Difficulties in investigating and treating fibrosing thyroid disorder (overlap of fibrosing variant of Hashimoto's thyroiditis and Riedel's thyroiditis).

A gentleman in his 90s presented with a slowly enlarging goitre over 18 months, causing manifestations of superior vena cava obstruction, dysphagia and hoarseness of voice. Investigations were suggestive of a fibrosing thyroid pathology. Surgical management was avoided due to high surgical risk. Treatment included prednisolone and tamoxifen with palliative management in the event of further medical deterioration. This article illustrates the difficulties in diagnosing and managing fibrosing thyroid diseases.

A Review of Thyroid Dysfunction Due to COVID-19.

Coronavirus disease 2019 (COVID-19) affects thyroid function. These changes are due to the direct impact of the virus on thyroid cells via angiotensin-converting-enzyme 2 (ACE2) receptors, inflammatory reaction, apoptosis in thyroid follicular cells, suppression of hypothalamus-pituitarythyroid axis, an increase in activity of adrenocortical axis, and excess cortisol release due to cytokine storm of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Euthyroid sick syndrome (ESS), thyroiditis, clinical and subclinical hypothyroidism, central hypothyroidism, exacerbation of underlying autoimmune thyroid disease, and clinical and subclinical hyperthyroidism can be associated with coronavirus. Adjuvants in coronavirus vaccines induce autoimmune/inflammatory syndrome known as vaccine adjuvants (ASIA) syndrome. Thyroiditis and Graves' disease have been reported to be associated with ASIA syndrome after some coronavirus vaccinations. Some coronavirus medications, such as hydroxychloroquine, monoclonal antibodies, lopinavir/ritonavir, remdesivir, naproxen, anticoagulants, and glucocorticoids can also affect thyroid tests, and correct diagnosis of thyroid disorders will be more difficult. Changes in thyroid tests may be one of the most important manifestations of COVID-19. These changes can be confusing for clinicians and can lead to inappropriate diagnoses and decisions. Prospective studies should be conducted in the future to increase epidemiological and clinical data and optimize the management of thyroid dysfunctions in patients with COVID-19.

Atypical Clinical Courses of Graves' Disease Confound Differential Diagnosis of Hyperthyroidism.

BACKGROUND: This study examined the appropriateness of the current paradigm for differential diagnosis of painless thyroiditis and Graves' disease (GD) in patients with thyrotoxicosis. METHODS: We retrospectively evaluated the clinical course of 343 consecutive patients with hyperthyroidism diagnosed by Tc-99m pertechnetate thyroid uptake (TcTU) testing at our hospital from January 2011 to December 2017. RESULTS: Of the 263 patients with normal or high TcTU levels (≥1.0%), 255 (97%) had unequivocal GD and 5 had spontaneous remission GD or atypical GD. Of the 10 patients with low TcTU levels (<1.0% and ≥0.5%), 7 had GD, while others had subclinical GD, spontaneous remission GD with later relapse, and painless thyroiditis. Of those with very low TcTU levels (<0.5%), most had thyroiditis (painless thyroiditis, 33/67 [49%]; subacute thyroiditis, 29/67 [43%]), and some were positive for anti-TSH receptor antibodies. CONCLUSION: Given that atypical GD may confound the diagnosis of thyrotoxicosis, it is essential to follow the patient as a tentative diagnosis, whatever the diagnosis. This is the first report clearly demonstrating that so far there is no gold standard for the diagnosis of GD. It is therefore urgent to establish a consensus on the definition of GD so that the specificity and sensitivity of future diagnostic tests can be determined.

Autoimmune Thyroid Diseases.

