2009; 2: 237.<\/li>\n
    37. Lambert-Messerlian G, McClain M, Haddow JE, et Firstand second-trimester thyroid hormone reference data in pregnant women: a FASTER (first- and second-trimester evaluation of risk for aneuploidy) research consortium study. Am J Obstet Gynecol 2008; 199: 62 e1-6.<\/li>\n
    38. La\u2019ulu SL, Roberts Ethnic differences in first trimester thyroid reference intervals. Clin Chem 2011; 57: 913-915.<\/li>\n
    39. Li C, Shan Z, Mao J, et al. Assessment of thyroid function during first-trimester pregnancy: what is the rational upper limit of serum TSH during the first trimester in Chinese pregnant women? J Clin Endocrinol Metab 2014; 99: 73-79.<\/li>\n
    40. Mannisto T, Surcel HM, Ruokonen A, et Early pregnancy reference intervals of thyroid hormone concentrations in a thyroid antibody-negative pregnant population. Thyroid 2011; 21: 291-298.<\/li>\n
    41. Medici M, de Rijke YB, Peeters RP, et Maternal early pregnancy and newborn thyroid hormone parameters: the Generation R study. J Clin En- docrinol Metab 2011; 97: 646-652.<\/li>\n
    42. Pearce EN, Oken E, Gillman MW, et al. Association of first-trimester thyroid function test values with thyroperoxidase antibody status, smok- ing, and multivitamin Endocr Pract 2008; 14: 33-39.<\/li>\n
    43. Quinn FA, Gridasov GN, Vdovenko SA, et Prevalence of abnormal thyroid stimulating hormone and thyroid peroxidase antibody-positive results in a population of pregnant women in the Samara region of the Russian Fed- eration. Clinical Chemical Laboratory Medicine 2005; 43(11): 1223-1226.<\/li>\n
    44. Springer D, Zima T, Limanova Z. Reference intervals in evaluation of maternal thyroid function during the first trimester of European Journal of Endocrinology, 2009; 160: 791-797.<\/li>\n
    45. Vaidya B, Anthony S, Bilous M, et al. Detection of thyroid dysfunction in early pregnancy: Universal screening or targeted high-risk case finding? The Journal of clinical endocrinology and metabolism 2007; 92: 203-207.<\/li>\n
    46. Negro R, Schwartz A, Gismondi R, et Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy. J Clin Endocrinol Metab 2010; 95:1699-707.<\/li>\n
    47. Dosiou C, Barnes J, Schwartz A, et Cost-effectiveness of universal and risk-based screening for autoimmune thyroid disease in pregnant women. The Journal of clinical endocrinology and metabolism 2012; 97: 1536-1546.<\/li>\n
    48. Potlukova E, Potluka O, Jiskra J, et Is age a risk factor for hypothyroidism in pregnancy? An analysis of 5223 pregnant women. The Journal of clinical endocrinology and metabolism 2012; 97: 1945-1952.<\/li>\n
    49. Bart\u00e1kov\u00e1 J, Potlukov\u00e1 E, Rogalewicz V, et Screening for autoim- mune thyroid disorders after spontaneous abortion is cost-saving and it improves the subsequent pregnancy rate. BMC Pregnancy Childbirth 2013; 13: 217.<\/li>\n
    50. Horacek J, Spitalnikov\u00e1 S, Dlabalova B, et Universal screening detects two-times more thyroid disorders in early pregnancy than targeted high-risk case finding. Eur J Endocrinol 2010; 163: 645-650.<\/li>\n
    51. Limanova Z, Springer Thyreopathy examination during pregnancy \u2013 results of pilot project]. Casopis lekaru ceskych 2011; 150: 389-393.<\/li>\n
    52. Springer D, Bartos V, Zima Reference intervals for thyroid markers in early pregnancy determined by 7 different analytical systems. Scand J Clin Lab Invest 2014; 74: 95-101.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

