Clinical Manifestation of Subacute Thyroiditis Triggered by SARS-CoV-2 Infection Can Be HLA-Dependent.

In the last two years, we have been struggling with the pandemic of SARS-CoV-2, the virus causing COVID-19. Several cases of subacute thyroiditis (SAT) have already been described as directly related to SARS-CoV-2 infection. The clinical course of SAT induced by SARS-CoV-2 can be entirely different from the classic SAT course, and one of the most important differences is a very rapid SAT onset observed in some patients, especially a phenomenon of the simultaneous presence of both diseases. The aim of this report is to compare HLA profile and clinical course of SAT in four patients, in whom SAT was considered as triggered by COVID-19, with special attention paid to the differences between a patient with rare simultaneous presence of SAT and COVID-19, and patients with longer time lag between the diseases. The unusual phenomenon of simultaneous occurrence of COVID-19 and SAT induced by SARS-CoV-2 infection can be HLA-dependent and related to the presence of homozygosity at HLA-B*35. Additionally, the clinical course of SAT triggered by COVID-19 can be HLA-related in regard to the risk of recurrence, and to a variety of other aspects, including severity of thyrotoxicosis.

Reversal of Abnormal CD4+ T Cell Metabolism Alleviates Thyroiditis by Deactivating the mTOR/HIF1a/Glycolysis Pathway.

Background: Hashimoto's thyroiditis (HT) is an autoimmune disease that features activation of thyroid antigen-specific helper T cells. HT patients have increased Th1 and Th17 T cell subsets. Glycolysis supports chronic activation of Th1 and Th17 T cells, but how this contributes to HT remains unknown. Methods: The metabolism of CD4+ T cells from 30 HT patients and 30 healthy controls was evaluated by determining the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR). Mice in a subacute thyroiditis (SAT) model were treated with 2DG, metformin, or combination. Metrics of mTOR/HIF-1α/HK2/glycolysis were measured by western blot and Seahorse assay methods. The severity of SAT was measured by flow cytometry and HE staining. Results: CD4+ T cells from HT patients had enhanced ECAR and OCR. Levels of Glut1, HK2, PKM2, and LDHA in cultured HT CD4+ T cells were elevated. The expression of HK2 and PKM2 in cultured SAT CD4+ T cells was elevated compared with the control group. Activation of the mTOR and HIF-1α pathways was significant in SAT mice, and expression of HIF-1α in the 2DG treated group was reduced. Treatment with 2DG and/or metformin significantly decreased the ratio of Th17 and Th1 T cells. Conclusions: Thyroiditis results in elevation of the mTOR/HIF-1α/HK2/glycolysis pathway in CD4+ T cells. The activation of this pathway is reduced by treatment with 2DG and metformin, which also reverted imbalances in CD4+ T cell differentiation.

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.

Subacute thyroiditis in a patient with psoriatic arthritis switched from secukinumab to adalimumab: a case report and literature review.

A 71-year-old Japanese female with psoriatic arthritis (PsA) was admitted for fever and neck pain. Her medication had been switched from secukinumab, an interleukin (IL)-17A inhibitor, to adalimumab, a tumour necrosis factor (TNF)-α inhibitor, due to secondary failure for PsA. She was diagnosed with subacute thyroiditis (SAT) on the basis of thyroid hormone levels and thyroid ultrasound findings. Her SAT symptoms improved with prednisolone administration (15 mg/day). Following the administration of ixekizumab, an IL-17A inhibitor, her PsA improved without SAT relapse. SAT mechanism associated with TNF inhibitors remains unknown, but cytokine imbalance may be involved.

Subacute thyroiditis as a presenting manifestation of COVID-19: a report of an exceedingly rare clinical entity.

The SARS-CoV-2 has wreaked havoc globally and has claimed innumerable lives all over the world. The symptoms of this disease may range from mild influenza-like symptoms to severe acute respiratory distress syndrome with high morbidity and mortality. With improved diagnostic techniques and better disease understanding, an increased number of cases are being reported with extrapulmonary manifestations of this disease ranging from renal and gastrointestinal to cardiac, hepatic, neurological and haematological dysfunction. Subacute thyroiditis is a self-limiting and painful thyroid gland inflammation most often secondary to viral infections. We report a case of subacute thyroiditis in a 58-year-old gentleman presenting with a painful swelling in the neck who was subsequently detected to be positive for SARS-CoV-2. We seek to highlight the broad clinical spectrum of the COVID-19 by reporting probably the first case of subacute thyroiditis possibly induced by SARS-CoV-2 infection from India.

