Incidencia y características clínicas de la enfermedad tiroidea en pacientes con neoplasias malignas tratados con inhibidores de punto de control inmunológico / Incidence and clinical characteristics of thyroid abnormalities in cancer patients treated with immune checkpoint inhibitors

Resumen Introducción: Los inhibidores del punto de control inmunológico (IPCi) son utilizados en los últimos años en el tratamiento de neoplasias malignas avanzadas, con ellos se ha logrado un aumento significativo de la supervivencia; sin embargo, su uso se ha asociado a incremento del riesgo de enfermedades autoinmunes. Objetivo: Describir la incidencia y las características clínicas de los pacientes tratados con IPCi que desarrollaron tiroidopatía. Métodos: Se revisaron retrospectivamente los expedientes de todos los pacientes que recibieron IPCi en los últimos tres años y se identificaron aquellos que desarrollaron anomalías tiroideas. Resultados: La prevalencia de tiroiditis fue de 7 %, con una incidencia de 21.4 % pacientes/mes. La mediana del tiempo para el desarrollo de tiroiditis fue de 63 días. La mayoría de los pacientes presentó síntomas leves o moderados y no requirió hospitalización, si bien todos menos uno desarrollaron hipotiroidismo permanente y requirieron terapia de reemplazo hormonal con levotiroxina. Conclusiones: La disfunción tiroidea secundaria a inmunoterapia es una entidad común en nuestra población. El cuadro clínico suele ser leve y no requiere suspender el tratamiento; sin embargo, debido a la alta incidencia de este evento adverso, los médicos no oncólogos deben estar familiarizados con su diagnóstico y tratamiento, para brindar un manejo multidisciplinario.

Abstract Introduction: Immune checkpoint inhibitors (ICI) are a group of drugs that have been used in recent years for the treatment of advanced malignancies such as melanoma, non-small cell lung cancer and other tumors, significantly increasing survival. However, the use of ICI has been associated with an increased risk of autoimmune diseases, with endocrine organs, specifically the thyroid, being highly susceptible to this phenomenon. Objective: To describe the incidence and clinical characteristics of patients treated with ICI who develop thyroid disease. Methods: The medical records of all patients who received ICI treatment within the last three years were retrospectively reviewed, with those who developed thyroid abnormalities being identified. Results: The prevalence of thyroiditis was 7 %, with an incidence of 21.4 % of patients-month. Median time for the development of thyroiditis was 63 days. Most patients had mild or moderate symptoms and did not require hospitalization, although all but one developed permanent hypothyroidism and required hormone replacement therapy with levothyroxine. Conclusions: Thyroid dysfunction secondary to immunotherapy is a common entity in our population. Clinical presentation is usually mild and does not require treatment discontinuation; however, due to the high incidence of these adverse events, non-oncology specialists must be familiar with the diagnosis and treatment of these alterations in order to provide multidisciplinary management.

Comparison between peak systolic velocity of the inferior thyroid artery and technetium-99m pertechnetate thyroid uptake in differentiating Graves' disease from thyroiditis

ABSTRACT Objectives The differentiation between the various etiologies of thyrotoxicosis, including those with hyperthyroidism (especially Graves' disease [GD], the most common cause of hyperthyroidism) and without hyperthyroidism (like thyroiditis), is an important step in planning specific therapy. Technetium-99m (99mTc) pertechnetate thyroid scanning is the gold standard in differentiating GD from thyroiditis. However, this technique has limited availability, is contraindicated in pregnancy and lactation, and is not helpful in cases with history of recent exposure to excess iodine. The aim of this study was to identify the diagnostic value of the peak systolic velocity of the inferior thyroid artery (PSV-ITA) assessed by color-flow Doppler ultrasound (CFDU) and compare the sensitivity and specificity of this method versus 99mTc pertechnetate thyroid uptake. Subjects and methods We prospectively analyzed 65 patients (46 with GD and 19 with thyroiditis). All patients were evaluated with clinical history and physical examination and underwent 99mTc pertechnetate scanning and measurement of TRAb levels and PSV-ITA values by CFDU. The diagnosis was based on findings from signs and symptoms, physical examination, and 99mTc pertechnetate uptake. Results Patients with GD had significantly higher mean PSV-ITA values than those with thyroiditis. At a mean PSV-ITA cutoff value of 30 cm/sec, PSV-ITA discriminated GD from thyroiditis with a sensitivity of 91% and specificity of 89%. Conclusion Measurement of PSV-ITA by CFDU is a good diagnostic approach to discriminate between GD and thyroiditis, with sensitivity and specificity values comparable to those of 99mTc pertechnetate thyroid uptake.

