Rizični čimbenici za karcinom štitne žlijezde: što danas radimo?

Thyroid cancer (TC) is the most common endocrine cancer today. The rising incidence of the differentiated papillary type cannot be entirely explained by early and meticulous diagnosis, since a proportion of large tumors has also been reported. In this review, we present the results of numerous investigations focused on possible factors causing increased TC incidence, such as chromosomal and genetic alterations, iodine intake, TSH level, autoimmune thyroid disease, gender, estrogen, obesity, lifestyle changes, and environmental pollutants. Up to now, only childhood exposure to ionizing radiation has been fully recognized as a risk factor. There is also a possibility that yet undiscovered carcinogens, especially during intrauterine life or early childhood, might be responsible for increased TC incidence as well as epigenetic changes. Therefore, more studies are necessary in order to further investigate the potential risk factors for TC and their mechanisms of action.Etiologija karcinoma štitnjače, kao najčešćeg endokrinog karcinoma intenzivno se istražuje, budući da je njegova incidencija zadnjih desetljeća u stalnom porastu, prvenstveno na račun diferenciranog papilarnog karcinoma. Jedan od glavnih razloga porasta incidencije je zasigurno dostupna i kvalitetna dijagnostika karcinoma u ranoj fazi, međutim, uočava se i porast broja većih tumora, što upućuje na zaključak da vjerojatno postoje i drugi uzroci. U ovom radu izloženi su rezultati brojnih istraživanja usmjerenih na ispitivanje potencijalnih čimbenika rizika koji se dovode u vezu s razvojem karcinoma štitne žlijezde, kao što su kromosomske/genske alteracije, unos joda, razina TSH, autoimuna bolest štitnjače, spol, estrogeni, debljina, životne navike i čimbenici okoliša, od kojih je jedini dokazani čimbenik rizika izlaganje ionizirajućem zračenju u djetinjstvu. Potrebna su daljnja istraživanja s ciljem ispitivanja mogućih čimbenika rizika i njihovih mehanizama djelovanja kako bi se moglo učinkovitije kontrolirati i usporiti pojavnost karcinoma štitnjače

The internal consistency and validity of the Vaccination Attitudes Examination Scale: A replication study

Background: Vaccinations are important preventative health behaviors. The recently developed Vaccination Attitudes Examination Scale (VAX) aims to measure the reasons behind refusal/hesitancy regarding vaccinations.  Purpose: The aim of this replication study is to conduct an independent test of the newly developed VAX scale in the U.K. We tested: (a) internal consistency (Cronbach’s alpha); (b) convergent validity by assessing its relationships with beliefs about medication, medical mistrust and perceived sensitivity to medicines; and (c) construct validity by testing how well the VAX scale discriminated between vaccinators and nonvaccinators.  Methods: A sample of 243 UK adults completed the VAX scale, the Beliefs about Medicines Questionnaire (BMQ), the Perceived Sensitivity to Medicines Scale (PSM) and the Medical Mistrust Index (MMI), in addition to demographics of age, gender, education levels and social deprivation. Participants were asked: (a) if they received an influenza vaccination in the past year; and (b) if they had a young child, had they vaccinated their young child against influenza in the past year.  Results: The VAX: (a) demonstrated high internal consistency (α=0.92); (b) was positively correlated with medical mistrust, beliefs about medicines and less strongly correlated with perceived sensitivity to medicines; and (c) successfully differentiated parental influenza vaccinators from non-vaccinators.  Conclusion: The VAX demonstrated good internal consistency, convergent and construct validity in an independent UK sample. It appears to be a useful measure to help us understand the health beliefs that promote or deter vaccination behavior