Comparison of thyroglobulin and thyroid peroxidase antibodies measured by five different kits in autoimmune thyroid diseases.

It is generally believed that the detection of thyroid peroxidase antibodies (TPOAb) is superior to that of thyroglobulin antibodies (TgAb) for the diagnosis of Hashimoto's thyroiditis. However, limited data are available on the comparison of TgAb and TPOAb prevalence as a diagnostic measurement for Hashimoto's thyroiditis using sensitive immunoassays. We herein used five different current immunoassay kits (A-E) to compare the prevalence of TgAb and TPOAb in Hashimoto's thyroiditis (n = 70), Graves' disease (n = 70), painless thyroiditis (n = 50), and healthy control subjects (n = 100). In patients with Hashimoto's thyroiditis, positive TgAb was significantly more frequent than positive TPOAb in kits A-D (mean ± SD of the four kits: 98.6 ± 1.7 vs 81.4 ± 2.0%). In patients with Graves' disease, TgAb prevalence was almost equivalent to that of TPOAb in five kits. Patients with painless thyroiditis exhibited positive TgAb significantly more frequently than positive TPOAb in kits A-D (73.5 ± 4.1 vs 33.0 ± 3.4%). The prevalence of TgAb alone was significantly higher than that of TPOAb alone in both Hashimoto's thyroiditis and painless thyroiditis in kits A-D. In kit E, TgAb and TPOAb prevalence did not differ significantly for any disease, and TgAb distribution was different from other kits. In conclusion, the prevalence of TgAb was higher than that of TPOAb in patients with Hashimoto's thyroiditis and painless thyroiditis using commercially available kits. We suggest that TgAb immunoassay is the first choice of screening test for thyroid autoimmune abnormalities in Japan.

Lesson of the month 1: Subacute thyroiditis: a rare cause of fever of unknown origin.

Fever of unknown origin (FUO) is sometimes a diagnostic dilemma for clinicians. Endocrine causes reported in the literature include subacute thyroiditis, thyrotoxicosis, adrenal insufficiency and pheochromocytoma. Among these, subacute thyroiditis is often overlooked as it can occasionally lack typical symptoms. This case illustrates the fact that subacute thyroiditis should be considered as a possible cause of fever even if signs and symptoms of hyperthyroidism and thyroid tenderness are absent.

[De Quervain thyroiditis. Corner points of the diagnosis]. / A szubakut de Quervain-thyreoiditis. A kórismézés sarokpontjai négy eset kapcsán.

Inflammatory disorders of the thyroid gland are divided into three groups according to their duration (acute, subacute and chronic). De Quervain's thyroiditis (also termed giant cell or granulomatous thyroiditis) is a subacute inflammation of the thyroid, which accounts for 5% of thyroid disorders. The etiology is unknown, it usually appears two weeks after an upper viral respiratory infection. The clinical feature includes neck pain, which is aggravated during swallowing, and radiates to the ear. On palpation, the thyroid is exquisitely tender. The erythrocyte sedimentation rate is markedly elevated, the leukocyte count, C-reactive protein are normal or slightly elevated. The natural history of granulomatous thyroiditis involves four phases: the destructive inflammation results temporarily in hyperthyroidism followed by euthyroidism. After a transient hypothyroidism the disease becomes inactive and the thyroid function is normalised. Ultrasonographic findings are diffuse hypoechogenic structures, but nodules may also occur. The disease often remains unrecognised, or the first phase of the disease is diagnosed and treated as hyperthyroidism. The diagnosis can be confirmed by the presence of the thyroid autoantibodies, radioiodine uptake and fine needle aspiration cytology. There is no special treatment, non-steroid anti-inflammatory drugs or steroid should be given to relieve the pain. The aim of the authors is to shed light the key points of diagnosis and differential diagnosis by the presentation of four slightly different cases.

Time-lag between symptom onset and laboratory findings in patients with subacute thyroiditis.

