bluuebunny/crossref_metadata_2025 huggingface dataset:
ODP501 New-Onset Graves’ Disease in a Patient with Recent Diagnosis of Covid-19 Infection
Authors: Ince Melda Sonmez , Daneshvar Farah , Esfandiari Nazanene
Published: November 2022

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 >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 (<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 (<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
ODP502 Nodular Pretibial Myxedema without Graves’ Orbitopathy: A Case Report
Authors: Veeramachaneni Ravali , Veeramachaneni Ravali , White-Cotsmire Alexander , Norwick Paige , Demidova Olga , Roseberg Arlene , del Rincon Juan P
Published: November 2022

Background

Nodular myxedema is an uncommon skin manifestation of autoimmune thyroid disease. Almost always associated with significant orbitopathy from the deposition of glycosaminoglycans by stimulated fibroblasts.

Clinical Case

A 57-year-old male presented to dermatology clinic with multiple, non-tender, non-erythematous, nodular lesions of the distal left leg, which had been increasing in size and number over the past one year. The initial clinical impression was lipoma, versus leiomyoma, versus pilomatricoma. The pathology report from punch biopsy of one of the lesions revealed diffuse dermal mucin deposition, consistent with pretibial myxedema. The patient was then referred to endocrinology. His symptoms included increasing fatigue and weight gain of 20.4 kilograms over the last 7 years. He had long-standing history of untreated hypothyroidism and tobacco use disorder. There was no known history of hyperthyroidism, neither thyromegaly, acropachy, nor any signs of orbitopathy were found on examination. Laboratory tests revealed a mildly elevated TSH (5.491 uIU/ml, reference 0.450-5.491 uIU/ml), normal free thyroxine (0.98 ng/dl, reference 0.45-1.80 ng/dl) and elevated anti-microsomal antibody (66. 0 IU/mL, reference <9. 00 IU/ml). Following the pathology report, thyroid stimulating immunoglobulin was requested and found to be elevated (322%, reference <140%). Thyroid ultrasound showed estimated volume of 5. 04 and 2.96 ml for the right and left thyroid lobes, respectively, and only one sub-centimeter nodule. Treatment with levothyroxine was started.

Conclusion

Thyroid dermopathy, including pretibial myxedema, is attributed to high serum concentrations of thyroid stimulating immunoglobulin leading fibroblasts to deposit mucopolysaccharides in the papillary and reticular dermis. The resulting nonpitting edema can occur anywhere in the skin, despite its notorious penchant for the anterior tibial region. Thyroid dermopathy is seen in 4.3% of patients with Graves’ disease in general, and 15% of patients with Graves’ orbitopathy 1 . Thyroid dermopathy is very rare in the absence of concurrent orbitopathy. Here we present a very unusual case of biopsy-confirmed nodular pretibial myxedema in the absence of current or remote history of known hyperthyroidism, and without any apparent orbitopathy.

Presentation: No date and time listed
ODP522 Thyroid Sarcoidosis: A Rare Manifestation of Systemic Sarcoidosis
Authors: Alameri Majid , Alnuaimi Abdulla , Wernig Florian
Published: November 2022

Introduction

Sarcoidosis is a multisystem granulomatous disease of unknown aetiology characterized by noncaseating granulomas. Thyroid infiltration remains extremely rare. If present, it can cause diffuse goitre and rarely a solitarythyroid nodule. Almost all patients are euthyroid. Here, we report a case of systemic sarcoidosis with thyroid involvement.

Case presentation

A21-year-old female of Nepalese origin with past medical history of Asthma presented with painful eyes and was diagnosed with bilateral anterior uveitis. Symptoms improved with topical Dexamethasone and Cyclopentolate. A screening chest radiograph showed significant hilar adenopathy. Chest CT scan confirmed extensive mediastinal adenopathy particularly in the right paratracheal, subcarinal and hilar node suggestive of sarcoidosis. Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) revealed non-necrotising granulomas. There was no evidence of tuberculosis on any materials obtained. TB-PCR and AFB were both negative. Further investigations showed raised serum ACE (163 units/L) with normal adjusted calcium levels and normal 24-hour urine calcium levels. During follow up, she developed palpable cervical and submandibular lymphadenopathy. Systemic examination revealed a smooth goitre and erythema nodosum. She did not have any neck pain and remained clinically euothyroid. Thyroid ultrasound showed several small microlobulated hypoechoic regions in both thyroid lobes, the largest measuring 7 mm in the right and left upper poles. Fine needle aspiration cytology revealed granulomata consistent with thyroid sarcoidosis. The thyroid MDT recommend conservative management with periodic clinical and biochemical assessment. She remains well at 6 months of follow up.

Conclusion

Sarcoid granulomata within the thyroid gland remains rare. This case report illustrates that in patients with known sarcoidosis, careful thyroid assessment should be carried out.

Presentation: No date and time listed
ODP523 Thyroid Storm in a Patient With Alemtuzumab Induced Graves’ Disease
Authors: AlShehri Sara , Alajmi Sarah , Ekhzaimy Aishah
Published: November 2022

Background

Thyroid storm (TS) is a rare and life-threatening medical emergency, most commonly caused by Graves’ disease (GD). GD can beinduced by immune reconstitution therapy (IRT) such as Alemtuzumab (ALZ), a humanized monoclonal antibody against CD52, which is shown to be effective in the treatment of relapsing-remitting multiple sclerosis (RRMS). Evidence shows that ALZ induced GD may be less aggressive than conventional GD. Below we present a rare case of thyroid storm developing in a patient with ALZ induced GD.