Hybrid SPECT/CT Somatostatin Receptor Imaging of Neuroendocrine Tumours

Cilj: Cilj rada bio je procijeniti doprinos jednofotonske emisijske tomografije / kompjutorizirane tomografije somatostatinskih receptora (SR SPECT/CT) s 99mTc-EDDA/HYNIC-Tyr3-oktreotidom (99mTc-Tektrotyd) u dijagnostici i procjeni proširenosti bolesti kod pacijenata oboljelih od neuroendokrinih tumora (NET-ova). Ispitanici i metode: Retrospektivno je analizirano 120 SR SPECT/CT snimanja pacijenata s patohistološki dokazanim NET-om s obzirom na vizualizaciju primarnih lezija i metastaza. U 45 pacijenata učinjena je i pozitronska emisijska tomografija 18F-fluorodeoksiglukozom (18F-FDG PET/CT) te su nalazi uspoređeni s nalazima SR SPECT/CT-a i vrijednostima kromogranina A. Rezultati: Od 120 pacijenata 47 (39 %) je na SR SPECT/CT upućeno nakon odstranjenja primarne lezije. Od preostala 73 pacijenta (61 %), u 56 (77 %) primarni je tumor bio vidljiv SR SPECT/CT-om, a u 9 (12 %) poznata lezija nije akumulirala radiofarmak. U 8 (11 %) pacijenata s NET-om nepoznatog primarnog sijela nalaz je bio negativan. Od 68 (57 %) pacijenta s dokazanim metastazama, u njih 57 (84 %) bile su vidljive SR SPECT/CT-om, a u 11 (16 %) nisu akumulirale radiofarmak. Od 45 (38 %) pacijenata kojima je učinjen i 18F-FDG PET/CT, u 27 (60 %) detekcija primarnih lezija i metastaza bila je sukladna nalazu SR SPECT/CT-a. Osjetljivost SR SPECT/CT-a bila je 77 % za primarne lezije i 84 % za metastaze, a 18F-FDG PET/CT-a 75 % za primarne lezije i 76 % za metastaze. Vrijednosti kromogranina A nisu pokazale statistički signifikantnu korelaciju s nalazima slikovne dijagnostike. Zaključci: SR SPECT/CT ima visoku osjetljivost za detekciju NET-ova. Osim toga, potvrđena je komplementarnost s 18F-FDG PET/CT-om te kod pacijenata s negativnim nalazom SR SPECT/CT-a treba učiniti 18F-FDG PET/CT i obrnuto.The aim: The aim of this study was to evaluate the significance of somatostatin receptor single-photon emission computed tomography/computed tomography (SR SPECT/CT) with 99mTc-EDDA/HYNIC-Tyr3-octreotide (99mTc-Tektrotyd) in diagnostics and staging of patients with neuroendocrine tumours. Patients and methods: We retrospectively enrolled 120 patients with histologically proven NET who underwent SR SPECT/CT between January 2013 and February 2017. The patients’ data and SR SPECT/CT findings regarding primary lesion and metastases were analysed. In 45 patients, 2-deoxy-2-18F-fluoroglucose positron emission computed tomography/computed tomography (18F-FDG PET/CT) was performed, and the findings were compared to SR SPECT/CT and chromogranin A values. Results: Out of 120 patients, 47 (39%) underwent SR SPECT/CT after surgical removal of the primary lesion. In 73 (61%) remaining patients, the primary lesion was detected on SR SPECT/CT in 56 (77%), in 9 (12%) lesion did not accumulate 99mTc-Tektrotyd. SR SPECT/CT was negative in the remaining 8 (11%) patients with unknown primary. Out of 68 patients (57%) with metastases, 57 (84%) were detected on SR SPECT/CT, while 11 did not accumulate 99mTc- Tektrotyd. 18F-FDG PET/CT was performed in 45 patients, and findings were concordant with SR SPECT/CT in 27 (60%). The the sensitivity of SR SPECT/CT was 77% for primary lesions and 84% for metastases, and sensitivity of 18F-FDG PET/CT was 75% 76%, respectively. In 70 (58%) patients with available chromogranin A no statistically significant correlation was found with imaging methods. Conclusion: In patients with NET and negative SR SPECT/CT findings, 18F-FDG PET/CT should be recommended and vice versa, because of the complementarity of these procedures

