1,720,976 research outputs found
COVID-induced thyroid autoimmunity
No full textBreakdown of self-tolerance to thyroid antigens (thyroperoxidase, thyroglobulin and the thyrotropin-receptor) is the driver of thyroid autoimmunity. It has been suggested that infectious disease might trigger autoimmune thyroid disease (AITD). Involvement of the thyroid has been reported during severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection, in the form of subacute thyroiditis in subjects with mild coronavirus disease 19 disease (COVID-19) and of painless, destructive thyroiditis in hospitalized patients with severe infection. In addition, cases of AITD, both Graves' disease (GD) and Hashimoto's thyroiditis (HT), have been reported in association with (SARS-CoV-2) infection. In this review, we focus on the relationship between SARS-CoV-2 infection and occurrence of AITD. Nine cases of GD strictly related to SARS-CoV-2 infection and only three cases of HT associated to COVID-19 infection have been reported. No study has demonstrated a role of AITD as a risk factor for a poor prognosis of COVID-19 infection
Calcifediol Rather Than Cholecalciferol for a Patient Submitted to Malabsortive Bariatric Surgery: A Case Report
Full text linkVitamin D deficiency following malabsorptive bariatric surgery can lead to osteomalacia. We report a patient with severe vitamin D deficiency following malabsorptive bariatric surgery successfully treated with calcifediol but not cholecalciferol. A 40-year-old woman, submitted to biliopancreatic diversion 20 years before and chronically treated with 50,000 IU cholecalciferol weekly, was admitted to our Endocrine Unit because of severe lower back pain, muscle weakness, and generalized muscular hypotrophy, associated with hypocalcemia and elevated PTH levels. Initial evaluation revealed low serum albumin, low albumin-corrected serum calcium (7.36 mg/dL), high serum PTH (240 pg/mL), bone-specific alkaline phosphatase (125 μg/L) and 1,25-dihydroxyvitamin D (112 pg/mL) concentrations, undetectable serum 25-hydroxyvitamin D (<7 ng/mL), and evidence of reduced liver function. Bone mineral density was markedly low. Normocalcemia was initially restored with intravenous albumin and calcium gluconate. Treatment with calcitriol (0.5 μg three times daily) and oral calcium carbonate (1000 mg daily) was simultaneously started and cholecalciferol was replaced with calcifediol [125 μg (5000 IU) daily)]. During follow-up the calcifediol dose was progressively tapered to 25 μg (1000 IU) daily and the calcitriol dose was progressively reduced and finally withdrawn. Serum albumin and other biochemical parameters normalized, bone mineral density significantly increased, and the patient's clinical conditions progressively improved, with a substantial recovery of autonomy. Serum vitamin D binding protein at the last observation was in the normal range. Our data suggest that calcifediol might be more efficacious than cholecalciferol for prevention and treatment of vitamin D deficiency in patients treated by malabsorptive bariatric surgery
The detection of serum IgM to thyroglobulin in subacute thyroiditis suggests a protective role of IgM in thyroid autoimmunity
No full textContext
The role of serum IgM in autoimmune thyroid diseases is uncertain.
Objective
We sought for IgM to thyroglobulin (Tg) in patients with subacute thyroiditis (SAT), which is characterized by high serum Tg levels, the possible de-novo appearance of IgG to Tg (TgAb-IgG) and no autoimmune sequelae.
Main Outcome Measures
TgAb-IgM and TgAb-IgG were detected by binding to Tg in ELISA. The upper reference limit of TgAb-IgM and TgAb-IgG was established in 40 normal subjects. TgAb-IgM were searched for in 16 SAT, 11 Hashimoto’s Thyroiditis (HT) and 8 Graves’ Disease (GD), all positive for TgAb-IgG. IgM binding to bovine serum albumin (BSA), keyhole limpet hemocyanin (KLH) and glucagon in ELISA was measured. Inhibition of TgAb-IgM binding to coated Tg was evaluated by pre-incubating serum samples or IgG-depleted samples with soluble Tg
Results
TgAb-IgM were positive in 10/16 SAT, 2/11 HT and 1/8 GD patients. TgAb-IgM were higher in SAT (0.95; 0.42-1.13) (median; 25th-75th percentiles) compared to HT (0.47; 0.45-0.51) and GD patients (0.35; 0.33-0.40) (p<0.005 for both). IgM binding of SAT sera to BSA, KLH and glucagon was significantly lower compared to Tg. Pre-incubation with soluble Tg reduced the binding of IgM to coated Tg by 18.2% for serum samples and by 35.0% and 42.1% for two IgG-depleted samples. TgAb-IgM levels were inversely, although non-significantly, correlated with Tg concentrations.
