Elevated Thyroid-stimulating Immunoglobulins Research Articles

Elevated serum thyroid stimulating immunoglobulin linked to failure of first-line intravenous methylprednisolone monotherapy in moderate-to-severe thyroid eye disease.

To assess factors associated with failure of intravenous methylprednisolone (IVMP) monotherapy as the first-line treatment for thyroid eye disease (TED) and to identify patients who might benefit from supplementing mycophenolate mofetil (MMF) to IVMP. Data for all patients with TED treated with IVMP according to the EUGOGO protocol in our center between 2016-2021 were retrospectively analysed. Forty-seven patients (mean age 51.32 ± 14 years, 27 females) were enrolled. The mean time from first reported symptoms to first IVMP treatment was 12.1 ± 5.59 months (range 0-120). The mean clinical activity score (CAS) before treatment and at a mean of 5 and 12.2 weeks after treatment initiation was 6.00, 2.96, and 1.81, respectively (P < 0.01). Twenty-one patients (44.68%) were recommended second-line treatment: nine due to no response or worsening of CAS, six due to partial response, four with good response but early relapse after completion of treatment, and one due to late relapse. Eighteen of those 21 patients received second-line treatment which included rituximab (n = 7), MMF (n = 6), a second course of IVMP (n = 4), and tocilizumab (n = 1). Serum thyroid-stimulating immunoglobulin (TSI) levels were higher in patients who received second-line treatment compared with patients who responded well to first-line IVMP monotherapy at presentation (2135% vs 1159%, P = 0.05) and after completion of first-line treatment (2201% vs. 986%, P = 0.043). TED patients requiring second-line treatment after failed IVMP monotherapy had higher baseline and post-first-line treatment serum TSI levels. Those with elevated TSI may benefit from dual therapy (IVMP and MMF) and require closer monitoring.

FRI486 Overactive Thyroid And Overactive Mind - An Intervened Relationship

Abstract Disclosure: S. Bilichodu Rangappa: None. S. Avula: None. Z.A. Anderson: None. A. Kumar: None. Introduction: Traditionally, psychiatric symptoms were thought to be common manifestation of hypothyroidism. However, in the recent times the trend has changed. Various studies have shown a strong association of hyperthyroidism and psychosis. Thyrotoxicosis is associated with various psychiatric symptoms such as anxiety, restlessness, emotional liability, depression, mania, and rarely acute psychosis. Association between thyroid and mental health is a long-known entity but poorly understood pathophysiology. Here we present a case of graves disease presenting as acute psychosis as initial presentation. Clinical Case: A 45-year-old male with no significant past medical history was brought to emergency department (ED) by police after he was found to be walking in front of a shopping mall and was severely agitated. On arrival to ED, he was found to be very restless, irritable, and aggressive. Patient was found to have persecutory delusions and auditory hallucinations. His blood pressure was elevated, and he had tachycardia. He was given Haloperidol to calm down. Patient was evaluated with blood work and urine toxicology. Blood work up showed thyroid stimulating hormone (TSH) of &amp;lt;0.01m IU/L, Free T4 of 4 ng/dl and Total T3 of 380 ng/dl. Patient was started on Methimazole and propranolol. On further work up for thyrotoxicosis there was elevated thyroid stimulating immunoglobulin (TSI) which was consistent with Grave’s disease. Ultrasound thyroid revealed diffuse enlarged thyroid with increased vascularity. Once the patient was stable, he was further interviewed, he gave a history of palpitations, increased anxiety, and weight loss for two months, but he didn’t seek any medical attention. By the time of discharge, he symptomatically improved and his Free T4 and total T3 trended down. Patient was discharged on methimazole 10 mg daily along with propranolol. Conclusion: Graves’s disease can mimic psychosis. Psychosis may develop in the wake of thyroid hormone excess. Future research is warranted to find out the relation between psychotic disorders and excess thyroid hormone and the pathological process involved. It also helps in having clear treatment guidelines which will reduce the morbidity and improves the quality of life. Identifying somatic causes for psychiatric issues will help in treating them and might lead to complete recovery and not needing any further psychiatric medications. Presentation: Friday, June 16, 2023