The role of 99mTc-MIBI in the evaluation of non-functional thyroid gland nodules

Cilj: Cilj studije je prikazati ulogu oslikavanja 99mTc metoksiizobutilizonitrilom (99mTc-MIBI) pomoću planarnog oslikavanja i jednofotonske emisijske tomografije “niskodoznom” kompjutoriziranom tomografijom (engl. single photon emission computerized tomography – computerized tomography, SPECT-CT), u obradi čvorova štitne žlijezde koji su afunkcionalni na oslikavanju 99mTc-pertehnetatom i potvrđeni ultrazvučnim pregledom. Ispitanici i metode: Retrospektivno su pregledani nalazi pacijenata kojima je učinjeno oslikavanje štitne žlijezde 99mTc-MIBI-jem i citološka punkcija u periodu od 2008. do 2018., te su uspoređeni s patohistološkim nalazom (engl. pathohistological diagnosis, PHD). Studije su snimljene gama-kamerom s kolimatorom visoke rezolucije na dva načina: planarno i tomografski (SPECT-CT). Rezultati citološke punkcije klasificirani su po Bethesda klasifikaciji dok su PHD rezultati klasificirani kao benigni ili maligni. Rezultati: U razdoblju od 2008. do 2018. snimljena je 271 studija štitne žlijezde 99mTc-MIBI-jem. Kod 42 pacijenta bili su zadovoljeni svi uključni kriteriji. Od ta 42 pacijenta s PHD nalazom 28 ih je bilo suspektno, odnosno čvor se na oslikavanju 99mTc-MIBI-jem prikazao kao hipermetabolički. Negativna prediktivna vrijednost metode iznosi 78,6 % (NPV = 11/(3+11) = 0,786), a pozitivna prediktivna vrijednost 18 % (PPV = 5/(5+23) = 0,179). Zaključak: S obzirom na visoku negativnu prediktivnu vrijednost, slikovna dijagnostika 99mTc-MIBI-jem može se preporučiti kao komplementarna metoda citološkoj punkciji u obradi čvorova u štitnoj žlijezdi.Aim: The objective of the study is to show the role of 99mTc methoxyisobutylisonitrile (99mTc-MIBI) with planar imaging and single photon emission tomography with “low dose” CT (SPECT-CT) in a work up of non-functioning thyroid nodules on imaging with 99mTc- pertechnetate, which were confirmed by ultrasound examination. Patients and methods: Patients who underwent thyroid imaging with 99mTc-MIBI in the period from 2008 to 2018 were reviewed. The findings were compared with PHD results. The imaging was performed on gamma camera with high resolution collimator as planar scintigraphy and SPECT-CT. The results of fine needle aspiration biopsy were classified by the Bethesda classification, while PHD results were classified, as benign or malignant. Results: In the period from 2008-2018, 271 thyroid imaging with 99mTc- MIBI were performed. In 42 patients all-inclusive criteria were met.Out of those 42 patients, 28 of the PHD findings were concordant with the imaging, i.e. a node was presented as hypermetabolic. The calculated negative predictive value of the procedure is 78.6% (NPV = 11/ (3+11) = 0,786), and positive predictive value 18% (PPV = 5/ (5+23) = 0.179). Conclusion: Given the high negative predictive value, obtained from our results, 99mTc -MIBI imaging may be recommended as a complementary diagnostic method to fine-needle aspiration (FNA) in work up of thyroid nodules

Thyroid hormones and antithyroid antibodies influence infertility treatment, reproductive outcome and indications for assisted reproduction

Cilj: Cilj istraživanja bio je utvrditi vrijednost rutinskog određivanja hormona štitnjače, autoprotutijela (antiperoksidazna – A-TPO, antitireoglobilinska A-Tg) u serumu te ultrazvučnog (UZ) pregleda štitnjače u procjeni ishoda liječenja neplodnih parova postupcima medicinski pomognute oplodnje. Ispitanice i metode: U istraživanje su uključene pacijentice (n = 222) s dijagnozom neplodnosti liječene u razdoblju od 2009. do 2015. godine postupcima medicinski pomognute oplodnje na Zavodu za humanu reprodukciju i Kliničkom zavodu za nuklearnu medicinu Kliničkog bolničkog centra u Rijeci. Pacijenticama je uzeta anamneza, učinjen je klinički i ultrazvučni pregled štitnjače, a određene su i koncentracije hormona i protutijela u serumu. Rezultati: Udio spontanih pobačaja bio je 29 % kod pacijentica s urednom funkcijom štitnjače, a 52 % kod pacijentica s autoimunom ili supkliničkom bolesti štitnjače. Zaključak: Povišene vrijednosti serumskih mikrosomalnih protutijela povezane su s češćim spontanim pobačajima nakon postupka medicinski pomognute oplodnje i u pacijentica koje imaju normalne serumske vrijednosti hormona štitnjače. Rutinsko određivanje hormona štitnjače i antitireoidnih antitijela u serumu te UZ pregled štitnjače može pomoći u utvrđivanju uzroka neplodnosti, probiru pacijentica s rizikom za spontani pobačaj te praćenju i liječenju neplodnosti.Aim: To estimate if the serum concentration of thyroid hormones, antithyroid antibodies and ultrasonographic examination of thyroid gland influence conception and reproductive outcome in infertile couples treated with methods of assisted reproduction Methods: Two hundred and twenty two (222) patients with infertility diagnosis have undergone a research during 2009 – 2015 in Department of human reproduction and Clinical department of nuclear medicine, University hospital Rijeka. The patients have undergone the anamnesis, clinical examination, ultrasound examination and we determined the levels of thyroid hormones and autoantibodies in serum. Results: The percent of patients with normal thyroid function who had spontaneous miscarriage was 29 %, whereas on patients with autoimune or subclinical thyroid gland disease was 52 %. Conclusion: Increased serum microsomal antibodies and increased incidence of miscarriage were observed also in infertile patients treated with methods of assisted reproduction with normal serum concentration of thyroid hormones. Routine determination of thyroid hormones, autoantibodies in serum and ultrasonographic examination of thyroid gland may be useful in infertility diagnosis, screening the patient with miscarriage risk, monitoring and treatment of infertility

