bluuebunny/crossref_metadata_2025 huggingface dataset:
ODP498 Myocardial Ischemia precipitating thyroid storm diagnosed during recovery through Wellen's wave: An ECG for an eye
Authors: Patra Shinjan , Roy Ayan
Published: November 2022

Introduction: Thyroid storm is a major life-threatening condition in a patient of thyrotoxicosis which can accelerate the cardiovascular morbidity in forms of tachycardia, arrythmia and congestive heart failure. It can be precipitated by acute coronary syndrome. Most literatures have reported acute coronary syndromes during the presentation itself but here we shall describe an intriguing case where the diagnosis was possible after the resolution of the thyroid storm. Clinical case: A 55-year-old graves’ disease patient had presented with classical features of thyroid storm which was precipitated by discontinuation of the anti-thyroid drugs. His initial electrocardiogram (ECG) showed sinus tachycardia. He was promptly started on intravenous fluid, 80 mg of daily carbimazole along with lugol's iodine and intravenous dexamethasone. Within 48 hours of treatment, his vitals became normal with resolution of the thyroid storm. His thyroid hormone status also showed marked improvement (free T4 falls from 90.31 ng/dl to 2.31 ng/dl) (normal range: 0.7 ng/dl-1.7 ng/dl). Due to his persistent jaw pain, mild chest discomfort and hiccough, ECG recordings were done in regular intervals. Interestingly it showed dynamic changes consisted of biphasic T waves. This ECG changes were seen after the resolution of the thyroid storm features. The cardiac enzymes were within normal limits. We thought of wellen's syndrome and sought urgent cardiological consultation. Coronary angiography reveals left anterior descending artery (LAD) obstruction and patient promptly underwent percutaneous transluminal angioplasty. Patient's angina equivalent symptoms had resolved remarkably. He recovered satisfactorily and was discharged after 5 days. Clinical lesson: Ischemic heart disease is a well-known co-morbidity in a case of thyroid storm which can be identified at the initial presentation. But here the dynamic changes of ECG appeared after the resolution of the thyroid storm. It was classical of type A wellen's wave which is a harbinger of imminent massive anterior myocardial wall infarction due to near-complete blockage of LAD. Initial sinus tachycardia probably had hindered the appearance of typical wellen's wave in this case. But as soon as the thyroid storm resolved, typical dynamic changes appeared in the form of wellen's wave. Early suspicion due to following serial dynamic ECG changes has prevented a major catastrophe in this case. This case highlights the importance of tracking serial ECG changes in a patient of thyroid storm which can unmask any underlying ischemic cardiac disease even after apparent improvement of the clinical status. This clinical case also reports a unique association of thyroid storm and type A wellen's syndrome.

Presentation: No date and time listed
ODP631 Infectious Disease Causing Damage Of The Adrenal Glands, A Life Threating Event
Authors: Saleem Marwa , Correa Ricardo
Published: November 2022

Introduction

Primary Adrenal Insufficiency (PAI) is not a common cause of adrenal insufficiency. The most common cause is Addison disease that is an autoimmune condition. Other causes include hemorrhage, infiltration, infections, necrosis and metastasis. We present a rare case of primary adrenal insufficiency caused by disseminated histoplasmosis.

Case presentation

87 yo male from the Midwest with a history of HTN, HLD, CAD s/p CABG was admitted to our hospital for fatigue and 15 lbs weight loss. In the ED, he was found to have persistent hypoglycemia (BG in the 50s mg/dl after several vials of D50%). He was admitted to ICU for continuous D10% infusion. His laboratory showed Na 137mmol/L, K 3.7mmol/L. Further work up for hypoglycemia showed BG of 53 mg/dl with C-peptide of 0.92ng/ml and Insulin <1uIU/ml. Due to the concern of non-insulin dependent hypoglycemia, AM cortisol was done which was low7ug/dl. Immediately, he was started on high dose hydrocortisone. Head CT was negative for pituitary lesions. CT showed lung nodules and bilateral peripherally calcified adrenal lesions 3.6 & 2.6 cm homogenous, well defined borders (HU 20-30). Adrenal hormones work up showed normal metanephrines, Aldosterone <1ng/dl and PRA 1.35ng/ml/h (0.25-5.82). ACTH stim test revealed cortisol level of 9. 0 ug/dl, 9.4 ug/dl, and 9.2 ug/dl at baseline, 30min and 1hr respectively with a baseline ACTH of 539. Lung biopsy showed necrotizing granuloma and fungal spores compatible with histoplasmosis. He was started on amphotericin then transition to itraconazole for 1 year. Additionally, the dose of HC was decrease and Fludrocortisone 0.1mg daily was added. He refused adrenal biopsy at that point and wanted to continue current treatment with a plan to repeat imaging in 3 months and possible adrenal biopsy depending on CT results. On follow-up, patient regained weight and hypoglycemia resolved. Repeated adrenal CT showed shrinkage of the adrenal nodules bilateral. He was continued on PAI replacement.