SAT462 TSI Versus TRAb In The Diagnosis Of Grave’s Disease

Abstract Disclosure: K. Ibrahim: None. K. Raju: None. M. Morkos: None. Objective: Improvement in the thyroid antibody titers can help in predicting the remission of Graves’ disease. We aimed to assess the level of elevation of the antibody titers, thyroid stimulating immunoglobulin (TSI) and thyroid receptor antibody (TRAb) in patients with Grave’s disease. Research and Design Methods: This is a retrospective cross-sectional study of patients diagnosed with Graves’ disease at an academic outpatient endocrinology clinic from August 2019 to November 2022. TSI and TRAb were measured synchronously during the initial assessment of the patients, titers were compared against the upper limit of normal to assess their level of elevation. TSI was measured using Semi-Quantitative Chemiluminescent Immunoassay and TRAb using Quantitative Electrochemiluminescent Immunoassay. SPSS® (version 28) was used for statistical analysis, descriptive statistics were utilized and paired-sample t-test was used to compare TSI And TRAb ratios. Results: We identified 41 patients who presented for initial assessment of Graves’ disease, 31 (75.6%) were female, 23 (56.1%) Caucasian, and 16 (39.0%) African American. Mean age (± standard deviation) 46.3 ± 14.2 years. Mean TSI 8.3 ± 15.9 IU/L (ref &amp;lt;0.55), TSI ratio of elevation above the upper limit of normal was 11.1 ± 15.3, Mean TRAb 8.9 ± 9.4 (ref ≤1.75), TRAb ratio of elevation above the upper limit of normal was 5.1 ± 5.4. The correlation coefficient for both TSI and TRAb ratios was 0.92 (p &amp;lt;0.001). One patient had a normal TSI but elevated TRAb level and two patients had a normal TRAb level but elevated TSI levels. Conclusion: TSI was more highly elevated above its normal range than TRAb. TSI can be a reasonable initial antibody test for patients with Graves’ disease to establish a baseline. Presentation: Saturday, June 17, 2023

Code Pseudo Stroke - A Case of Hypokalaemic Periodic Paralysis Mimicking Stroke.

Hypokalaemic periodic paralysis is an acute flaccid paralysis secondary to hypokalaemia, triggered by hyperthyroidism, environmental elements such as a high carbohydrate intake or rest after intense exercise, and an underlying genetic component with mutations in the muscle ion channels.The pursuit of code stroke protocol in the in-patient setting must bear in mind reversible but potentially fatal and disabling alternative diagnoses such as stroke mimics including hypokalaemic periodic paralysis.Stroke mimics defined as acute onset neurological deficits that are not related to vascular cause are a true challenge, multiple scales have been created to distinguish them from an actual stroke, such as the Recognition of Stroke in the Emergency Room (ROSIER) scale.

PSAT348 Falsely Elevated TSI Antibody Without Causing Hyperthyroidism, in a Hypothyroid Patient

