Unexpected conversion from hypothyroidism to an euthyroid state due to Graves’ disease in a patient with an ectopic thyroid

A 15-year-old woman was diagnosed with hypothyroidism and unilateral ectopic thyroid. Levothyroxine treatment was introduced; however, the patient was non-compliant and took the medication irregularly. When she presented to an endocrinologist at the age of 30, she had not been using levothyroxine for at least 6 months. Surprisingly, she was clinically and biochemically euthyroid. Due to decreased echogenicity on ultrasound examination, enhanced vascularization on Color Doppler examination and increased concentration of anti-TSH receptor autoantibodies, she was diagnosed with Graves’ disease. Eventually, she underwent total thyroidectomy due to diagnosis of follicular neoplasm in fine-needle aspiration biopsy of the focal lesion found in the thyroid gland. To our knowledge, our patient is the first described with ectopic thyroid, presenting a nodular variant of Graves’ disease and no signs of orbitopathy, who was initially hypothyroid and became euthyroid in the course of autoimmune thyroid disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12020-013-0117-6) contains supplementary material, which is available to authorized users

Rola radioterapii oczodołów w leczeniu orbitopatii tarczycowej — aktualny stan wiedzy

The treatment of Graves’ orbitopathy (GO) remains a diagnostic and therapeutic challenge for clinicians worldwide. The elimination of risk factors, such as encouraging smoking cessation and achieving euthyroidism, are the most important and usually sufficient treatment methods in most mild cases. A course of selenium may also be beneficial. High-dose systemic corticosteroid therapy remains the first-line therapy in moderate-to-severe orbitopathy; however in some patients such treatment may be insufficient. Radiotherapy for GO has been used for decades and is considered to be effective in active GO, although less than systemic corticosteroids. Unfortunately, there are only eight randomised studies that may be analysed to assess its true effectiveness and applicability. It has been indicated that radiotherapy affects mainly eye motility and soft tissue changes, with almost no influence on exophthalmos. The combination of these two therapies has proven to be even more effective than either treatment alone, especially in subjects with resistant or recurrent GO. Orbital radiotherapy seems to be a safe procedure with few adverse effects observed long after the therapy. It should be avoided in patients with retinopathy, due to diabetes mellitus and hypertension, and in young subjects (< 35 years old). Orbital radiotherapy, as a safe and generally effective second-line therapy, is used in some countries as a supporting method during the second course of systemic corticosteroid therapy, if the response to the first course is unsatisfactory. Further randomised, double-blind studies are needed to confirm fully its clinical usefulness. (Endokrynol Pol 2014; 65 (5): 388–396)Leczenie orbitopatii tarczycowej w przebiegu choroby Gravesa-Basedowa (GO, Graves’ orbitopathy) nadal pozostaje dla klinicystów z całegoświata dużym wyzwaniem terapeutycznym. Modyfikacja czynników ryzyka poprzez zaprzestanie palenia papierosów, wyrównaniehormonalne czy środki działające miejscowo uważane są za najważniejsze, a zarazem najskuteczniejsze metody leczenia w przypadkułagodnej GO. Korzyści może przynieść również stosowanie preparatów selenu. Leczenie dożylne preparatami glikokortykosteroidówpozostaje terapią pierwszego rzutu w przypadku umiarkowanej oraz ciężkiej GO, chociaż u niektórych pacjentów takie leczenie jest niewystarczające.Radioterapia jest stosowana w leczeniu GO od wielu dziesięcioleci i jest uznawana za skuteczną w przypadku aktywnejpostaci choroby, jednak dającą gorsze wyniki niż systemowa terapia glikokortykosteroidami. Aktualnie dostępnych jest jedynie 8 randomizowanychprac, które dostarczają rzetelnych informacji do analizy skuteczności i radioterapii w GO. Wykazano, że efektem radioterapiijest głównie zwiększenie ruchomości gałek ocznych oraz pozytywny wpływ na zmiany patologiczne tkanek miękkich oczodołu, bez istotnegowpływu na stopień wytrzeszczu. Połączenie obu metod leczenia okazało się być bardziej efektywne niż każda z terapii zastosowanaosobno, szczególnie w przypadku opornej bądź nawracającej GO. Radioterapia oczodołów wydaje się metodą bezpieczną, obarczonąniewielkim ryzykiem działań niepożądanych, pojawiających się długo po zakończeniu leczenia. Jednak powinno się unikać tej metodyu pacjentów z retinopatią w przebiegu cukrzycy bądź nadciśnienia tętniczego oraz u osób młodych (< 35 rż.). Radioterapia oczodołów,jako bezpieczna i efektywna metoda leczenia drugiego rzutu, jest wykorzystywana w niektórych krajach jako leczenie wspomagającedrugi kurs steroidoterapii systemowej, jeżeli poprawa po pierwszym kursie nie była zadowalająca. Jednak dalsze, randomizowane badaniaz podwójnie ślepą próbą są nieodzowne, aby potwierdzić skuteczność tej terapii. (Endokrynol Pol 2014; 65 (5): 388–396

