Zaburzenia czynności tarczy indukowane amiodaronem w regionie bogatym w jod: dane epidemiologiczne i kliniczne

Introduction: The present study aims to evaluate the incidence, types, timing and risk factors in amiodarone (AMD)-induced thyroid dysfunction. Material and methods: The study comprised 229 patients from an iodine-replete area (115 women, 114 men, mean age 63.8 &plusmn; 9.2 years), chronically treated with AMD. The cases were clinically investigated prior to, and during treatment, by thyroid 2D and color Doppler flow sonography, thyroid function tests (TSH, FT3, FT4), and antithyroid antibodies. Results: Of 88 patients (38.4%) who developed thyroid dysfunction, 47 (20.5%) presented AMD-induced thyrotoxicosis (AIT) and 41 (17.9%) AMD-induced hypothyroidism (AIH). There is an evident prevalence of subclinical AIH (29 cases), compared to subclinical AIT (three cases). Regarding clinical forms, these prevailed in AIT (44 patients) (p < 0.001, Fisher&#8217;s exact test). Thyrotoxic patients were classified in pathogenic types as follows: 11 cases as type 1, 15 cases as type 2, and 21 cases as mixed form. The most important risk factor for the development of thyroid dysfunction was represented by the underlying thyroid pathology. The patients with previous thyroid abnormalities (diffuse or nodular goitre and/or positive antithyroid antibodies) developed earlier thyroid dysfunction compared to those with an apparently normal thyroid gland. The thyroid dysfunction occurrence was heterogeneous (4&#8211;84 months). Thyrotoxicosis involved especially young ages, while AIH affected later years.The daily dose, the duration of the treatment and the cumulative dose of AMD do not represent risk factors in thyroid dysfunction development. The determination of serum AMD and desethylamiodarone concentrations does not offer benefits in the diagnosis and treatment of thyroid dysfunction. Conclusions: In the present study, the incidence of AIH was similar to that reported in iodine-replete areas. The incidence of AIT was higher that previously reported, a fact underlining the importance of the proper screening and monitoring of patients. Cases with previous thyroid morphologic and/or immunologic abnormalities require frequent monitoring.Wstęp: Badanie przeprowadzono w celu oceny zapadalności na zaburzenia czynności tarczycy indukowane amiodaronem (AMD). Materiał i metody: Badanie obejmowało 229 chorych zamieszkujących region bogaty w jod (115 kobiet, 114 mężczyzn; średnia wieku 63,8 &plusmn; 9,2 roku), długoterminowo leczonych AMD. Przed i w trakcie terapii u uczestników przeprowadzono ocenę kliniczną, badanie USG 2D i techniką kolorowego doplera, testy czynności tarczycy (TSH, FT3, FT4) oraz oznaczono przeciwciała przeciwtarczycowe. Wyniki: Spośród 88 chorych (38,4%), u których rozwinęły się zaburzenia czynności tarczycy, u 47 (20,5%) stwierdzono indukowaną AMD tyreotoksykozę (AIT), a u 41 (17,9%) &#8212; indukowaną AMD niedoczynność tarczycy (AIH). W badanej grupie odnotowano zdecydowanie więcej przypadków subklinicznej AIH (29 przypadków) niż subklinicznej AIT (3 przypadków). Porównanie częstości jawnych klinicznie postaci zaburzeń czynności tarczycy wykazało przewagę AIT (44 chorych) (p < 0,001, dokładny test Fishera). Osoby z tyreotoksykozą sklasyfikowano w zależności od typu patogenetycznego: 11 przypadków jako typ 1, 15 przypadków jako typ 2 i 21 przypadków jako postać mieszaną. Najważniejszym czynnikiem ryzyka rozwoju badanych zaburzeń były choroby tarczycy. U chorych, u których wcześniej stwierdzono nieprawidłowości w badaniach tarczycy (wole rozlane lub guzkowe i/lub obecność przeciwciał przeciwtarczycowych), zaburzenia czynności gruczołu rozwijały się wcześniej niż u osób, u których wyniki badań były prawidłowe. Zaburzenia czynności tarczycy pojawiały się sie w różnym czasie (w ciągu 4&#8211;84 miesięcy). Tyreotoksykoza występowała głównie u osób młodych, natomiast AIH rozwijała sie w późniejszym wieku. Dawka dobowa, czas trwania terapii i skumulowana dawka AMD nie stanowiły czynników ryzyka rozwoju zaburzeń czynności tarczycy. Określenie stężeń AMD i desetylamiodaronu w surowicy nie było pomocne w rozpoznaniu i leczeniu zaburzeń czynności tarczycy. Wnioski: Zapadalność na AIH w badanej grupie była podobna, jak w innych regionach bogatych w jod. Liczba nowych przypadków AIT była większa niż opisywana wcześniej, co podkreśla znaczenie badań przesiewowych i monitorowania pacjentów. Zwłaszcza osoby z nieprawidłowościami w zakresie budowy tarczycy i zaburzeniami immunologicznymi wymagają częstych badań kontrolnych