Immune-Endocrine characteristics of autoimmune thyroid disease during pregnancy

Cilj istraživanja: Autoimuna bolest štitne žlijezde (engl.: autoimmune thyroid disease-AITD) je najčešći organ specifični autoimuni poremećaj koji obuhvaća dva glavna klinička entiteta: Gravesovu bolest i Hashimotov tireoiditis. Za obje bolesti karakteristična je prisutnost organ specifičnih autoprotutijela na tri glavna tireoidna antigena: TSH receptor, tireoperoksidazu i tireoglobulin. Proupalni T pomoćnički tip 1 stanica (Th1) i Th1 citokini imaju ključnu ulogu u patogenezi organ specifičnih autoimunih bolesti, dok se zaštitna uloga pripisuje T pomoćničkim limfocitima tipa 2 (Th2) i Th 2 citokinima. U zdravoj trudnoći dominira Th2 nad Th1 imunosti čime se objašnjava poboljšanje autoimunih bolesti tijekom trudnoće, dok poslije poroda zbog promjene Th1/Th2 omjera često dolazi do pogoršanja AITD. Ukoliko je AITD induciran Th1 mehanizmima, pomak Th2 u Th1 odgovor mogao bi objasniti pogoršanje AITD postpartalno. Međutim, točan patofiziološki mehanizam ovog fenomena nije poznat. NKT i T regulacijske stanice predstavljaju stanične subpopulacije s velikom ulogom u prevenciji autoimunosti i toleranciji alogenih transplantata. Promjene imunoloških parametara tijekom AITD nisu dovoljno razjašnjene, osobito one tijekom trudnoće. Naš cilj je bio ispitati utjecaj imunološkog sustava tijekom trudnoće i nakon poroda na razvoj AITD, tj. utjecaj Th, NK, NKT i T regulacijskih limfocitnih subpopulacija (Tregs) te korelirati rezultate s nalazima hormona i usporediti ih sa onima u zdravih trudnica. Ispitanici i metode: Ispitali smo prisustvo AITD u ispitanica u trudnoći i postpartalno uz pomoć određivanja hormonskog statusa, titra tireoidnih autoprotutijela i ultrazvučnog pregleda štitnjače (UZV) i rezultate usporedili s kontrolama. Nakon unutarstaničnog i površinskog bojanja uz pomoć protočne citometrije analizirali smo fenotip i citolitički VI potencijal izoliranih mononuklearnih stanica periferne krvi ispitanica u trudnoći i u postporođajnom razdoblju te u kontrola. Rezultati: Srednja vrijednost TSH tijekom normalne trudnoće raste, ali bez značajne razlike u odnosu na kontrolnu skupinu žena, dok postpartalno pada. U trudnoći razina FT4 pada i statistički je značajno niža nego u kontrola, a postpartalno raste i značajno je viša u odnosu na trudnoću. Udio eutireoidnih ispitanica u trudnoći s povišenim titrom tireoidnih autoprotutijela je 16%, dok je postpartalno udio eutireoidnih ispitanica s povišenim titrom autoprotutijela 24%. Srednji TSH je u eutireoidnih trudnica s povišenim protutijelima veći u odnosu na kontrolne trudnice, ali bez statističke značajnosti. Od ukupnog broja ispitanica u trudnoći, 8,6%, je imalo subkl./kl.hipotireozu, a 2,7% subkl./kl. hipertireozu. Od ukupnog broja ispitanica postpartalno, 14% je imalo subkl./kl. hipotireozu, a 2,6% ispitanica subkl./kl hipertireozu. U 6,5% ispitanica dijagnosticirali smo postpartalni tireoiditis. U 25% ispitanica u trudnoći i 41,5 % ispitanica postpartalno smo dokazali prisustvo tireoidne autoimunosti. Stanice urođene imunosti: NKT i Tregs su povišene tijekom zdrave trudnoće, te trudnoće s hipotireozom i hipertireozom, kao i postpartalno u svim ispitivanim skupinama. NKT stanice su snižene u trudnica s pozitivnim protutijelima upućujući na smanjenje protektivne uloge NKT stanica u trudnoći pod djelovanjem protutijela. Ukupni perforin je snižen u zdravih trudnica, ali povišen u trudnica s pozitivnim protutijelima, hipotireozom i hipertireozom, te postpartalno, ukazujući na povećani citolitički potencijal ovih stanica pokrenut autoimunim procesom. Zaključak: Trudnoća i postpartalno razdoblje utječu na tijek AITD, a tireoidna autoimunost utječe na funkciju štitnjače u trudnoći i postpartalno. NKT i Treg stanice imaju važnu ulogu u regulaciji autoimunosti u ispitanica s AITD tijekom trudnoće i postporođThe aim: Autoimmune thyroid disease (AITD) is the organ specific autoimmune disorder. It comprises two major clinical entities: Graves’ disease and Hashimoto's thyroiditis, both characterised by the presence of thyroid specific autoantibodies directed against three major thyroid antigens: TSH receptor, thyroid peroxidase and thyroglobulin. It has been established that the proinflammatory, T helper cell 1 (Th1) type and Th1 cytokines play the major role in the pathogenesis of organ specific autoimmune diseases while the protective role goes to T helper cell 2 (Th2) type and Th2 cytokines. Normal pregnancy is characterised by Th2 domination over Th1 immunity which explains the amelioration of autoimmune disorders. However, after delivery, the Th1/Th2 ratio changes and exacerbation of autoimmune disorders usually occurs. If AITD is induced by Th1 mechanisms, the Th2/Th1 switch could explain the aggravation of AITD after delivery. Still, the exact patophysiological mechanism remains unclear. NKT and regulatory T cells are considered to have a central role in prevention of autoimmunity and maintaining tolerance of allogenic transplants. The alterations of immunological parameters during AITD remain unclear, especially those concerning AITD during pregnancy. Our aim was to investigate the influence of the immunological parameters during pregnancy and in the postpartum on the development of AITD, more precisely the influence of Th, NK, NKT and T regulatory cells, to correlate the results with the hormone levels and to compare them with healthy pregnant and non pregnant women. Patients and Methods: We investigated the presence of AITD in women during pregnancy and after delivery by analysing the thyroid hormone levels, thyroid antibody titres and ultrasound examination. We compared the results with healthy pregnant and postpartum VIII women and non pregnant controls. The phenotype and cytolytic potential of peripheral blood mononuclear cells of non pregnant, pregnant and postpartum women was analysed by flow cytometry after intracellular and surface staining. Results: The mean TSH level gradually increases during pregnancy, although not significantly compared to non pregnant women. It falls in the postpartum and is significantly lower compared to the second half of pregnancy. The mean FT4 level decreases during pregnancy and is significantly lower compared to non pregnant women, while in the postpartum it is significantly higher than during pregnancy. Positive autoantibodieas were found in 16% of euthyroid pregnant and 24% of euthyroid postpartum women. The mean TSH level in euthyroid pregnant women with positive antibodies was slightly, but not significantly, higher compared to control pregnancy. Subclinical or overt hypothyroidism was diagnosed in 8,6 % of pregnant and 14% of postpartum women while 2, 7 % of pregnant and 2,6% of postpartum women were in subclinical or overt hyperthyroidism. Postpartum thyroiditis was diagnosed in 6,5% of women. Thyroid autoimmunity was found in 25% of pregnant and 41,5 % of postpartum women. The cells of innate immunity: NKT and Tregs were elevated in healthy pregnancies and in pregnancies with hypo-and hyperthyroidism, as well as postpartum in all experimental groups. NKT cells were reduced in pregnant women with positive antibodies indicating a decrease in NKT cell protective effect of pregnancy under the action of antibodies. Total perforin was decreased in healthy pregnancy, but higher in patients with positive antibodies, hypo-and hyperthyroidism and postpartum indicating the increased cytolytic potential of these cells in autoimmune process. Conclusion: The pregnancy and postpartum influence the course of AITD, while thyroid autoimmunity also has an impact on the thyroid function during gestation and in the early postpartum. Both, NKT and T reg cells play an important role in regulation of autoimmunity in pregnant and postpartum women with AITD