Clinical Case

A 39 year-old female non-smoker, known to have RRMS, wasstarted on ALZ. Presented to our emergency room13months later with palpitation, diarrhea and oligomenorrhea. Found to have TSH of 0. 007 mIU/L (0.250-5), T4 50 pmol/L (11.5- 22.7), thyroid scan demonstrated diffusely enlarged thyroid gland with increased tracer uptake compatible withGD. Our impression was ALZ- induced GD (not in thyroid storm),she wasstarted on carbimazole and propranolol and discharged home. Neurology team gave hera second cycle of ALZas she was euthyroid on carbimazole. One month later, the patient presented to our emergency room with nausea and vomiting. On examination, she was febrile 38.2°C, tachycardic reaching 140 beats/min (regular). Her blood pressure was 138/87 mmhg. The patient was agitated, anxious, alert and oriented. She was diaphoretic with mild peripheral oedema and had pulmonary crackles. The thyroid was diffusely enlarged with no signs of graves’ ophthalmopathy, or pretibial myxedema. On the Burch-Wartofsky Point Scale for thyroid storm, she scored 60. The patient was admitted to the intensive care unit (ICU), with endocrinology and neurology consultation. Laboratory investigation revealed TSH of 0. 009 mIU/L, T3 26.5 pmol/L (3.39-5.82) T4 65 pmol/L, positive thyroid peroxidase antibody 183 units (>100 positive). Despite treatment with maximum dose of carbimazole, B-blocker, hydrocortisone, and potassium iodide her T4 was not improving, and her liver function was deteriorating. Finally, she underwent total thyroidectomy. Three days post total thyroidectomy, the patient clinically improved. Steroids were stopped and the B-blocker dose was gradually tapered. She was then maintained on Levothyroxine.

Conclusion

It is thought that ALZ- induced GD behaves less aggressive than the conventional GD as spontaneous and/or drug-induced remission may be more likely. However, physicians should be aware that severe thyrotoxicosis and thyroid storm can happen which required prompt recognition and aggressive therapy.

Presentation: No date and time listed
ODP529 Update on the Prevalence and Pathogenesis of Central Hypothyroidism
Authors: Heshmati Hassan M , Fatourechi Vahab
Published: November 2022

Background

Central hypothyroidism (CH) is a rare form of hypothyroidism characterized by insufficient stimulation of a normal thyroid gland by the thyroid-stimulating hormone (TSH). It can be of pituitary origin (secondary hypothyroidism) or hypothalamic origin (tertiary hypothyroidism). The diagnosis is suspected by the finding of low serum free thyroxine associated with low, normal, or slightly elevated serum TSH, in the absence of goiter. This review presents an update on the prevalence and pathogenesis of different types of CH.

Methods

A systematic search of literature was conducted using the search terms hypothyroidism, central hypothyroidism, congenital central hypothyroidism, acquired central hypothyroidism, TSH deficiency, prevalence, and pathogenesis.

Results

The prevalence of overt hypothyroidism in the US population is at least 0.3% and the prevalence of subclinical hypothyroidism ranges from 4% to 10%. Primary hypothyroidism is more prevalent in females. The prevalence of CH ranges from 1: 13,000 to 1: 120,000. CH is observed in less than 1% of hypothyroid subjects, with no evidence of sex predominance. Itcan occur prenatally (congenital CH) or after birth (acquired CH). Congenital CH, which is a rare cause of CH (prevalence around 1: 13,000), may result from genetic/malformative causes [e. g., pituitary-specific transcription factor defects, TSH-beta subunit gene mutations, isolated TSH-releasing hormone (TRH) deficiency, TRH receptor gene mutation, immunoglobulin superfamily member 1 deficiency, De Morsier syndrome, Prader Willi syndrome]. In 60% of the cases, congenital CH is associated with other pituitary hormone deficiencies and in 40% of the cases, congenital CH is due to isolated TSH deficiency. Acquired CH, which is the most common cause of CH andusually associated with other pituitary hormone deficiencies, results from the destruction or inhibition of the pituitary and/or hypothalamus. In decreasing order of frequency, acquired CH can be secondary to invasive and/or compressive lesions (e. g., pituitary macroadenomas, craniopharyngiomas, pituitary metastases, carotid aneurysm), iatrogenic factors (e. g., surgery or irradiation, glucocorticoids, dopaminergic drugs, somatostatin analogs, immune checkpoint inhibitors), trauma (e. g., brain injury), vascular causes (e. g., pituitary apoplexy, postpartum pituitary necrosis, hemorrhage), autoimmunity (e. g., lymphocytic hypophysitis), infiltrative lesions (e. g., hemochromatosis, sarcoidosis), and infections (e. g., tuberculosis, syphilis).

Conclusion

CH is a rare cause of hypothyroidism resulting from a variety of congenital or acquired causes. Acquired CH is the most common cause of CH. In many cases, both congenital and acquired CH are associated with multiple pituitary hormone deficiencies. Isolated TSH deficiency is rare and usually of congenital origin.

