Background/Objective: Autoimmune thyroid diseases (AITD) affect 2 to 5% of the general population. This study aimed to determine changes in activity of A-Tg and A-TPO antibodies before, during, and after pregnancy in women with previous AITD. Methods: This was a single-center study with a retrospective review of the medical records of 30 female patients aged 25-41 years who came to our endocrinology service in the city of Santo André, state of São Paulo, Brazil, to investigate thyroid diseases. The following data were reviewed: total triiodothyronine (totalT3), total thyroxine (totalT4), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and anti-TSH receptor antibodies (anti-TSH receptor or anti-thyrotropin receptor antibodies (TRAb), anti-thyroid peroxidase (A-TPO), and anti-thyroglobulin (A-Tg)). These data were reviewed for 30 patients before and during the three trimesters of pregnancy and during the three months after pregnancy. Results: During gestation, we observed a progressive decrease in the blood values of A-TPO and A-Tg, which reached their lowest values in the third trimester of pregnancy, but after birth, they returned to values statistically equivalent to those before pregnancy. Analyzing the three trimesters and the post-pregnancy period, A-TPO increased 192% between the first trimester and postpartum (p = 0.009); it increased 627% between the second trimester and postpartum (p < 0.001); and it increased >1000% between the third trimester and postpartum (p < 0.001). There was no significant difference in the A-TPO values between the pre- and post-gestational periods (p = 1.00), between the first and second trimesters (p = 0.080), or between the second and third trimesters (p = 0.247). Conclusions: According to the results presented here, we observed changes in the activities of A-Tg and A-TPO antibodies during and after pregnancy in women with previous AITD. In women who intend to become pregnant, are pregnant, or have given birth within three months, it is essential to monitor A-TPO, A-Tg, and thyroid function as well as serum thyroid hormones and TSH to identify thyroid dysfunction in a timely manner and adjust the treatment strategy to avoid the deleterious effects of hypothyroidism on both mother and baby during and after pregnancy.

BACKGROUND: Recent studies have suggested that serum autotaxin (ATX) may be a promising diagnostic biomarker in differentiating between Graves\' disease (GD) and thyroiditis, as well as serving as a monitoring biomarker for GD. This study will evaluate the use of serum ATX as a diagnostic biomarker in these conditions.
METHODS: In this prospective interventional study, blood samples were collected from the patients who met both inclusion and exclusion criteria, and serum ATX levels were measured by using the MyBioSource human Autotaxin ELISA kit.
RESULTS: A total of 32 patients were enrolled, of which 18.8% were newly diagnosed with GD, 21.9% were thyroiditis, and 59.3% were on treatment for GD. Serum autotaxin antigen was significantly higher in GD patients than in thyroiditis (603.3217 ± 444.24 v/s 214.74 ± 55.91, P = <.005). Serum ATX measurement successfully discriminated GD patients from thyroiditis (AUC = 0.952, 95%CI: 0.00-1.00) with an optimal cutoff value of ≥257.20 ng/L (sensitivity = 100 and specificity = 81.71). Monitoring the efficacy of serum ATX was analyzed and showed a significant difference.
CONCLUSIONS: The serum ATX was higher in subjects with GD as compared to thyroiditis, and ATX levels were found to be decreased during the treatment period. In conclusion, serum ATX can be used as a diagnostic and monitoring biomarker in GD.

A common immune-related adverse event (irAE) with immune checkpoint inhibitors (ICIs) is thyroid dysfunction (TD-irAEs). The clinical presentation can be varied, and its association with prognosis remains unclear. We investigated the characteristics of TD-irAEs and their association with clinical outcomes among cancer patients treated with ICIs in a real-life setting. Response to treatment was assessed using RECIST v1.1. We calculated the probability of recurrence and survival associated with TD-irAEs using multivariable-adjusted regression and Cox proportional hazards models. In this single-center retrospective analysis, we included 238 patients (72% male) with a median age of 69.5 years. Primary tumors were melanoma (23.1%), lung (60.5%), or urothelial cancer (16.4%), treated with atezolizumab (23.1%), pembrolizumab (44.5%), ipilimumab (0.4%), and/or nivolumab (25.6%). Seventy (29%) patients developed TD-irAEs in a median time of 69 days (41-181). The incidence of TD-irAEs with combination therapy was higher than with monotherapy (67% vs 6.3%, P = 0.011). TD-irAE patients showed a higher objective response rate (ORR) than those without TD-irAEs (60% vs 42.3%, P = 0.013) and longer overall survival (OS) 45 vs 16 months, P < 0.006. Patients who developed TD-irAEs had a relative reduction of 77% (OR 0.23, 95% CI 0.11-0.47) in the risk of progression and of 47% in the risk of mortality (HR 0.53, 95% CI 0.36-0.80), independent of age, sex, primary tumor, or ICI regimen. TD-irAEs occur in nearly 30% of our patients receiving ICIs. In our analysis, TD-irAEs appeared to be associated with higher ORR and longer OS and showed a reduction in the risk of progression and mortality.

Bailing capsule (BLC), a drug that is clinically administered to modulate the autoimmune system, exhibits promising therapeutic potential in the treatment of thyroiditis. This study elucidates the chemical profile of BLC and its potential therapeutic mechanism in thyroiditis, leveraging network pharmacology and molecular docking techniques. Utilizing ultra-high-performance liquid chromatography coupled with linear trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS), 58 compounds were identified, the majority of which were nucleosides and amino acids. Utilizing the ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC QqQ MS/MS) strategy, 16 representative active components from six batches of BLCs were simultaneously determined. Network pharmacology analysis further revealed that the active components included 5\'-adenylate, guanosine, adenosine, cordycepin, inosine, 5\'-guanylic acid, and l-lysine. Targets with higher connectivity included AKT1, MAPK3, RAC1, and PIK3CA. The signaling pathways primarily focused on thyroid hormone regulation and the Ras, PI3K/AKT, and MAPK pathways, all of which were intricately linked to inflammatory immunity and hormonal regulation. Molecular docking analysis corroborated the findings from network pharmacology, revealing that adenosine, guanosine, and cordycepin exhibited strong affinity toward AKT1, MAPK3, PIK3CA, and RAC1. Overall, this study successfully elucidated the material basis and preliminary mechanism underlying BLC\'s intervention in thyroiditis, thus laying a solid basis for further exploration of its in-depth mechanisms.

OBJECTIVE: To identify clinical, biological and pathological risk factors for the incidental discovery of papillary thyroid microcarcinomas (PTMCs) in patients undergoing thyroidectomy for presumed benign conditions.
METHODS: Cross sectional, single center study, involving all consecutive patients (N = 3015) who were submitted to thyroid surgery between 2001-2019. All medical files were retrospectively reviewed. A total of 1961 patients in the benign group and 145 patients in PTMC group were analyzed.
RESULTS: No significant differences in age, sex, body mass index, smoking status, thyroid volume or weight and preoperative thyroxine treatment between benign and PTMC groups were observed. Circulating anti- thyroid antibodies, histological thyroiditis and serum thyrotropin (TSH) were significantly associated with PTMC in univariable analysis. Independent risk factors for incidental PTMC by multivariable analysis where possible (OR: 1.51, 95% CI: 0.99-2.28) and certain (OR: 1.74, 95% CI: 1.09-2.78) thyroid autoimmunity (p = 0.002) and higher serum TSH (OR: 1.25, 95% CI: 1.08-1.45, p = 0.03), whereas thyroid lobectomy was associated with a lower risk of PTMC (OR: 0.40, 95% CI: 0.24-0.67, p < 0.001). The most frequent genetic alteration was BRAFV600E mutation, found in 56.3% of PTMC submitted to DNA sequencing. No association between clinical, biological or histological characteristics of PTMC and BRAFV600E mutation was observed.
CONCLUSIONS: Thyroid autoimmunity and higher preoperative serum TSH level were independent predictors of PTMC incidentally discovered during thyroid surgery. Larger prospective studies are needed to better identify possible risk factors for papillary thyroid carcinoma initiation and progression.

Targeted and immune-based treatments represent significant innovations in oncology and impressively improve the prognosis of many tumor diseases. Their now widespread use as a standard treatment for several malignant diseases increasingly requires knowledge of how to deal with new adverse events (AE) induced by oncological agents in centers and routine practice [12, 13]. For example, the blockade of specific checkpoints of the inhibitory immune system by immune checkpoint inhibitors (ICI) causes the loss of immune tolerance to the body\'s own tissue with the occurrence of endocrine immune-related AE (irAE) in approximately 10% of patients treated with ICI [3, 11]. Targeted treatments, such as with tyrosine kinase inhibitors (TKI), mammalian target of rapamycin (mTOR) and phosphoinositide 3‑kinase (PI3K) inhibitors often lead to disorders of glucose metabolism and thyroid gland dysfunction. The challenges of maintaining bone health during endocrine therapy in patients with prostate and hormone receptor-positive breast cancer and in the endocrine follow-up care of childhood cancer survivors are well-known and are becoming increasingly more important for the long-term prognosis and quality of life [5, 20]. However, although the recommendations for a systematic management of endocrine side effects of these relatively new tumor therapies can be found in guidelines, they are not yet established in routine clinical care [15, 19]. A close interdisciplinary cooperation is required for optimal care of people with cancer [7]. The development of such interdisciplinary cross-sectoral treatment structures is important as tumor treatment is primarily carried out by hematologists or oncologists, while the management of AE induced by oncological agents increasingly involves primary care physicians including internists and in the case of endocrine AE requires the specific expertise of endocrinologists and diabetologists.
UNASSIGNED: Zielgerichtete und immunbasierte Therapien stellen wesentliche Innovationen in der Onkologie dar und verbessern eindrücklich die Prognose vieler Tumorerkrankungen. Ihr inzwischen weit verbreiteter Einsatz erfordert zunehmend Kenntnisse im Umgang auch außerhalb von Zentren und im Praxisalltag [12, 13]. So bedingt die Blockade spezifischer Kontrollpunkte des inhibierenden Immunsystems durch Immuncheckpointinhibitoren (ICI) den Verlust der Immuntoleranz gegenüber körpereigenem Gewebe mit Auftreten endokriner immunvermittelter unerwünschter Ereignisse („immune-related adverse events“ [irAE]) bei etwa 10 % der mit ICI behandelten Patienten. Unter zielgerichteten Therapien beispielsweise mit Tyrosinkinaseinhibitoren (TKI), Mammalian-target-of-rapamycin(mTOR)- und Phosphoinositid-3-Kinase(PI3K)-Inhibitoren treten häufig Störungen des Glukosestoffwechsels sowie der Schilddrüsenfunktion auf [3, 11]. Die Herausforderungen in Bezug auf den Erhalt der Knochengesundheit unter endokriner Therapie bei Patienten mit Prostatakarzinom oder Hormonrezeptor-positivem Mammakarzinom sowie in der endokrinologischen Nachsorge von Menschen, die eine Krebserkrankung im Kindesalter überstanden haben, sind wohlbekannt und sind zunehmend von Bedeutung für die Langzeitprognose und Lebensqualität [5, 20]. Hingegen ist das Management endokriner unerwünschter Ereignisse („adverse events“ [AE]) der relativ neuen Tumortherapien zwar bereits in Leitlinien und Empfehlungen beschrieben, aber in der klinischen Routineversorgung noch nicht etabliert [15, 19]. Es bedarf einer engen interdisziplinären Zusammenarbeit, um Menschen mit Krebserkrankung optimal zu versorgen [7]. Die Entwicklung interdisziplinärer transsektoraler Versorgungsstrukturen ist insofern bedeutsam, als die Tumortherapie primär durch den Hämato- bzw. Onkologen erfolgt, während das Management von onkologikainduzierten AE inzwischen auch die primärversorgenden Hausärzte und Internisten tangiert und endokrine AE die fachspezifische Expertise der Endokrinologen und Diabetologen erfordern.