Conclusions
Tg leak associated with thyroid injury induces the production of specific TgAb-IgM, which in turn, increasing the clearance of Tg, might prevent the establishment of a persistent thyroid autoimmune response
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Evaluation of predictive factors for the development of endocrine immune related adverse events during therapy with immune check point inhibitors and detection of their targets in endocrine glands
No full textContext and aims: Immune check point inhibitors (ICIs) are a promising novel anti-tumoral treatment for cancer that have been shown to increase the overall survival of patients with different tumors. The hyperactivation of immune system against the cancer induced by ICIs may also favor the onset of inflammatory reaction known as immune related adverse events (irAEs). Endocrinological irAEs are common, especially thyroid dysfunction, involving more than 50% of subjects treated with ICIs. To date, many questions remain unanswered on the incidence, prevalence, and pathogenesis of irAEs as well as the physiologic role of PD-L1 and CTLA-4 (the target of ICIs) in endocrine tissues. Moreover, although most endocrine irAEs are mild and self-limited, some reactions can be severe and potentially life-threatening and evidence on the best management of these conditions is lacking. The main aims of the study were 1) To identify the risk factors associated with the onset of endocrine irAEs; 2) To better characterize thyroid dysfunction induced by ICIs to favor management and treatment; 3) To evaluate the expression of PD-L1 in normal thyroid tissue and in Grave’s disease (GD). Methods: For the first aim, we prospectively followed a cohort of 118 patients before starting immunotherapy and during ICIs treatment. At screening visit and during follow-up we recorded clinical data and performed measurement of thyroid hormone, thyroid antibodies, cortisol, ACTH. Neck ultrasound was performed before starting immunotherapy and one year later. For the second aim, we conducted two different retrospective study. In the first study (part 1), we studied 20 consecutive patients who had normal thyroid function before starting immunotherapy and then experienced thyrotoxicosis upon PD1 or PD-L1 blockade. Clinical assessment was combined with thyroid ultrasound, 99mTechnecium scintiscan and longitudinal thyroid function tests. In the second study (part 2), we compared the course of thyrotoxicosis of 4 patients treated with oral prednisone at the dosage of 25 mg/day (tapered to discontinuation in three weeks) and an enlarged thyroid volume to that of 8 patients with similar thyroid volume who were left untreated. For the third aim, we analyzed the immunohistochemistry (IHC) expression of PD-L1 in 25 normal thyroid tissues and in 25 samples from Graves’ disease (GD) patients. IHC was correlated with clinical and biochemical data at the diagnosis of GD. Results: Prospective study: 87 patients of 118 (73%) experienced at least one endocrine irAEs being thyrotoxicosis the most prevalent. Patients with positive TgAbs and TPOAbs before starting immunotherapy were more prone to develop hypothyroidism during ICIs treatment. Moreover, patients treated with an association therapy (Nivolumab plus Ipilimumab) and patients treated with Avelumab showed a higher rate of endocrine iRAes. Thyroid volume significantly decreased in patients with positive TgAbs and TPOAbs at baseline who experienced hypothyroidism during follow-up. Retrospective study (part 1): Five patients had normal scintigraphic uptake (Sci+), no serum TRAbs and remained hyperthyroid throughout follow-up. The other 15 patients had no scintigraphic uptake (Sci-) and experienced destructive thyrotoxicosis followed by hypothyroidism (N= 9) or euthyroidism (N= 6). Hypothyroidism was more readily seen in those with normal thyroid volume than in those with goiter (P= 0.04). Among Sci- subjects, a larger thyroid volume was associated to a longer time to remission (P<0.05). Methimazole (MMI) was effective only in Sci+ subjects (P<0.05). Retrospective study (part 2): The levels of thyroid hormones were lower in subjects treated with steroids compared to those who were left untreated. The time to remission of thyrotoxicosis was 24 days in patients treated with steroids and 120 days in untreated patients (P<0.001). At 6 months, the