Presentation: No date and time listed
ODP530 When "Taller-Than-Wide" Is Not Taller-Than-Wide
Authors: Khan Anum , Paduri Swetha , Elahi Amna , Patel Sabah , Anbari Raghda A , Veeramachaneni Ravali , Siddiqui Mahwash , Carvajal Karen , Shrestha Isha , Barsano Charles
Published: November 2022

The thyroid nodule ultrasonic characteristic referred to as "Taller-than-Wide" (TtW) is defined as a nodule's anterior-posterior diameter/left-right diameter ratio (i. e. AP/LR ratio) on transverse view. This characteristic is regarded as a major feature suggesting malignancy. On the Amer College of Radiology's TIRADS ("Thyroid Imaging Reporting and Data System") guidelines, TtW status usually indicates the need for an aspiration biopsy (FNA). Given this importance, and the subjective and technical limitations of ultrasonic linear measurements of nodule diameters, it would be prudent to be aware of the probabilities that an AP/LR ratio may be under-estimated or over-estimated, potentially causing a false-negative or false-positive TtW interpretation, respectively. To assess these probabilities two approaches were taken. Eight observers were trained how to carefully measure the AP and LR diameters of thyroid nodules by ultrasound. The observers measured these diameters on the same transverse image from each of 34 benign thyroid nodules without knowledge of the measurements obtained by other observers. Thus, 272 independently obtained, rank-ordered individual AP/LR ratios (34 nodules×8 observations each) were plotted on the y-axis against themean AP/LR for each nodule (34mean AP/LRs, regarded as the consensus "true" AP/LRs for the corresponding nodule). By Spearman's rank correlation method, variations in individual AP/LR ratios (i. e., the individualAP/LR ratios minus their correspondingmean AP/LR ratios) were plotted on the x-axis as a function of their rank-ordered fraction of the total population on the y-axis. By this method, the top 20% ofindividual AP/LR ratios were 0. 075 to 0.550 greater than their correspondingmean AP/LRs. The bottom 20% ofindividual AP/LR ratios were 0. 085 to 0.300 lower than their correspondingmean AP/LR ratios. To determine the clinical significance of these variations, theindividual AP/LR rations of the 34 nodules were plotted on the y-axis as a function of their correspondingmean AP/LR ratios. Of the 28 nodules whosemean AP/LR ratios were <1, 31 (13.8%) of the 224 associated individual AP/LR ratios (28×8) were read as >1 (False Pos TtW status). Of the 6 nodules whosemean AP/LR ratios were >1, 6 (12.5%) of their 48individualAP/LR ratios (6×8) were read as <1 (False Neg TtW status). In conclusion, although interpretive deviations in the AP/LR ratio are common and frequently large, their clinical consequences in terms of generating false positive and false negative attributions of Taller-than-Wide nodular status are fortunately much less frequent (13.8% and 12.5%, respectively). None of the authors have any relevant disclosures.

Presentation: No date and time listed
ODP532 Fractionated Radioactive Iodine Therapy in Management of Differentiated Thyroid Cancer
Authors: Khan Adeel Ahmad , Karuppasamy Gowri , Yousaf Zohaib , Zawahreh Amer Ibrahim , Khan Aisha Noor , Rohani Zaina Seros , Naem Emad , Zirie Mahmoud Ali Humeidan , Jaber Tania
Published: November 2022

Introduction

Management of differentiated thyroid cancer (DTC) requires individualized treatment plans that are tailored to the risk of disease recurrence. Radioactive iodine treatment (RIT) remains a treatment modality that is valuable in certain patients with DTC. The lack of institutional availability and travel bans imposed by the COVID-19 pandemic did not allow a subset of our patients to get intermediate or high-dose RIT. As an alternative, fractionated low-dose RITs given over a short time interval have been used. We aim to study the response to therapy in this patient population.

Materials and methods

This retrospective study was performed at a tertiary care hospital in Qatar. Between 2015-2020, patients who completed at least 2 doses of low-dose RIT within 6-12 months with at least one staging visit 3-6 months after their last treatment were included in the study.

Results

69 patients met our inclusion criteria, 30 (43.5%) of whom were males and 39 (56.5%) females. The mean age at diagnosis was 40.7 +/- 9.35 years. Classic papillary thyroid cancer was the predominant histological variant (76.6%). Based on surgical pathology, the initial risk of disease recurrence was high in 24 (34.8%) patients, intermediate in 21 (30.4%) patients, and low in 21 (30.4%) patients. 3 (4.3%) patients did not have complete data for classification. Lymphatic invasion was noted in 16 (23.2%), vascular invasion in 15 (21.7%), positive margins in 30 (43.5%) and extra-nodal invasion in 10 (14.5%) patients. Patients underwent between 2-6 fractionated RITs, with the majority having undergone 2. In the low-risk group, 9 (42.9%) patients had an excellent response to therapy at last follow-up, 3 (14.3%) had the persistent structural disease, and 9 (42.8%) patients had an indeterminate response. In the intermediate-risk group, 7 (33.4%) patients had excellent response, 2 (9.5%) had the biochemically persistent disease, 8 (38.1%) had the structurally persistent disease, and 4 (19%) had an indeterminate response. In the high-risk group, 5 (20.8%) patients had excellent response, 13 (54.2%) had a structurally persistent disease, and 6 (25%) patients had an indeterminate response to therapy.

