Robotic transaxillary thyroidectomy: time to expand indications?

In 2016, the American Thyroid Association published a statement on remote-access thyroid surgery claiming that it should be reserved to patients with thyroid nodule ≤ 3 cm, thyroid lobe < 6 cm and without thyroiditis. We retrospectively enrolled all patients who underwent robotic transaxillary thyroidectomy between February 2012 and March 2022. We compared surgical outcomes between patients who presented a thyroid gland with a nodule ≤ 3 cm, thyroid lobe < 6 cm and without thyroiditis (Group A) and patients without these features (Group B). The rate of overall complications resulted comparable (p = 0.399), as well as the operative time (p = 0.477) and the hospital stay (p = 0.305). Moreover, bleeding resulted associated to thyroid nodule > 3 cm (p = 0.015), although all bleedings but one occurred in the remote-access site from the axilla to the neck. In experienced hands, robotic transaxillary thyroidectomy is feasible and safe even in patients with large thyroid nodules or thyroiditis.

Case report: Hashimoto's thyroiditis after CD19 chimeric antigen receptor T-cell therapy.

Chimeric antigen receptor (CAR)-T cell therapy is a novel cell therapeutic approach that is increasingly being used to treat patients with relapsed refractory B-cell lymphoma. Despite the efficacy of CAR T cell therapy, it has various adverse effects that can affect any organ in the body. The application of immune checkpoint inhibitors such as programmed death 1 (PD-1), programmed death ligand 1 (PDL-1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies has previously been reported to be associated with immune-related adverse events such as thyroid dysfunction and thyroiditis. Reports of immune-related adverse reactions after CAR T therapy are currently extremely rare, with only one case of a cytokine storm (CRS) combined with severe arthritis in a patient with ALL after treatment. Here, we describe two cases of Hashimoto's thyroiditis secondary to CAR T therapy. Two patients with relapsed refractory diffuse large B-cell lymphoma developed elevated peroxidase and globulin antibodies secondary to CAR-T cell therapy and developed Hashimoto's thyroiditis. Complete remission was achieved in two patients at 1 and 3 months after CAR-T cell therapy. The inflammation of the thyroid tissue may be directly or indirectly related to CAR T cell therapy, and the mechanisms needs to be further investigated.

Silent thyroiditis following vaccination against COVID-19: report of two cases.

PURPOSE: It is well established that thyroiditis and other thyroid disorders can be induced by COVID-19 infection, but there is limited information about the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We report two cases of thyrotoxicosis following SARS-CoV-2 vaccine. METHODS AND RESULTS: Two young health care peoples (wife and husband) received a first dose of SARS-CoV-2 vaccine, and few weeks later developed clinical manifestations of thyroid hyperactivity, with increased thyroid hormone levels on thyroid function tests, suppressed thyroid-stimulating hormone and negative antithyroid antibodies, despite being healthy before vaccination. They were diagnosed at the 4th week after first dose of SARS-Cov-2 vaccine as silent thyroiditis and followed without treatment, since their symptoms were not severe. At the 6th week, the patients became wholly asymptomatic and their thyroid function returned to normal. CONCLUSIONS: Thyrotoxicosis can occur after SARS-CoV-2 vaccination probably related to silent thyroiditis.

Thyroid as a target of adjuvant autoimmunity/inflammatory syndrome due to mRNA-based SARS-CoV2 vaccination: from Graves' disease to silent thyroiditis.

BACKGROUND: As COVID-19 became a pandemic, the urgent need to find an effective treatment vaccine has been a major objective. Vaccines contain adjuvants which are not exempt from adverse effects and can trigger the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). There is very little information about autoimmune endocrine disease and the ASIA after the use of mRNA-based SARS-CoV2 vaccination. CASE SERIES: We report three cases and also review the literature showing that the thyroid gland can be involved in the ASIA induced by the mRNA-based SARS-CoV2 vaccination. We present the first case to date of silent thyroiditis described in the context of SARS-CoV2 vaccination with Pfizer/BioNTech. Also, we discuss the first subacute thyroiditis in the context of SARS-CoV2 vaccination with the Moderna's vaccine. Finally, we provide another case to be added to existing evidence on Graves' disease occurring post-vaccination with the Pfizer/BioNTech vaccine. DISCUSSION: Adjuvants play an important role in vaccines. Their ability to increase the immunogenicity of the active ingredient is necessary to achieve the desired immune response. Both the Moderna and the Pfizer/BioNTech vaccines use mRNA coding for the SARS-CoV2 S protein enhanced by adjuvants. In addition, the cross-reactivity between SARS-CoV2 and thyroid antigens has been reported. This would explain, at least, some of the autoimmune/inflammatory reactions produced during and after SARS-CoV2 infection and vaccination. CONCLUSION: The autoimmune/inflammatory syndrome induced by adjuvants involving the thyroid could be an adverse effect of SARS-CoV2 vaccination and could be underdiagnosed.