OBJECTIVE: The objective of this study was to delineate the frequency of delayed diagnosis in cases of subacute thyroiditis (SAT) and intervals between onset of clinical symptoms and appearance of abnormal laboratory findings. METHODS: We reviewed the medical records of 27 patients (7 men and 20 women) with SAT who visited our hospital between 2007 and 2013. RESULTS: On presentation to the hospital, 5 of 27 SAT cases (18.5%) showed normal laboratory findings. Among these 5 cases, the mean interval between symptom onset and thyrotropin (TSH) suppression was 6.3 weeks, and the mean interval to elevation of fT4 was 6.7 weeks. The longest interval from symptom onset to appearance of an abnormal laboratory finding was 11 weeks. CONCLUSION: Sometimes time-lag exists between onset of clinical symptoms and the appearance of abnormal laboratory findings in patients with SAT. The possibility of this disease should not be excluded from the differential diagnoses for patients with clinical symptoms consistent with SAT but showing normal laboratory findings.

[Sub-acute thyroiditis in a patient on immunosuppressive treatment]. / Tiroidite subacuta in un paziente in trattamento immunosoppressivo.

Sub-acute thyroiditis or De Quervain's thyroiditis is a viral, inflammatory disease which causes the serum release of thyroidal hormones and hyperthyroidism. The pathogenesis of thyroid follicle damage is unclear because the exclusive viral action or a concomitant autoimmune component, determined by the lymphoid infiltrate remain to be assessed. We describe the case of a patient under immunosuppressive treatment, who developed sub-acute thyroiditis with hormone release and hyperthyroidism. The patient, while was under immunosuppressive treatment for kidney transplant, exhibited a clinical picture and hormonal profile of hyperthyroidism. Thyroid scintiscan exhibited an extremely low uptake. Fine-needle cytologic diagnosis was granulomatous sub-acute thyroiditis (De Quervain's thyroiditis). This case suggests the primary or even exclusive role of the viral infection in hormone release and hyperthyroidism in sub-acute thyroiditis, excluding an autoimmune component.

Return to play after thyroiditis in a football athlete.

A collegiate football athlete presented to his athletic trainer with acute chest pain during practice. Subsequent workup revealed that the patient was in the hyperthyroid state of subacute thyroiditis. There are no published case reports or existing guidelines to guide clinicians on making the decision of when it is safe to return to play after hyperthyroid crisis. Return to play in cases of subacute thyroiditis should include resolution of symptoms, trending of thyroid function tests to euthyroid state, consideration of cardiovascular factors, and a graded return to play.

Thyroid: an unusual hideout for sarcoidosis.

OBJECTIVE: To present a case of dysphagia secondary to a progressively increasing nontoxic multinodular goiter caused by sarcoidosis. METHODS: We summarize the clinical presentation and pertinent pathology in a patient with sarcoidosis involving the thyroid gland. A review of literature regarding this topic is also presented. RESULTS: A 54-year-old man was noted to have asymptomatic nontoxic thyromegaly. Biopsy of right thyroid nodule was benign while the biopsy from the isthmus nodule was nondiagnostic. He presented with acute onset of dysphagia two months later and the work-up for gastrointestinal causes was negative. Chest imaging showed left-sided lymphadenopathy, and biopsy of a lymph node showed sarcoidosis. Two years after the initial presentation a repeat biopsy of the isthmus nodule was again reported as nondiagnostic. Because he had persistent dysphagia, he underwent total thyroidectomy with resolution of dysphagia. Histopathological examination of the thyroid revealed non necrotizing granulomas consistent with sarcoidosis. CONCLUSION: This case brings to light this uncommon etiology of a nontoxic multinodular goiter. Involvement of the thyroid gland by sarcoidosis is very rare. It has been reported in 4.2 to 4.6% of patients with sarcoidosis. In patients with pulmonary or extrapulmonary sarcoidosis and associated thyromegaly, possible involvement of the thyroid by this process should be considered.

Subacute thyroiditis in a patient with juvenile idiopathic arthritis undergoing etanercept treatment: a case report and review of the literature.