Clinical, ultrasonographical and histopathological aspects in Hashimoto’s thyroiditis associated with malignant and benign thyroid nodules

Wstęp: Podawane w literaturze dane na temat rozpowszechnienia przewlekłego autoimmunologicznego zapalenia tarczycy związanegoze zróżnicowanym rakiem tarczycy (DTC, differentiated thyroid cancer) cechuje duża rozpiętość. Celem badania była ocena wybranych cechepidemiologicznych, klinicznych, ultrasonograficznych i histopatologicznych operowanych guzków tarczycy u pacjentów z rozlanymautoimmunologicznym zapaleniem tarczycy.Materiał i metody: Do badania włączono 411 przypadków choroby Hashimoto (HT, Hashimoto thyroiditis), z czego 118 pacjentów zgłosiłosię do lekarza z powodu choroby guzkowej tarczycy (TND, thyroid nodular disease). Tyroidektomię wykonano u 76 pacjentów, przy czymu 24 pacjentów badanie histopatologiczne wykazało DTC, a u pozostałych 52 — zmiany łagodne. Postacie DTC były następujące: rakbrodawkowaty tarczycy (PTC, papillary thyroid cancer) (n = 6), wariant pęcherzykowy PTC (FVPTC, follicular variant of papillary thyroidcancer) (n = 6), mikroraki brodawkowate (n = 8), rak pęcherzykowy tarczycy (n = 1) i postać mieszana (klasyczny PTC i FVPTC) (n = 3).Większość guzków łagodnych stanowiły gruczolaki pęcherzykowe (48%) i wole koloidalne (40,3%).Wyniki: Cechy ultrasonograficzne związane z ryzykiem rozpoznania nowotworu złośliwego w przypadkach HT związanej z TND obejmowały:litą strukturę, hipoechogenność i mikrozwapnienia. Charakter brzegów, kształt guzkowaty i typ unaczynienia nie wydają sięużytecznymi parametrami w identyfikacji guzków złośliwych w HT. Biopsja aspiracyjna cienkoigłowa (BAC) wykazała w przypadkachDTC różne obrazy cytologiczne: złośliwy (10), nieokreślony (8), łagodny (2) i niediagnostyczny (4). W grupie z guzkami łagodnymi nieokreślonyobraz cytologiczny stanowił duży procent wyników (n = 12).Wnioski: Częstość występowania TND związanego z HT wyniosła 28,7%. Wśród 76 operowanych pacjentów DTC stwierdzono w 31,5%przypadków. Dokładność BAC w rozpoznaniu przedoperacyjnym cechowała się większą czułością (90,0%) i swoistością (61,5%) w porównaniuz kryteriami ultrasonograficznymi. Intriduction: The reported prevalence of chronic autoimmune thyroiditis associated with differentiated thyroid cancer (DTC) is heterogeneous.The aim of this study was to evaluate some epidemiological, clinical, sonographical and histological features of operated thyroidnodules with background diffuse autoimmune thyroiditis.Material and methods: The study included 411 cases with Hashimoto’s thyroiditis (HT), of which 118 presented thyroid nodular disease(TND). Thyroidectomy was performed in 76 cases. Of these patients, 24 presented histologically confirmed DTC and 52 benign lesions.DTC types were as follows: papillary thyroid cancer (PTC) (n = 6), follicular variant of PTC (FVPTC) (n = 6), papillary microcarcinomas(n = 8), follicular thyroid carcinoma (n = 1) and the mixed form (classic PTC and FVPTC) (n = 3). The benign nodules were dominatedby: follicular adenoma (48%), and colloid goitre (40.3%).Results: The sonographic features with predictive risk for malignancy in cases with HT associated with TND were represented by: solidcomposition, hypoechogenicity and microcalcifications. The characters of margins, the nodular shape and the type of vascularity do notseem to be as useful for identification of malignant nodules in HT. Fine needle-aspiration biopsy (FNAB) showed in DTC cases differentcytological smears: malignant (ten), indeterminate (eight), benign (two), and non-diagnostic (four). In the group of benign nodules, theindeterminate smears represented also a significant percentage (n = 12).Conclusions: The incidence of TND associated with HT was 28.7%. Among 76 operated cases, 31.5% presented DTC. The accuracyof FNAB in the preoperative diagnosis showed higher sensitivity (90.0%) and specificity (61.5%) compared to sonographic criteria