Rozpiętość rozkładu objętości erytrocytów — nowy marker zaostrzenia niewydolności krążenia u pacjentów z niedoczynnością tarczycy po leczeniu jodem promieniotwórczym

Introduction: Cardiovascular diseases constitute a major cause of health problems and death in developed countries across the world. The increased value of the index of distribution of red blood cells volume (RDW) may be a prognostic marker in patients diagnosed with chronic heart failure (CHF). Hypothyroid patients present higher RDW values if compared to healthy controls. Taking into consideration that RDW might be both affected by thyroid status and CHF, we decided to determine the effect of concomitant hypothyroidism following radioiodine therapy (RIT) and CHF on hematological parameters. Materials and methods: Patients with toxic nodular goiter and heart failure with concomitant anemia were included. Patients underwent treatment with radioiodine before the planned heart transplant or pacemaker implantation (combined ICD/CRT-D). After RIT patients were divided into the three subgroups: with overt hypothyroidism (TSH ≥ 10µIU/mL, Group I), subclinically hypothyroid patients (TSH 4.3-9.0 µIU/mL, Group II) and with high-normal level of TSH (2.6-4.2 µIU/mL, Group III). Results: Significant correlation between TSH and RDW was observed (r=0.46; P < 0.0001) after RIT, whereas no correlation between serum TSH levels and TIBC and Fe was observed. In Group I significant correlation between TSH and RDW (r= 0.48; P = 0.002) after RIT was observed, whereas in two other subgroups there were no significant correlation. Conclusions: Subclinical hypothyroidism or high-normal levels of TSH did not affect RDW in a significant manner in the studied population. Our results demonstrates that overt hypothyroidism may contribute to deterioration of CHF reflected in changes of RDW value. Wstęp: Choroby sercowo-naczyniowe stanowią główną przyczynę problemów zdrowotnych i zgonów w krajach wysoko uprzemysłowionych na całym świecie. Podwyższona wartość rozpiętości rozkładu objętości erytrocytów (RDW) może stanowić marker prognostyczny u pacjentów z przewlekłą niewydolnością serca (PNS). Pacjenci z niedoczynnością tarczycy mają wyższe wartości RDW w porównaniu z osobami zdrowymi. Biorąc pod uwagę, że RDW może być zmienione zarówno przez stan czynnościowy tarczycy, jak i PNS, autorzy niniejszej pracy postanowili ustalić wpływ współistniejącej niedoczynności tarczycy spowodowanej terapią jodem promieniotwórczym (RIT) i PNS na parametry hematologiczne. Materiały i metody: Włączono pacjentów z wolem guzkowym toksycznym, PNS oraz towarzyszącą niedokrwistością. U pacjentów prze­prowadzono RIT przed planowanym przeszczepieniem serca lub implantacją urządzenia resynchronizującego lub defibrylatora (ICD/CRT-D). Po RIT pacjentów podzielono na 3 podgrupy: z jawną niedoczynnością tarczycy (TSH ≥ 10 μIU/mL — grupa I), z subkliniczną niedoczynnością (TSH 4,3–9,0 μIU/mL — grupa II) oraz z TSH w górnej granicy normy (2,6–4,2 μIU/mL — grupa III). Wyniki: Zaobserwowano istotną korelację między TSH i RDW (r = 0,46; P &lt; 0,0001) po RIT, podczas gdy nie zaobserwowano kore­lacji między stężeniem TSH i stężeniem żelaza oraz TIBC. W grupie I zaobserwowano istotną korelację między TSH i RDW (r = 0,48; P = 0,002) po RIT, jakkolwiek w dwóch pozostałych podgrupach nie zaobserwowano istotnej korelacji. Wnioski: Subkliniczna niedoczynność tarczycy, jak i wartości TSH w górnej granicy normy nie wpływały na RDW w sposób istotny w grupie badanej. Wyniki wskazują, że jawna niedoczynność tarczycy może przyczynić się do zaostrzenia PNS odzwierciedlonej zmianą wartości RDW