Discussion

Histoplasmosis is a fungal infection caused by (H. capsulatum), found in soil contaminated with bird or bat droppings. Infection usually limited to respiratory disease in immunocompetent host but may cause disseminated infection in immunocompromised patient which can involve any organ system. Less commonly, disseminated type may occur in an immunocompetent host with the adrenal gland being the most common infected organ. Treatment involves systemic antifungal therapy; ketoconazole or itraconazole for mild-moderate forms and amphotericin B for 12-18 months for severe ones. Relapse rate is high; ∼ 7.5% and most patients require long-term glucocorticoid replacement. Because unrecognized disseminated histoplasmosis accompanying PAI usually results in a high mortality rate, considerable suspicion and appropriate investigations are necessary for correct diagnosis of this rare but treatable disease.

Presentation: No date and time listed
ODP503 Non-Small Cell Lung Cancer Metastatic to the Thyroid Gland
Authors: Pessoa Carolina Mendes , Madhavan Parvathy
Published: November 2022

Introduction

Metastatic disease affecting the thyroid gland is an uncommon phenomenon, with the most common primary sites being kidney, breast, lung and gastrointestinal tract. Thyroid metastases frequently occur simultaneously with spread to other sites and are rarely symptomatic. Clinical case: 73-year-old female with remote history of stage IA (T1c, N0, M0) invasive lobular carcinoma of the right breast treated with lumpectomy, radiation and tamoxifen, previous tobacco use, remote exposure to radiation during Chernobyl nuclear accident, developed progressive dyspnea on exertion. She was found to have a large left-sided pleural effusion. Thoracentesis was performed, and the cytology revealed adenocarcinoma with features favoring lung primary. Further imaging showed a left lower lobe mass with central necrosis and left hilar adenopathy, multiple pleural masses, and a small solitary brain lesion. PET-CT also demonstrated, amongst other findings, an FDG avid left lower pole thyroid nodule. Thyroid ultrasound was obtained to further characterize the lesion, which demonstrated a 0.8×1.3×1.3 cm solid hypoechoic nodule in the left mid lobe, which was thought to be corresponding to the PET avid nodule. Two additional nodules, a mixed cystic and solid measuring 1.7×2.1×2.9 cm on the right lobe, and another left-sided solid isoechoic measuring 0.8×0.7×0.9 cm, were noted. Thyroid FNA of the 1.3 cm PET avid nodule revealed rare cells in clusters, with large pale nuclei and prominent nucleoli, some with intracytoplasmic vacuoles, morphologically similar to those seen in the prior pleural fluid. Thin prep was stained with antibody to thyroglobulin, and the malignant cells showed lack of staining, supporting the diagnosis of metastatic lung cancer. Thyroid function tests were normal. Given lack of compressive symptoms, patient was maintained on her primary oncologic treatment with carboplatin and pemetrexed, and stereotactic radiation for the brain metastasis. Repeat PET-CT, performed approximately 8 months after the initial scan, showed mildly decreased focal FDG activity in the thyroid lesion.

Discussion

In this scenario, a patient with primary lung malignancy was found to have an FDG avid thyroid nodule which on FNA proved to be a metastatic lesion. Per some studies, such lesions can be seen in 1.4%–3% of patients who undergo surgery for suspected malignancy in the thyroid gland. Management of metastatic thyroid cancers depends on multiple factors including the primary malignancy location and staging, patient comorbidities, compressive symptoms, etc. Surgical management may be of benefit in isolated lesions in the thyroid.

Conclusion

When evaluating thyroid nodules in patients with known history of malignancy, it is important to consider the differential of metastatic lesions and to perform a thorough evaluation including fine-needle aspiration for clinical elucidation and management.

Presentation: No date and time listed
ODP505 Polymorphisms of ITM2A rs1751094 on×Chromosome Is Associated with intractable Graves’ disease in Korean Children
Authors: Ahn Moonbae , Cho Kyoung Soon , Ho Jung Min , Suh Byung-Kyu , Kim Sung Eun , Cho Won Kyoung , Kim Mirae , Baek In-Cheol , Kim Tai-Gyu , Shin Chungwoo , Jeong Jang Min , Ju Choi Young , Lee Na Yeong , Kim Seul K , Kim Shin Hee
Published: November 2022

Background

Autoimmune thyroid diseases (AITDs) are female predominant and much attention has been focused on integral membrane protein 2A (ITM2A) on the X chromosome as Grave's disease (GD) susceptible locus.

Methods

We genotyped ITM2A rs1751094 single nucleotide polymorphism (SNP) in 166 patients (142 females and 24 males) diagnosed with AITD (67 HD and 99 GD cases). The mean age (±SD) of GD patients at enrollment was 14.4 ± 3.5 years and HD patients was 13.8 ± 3.5 years. In GD patients, 49 patients (49/99, 49.5%) had thyroid-associated ophthalmopathy (TAO). Among the 85 GD patients, 60 patients (60/85, 70.6%) were intractable GD. The data were analyzed by sex-stratified or combined with 198 healthy Korean individuals (97 females and 101 males).