ARFI elastography for the evaluation of diffuse thyroid gland pathology: Preliminary results

AIM: To assess whether acoustic radiation force impulse (ARFI) elastography can differentiate normal from pathological thyroid parenchyma

Age-related neoplastic risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germ line RET Cys634Trp (TGC > TGG) mutation

RET testing in multiple endocrine neoplasia type 2 for molecular diagnosis is the paradigm for the practice of clinical cancer genetics. However, precise data for distinct mutation-based risk profiles are not available. Here, we survey the clinical profile for one specific genotype as a model, TGC to TGG in codon 634 (C634W). By international efforts, we ascertained all available carriers of the RET C634W mutation. Age at diagnosis, penetrance, and clinical complications were analyzed for medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism (HPT), as well as overall survival. Our series comprises 92 carriers from 20 unrelated families worldwide. Sixty-eight subjects had MTC diagnosed at age 3-72 years (mean 29). Lymph node metastases were observed in 16 subjects aged 20-72 and distant metastases in 4 subjects aged 28-69. Forty-one subjects had pheochromocytoma detected at age 18-67 (mean 36). Amongst the 28 subjects with MTC and pheochromocytoma, six developed pheochromocytoma before MTC. Six subjects had HPT diagnosed at age 26-52 (mean 39). Eighteen subjects died; of the 16 with known causes of death, 8 died of pheochromocytoma and 4 of MTC. Penetrance for MTC is 52% by age 130 and 83% by age 50, for pheochromocytoma penetrance is 20% by age 30 and 67% by age 50, and for HPT penetrance is 3% by age 30 and 21% by age 50. These data provide, for the first time, RET C634W-specific neoplastic risk and age-related penetrance profiles. The data may facilitate risk assessment and genetic counseling

Odanacatib for the treatment of postmenopausal osteoporosis : Results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT Extension study

Background Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42–0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40–0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66–0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95–1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90–1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% [136/8043] vs 1·3% [104/8028], HR 1·32, 1·02–1·70; p=0·034), but not myocardial infarction (0·7% [60/8043] vs 0·9% [74/8028], HR 0·82, 0·58–1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% [401/8043] vs 4·4% [356/8028], 0·98–1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 [5·0%] of 8043 vs 343 [4·3%] of 8028, HR 1·17, 1·02–1·36; p=0·029, as did stroke (2·3% [187/8043] vs 1·7% [137/8028], HR 1·37, 1·10–1·71; p=0·0051). Interpretation Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis