Hashimoto's Thyroiditis Negatively Influences Intracytoplasmic Sperm Injection Outcome in Euthyroid Women on T4 Substitution Therapy: A Retrospective Study.

OBJECTIVE: The objective of this study was to analyze the impact of thyroid autoimmunity (TAI) on reproductive outcome parameters of intracytoplasmic sperm injection (ICSI) cycles as compared to TAI-negative ICSI cycles. DESIGN: In this single in vitro fertilization (IVF) center retrospective study, 86 infertile women with elevated thyroid peroxidase or TGAb levels, but euthyroid after thyroxine replacement (study group), were compared to 69 female patients with no thyroid abnormalities (controls). Following ICSI treatment fertilization rate (FR), clinical pregnancy rate (CPR), miscarriage rate (MR), and live birth rate (LBR) were analyzed. MATERIALS, SETTING, METHODS: All subjects with various infertility factors were treated with ICSI in university-based IVF center. Patients in the study group received thyroxine replacement and were euthyroid at IVF treatment. Before the IVF cycles, endocrinological parameters were uniformly assessed: thyroid function and antibodies, reproductive hormones (anti-Müllerian hormone [AMH], follicular stimulating hormone [FSH], luteinizing hormone, E2, PRL, testosterone, DHEAS, 17-OHP, AD) and OGTT (0-60-120 min glucose and insulin). Following descriptive comparison of laboratory parameters, age-adjusted analyses of FR, CPR, MR, and LBR were performed. RESULTS: TAI-positive women were older (mean age 35.31 ± 4.95 vs. 32.15 ± 4.87 years; p = 0.002), had higher FSH (8.4 ± 3.4 vs. 7.4 ± 2.32 U/L; p = 0.024), higher E2 (53.94 ± 47.61 vs. 42.93 ± 18.92 pg/mL; p = 0.025) levels, while AMH (2.88 ± 2.62 vs. 3.61 ± 1.69 ng/mL; p = 0.0002) was lower. There were no differences in TSH levels (1.64 ± 0.96 vs. 1.66 ± 0.65 µIU/mL; p = 0.652) between the two groups. FT3 (2.63 ± 0.58 vs. 2.98 ± 0.55 pg/mL; p = 0.002) was lower and FT4 (1.3 ± 0.29 vs. 1.13 ± 0.21 ng/dL; p = 0.0002) was higher in the TAI-positive group, reflecting clinically irrelevant differences. Egg cell counts (6 ± 3.8 vs. 7.5 ± 3.95; p = 0.015) were lower in TAI and remained so following age adjustment. Although the overall ICSI FR did not differ (62.9% vs. 69.1%, p = 0.12), it was lower for patients under 35 with TAI showing decreasing differences in line with age. The CPR (36.04% vs. 69.56%; p < 0.001) and LBR (23.25% vs. 60.86%; p < 0.001) were lower, the MR (35.48% vs. 12.5%; p = 0.024) was higher in the TAI group, and these differences remained after age adjustment. LIMITATIONS: Since the higher age of the study group may interfere with the effect of TAI, age adjustment calculations were necessary to perform to eliminate this confounding factor. CONCLUSION: Despite optimal thyroid supplementation in clinical or subclinical hypothyroidism, the presence of TAI negatively influences CPR and is connected to a higher MR, thus resulting in a lower LBR after ICSI. Decreased FR with ICSI in TAI patients may also contribute to poorer outcomes, especially in younger women.

Hyperthyroidism.

Thyrotoxicosis causes a variety of symptoms and adverse health outcomes. Hyperthyroidism refers to increased thyroid hormone synthesis and secretion, most commonly from Graves' disease or toxic nodular goitre, whereas thyroiditis (typically autoimmune, viral, or drug induced) causes thyrotoxicosis without hyperthyroidism. The diagnosis is based on suppressed serum concentrations of thyroid-stimulating hormone (TSH), accompanied by free thyroxine and total or free tri-iodothyronine concentrations, which are raised (overt hyperthyroidism) or within range (subclinical hyperthyroidism). The underlying cause is determined by clinical assessment, detection of TSH-receptor antibodies and, if necessary, radionuclide thyroid scintigraphy. Treatment options for hyperthyroidism include antithyroid drugs, radioactive iodine, and thyroidectomy, whereas thyroiditis is managed symptomatically or with glucocorticoid therapy. In Graves' disease, first-line treatment is a 12-18-month course of antithyroid drugs, whereas for goitre, radioactive iodine or surgery are preferred for toxic nodules or goitres. Evidence also supports long-term treatment with antithyroid drugs as an option for patients with Graves' disease and toxic nodular goitre.

