Prior History Of Thyroid Disease Research Articles

FRI553 ICI-induced Thyroid Ophthalmopathy With De Novo Graves’ Disease

Abstract Disclosure: S.I. Moctezuma: None. J. Perlman: None. J.S. Mammen: None. Background: Immune checkpoint inhibitors frequently target the thyroid gland. However, immune checkpoint inhibitor (ICI)-induced Graves’ disease (GD) is rare. To our knowledge, there are no reported cases of thyroid eye disease after immune checkpoint inhibitor therapy in patients with newly positive anti-thyroid antibodies. Clinical Case: An 81-year-old man developed thyroiditis within three weeks of a single dose of ipilimumab/nivolumab for the treatment of metastatic cholangiocarcinoma. ICI therapy was discontinued for cardiotoxicity. He presented one year later with onset of periorbital edema, pain with downgaze, redness, irritation and progressive proptosis with diplopia. He did not have a prior history of thyroid disease. Thyroid function tests before the start of ICI therapy revealed euthyroidism [TSH 2.982 uIU/mL (0.55 - 4.78)]. Symptoms of palpitations, weight loss, and hyper-defecation that characterized his initial presentation with thyroiditis were absent at the time of onset of eye disease. At presentation of thyrotoxicosis his TSH was <0.01 uIU/mL, free T4 3.6 ng/dL (0.89 - 1.76) total T3 190 ng/dL (60-180) Thyroid-peroxidase autoantibodies (TPOAb) and thyroid-stimulating immunoglobulin (TSI) were negative. When his visual symptoms appeared, TPOAb remained negative while a repeat TSI antibody was positive [0.64 IU/L (0.00 - 0.55)]. Thyroid ultrasound at the time of thyroiditis revealed a heterogeneous gland without discrete nodules and a normal vascular flow. Most cases of ICI-induced GD have been reported at the start of therapy, particularly in the first 6 weeks, although thyrotoxicosis has been described to occur as late as 224 days after starting PD-1 inhibitor. GD is more frequently reported with combination anti-CTLA-4 and anti-PD-1 therapy. Patients with thyroid ICI-induced adverse events experience either isolated hypothyroidism or thyroiditis spontaneously evolving towards hypothyroidism. However, ICI-induced GD is more likely to have a relapsing-remitting disease. In 2021, Peiffert et al. described the antibody profile for 243 patients with ICI-induced thyrotoxicosis. In this case series, 5 patients developed thyrotoxicosis with positive thyrotropin-receptor antibodies (TRAb). Only 2 patients had a typical clinical presentation of GD. TSI antibodies were not reported. Furthermore, none of the patients with positive TRAb had Graves’ ophthalmopathy. Conclusion: Our case demonstrates the acquisition of auto-antibodies capable of mediating Graves’ disease, and raises the possibility that thyroid eye disease-like orbital inflammation may occur as a side effect of immune checkpoint inhibitor therapy. These symptoms developed as late as one year after initiation of therapy. As with sporadic cases, this can occur in the absence of clinically significant hyperthyroidism. Presentation: Friday, June 16, 2023

Study of correlation of hypothyroidism with diabetic microvascular complications in type 2 diabetic adult Indian females

Background: Patients with type 2 diabetes mellitus are more prone to thyroid disorders. Hypothyroidism in them leads to an aggravation of microvascular complications. Screening for thyroid dysfunction in diabetic patients will allow early treatment of hypothyroidism. The aim of this study is to assess the correlation of hypothyroidism with diabetic microvascular complications. Methods: This is a cross‑sectional study that was conducted at department of medicine GSVM Medical College, Kanpur. 200 female patients with type 2 diabetes mellitus attending the out‑patient department were included. Subjects with any prior history of thyroid disease, chronic liver disease, or acute illness were excluded from the study. Results: Our study describes 14% prevalence of hypothyroidism (subclinical hypothyroidism 13.5%) among 200 diabetic subjects. Among hypothyroid patients 64.29% patients had nephropathy, 60.71% patients had neuropathy, 64.29% patients had retinopathy whereas euthyroid patients had 26.74%, 25% and 29.07% nephropathy, neuropathy, and retinopathy respectively. Conclusions: The prevalence of hypothyroidism was 14% among female patients with type 2 diabetes mellitus in this study. Overt hypothyroidism was 0.5 % and subclinical hypothyroidism was more common (13.5%) among the study subjects. Patients having hypothyroidism were more likely to be having diabetic nephropathy, neuropathy, and retinopathy.