Chemo-enzymatic synthesis and biological activity evaluation of propenylbenzene derivatives

Propenylbenzenes, including isosafrole, anethole, isoeugenol, and their derivatives, are natural compounds found in essential oils from various plants. Compounds of this group are important and valuable, and are used in the flavour and fragrance industries as well as the pharmaceutical and cosmetic industries. The aim of this study was to develop an efficient process for synthesising oxygenated derivatives of these compounds and evaluate their potential biological activities. In this paper, we propose a two-step chemo-enzymatic method. The first step involves the synthesis of corresponding diols 1b–5b from propenylbenzenes 1a–5avia lipase catalysed epoxidation followed by epoxide hydrolysis. The second step involves the microbial oxidation of a diasteroisomeric mixture of diols 1b–5b to yield the corresponding hydroxy ketones 1c–4c, which in this study was performed on a preparative scale using Dietzia sp. DSM44016, Rhodococcus erythropolis DSM44534, R. erythropolis PCM2150, and Rhodococcus ruber PCM2166. Application of scaled-up processes allowed to obtain hydroxy ketones 1-4c with the following yield range 36–62.5%. The propenylbenzene derivatives thus obtained and the starting compounds were tested for various biological activities, including antimicrobial, antioxidant, haemolytic, and anticancer activities, and their impact on membrane fluidity. Fungistatic activity assay against selected strains of Candida albicans results in MIC50 value varied from 37 to 124 μg/mL for compounds 1a, 3a–c, 4a,b, and 5a,b. The highest antiradical activity was shown by propenylbenzenes 1-5a with a double bond in their structure with EC50 value ranged from 19 to 31 μg/mL. Haemolytic activity assay showed no cytotoxicity of the tested compounds on human RBCs whereas, compounds 2b–4b and 2c–4c affected the fluidity of the RBCs membrane. The tested compounds depending on their concentration showed different antiproliferative activity against HepG2, Caco-2, and MG63. The results indicate the potential utility of these compounds as fungistatics, antioxidants, and proliferation inhibitors of selected cell lines

A systematic review and meta-analysis of effect of vitamin D levels on the incidence of COVID-19

Background: Coronavirus disease 2019 (COVID-19) is a disease primarily affecting the respiratory tract, however due to the nature of the pathogenesis it is able to affect the whole body. So far, no causative treatment has been found and the main strategy when dealing with COVID-19 relies on widespread vaccination programs and symptomatic treatment. Vitamin D due to its ability to modulate the immunological system has been proposed as a factor playing role in the organism response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, we decided to perform this meta-analysis which aimed to establish a connection between vitamin D status and COVID-19 infection.Methods: Study was designed as a systematic review and meta-analysis. PubMed, EMBASE, Web of Science, Cochrane Collaboration Databases and Scopus electronic databases were searched for relevant studies from database inception to May 10th, 2021. Mean differences (MDs) with their 95% confidence intervals (CI) were calculated.Results: Thirteen studies providing data for 14,485 participants met the inclusion criteria. Mean vitamin D levels in SARS-CoV-2 negative patients was 17.7 ± 6.9 ng/mL compared to SARS-CoV-2 positive patients 14.1 ± 8.2 ng/mL (MD = 3.93; 95% CI 2.84–5.02; I2 = 99%; p &lt; 0.001).Conclusions: Low serum vitamin D levels are statistically significantly associated with the risk of COVID-19 infection. Supplementation of vitamin D especially in the deficiency risk groups is indicated

Financial Ombudsman – Analysis of Activities in the field of alternative disputes resolution