Acute Thyroiditis and Bilateral Optic Neuritis following SARS-CoV-2 Vaccination with CoronaVac: A Case Report.

PURPOSE: To describe a case of acute thyroiditis and bilateral optic neuritis associated with SARS-CoV-2 vaccination. METHODS: A single case report from a tertiary referral center. RESULTS: The patient described in the following case report developed acute thyroiditis and bilateral optic neuritis following SARS-CoV-2 vaccination. The patient underwent pulse therapy followed by oral tapering corticosteroid therapy with an improvement of the bilateral disc swelling and the visual field, and recovery of thyroid-stimulating hormone to the normal limits. CONCLUSION: Although the association between immunization and the onset of demyelinating manifestations of the central nervous system is well documented, this is the first reported case of bilateral optic neuritis and acute thyroiditis and subsequent to administration of vaccination against SARS-CoV-2.

Pembrolizumab-Induced Thyroiditis Shows PD-L1Expressing Histiocytes and Infiltrating T Cells in Thyroid Tissue - A Case Report.

Context: Immune-related adverse events frequently take place after initiation of immune checkpoint inhibitors (ICI) therapy. The thyroid gland is the endocrine organ most commonly affected by ICI therapy, the pathological mechanism is still poorly understood. Case Description: A 60-year old Upper Austrian male melanoma patient under pembrolizumab therapy received thyroidectomy because of a suspicious FDG avid thyroid nodule. Histopathology showed a pattern comparable with thyroiditis de Quervain. The inflammatory process consisted predominantly of T lymphocytes with a dominance of CD4+ T helper cells. In addition CD68+ histiocytes co-expressing PD-L1 were observed. Conclusion: Clusters of perifollicular histiocytes expressing PD-L1 were observed in this case of pembrolizumab induced thyroiditis - probably induced by the former ICI therapy. This finding might indicate the initial target for the breakdown of self tolerance. In context with other data the immunological process seems to be driven by CD3+ lymphocytes infiltrating the thyroid.

The cytokine storm and thyroid hormone changes in COVID-19.

BACKGROUND: COVID-19 is now a worldwide pandemic. Among the many extra-pulmonary manifestations of COVID-19, recent evidence suggested a possible occurrence of thyroid dysfunction. PURPOSE: The Aim of the present review is to summarize available studies regarding thyroid function alterations in patients with COVID-19 and to overview the possible physio-pathological explanations. CONCLUSIONS: The repercussions of the thyroid of COVID-19 seem to be related, in part, with the occurrence of a "cytokine storm" that would, in turn, induce a "non-thyroidal illness". Some specific cytokines and chemokines appear to have a direct role on the hypothalamus-pituitary-thyroid axis. On the other hand, some authors have observed an increased incidence of a destructive thyroiditis, either subacute or painless, in patients with COVID-19. The hypothesis of a direct infection of the thyroid by SARS-Cov-2 stems from the observation that its receptor, ACE2, is strongly expressed in thyroid tissue. Lastly, it is highly probable that some pharmaceutical agents largely used for the treatment of COVID-19 can act as confounding factors in the laboratory evaluation of thyroid function parameters.

Thyroid complications of SARS and coronavirus disease 2019 (COVID-19).