Abstract Introduction Hashimoto's thyroiditis and Graves’ disease are the most common causes for Hypothyroidism and Hyperthyroidism respectively. There are case reports of co-existence of these two disorders in the same patient (1) which causes an alternating clinical course of both hypothyroidism and hyperthyroidism. The Graves’ disease specific Thyroid Stimulating Immunoglobulin (TSI) antibody is reported to have a very high sensitivity and specificity. However, the presence of TSI antibody in a long-standing hypothyroid patient without developing hyperthyroidism, is of extreme rare occurrence. Case Description Our patient is a 58-year-old Caucasian female who has a history of hypothyroidism that was diagnosed in 1990. She was initiated on levothyroxine and had maintained a stable dose of 100 mcg daily for many years. During the initial visit at our endocrinology clinic in December 2020, the patient's labs were consistent with iatrogenic thyrotoxicosis due to a low TSH 0.233 (0.30-4.00 uIU/ml), normal Free T4 1.33 (0.80-1.80 ng/dl) and normal Free T3 2.28 (2.0-4.40 pg/ml). TPO antibody was negative at 11 (0-34 IU/mL). The levothyroxine dose was reduced to 88 mcg daily, but patient did not obtain follow-up labs for many months. In August 2021, the TSH was noted to be normal at 2.29. Patient was also diagnosed with multinodular goiter with the presence bilateral sub centimeter thyroid nodules which had remained stable over the years. However, thyroid ultrasound in December 2020 showed a 1.8 cm left mid to lower pole nodule that was biopsied and reported to be Bethesda category III with benign Afirma Genomic sequencing classifier. Subsequently, patient reported experiencing swelling and pain of bilateral fingers and underwent evaluation by rheumatologist who ordered a panel of blood tests to assess for autoimmune conditions. Interestingly, thyroid antibodies were also assessed, and it came back remarkable for elevated the Graves’ disease specific TSI antibody level 221% (&amp;lt; 140%) and elevated anti-thyroglobulin (TG) antibody 40.6 (&amp;lt;4.1). Patient's medication list was verified, and she was not on any high-dose biotin supplementation, and she denied experiencing any hyperthyroid symptoms. The corresponding thyroid labs were unremarkable with normal TSH 2.2, normal free T4 1.33 and normal free T3 2.28. Patient was reassured about the normal thyroid labs and advised that her symptoms are not thyroid related. The repeat TSH level continues to remain normal and was 2.18 in December 2021. Conclusion Although the presence of TSI antibody has a high positive predictive value for diagnosing Graves’ disease, a falsely elevated TSI antibody, can rarely occur without causing any clinical consequences. Reference (1) Alvin Mathew A, Papaly R, et al. Elevated Graves’ Disease-Specific Thyroid-Stimulating Immunoglobulin and Thyroid Stimulating Hormone Receptor Antibody in a Patient With Subacute Thyroiditis. Cureus 13(11): e19448. doi: 10.7759/cureus.19448 Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

A Rare Case of Aggressive Ectopic Thyroid Cancer in a Patient With Graves Disease

Background: Ectopic thyroid tissue is a rare entity with a prevalence of 1 per 300,000 persons. Malignancy in ectopic thyroid tissue is reported in <1% of these cases.[1] We report a case of aggressive papillary carcinoma in ectopic thyroid gland in a patient with Graves’ disease. Case: A 65-year old woman was incidentally found to have a 3.1 cm mass with coarse calcifications in the superior mediastinum on CT scan of chest. Ultrasound confirmed the presence of hypoechoic mass which was separate from thyroid. Additionally, a 0.5cm TI-Rad 4 left thyroid lobe nodule was found. FNA of the mediastinal mass was suspicious for follicular thyroid neoplasm. Thyramir testing was positive for BRAF V600E and TERT c-124C>T mutations. Thyroid function tests showed frank hyperthyroidism and elevated thyroid stimulating immunoglobulins. Thyroid uptake and scan showed diffuse uptake of 67% at 24 hours.The patient underwent simultaneous excision of mediastinal mass and total thyroidectomy. The pathology of mediastinal mass showed papillary thyroid cancer with tall and sclerosis features with one involved lymph node. The pathology of thyroid gland did not show any malignancy. She was treated with 100 mCi I-131. Post treatment Whole Body Nuclear Scan after treatment revealed metastatic disease in left lower lung area.Discussion: Ectopic thyroid gland is usually found anywhere between forman caecum and mediastinum. It is rare to find ectopic thyroid tissue in the presence of eutopic thyroid gland which can create a diagnostic dilemma. Only a very few case reports of thyroid cancer arising from ectopic thyroid tissue have been reported. Our case is unique as the eutopic thyroid gland had Graves’ disease with no malignancy but the ectopic thyroid tissue developed aggressive papillary thyroid cancer. There are no specific guidelines for the management of carcinoma in ectopic thyroid glands, possibly due to the rarity of the condition. Our case has a clear metastasis to the lungs. However, it is important to differentiate ectopic thyroid tissue with carcinoma from thyroid cancer metastasis which can be difficult at times. Without specific guidelines for the management of cancer in ectopic thyroids, an individualised approach can be taken using the same therapeutic principals used in the management of eutopic thyroid cancer. Additionally, a finding of a normal thyroid gland or a benign condition in the thyroid gland should not exclude the diagnosis of malignancy in ectopic thyroid tissues.1) Vázquez, Oscar R., et al. “Ectopic papillary thyroid cancer with distant metastasis.” Case reports in endocrinology 2018 (2018).