Immune-Endocrine characteristics of autoimmune thyroid disease during pregnancy

Cilj istraživanja: Autoimuna bolest štitne žlijezde (engl.: autoimmune thyroid disease-AITD) je najčešći organ specifični autoimuni poremećaj koji obuhvaća dva glavna klinička entiteta: Gravesovu bolest i Hashimotov tireoiditis. Za obje bolesti karakteristična je prisutnost organ specifičnih autoprotutijela na tri glavna tireoidna antigena: TSH receptor, tireoperoksidazu i tireoglobulin. Proupalni T pomoćnički tip 1 stanica (Th1) i Th1 citokini imaju ključnu ulogu u patogenezi organ specifičnih autoimunih bolesti, dok se zaštitna uloga pripisuje T pomoćničkim limfocitima tipa 2 (Th2) i Th 2 citokinima. U zdravoj trudnoći dominira Th2 nad Th1 imunosti čime se objašnjava poboljšanje autoimunih bolesti tijekom trudnoće, dok poslije poroda zbog promjene Th1/Th2 omjera često dolazi do pogoršanja AITD. Ukoliko je AITD induciran Th1 mehanizmima, pomak Th2 u Th1 odgovor mogao bi objasniti pogoršanje AITD postpartalno. Međutim, točan patofiziološki mehanizam ovog fenomena nije poznat. NKT i T regulacijske stanice predstavljaju stanične subpopulacije s velikom ulogom u prevenciji autoimunosti i toleranciji alogenih transplantata. Promjene imunoloških parametara tijekom AITD nisu dovoljno razjašnjene, osobito one tijekom trudnoće. Naš cilj je bio ispitati utjecaj imunološkog sustava tijekom trudnoće i nakon poroda na razvoj AITD, tj. utjecaj Th, NK, NKT i T regulacijskih limfocitnih subpopulacija (Tregs) te korelirati rezultate s nalazima hormona i usporediti ih sa onima u zdravih trudnica. Ispitanici i metode: Ispitali smo prisustvo AITD u ispitanica u trudnoći i postpartalno uz pomoć određivanja hormonskog statusa, titra tireoidnih autoprotutijela i ultrazvučnog pregleda štitnjače (UZV) i rezultate usporedili s kontrolama. Nakon unutarstaničnog i površinskog bojanja uz pomoć protočne citometrije analizirali smo fenotip i citolitički VI potencijal izoliranih mononuklearnih stanica periferne krvi ispitanica u trudnoći i u postporođajnom razdoblju te u kontrola. Rezultati: Srednja vrijednost TSH tijekom normalne trudnoće raste, ali bez značajne razlike u odnosu na kontrolnu skupinu žena, dok postpartalno pada. U trudnoći razina FT4 pada i statistički je značajno niža nego u kontrola, a postpartalno raste i značajno je viša u odnosu na trudnoću. Udio eutireoidnih ispitanica u trudnoći s povišenim titrom tireoidnih autoprotutijela je 16%, dok je postpartalno udio eutireoidnih ispitanica s povišenim titrom autoprotutijela 24%. Srednji TSH je u eutireoidnih trudnica s povišenim protutijelima veći u odnosu na kontrolne trudnice, ali bez statističke značajnosti. Od ukupnog broja ispitanica u trudnoći, 8,6%, je imalo subkl./kl.hipotireozu, a 2,7% subkl./kl. hipertireozu. Od ukupnog broja ispitanica postpartalno, 14% je imalo subkl./kl. hipotireozu, a 2,6% ispitanica subkl./kl hipertireozu. U 6,5% ispitanica dijagnosticirali smo postpartalni tireoiditis. U 25% ispitanica u trudnoći i 41,5 % ispitanica postpartalno smo dokazali prisustvo tireoidne autoimunosti. Stanice urođene imunosti: NKT i Tregs su povišene tijekom zdrave trudnoće, te trudnoće s hipotireozom i hipertireozom, kao i postpartalno u svim ispitivanim skupinama. NKT stanice su snižene u trudnica s pozitivnim protutijelima upućujući na smanjenje protektivne uloge NKT stanica u trudnoći pod djelovanjem protutijela. Ukupni perforin je snižen u zdravih trudnica, ali povišen u trudnica s pozitivnim protutijelima, hipotireozom i hipertireozom, te postpartalno, ukazujući na povećani citolitički potencijal ovih stanica pokrenut autoimunim procesom. Zaključak: Trudnoća i postpartalno razdoblje utječu na tijek AITD, a tireoidna autoimunost utječe na funkciju štitnjače u trudnoći i postpartalno. NKT i Treg stanice imaju važnu ulogu u regulaciji autoimunosti u ispitanica s AITD tijekom trudnoće i postporođThe aim: Autoimmune thyroid