Conclusion

A similar response to therapy has been reported in the literature in the low and high-risk recurrence groups, suggesting that additional RIT may not be beneficial. In the intermediate risk of recurrence group, there is a higher percentage of patients with structural evidence of disease compared to what is reported in the literature, suggesting that perhaps a single intermediate or high dose RIT may be more beneficial. Either way, the c urrent management of DTC should be based on dynamic risk assessment to guide the need for further therapies.

Presentation: No date and time listed
ODP574 Characteristics of Grave's Disease Among Children and Adolescents in KSA
Authors: Alradadi Rasha , Omar Noura , Alhusayni Renad , Altaleb Mawaddah , Alraddadi Reem , Abdullah Sundus , Almokhtar Amirah , Muhawish Shahad , Alamri Randa
Published: November 2022

Background

Graves’ disease (GD) is an autoimmune thyroid condition that causes hyperthyroidism in children and adolescents through stimulation by thyroid receptor antibodies.

Objective

The aim of this study is to determine the characteristics of Graves’ disease in children and adolescents in Medina, the Kingdom of Saudi Arabia, with comparison to those seen in other countries.

Methods

This is a retrospective chart review of children and adolescents diagnosed with Graves’ disease between January 2010 and May 2021.

Results

Fifty-eight patients aged 12. 02 ± 4.85 years were identified, of which 44 (75.9%) were females. Exophthalmos (63.8%), neck swelling (60.3%), palpitation (46.6%), and tremors (29.3%) were the most common presenting manifestations. Vitiligo and alopecia were the only autoimmune diseases seen in our patients with (1.72%) each. One (1.72%) patient was treated with radioactive iodine, 54 (93.1%) received carbimazole, and 6 (10.3%) underwent thyroidectomy.

Conclusion

In our study we found that Graves’ disease is more common in females. Neck swelling, palpitation, and tremor were the main manifestations. Compared with other countries, there was a higher frequency of exophthalmos and lower frequencies of associated autoimmune conditions. The primary treatment was antithyroid medication, whereas thyroidectomy and radioiodine were used less frequently.

Presentation: No date and time listed
ODP578 Utility of the ACR-TIRADS Score – A Survey of Primary Care Providers
Authors: Wang Yiqiao (Daniel) , He Jialin , Wang Stephen , Ji Catherine , Yu Catherine
Published: November 2022

Background

The American College of Radiology – Thyroid Imaging Reporting and Data System (ACR-TIRADS) score is an ultrasound-based tool used to assess the risk of malignancy in thyroid nodules. Despite evidence supporting its efficacy, the use of this score in clinical practice has not yet been reported. Since primary care providers commonly identify and manage thyroid nodules, we aimed to determine 1) current diagnostic approach to thyroid nodules and 2) perceived utility of ACR-TIRADS in Canadian primary care providers.

Methods

We conducted a cross-sectional survey study with family medicine physicians and nurse practitioners working in Canada. The 23-question survey was developed and distributed electronically on Qualtrics using convenience sampling from August 31 2021 to January 3, 2022. Sociodemographic and other quantitative questions using Likert scales were analyzed using descriptive statistics; Likert scale responses were analyzed as proportion of individuals who agreed or strongly agreed. Qualitative data from free text answers was assessed using content analysis.

Results

One hundred and four primary care providers responded to our survey. Of these, 90 (87%) completed the entire survey and were included. Fifty-six percent were female, 58% were aged <40 years, and 48% were in practice for five or fewer years. In terms of management of thyroid nodules, only 47% were confident in their ability to risk-stratify. Ninety-four percent of participants risk-stratified using imaging characteristics, but only 57% of respondents reported using a risk stratification tool. Despite 64% percent of participants agreeing with being familiar with the ACR-TIRADS score, only 28% used this scoring system, and 80% of participants had a desire to learn more about it. Only 68% of physicians believed the score was present on ultrasound reports, and <5% requested it on reports themselves. After being shown a diagram demonstrating the ACR-TIRADS scoring system, 93% thought that the ACR-TIRADS score was useful. Of the 31 (34%) participants who were not initially familiar with the score, 61% would use the ACR-TIRADS score more, and 77% would ask radiology to report the ACR-TIRADS score more often. In terms of qualitative data, respondents believed educational tools and increased reporting by radiologists would increase use of ACR-TIRADS.

Conclusion

In this Canadian survey study, the majority of respondents were not confident with risk stratification of thyroid nodules, and only half used a risk stratification tool. With education, almost all participants thought ACR-TIRADS was useful, and most participants would use it more often. Further interventions to educate primary care providers regarding the ACR-TIRADS score may help enhance its uptake and improve systematic management of thyroid nodules.

Presentation: No date and time listed
ODP614 Two cases of Graves Disease Associated Hypokalemic Periodic Paralysis
Authors: Reddy Bendaram Snigdha , Azmath Misbah , Luthra Pooja , Dulipsingh Latha
Published: November 2022

Introduction

Periodic paralysis (PP) is a rare neuromuscular disorder due to a defect in ion channels in muscle, characterized by episodes of painless muscle weakness or paralysis, which may be precipitated by heavy exercise or high-carbohydrate meals. Hypokalemic PP (HPP) is most common of the periodic paralyses, however is still very rare, with an estimated prevalence of 1 in 100,000. An acquired form of hypokalemic PP can be seen in thyrotoxicosis of any cause. We present 2 cases of HPP due to thyrotoxicosis.