Challenging Thyroid Cases in Clinical Practice

Thyroid disorders are prevalent, and their manifestations are divergent and sometimes it is very challenging to diagnose and deal with some Thyroid cases in clinical practice. Here seven different challenging cases will be discussed that will help clinicians to diagnose and treat such cases in dayto- day clinical practice. First case enlightened us that Thyroid function should not be assessed in seriously ill patients unless there is a strong suspicion of thyroid dysfunction, since there are many other factors in acutely or chronically ill euthyroid patients that influence thyroid function tests. The second case taught us that there is assay interference with Biotin ingestion and patients taking Biotin should hold the supplement for two days prior to assessing thyroid function. Subacute thyroiditis is a self-limiting inflammatory condition of the thyroid gland and COVID-19 virus infection may be associated with subacute thyroiditis as a complication that may occur in patients without any previous thyroid disorder that is revealed in third case. In Secondary hypothyroidism/Hypopituitarism, TSH may be low, normal, or even slightly elevated due to inactive TSH isoform in blood. The fourth case shows us that only TSH testing in clinical practice leads to missing Secondary hypothyroidism/Hypopituitarism. Learning from fifth case is that during monitoring of thyrotoxic patients taking ATDs, serum TSH may remain suppressed for several months after starting therapy and it is therefore not a good parameter for monitoring therapy early during treatment, rather we should rely on FT4 and FT3. The sixth case enlightened us that in case of low TSH in early pregnancy, Gestational transient Thyrotoxicosis should be excluded which is commonly associated with hyperemesis gravidarum with no prior history of thyroid disease, no stigmata of Graves’ disease (Goiter, ophthalmopathy) and a self-limited mild disorder. In poorly compliant patients, there may be a combination of high FT4 and high TSH that is revealed in the seventh case. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 189

A STUDY ON PREVALENCE OF HYPOTHYROIDISM (CLINICAL/SUBCLINICAL) IN DIABETES MELLITUS AND CORRELATION OF HbA1C LEVELS WITH TSH LEVELS IN WESTERN UTTAR PRADESH

Background and Aims: Patients with type 2 diabetes mellitus are more prone to thyroid disorders. Hypothyroidism The aim of this study was to study the prevalence of Hypothyroidism (Clinical/Subclinical) in Diabetic patients and to study the correlation of HbA1c levels with TSH levels. This is a prospective Methods: observational study that was conducted at departments of Medicine Rama medical College , Hapur, U.P between January 2021 to August 2022 were selected by using Random Sampling Techniques. 50 patients with type 2 diabetes mellitus attending the out-patient department without any prior history of thyroid disease, were recruited for the study. Thyroid function test was done in all subjects using chemiluminescent immunoassay method. Prevalence of thyroid disorders was Results: found to be signicantly more in females, highest in the age group of 61-70 years, with duration of diabetes mellitus >10 years, and especially in those who had high FBS, PPBS and HbA1c levels signifying poor control of diabetes. There Conclusion: is a positive correlation with the incremental pattern of prevalence of hypothyroidism in patients with diabetes mellitus (30%). Patient who are suffering from diabetes mellitus should be screened for hypothyroidism and treated effectively because it helps in better control of diabetes

The effect of thyroid dysfunction on breast cancer risk: an updated meta-analysis.

In a previous systematic review and meta-analysis of studies reporting associations between hyper-/hypothyroidism and breast cancer incidence published through 29 January 2019, we identified a higher risk with diagnosed hyperthyroidism compared to euthyroidism, but no association with diagnosed hypothyroidism. This 2-year updated meta-analysis aims to investigate the role of menopause in this association and the dose-response relationship with blood levels of thyroid-stimulating hormone (TSH) and thyroid hormones. After the exclusion of studies with only mortality follow-up, with thyroid dysfunction evaluated as a cancer biomarker or after prior breast cancer diagnosis, we reviewed 25 studies that were published up to 01 December 2021 and identified in MEDLINE, the COCHRANE library, Embase, or Web of Science; of these, 9 were included in the previous meta-analysis. Risk estimates from 22 of the 25 studies were included in the meta-analysis and pooled using random-effects models. Compared to euthyroidism, hyperthyroidism and hypothyroidism diagnoses were associated with higher (pooled risk ratio (RR): 1.12, 95% CI: 1.06-1.18, 3829 exposed cases) and lower risks (RR = 0.93, 95% CI: 0.86-1.00, 5632 exposed cases) of breast cancer, respectively. The increased risk after hyperthyroidism was greater among postmenopausal women (RR = 1.19, 95% CI 1.09-1.30) and the decreased risk after hypothyroidism was more pronounced among premenopausal women (RR = 0.69, 95% CI 0.53-0.89). Among women with no prior history of thyroid disease, every 1 mIU/L increase in TSH level was associated with a 0.8% (95% CI > 0-1.5%) lower risk of breast cancer. In conclusion, this meta-analysis supports an association between thyroid hormone levels and breast cancer risk, which could be modified by menopausal status.

Thyroid Dysfunction among the Patients with Critical COVID-19.