Correlation between remnant thyroid gland I-131 uptake and serum thyroglobulin levels: can we rely on I-131 whole body scans?

BACKGROUND: I-131 treatment (RAI) decision relies heavily on serum thyroglobulin (Tg) levels, as higher Tg levels are assumed to be correlated with higher I-131 uptake. Tg elevation, negative iodine scintigraphy (TENIS) definition is becoming more clinically relevant as alternative treatment methods are available. This study examined the correlation between Tg levels with I-131 uptake in remnant thyroid gland to evaluate the reliability of serum Tg levels in predicting I-131 uptake. METHODS: From March 2012 to July 2019, 281 papillary thyroid cancer patients treated with 150 mCi RAI were retrospectively enrolled. Early (2nd day) and Delayed (7th day) post-RAI whole-body scan (WBS) neck counts were correlated with clinical and pathologic findings. Patients with normal neck ultrasound and undetectable level of serum Tg (< 0.2 ng/mL) and thyroglobulin antibody (TgAb) (< 10 IU/mL) were defined as ablation success within 2 years after I-131 ablation. RESULTS: Thyroid gland weight, tumor size and thyroiditis were independent factors of preoperative serum Tg levels. Serum off-Tg levels correlated with Early and Delayed WBS neck counts, and thyroiditis pathology contributed to lower neck counts in both Early and Delayed WBSs. In multivariable analysis, Delayed WBS neck count, serum off-Tg and off-TgAb were significant factors for predicting ablation success. CONCLUSION: I-131 uptake and retention in remnant thyroid gland correlates with serum off-Tg levels, thyroiditis, and ablation success in thyroid cancer patients receiving high-dose I-131 therapy. Semi-quantitative I-131 analysis with Early and Delayed WBSs provides additional information in evaluating ablation success, with the potential application for metastasis treatment response evaluation.

Herbal medicine for Hashimoto's thyroiditis: A systematic review and network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Conventional treatments for Hashimoto's thyroiditis (HT) are limited. Herbal medicines (HM) are considered a potential intervention for the treatment of HT. AIM OF THE STUDY: This study aimed to investigate the efficacy and safety of HM for HT. MATERIALS AND METHODS: A Bayesian network meta-analysis was conducted for patients with HT in randomized controlled trials identified in PubMed, Cochrane Library, Web of Science, EMBASE, Chinese Clinical Trial Registry (Chi CTR), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (the VIP), China Chinese Biomedical Database (CBM), and Wanfang Database were searched from their inception to Oct 1, 2022. Outcomes included the primary outcome (TPOAb), secondary outcomes (TSH, TGAb, FT3, FT4, and traditional Chinese medicine symptom scores), and adverse events. This study was registered in PROSPERO (CRD42022363640). RESULTS: Sixteen trials were reviewed and 16 HM formulae were compared. Compared with non-drug therapy (NDT), all therapies, except for Tiaoqi-Qingjie Therapy, reduced the primary outcome of TPOAb with different levels of effectiveness, ranging from 0.01 (95%CI 0.00, 0.02) to 0.92 (95%CI 0.56, 1.53). Ranking probability analysis indicated that Yiqi Huayu Recipe, Liqi Xiaoying decoction, and Shugan Sanjie therapy reduced thyroid antibody levels the most, including TPOAb (100.0%, 90.9%, and 90.3%, respectively) and TGAb (98.3%, 94.4%, and 87.3%, respectively). All HMs displayed a significant effect on the TCM Symptom score and possibly benefitted the treatment of HT, ranging from 6.62 (95% CI 2.06, 21.24) to 94.50 (95% CI 15.97, 559.14). No serious adverse events were reported. CONCLUSIONS: Herbal medicines may be effective in the treatment of HT, especially in reducing thyroid antibody levels and improving clinical symptoms without affecting thyroid function. However, these results should be considered preliminary and further verified using high-quality evidence.