disease (AITD) is the organ specific autoimmune disorder. It comprises two major clinical entities: Graves’ disease and Hashimoto's thyroiditis, both characterised by the presence of thyroid specific autoantibodies directed against three major thyroid antigens: TSH receptor, thyroid peroxidase and thyroglobulin. It has been established that the proinflammatory, T helper cell 1 (Th1) type and Th1 cytokines play the major role in the pathogenesis of organ specific autoimmune diseases while the protective role goes to T helper cell 2 (Th2) type and Th2 cytokines. Normal pregnancy is characterised by Th2 domination over Th1 immunity which explains the amelioration of autoimmune disorders. However, after delivery, the Th1/Th2 ratio changes and exacerbation of autoimmune disorders usually occurs. If AITD is induced by Th1 mechanisms, the Th2/Th1 switch could explain the aggravation of AITD after delivery. Still, the exact patophysiological mechanism remains unclear. NKT and regulatory T cells are considered to have a central role in prevention of autoimmunity and maintaining tolerance of allogenic transplants. The alterations of immunological parameters during AITD remain unclear, especially those concerning AITD during pregnancy. Our aim was to investigate the influence of the immunological parameters during pregnancy and in the postpartum on the development of AITD, more precisely the influence of Th, NK, NKT and T regulatory cells, to correlate the results with the hormone levels and to compare them with healthy pregnant and non pregnant women. Patients and Methods: We investigated the presence of AITD in women during pregnancy and after delivery by analysing the thyroid hormone levels, thyroid antibody titres and ultrasound examination. We compared the results with healthy pregnant and postpartum VIII women and non pregnant controls. The phenotype and cytolytic potential of peripheral blood mononuclear cells of non pregnant, pregnant and postpartum women was analysed by flow cytometry after intracellular and surface staining. Results: The mean TSH level gradually increases during pregnancy, although not significantly compared to non pregnant women. It falls in the postpartum and is significantly lower compared to the second half of pregnancy. The mean FT4 level decreases during pregnancy and is significantly lower compared to non pregnant women, while in the postpartum it is significantly higher than during pregnancy. Positive autoantibodieas were found in 16% of euthyroid pregnant and 24% of euthyroid postpartum women. The mean TSH level in euthyroid pregnant women with positive antibodies was slightly, but not significantly, higher compared to control pregnancy. Subclinical or overt hypothyroidism was diagnosed in 8,6 % of pregnant and 14% of postpartum women while 2, 7 % of pregnant and 2,6% of postpartum women were in subclinical or overt hyperthyroidism. Postpartum thyroiditis was diagnosed in 6,5% of women. Thyroid autoimmunity was found in 25% of pregnant and 41,5 % of postpartum women. The cells of innate immunity: NKT and Tregs were elevated in healthy pregnancies and in pregnancies with hypo-and hyperthyroidism, as well as postpartum in all experimental groups. NKT cells were reduced in pregnant women with positive antibodies indicating a decrease in NKT cell protective effect of pregnancy under the action of antibodies. Total perforin was decreased in healthy pregnancy, but higher in patients with positive antibodies, hypo-and hyperthyroidism and postpartum indicating the increased cytolytic potential of these cells in autoimmune process. Conclusion: The pregnancy and postpartum influence the course of AITD, while thyroid autoimmunity also has an impact on the thyroid function during gestation and in the early postpartum. Both, NKT and T reg cells play an important role in regulation of autoimmunity in pregnant and postpartum women with AITD