rate of hypothyroidism was similar in both groups (4/4 in steroid group vs 7/8 in untreated group, P=0.74) and no difference was found in tumor progression (P=0.89). IHC study: The expression of PD-L1 was higher in samples from GD subjects compared to controls. The expression of PD-L1 was directly correlated to the levels of lymphocytic infiltration in GD. The levels of TgAbs and TPOAbs at diagnosis of GD was correlated with the expression of PD-L1 at univariate analysis but no at multivariate analysis. Conclusions: 1) patients with positive TgAbs and TPOAbs have an increased risk to develop hypothyroidism during ICIs treatment; 2) patients treated with an association therapy (anti-PD1/PD-L1 and anti-CTLA-4) have an increased risk to develop endocrine irAEs; 3) IgG subclasses have a role in the risk of develop endocrine irAEs, especially destructive thyrotoxicosis; 4) patients treated with anti-PD1 or anti-PD-L1 drugs may undergo two types of thyrotoxicosis which do not differ in severity at their onset. Thyroid scintigraphy and ultrasound are useful, low invasive and low cost-benefit tools in the management of thyrotoxicosis induced by PD1 and PD-L1 blockade; 5) in patients with a poor performance status experiencing a severe destructive thyrotoxicosis induced by PD-1 blockade, a short period of administration of oral prednisone is effective in obtaining a quick reduction of the levels of thyroid hormones and related symptoms; 6) the expression of PD-L1 on thyroid cells is higher in subjects with GD compared to healthy controls and is directly corelated to the levels of lymphocytic infiltration
Nel morbo di Basedow il volume tiroideo stimato con l'ecografia e l'elemento determinante la gravita dell'ipertiroidismo e il tipo di trattamento definitivo
No full textIntroduzione. Il morbo di Basedow rappresenta la causa più comune di ipertiroidismo nel mondo occidentale, con una prevalenza stimata di 20-50 casi ogni 100.000 persone. Sebbene l’ipertiroidismo sia la manifestazione più comune di malattia, sono solitamente presenti anche manifestazione extratiroidee, di cui la più comune è l’oftalmopatia basedowiana. Numerosi fattori di rischio genetici ed ambientali sono stati identificati ma la patogenesi della malattia non è chiara. Sia l’immunità mediata dalle cellule T che quella mediata dalle cellule B contribuiscono alla patogenesi. La perdita della tolleranza nei confronti di antigeni tiroidei determina l’attivazione del sistema immunitario, con produzione di anticorpi diretti contro differenti autoantigeni, di cui i più importanti sono quelli contro il recettore del TSH (TSHR-Ab, TRAb). Questi anticorpi hanno solitamente attività stimolante il recettore del TSH (TSHR stimulatingantibodies, TSAb) mentreiTRAb con attività bloccante il recettore del TSH (TSHR blockingantibodies, TBAb) possono essere presenti nella forma atrofica della tiroidite di Hashimoto. Oltre il 95% dei pazienti affetti da morbo di Basedow hanno TRAbcircolanti che possono essere misurati mediante i “bindingassays”o i “functionalassays”. I bindingassayvalutanola capacità del siero del paziente di inibire il legame tra il TSH marcato (o un anticorpo monoclonale anti-TSHR marcato) e il TSHR (TBI).Ifunctionalassayvalutano invece la capacità del siero di stimolare il TSHR (TSAb) o di bloccare l’azione del TSH (TBAb). E’ stato riportato che oltre il 90% dei soggetti con morbo di Basedow sono positivi anche per gli AbTg e gli AbTPO, sebbene il ruolo di questi anticorpi nella patogenesi e nel decorso clinico della malattia siastato poco studiato. Clinicamente il morbo di Basedow si presenta con i sintomi e i segni caratteristici dell’ipertiroidismo (palpitazioni, intolleranza al caldo, senso di agitazione, cute sudata) anche se la presentazione può essere più sfumata, soprattutto nei soggetti anziani. L’oftalmopatia basedowiana insorge spesso contestualmente all’ipertiroidismo, anche se talora può precederlo o seguirlo anche di molti anni. Il trattamento del morbo di Basedow si basa sulla terapia medica (antitiroidei di sintesi) o sul trattamento definitivo (terapia radiometabolicao tiroidectomia totale). Nessuno dei trattamenti è scevro da complicanze e diversi fattori entrano in gioco nella scelta terapeutica (caratteristiche ecografiche, gravità dell’ipertiroidismo, presenza di oftalmopatia basedowiana, preferenze del paziente, esperienza del centro).