Antecedentes históricos de la enfermedad relacionada con IgG4 / Historical history of IgG4­related disease

El concepto de enfermedad relacionada a IgG4 se introdujo en la literatura médica hace menos de dos décadas. Este surgió a raíz del registro creciente de manifestaciones extrapancreáticas asociadas a la pancreatitis esclerosante linfoplasmocitaria y a la detección concomitante de niveles séricos aumentados de IgG4 en estos pacientes. Por siglos, muchas manifestaciones de esta enfermedad fueron designadas por epónimos y consideradas idiopáticas. Ya hace más de setenta años, Norman Barrett unió dentro de un mismo grupo patológico algunas de las distintas manifestaciones de esta enfermedad al observar las similitudes macro­ y microscópicas en ellas, aunque no se pudo corroborar una misma etiopatogenia hasta comienzos de este siglo. Se revisó aquí la evolución histórica de esta entidad. (AU)

Natural Killer Cells and Thyroid Diseases

Abnormal production of thyroid hormone is one of the common endocrine disorders, and thyroid hormone production declines with age. The aging process also negatively affects the immune system. An interaction between endocrine system and the immune system has been proposed to be bidirectional. Emerging evidence suggests an interaction between a lymphocyte population, called natural killer (NK) cells and thyroid gland function. Here, we review the relationship between NK cells and thyroid function and disease.

Ultrasound elastography of the thyroid: principles and current status

Ultrasound (US) elastography has been introduced as a non-invasive technique for evaluating thyroid diseases. This paper presents a detailed description of the technical principles, peculiarities, and limitations of US elastography techniques, including strain elastography and shear-wave elastography. This review was conducted from a clinical perspective, and aimed to assess the usefulness of US elastography for thyroid diseases in specific clinical scenarios. Although its main focus is on thyroid nodules, the applications of US elastography for other thyroid diseases, such as diffuse thyroid diseases and thyroiditis, are also presented. Furthermore, unresolved questions and directions for future research are also discussed.

Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility

Thyroid disorders are common, affecting more than 10% of people in the US, and laboratory tests are integral in the management of these conditions. The repertoire of thyroid tests includes blood tests for thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine, thyroglobulin (Tg), thyroglobulin antibodies (Tg-Ab), thyroid peroxidase antibodies (TPO-Ab), TSH receptor antibodies (TRAb), and calcitonin. TSH and free thyroid hormone tests are frequently used to assess the functional status of the thyroid. TPO-Ab and TRAb tests are used to diagnose Hashimoto's thyroiditis and Graves' disease, respectively. Tg and calcitonin are important tumor markers used in the management of differentiated thyroid carcinoma and medullary thyroid carcinoma (MTC), respectively. Procalcitonin may replace calcitonin as a biomarker for MTC. Apart from understanding normal thyroid physiology, it is important to be familiar with the possible pitfalls and caveats in the use of these tests so that they can be interpreted properly and accurately. When results are discordant, clinicians and laboratorians should be mindful of possible assay interferences and/or the effects of concurrent medications. In addition, thyroid function may appear abnormal in the absence of actual thyroid dysfunction during pregnancy and in critical illness. Hence, it is important to consider the clinical context when interpreting results. This review aims to describe the above-mentioned blood tests used in the diagnosis and management of thyroid disorders, as well as the pitfalls in their interpretation. With due knowledge and care, clinicians and laboratorians will be able to fully appreciate the clinical utility of these important laboratory tests.