Autoimmune thyroid diseases (AITDs) include a wide spectrum of thyroid diseases affecting more commonly women than men. The most frequent forms are Graves' Disease (GD) and Hashimoto's thyroiditis / Autoimmune Thyroiditis (AIT), but there are also other immunogenic destructive forms of thyroiditis, that is, silent and postpartum thyroiditis. In the last decade, AITDs and other inflammatory thyroid diseases related to anti-tumor molecular drugs are more frequently seen due to the widespread use of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICPIs). Autoimmune thyroiditis related to SARS-CoV-2 infection has been a novel entity in recent years. Graves' Disease and AIT may shift from hyperthyroidism to hypothyroidism, which may complicate the differential diagnosis and further treatment strategy. Moreover, all AITDs may manifest with thyrotoxicosis (a clinical condition marked with high serum levels of thyroid hormones) which has to be distinguished from hyperthyroidism (increased thyroid hormone production and secretion as a result of hyperfunctioning thyroid gland) due to different therapeutic approaches. Nuclear medicine techniques, such as radioiodine uptake (RAIU) and thyroid scintigraphy, using 99mTc- pertechnetate (Na[99mTc]TcO4) or 123-Iodine (Na[123I]I), have a crucial role in the differential diagnosis. Measurement of thyroid antibodies, e.g. thyroid peroxidase antibodies (TPO) and thyrotropin receptor antibodies (TRAb), as well as thyroid ultrasound, are complementary methods in the evaluation of thyroid disorders.

IgG4-related sclerosing thyroiditis (Riedel-Struma): a review of clinicopathological features and management.

We present a thorough review of the literature on Riedel thyroiditis (RT) with emphasis on aetiology, diagnosis and management, using the PubMed, Sinomed, and China National Knowledge Infrastructure databases. Although the exact aetiology of RT remains obscure, the histopathological features are consistent with a localized form of IgG4-related systemic disease (IgG4-RSD). Nevertheless, IgG4-RSD as a systemic fibroinflammatory disorder per se rarely affects the thyroid in the context of multiorgan manifestations. The initial diagnosis of RT is based on clinical history and imaging, but confirmation by histopathological examination is mandatory. In contrast to the historical surgical approach, glucocorticosteroid therapy is currently considered first line therapy, in line with the RT currently being viewed as a manifestation of, or analogous to, IgG4-RSD. For disease relapse, immunomodulatory agents (azathioprine, methotrexate, rituximab) can be used.

Goiter and Abdominal Mass: A Rare Presentation of Riedel's Thyroiditis.

Riedel's thyroiditis (RT) is a rare inflammatory autoimmune disease, often associated with various forms of systemic fibrosis such as sclerosing mesenteritis (SM). A woman in her late 30s presented with a diffusely enlarged firm goiter and a mesenteric mass complicated by biliary obstruction and hydronephrosis. Labs and thyroid ultrasound were consistent with autoimmune thyroiditis. Abdominal imaging demonstrated a mesenteric mass that encased mesenteric vessels and ureter. Flow cytometry and infectious workup were negative. Both thyroid and mesenteric biopsies revealed dense fibrosis with patchy lymphoplasmacytic aggregates, no evidence of carcinoma, lymphoma, or IgG4-related disease, which confirmed diagnoses of RT and SM. She improved clinically with steroids. The coincidental timing of thyroid enlargement and the mesenteric mass, and the similarity in histology suggest an association between RT and SM. Overall, the case highlights the challenges in diagnosing RT given its rarity and emphasises the importance of early treatment to prevent systemic involvement.

A Rare Case of Painless Destructive Thyroiditis Resulting in Thyroid Storm.

Thyroid storm is a life-threatening clinical condition that is usually triggered by untreated or interrupted treatment of Graves' disease, leading to the sudden onset of severe thyrotoxicosis, which requires an immediate diagnosis and treatment based on diagnostic criteria. Cases of thyroid storm caused by painless/painless subacute thyroiditis are very rare. We herein report an 85-year-old man with features of severe thyrotoxicosis caused by painless/painless subacute thyroiditis who had no uptake of 99mTcO4 and was negative for thyroid-stimulating hormone receptor antibodies. In thyroid storm patients in whom the findings are inconsistent with Graves' disease, careful follow-up and management are necessary, assuming the possibility of painless or painless subacute thyroiditis.

Takotsubo cardiomyopathy with left ventricle thrombus caused by subacute thyroiditis.