Since the angiotensin-converting enzyme (ACE) is the functional receptor for SARS-CoV-2, predominantly expressed by the alveoli, SARS-CoV-2 primarily involves the lungs. Aside from the lungs, ACE is expressed in other organs, including the thyroid gland. This study aimed to evaluate the incidence of thyroid dysfunction (TD) in patients admitted to the intensive care unit (ICU) with critical COVID-19, with inflammatory markers and disease severity, compared to patients with normal thyroid function. This retrospective study included 52 patients admitted to the ICU with PCR-confirmed critical COVID-19 between April 2020 and September 2021.Thyroid function tests were obtained within the first three days after ICU admission. TD was defined as the detection of any abnormal level in thyroid-stimulating hormone (TSH), free thyroxine hormone (FT4), and free triiodothyronine hormone (FT3).None of the patients had a prior history of thyroid disease or received medications related to thyroid diseases. TD was detected in 34 patients (65.4%). The majority of patients (67%) required extracorporeal membrane oxygenation (ECMO), with a higher frequency in patients with TD (74%). Patients with and without TD were similar concerning age, gender, and the need for ECMO. Patients with TD had significantly decreased levels of TSH, FT3, and FT4 (p=0.002, <0.001, =0.005, respectively); a significantly greater acute physiology and chronic health evaluation II (APACHE-II) score (p=0.048); a significantly higher white blood cell count (p=0.031) and elevated levels of procalcitonin (p=0.003), C-reactive protein (p=0.049) and cardiac troponin T (p=0.025). Other parameters, such as ICU stay, sequential organ failure assessment [SOFA] score, and mortality, did not differ significantly (p=0.449, p=0.315, p=0.142, respectively). Our findings suggest that patients admitted to the ICU with critical COVID-19 are at an increased risk for the development of TD, which should also be taken into account in relation to inflammatory markers, cardiac troponin T levels, and APACHE-II scores.

Painless Thyroiditis After Covid-19 Vaccination: A case Report

Background: Subacute thyroiditis is an inflammatory disease associated with vaccinations. There have been reports of subacute painful thyroiditis following SARS-CoV-2 vaccination. However, only a few cases of painless thyroiditis have been reported and mostly were after mRNA vaccine. The authors presented a case of painless thyroiditis after viral vector SARS-CoV-2 vaccine. Case Report: A 60-year-old woman, who had no prior history of thyroid disease, presented with atrial fibrillation and no enlarged thyroid gland or neck pain. She had received ChAdOx1 nCoV-19 vaccine from AstraZeneca two weeks prior to the onset of symptoms. Her blood tests revealed primary thyrotoxicosis, and thyroid uptake confirmed thyroiditis. Discussion: Vaccine-induced thyroiditis has been reported in viral vaccines. The pathophysiology of SARS-CoV-2 vaccine-induced thyroiditis is still unknown. It is possible that the immune response to the SARS-CoV-2 vaccine will also cross-react and cause thyroiditis. Conclusion: It is possible that SARS-CoV-2 vaccine can cause painless thyroiditis. Keywords: Covid-19; SARS-CoV-2; Thyroiditis; Vaccine

PSAT324 Altered Mental Status, Hypercalcemia, and Atrial Fibrillation Induced by Post-Parathyroidectomy Thyroiditis

Abstract Background Parathyroidectomy-induced thyroiditis is a rare but possibly underreported phenomenon. It has been reported in primary, secondary, and tertiary hyperparathyroidism, and typically presents with transient thyrotoxicosis in the days to weeks following surgery. Clinical Case A 66-year-old man with end stage renal disease complicated by tertiary hyperparathyroidism and no prior history of thyroid disease or cardiac dysrhythmia was admitted for parathyroidectomy. A multinodular goiter and four enlarged parathyroid glands were identified intraoperatively. With significant thyroid retraction, removal of the inferior parathyroid glands, left superior parathyroid gland, and one-half of the right superior parathyroid gland was successfully performed without complication. Despite normalization of the parathyroid hormone level after surgery, the patient's preoperative hypercalcemia was noted to paradoxically worsen, rising from a corrected total calcium of 10.9 mg/dL (ref. 8.5-10.4 mg/dL) to 12.2 mg/dL. This was observed concurrently with the development of worsening mental status and new onset atrial fibrillation with rapid ventricular rate, prompting beta blockade initiation. Administration of intravenous crystalloid and subcutaneous calcitonin rapidly normalized his serum calcium but did not resolve the altered mentation or cardiac arrhythmia. Thyroid function tests revealed thyroid stimulating hormone 0.05 mIU/L (ref. 0.49-4.67 mIU/L), free thyroxine (T4) 3.8 ng/dL (ref. 0.7-1.9 ng/dL), and total triiodothyronine 144 ng/dL (ref. 60-181 ng/dL). Thyroid stimulating immunoglobulin was negative, and a thyroid ultrasound demonstrated multiple bilateral thyroid nodules with no evidence of increased vascularity of the gland. Serial thyroid function tests over several days revealed spontaneous biochemical improvement in the patient's T4-thyrotoxicosis that correlated with improved mentation. An exhaustive metabolic, infectious, and radiologic work-up yielded no alternative explanation for his initial change in mental status. By postoperative day 6, his cardiac dysrhythmia and altered mentation completely resolved, and the free T4 improved to 2.1 ng/dL, allowing for hospital discharge. His free T4 normalized a week later. Conclusion Our patient's postoperative course appears to have been driven by surgically induced thyroiditis. There are no current recommendations for routine postoperative screening for parathyroidectomy-induced thyroiditis, but biochemical testing should be considered if signs or symptoms of thyrotoxicosis such as unexplained altered mentation, cardiac dysrhythmias, and/or worsening hypercalcemia emerge. Doing so may allow for a rapid and cost-effective approach towards a unifying diagnosis. Bilateral cervical exploration is a known risk factor. Other possible risk factors include the presence of a multinodular goiter and significant intraoperative thyroid retraction, though further characterization of these is needed. Treatment is supportive, as cases typically self-resolve. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP501 New-Onset Graves’ Disease in a Patient with Recent Diagnosis of Covid-19 Infection