We have reviewed the available literature on thyroid diseases and coronavirus disease 2019 (COVID-19), and data from the previous coronavirus pandemic, the severe acute respiratory syndrome (SARS) epidemic. We learned that both SARS and COVID-19 patients had thyroid abnormalities. In the limited number of SARS cases, where it was examined, decreased serum T3, T4 and TSH levels were detected. In a study of survivors of SARS approximately 7% of the patients had hypothyroidism. In the previous evaluation evidence was found that pituitary function was also affected in SARS. Others suggested a hypothalamic-pituitary-adrenal axis dysfunction. One result published recently indicates that a primary injury to the thyroid gland itself may play a key role in the pathogenesis of thyroid disorders in COVID-19 patients, too. Subacute thyroiditis, autoimmune thyroiditis and an atypical form of thyroiditis are complications of COVID-19. Thyroid hormone dysfunction affects the outcome by increasing mortality in critical illnesses like acute respiratory distress syndrome, which is a leading complication in COVID-19. Angiotensin-converting enzyme 2 is a membrane-bound enzyme, which is also expressed in the thyroid gland and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses it for docking, entering as well as replication. Based on the available results obtained in the SARS-CoV-2 pandemic, beside others, we suggest that it is necessary to monitor thyroid hormones in COVID-19.

Imaging spectrum of adverse events of immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs), a form of immunotherapy, are increasingly used for a variety of malignancies and have been linked to numerous treatment-related side effects known as immune-related adverse events (irAEs). IrAEs can affect multiple organ systems and are important to recognise in order to avoid misinterpretation as progressive tumour and to ensure appropriate management. In this pictorial review, we will briefly discuss radiological response criteria of immunotherapy and describe the imaging appearances of the wide spectrum of these ICI-associated toxicities.

Case report series: revisiting third and fourth pharyngeal arch anomalies, - are they thymopharyngeal duct remnants?

BACKGROUND: Pharyngeal arch anomalies are the second most common form of head and neck congenital defect. The second arch anomalies are the most common, and compromise 95% of cases. Little is known about the 3rd and 4th arch anomalies as they are extremely rare. They most commonly present in childhood with sudden severe left lateral neck infection and abscess formation with considerable tendency to recur, contributing to significant mortality and morbidity in those patients. CASE PRESENTATION: Here we present four cases finally diagnosed as third or fourth pharyngeal arch anomalies, with more than 20 years of follow-up following their definitive surgery. The possibility that they are thymopharyngeal duct remnants is discussed. CONCLUSION: Meticulous open radical surgical excision of all involved paralaryngeal, parapharyngeal and thyroid tissue, with preservation of the superior and recurrent laryngeal nerves, is required for cure of recurrent cases.

Association of autoimmunity with survival in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs) that occur as a consequence of enhanced immune response due to T-cell activation. The objective of this retrospective study was to investigate the association between irAEs and disease outcome in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: This study included 89 patients with R/M HNSCC who were treated with nivolumab in our center from October 2015 to January 2020. Overall survival (OS) and post-progression survival (PPS) were calculated from the date of nivolumab initiation or from the date of progression on nivolumab respectively to the date of death or censored at the last date of follow up. RESULTS: Twenty-four patients (27%) developed irAEs, with more common thyroiditis (N = 13, 14.6%). ORR did not differ between patients with irAEs (29.2%) and patients without irAEs (21.9%, p = 0.576). Median PFS was similar between the two groups (3.1 months for patients with irAEs vs. 2.6 months for patients without irAEs, p = 0.412). Median OS was significantly longer in patients with irAEs (17.9 vs. 6.3 months in patients without irAEs, log-rank p = 0.004). Additionally, median PPS was significantly improved in patients who developed irAEs (10.2 months vs. 2.8 months for patients without irAEs, log-rank p = 0.001). In multivariate analysis, the development of irAEs and response to nivolumab were shown to be independent prognostic factors for favorable OS and PPS. CONCLUSIONS: The development of irAEs is a strong predictor of improved survival in patients with advanced HNSCC treated with nivolumab.