We report a rare case of takotsubo cardiomyopathy caused by subacute thyroiditis in a man in his 50s. He went to the doctor with complaints of loss of appetite, diarrhoea, chills and general malaise. He had consciousness disturbance, thyrotoxicosis and thyroid-stimulating hormone (TSH) suppression. Thyroglobulin and C reactive protein levels in the blood were elevated, but TSH receptor antibody, thyroid-stimulating antibody, antithyroglobulin antibody and antithyroid peroxidase antibody were not. We began treatment with prednisolone and propranolol after he was diagnosed with thyroid storm caused by subacute thyroiditis. The ECG revealed inverted T waves on the fifth day after admission. He was newly diagnosed with takotsubo cardiomyopathy on the day. A large thrombus was detected in the left ventricle, requiring anticoagulation therapy. Thus, even if there are no findings of takotsubo cardiomyopathy or thrombus at the onset of thyroid storm, appropriate monitoring is required because they can develop during the treatment course.

Covid-induced thyroiditis.

Thyroiditis is one of the manifestations of novel Covid-19 virus. Thyroid function test (TFTs) shows typical features of hyperthyroidism. Inflammatory markers and thyroid scan give clue to the diagnosis. This report is about a 39-year-old female who presented with signs and symptoms of thyrotoxicosis along with pain in the neck, odynophagia, and intermittent fever after recovering from Covid-19 a few weeks back. She had no significant history of past medical or endocrine disease. TFTs revealed high T3 and T4 and low TSH. Thyroid scan revealed decrease uptake and ESR was 115. She was started on NSAID, steroids, and beta blocker. Four weeks later, she reverted with the resolution of symptoms and normal TFTs.

Painless thyroiditis mimicking relapse of hyperthyroidism during or after potassium iodide or thionamide therapy for Graves' disease resulting in remission.

The diagnosis of painless thyroiditis (PT) during antithyroid drug (ATD) treatment of Graves' disease (GD) is difficult. We evaluated the thyroidal radioactive iodine uptake (RAIU) in 100 patients with relapsed thyrotoxicosis during or after careful ATD treatment. The RAIU was <5%/5 h in 35 patients (35%) (Group A - PT), 5%-15%/5 h in 6 patients (6%) (Group B - indefinite) and >15%/5 h in 59 patients (59%) (Group C - relapsed GD [rGD]). TSH receptor antibody (TBII) was positive in 4 (11.4%), 3 (50.0%) and 39 (only 66.1%) patients in Groups A, B and C, respectively. In Group A, the serum fT4 level spontaneously normalized after 35 (26-56) days, sometimes followed by transient hypothyroidism, confirming the diagnosis of PT. Nineteen (54.3%) had been treated with potassium iodide, and PT frequently occurred ironically when the ATD dosage was reduced. PT repeatedly occurred in nine patients. All went into remission smoothly or developed hypothyroidism, except one patient with strongly positive TBII who developed rGD after the resolution of PT (PT on GD). In 10 (50%) of 20 patients with negative TBII despite rGD in Group C, TBII became positive afterwards. In conclusion, it is important to recognize that PT can occur in the clinical course of GD, resulting in frequent remission despite relapse of PT. The thyroid function reflects the balance between the stimulating TBII activity and the responsiveness of the thyroid tissue (sometimes unresponsive and other times autostimulated). The RAIU is still a valuable tool in cases of ambiguous thyrotoxicosis.

Painless thyroiditis incidentally diagnosed following SARS-CoV-2 infection.

A euthyroid woman in her 50s with papillary thyroid cancer and primary hyperparathyroidism was referred to our hospital for surgery. Her surgery was scheduled for 4 months later but was postponed because she was diagnosed with COVID-19. Five months after the first visit, she was admitted to our hospital to undergo the planned thyroid lobectomy and parathyroidectomy. Her blood tests on admission showed thyrotoxicosis, with negative thyroid-stimulating hormone receptor and thyroid-stimulating antibody. Notably, her anti-thyroglobulin antibody and anti-thyroid peroxidase antibody, which were originally negative, became positive after SARS-CoV-2 infection. She was diagnosed with painless thyroiditis. Her general condition and vital signs were stable, and the surgery was cautiously performed. Histopathological examination of the resected thyroid revealed papillary thyroid carcinoma, and the findings were consistent with painless thyroiditis. Her postoperative course was uneventful, and her thyroid function improved 2 weeks after the operation.

Lessons of the month 1: A diagnostic dilemma: thyroid abscess or subacute thyroiditis?