Abstract Background Thyroid disorders have been described in patients with Covid-19 infection. Although thyrotoxicosis secondary to thyroiditis is mostly reported in several publications worldwide in patients infected with Covid-19, new-onset Graves’ disease is rarely reported. Clinical Case A 41-year-old female without significant past medical history presented to emergency room with nausea, vomiting, palpitations and syncope. She was diagnosed with COVID-19 infection five days prior to her presentation. On admission, patient was normotensive, tachycardic with heart rate of 135 beats/min, and oxygen saturation &amp;gt;90% on room air. Thyroid exam was unremarkable. Initial labs showed suppressed TSH, elevated free T4 of 2.58 ng/dL (0.76–1.70 ng/dL) and elevated total T3 of 210 ng/dL (80–175 ng/dL). The computed tomography pulmonary angiogram (CTPE) was negative for pulmonary embolism. Transthoracic echocardiogram (TTE) showed moderate cardiac effusion without tamponade. Patient had no prior history of thyroid disease, but her mother had hypothyroidism. With Burch-Wartofsky score of 50, treatment for thyroid storm was initiated: Hydrocortisone, propranolol, and propylthiouracil (PTU), followed by cholestyramine, and super saturated potassium iodide (SSKI). Shortly after, patient developed hypotension requiring norepinephrine infusion and transfer to intensive care unit. Repeat TTE showed ejection fraction of 50%, moderate pericardial effusion without tamponade, and global hypokinesis suggestive of myocarditis. Propranolol was held. Although patient's blood pressure improved overnight, patient developed shock liver with AST elevated at 4,095 IU/L (8-30 IU/L), ALT at 2,837 IU/L (&amp;lt;35 IU/L), and total bilirubin at 1.6 mg/dl (0.2-1.2 mg/dl) compared to normal values on admission. PTU was discontinued after two doses due to elevated liver enzymes. Thyroid scan showed diffuse mildly increased radiotracer uptake suggestive of autoimmune thyroid disease. Thyroid stimulating immunoglobulin (TSI) was elevated at 6.5 IU/L (&amp;lt;0.55IU/L) with thyrotropin receptor antibody (TRAb) of 8.39 IU/L (0. 00 - 1.75 IU/L) suggestive of Graves’ disease. On discharge, patient was asymptomatic. At outpatient follow up, patient had improvement in liver enzymes and mild hyperthyroidism, methimazole was started with the plan for close monitoring of liver enzymes and thyroid function tests. Conclusion New-onset Graves’ disease can occur in the setting of Covid-19 infection. It is crucial to report this type of cases to gain more insights in the exact relationship between thyroid disease and Covid-19 infection. Physicians should be aware of the possibility of Graves’ disease in addition to thyroiditis in the setting of thyrotoxicosis and Covid-19 infection. Making the right diagnosis is essential as treatment and course of disease are very different. Presentation: No date and time listed

Focal Thyroid Incidentalomas on 18F-FDG PET/CT: A Systematic Review and Meta-Analysis on Prevalence, Risk of Malignancy and Inconclusive Fine Needle Aspiration.

BackgroundThe rising demand for 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) has led to an increase of thyroid incidentalomas. Current guidelines are restricted in giving options to tailor diagnostics and to suit the individual patient.ObjectivesWe aimed at exploring the extent of potential overdiagnostics by performing a systematic review and meta-analysis of the literature on the prevalence, the risk of malignancy (ROM) and the risk of inconclusive FNAC (ROIF) of focal thyroid incidentalomas (FTI) on 18F-FDG PET/CT.Data SourcesA literature search in MEDLINE, Embase and Web of Science was performed to identify relevant studies.Study SelectionStudies providing information on the prevalence and/or ROM of FTI on 18F-FDG PET/CT in patients with no prior history of thyroid disease were selected by two authors independently. Sixty-one studies met the inclusion criteria.Data AnalysisA random effects meta-analysis on prevalence, ROM and ROIF with 95% confidence intervals (CIs) was performed. Heterogeneity and publication bias were tested. Risk of bias was assessed using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool.Data SynthesisFifty studies were suitable for prevalence analysis. In total, 12,943 FTI were identified in 640,616 patients. The pooled prevalence was 2.22% (95% CI = 1.90% - 2.54%, I2 = 99%). 5151 FTI had cyto- or histopathology results available. The pooled ROM was 30.8% (95% CI = 28.1% - 33.4%, I2 = 57%). 1308 (83%) of malignant nodules were papillary thyroid carcinoma (PTC). The pooled ROIF was 20.8% (95% CI = 13.7% - 27.9%, I2 = 92%).LimitationsThe main limitations were the low to moderate methodological quality of the studies and the moderate to high heterogeneity of the results.ConclusionFTI are a common finding on 18F-FDG PET/CTs. Nodules are malignant in approximately one third of the cases, with the majority being PTC. Cytology results are non-diagnostic or indeterminate in one fifth of FNACs. These findings reveal the potential risk of overdiagnostics of FTI and emphasize that the workup of FTI should be performed within the context of the patient’s disease and that guidelines should adopt this patient tailored approach.