Tiroiditis y pancreatitis como presentación simultánea en una paciente con nefritis lúpica. Reporte de caso / Thyroiditis and pancreatitis as a simultaneous presentation in a patient with lupus nephritis. Case report

RESUMEN El lupus eritematoso sistémico se puede presentar con un amplio espectro de síntomas que en algunas ocasiones pueden enmascarar complicaciones graves asociadas a la misma enfermedad. Dentro de estas la pancreatitis es una causa poco común, y sin embargo de alta mortalidad, especialmente en pacientes con un tratamiento no oportuno. Reportamos el caso de una paciente que cursa con lupus eritematoso sistémico con compromiso renal y de sistema nervioso central, de reciente aparición, que se asocia a la aparición de pancreatitis y tiroiditis, presentando evolución satisfactoria con esquema terapéutico de ciclofosfamida y prednisolona.

ABSTRACT Systemic lupus erythematosus can present with a broad spectrum of symptoms that on some occasions may mask serious complications associated with the same disease. Within these, pancreatitis is an uncommon but high-mortality cause, especially in patients with non-oportune treatment. We report the case of a patient with systemic lupus eryt-hematosus with recent renal and central nervous system involvement that is associated with the onset of pancreatitis and thyroiditis. A satisfactory outcome was obtained with a cyclophosphamide and prednisolone therapeutic regimen.

Thyroid nodules with discordant results of ultrasonographic and fine-needle aspiration findings

As the detection of thyroid nodules increases, it is important to differentiate whether thyroid nodules are malignant or not. Ultrasonography-guided fine-needle aspiration cytology is the standard method to diagnose thyroid nodules. Ultrasonographic findings of thyroid nodules can predict the risk of malignancy, and fine-needle aspiration allows the examination of cytopathology of thyroid nodules. However, both are not perfect, with a certain degree of false negative or false positive results. Therefore, we can face thyroid nodules with discordant results of ultrasonographic and fine-needle aspiration findings. In the case of benign features on ultrasonography with malignant cytology, follicular thyroid cancer, follicular variant papillary thyroid cancer, cystic or degenerative changes of thyroid cancer, and thyroiditis are candidates for diagnosis. In contrast, for the nodules with ultrasonographic features of highly suspicious of malignancy but benign cytology, we can consider the possibility of thyroiditis, changes of benign nodule, and cystic changes of thyroid cancer. These various conditions may result in discordant results of ultrasonographic features and fine-needle aspiration cytology, which need special attention not to miss the diagnosis of malignant nodules.

A Case of Aggravation of Thyroid Goiter after Treatment with PD-1 Inhibitor for Breast Cancer in Patients with Underlying Hashimoto's Thyroiditis

Anti-programmed cell death-1 (PD-1) humanized monoclonal antibody inhibits PD-1 activity by binding to the PD-1 receptor on T-cells and blocking PD-1 ligands and induces immune tolerance of cancer cells. It has been widely used for various kinds of cancer treatment. However, many immune-related adverse events (irAEs) have been reported because it modulates our immune system. In this case study, we reported a case of 42-year-old woman with Hashimoto's thyroiditis who showed rapid aggravation of thyroid goiter and acute hyperventilation syndrome after treatment with PD-1 inhibitor as a neoadjuvant chemotherapy for breast cancer.

Recurrent Painless Thyroiditis in Patients with History of Postpartum Thyroiditis

It is well known that the long-term prognosis of postpartum thyroiditis (PPT) is excellent except recurrent PPT in subsequent pregnancies and risk of progression to permanent hypothyroidism in some patients. However, the prospective observation of PPT patients who have neither consecutive gestation nor any evidence of hypothyroidism were limited. We describe three patients who have history of PPT and showed repeated painless thyroiditis in the span of more than ten years. The clinical courses of repeated painless thyroiditis were the transient thyrotoxicosis, self-limited, and not related to pregnancy. Based on the clinical courses of our three patients, it is recommended to remember that transient painless thyroiditis could be repeated as a possible long-term course of the patients with history of PPT.