Case 1

27 year old Asian male presented to the ED due to sudden onset of acute weakness/near paralysis in lower extremities, with weakness of bilateral upper extremities. He was found to be hypokalemic with a potassium of 2.0 mmol/L (3.5-5.1). At the same time, he was also found to be hyperthyroid with a suppressed TSH of 0.03 uIU/Ml (0.35-5.5) and a free T4 2.2 ng/mL (0.5-1.3), Total T3 225 ng/Dl (70-204), Free T3 5.9 pg/mL (1.5-4.1). TSI antibodies elevated at 1.39 IU/L (<0.10). He was started on potassium supplements and methimazole. At a 3-month follow-up, patient reported no further episodes of weakness or paralysis.

Case 2

23 year old White male presented to ED with severe muscle weakness and was found to have hypokalemia of 2 mmol/L (3.5-5.1). On further labs, TSH was undetectable at less than 0.01 uIU/mL (0.35-4.94), Free T4 2.81 ng/dL (0.61-1.82), Total T3 of 451 ng/dL(48-178), TSI antibodies were positive at 178%(</=122%). Nuclear uptake scan confirmed Graves’ disease with radioactive iodine uptake of 58.1% at 4 hours and 70% at 24 hours with homogenous uptake in the entire gland and no evidence of hot or cold nodules. He was started on methimazole and propranolol for tachycardia and palpitations and potassium supplements. Muscle weakness resolved on treatment methimazole.

Discussion and conclusion

We present two cases of HPP likely caused by Graves’ disease. Both patients presented with hypokalemia and further workup revealed underlying thyrotoxicosis. The exact mechanism behind HPP due to thyrotoxicosis is not well understood. It is proposed that excess thyroid hormone may predispose to paralytic episodes by increasing the susceptibility to the hypokalemic action of epinephrine or insulin. This condition has been most widely reported in Asian populations, in which the incidence is approximately 2% in contrast to non-asian population with incidence of 0.1 to 0.2%, and is more common in men. Treatment of thyrotoxicosis with restoration and maintenance of euthyroid state ceases attacks. To summarize, few case series report the association of HPP with Graves’ disease. These patients usually present acutely with severe muscle weakness or paralysis. In conclusion, in diagnosis of HPP, possibility of thyrotoxicosis should be considered, especially in the absence of family history of PP.

Presentation: No date and time listed
OR09-4 Novel Murine Models of BrafV600E driven Papillary Thyroid Cancer
Authors: Casado Medrano Victoria , Franco Aime , O’Neill Alison , Scheerer Michele , Spangler Zachary , Purvis Grace
Published: November 2022

Thyroid cancer is the most prevalent endocrine malignancy and is estimated to have affected 52,890 individuals in the United States in the year 2020. Papillary thyroid cancer (PTC) accounts for up to 80% of all thyroid cancer diagnoses. Within PTC, BRAFV600E is the most common mutation in adults and the second most common mutation in pediatrics. While there are several validated human thyroid cancer cell lines harboring BRAF mutations, no pediatric derived cell line has been established to date, limiting generalizations in pediatric disease. Patient-derived pre-clinical models are valuable tools but are limited due to their need to be studied in vitro or in an immunocompromised host. However, in vivo mouse models recapitulate the complex interactions between tumor cells, the immune system, and components of the microenvironment, allowing more comprehensive investigation of thyroid oncogenesis and response to therapy. In this study we describe a new subcutaneous mouse model that can be used to understand differences between pediatric onset and adult onset PTC.

We have developed multiple independent, congenic murine cell lines from different stages of thyroid cancer progression. Two independent BRAFV600E-driven cell lines harboring the same genetic mutations were utilized in this study, one representing a well-differentiated tumor (WD) and one representing a poorly-differentiated tumor (PD). Despite coming from different stages of disease, both cell lines showed similar expression of the thyroid specific genes: Pax8, Ttf1, Tg, and Slc5a5, but expression of Pax8, Tg, and Slc5a5 was lower compared to WT thyrocytes. Activation of the Pi3Kinase pathway and the Akt Pathway were assessed via western blot analysis. The WD cell line had increased pERK activation compared to the PD cell line, and the PD cell line had increased pAKT compared to WD cell line.

Both cell lines were injected subcutaneously into the hind flank of Wt SJV129 mice of pediatric age (4-5 weeks) and adult age (20-22 weeks). These animals were monitored for 10 weeks post injection. While the PD cell line developed tumors at approximately the same rate and penetrance in both age groups, tumors reached end point more rapidly in the adult cohort. Adult hosts injected with the WD cell line developed tumors more rapidly than in pediatric hosts, however, tumors receded in both cohorts.

While adult and pediatric thyroid cancer share common driving mutations, there are distinct differences in disease pathogenesis between these patient populations. There are known differences in the immune system, metabolism, and other variables between pediatrics and adults. However, it is unknown what causes the difference in PTC pathogenesis between pediatric versus adult patients. We believe these new models provide a great opportunity to evaluate the role of age in PTC development and progression.