Short- and long-term outcomes of patients with hyper or hypothyroidism following COVID vaccine.

Since the beginning of the wide-scale anti-Coronavirus disease 2019 (COVID-19) vaccination program, sporadic cases of thyroid disease following vaccination have been reported. We describe 19 consecutive cases of COVID vaccine-related thyroid disease. Medical records were reviewed for 9 patients with Graves' disease (GD) and 10 with Thyroiditis, all of whom were diagnosed following COVID-19 vaccination. In the GD group, the median age was 45.5 years, female/male(F/M) ratio 5:4, thyroid-stimulating immunoglobulins were elevated in seven patients. The median time from vaccination to diagnosis was 3 months. Methimazole treatment was given to all but one patient. At a median follow-up of 8.5 months from vaccination, three patients were still on methimazole, five went into remission (data were missing for one). In the Thyroiditis group, the median age was 47 years, the F/M ratio 7:3. Thyroiditis was diagnosed after the first, second, and third doses in one, two, and seven patients, respectively. The median time from vaccination to diagnosis was 2 months. TPO antibodies were positive in three patients. All patients were euthyroid off medication at the last visit. Six patients were diagnosed in the hypothyroid phase at 2.5 months from vaccination. Four resolved spontaneously at 3, 6, 4, and 8 months; the other two were treated with thyroxine at 1.5 and 2 months from vaccination and remained on treatment at their last visit, at 11.5 and 8.5 months, respectively. Thyroid disease should be included among possible complications of COVID-19 vaccine and either a late onset or delayed diagnosis should be considered.

Optimal levothyroxine dose to achieve euthyroidism in patients with primary hypothyroidism: analysis according to etiology.

INTRODUCTION: Levothyroxine (LT4) has been considered the standard of care for treatment of hypothyroidism. Current recommendations suggest a LT4 dose between 1.6-1.8 µg/kg/day. The aim of this study was to evaluate the LT4 dose for adult patients with primary hypothyroidism of different etiologies who reached euthyroidism. METHODS: A cross-sectional study was performed from the retrospective review of the charts of patients with primary hypothyroidism in treatment with LT4. Subjects were classified according to TSH level in overtreated (TSH < 0.4 µIU/ml), euthyroid (TSH 0.40-4.20), and undertreated (TSH >4.2) and according to the etiology of hypothyroidism. A stepwise logistic regression model was performed to evaluate the variables associated with TSH<0.4 µIU/ml. RESULTS: 955 patients were included. 75.13% of the patients had an adequate LT4 replacement. LT4 dose to achieve euthyroidism was higher in patients with a history of radioiodine therapy (1.92 µg/kg) and thyroid surgery (1.52 µg/kg), while the LT4 dose required to achieve euthyroidism in patients with Hashimoto's thyroiditis and atrophic thyroiditis was lower than that reported in previous studies (1.25 and 1.08 µg/kg, respectively). The variables that were associated with a higher probability of TSH<0.4 µIU/ml were male gender, Hashimoto's thyroiditis, radioiodine therapy, and thyroid surgery. MAJOR CONCLUSION: LT4 dose required to achieve euthyroidism in patients with hypothyroidism varies according to the etiology, being higher in patients with hypothyroidism due to radioiodine therapy and thyroid surgery. Patients with hypothyroidism due to Hashimoto's thyroiditis and atrophic thyroiditis require a lower dose than current recommendations.