Tratamiento médico del hipertiroidismo / Medical treatment of hyperthyroidism

El hipertiroidismo es una enfermedad común que afecta a un 0.2 % de la población en Europa. Aun siendo un síndrome, el tratamiento varía dependiendo de la causa. Los mecanismos patogénicos de cada una de las etiologías dictan la selección del tratamiento, siendo el hipertiroidismo un buen modelo de medicina de precisión, por cuanto una vez conocida la patogenia se personaliza el tratamiento. En este capítulo se considera el tratamiento de las causas más comunes como son la enfermedad de Graves-Basedow, el bocio multinodular y adenoma tóxico, causas menos frecuentes que incluyen diverso tipo de tiroiditis y causas raras como los tirotropinomas, e hipertiroidismo por patologías obstétricas y ginecológicas. Para el tratamiento médico de estas condiciones disponemos de un arsenal que incluye drogas antitiroideas, beta-bloqueadores, glucocorticoides, análogos de la somatostatina, agonistas dopaminérgicos, ácido iopanoico e, incluso, agentes antineoplásicos. El tratamiento con radioyodo es objeto de otro trabajo aparte

Hyperthyroidism is a rather common disease that affects 0.2 % of general population in Europe. There are many causes as well as various pathogenic mechanisms inducing a hypersecretion of thyroid hormones. Therefore, treatments are selected for each cause to obtain the highest therapeutic benefit. Is this chapter we consider the treatment of common causes such as Graves-disease, toxic multinodular goiter, toxic adenoma and other more infrequent entities such as several subtypes of thyroiditis and, finally, we briefly comment on rare cases of thyroid hyperfunction

[Thyroid dysfunctions secondary to cancer immunotherapy]. / Les dysthyroïdies sous immunothérapie anti-cancéreuse.

The immune checkpoint inhibitors (CPI) such as anti-PD(L)1 or anti-CTLA4 had improved long-term patients' outcomes in different malignancies. Thyroid disorders are the most frequent endocrine side effects from CPI reported in clinical trials and in clinical routine practice. The incidence of thyroid dysfunction is variable according to ICP used (more frequent under anti-programmed cell death 1 (PD1) or anti-programmed cell death-ligand 1 (PDL1)). Most thyroid dysfunctions have been reported to occur 2 to 4 courses after CPI initiation. The clinical symptoms are generally nonspecific (asthenia, weight change, rarely cardiac rhythm disorder). These thyroid dysfunctions are commonly painless thyroiditis with a biphasic evolution: thyrotoxicosis followed by a secondary hypothyroidism frequently definitive. Diagnosis is made on a thyroid test (TSH and FT4). In most cases, no further exam is necessary. Beta blockers therapy is recommended in symptomatic thyrotoxicosis with palpitations. Thyroid hormones therapy will be introduced quickly in case of hypothyroidism. Thyroid dysfunctions are not a contra-indication to the continuation of immunotherapy. Due to the high frequency of these complications, close monitoring of the thyroid status is recommended under CPI.

Acute Thyroiditis Associated with Brucellosis: A Case Report.

Brucella thyroiditis represents an extremely rare focal form of brucellosis. In this case report we describe a 55 years old male, diagnosed with brucellosis and peripheral arthritis with subsequent development of acute thyroiditis. The symptoms duration consistent with brucellosis started two weeks before establishing the diagnosis. Only a day after diagnosis and initiation of antibrucellar treatment, acute non-suppurative thyroiditis suddenly manifested. Thyroiditis was diagnosed with clinical inspection and confirmed by ultrasound investigation. With the appropriate antibrucellar treatment, complete cure of thyroid affection was reached in ten days and the patient remained well during the follow-up period of two and a half years. In conclusion, in brucellosis endemic regions brucellosis should be included in the diagnostic consideration in patients with acute non-suppurative thyroiditis. Early recognition and adequate treatment of brucella thyroiditis results in favorable outcome.

A Case of Dynamic Evolution of Thyrotoxicosis on Follow-up.

A 55-year female patient presented with subacute thyroiditis (SAT) with a unique dynamic evolution, along with changes in the level of antithyroglobulin antibody, which has been rarely reported. Her thyrotoxicosis gradually worsened over the next three months. Severe hypothyroidism then rapidly developed and did not resolve. For the whole disease course, antithyroglobulin antibody levels were significantly increased, indicating dynamic changes in thyroid function. It has been suggested that the duration of thyrotoxicosis in SAT is highly variable, which is probably related to an underlying autoimmune mechanism. It is therefore, necessary to rule out other causes of thyroiditis.