SAT-683 A Case of Autoimmune Polyglandular Syndrome Type 2 and Guillain-Barré Syndrome

Background: Autoimmune polyglandular syndrome type 2 (APS2) is defined by the occurrence of two or more autoimmune diseases, with Addison’s disease being most prevalent, and autoimmune thyroid disease and type 1 diabetes mellitus also being common. Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculopathy that is also autoimmune in nature, resulting in ascending muscle weakness or paralysis.Clinical Case: A 49 year old female with past medical history of vitiligo, subclinical hyperthyroidism, and Guillain-Barré syndrome (GBS) presented to our institution with fatigue, nausea, vomiting, polyuria, and polydipsia. She had no history of diabetes. Her history was also significant for GBS, diagnosed 5 months prior to her current admission. She was treated with intravenous immunoglobulin (IVIG) and had partial improvement of motor impairment. On exam, she was noted to have dry mucous membranes, epigastric tenderness, and patches of hyopigmented skin. Laboratory studies were consistent with diabetic ketoacidosis, and she was admitted to the ICU for management.Labs from 5 months prior were significant for a HbA1c of 6.4% (4.0-5.6%), TSH <0.002 mIU/L (0.350-4.7 mIU/L), total T3 154.9 ng/dL (79-149 ng/dL), and free T4 1.7 ng/dL (0.7-1.9 ng/dL), and elevated thyroid stimulating immunoglobulin.During the current admission, HbA1c had risen to 13.6%, C-Peptide 0.6 ng/mL (1.1-4.4 ng/mL) and GAD-65 antibody >250 IU/mL (<5 IU/mL), consistent with a diagnosis of late-onset type 1 diabetes. Repeat thyroid function tests (TSH <0.002 mIU/L, total T3 74 ng/dL, and free T4 1.2 ng/dL), were consistent with subclinical hyperthyroidism. A 21-hydoxylase antibody level was 13 U/mL (<1 U/mL), but cortisol rose appropriately in response to cosyntropin. Based on the patient’s constellation of vitiligo, autoimmune thyroid disease, type 1 diabetes, and elevated 21-hydroxylase antibodies, she was diagnosed with APS2.Conclusion: We present an unusual case of a patient with APS2, who was diagnosed with type 1 diabetes 5 months after developing GBS and being treated with IVIG. Prior reports demonstrate an association between GBS and other autoimmune diseases, including one case report of GBS in a patient with APS2. HLA DR3 has been associated with APS2, type 1 diabetes, Addison’s disease and Grave’s disease. Its association with GBS is less clear, although HLA DR3 was increased in one Mexican cohort with GBS. This case report adds to the literature suggesting an association with GBS and other autoimmune diseases, specifically, with APS2.