Late Breaking Abstracts

Late Breaking Abstracts

A Grave Case of COVID-19: SARS-CoV-2 Induced Autoimmune Hyperthyroidism

Background: Autoimmune hyperthyroidism also known as Graves’ disease is the leading cause of hyperthyroidism. The pathogenesis of Graves’ disease is still an area of active research. We present a case of Graves’ disease, which developed following SARS-CoV2 infection. Clinical Case: A 43-year-old man with no prior history of thyroid disease, presented for evaluation due to fatigue palpitations, tremors, and hair loss in June 2020. Earlier that month, he was diagnosed with SARS-CoV2 infection and his thyroid function tests (TFTs) during a visit to the emergency department revealed thyroid stimulating hormone (TSH) level of <0.010 mIU/L (0.35-4.94) with a free T4 (FT4) 1.4 ng/dL (0.7-1.5); consistent with subclinical hyperthyroidism. He continued to report palpitations and tremors and further workup was done. A thyroid ultrasound showed two sub-centimeter nodules. A thyroid uptake scan followed, which showed heterogeneous activity in the thyroid gland, (12% and 32% uptake at 6 and 24 hours respectively) with focal increased uptake in the medial lobes, without cold nodules or hot nodules. Repeat TFTs one month later showed a suppressed TSH <0.010 mIU/L, and a normal FT4 1.3 ng/dL. Given suspicion for Graves’ disease, further labs were ordered. Thyroid stimulating immunoglobulin (TSI) were found to be elevated at 173 % baseline (<=140). Thyroid peroxidase (TPO) antibodies and thyroglobulin antibodies were also elevated at 362 IU/mL H* (<=9) and 2 IU/mL H* (<=1) respectively. The overall picture was consistent with evolving early Graves’ disease. Conclusion: Multiple factors are frequently cited in the pathogenesis of autoimmune hyperthyroidism including viral and bacterial infections1 and there have been several reported cases of autoimmune disease related to SARS-CoV2 infection2. This case is one of several emerging cases of autoimmune hyperthyroidism possibly linked to COVID-19.

A Case of T3 Thyrotoxicosis With Concomitant Follicular Thyroid Carcinoma

Introduction: The coexistence of hyperthyroidism and thyroid cancer is considered a rare event. In these cases, the follicular thyroid carcinoma subtype is an even more rare finding. It is highly unlikely to find follicular carcinoma in a hyperactive thyroid nodule. Clinical Case: We report a case of an 85-year-old female with a past medical history of atrial fibrillation presenting to the clinic after she has noticed enlargement of her neck two weeks prior. The patient was seen by her primary care physician who ordered a CT neck that revealed a goiter and the patient was subsequently referred to our clinic. On further questioning, the patient denied palpitations, sweats, difficulty swallowing, heat or cold intolerance, weight changes, bowel changes, or any other complaints. The patient denied any prior history of thyroid disease or exposure to goitrogens. Her past medical history was not significant for any auto-immune related diseases. She denied any family history of thyroid disease or malignancy. On physical examination, the patient had a normal eye exam and mild goiter with a small palpated right thyroid nodule. Initial thyroid ultrasound revealed a heterogenous right lobe measuring 7.1 cm x 7.3 cm x 5.9 cm with one superior nodule measuring 1.3 cm x 0.7 cm x 0.8 cm and a heterogenous left lobe measuring 2.0 cm x 1.5 cm x 1.1 cm. Laboratory blood work up revealed total T4 of 10.5 μg/dL(normal: 5.0 to 12.0μg/dL), elevated total T3 at 322 ng/dl (normal: 80-220 ng/dL), suppressed TSH <0.01 uIU/mL (normal: 0.40-4.00 uIU/mL), markedly elevated thyroglobulin 2828 ng/mL(normal: 1-84 ng/mL), as well as elevated anti-TPO Ab 63.5 IU/mL (10.0-35.0 IU/mL). The patient underwent a thyroid uptake scan that revealed increased uptake in the right lobe. Three months after presentation, the patient underwent fine-needle aspiration (FNA) which was benign (Bethesda classification II). A decision was made to start the patient on Methimazole and the subsequent thyroid profile showed an improvement in her T3 and TSH, but thyroglobulin continued to uptrend despite treatment. The patient then underwent another thyroid ultrasound one year later that revealed increased right lobe size to 10.3 cm x 6.3 cm x 6.4 cm with enlargement of the superior nodule to 8.5 cm x 4.6 cm x 6.4 cm. The left lobe was also enlarged from the prior scan measuring 3.9 cm x 1.2 cm x 1.0 cm. The patient underwent a second FNA from that nodule which also revealed benign hyperplastic nodule (Bethesda classification II). Despite the benign FNA finding, a decision was made to perform genetic testing given the rapid progressive enlargement of the nodule. The genetic testing revealed TERT promoter gene mutation with a high risk for malignancy. The patient then underwent total thyroidectomy and the pathological analysis showed a 9 cm follicular thyroid carcinoma of the right nodule. The patient then underwent successful I-131 radioactive Iodine ablation. Subsequent thyroid ultrasounds were negative and TSH continued to downtrend while the patient continued to take thyroid hormone replacement. This patient’s presentation is unique in many aspects. The patient presented with a hyperactive hot nodule while follicular carcinoma of the thyroid gland is typically associated with clinical euthyroidism and a scan showing a cold nodule(1). In a study of 425 hyperthyroid patients, thyroid cancer was diagnosed in 7 (1.65%) hyperthyroid patients, and histological examination revealed the presence of papillary carcinoma in 5 cases and follicular carcinoma in only 2 cases (2). Our patient also had two negative FNAs despite the presence of follicular carcinoma. Hence, we are shedding the light on the importance of genetic testing in the setting of negative FNA for rapidly enlarging thyroid nodules. Conclusion: We urge physician’s awareness that on rare occasions, follicular thyroid carcinoma can be present in a hyperactive thyroid with a hot nodule. In the presence of negative FNA, hyperfunctioning rapidly growing thyroid nodules should be carefully evaluated by further genetic testing for the presence of concurrent malignancy.