      *All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.   T\u011bhotenstv\u00ed je komplexn\u00ed fyziologick\u00fd proces, p\u0159i kter\u00e9m prob\u00edh\u00e1 \u0159ada hormon\u00e1ln\u00edch a metabolick\u00fdch zm\u011bn. T\u011bmito zm\u011bnami i z\u00e1t\u011b\u017e\u00ed, kter\u00e1 je na \u0161t\u00edtnou \u017el\u00e1zu b\u011bhem t\u011bhotenstv\u00ed kladena, m\u016f\u017ee b\u00fdt iniciov\u00e1na porucha<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[289],"tags":[1054,1046,1052,1047,660,1048,1049,1050,1053,1051],"class_list":["post-1596","post","type-post","status-publish","format-standard","hentry","category-biochemistry","tag-anti-thyroperoxidase-antibodies","tag-anti-tpo-protilatky-en","tag-autoimmune-thyroid-disease","tag-autoimunitni-onemocneni-en","tag-pregnancy","tag-screening-en","tag-stitna-zlaza-en","tag-tehotenstvi-en","tag-thyroid-stimulating-hormone","tag-tsh-en","typ_clanku-review-article"],"acf":{"abstrakt":"

      Thyroid hormones are crucial for the growth and maturation of many target tissues, especially the brain and skeleton. During critical periods in the first third of pregnancy, maternal thyroxine is essential for the foetal development as it supplies the thyroid hormone-dependent tissues. The ontogeny of mature thyroid function involves organogenesis and maturation of the hypothalamus, pituitary, and the thyroid gland; and it is almost complete by the 12th \u2013 14th gestational weeks. In case of maternal hypothyroidism, substitution with levothyroxine must start in the early pregnancy. After the 14th gestational week, the foetal brain development may already be irreversibly
      \naffected by lack of thyroid hormones. The prevalence of manifest hypothyroidism in pregnancy reaches about 0.3-0.5%. The prevalence of subclinical hypothyroidism varies between 4-17%, strongly depending on the definition of the upper TSH cut-off limit. Hyperthyroidism occurs in 0.1%\u20131% of all pregnancies. Positivity for antibodies against thyroid peroxidase (TPOAb) is common in women of childbearing age and has been reported between 5.1% and 12.4%. TPOAb-positivity may be regarded as a manifestation of a general autoimmune state which may alter the fertilization and implantation process or cause early missed abortions. Women positive for TPOAb are at a significant risk of developing hypothyroidism during pregnancy and postpartum. The laboratory diagnosis of thyroid dysfunction during pregnancy is based upon serum TSH concentration. Results of multiple international studies point towards creation of trimester-specific reference intervals for TSH in pregnancy. TSH in pregnancy is physiologically lower compared to the non-pregnant population. Screening for hypothyroidism in pregnancy is controversial, and its implementation varies from a country to a country. Until now, the case-finding approach of screening of the high-risk women is preferred in most countries. However, numerous studies have shown that one-third to one-half of women with thyroid disorders escape the case-finding approach. Screening for thyroid disorders in pregnancy should include assessment of both TSH and TPOAb, regardless the screening approach.
      \nThe present review summarizes the current knowledge on the causes of thyroid dysfunction in pregnancy and its effects on pregnancy course and foetal development. We display an overview of the analytical methods and their reference intervals in pregnancy.<\/p>\n

      Keywords:<\/strong> autoimmune thyroid disease, pregnancy, screening, thyroid-stimulating hormone, anti-thyroperoxidase
      \nantibodies<\/p>\n","casopis":[{"ID":1513,"post_author":"7","post_date":"2018-11-05 11:53:53","post_date_gmt":"2018-11-05 10:53:53","post_content":"

        \r\n \t
      • Genetically important aberrations in patients with mye-lodysplastic syndrome and laboratory methods of their detection<\/li>\r\n \t
      • Molecular \u2013 genetic diagnostics of Human Papillomavirus (HPV) and monitoring of HPV patients<\/li>\r\n \t
      • Laboratory diagnostic possibilities for Clostridium difficile infections<\/li>\r\n \t
      • Chorangiosis of Placenta - Disorder of Unclear Etiology (Case Report and Overview of Current Knowledge)<\/li>\r\n \t
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