Presentation: Saturday, June 11, 2022 12:15 p.m. - 12:30 p.m.
OR09-6 Identification of MicroRNAs Critical to the Lymph Node Metastatic Process of Thyroid Cancer
Authors: Barreto Icléia S , Bezerra Mateus L , Bufalo Natassia E , Cunha Lucas L , Freitas Leandro L L , Geraldo Murilo V , Matos Alexandre H B , Rabi Larissa T , Tincani Alfio J , Tincani Priscila C , Ward Laura S , Peres Karina C
Published: November 2022

The identification of thyroid tumors with the potential for poor evolution is a major concern, as current management can range from simple active surveillance to aggressive therapeutic measures. MicroRNAs are small non-coding RNAs that play a key role in the regulation of gene expression and therefore in the pathogenesis and progression of different types of cancers. Here we employed several bioinformatics tools to investigate deregulated miRNAs in the lymph node metastasis (LNM) of two different types of thyroid tumors. Using thyroid cancer RNA-seq data available on Gene Expression Omnibus (GEO), we identified 14 common deregulated miRNAs in LNM of both medullary and papillary thyroid carcinomas, three of them still negatively deregulated when compared to their respective primary tumor: miR-199a-3p, miR-199a-5p, and miR-148a-5p. Public data available on TCGA confirmed the downregulation of miR-148a-5p in LNM and tumors with advanced AJCC stage. Looking at their predicted target genes, ITGA3, PVRL1 (also called NECTIN1), SNN, and FBXO28 genes were confirmed as positively deregulated in LNM papillary thyroid carcinomas when compared to normal tissues. Public data available on TCGA once again confirmed higher expression of the ITGA3 gene in LNM, larger and invasive tumors (T4a), and stage III and IV. Similar results were observed for PVRL1 (NECTIN1) and FBXO28, but not for SNN. These bioinformatic analysis findings suggest that miR-199a-3p, miR-199a-5p, and miR-148a-5p dysregulation, leading to epithelial-mesenchymal transition and cell adhesion failure, are associated with thyroid tumors’ LNM.

Presentation: Saturday, June 11, 2022 12:45 p.m. - 1:00 p.m.
OR11-3 Steroid Treatment in the Management of Destructive Thyrotoxicosis Induced by PD1 Blockade
Authors: Antonangeli Lucia , Antonuzzo Andrea , Brogioni Sandra , Chella Antonio , Cremolini Chiara , Latrofa Francesco , Lupi Isabella , Marcocci Claudio , Montanelli Lucia , Pierotti Laura , Santini Ferruccio , Sardella Chiara , Sgrò Daniele , Viola Nicola , Brancatella Alessandro
Published: November 2022

Background

Destructive thyroiditis is the most common endocrine immune related adverse event (iRAEs) in patients treated with anti-PD1/PD-L1 agents. Given its self-limited course, current guidelines recommend no treatment for this iRAE. Nevertheless in patients with enlarged thyroid volume and a poor performance status, thyrotoxicosis may be particularly severe and harmful. Aim of the study is to evaluate if steroid treatment might be useful in improving thyrotoxicosis in subjects with a poor performance status.

Methods

We conducted a case-control study, comparing the course of thyrotoxicosis of 4 patients treated with oral prednisone at the dosage of 25 mg/d (tapered to discontinuation in three weeks) and an enlarged thyroid volume to that of 8 patients with similar thyroid volume who were left untreated.

Results

No difference was found between the two groups at the onset of thyrotoxicosis (time 0) in demographic characteristics and in the levels of thyroid hormones. The levels of thyroid hormones were lower in subjects treated with prednisone compared to those untreated at time 7, 14, 21, 28, 35, 42, 60 and 90 days (P<0.05 at each time). The median time to remission of thyrotoxicosis was 24 days in patients treated with steroids and 92 days in untreated patients (P<0.001). At 6 months, the rate of evolution to hypothyroidism was similar in the 2 groups (4/4 in steroid group vs 7/8 in untreated group, P=0.74) and no difference was found in tumor progression (Progression free survival in treated group 5.1 months vs 5.0 months in untreated patients, P=0.89).

Conclusion

A short period of prednisone therapy is useful to restore more quickly euthyroidism in patients with a poor performance status and a severe destructive thyrotoxicosis induced by PD-1 blockade. This treatment does not impair the efficacy of immunotherapy.

Presentation: Sunday, June 12, 2022 11:30 a.m. - 11:45 a.m.
OR19-3 Differential Interactions of Vitamin D Binding Protein and Vitamin D Receptor in Different Ethnic Groups with Aggressive Thyroid Cancer
Authors: Gray Austin , Laxa Ria , Perez Mia , Rood Kristiana , Simental Alfred , Yamauchi Celina Romi , Khan Salma
Published: November 2022