Results

Target SNP fits the HWE. In patients with AITD (n = 166), the genotype and allele frequencies of rs1751094 AC (OR=2.5, corrected P (Pc) = 0. 000), C (OR=2. 0, Pc = 0. 000) were higher and those of AA/A (OR=0.3, Pc = 0. 000), A (OR=0.5, Pc = 0. 000) were lower than those in controls (n = 198) (Table 3). In female AITD patients (n = 143), those of rs1751094 CC (OR=2.4, Pc = 0. 031), C (OR=1.8, Pc = 0. 003) were higher and those of rs1751094 AA (OR=0.5, Pc = 0. 027), A (OR=0.6, Pc = 0. 003) were lower than those of female controls (n = 97). In patients with GD (n = 99), rs1751094 CC/C (OR=3.5, Pc = 0. 000) and C (OR=3.4, Pc = 0. 000) were higher those in controls (n = 198). In intractable GD Patients (n = 60), rs1751094 AC (OR=2.2, Pc = 0. 026) and C (OR=2.5, Pc = 0. 000) were higher than those in controls. In GD with TAO (n=49), rs1751094 CC/C (OR=2.9, Pc = 0. 003), C (OR=3.3, Pc = 0. 000) were higher than those in controls. In patients with HT (n = 67), the genotype frequencies of rs1751094 AC (OR=3. 0, Pc = 0. 000) was higher and those of AA/A (OR=0.4, Pc = 0. 002) were lower than those in controls (n = 198).

Conclusions

Polymorphisms in ITM2A rs1751094 on the X chromosome might be associated with AITD in Korean children.

Presentation: No date and time listed
ODP517 Successful Treatment of Myxedema Coma after SARS-CoV-2 infection with Combination Oral Levothyroxine and Liothyronine
Authors: Dimayuga Diana Colleen , Villa Michael
Published: November 2022

Introduction

Myxedema coma (MC) is a rare, extreme form of hypothyroidism. It can be triggered by numerous factors including severe illness, trauma and infection. With the emergence of COVID, one may ask if COVID infection can lead to myxedema coma. Prompt infusion of levothyroxine is the consensus treatment. However, in areas where the IV form is unavailable, oral levothyroxine and liothyronine can be an option.

Case

This is a case of a 64-year-old Filipino female with no known comorbidities, no history of neck radiation or thyroid surgery. She was hospitalized for 28 days a month prior to this admission for severe COVID and and was discharged well. One day after discharge, she was noted to have decrease in sensorium with no other apparent cause.

On examination, the patient was unresponsive with a blood pressure of 60/40 mmHg, heart rate of 52 bpm, temperature 36°C and oxygen saturation of 96% at 7lpm. Examination of the neck showed no mass or scar, and the rest of systemic exam was unremarkable. Her initial bloodwork showed: Hemoglobin 7 gm/dl, Creatinine 2.4 mg/dl, sodium 132 mmol/L and RBS 66 mg/dl. Thyroid stimulating hormone was 33.26 uIU/mL (NV 0.55 - 4.78 uIU/mL), free thyroxine (T4) level of 0. 07 ng/dl (NV 0.89-1.76 ng/dL) and a random serum cortisol 37.3 ug/dL. Anti-TPO was negative.

IV hydrocortisone 100mg was administered until adrenal insufficiency was ruled out. Due to the unavailability of IV formulations, a loading dose of 100mcg of levothyroxine tablet and 25mcg liothyronine tablet was given thru NGT. Intensive supportive care was given. Adjustment of levothyroxine dosage was based on clinical response. The patient responded well to treatment and was discharged improved after 3 weeks.

The temporal relationship between the patient's clinical manifestations and her recent infection, in the absence of other risk factors, made the authors consider that her myxedema coma was most likely precipitated by COVID. The proposed mechanism is via the ACE2 receptors highly expressed in the thyroid gland. SARS-CoV-2 hijacks these receptors in order to enter the thyroid, destroy follicular cells and stop the ability to produce T3 and T4.

Conclusion

Myxedema coma occurs when a precipitating factor disrupts thyroid hormone regulation and it bears a grim prognosis. Among patients with COVID and even those who have recovered, an increased suspicion of hypothyroidism is necessary to diagnose the condition at a stage that is early enough to avoid myxedema coma. In areas where parenteral levothyroxine is not available, this case shows that administration of combination oral levothyroxine and liothyronine for myxedema may be successful.

Presentation: No date and time listed
ODP528 Unwrapping The Mystery in a Hormonal Sandwich - Intra-thyroid Parathyroid with Thyroid Papillary Microcarcinoma
Authors: Arora Gunjan , Patel Toral , Qureshi Faisal
Published: November 2022

Case presentation

A 60-year-old female with Bipolar disorder (discontinued Lithium > 15 years prior), primary hyperparathyroidism and thyroid nodules (largest ∼2 cm) presented to the Endocrinologist for regular follow-up. She had previously not met the criteria for surgical intervention for hyperparathyroidism. Moreover, thyroid nodules were stable - TSH remained within the normal range and FNA-guided biopsy was negative for malignancy. Recently, however, she was noted to have rising serum calcium levels - peak of 11.5 mg/dL (8.6 - 10.3 mg/dL) in conjunction with elevated PTH 150 pg/mL (12 - 88 pg/mL). Localization studies revealed an unusual picture - with the parathyroid ultrasound showing a possible right inferior location while the sestamibi scan pointing to a possible left inferior area. Preoperative thyroid ultrasound showed findings consistent with multinodular goiter. In light of these results, bilateral neck dissection with parathyroidectomy was recommended. Intra-operatively, two left sided parathyroid glands each approximately 100 mg were excised in addition to a larger ∼700 mg right sided gland. However, the right inferior gland could not be located. The right thyroid lobe was noted to have a whitish, firm nodule and was excised. Final pathology report showed three gland parathyroid hyperplasia (two left inferior and one right superior) and tissue extracted from the right thyroid lobe serendipitously contained one normal appearing parathyroid gland, a benign calcified cystic nodule and a focus of thyroid papillary microcarcinoma (1.6 mm) limited to thyroid with negative margins. Post-operatively, she continued regular follow up and active surveillance of hormonal levels with the Endocrinology service.