Introducción: La levotiroxina (LT4) se considera el estándar de tratamiento del hipotiroidismo. Las recomendaciones actuales sugieren una dosis de LT4 entre 1,6-1,8 µg/kg/día. El objetivo de este estudio fue evaluar la dosis de LT4 en pacientes adultos con hipotiroidismo primario de diferentes etiologías que alcanzaron el eutiroidismo. Métodos: Estudio transversal a partir de la revisión retrospectiva de historias clínicas de pacientes con hipotiroidismo primario en tratamiento con LT4. Los sujetos se clasificaron según el nivel de TSH en sobretratados (TSH<0,4 µUI/ml), eutiroideos (TSH 0,40-4,20) y subtratados (TSH>4,2) y según la etiología del hipotiroidismo. Se realizó un modelo de regresión logística escalonada para evaluar las variables asociadas con TSH <0,4 µUI/ml. Resultados: Se incluyeron 955 pacientes. El 75,13% tuvo un reemplazo adecuado de LT4. La dosis de LT4 para lograr el eutiroidismo fue mayor en pacientes con antecedentes de terapia con yodo radiactivo (1,92 µg/kg) y cirugía de tiroides (1,52 µg/kg), mientras que la dosis de LT4 para lograr el eutiroidismo en pacientes con tiroiditis de Hashimoto y tiroiditis atrófica fue menor que el reportado en estudios previos (1,25 y 1,08 µg/kg, respectivamente). Las variables que se asociaron con una mayor probabilidad de TSH<0,4 µUI/ml fueron el sexo masculino, tiroiditis de Hashimoto, terapia con yodo radiactivo y cirugía de tiroides. Conclusión principal: La dosis de LT4 necesaria para alcanzar el eutiroidismo en pacientes con hipotiroidismo varía según la etiología, siendo mayor en pacientes con hipotiroidismo por tratamiento con yodo radiactivo y cirugía tiroidea. Los pacientes con hipotiroidismo debido a tiroiditis de Hashimoto y tiroiditis atrófica requieren una dosis más baja que las recomendaciones actuales.

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.

Multiple endocrinopathies, hypercalcaemia and pancreatitis following combined immune checkpoint inhibitor use- case report and review of literature.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a novel class of oncological agents which are used to treat a number of malignancies. To date seven agents have been approved by the Food and Drug Administration (FDA) to treat both solid and haematological malignancies. Despite their efficacy they have been associated with a number of endocrinopathies. We report a unique case of hypophysitis, thyroiditis, severe hypercalcaemia and pancreatitis following combined ICI therapy. CASE PRESENTATION: A 46-year old Caucasian female with a background history of malignant melanoma and lung metastases presented to the emergency department with lethargy, nausea, palpitations and tremors. She had been started on a combination of nivolumab and ipilimumab 24 weeks earlier. Initial investigations revealed thyrotoxicosis with a thyroid stimulating hormone (TSH) of < 0.01 (0.38-5.33) mIU/L, free T4 of 66.9 (7-16) pmol/.L. TSH receptor and thyroperoxidase antibodies were negative. She was diagnosed with thyroiditis and treated with a beta blocker. Six weeks later she represented with polyuria and polydipsia. A corrected calcium of 3.54 (2.2-2.5) mmol/l and parathyroid hormone (PTH) of 9 (10-65) pg/ml confirmed a diagnosis of non-PTH mediated hypercalcaemia. PTH-related peptide and 1, 25-dihydroxycholecalciferol levels were within the normal range. Cross-sectional imaging and a bone scan out ruled bone metastases but did reveal an incidental finding of acute pancreatitis - both glucose and amylase levels were normal. The patient was treated with intravenous hydration and zoledronic acid. Assessment of the hypothalamic-pituitary-adrenal (HPA) axis uncovered adrenocorticotrophic hormone (ACTH) deficiency with a morning cortisol of 17 nmol/L. A pituitary Magnetic Resonance Image (MRI) was unremarkable. Given her excellent response to ICI therapy she remained on ipilimumab and nivolumab. On follow-up this patient's thyrotoxicosis had resolved without anti-thyroid mediations - consistent with a diagnosis of thyroiditis secondary to nivolumab use. Calcium levels normalised rapidly and remained normal. ACTH deficiency persisted, and she is maintained on oral prednisolone. CONCLUSION: This is a remarkable case in which ACTH deficiency due to hypophysitis; thyroiditis; hypercalcaemia and pancreatitis developed in the same patient on ipilimumab and nivolumab combination therapy. We postulate that hypercalcaemia in this case was secondary to a combination of hyperthyroidism and secondary adrenal insufficiency.