Massive Thymic Hyperplasia Secondary to Graves Disease

Graves disease (GD) has a well-known association with thymic hyperplasia, which is seen histo-logically in up to 38% of patients with GD. However, there have only been approximately 100 documented cases of Graves-associated massive thymic hyperplasia. Potential mechanisms of thymic pathology are reviewed. A 24-year-old female presented to the emergency department with dyspnea, palpitations, tachycardia, anxiety, and weight loss. She was evaluated for hyperthyroidism using labs (thyroid-stimulating hormone, free thyroxine, thyroid-stimulating immunoglobulins) and imaging (radioactive iodine uptake [RAIU] scan), leading to treatment with radioiodine. A computed tomography angiogram of the chest was also performed to evaluate for pulmonary embolism given the patient's presenting symptoms. Our patient was found to have undetectable thyroid-stimulating hormone, elevated free thyroxine (2.9 ng/dL), and elevated thyroid-stimulating immunoglobulins (399%). Diagnosis of GD was confirmed on RAIU scan. The computed tomography chest angiogram demonstrated a significant anterior mediastinal mass (7.9 × 6.9 × 6.3 cm). Treatment with radioiodine led to reduction of the mass by 76% in volume. While the patient's thyroid labs and RAIU scan were consistent with GD, the presence of massive thymic hyperplasia was atypical. However, the resolution of thymic hyperplasia after radioiodine therapy, without the use of thymectomy, was similar to other reported cases.

Role of Maternal Thyroid-Stimulating Immunoglobulin in Graves' Disease for Predicting Perinatal Thyroid Dysfunction.

Objective To assess maternal thyroid-stimulating immunoglobulin (TSI) as a predictor of neonatal thyroid hyperthyroidism in pregnancies complicated by Graves' disease. Methods This is a 10-year retrospective study of patients with a history of Graves' disease and elevated TSI activity level defined as 1.3 times the normal. All subjects underwent cordocentesis for ultrasound findings of suspected fetal thyrotoxicosis (fetal tachycardia, oligohydramnios, hydrops, and thyromegaly). Neonatal diagnosis was made based on neonatal thyroid function testing or symptoms. Results Fourteen patients were included in the study, seven with active Graves' disease requiring antithyroid drug (“ATD group”) and seven with iatrogenic hypothyroidism on levothyroxine (“levothyroxine group”). Four cases (57%) of neonatal thyrotoxicosis were diagnosed in the levothyroxine group compared with two cases (28%) in the ATD group. The lowest maternal TSI level at which a neonate did not develop hyperthyroidism was 2.6 for the levothyroxine group and 2.5 for the ATD group. The odds ratio of a neonate from the levothyroxine group developing hyperthyroidism compared with one from the ATD group is 3.3 (95% confidence interval: 0.4–30.7). Conclusion For patients with Graves' disease, those with iatrogenic hypothyroidism and TSI > 2.5 times the basal level are at the highest risk for neonatal thyrotoxicosis.

SAT-621 An Atypical Case of Nivolumab-Induced Thyroiditis with Persistently Elevated Thyroid-Stimulating Immunoglobulin