Manipulacje i oszustwa na rynku kapitałowym są zjawiskiem częstym, choć niedozwolonym przez prawo. Jest wiele kategorii wśród mechanizmów manipulowania rynkiem kapitałowym, jednak konsumenci mają możliwość obrony przed tego rodzaju przestępstwami. Istnieje również wiele możliwości zapobiegania opisanym przestępstwom, zarówno ze strony konsumenta, jak i organów rządowych. Jednak ilość pojawiających się w tym dziele zarzutów pokazuje zarówno znikomą wiedzę społeczeństwa, jak i brak działań ze strony państwa.Article presents the institution of Financial Ombudsman, who takes actions for benefit of the financial services market’s clients. Author sets out with the aim of presenting complaining procedure and analyzing present activities of Financial Ombudsman and future possible changes in Alternative Dispute Resolution sector

Ektopia tarczycy — wyzwania diagnostyczne i terapeutyczne przed wprowadzeniem przesiewowego badania TSH noworodków i po nim

Despite TSH screening in newborns is currently conducted in most developed countries, patients with thyroid ectopy born before the procedure was introduced or those in whom the screening failed to establish diagnosis, might still appear. In the paper we revise the current state of knowledge regarding the clinical presentation, diagnosis and treatment of patients with thyroid ectopy. As an example, we report diagnostic and therapeutic difficulties in our three patients with thyroid ectopy remaining undiagnosed and untreated during early childhood. Introduction of neonatal screening for congenital hypothyroidism does not guarantee that all patients with thyroid ectopy will be correctly diagnosed and properly treated due to the possibility of falsely negative result of TSH screening or lack of compliance from parents. Visualization of an ectopic thyroid on ultrasound examination may be challenging for unexperienced sonographists; muscles in the thyroid bed may be misdiagnosed as heterogeneous and hypoechogenic thyroid gland with features suggesting autoimmune thyroid disease. Thyroid scintiscan is crucial for confirmation of the diagnosis of thyroid ectopy. In conclusion, hypothyroidism due to thyroid developmental anomaly should be taken into consideration in case of hypothyroidism and normal thyroid autoantibodies in a patient at any age.Mimo wprowadzenia przesiewowego badania TSH u noworodków w większości krajów rozwiniętych, w praktyce klinicznej wciąż możemy spotkać pacjentów z ektopią tarczycy, urodzonych zanim procedura została wdrożona lub u których badanie przesiewowe nie doprowadziło do wykrycia wady. W pracy dokonano przeglądu aktualnego stanu wiedzy w odniesieniu do obrazu klinicznego, diagnostyki i leczenia pacjentów z ektopią tarczycy. Jako przykład autorzy prezentują diagnostyczne i terapeutyczne wyzwania u trzech pacjentek z ektopią tarczycy, którzy nie zostali zdiagnozowani i/lub właściwie leczeni we wczesnym dzieciństwie. Wprowadzenie badań przesiewowych noworodków w kierunku wrodzonej niedoczynności tarczycy nie gwarantuje, że wszyscy pacjenci z ektopią tarczycy będą prawidłowo rozpoznani i adekwatnie leczeni, z uwagi na prawdopodobieństwo fałszywie ujemnego wyniku przesiewowego badania TSH lub brak współpracy rodziców dziecka. Uwidocznienie ektopowo położonej tarczycy w badaniu ultrasonograficznym może być wyzwaniem dla niedoświadczonych sonografistów; mięśnie wpuklające się do loży tarczycy mogą zostać łatwo zinterpretowane jako miąższ tarczycy o niejednorodnej i ob­niżonej echogeniczności, co może sugerować autoimmunizacyjną chorobę tarczycy. Badanie scyntygraficzne tarczycy jest niezbędne do potwierdzenia diagnozy ektopii tarczycy. Podsumowując, niedoczynność tarczycy na podłożu wady rozwojowej należy uwzględniać w diagnostyce różnicowej przyczyn niedoczynności z prawidłowymi wartościami przeciwciał przeciwtarczycowych u pacjenta w każdym wieku.

Covalent defects restrict supramolecular self-assembly of homopolypeptides: case study of β2-fibrils of poly-L-glutamic acid.