Thyroid cancer affects ethnic groups at different rates and severity. Despite this, thyroid cancer health disparities are still an understudied area. Our laboratory has shown a differential expression of vitamin D binding protein (DBP) in Filipino Americans (FA) versus European Americans (EA) [1]. Higher DBP levels correlate to a better prognosis. A study has revealed a DBP-dependent vitamin D receptor (VDR) promoter activation. In this study, we investigated whether VDR and DBP are expressed differentially in different ethnic groups, such as African Americans (AA), Hispanic Americans (HA), EA, and FA. We were also able to determine the differential DBP polymorphisms, VDR variant expressions, and DBP-VDR interactions within different ethnicities. By PCR-Restriction Fragment Length Polymorphism (PCR-RFLP), we determined a higher frequency of DBP gene polymorphism in FA versus EA. Analyzing the Cancer Genome Atlas (TCGA) thyroid cancer datasets with the UALCAN assay, we found the differential expressions of DBP and VDR genes based on cancer stages, sample types, race, and histological subtypes. By immunohistochemistry, we detected strong nuclear VDR (nVDR) and very low membranous VDR (mVDR) expression that correlated with low DBP in FA thyroid cancer tissues. In contrast, there was a higher expression of both mVDR and DBP in HA versus the other ethnicities. Co-immunoprecipitation analysis revealed a stronger DBP interaction with mVDR in FA compared to other ethnicities. Our data suggest that low DBP correlates with low mVDR in FA, whereas high DBP correlates with high mVDR in the other ethnicities. In conclusion, the strong interaction of DBP with mVDR in FA may implicate the potential role of DBP-mVDR crosstalk in aggressive thyroid cancer. Future research goals will be aimed at determining pathways involved in BDP-mVDR crosstalk in thyroid cancer health disparities.

B. Mull, R. Davis, I. Munir, M.C. Perez, A.A. Simental, S. Khan, Differential expression of Vitamin D binding protein in thyroid cancer health disparities, Oncotarget 12(7) (2021) 596-607.

Presentation: Monday, June 13, 2022 11:30 a.m. - 11:45 p.m.
PSAT271 The Impact of Maternal Autoimmune thyroid disease on neonatal thyroid conditions in Urban City Population
Authors: Murthy Deepa Badrinath , Mally Pradeep , Shah Bina
Published: November 2022

Background

There is a wide spectrum of maternal autoimmune thyroid disorders (AITD) in pregnancy ranging from Graves’ hyperthyroidism (GD) to Hashimoto thyroiditis (HT), both of which share similar immunological properties. A variety of maternal thyroid autoantibodies can cross transplacentally which may potentially cause varying degrees of neonatal thyroid dysfunction.

Objective

To study the neonatal outcomes of thyroid function in mothers with AITD in urban setting.

Methods

Mothers with AITD and newborns were included for retrospective analysis over 12 months. AITD encompassed all mothers diagnosed prior/during pregnancy with either HT or GD.

Results

Maternal Data: A total of 147 mothers were included (HT 87%, GD 13.6%). Among mothers with HT, thyroid auto-Abs were tested in 51/127 (40%) mothers, of which 32/47(68%) were positive for TPO, 11/21(2%) positive for ATA, 2/6(33%) positive for TSI, 1/2 (50%) positive for TRAb. L-Thyroxine was administered to 90% HT mothers. Among mothers with GD, thyroid auto-Abs were tested in 17/20 (85%) mothers, of which 7/17(41%) were positive for TSI, 6/10(60%) positive for TRAb, 7/14(50%) were positive for TPO, 3/5 positive for ATA. Methimazole (MMI) was administered to 25% GD mothers.

Neonatal outcome: A total of 150 neonates (115 FT, 35 PT) were born to AITD mothers. Newborn screen was abnormal in 2 infants. 7 neonates (4.6%) were tested for thyroid auto-Abs, of which 1/2 was positive for TPO, 1/2 positive for ATA, 3/3 negative for TSI, 5/5 negative for TRAb. Serum TFTs were performed in 62/150 neonates; majority 57/62(92%) were normal, 3 had mild compensated hyperthyrotropinemia (mean TSH 17.1 mIU/L, FT4 1.93 ng/dl) and were followed elsewhere. 2 neonates developed congenital hypothyroidism requiring L-Thyroxine. Infant 1: TSH 4.56mIU/L, FT4 1.1 ng/dl, TPO and ATA positive on DOL7 and had ectopic thyroid, infant born to TPO positive HT mother on Synthroid. Infant 2: TSH 149.5mIU/L, FT4 0.8 ng/dl, TSI negative on DOL7 and had hyperemic thyroid, born to TSI, TPO and TRAb positive GD mother on MMI. Overall, only 3.3% of neonates had evidence of thyroid function abnormality which may have either been transient or permanent.

Conclusion

Although rare, mothers with AITD might potentially impair neonatal thyroid function. This may be due to various thyroid auto-Abs or anti- thyroid medication that cross transplacentally. Maternal history of AITD should therefore raise suspicion to screen neonates and thus warrants continued vigilance.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT296 Graves’ Disease and Hurthle Cell Carcinoma: A Rare Presentation
Authors: Bhatt Plukshi J , Madhavan Parvathy
Published: November 2022

Introduction

Hurthle cell carcinoma is a rare thyroid malignancy, only accounting for 3-5% of all thyroid malignancies. Thyroid tumors are classified as Hurthle cell carcinomas when they contain more than 75% Hurthle cells. Hurthle cells are oncocytic cells with an acidic cytoplasm and can contain up to 5,000 mitochondria. In the thyroid, oncocytic changes are associated with conditions such as cell-mediated autoimmune thyroiditis, humoral-mediated hyperthyroidism (Graves’ disease), and hyperplastic nodules seen in multinodular goiters.