BACKGROUND: The anti-PD1 monoclonal antibody nivolumab, approved for treatment of several cancers, is associated with ~ 3% rate of hyperthyroidism. Most cases are due to destructive thyroiditis. Stimulating antibodies against the TSH receptor (TSH-R) have not been reported in nivolumab-associated thyroiditis. CLINICAL CASE: A 68-year old man developed hyperthyroidism several months after completion of nivolumab for renal carcinoma. Thyroid function tests were normal prior to nivolumab. Only 4 doses of nivolumab were given over 2 months due to poor tumor response. During this time the patient’s TSH declined minimally (baseline 1.06 uIU/mL, subsequent values 0.35-0.51uIU/mL, normal 0.6-3.3 uIU/mL) and Free T4 remained within or close to the normal reference range. The patient had no symptoms or signs of hyperthyroidism. One month after the final dose of nivolumab, TSH increased slightly to 4.3 uIU/mL. However, 3 weeks later, TSH became suppressed and Free T4 rose to 4.92 ng/dL (0.71-1.4). The patient was asymptomatic. Exam was unremarkable except brisk deep tendon reflexes. Ten days later, free T4 rose further to > 6.99 ng/dL and remained similarly elevated, with Free T3 of > 22.8 pg/mL (2.45-5.93 pg/mL), for several more weeks. During this time, the patient lost 12 pounds and complained of poor appetite. He remained hemodynamically stable with beta-blockers. Antibodies against thyroid peroxidase (TPO) were negative, but antibodies against the TSH-R (thyroid-stimulating immunoglobulin or TSI) were elevated at 1.5 (< 1.3). Because of the elevated TSI and the persistent marked elevation of Free T4 and FT3 for > 1 month after onset of hyperthyroidism, thyroid uptake and scan were obtained to evaluate for Graves’ hyperthyroidism. The 24-hour uptake of I-131 was 0.7% and the scan showed almost no tracer uptake in the thyroid, consistent with thyroiditis. Shortly thereafter, the FT4 and FT3 began to decrease, and the patient’s weight loss stabilized. The Free T3 normalized 2 months after the hyperthyroidism was first detected, and the Free T4 stabilized to just above the reference range, without specific treatment. The TSI remained positive at 1.8. CONCLUSION: This is the first reported case, to our knowledge, of nivolumab-associated thyroiditis with positive TSH-R stimulating antibodies and negative anti-TPO antibodies. Thus, antibody profile alone should not be used to diagnose Graves’ disease in a patient receiving nivolumab. REFERENCE: (1) Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, Tolaney SM. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA Oncol. 2018;4(2):173

Diagnosis of Pediatric Hyperthyroidism: Technetium 99 Uptake Versus Thyroid Stimulating Immunoglobulins

Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with (123)I or (99)Tc ((99m)Tc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with (99m)Tc uptake for diagnosis of pediatric hyperthyroidism. We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and (99m)Tc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. (99m)Tc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI-. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. (99m)Tc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of (99m)Tc (two and a half times as much as TSI), it is reasonable to reserve (99m)Tc uptake assessment for hyperthyroidism of unclear etiology and negative TSI.

Early and Mid-Term Results of Drug-Eluting Stent Implantation in Unprotected Left Main

The development of Graves disease (GD) after subacute thyroiditis (SAT) is rare, with approximately 31 reported cases, of which only 5 occurred in men. We describe a case of GD diagnosed based on newly elevated thyroid-stimulating immunoglobulin (TSI) and thyroid-stimulating hormone (TSH) receptor autoantibody (TRAb) levels after SAT.A 32-year-old Chinese man presented with right anterior neck pain, swelling, sore throat, cough, and fever. He had a diffuse tender goiter but no proptosis, lid lag, or stare. His TSH level was 0.03 mIU/mL (normal range [NR] 0.45-5.33 mIU/mL), serum free thyroxine (FT4) level was 2.40 ng/dL (NR 0.61-1.44 ng/dL), total triiodothyronine (TT3) level was 113 ng/dL (NR 87-178 ng/dL), TSI level was <0.10 IU/L (NR < 0.10 IU/L), and erythrocyte sedimentation rate was 21 mm/h (NR < 15 mm/h). After 7 weeks of prednisone, the symptoms resolved, FT4 level was 0.95 ng/dL, and TT3 level was 91 ng/dL. At 11 weeks after SAT onset, the TSH level was <0.01 mIU/mL, TT3 level was 257 ng/dL, FT4 level was 3.03 ng/dL, TSI level was 1.94 IU/L, then 3.42 IU/L 2 weeks later, TRAb level was 8.72 IU/L (NR < 2 IU/L), and erythrocyte sedimentation rate was 4 mm/h. After 1 month of methimazole, the FT4 level was 1.32 ng/dL and TT3 level was 110 ng/dL. Genetic testing revealed human leukocyte antigen-B35 and DRB1∗15:01 positivity.GD after SAT is thought to be due to the activation of thyroid autoimmunity induced by SAT in genetically susceptible individuals.This case illustrates the induction of thyroid autoimmunity after SAT, resulting in GD, supporting TSI and/or TRAb testing if hyperthyroidism recurs. The presence of HLA alleles associated with SAT and GD suggests a genetic contribution to the development of thyroid autoimmunity.