Poly-L-glutamic acid (PLGA) often serves as a model in studies on amyloid fibrils and conformational transitions in proteins, and as a precursor for synthetic biomaterials. Aggregation of PLGA chains and formation of amyloid-like fibrils was shown to continue on higher levels of superstructural self-assembly coinciding with the appearance of so-called β2-sheet conformation manifesting in dramatic redshift of infrared amide I' band below 1600 cm(-1). This spectral hallmark has been attributed to network of bifurcated hydrogen bonds coupling C = O and N-D (N-H) groups of the main chains to glutamate side chains. However, other authors reported that, under essentially identical conditions, PLGA forms the conventional in terms of infrared characteristics β1-sheet structure (exciton-split amide I' band with peaks at ca. 1616 and 1683 cm(-1)). Here we attempt to shed light on this discrepancy by studying the effect of increasing concentration of intentionally induced defects in PLGA on the tendency to form β1/β2-type aggregates using infrared spectroscopy. We have employed carbodiimide-mediated covalent modification of Glu side chains with n-butylamine (NBA), as well as electrostatics-driven inclusion of polylysine chains, as two different ways to trigger structural defects in PLGA. Our study depicts a clear correlation between concentration of defects in PLGA and increasing tendency to depart from the β2-structure toward the one less demanding in terms of chemical uniformity of side chains: β1-structure. The varying predisposition to form β1- or β2-type aggregates assessed by infrared absorption was compared with the degree of morphological order observed in electron microscopy images. Our results are discussed in the context of latent covalent defects in homopolypeptides (especially with side chains capable of hydrogen-bonding) that could obscure their actual propensities to adopt different conformations, and limit applications in the field of synthetic biomaterials

The Development of Optomechanical Sensors—Integrating Diffractive Optical Structures for Enhanced Sensitivity

The term optomechanical sensors describes devices based on coupling the optical and mechanical sensing principles. The presence of a target analyte leads to a mechanical change, which, in turn, determines an alteration in the light propagation. Having higher sensitivity in comparison with the individual technologies upon which they are based, the optomechanical devices are used in biosensing, humidity, temperature, and gases detection. This perspective focuses on a particular class, namely on devices based on diffractive optical structures (DOS). Many configurations have been developed, including cantilever- and MEMS-type devices, fiber Bragg grating sensors, and cavity optomechanical sensing devices. These state-of-the-art sensors operate on the principle of a mechanical transducer coupled with a diffractive element resulting in a variation in the intensity or wavelength of the diffracted light in the presence of the target analyte. Therefore, as DOS can further enhance the sensitivity and selectivity, we present the individual mechanical and optical transducing methods and demonstrate how the DOS introduction can lead to an enhanced sensitivity and selectivity. Their (low-) cost manufacturing and their integration in new sensing platforms with great adaptability across many sensing areas are discussed, being foreseen that their implementation on wider application areas will further increase

Covalent Defects Restrict Supramolecular Self-Assembly of Homopolypeptides: Case Study of β₂-Fibrils of Poly-L-Glutamic Acid

<div><p>Poly-L-glutamic acid (PLGA) often serves as a model in studies on amyloid fibrils and conformational transitions in proteins, and as a precursor for synthetic biomaterials. Aggregation of PLGA chains and formation of amyloid-like fibrils was shown to continue on higher levels of superstructural self-assembly coinciding with the appearance of so-called β₂-sheet conformation manifesting in dramatic redshift of infrared amide I′ band below 1600 cm⁻¹. This spectral hallmark has been attributed to network of bifurcated hydrogen bonds coupling C = O and N-D (N-H) groups of the main chains to glutamate side chains. However, other authors reported that, under essentially identical conditions, PLGA forms the conventional in terms of infrared characteristics β₁-sheet structure (exciton-split amide I′ band with peaks at ca. 1616 and 1683 cm⁻¹). Here we attempt to shed light on this discrepancy by studying the effect of increasing concentration of intentionally induced defects in PLGA on the tendency to form β₁/β₂-type aggregates using infrared spectroscopy. We have employed carbodiimide-mediated covalent modification of Glu side chains with n-butylamine (NBA), as well as electrostatics-driven inclusion of polylysine chains, as two different ways to trigger structural defects in PLGA. Our study depicts a clear correlation between concentration of defects in PLGA and increasing tendency to depart from the β₂-structure toward the one less demanding in terms of chemical uniformity of side chains: β₁-structure. The varying predisposition to form β₁- or β₂-type aggregates assessed by infrared absorption was compared with the degree of morphological order observed in electron microscopy images. Our results are discussed in the context of latent covalent defects in homopolypeptides (especially with side chains capable of hydrogen-bonding) that could obscure their actual propensities to adopt different conformations, and limit applications in the field of synthetic biomaterials.</p></div