Thyroid Nodule – Diagnostic and Therapeutic Challenge

Karcinom štitnjače koji se obično prezentira kao čvor u štitnjači čini tek 1 % svih malignoma, no s druge strane čvorove u štitnjači nalazimo u više od polovice svjetske populacije. Navedena statistika svakako nije zanemariva te se nameće potreba za postojanjem stanadardiziranog usmjerenog dijagnostičkog i terapijskog pristupa kojim bi se riješio problem prekomjernog dijagnosticiranja, a da se pri tome ne propusti prepoznati pacijente kojima je medicinska intervencija uistinu potrebna. Nakon otkrivanja čvora u štitnjači dijagnostički se proces sastoji od pretraga koje služe za procjenu funkcionalnog statusa (hormonalni status, scintigrafija), pretraga koje prikazuju izgled i građu štitnjače i čvora ili čvorova (ultrazvuk) te pretraga koje opisuju staničnu građu čvora i promjena nađenih u štitnjači (citološka analiza). Procjena i liječenje ovih pacijenata više se ne temelje na univerzalnom, već na personaliziranom pristupu koji zagovara pažljivu i racionalnu procjenu svake lezije unutar zadanog kliničkog konteksta kako bi se što preciznije utvrdila vjerojatnost zloćudne etiologije i reducirala primjena nepotrebnih dijagnostičkih i terapijskih postupaka. Udio malignih čvorova je malen, svega 5 %, što znači da tek maleni broj čvorova u štitnjači uistinu zahtijeva intenzivnu obradu i kirurško liječenje, dok se, u pravilu, u većine pacijenata s benignim čvorovima nakon odgovarajuće početne evalvacije postupa konzervativno te se učestalost naknadnih kontrola može svesti na minimum.Thyroid cancer, which usually presents as a thyroid nodule, accounts for only 1% of all malignancies, but on the other hand, thyroid nodules are found in more than half of the world’s population. The aforementioned statistics certainly cannot be ignored and therefore a standardized, focused diagnostic and therapeutic approach, which will solve the problem of overdiagnosis without failing to recognize patients who really need medical intervention, is necessary. Upon detection of a nodule in the thyroid gland, the diagnostic process consists of tests that estimate the functional status (hormonal status, scintigraphy), test which reveals the appearance and structure of the thyroid gland and the nodule or nodules (ultrasound), and tests that describe the cellular structure of the nodule and the changes found in the thyroid gland (cytological analysis). The assessment and treatment of these patients is no longer based on a universal, but rather on a personalized approach that advocates a careful and rational evaluation of each lesion within the given clinical context in order to determine as precisely as possible the probability of malignant etiology and to reduce the application of unnecessary diagnostic and therapeutic procedures. The proportion of malignant nodules is small, only 5%, which means that only a small number of nodules in the thyroid gland truly requires intensive evaluation and surgical treatment, while most of the patients have benign nodules which can be treated conservatively after an appropriate initial assassment with frequency of subsequent controls reduced to minimum