Discussion

It has been estimated that 2 - 15% of patients with primary hyperparathyroidism have concomitant papillary thyroid cancer, most of which are microcarcinomas. Microcarcinoma is defined as a focus of thyroid cancer < 1 cm in size. Previously, microcarcinomas were treated aggressively with thyroidectomy. However, this topic has recently stirred much discussion and debate amongst experts. Current data suggests that microcarcinomas can be managed equally well with either immediate surgical excision or active surveillance. A retrospective study concluded that roughly 10% of papillary thyroid microcarcinoma exhibited progressive clinical course while less than 1% resulted in mortality. Therefore, there is a pressing need to raise awareness about this topic and educate both the medical as well as general community regarding treatment options and bring to attention that active surveillance under the guidance of an expert, although underutilized, is an effective strategy, with excellent outcomes.

Presentation: No date and time listed
ODP646 Deficient NNT Reduces Mitochondrial Mass and Cholesterol Trafficking in the Adrenal Cortex, Accumulating ROS and Impairing Steroids Production
Authors: Antonini Sonir , Bodoni Aline Faccioli , Coeli-Lacchini Fernanda , Gebenlian Juliana L , Moreira Ayrton C , Elias Lucila L , Junior Wilson Araujo Silva , Castro Margaret , Leopoldino Andreia Machado
Published: November 2022

Background

The mitochondrial enzyme nicotinamide nucleotide transhydrogenase (NNT) is essential in the antioxidant defense mechanisms. In addition, adrenal cortex cells appear to require NNT for normal steroidogenesis. However, to date, the mechanisms involved in NNT regulation of steroidogenesis are not fully understood.

Aim

To assess how NNT regulates steroidogenesis by characterizing how a loss-of-function NNT mutation impairs antioxidants mechanisms in adrenal cells resulting in FGD.

Methods

Genomic DNA of a boy with FGD was evaluated by whole-exome sequencing (WES). Candidate variants were analyzed in silico and confirmed by Sanger sequencing. Genotype-phenotype association of a new homozygous loss-of-function NNT variant with FGD was assessed in vitro. We built a stable knockdown model of the NNT gene in the H295R adrenal cell line using CRISPR Cas9 technology. We evaluated the effect of alterations in NNT on Cholesterol Trafficking (NBD-Cholesterol) and mitochondrial parameters (DCFDA and Mitotracker) as well as on adrenal steroidogenesis by cortisol (RIA) and aldosterone (ELISA) production. In this NNT stable knockdown model, we inserted the commercial plasmid NNT HaloTag human ORF in pFN21A (FHC01572) containing the wild type (WT) sequence of the NNT gene and the direct site mutagenesis.

Results

WES revealed the NNT p. G866D pathogenic variant in the affected patient. The familial pedigree analysis confirmed the segregation of this variant with FGD in homozygosis. The clone selected after NNT modification by the CRISPR- Cas9 system showed a 75% reduction in NNT protein expression. The NNT-deficient cell clone increased reactive oxygen species (ROS) production (p<0. 0001), decreased mitochondrial mass (p<0. 0001), and decreased density (p=0. 03) of cholesterol lipid droplets as well as cortisol (p<0,0001) and aldosterone (p=0. 006) secretion. Reexpression of NNT in an NNT-deficient cell clone restored the ROS levels (p<0. 0001). Compared to wild-type (WT), both under basal and oxidative stress conditions after stimulation of 10uM forskolin, homozygous p. G866D NNT exhibited increased ROS production (p=0. 0002; p<0. 0001, respectively).

Conclusions

Deficient NNT decreases mitochondrial mass and impairs cholesterol trafficking by reducing cholesterol droplets mass, leading to the loss of antioxidants mechanisms and accumulation of ROS. NNT impairment in adrenal cells decreases cortisol and aldosterone secretion. Altogether, these data enlighten the mechanisms by which NNT mutations result in primary adrenal insufficiency.

Presentation: No date and time listed
ODP531 Worsening of pretibial myxedema following repeated doses of radioiodine treatment in a patient with hyperthyroid Graves’ disease
Authors: Thewjitcharoen Yotsapon , Chatchomchuan Waralee , Wanothayaroj Ekgaluck , Veerasomboonsin Veekij , Nakasatien Soontaree , Himathongkam Thep
Published: November 2022

Introduction

The development of new-onset pretibial myxedema following radioiodine (RAI) treatment has been occasionally reported from the probable influences of thyrotropin receptor antibodies (TRAbs) similar to the RAI-associated Graves’ ophthalmopathy (GO). However, the worsening of pre-existing pretibial myxedema after RAI treatment has never been reported. Herein, we report an interesting case of fluctuating clinical course of pretibial myxedema following treatments of hyperthyroid Graves’ disease for over 3 years.