Safety of current immune checkpoint inhibitors in non-small cell lung cancer.

Introduction: Immune checkpoint inhibitors (ICIs) achieved response rates around 20% in advanced non-small cell lung cancer (NSCLC) with 8% of patients becoming long-term survivors. Outcomes have improved with the addition of chemotherapy to immunotherapy or the combination of anti-PD(L)1 with anti-CTLA-4 agents.Areas covered: The incidence of immune-related adverse events (irAEs) in patients with NSCLC treated with ICIs varied across clinical trials and real-life studies. The onset of irAEs was 10 weeks. Toxic deaths from irAEs following anti-PD(L)1 administration resulted mainly from pneumonitis. Some irAEs such as rash and thyroiditis were probably associated with better clinical outcomes, though confounding biases exist. Investigations are on-going to determine ideal biomarkers to predict the occurrence, to screen for and to diagnose irAEs.Expert opinion: Prevention, anticipation, detection, treatment and careful monitoring are the five principles that characterize our management of irAEs. Distinguishing immune-induced pneumonitis from progression, pseudo progression, hyper progression, or other etiologies (COVID-19) can be particularly challenging in lung cancer due to the baseline vulnerable pulmonary function and thus requires caution and teamwork. We treat patients according to institutional and international guidelines and we only rechallenge them with ICIs after resolution of the AE and corticosteroid tapering.

Enfermedad de Graves con autoanticuerpos contra el receptor de la TSH negativos: a propósito de 5 casos / Graves disease with negative TSH receptor antibodies: A presentation of 5 cases

No disponible

Plasmaféresis tiroidea / Thyroid plasmapheresis

No disponible

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

Compared with classic Hashimoto's thyroiditis, chronic autoimmune serum-negative thyroiditis requires a lower substitution dose of L-thyroxine to correct hypothyroidism.

PURPOSE: Serum-negative-chronic-autoimmune-thyroiditis (SN-CAT) is considered a milder variant of classic Hashimoto's thyroiditis (CHT). However, its prevalence remains unknown and it is still unclear whether SN-CAT behaves differently in terms of L-thyroxine (LT4) substitution treatment of hypothyroidism. Aims of this study were to estimate the prevalence of SN-CAT in a large series of hypothyroid patients and to compare LT4 requirements in hypothyroid patients with SN-CAT and CHT. METHODS: Five-hundred-eighty-one consecutive patients with primary-autoimmune-hypothyroidism were enrolled in a cross-sectional study. LT4 requirements and thyroid-volume changes were longitudinally evaluated in 49 hypothyroid patients with SN-CAT and in 98 sex and age-matched hypothyroid patients with CHT. RESULTS: In our series the prevalence of SN-CAT was 20.8%. At diagnosis, patients in the CHT and SN-CAT groups had similar male/female ratio, age and BMI, while serum TSH and thyroid-volume were significantly greater in the CHT group. In the longitudinal study, during a follow-up of 8.9 ± 4.6 years, 8 out of 49 (16.3%) SN-CAT patients developed positive tests for of circulating TPO-Ab and/or Tg-Ab. Thyroid-volume significantly decreased in CHT patients, but not in those with SN-CAT. The maximum daily substitution dose of LT4 was smaller in SN-CAT patients as compared with the CHT ones. Multivariate analysis showed that age, BMI, basal TSH and thyroid antibody status independently and significantly predicted the maximum daily substitution dose of LT4. CONCLUSIONS: SN-CAT accounts for a significant proportion of patients with autoimmune hypothyroidism. Compared with hypothyroid patients diagnosed with CHT, the SN-CAT ones require smaller doses of LT4 to correct their hypothyroidism.

Monitoring of Thyroid Malfunction and Therapies in Pregnancy and the Postpartum Period: A Systematic Updated Critical Review of the Literature.