SAT-492 Impending Thyroid Storm Induced by Checkpoint Inhibitors

Introduction:Thyroid storm is a rare but life threatening condition due to thyroid hormone excess and is usually caused by Graves disease, toxic nodular goiter or rarely due to thyroiditis. Immune checkpoint inhibitors (ICI) are a novel choice for treating cancers, and carry a risk for development of endocrinopathies. We report a case of impending thyroid storm 5 weeks after initiation of ICI.Case Presentation:81-year-old Caucasian male with metastatic renal cell carcinoma presented with generalized weakness and fatigue 5 weeks after ipilimumab and nivolumab were started. He had no prior history of thyroid disease and had normal thyroid functions before the treatment. He complained of palpitations, heat intolerance and loose stools on admission. On examination he was disoriented, tachycardic (128bpm) with new onset atrial fibrillation, had moist skin and brisk reflexes. He had non-tender thyroid, no thyromegaly, and no nodules palpated. Burch-Wartofsky score was 35, suggesting impending thyroid storm. Laboratory investigation showed elevated free T4 (>7.77), elevated free T3 (8.6) with a suppressed TSH (< 0.02). He had positive anti-TPO but Thyrotropin receptor antibody was negative. He was treated with propranolol 40 mg three times daily, prednisone 40 daily, methimazole 30mg three times a day with significant improvement in free T4 (5.67) within first 48 hours.Discussion:Imipimumab and nivolumab are monoclonal antibodies against cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed death receptor-1 (PD-1) respectively. The reported incidence of thyroid dysfunction after combined imipimumab and nivolumab therapy can be as high as 22%1. Thyroiditis could present as early as 2-6 weeks 2 after treatment, and hypothyroidism tends to present between 5 months and 3 years3. According to a current consensus4, baseline TSH and FT4 should be drawn prior to initiating ICI. Thyroid storm is a clinical diagnosis and Burch-Wartofsky score can help in diagnosis. A high degree of suspicion and prompt diagnosis of thyroid storm and treatment is of utmost importance especially in this patient population. Rapid improvements in thyroid hormone levels suggest thyroiditis as a potential cause for thyrotoxicosis.Conclusion:ICI induced thyroid disease is not an uncommon condition. It could present as either thyrotoxicosis or hypothyroidism. Both patient and clinician should be aware of potential signs and symptoms of thyroid storm for early recognition and timely treatment of this life-threatening condition.[1] Byun DJ et al.Nat Rev Endocrinol. 2017 Apr;13(4):195-207 [2] Iyer PC et al. Thyroid. 2018 Oct;28(10):1243-1251 [3] Endocr Relat Cancer. 2014 Mar 7;21(2):371-81 [4] Puzanov et al. Journal for ImmunoTherapy of Cancer (2017) 5:95