We report on a 24-year-old woman with juvenile idiopathic arthritis (JIA) who developed subacute thyroiditis (SAT) while being treated with etanercept. She had suffered from JIA for 12 years, and her arthritis proved refractory to treatment with ibuprofen, prednisolone, and methotrexate. For the past 5 years, the patient had been treated successfully with etanercept at 25 mg/week. The patient more recently complained of high fever and lassitude, and presented with anterior neck swelling and tenderness. Palpation of the thyroid gland revealed it to be warm, erythematous, tender, and diffusely swollen. Laboratory tests revealed an increased erythrocyte sedimentation rate and C-reactive protein level. Thyroid function tests revealed decreased levels of thyrotropin-stimulating hormone, increased levels of free triiodothyronine, free thyroxine, and thyroglobulin, and an absence of thyroid autoantibodies. Sonography showed a diffusely reduced predominantly hypoechoic thyroid gland. Unenhanced computed tomography of the neck showed a homogeneously and mildly reduced thyroid gland. Serum titers of several viruses were not significant and so were considered unlikely to be the pathogens. On the basis of these presented findings, we diagnosed SAT, and etanercept therapy was withdrawn. The patient was treated with antibiotics and an increased prednisolone dose was initiated. She became symptom free and showed improved laboratory test results within 2 weeks, and was euthyroid by 3 months. Three months later, the patient developed hypothyroidism, although 6 months further on, the patient was asymptomatic on prednisolone, methotrexate, and levothyroxine therapy. In conclusion, whether SAT is a specific adverse event in this case in response to etanercept remains unclear. Nevertheless, the possibility of SAT should be considered in such patients on etanercept treatment.

Subacute thyroiditis manifesting as a thyroid mass, vocal cord paralysis, and hypercalcemia.

OBJECTIVE: To report a case of subacute thyroiditis manifesting as a thyroid mass, vocal cord paralysis, and hypercalcemia. METHODS: We describe the clinical, laboratory, and radiologic findings in a patient with an unusual clinical course of subacute thyroiditis. RESULTS: A 65-year-old woman presented with a hoarse voice and an enlarging tender mass in the right side of the neck. On admission, thyroid function was consistent with thyrotoxicosis from subacute thyroiditis. Laboratory studies showed a corrected serum calcium concentration of 11.4 mg/dL, intact parathyroid hormone of 125 pg/mL, 25-hydroxyvitamin D of 12 ng/mL, and creatinine of 1.8 mg/dL. Computed tomography of the neck without use of a contrast agent showed a heterogeneous mass in the right side of the neck in conjunction with deviation of the trachea from right to left but without invasion of the trachea. Thyroid ultrasonography disclosed a heterogeneous mass in the right thyroid lobe measuring 4.7 cm by 5.5 cm by 4.5 cm. Flexible laryngoscopy revealed right vocal cord paralysis. Treatment with a course of prednisone yielded normalization of the serum calcium level, improvement in her voice, and a decrease in size of the thyroid mass. Four months after initial presentation of the patient, thyroid hormone levels became normal, she was clinically euthyroid, and she had a full recovery of her voice. Her serum calcium concentration was normal (9.8 mg/dL) in association with a near-normal parathyroid hormone level of 90 pg/mL. The 25-hydroxyvitamin D and creatinine values were also normal. Repeated thyroid ultrasonography showed a smaller right thyroid lobe with a dominant nodule measuring 2.0 cm by 1.3 cm by 1.4 cm in the right upper pole. CONCLUSION: This case illustrates that subacute thyroiditis can have the unusual initial manifestations of a thyroid mass, vocal cord paralysis, and hypercalcemia. In similar patients, a trial of corticosteroid therapy may be warranted in an effort to improve clinical symptoms and thus avoid unnecessary surgical treatment.

[Atypical presentation of subacute thyroiditis]. / Atypische Präsentation einer Thyreoiditis de Quervain.

HISTORY AND ADMISSION FINDINGS: A 41-year-old woman had been treated with an antibiotic for a sore throat and a tender neck. Later, moderate hyperthyroidism developed and was treated with antithyroid drugs. She presented herself for further work-up when neck pain and malaise persisted. On palpation, the thyroid was tender and firm, but not enlarged. Signs and symptoms indicated moderate hyperthyroidism. INVESTIGATIONS: Laboratory findings included suppressed TSH, elevated thyroid hormones, and both elevated erythrocyte sedimentation rate and CRP. On ultrasound, the thyroid was found to be of normal size but severely hypoechoic. A thyroid scan showed low uptake of technetium. TREATMENT AND COURSE: The findings supported the diagnosis of subacute thyroiditis. Prednisolone treatment provided relief of pain within 2 days. The patient later developed hypothyroidism suggestive of Hashimoto's thyroiditis and required thyroxin supplementation.