Obesity-related thyroiditis in childhood: relationship with insulin resistance.

Background Thyroid dysfunction is the most common hormonal abnormality in obesity. It should actually be considered as an adaptation response to fat excess. However, little has been reported on the morphology of the thyroid gland, and no data regarding the relationship between thyroid gland changes and metabolic parameters are available in obese adolescents. Objective The study aimed to evaluate the frequency of non-autoimmune thyroiditis in obese adolescents and compare the metabolic status of patients with or without thyroiditis. Methods A total of 218 obese children and 49 age-matched control healthy children were included. Thyroid ultrasonography (USG) was performed in all participants, as well as thyroid hormone levels, thyroid antibodies (Abs), lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (HsCRP) were determined. Obese children were divided into three groups according to the presence of thyroid autoantibodies and USG findings of thyroiditis (Group-1: Abs [-], normal thyroid morphology/Group-2: Abs [+], abnormal thyroid morphology/Group-3: Abs [-], abnormal thyroid morphology). The relationship between body mass index, metabolic parameters and thyroid gland status was analyzed. Results Seventy-two of 218 obese patients (33%) had non-autoimmune thyroiditis (Group-3). The rate of insulin resistance was significantly higher in Group-3 than in Group-1 (p = 0.024). Similarly, the frequency of metabolic syndrome (MS) was higher in Group-3 (44.3%) than in Group-1 (27.1%) (p = 0.014). Conclusions Obese adolescents with non-autoimmune thyroiditis had a higher incidence of insulin resistance. This finding supported the hypothesis that insulin resistance may have an effect on thyroid morphology. Further randomized trials investigating this relationship are required.

Subsequent thyroid disorders associated with treatment strategy in head and neck cancer patients: a nationwide cohort study.

BACKGROUND: We investigated the risk of thyroid disorders, namely hypothyroidism, thyrotoxicosis and thyroiditis, in head and neck cancer patients undergoing multimodal treatment. METHODS: A cohort study design using Taiwan's National Health Insurance Research Database was used to assess head and neck cancer patients over 20 years old. The cohort was divided into one group who underwent primary tumor excision only (PTE) and another with additional neck dissection (PTE + ND). The tumor sites were stratified to estimate the tumor-site-specific risk of thyroid disorders. The effect of subsequent resurgery, radiotherapy (RT), chemotherapy (CT), and concomitant (CCRT) or sequential chemoradiation therapy (sequential CT+ RT) on the risk of thyroid disorders was explored. RESULTS: For 1999-2012, 7460 patients who underwent PTE + ND and 3730 who underwent PTE were enrolled and followed-up until the end of 2013. There were 122 and 50 patients in the two groups, respectively, who developed thyroid disorders, with no statistical difference between the groups. Patients with hypopharyngeal, oropharyngeal, or laryngeal cancer in the PTE + ND group had a higher risk of thyroid disorders (adjusted HR: 1.50, 95% CI: 0.67-3.38) than those in the PTE group when adjusted for covariates and mortality. Patients who underwent subsequent RT (adjusted HR: 3.64, 95% CI: 1.05-2.77) and CCRT (adjusted HR: 1.70, 95% CI: 1.05-2.77) after PTE + ND had a significantly higher risk of thyroid disorders. CONCLUSION: RT results in a major risk of subsequent thyroid disorders, and ND may exacerbate this effect. Physicians should monitor thyroid function from two years after treatment initiation, especially in patients who undergo ND and subsequent RT.

Continued administration of pembrolizumab for adenocarcinoma of the lung after the onset of fulminant type 1 diabetes mellitus as an immune-related adverse effect: A case report.

A 61-year-old woman with stage IVA lung adenocarcinoma exhibited high PD-L1 expression. Pembrolizumab was administered as second-line therapy. She developed destructive thyroiditis and her thyroid function started to decline during the administration of three to five courses. She was subsequently diagnosed with fulminant type 1 diabetes mellitus and ketoacidosis during the eighth course and insulin treatment was initiated. Pembrolizumab remained effective and was continued for 21 courses, even after the onset of diabetes mellitus. Immune-checkpoint inhibitor treatment can be continued with hormone replacement even after the development of type 1 diabetes mellitus as an immune-related adverse event.