Case Report

A 49-year-old Thai woman with underlying hyperthyroid Graves’ disease with GO and pretibial myxedema for 1 year came to our hospital for relapsed hyperthyroidism and active, moderate-to-severe GO in 2019. A plague form of pretibial myxedema with indurated hyperpigmented lesion was found on both legs. Intravenous pulse methylprednisolone (IVMP) was given to control her active GO. Both GO and pretibial myxedema significantly improved after IVMP treatments. Then, RAI (30 mCi) was administered at 1 month later as a definitive treatment. Low dose of oral prednisolone (20 mg/ day) was also given before and after RAI treatment. Transient hypothyroidism developed at 4 months post-RAI and the estimated weights of the thyroid decreased from 60 grams to 30 grams. However, hyperthyroidism relapsed again within 6 months post-RAI treatment. At that time, her pretibial myxedema flared up slightly but her GO was still inactive. Eventually, a second dose of RAI (20 mCi) was given at 11 months apart from the first RAI administration. Low dose of oral prednisolone was also given. She developed post-radiation thyroiditis at 4 months after RAI with worsening of pretibial myxedema and mild exacerbation of GO. Topical corticosteroid ointment was given for pretibial myxedema and only local supportive measures was applied to treat GO. Finally, permanent hypothyroidism was achieved at 6 months after the second course of RAI. Currently, her pretibial myxedema is stable without further flareup.

Conclusion

Our case highlights the potential of RAI treatment to precipitate both GO and pretibial myxedema in patients with pre-existing skin lesions. Low dose prednisolone prophylaxis might not ensure preventative effect in exacerbation. Whether the risk of worsening of pretibial myxedema is higher in patients with persistent hyperthyroidism requiring a second dose of RAI is a question that warrants further studies.

Presentation: No date and time listed
ODP585 Occult metastatic medullary thyroid carcinoma without detectable primary tumor.
Authors: Chevais Anastassia , Mikheenkov Alexander , Soldatova Tatiana , Zlotnikova Olga , Lapshina Anastasia , Beltsevich Dmitry
Published: November 2022

Background

Occult thyroid cancer is a particularly rare type of thyroid carcinomas. The absolute majority is presented by papillary thyroid carcinoma. We report a case of a medullary thyroid carcinoma (MTC) that was detected as a primary tumor neither on preoperative ultrasound examination nor on postoperative morphological examination.

Case

A 57-year-old patient with no personal or family history of thyroid disease presented to the surgeon with the complaint of swelling in the cervical lymph nodes. Ultrasonography of the thyroid showed a hypoechoic 4 mm zone with peripheral calcification in the right lobe and two suspicious malignant lymph nodes 14×12 mm and 10×7 mm in the right paratracheal region. A blood test revealed no abnormalities in thyroid function (TSH 0.9 mUI/L, fT3 4.25 pmol/l, fT4 10.2 pmol/l). However, the calcitonin (CT) and the carcinoembryonic antigen (CEA) levels were significantly elevated – 144 pg/ml (N for male <12) and 28 pg/ml (N <5). We performed an ultrasound-guided fine-needle aspiration (FNA) cytology from the thyroid nodule with subsequent FNA-CT measurement which showed no signs of MTC (cells, adequate CT level). On the other hand, FNA of the lymph node revealed cytomorphology characteristics of MTC and according to FNA-CT measurement, the CT concentration exceeded the upper reporting range of 2000 pg/ml. We carried out the measurement of stimulated CT. Taking into account the significant CT level increase (0 min – 168 pg/ml, 2 min – 1050 pg/ml, 5 min – 857 pg/ml), we excluded the extrathyroidal CT production. Genetic analysis demonstrated the absence of usual RET mutation. Computed tomography was carried out showing multiple calcifications up to 6 mm in diameter in the lung. On the cervical scan: the right upper paratracheal lymph node (11 mm) and a 6 mm mass with calcification in the structure along the front line of the right main bronchus (at the level of the bifurcation), the rest of the lymph nodes were not enlarged. The patient underwent total thyroidectomy with central lymph node dissection. On the section in the middle third of the lobe, there was a dense, yellowish-grey knot of 5 mm in size and 8 lymph nodes 5-15 mm. Surprisingly the right lobe node was represented by colloid goiter with foci of fibrosis and calcifications. In two of the eight cervical nodes, we identified nodal metastases that contained a component of MTC. The primary tumor was not detected even after thorough and complete pathologic examination and immunohistochemical study of the thyroid. Postoperative CT level (third day after surgery) has fallen to 5.45 pg/ml.

Conclusion

Metastatic medullary thyroid carcinoma without detectable primary tumor is a rare but real occurrence that might be encountered in practice. The lack of malignant findings in the thyroid gland during preoperative examination complicates the diagnostic.