Thyroid abscess is rare but potentially fatal, whereas subclinical thyroiditis is a self-limiting condition that is more commonly seen. The clinical features of both diseases can be overlapping but the treatment approach differs. We report a case of a painful left thyroid nodule not responding to conventional therapy for thyroiditis or thyroid abscess.

Prediction model of Graves' disease in general clinical practice based on complete blood count and biochemistry profile.

Although untreated Graves' disease (GD) is associated with a higher risk of cardiac complications and mortality, there is no well-established way to predict the onset of thyrotoxicosis in clinical practice. The aim of this study was to identify important variables that will make it possible to predict GD and thyrotoxicosis (GD + painless thyroiditis (PT)) by using a machine-learning-based model based on complete blood count and standard biochemistry profile data. We identified 19,335 newly diagnosed GD patients, 3,267 PT patients, and 4,159 subjects without any thyroid disease. We built a GD prediction model based on information obtained from subjects regarding sex, age, a complete blood count, and a standard biochemistry profile. We built the model in the training set and evaluated the performance of the model in the test set by using the artificial intelligence software Prediction One. Our machine learning-based model showed high discriminative ability to predict GD in the test set (area under the curve [AUC] 0.99). The main contributing factors to predict GD included age and serum creatinine, total cholesterol, alkaline phosphatase, and total protein levels. We still found high discriminative ability even when we restricted the variables to these five most contributory factors in our prediction model (AUC 0.97) built by using artificial intelligence software showed high GD prediction ability based on information regarding only five factors.

Sub-Acute Thyroiditis presenting as pyrexia of unknown origin: A rare case with literature review.

Pyrexia of unknown origin (PUO) is a challenging entity in medical practice from a diagnostic point of view. Sub-Acute Thyroiditis (SAT), that is an inflammatory condition of thyroid, self-limiting and easily treatable, is a very rare cause for PUO with a few published cases and unfortunately not considered in routine for the differential diagnosis (DD) of PUO. Usually, it presents with mild thyrotoxicosis signs and symptoms, painful goiter, and rarely with cervical Lymph adenopathy. Thyroid antibodies might be negative, but inflammatory markers are usually raised. Anti-inflammatory drugs (NSAID) and steroids are a simple but very effective treatment. We present our experience for diagnosing and treating a female patient presenting with PUO. She was diagnosed as a case of sub-acute Thyroiditis on nuclear thyroid scan, High resolution ultrasound (HR-USG) of Thyroid and radioimmunoassay (RIA) for thyroid hormones and thyroid antibodies. The Patient was successfully treated with NSAIDs and steroids. The consent of the patient was taken to publish her case.

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.

Serum diiodotyrosine - a biomarker to differentiate destructive thyroiditis from Graves' disease.

OBJECTIVE: Conventional diagnostic methods are limited in their ability to differentiate destructive thyroiditis from Graves' disease. We hypothesised that serum diiodotyrosine (DIT) and monoiodotyrosine (MIT) levels could be biomarkers for differentiating destructive thyroiditis from Graves' disease. DESIGN: Patients with destructive thyroiditis (n = 13) and Graves' disease (n = 22) were enrolled in this cross-sectional study. METHODS: We assayed the serum DIT and MIT levels using liquid chromatography-tandem mass spectrometry. A receiver operating characteristic (ROC) curve analysis was used to determine the sensitivity and specificity of the serum DIT and MIT levels as biomarkers for differentiating destructive thyroiditis from Graves' disease. RESULTS: The serum DIT and MIT levels were significantly higher in patients with destructive thyroiditis than in those with Graves' disease. The ROC curve analysis showed that the serum DIT levels (≥359.9 pg/mL) differentiated destructive thyroiditis from Graves' disease, significantly, with 100.0% sensitivity and 95.5% specificity (P < 0.001). The diagnostic accuracy of the serum MIT levels (≥119.4 pg/mL) was not as high as that of the serum DIT levels (sensitivity, 84.6%; specificity, 77.3%; P = 0.001). CONCLUSIONS: The serum DIT levels may serve as a novel diagnostic biomarker for differentiating destructive thyroiditis from Graves' disease.