Prevalence of autoimmune thyroiditis in patients with type 1 diabetes: a long-term follow-up study

PURPOSE: Type 1 diabetes mellitus (DM) is associated with autoimmune diseases such as thyroiditis. Therefore, we aimed to investigate the prevalence of autoimmune thyroiditis in patients with type 1 DM. METHODS: A total of 102 patients who were diagnosed and followed up (mean age, 8.1±4.0 years) in Ajou University Hospital were enrolled in this study. All the patients were evaluated for beta cell autoimmunity, including insulin autoantibody, glutamic acid decarboxylase antibodies (GADA), and islet cell antibody. Moreover, autoantibodies to thyroid peroxidase and thyroglobulin were assessed at initial diagnosis and annually thereafter. RESULTS: The mean patient age (49 men and 53 women) was 19.2±4.8 years. The prevalence of at least one thyroid antibody was 30.4%. Patients with thyroid anti­bodies had a significantly higher frequency of GADA at the time of the diagnosis. Autoimmune thyroiditis was more prevalent in the older age group. GADA was a significant risk factor for development of thyroid autoantibodies after diagnosis of type 1 DM (odds ratio, 4.45; 95% confidence interval, 1.399–14.153). CONCLUSIONS: In patients with type 1 DM, the prevalence of autoimmune thyroiditis was higher than in the general population. Moreover, GADA positivity at diagnosis was associated with thyroid autoimmunity.

Utility of Quantitative Parameters from Single-Photon Emission Computed Tomography/Computed Tomography in Patients with Destructive Thyroiditis

OBJECTIVE: Quantitative parameters from Tc-99m pertechnetate single-photon emission computed tomography/computed tomography (SPECT/CT) are emerging as novel diagnostic markers for functional thyroid diseases. We intended to assess the utility of SPECT/CT parameters in patients with destructive thyroiditis. MATERIALS AND METHODS: Thirty-five destructive thyroiditis patients (7 males and 28 females; mean age, 47.3 ± 13.0 years) and 20 euthyroid patients (6 males and 14 females; mean age, 45.0 ± 14.8 years) who underwent Tc-99m pertechnetate quantitative SPECT/CT were retrospectively enrolled. Quantitative parameters from the SPECT/CT (%uptake, standardized uptake value [SUV], thyroid volume, and functional thyroid mass [SUVmean × thyroid volume]) and thyroid hormone levels were investigated to assess correlations and predict the prognosis for destructive thyroiditis. The occurrence of hypothyroidism was the outcome for prognosis. RESULTS: All the SPECT/CT quantitative parameters were significantly lower in the 35 destructive thyroiditis patients compared to the 20 euthyroid patients using the same SPECT/CT scanner and protocol (p < 0.001 for all parameters). T3 and free T4 did not correlate with any SPECT/CT parameters, but thyroid-stimulating hormone (TSH) significantly correlated with %uptake (p = 0.004), SUVmean (p < 0.001), SUVmax (p = 0.002), and functional thyroid mass (p < 0.001). Of the 35 destructive thyroiditis patients, 16 progressed to hypothyroidism. On univariate and multivariate analyses, only T3 levels were associated with the later occurrence of hypothyroidism (p = 0.002, exp(β) = 1.022, 95% confidence interval: 1.008 – 1.035). CONCLUSION: Novel quantitative SPECT/CT parameters could discriminate patients with destructive thyroiditis from euthyroid patients, suggesting the robustness of the quantitative SPECT/CT approach. However, disease progression of destructive thyroiditis could not be predicted using the parameters, as these only correlated with TSH, but not with T3, the sole predictor of the later occurrence of hypothyroidism.