Scopo della tesi. Valutare le caratteristiche biochimiche ed ecografiche di un’ampia casistica di pazienti affetti da morbo di Basedow, come queste caratteristiche si correlino tra di loro e come influenzino il decorso della malattia e le scelte terapeutiche.
Materiali e metodi. Abbiamo identificato retrospettivamente139 pazienti consecutivi con morbo di Basedow e conTRAb positivi al TBI. Di questi 74 erano giunti alla nostra attenzione al momento dell’esordio della malattia e pertanto non avevano mai assunto anti-tiroidei di sintesi. Abbiamo raccolto i dati riguardanti la funzione tiroidea (FT4, FT3 e TSH), il titolo degli anticorpi (AbTg, AbTPO e TRAb), le caratteristiche ecografiche (volume tiroideo, ecogenicità, presenza di noduli), il tipo di terapia definitiva, se eseguita, e la presenza di oftalmopatia basedowiana media o grave e attiva.
Risultati.Il VTS correla con il grado di ipoecogenicità della ghiandola ed entrambisi correlano positivamente con AbTg, AbTPO e TRAb. I pazienti con ghiandola più ipoecogena hanno inoltre valori più elevati di AbTg, AbTPO e TRAb. Il titolo degli AbTPOsi correla positivamente con il titolo dei TRAb edegli AbTg. Gli AbTg non si correlano con i TRAb. Suddividendo i pazienti in tre gruppi in base al tipo di trattamento eseguito (medico, radioiodio o tiroidectomia totale), i pazienti con VTS maggiore, con più elevato titolo di TRAb e con oftalmopatia basedowiana graveerano andati più spesso incontro a tiroidectomia totale. Nessun parametro di laboratoriosi correla con l’oftalmopatia media o grave. I livelli di FT3 ed FT4 all’esordio di malattia (valutato nei 74 pazienti mai trattati) si correlano con il titolo dei TRAb e con il VTS. All’analisi multivariata il VTS è l’unico fattore indipendente che influisce sui livelli di FT3 e di FT4 all’esordio. Il rapporto FT3/FT4 si correla positivamente con il VTS e negativamente con il titolo degli AbTg.
Discussione.La percentuale di pazienti con AbTg e AbTPO entrambi negativi è risultata più elevata di quanto riportato in letteratura. Sulla base delle caratteristiche di laboratorio ed ecograficheè possibile identificare due fenotipi di morbo diBasedow, uno “tiroiditico” caratterizzato da elevati livelli di AbTg, AbTPO, volume tiroideo maggiore e maggiore ipoecogenicità e uno “non tiroiditico” caratterizzato da bassi livelli di anticorpi, volume tiroideo inferiore e minore ipoecogenicità. I livelli di AbTg e AbTPO non influenzano la gravità dell’ipertiroidismo all’esordio di malattia. I livelli di FT3 ed FT4 all’esordio di malattia sono influenzati dai livelli dei TRAb e dal volume tiroideo. Sebbene questi risultati concordino con dati già riportati in letteratura, in nessun lavoro l’ecografia tiroidea era emersa come il fattore determinante la gravità dell’ipertiroidismo e la scelta terapeutica. In contrasto con quanto descritto in alcuni lavori, nessun fattore di laboratorio ed ecografico si associa con il rischio di sviluppare l’oftalmopatia basedowiana media o grave. Infine i nostri dati dimostrano l’elevata sensibilità ed affidabilità del dosaggio dei TRAb con metodica TBI.
Conclusioni.Tra ipazienti con morbo di Basedow e TRAb positivi, la percentuale di soggetti con AbTg e AbTPO negativi è più elevata di quanto riportato in precedenza. I pazienti con AbTg e AbTPO negativi presentanocaratteristiche ecografiche peculiari. L’ecografia tiroidea è l’unico fattore indipendente che determina la gravità dell’ipertiroidismo all’esordio di malattia. I pazienti con volumi tiroidei maggiori vanno più spesso incontro a tiroidectomia totale. Nel nostro centro la presenza di oftalmopatia basedowiana grave è un fattore determinante per la scelta del trattamento definitivo. Infine, il dosaggio dei TRAb con metodica TBI è altamente sensibile e affidabile
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