PURPOSE: From the very beginning of pregnancy, the maternal thyroid has to adapt to increased thyroid hormone secretion of up to 50%. This is paralleled by changes in thyroid-stimulating hormone secretion and by the thyroid-topic action of human chorionic gonadotropin. Thus, hypothyroidism and hyperthyroidism may occur. Many women exhibit preexisting thyroid diseases. This review tries to add the most recently published approaches to diagnosing thyroid malfunction in pregnancy to existing guidelines. METHODS: Different literature-based approaches to diagnosing thyroid malfunction during pregnancy and the postpartum period were applied. To diagnose thyroid malfunction in pregnancy, trimester-specific reference ranges for thyroid-stimulating hormone and T4 are used. RESULTS: Definitions of thyroid malfunction are given. Treatment schedules for various thyroid diseases were reviewed and, on the basis of recent findings, were revised where necessary. For a daily clinical workup, this outline not only suggests diagnostic and therapeutic steps but also refers to frequent pitfalls and misinterpretations of laboratory data. CONCLUSIONS: Although the body of knowledge is increasing rapidly, the authors believe that this review is able to present new ideas concerning diagnostic and therapeutic tools for thyroid malfunction in pregnancy and the postpartum period. Nevertheless, there seems to remain room for individual approaches based on the personal experience of physicians who deal with these issues regularly.

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.

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.

Serum autotaxin levels are associated with Graves' disease.

Graves' Disease is a representative autoimmune thyroid disease that presents with hyperthyroidism. Emerging evidence has shown the involvement of lysophosphatidic acid (LPA) and its producing enzyme, autotaxin (ATX), in the pathogenesis of various diseases; among them, the involvement of the ATX/LPA axis in some immunological disturbances has been proposed. In this study, we investigated the association between serum ATX levels and Graves' disease. We measured the levels of serum total ATX and ATX isoforms (classical ATX and novel ATX) in patients with untreated Graves' disease, Graves' disease treated with anti-thyroid drugs, patients with subacute thyroiditis, silent thyroiditis, Plummer's disease, or Hashimoto's thyroiditis, and patients who had undergone a total thyroidectomy, as well as normal subjects. The serum total ATX and ATX isoform levels were higher in the patients with Graves' disease, compared with the levels in the healthy subjects and the patients with subacute thyroiditis. Treatment with anti-thyroid drugs significantly decreased the serum ATX levels. The serum ATX levels and the changes in serum ATX levels during treatment were moderately or strongly correlated with the serum concentrations or the changes in thyroid hormones. However, the administration of T3 or T4 did not increase the expression or serum levels of ATX in 3T3L1 adipocytes or wild-type mice. In conclusion, the serum ATX levels were higher in subjects with Graves' disease, possibly because of a mechanism that does not involve hyperthyroidism. These results suggest the possible involvement of the ATX/LPA axis in the pathogenesis of Graves' disease.

Riedel's thyroiditis: clinical presentation, treatment and outcomes.

BACKGROUND: Riedel´s thyroiditis (RT) is a rare inflammatory disease of the thyroid gland, causing compression and fibrosis of adjacent tissues. Typically the goiter is hard and firm. Hoarseness, dyspnea, and dysphagia may be present. METHODS: We retrospectively reviewed all patients known by us with RT in addition to all patients with appropriate ICD-10 codes evaluated at the Karolinska University Hospital 2003-2015. Clinical, biochemical, and histological data of patients with RT were recorded in detail. Histological preparations were re-examined when available. RESULTS: RT was diagnosed in six patients. Five were females and the median age at first presentation was 50 years (25-81 years). Median follow-up time was 3.75 years (1-22 years). At diagnosis five had hypothyroidism. Four had extrathyroidal manifestations, and one of these had also distant fibrosis. One patient had a clear IgG4/IgG ratio over 40%. One patient was treated with tracheostomy, one with isthmectomy and one with total thyroidectomy. Four had been treated with glucocorticoids, four with tamoxifen, and two with both drugs. One had also been treated with mycophenolate mofetil combined with Rituximab. At the end of follow-up four was doing fine, one had recurrent episodes of inflammation and one had died of possible complications to RT. CONCLUSION: It is important to recognize RT and give adequate treatment. Steroids are still the mainstay of therapy but other medications against fibrosclerosis can be considered. Wakefulness of other fibrosing manifestations is essential. Immunohistochemistry can show whether IgG-4 plasma cells are increased which could lead to fibrosis in other organs.