Association Kikuchi disease with Hashimoto thyroiditis: a case report and literature review

Kikuchi-Fujimoto disease (KFD) is a benign and self-limited disease characterized by fever and lymphadenopathy. The etiology of KFD is unknown, but an autoimmune cause has been suggested. Hashimoto thyroiditis is the most common autoimmune thyroid disorder in children and is known to be associated with other autoimmune diseases. Only a few cases of Hashimoto thyroiditis associated with KFD have been documented. We report a case of a 16-year-old girl who was first diagnosed with KFD and developed Hashimoto thyroiditis 2 years and 6 months later during her follow-up period. Physicians of patients with KFD should consider the possibility of autoimmune diseases like Hashimoto’s thyroiditis.

Tiroiditis de Riedel, una entidad fácilmente confundible con carcinoma anaplásico tiroideo / Riedel's thyroiditis, an entity easily confused with anaplastic thyroid carcinoma

INTRODUCTION: Riedel´s thyroiditis is a thyroid inflammation with invasive fibrosis. CASE REPORT: Female 84 years old, studied by dysphagia to liquids and dysphonia, with cervical mass poorly demarcated and immobile. Computed Tomography (CT) (CT) showed tumor that diverted the trachea and esophagus compressed. Fine Needle Aspiration (FNA) obtained cells with atypia. Thyroidectomy was performed, appreciating a stony tumor which included the right recurrent laryngeal nerve. Given the high suspicion of thyroid malignancy tracheostomy it was performed. The pathology report as fibrosing Riedel thyroiditis. DISCUSSION: This is the less common type of chronic thyroiditis. Etiology is unknown. The normal thyroid parenchyma is replaced by fibrous connective tissue. Clinically usually a hard mass, fast growing, why is confused with thyroid carcinoma and Hashimoto's thyroiditis. It´ss more common in women and is usually bilateral. The CT or MRI (Magnetic Resonance Imaging) help assess the extent. Puncturing the mass could give us the diagnosis but is often difficult. Treatment to relieve symptoms or rule out malignancy is surgery. The prognosis is usually good. CONCLUSIONS: Riedel´s thyroiditis is an entity with histopathologic diagnosis essential

Atypical Thyroiditis Following Influenza B Infection

Viral infections are known to be a predisposing factor for subacute (De Quervain's) thyroiditis. In this report, we document a novel case of thyroiditis, with an atypical presentation, following an influenza B infection. A 13-year-old previously healthy female visited the outpatient clinic complaining of right neck pain. She had been diagnosed with an influenza B infection at a local clinic 3 weeks earlier. All laboratory tests were normal. A thyroid ultrasound showed an ill-defined hypoechoic mass (1.0×0.5×1.5 cm) in the right lower thyroid, and scintigraphy of the thyroid with Technetium-99m (99m-Tc) demonstrated the normal uptake of the radiotracer. Fine-needle aspiration from the nodule showed the presence of a few neutrophils. To the best of our knowledge, this is the first case of atypical thyroiditis associated with an influenza B infection described in the literature. Influenza B infection should be considered as a possible cause of atypical thyroiditis.

Sweet's Syndrome Associated with Graves' Disease

Sweet's syndrome, or acute febrile neutrophilic dermatosis, occurs in association with autoimmune diseases such as Hashimoto's thyroiditis but is rare in Graves' disease, in which all cases are induced by propylthiouracil (PTU). We report a case of Sweet's syndrome in a patient with Graves' disease treated with methimazole (MMI) during three weeks. A 34-year-old man presented with the acute onset of high fever, skin rashes on the whole body, arthralgia, and acroparesthesia. Laboratory results showed leukocytosis and elevated C-reactive protein. MMI first stopped and antibiotics and antihistamine therapy started, but his symptoms dramatically improved after oral prednisolone. Graves' disease has again been treated by MMI because of his aggravated ophthalmopathy. After one year of retreatment with MMI, there has been no recurrence of Sweet's syndrome, supporting that Sweet's syndrome in this case was not related to MMI exposure. To our knowledge, this is the first report of Sweet's syndrome associated with Graves' disease per se but not PTU or MMI use.