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BACKGROUND: Anti-programmed cell death-1 (ligand-1) antibody [PD-(L)1-Ab] can cause destructive thyroiditis and/or hypothyroidism. In addition, tyrosine kinase inhibitors (TKIs) frequently induce hypothyroidism. The aim of this prospective study is to examine the incidence and clinical characteristics of thyroid dysfunction induced by combination therapy of a PD-(L)1-Ab and TKI [PD-(L)1-Ab/TKI].
METHODS: A total of 757 patients treated with PD-(L)1-Ab or PD-(L)1-Ab/TKI were evaluated for anti-thyroid antibodies (ATAs) at baseline and for thyroid function for 48 weeks after treatment initiation and then observed until the last visit.
RESULTS: The cumulative incidences of destructive thyroiditis [4/23 (17.4%) vs. 45/734 (6.1%) patients, p < 0.001], isolated hypothyroidism [10/23 (43.5%) vs. 29/734 (4.0%) patients, p < 0.001], and all thyroid dysfunction [14/23 (60.9%) vs. 74/734 (10.1%) patients, p < 0.001] were significantly higher in the PD-(L)1-Ab/TKI group than PD-(L)1-Ab group, respectively. All patients positive for ATAs at baseline developed thyroid dysfunction after PD-(L)1-Ab/TKI treatment, a significantly higher incidence than that in those negative for ATAs at baseline [4/4 (100%) vs. 10/19 (52.6%) patients, p = 0.026].
CONCLUSIONS: The addition of TKIs increased the risk of thyroid dysfunction induced by PD-(L)1-Ab, with the risk being higher in patients positive for baseline ATAs.

BACKGROUND: Artificial intelligence (AI) chatbots have become a major source of general and medical information, though their accuracy and completeness are still being assessed. Their utility to answer questions surrounding immune-related adverse events (irAEs), common and potentially dangerous toxicities from cancer immunotherapy, are not well defined.
METHODS: We developed 50 distinct questions with answers in available guidelines surrounding 10 irAE categories and queried two AI chatbots (ChatGPT and Bard), along with an additional 20 patient-specific scenarios. Experts in irAE management scored answers for accuracy and completion using a Likert scale ranging from 1 (least accurate/complete) to 4 (most accurate/complete). Answers across categories and across engines were compared.
RESULTS: Overall, both engines scored highly for accuracy (mean scores for ChatGPT and Bard were 3.87 vs 3.5, p<0.01) and completeness (3.83 vs 3.46, p<0.01). Scores of 1-2 (completely or mostly inaccurate or incomplete) were particularly rare for ChatGPT (6/800 answer-ratings, 0.75%). Of the 50 questions, all eight physician raters gave ChatGPT a rating of 4 (fully accurate or complete) for 22 questions (for accuracy) and 16 questions (for completeness). In the 20 patient scenarios, the average accuracy score was 3.725 (median 4) and the average completeness was 3.61 (median 4).
CONCLUSIONS: AI chatbots provided largely accurate and complete information regarding irAEs, and wildly inaccurate information (\"hallucinations\") was uncommon. However, until accuracy and completeness increases further, appropriate guidelines remain the gold standard to follow.

Hashimoto encephalopathy presents with a myriad of neuropsychiatric features in the background of elevated antithyroid antibodies and it may or may not be associated with Hashimoto thyroiditis. It is a diagnosis of exclusion. Here, we present the case of a hypothyroid woman in her 30s, with a 5-year history of chronic progressive gait ataxia along with hand and head tremor, inattention and electroencephalogram (EEG) suggestive of interictal epileptiform discharges without any clinical seizures. The patient had very high titres of anti-thyroid peroxidase antibodies >2000 IU/mL and was on very high-dose levothyroxine replacement therapy. She responded to intravenous pulse corticosteroids. Improvement was noted both clinically and on subsequent EEGs. Pure cerebellar syndrome without frank encephalopathy can also be a rare presentation of Hashimoto encephalopathy. This highlights the importance of antithyroid antibodies testing even in cases of pure cerebellar syndrome to rule out Hashimoto encephalopathy associated ataxia.