Presentation: No date and time listed
ODP590 Combined Orbital Irradiation and Systemic Steroids in the Management of Progressive Thyroid Eye Disease
Authors: Capellan Maria Leonora , Tiu Leo
Published: November 2022

We present a case of a 62-year-old female with Multinodular Toxic Goiter who later developed Grave's Ophthalmopathy. She had an elevated baseline TRAb with an orbital MRI that showed bilateral proptosis with enlarged bilateral medial and lateral recti and extraocular muscles of the superior complex. She was initially treated with oral steroids which led to resolution of her visual complaints. However, due to recurrence of an active ophthalmopathy, she was subsequently given pulsing corticosteroid therapy. This was followed by radiotherapy due to minimal improvement in double vision. After completion of treatment, inflammatory ophthalmologic signs and symptoms were significantly improved. Radiotherapy in combination with glucocorticoids, particularly in the presence of diplopia or restriction of extraocular motility, should be considered in the management of active thyroid associated orbitopathy.

Presentation: No date and time listed
OR04-1 The Developmental Origin and the Specification of the Adrenal Cortex in Humans and Cynomolgus Monkeys
Authors: Cheng Keren , Moriwaki Taku , Seita Yasunari , Sasaki Kotaro
Published: November 2022

The adrenal cortex and gonads are the two major endocrine hubs that participate in the hormonal regulation of vital aspects of mammalian homeostasis. Accordingly, their developmental aberrancies drive various congenital and adult-onset diseases. Lineage tracing studies in mice reveal that the adrenal cortex and gonads originate from a common progenitor, the adrenogonadal primordium. However, the specification pathways of the adrenal cortex and gonads and their lineage relationship remain poorly understood in humans. Here, we conduct the high resolution spatial and temporal lineage trajectory mapping of early human adrenal and gonadal lineages using single cell transcriptomics and histologic profiling on human embryos at 3-8 week post fertilization. We find that in humans, the adrenocortical lineage originates in a temporally and spatially distinct fashion from the gonadal lineage, arising earlier and more anteriorly within the coelomic epithelium. The adrenal primordium arises from adrenogenic coelomic epithelium via an epithelial-to-mesenchymal-like transition, which then progresses into the steroidogenic fetal zone via both direct and indirect routes. Notably, we find that adrenocortical and gonadal lineages exhibit distinct HOX codes, suggesting distinct anterior-posterior regionalization. Together, our assessment of the early divergence of these lineages challenges the paradigm established in rodents and present evidence that the specification programs directing the formation of adrenal glands and gonads differ between rodents and humans. The molecular details of early lineage diversification of human adrenals and gonads will serve as both a framework for understanding the molecular pathology of human disorders.

Presentation: Saturday, June 11, 2022 11:30 a.m. - 11:45 a.m.
OR19-1 Ncor1 Regulates the Expression of Dhcr24, which Controls de novo Cholesterol Synthesis in the Adrenal Gland Inner Cortex
Authors: Huang Chen-Che Jeff , Kang Yuan , Zheng Huifei
Published: November 2022

In many types of cells and tissues, the nuclear receptor corepressor 1 (Ncor1) is known as a main corepressor that interacts with thyroid hormone receptors (i.e., TRα, TRβ1, and TRβ2). In the absence of thyroid hormone (T3), NCOR1 is recruited by TRs to inhibit gene transcription. In the liver, the deletion of Ncor1 increases hepatic triglyceride levels. However, the detailed mechanism of how NCOR1 is involved in thyroid hormone signaling in different types of tissues is not fully understood. Our previous study showed that TRβ1 is expressed in the adrenal gland inner cortex and T3 treatment leads to the hypertrophy of this area. To determine the role of NCOR1 in the regulation of thyroid hormone signaling in adrenocortical cells, we generated the mice with a conditional deletion of Ncor1 in the adrenal cortex by crossing the Ncor1 floxed mice with the steroidogenic factor 1 (SF1) Cre mice. The RNA-seq data showed that only 76 genes were differentially expressed in adrenal glands due to the deletion of Ncor1 in adrenocortical cells. Gene ontology (GO) analysis revealed that 'cholesterol synthesis’ was the top GO term associated with these 76 genes. Interestingly, 24-dehydrocholesterol reductase (Dhcr24), the key enzyme for cholesterol synthesis, was upregulated in knockout mice adrenal glands in both sexes. This phenotype fits the results in our previous studies that (1) Dhcr24 is significantly increased under T3 treatment in wild-type mice adrenal glands and (2) the DHCR24-expressing zone in the inner cortex is the primary responsive adrenal cortical layer under T3 treatment which leads to increased lipid accumulation in this area. To further study how DHCR24 is involved in this T3-induced lipid accumulation in the adrenal gland inner cortex, we generated Dhcr24 conditional knockout mice. We found that the T3-induced lipid accumulation in the adrenal gland inner cortex was sharply decreased in the Dhcr24;Sf1-Cre mice. In summary, with the Ncor1 conditional knockout mice, we found that the regulation of the cholesterol synthesis through DHCR24 is the primary function of NCOR1 in the adrenal gland inner cortex; by using the Dhcr24 conditional knockout mice, we further confirmed that the T3-induced lipid accumulation in the adrenal inner cortex can be blocked by the deletion of DHCR24. This study used genetic mouse models to decipher the connection between nuclear receptor corepressor Ncor1, the cholesterol synthesis enzyme Dhcr24, and how they control de novo cholesterol synthesis in the adrenal gland inner cortex.