The significance of serum thyroglobulin measurement before and after the treatment of toxic nodular goiter with 131I

Thyroglobulin is routinely used as tumor marker in follow upa of patients with toxic nodular goiter. The aim of this studya was to evaluate the role of thyroglobulin measurement prior to and after radioiodine therapy and to compare the results with the therapy outcome

Nuclear medicine diagnostics of cardiac amyloidosis

Amiloidoza srca nastaje uslijed nakupljanja nepravilno savijenih ili polimeriziranih bjelančevina, najčešće transtiretina ili lakih lanaca imunoglobulina u intersticiju miokarda. Bolest se još uvijek teško otkriva jer se na nju kao mogući uzrok zatajivanja srca rijetko pomišlja. Dijagnoza se postavlja na temelju kliničke slike, anamnestičkih podataka, nalaza srčanih biomarkera, promjena u elektrokardiogramu, ehokardiografskom nalazu i/ili magnetskoj rezonanciji, koji zajedno mogu upućivati na dijagnozu. Donedavno je biopsija miokarda bila jedina pouzdana dijagnostička metoda za dokaz ove bolesti. Nuklearna medicina nudi mogućnost neinvazivnog postavljanja dijagnoze, no samo u pacijenata koji zadovoljavaju određene kliničke kriterije. Koriste se radiofarmaci obilježeni gama i pozitronskim emiterima namijenjeni prikazu skeleta ili direktnoj vizualizaciji amiloidnih plakova koji se nakupljaju u miokardu zahvaćenom amiloidozom. Dijagnostička vrijednost scintigrafije ovisi o korištenju te metode u ispravnom kliničkom kontekstu te o poznavanju i postupanju prema dijagnostičkom algoritmu. Posljednjih se godina transtiretinska amiloidoza sve više prepoznaje kao uzrok zatajivanja srca, a razvijaju se i nove terapijske mogućnosti. Stoga je interes za dijagnostiku, posebno nuklearno-medicinske metode povećan, a provode se i brojna istraživanja, naročito u području PET/CT dijagnostike.Cardiac amyloidosis develops due to the accumulation of misfolded or polymerized proteins, most commonly transthyretin or light chains of immunoglobulins in the myocardial extracellular tissue. The disease is still hard to detect because it is rarely suspected as a possible cause of heart failure. The diagnosis is made on the basis of clinical symptoms, patient history, cardiac biomarkers, changes in the electrocardiogram, echocardiographic findings and/or magnetic resonance imaging, which together may indicate the diagnosis. Until recently endomyocardial biopsy was the only reliable diagnostic method to correctly diagnose this disease, but it is an invasive procedure. Nuclear medicine offers the possibility of non-invasive diagnosis, but only in patients fulfilling typical clinical criteria. Gamma- and positron emitting radiopharmaceuticals used for skeletal imaging and direct visualization of amyloid plaques accumulate in the myocardium affected by amyloidosis. The diagnostic value of scintigraphy depends on the use of this method in the correct clinical setting and according to the diagnostic algorithm. In recent years, transthyretin amyloidosis has become increasingly recognized as the cause of heart failure and new therapeutic options are being developed. Therefore, the interest in diagnostics, especially scintigraphy, has increased and numerous research studies are being conducted, especially in the field of PET/CT diagnostics