SAT-514 Nivolumab Related Primary Hypothyroidism: 3 Years of Follow-Up

BACKGROUND: Primary hypothyroidism is one of the most common endocrinopathies related to the use of nivolumab, a monoclonal antibody against the immune checkpoint molecule programmed death-1 (PD-1). The long-term course of this condition, especially after the completion of nivolumab treatment, has not been widely reported.CLINICAL CASE: A 70-year-old man presented with weight gain despite poor appetite, cold intolerance, and constipation. He noticed these symptoms after receiving the first three months of treatment with nivolumab for renal cell carcinoma. His heart rate was 66, blood pressure was 130/79 mm Hg, and body mass index was 28.3. The thyroid gland was normal-sized without palpable nodules, deep tendon reflexes were normal, and cardiac and pulmonary exams were unremarkable. Laboratory test results were consistent with primary hypothyroidism: thyroid-stimulating hormone (TSH) was elevated at 97.11 mIU/L (normal, 0.35-4.70 mIU/L), and total thyroxine was less than 1 mcg/dL (normal, 4.5-12.0 mcg/dL). Both anti-TPO antibody (222.6 IU/ml, normal<5.6 IU/ml) and anti-thyroglobulin antibody (10.6 IU/ml, normal <4.1 IU/ml) levels were elevated. There was no prior history of thyroid disease; two of the patient’s sisters had chronic hypothyroidism. Treatment with levothyroxine resulted in rapid resolution of symptoms. With dose titration of levothyroxine over the course of a few months, the patient achieved biochemical euthyroidism. Nivolumab therapy was continued for more than two years, during which a stable levothyroxine dose was maintained, and the patient remained clinically and biochemically euthyroid. Ultimately the renal cell carcinoma was determined to be in remission, and nivolumab therapy was stopped. Subsequently, the anti-TPO antibody titer was observed to have returned to the normal range (2.3 IU/ml). However, as of five months following discontinuation of nivolumab, and 32 months since the onset of thyroid dysfunction, the patient’s hypothyroidism persists as reflected by non-suppressed TSH values on levothyroxine treatment.CONCLUSION: We have observed the course of nivolumab-induced primary hypothyroidism over almost three years in an individual patient. The hypothyroidism has persisted, requiring ongoing levothyroxine replacement at a dose of approximately 1.4 mcg/kg daily. An interesting feature of this case is the disappearance of anti-TPO antibody positivity after discontinuation of nivolumab. We speculate that the ongoing hypothyroidism despite the absence of detectable autoantibodies may be related to progressive thyroid cell apoptosis. Further long-term observations will determine whether permanence of nivolumab-induced hypothyroidism is the rule.

MON-471 The Broken Heart That Hid Behind the Goiter

Most goiters grow slowly over many years and are often asymptomatic. Although substernal goiters are estimated to represent between 5-24% of all mediastinal masses [1], a majority are benign. Symptoms may include neck fullness, nocturnal or positional dyspnea, or dysphagia due to tracheal and/or esophageal compression [2-3]. We present a case of a patient with new onset dyspnea that was initially attributed to a large intrathoracic goiter, but ultimately was found to be due to severe heart failure.A 72-year-old man with a history of HTN, type 2 diabetes, and moderate aortic regurgitation presented to his primary care physician with exertional dyspnea, dry cough, and bilateral leg edema for 2 months. He was referred to pulmonology and a chest CT showed a large intrathoracic goiter, measuring 8.5 x 4.6 x 5.3 cm, extending from the left limb of the thyroid into the mediastinum with rightward tracheal and leftward aortic arch displacement. The patient had no prior history of thyroid disease, cancer, or neck radiation. He denied neck fullness, dysphagia, positional or nocturnal dyspnea, though his exertional dyspnea was progressive. Labs revealed that the patient was biochemically euthyroid. Due to concern for malignancy, the patient underwent a biopsy via EBUS/bronchoscopy, which was non-diagnostic. The case was ultimately discussed at cardiothoracic tumor board, and it was determined that since the mass had likely been present for several years and with the surgical risks being high, to continue monitoring with serial imaging.At this point, the patient’s dyspnea and edema continued to worsen, and he was evaluated with an echocardiogram which showed a severe worsening of ejection fraction in just three months, from 53% to 5%, with global hypokinesis. He was started on diuretics and medical therapy with prominent improvement in his dyspnea. His cardiology team felt this acute decompensation was likely due to coronary artery disease and recommended left heart cardiac catheterization, however the patient declined.Goiters tend to be asymptomatic and grow slowly over time. Given their intra-thoracic location and ability to prominently deviate the mediastinum, it can be tempting to attribute respiratory symptoms to large substernal goiters. However, when a patient develops acute symptoms, one must always rule out alternative diagnoses.

Thyroid dysfunction in patients with type 2 diabetes mellitus and its association with diabetic complications.

Background and Aims:Patients with type 2 diabetes mellitus are more prone to thyroid disorders. Hypothyroidism in them leads to an aggravation of microvascular complications. Diabetic patients with hypothyroidism also are at an increased risk of cardiovascular disease. Screening for thyroid dysfunction in diabetic patients will allow early treatment of hypothyroidism. The aim of this study was to assess the level of thyroid dysfunction in patients with type 2 diabetes mellitus and to identify the association of thyroid dysfunction with diabetic complications.Methods:This is a cross-sectional study that was conducted at departments of Medicine & Endocrinology in JIPMER, Pondicherry, between June 2016 and May 2019. 331 patients with type 2 diabetes mellitus attending the out-patient department without any prior history of thyroid disease, chronic liver disease or acute illness were recruited for the study. All subjects were screened for diabetic complications (nephropathy, neuropathy, retinopathy & cardiovascular disease). Thyroid function test was done in all subjects using chemiluminescent immunoassay method.Results:Hypothyroidism was seen in 13.9%, while hyperthyroidism was observed in 3.6% of the study subjects. Thyroid dysfunction was more common among females than males. No correlation was seen between thyroid dysfunction and diabetic complications in the study subjects.Conclusion:The prevalence of thyroid dysfunction is 17.5% in patients with type 2 diabetes mellitus. Thyroid dysfunction did not have any correlation with diabetic complications.