Spectrum and Prognostic Significance of Arrhythmias on Ambulatory Holter Electrocardiogram in Hypertrophic Cardiomyopathy

The development of Graves disease (GD) after subacute thyroiditis (SAT) is rare, with approximately 31 reported cases, of which only 5 occurred in men. We describe a case of GD diagnosed based on newly elevated thyroid-stimulating immunoglobulin (TSI) and thyroid-stimulating hormone (TSH) receptor autoantibody (TRAb) levels after SAT.A 32-year-old Chinese man presented with right anterior neck pain, swelling, sore throat, cough, and fever. He had a diffuse tender goiter but no proptosis, lid lag, or stare. His TSH level was 0.03 mIU/mL (normal range [NR] 0.45-5.33 mIU/mL), serum free thyroxine (FT4) level was 2.40 ng/dL (NR 0.61-1.44 ng/dL), total triiodothyronine (TT3) level was 113 ng/dL (NR 87-178 ng/dL), TSI level was <0.10 IU/L (NR < 0.10 IU/L), and erythrocyte sedimentation rate was 21 mm/h (NR < 15 mm/h). After 7 weeks of prednisone, the symptoms resolved, FT4 level was 0.95 ng/dL, and TT3 level was 91 ng/dL. At 11 weeks after SAT onset, the TSH level was <0.01 mIU/mL, TT3 level was 257 ng/dL, FT4 level was 3.03 ng/dL, TSI level was 1.94 IU/L, then 3.42 IU/L 2 weeks later, TRAb level was 8.72 IU/L (NR < 2 IU/L), and erythrocyte sedimentation rate was 4 mm/h. After 1 month of methimazole, the FT4 level was 1.32 ng/dL and TT3 level was 110 ng/dL. Genetic testing revealed human leukocyte antigen-B35 and DRB1∗15:01 positivity.GD after SAT is thought to be due to the activation of thyroid autoimmunity induced by SAT in genetically susceptible individuals.This case illustrates the induction of thyroid autoimmunity after SAT, resulting in GD, supporting TSI and/or TRAb testing if hyperthyroidism recurs. The presence of HLA alleles associated with SAT and GD suggests a genetic contribution to the development of thyroid autoimmunity.

Hashitoxicosis in children: Clinical features and natural history

To determine the incidence, natural history, and clinical characteristics of Hashitoxicosis (Htx) in pediatric patients with autoimmune thyroiditis. Medical records of children diagnosed with Hashimoto thyroiditis between 1993 and 2002 were reviewed. The clinical course of patients presenting with hyperthyroidism was determined. Variables including sex, age, family history, thyroid hormone levels, anti-thyroid antibody titers, 123 I thyroid scan results, and presenting features were investigated as possible predisposing factors for the development of Htx. Out of 69 patients with autoimmune thyroiditis, 8 were diagnosed with Htx. The duration of hyperthyroidism ranged from 31 to 168 days. Three patients became hypothyroid after an average of 46.3 +/- 13.2 days, and 5 patients became euthyroid after an average of 112.8 +/- 59.8 days. Additional findings included an elevated thyroid stimulating immunoglobulin (TSI) titer in 3 of the 8 patients with Htx, and increased uptake on 123 I scan in 2 patients. Htx is an uncommon yet important cause of hyperthyroidism in children that has a variable clinical course. The diagnosis may be complicated, as presenting features sometimes exhibit significant overlap with Graves' disease. No factors predisposing to the development of Htx were identified.