Presentation: Monday, June 13, 2022 11:00 a.m. - 11:15 a.m.
PSAT252 Primary Papillary Thyroid Carcinoma Arising from a Thyroglossal Duct Cyst
Authors: Kesavan Chary Priyanka , Bright Tamis , Ur Rehman Aziz
Published: November 2022

Background

Thyroglossal duct cysts (TGDC) are remnants of the thyroglossal duct tract that do not atrophy and disappear, instead undergoing cystic expansion and often presenting as a midline neck mass. Rarely, carcinomas of the thyroglossal duct cyst occur, either arising as a primary carcinoma or as a cystic metastasis from a primary thyroid cancer; the former are particularly rare. These thyroglossal duct cyst carcinomas most commonly present in the adult population.

Case Report

We present the case of a 32-year-old female without any significant past medical history who presented with a non-tender midline neck mass identified as a thyroglossal duct cyst and completely excised; pathology results were positive for a primary papillary thyroid carcinoma with a tumor measuring 1.3 cm in diameter within the TGDC. Thyroid Ultrasound also showed the presence of two nodules measuring 1.4 cm on the right and 1.2 cm on the left, respectively, with fine needle aspiration (FNA) of both the nodules confirming papillary thyroid carcinoma as well. Lymph node FNA was negative for metastatic carcinoma. The patient underwent a thyroidectomy which definitively confirmed both a classic papillary carcinoma as well as an encapsulated, non-invasive follicular variant. In keeping with the original finding of the patient having a primary thyroglossal duct cyst carcinoma, samples from the thyroidectomy had negative tumor margins, and were also negative for any angioinvasion, lymphatic invasion, or extrathyroidal extension.

Conclusion

While thyroglossal duct cysts are the most common type of congenital neck cyst, primary carcinomas arising from thyroglossal duct cysts are rare. Masses that occur anywhere along the thyroglossal duct tract should be investigated for malignancy, with additional investigation of the thyroid gland for either a primary or secondary thyroid cancer.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT261 Use of Steroids Pre- and Post-Teprotumumab in Thyroid Eye Disease Patients
Authors: Holt Robert J , Qashqai Anahita , Vesel Claudia , Taylor Stephanie D , Barretto Naina
Published: November 2022

Background

Thyroid eye disease (TED), an autoimmune disease, causes inflammation of the periorbital fat and muscle often leading to eye-bulging (proptosis), double-vision (diplopia), pain, redness and swelling. Steroids are effective in reducing inflammation, but have limited efficacy for proptosis and diplopia, and higher doses can be associated with adverse effects. Teprotumumab, an anti-insulin like growth factor-1 receptor inhibitory antibody, demonstrates significant improvements in proptosis, diplopia and inflammatory symptoms.1 Here we examined steroid use in the period leading up to, and the period after a full course of teprotumumab.

Methods

Deidentified claims data (IQVIA) from patients completing 8 infusions of teprotumumab (full course) before Dec 31, 2020 were examined for steroid use before and after treatment. To ensure that claims data were adequately captured, patients must have been in the database for at least 1 year before and 6 months after teprotumumab and have had a claim within 4 months of the first dose. The median cumulative dose of steroids (prednisone equivalent) was also determined.

Results

565 patients met the inclusion criteria with a mean age of 59.5 (13.3) years. 407 (72%) were female and 158 (28%) were male. 460 (81%) had ≥1 steroid prescription at any time before, during, or after teprotumumab within 69 months before teprotumumab and 16 months afterward with 78% use before, 10% use during and 25% after. 314 (56%) had ≥1 steroid prescription within 1 year before or 6 months after a course of teprotumumab. Of 283 patients who received steroids within 1 year pre-teprotumumab, the median cumulative dose per patient (MCDPP) increased from 295 to 607 mg 3-0 months prior to teprotumumab initiation and 82% (233) stopped steroid use after teprotumumab initiation. The MCDPP decreased by 80% (607mg to 120mg) in the 0-3 months pre-teprotumumab to 3-6 months post-teprotumumab. Finally, the number of patients receiving steroids 3-6 months after teprotumumab decreased by 74% from 3-0 months pre-teprotumumab.

Conclusions

While reasons for the escalating incidence, and magnitude, of steroid use pre-teprotumumab and reduced use post-teprotumumab could not be definitively determined, remote steroid use increased up until teprotumumab initiation with a majority of patients who had a steroid in the year preceding teprotumumab having no steroid use in the 6 months after teprotumumab. Further, the number of patients receiving steroids and the median cumulative dose of steroids post-teprotumumab was reduced by more than 70% and 80%, respectively from pre-teprotumumab doses, indicating that teprotumumab is a steroid sparing agent. Follow-up analyses will confirm the duration of this effect.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT267 Performance of ThyroSeq V3 molecular testing in assessing indeterminate thyroid nodules for thyroid cancer at an urban endocrinology clinic.
Authors: Bao Ginny , Chang Christine , Yin Anthony
Published: November 2022

Introduction

While fine needle aspiration (FNA) biopsy can accurately classify thyroid nodules as benign versus malignant in most cases, roughly 20% of cases remain indeterminate. Molecular testing can assist with risk stratification of indeterminate nodules, with the goal to identify benign nodules and therefore decrease further testing. We aimed to validate the accuracy of ThyroSeq v3 molecular testing for predicting malignancy in real-world practice in a diverse, urban setting.