Eponym : de Quervain thyroiditis.

de Quervain thyroiditis is a self-limited inflammatory disorder of the thyroid gland. It is an uncommon disease in adults and very rare in children. Fritz de Quervain, a Swiss surgeon, who was an authority on thyroid disease, described the unique pathology of this disease. Granulomatous changes with giant cells in thyroid tissue are the pathological findings. Viral infection in genetically predisposed individuals has been proposed as the pathogenesis of the disease. Clinical hallmarks for the diagnosis are painful thyroid enlargement, elevated erythrocyte sedimentation rate, and C-reactive protein as well as decreased uptake of the thyroid gland on thyroid scintigraphy. In addition, thyrotoxicosis is present in about 50% of cases in early phase of the disease. Serum thyroglobulin level is usually elevated. Only symptomatic treatment with analgesics is usually required for pain relief. Glucocorticoid therapy may be used in severely ill patients. de Quervain thyroiditis is generally completely resolved without complications in 6-12 months. However, permanent hypothyroidism and recurrent disease have been reported in some patients.

Fever of unknown origin: clinical overview of classic and current concepts.

Fever of unknown origin (FUO) refers to disorders that present with prolonged and perplexing fevers that are difficult to diagnose. This article presents a clinical overview of classic and current causes of FUOs, which may be due to infectious, rheumatic/inflammatory, neoplastic, or miscellaneous disorders. Comprehensive but nonfocused diagnostic testing is ineffective and should be avoided. The FUO workup should be directed by the key history, physical, and laboratory findings in clinical presentation. The clinical syndromic approach in the differential diagnosis of FUOs is emphasized, and the diagnostic importance and significance of fever patterns are discussed.

Long-term outcome of thyroid function after amiodarone-induced thyrotoxicosis, as compared to subacute thyroiditis.

BACKGROUND: Two main forms of amiodarone- induced thyrotoxicosis (AIT) exist: type 1 AIT is a condition of true hyperthyroidism developing in patients with pre-existing thyroid disorders, and usually requires thyroid ablative treatment. On the other hand, type 2 AIT is a form of destructive thyroiditis occurring in normal thyroids, the management of which usually consists in glucocorticoid treatment. AIM: To assess the long-term outcome of thyroid function in a prospective study of type 2 AIT patients, as compared to patients with De Quervain's subacute thyroiditis (SAT). PATIENTS AND METHODS: Sixty consecutive patients with type 2 AIT were evaluated during oral glucocorticoid treatment (oral prednisone 30 mg/day, gradually tapered and withdrawn over a 3-month period) and followed for 38+/-4 months (range 6-72) thereafter. Sixty consecutive patients with SAT, referred to our Institutes during the same period and treated with the same therapeutic schedule, served as controls. RESULTS: Type 2 AIT patients were older (p<0.0001) and showed a larger male preponderance (M:F 3.6:1 vs 0.5:1, p<0.0001) than SAT patients. Mean serum free T4 (FT4) and free T3 (FT3) concentrations at diagnosis were increased in both conditions, but higher in type 2 AIT than in SAT (FT4 47.6+/-18.8 and 29.6+/-8.3 pmol/l, respectively, p<0.0001; FT3 15.4+/-7.0 and 11.2+/-3.0 pmol/l, respectively, p<0.001). Correction of thyrotoxicosis was obtained in all patients in both groups, but restoration of euthyroidism occurred earlier in SAT than in type 2 AIT (p=0.006). Ten type 2 AIT patients (17%) and 3 SAT patients (5%, p<0.03) became permanently hypothyroid after glucocorticoid withdrawal and required levothyroxine replacement. CONCLUSIONS: A relevant proportion of type 2 AIT patients develop permanent hypothyroidism after correction of thyrotoxicosis. Thus, periodic surveillance of thyroid status is required after type 2 AIT.