Orbital fibroblasts from thyroid‐associated ophthalmopathy patients secret IL‐6 via up‐regulation of IGF‐1 by activating the NF‐kB pathway

AbstractPurposeInterleukin (IL)‐6 plays as a modulator for functions of lymphocytes. Significantly higher level of IL‐6 has been observed in primary orbital tissue cultures of thyroid‐associated ophthalmopathy (TAO) patients compared to those of non‐TAO patients. In the current study, we investigated the issue of whether of how orbital fibroblasts (OFs) from TAO patients significantly secret higher level of IL‐6.MethodsHuman OFs were obtained from orbital fat from decompression surgery in patients with TAO or from upper lid blepharoplasties in patients with no prior history of thyroid disease. The levels of IL‐6 and insulin‐like growth factor (IGF)‐1 in culture media of OFs were determined by using an ELISA kit. The NF‐kB activity of OFs was determined by measuring the level of IkB degradation and IKKa/ IKKb/NF‐kBp65 phosphorylation.ResultsCultured OFs from TAO patients significantly secreted higher level of IL‐6 and IGF‐1, compared with those of control groups. In addition, treatment with IGF‐1 induced secretion of IL‐6 in OFs from TAO patients. The levels of IkB degradation and IKKa/IKKb/NF‐kBp65 phosphorylation were higher in non‐treated OFs of TAO patients than those of control groups. Furthermore, treatment with Bay 11‐7082, an inhibitor of NF‐kB pathway, reduced the secretion of IL‐6 and IGF‐1 in OFs from TAO patients.ConclusionsThese results suggest that IL‐6 secretion is dependent on NF‐kB/IGF‐1 pathway in OFs from TAO patients. These findings also show that NF‐kB/IGF‐1/IL‐6 pathway may be a reasonable target of therapeutic intervention in the case of TAO.

SUN-563 TSH Elevation after Seizure: An Underappreciated Cause of Nonthyroidal Illness Syndrome

Introduction: TSH is commonly assessed at hospital admission to exclude thyroid dysfunction as the cause of a patient’s presentation. However, thyroid function tests (TFTs) are commonly altered as a result of the condition leading to the presentation, referred to as nonthyroidal illness syndrome (NTIS). Thus, it is often difficult to interpret the true meaning of abnormal TFTs in hospitalized patient. In fact, hypothalamic-pituitary-thyroid axis can be altered in up to 75% of hospitalized patient (1). Typically, the TSH in NTIS is normal or low, but can temporarily rise above normal as the patient recovers from NTIS (2). We present the case of a patient who had significant TSH elevation immediately after a prolonged seizure. Clinical Case: A 93-year-old female with past medical history of seizure disorder on Levetiracetam, presented with a prolonged seizure. Her blood count, metabolic profile, and Levetiracetam level were all unremarkable. There were no acute changes on a noncontrast head CT. Her only notable test result was TSH 26.30 MIU/L (normal range 0.27-4.20 MIU/L) with a Free T4 1.2 ng/dL (normal range 0.9-1.7 ng/dL). She had no prior history of thyroid disease or family history of thyroid conditions. Endocrinology was consulted for the interpretation of her TFTs. The differential diagnosis included subclinical hypothyroidism and NTIS. TSH and Free T4 were rechecked two days later and were then both within normal range. The patient was diagnosed as euthyroid with transient TSH elevation due to seizure. Conclusions: The case highlights, generally, that TFTs can be unreliable in an acute illness, and that seizures may cause an acute, transient rise in TSH. In our case, the patient’s TSH elevation, occurring after a seizure, normalized on repeat testing two days later. In studies on TSH levels following ECT-induced seizures in depressed patients, researchers demonstrated transient TSH elevations (3). Wada et al. reported a similar case of a patient with non-convulsive status epilepticus with TSH elevation that normalized spontaneously (4). We advise that the diagnosis of subclinical hypothyroidism not be made in a patient presenting with a recent seizure, as the seizure itself may be the cause of elevated TSH. As with most cases of NTIS, follow up over time may reveal that the patient is, in fact, euthyroid.

Evaluation and management of the pediatric thyroid nodule.

Thyroid nodules are commonly diagnosed in adults. Although rare in children, the risk for thyroid cancer is much higher in the pediatric population compared with adults. Presenting as either a solitary nodule or a multinodular goiter, thyroid nodular disease in children requires a thorough workup that includes a detailed clinical examination comprised of prior history of thyroid disease in the patient or in their family, history of radiation exposure, careful palpation of the thyroid and lymph nodes, blood tests, ultrasonography, and cytological assessment. Thyroid surgery is the gold-standard treatment for pediatric thyroid nodules; nonetheless, the extent of surgery remains controversial. Because surgery is not without risk, the decision matrix necessitates focus on the benefits of surgery for the child contingent upon all the preoperative exams. New diagnostic technology such as molecular testing with fine needle aspiration biopsy may help distinguish between benign and malignant lesions while potentially decreasing surgery for benign disease. The objective of this review is to summarize new concepts in clinical disease management of nodular thyroid disease in the pediatric population, including patient history, medical examination, and diagnosis workup.