Case Presentation

A 64-year-old Polish female with a medical history of hypertension, hyperlipidemia, and smoking presented with fatigue, weight loss of 18kg in 6 months, palpitations, tremors, anxiety, heat intolerance, and diarrhea. Family history was pertinent for thyroid lobectomy in older sister and thyroidectomy in niece with reportedly benign pathology. She denied any family history of thyroid cancer. She resided 1,000 kilometers away from Chernobyl at the time of the nuclear accident.

Diagnosis and Treatment

Hyperthyroidism was attributed to Graves’ disease, and she was started on methimazole with improvement in symptoms. Fine needle aspiration of 3.4cm right thyroid nodule showed moderate to high cellularity with abundant discohesive Hurthle cells with granular cytoplasm, large nuclei with prominent nucleoli and mild nuclear atypia consistent with Hurthle cell carcinoma with a 25-40% risk of malignancy. She had a total thyroidectomy that revealed a 3cm minimally invasive Hurthle cell carcinoma with a benign lymph node. She was started on levothyroxine 100mcg. Post-surgery labs showed thyroglobulin 3 ng/mL [1.3-31.8], undetectable thyroglobulin antibody, suppressed TSH and normal calcium levels. Further course was complicated by Graves’ orbitopathy, worsened by smoking. She was started on teprotumumab and tapered dexamethasone before receiving 30 mCi radioactive iodine for remnant ablation.

Discussion and Conclusion

Graves’ disease is the most common cause of hyperthyroidism accounting for 60%- 80% of hyperthyroid cases. Graves’ disease has been reported to be associated with aggressive thyroid carcinomas, 88%being papillary thyroid cancers. Some studies note an increased mortality in patients with differentiated thyroid cancer associated with Graves’ disease when compared to euthyroid controls. Hurthle cell carcinoma is a rare thyroid malignancy and is uncommonly seen in conjunction with Graves’ disease.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT320 Does Iodine Deficiency Increase the Risk of Subacute Thyroiditis after Postcovit Period?
Authors: Kale Banu
Published: November 2022

Subacute thyroiditis (SAT, de Quervain thyroiditis) is usually a self-limiting inflammatory condition of thyroid. The clinical presentation usually includes painful diffuse goiter with thyrotoxicosis. Post-viral subacute thyroiditis has been reported following viral infection. A limited number of SAT after covit infection have been reported in literatura up to now.

This abstract reports two cases of SAT after covit infection. Thyroid ultrasonography of the patients indicate enlarged hypoechoic thyroid with decreased vascularity and heterogenous echotexture. Elevated CRP is detected at the time of SAT diagnosis. There is a difference between these two cases and previouse described ones in litratura. Urinary iodine exclusion detected as lower than normal ranges. Does iodine deficiency increase the risk of subacute thyroiditis after postcovit period?

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT322 A "Natural Thyroid Booster" Induced Hyperthyroidism
Authors: Ziganshina Anna , Joseph Jalaja
Published: November 2022

Background

In the recent years market got filled with a variety of freely available and not FDA regulated supplements that claim to ensure thyroid gland "support", "activation", "boost", "restoration", "drive", "edge", "strength" and a midst of other positive effects. These supplements are often not considered as medications and often are not reported during medication reconciliation. We present a case of hyperthyroidism in a patient using a supplement containing potassium iodide

Clinical Case

54-year-old male with newly diagnosed atrial fibrillation in Feb 2021 presented in September 2021 with non-ST elevation myocardial infarction. He continued to have persistent atrial fibrillation. At presentation TSH was nearly suppressed at 0.02 MIU/ml, FT4 was normal at 1.6 ng/dl, TT3 increased at 241 ng/dL. During endocrinology evaluation in October 2021 thyroid function values remained the same, TSI and TRAB were negative and TGAB were increased at 8 IU/ml. Imaging studies were not consistent with thyroiditis (heterogenous and hypervascular gland on ultrasound, normal RAI), a possibility of antibody negative Graves’ disease was entertained, however thyroid function tests in November 2021 were quite different and showed elevated TSH of 71 MIU/L, FT4 low at 0.3 ng/dl, low TT3 at 48 ng/dl. At this time patient recalled being on thyroid supplement in the recent past, per patient he did not realize that it was relevant information to disclose to the physician. He was on "Thyroid PX" from September 2020 to February 2021 per recommendation from naturopathic doctor for symptomatic subclinical hypothyroidism when in September 2020 TSH was noticed to be mildly elevated at 6.73 MIU/ml, FT4 normal at 1. 0 ng/dl and TT3 normal at 99 ng/dl.

Conclusion

This case represents an example of thyroid supplement use related thyrotoxicosis. He was taking "megadoses" (80 times the recommended daily dose) of iodine that likely have caused Jod-Basedow phenomenon, which is a hyperthyroidism following exposure to the excess of iodine. Among documented ingredients of "Thyroid PX" are potassium iodide, cholecalciferol, methylcobalamim, Ashwagandha root, Ginger root, Nettle leaf and others. Each capsule contains 6000mcg of Potassium Iodide (daily dose – 2 capsules) with recommended daily iodine dose for adults of 150mcg. Hyperthyroid stage was followed by the stage of profound hypothyroidism. The patient could have been predisposed to Jod-Basedow phenomenon due to Hashimoto thyroiditis. This illustrates an importance of obtaining detailed history of use of any/thyroid supplements in all patients with unexplained hyperthyroidism.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.