Surgical Treatment for Riedel's Thyroiditis: a Case Report

Riedel's thyroiditis is a rare fibrotic condition that results in the destruction of the thyroid and infiltration into surrounding tissues. The exact etiology is not yet clear, although systemic fibrosing disorder, a variant of Hashimoto's thyroiditis, a primary inflammatory disorder of the thyroid, and even a manifestation of end-stage subacute thyroiditis has been suggested. Although various treatments have been applied, no definitive treatment has yet been established. We report a case of Riedel's thyroiditis treated without complications using microscopic surgery. A 54-year-old man visited our clinic presenting with neck tightness and a left neck mass. A gun biopsy revealed a benign thyroid mass, although the radiologic findings showed a malignant thyroid tumor with invasion into the trachea and strap muscles. The patient underwent a left hemi-thyroidectomy and shaving of the trachea, esophagus and recurrent laryngeal nerve under microscopy. The final pathology revealed Riedel's thyroiditis combined with Hashimoto's thyroiditis. The patient had symptomatic relief without vocal fold paralysis and hypocalcemia. Surgical treatment using microscopic dissection can be considered to be one of treatment option for Riedel's thyroiditis.

Parry-Romberg Syndrome Associated with Hypothyroidism

PURPOSE: We report a case of Parry-Romberg syndrome associated with right enophthalmos, hypotropia, up-gaze limitation, en coup the sabre, morphea, and hypothyroidism. CASE SUMMARY: A 41-year-old woman presented with slowly progressive right enophthalmos that started 5 years previous. With a Hertel exophthalmometer, the right eye measured 10 mm, and the left eye 13 mm. Right enophthalmos and atrophy of subcutaneous tissues of right side orbit were observed. Axial scan of computerized tomography shows atrophy of right side orbital subcutaneous tissues without bony abnormality. At primary gaze, 4 prism diopter hypotropia was observed in the right eye. Up-gaze was limited in both eyes. Visual acuity was 1.0 in both eyes. No specific sign was found in her anterior segment. The patient had experienced right side alopecia 20 years prior and had undergone biopsy, which proved morphea. Linear en coup de sabre morphea was found on the right forehead and scalp. Hypothyroidism due to Hashimoto's thyroiditis was diagnosed based on a blood test, which also showed positive antinuclear antibody. Thus, the patient was diagnosed with Parry-Romberg syndrome associated with hypothyroidism. CONCLUSIONS: Clinicians need to consider the rare disease Parry-Romberg syndrome when a patient with ophthalmologic symptoms such as enopthlamos or eye movement disorders is accompanied by dermatologic symptoms such as linear en coup de sabre morphea or alopecia.

The effect of Korean traditional alternative medicine products on thyroid function level in post-total thyroidectomy patients: A pilot study

PURPOSE: Although many Koreans consume traditional alternative remedial products to alleviate symptoms of fatigue, there have been no studies on their effect on thyroid function levels in thyroidectomized patients on levothyroxine replacement. The aim of this study was to assess the effect of Korean traditional alternative remedies on thyroid function levels in post total thyroidectomy patients.METHODS: A retrospective review of medical records from a single tertiary referral center was performed on patients who received total thyroidectomy from 2010 to 2015 and became euthyroid postoperatively. Gender, age, body mass index, preoperative thyroid function test results, interval to first hypothyroidism occurrence, recurrence of hypothyroidism, number and types of alternative remedy were evaluated.RESULTS: Postoperative hypothyroidism occurred among 174 out of 917 patients (18.9%) and 100 (57.5%) of them had a history of alternative medication usage. The first episode of hypothyroidism occurred at median of 38.5 months after operation in the 100 patients. Six of the 100 patients received an increased dosage of levothyroxine due to severe hypothyroidism but the rest received the same dose and were requested not to consume alternative products. All patients recovered to euthyroid status afterwards. Thirty-three patients subsequently experienced recurrence even after being restricted from consuming alternative remedial products. Apart from thyroiditis on pathology reports (P=0.001), there were no variables significantly related to the recurrent hypothyroidism.CONCLUSION: This pilot study demonstrated the possible role of consumption patterns of traditional alternative remedial products in thyroidectomized patients under hormone supplement in restoring euthyroid status without levothyroxine increase.