Methods

This was a retrospective, cohort study of 41 adults with 43 indeterminate thyroid nodules, for which molecular analysis using the multigene classifier (GC) ThyroSeq v3 was performed at an outpatient endocrinology practice in San Francisco, CA between December 2011 and December 2021. The primary outcome was positive predictive value for malignancy in indeterminate thyroid nodules, using ThyroSeq v3. The secondary outcome was prediction of cancer by specific genetic alterations.

Results

Most patients were female (78.0%), with a median age of 56 years (range 30-84). Nodules were classified as low (n=28; 65.1%), low-intermediate (n=2; 4.7%), or intermediate-high (n=12; 27.9%) risk for malignancy using ThyroSeq v3. Risk could not be assessed in one nodule due to inadequate sample[1] . Of patients with low-risk nodules, only 1 underwent total thyroidectomy due to compressive symptoms[2] . Of patients with low-intermediate or intermediate-high risk nodules, most (13/14) underwent surgical resection[3] . Papillary thyroid cancer was identified in 72.7% (8/11) patients with intermediate-high risk nodules who underwent surgery. In patients with papillary thyroid cancer, the most common mutation was BRAF V600E (n=5). Among indeterminate nodules (Bethesda III and IV cytology[4]), the positive predictive value of ThyroSeq v3 was 54.5%[5] .

Conclusions

Of patients with thyroid nodules of indeterminate risk based on FNA biopsy and intermediate to high risk for malignancy as determined by ThyroSeq v3 molecular sequencing, most underwent surgical resection and were found to have thyroid cancer in most cases, with BRAF V600E being the most common mutation. ThyroSeq v3 is a useful stratification tool for those patients with indeterminate nodules.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT278 A Curious Case of Thyroglossal Duct Cancer
Authors: Faisal Sobia , Ibrahim Waleed , Gunay Canan
Published: November 2022

Introduction

Thyroglossal duct (TGD) cyst is a common congenital anomaly. Thyroid cancer rarely occurs in TGD cysts, affecting less than 1% of cysts. Here we present a case of TGD cancer presenting as a central neck mass.

Case Presentation

60 y.o female presented to her primary care physician with a neck mass without any compressive symptoms. She had no history of head/neck radiation exposure and no family history of thyroid cancer. She was noted to have a non-tender central neck mass with palpable cervical lymphadenopathy. Neck ultrasound revealed a 5.7 cm multilobulated cystic and solid mass anterior to the thyroid gland. CT scan of the neck revealed a lobulated mixed solid cystic mass at the level of the thyroid cartilage projecting anteriorly, with an abnormal right submandibular lymph node measuring 2.2×1.0 cm.

She was evaluated by ENT and underwent resection of the neck mass and the hyoid bone (Sistrunk's procedure). Level 1b lymph node was also removed. Operative findings were concerning for a malignant process. This was confirmed on pathology with findings of TGD papillary thyroid cancer (PTC) and level 1b lymph node demonstrating metastatic PTC with cystic features.

She was then referred to endocrine. Thyroid ultrasound revealed multiple bilateral intermediate suspicion nodules. Left inferior thyroid nodule was noted to have high suspicion sonographic features with abnormal right sided level 2 and 3 lymph nodes. She was referred for total thyroidectomy, pathology revealed multifocal PTC with lymph node involvement with extra nodal extension and metastasis to the left sternohyiod muscle, pT2, pN1b, AJCC stage 2.

6-week post-surgical labs revealed TSH of 1.69 mIU/L (ref range 0.40-4.50), thyroglobulin level of 0.8 ng/ml (ref range athyrotic <0.1), with undetectable thyroglobulin antibodies <1 IU/ml (ref range < or = 1 IU/mL). She underwent RAI with 104.6 mci. I-131 Metastatic survey revealed increased uptake in the thyroid bed, otherwise no increased activity elsewhere. Stimulated TSH and Thyroglobulin levels were done but not collected appropriately and therefore not mentioned here. Repeat labs 12 weeks after RAI revealed a TSH of 2.86 mIU/L, Thyroglobulin level of 0.2 ng/ml, and undetectable Thyroglobulin antibody.

Conclusion

There are no standardized guidelines for management of TGD cancer given the rarity of this condition. FNAB (Fine need aspiration biopsy) may be associated with high false negatives due to inadequate sampling, given the cystic nature of these lesions. In majority of these cases definitive diagnosis of cancer is made after excision of the TGD cyst. Some experts favor a conservative approach via Sistrunk's procedure and pursuing total thyroidectomy if there is high suspicion of thyroid gland involvement as well. Whereas other authors have suggested a more aggressive approach with total thyroidectomy even without evidence of concomitant involvement of the thyroid gland.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT282 A Case of Papillary Thyroid Cancer in a Thyroglossal Duct Cyst
Authors: Priyanka Mahali Lakshmi , Whitlatch Hilary B , Stefan Simona
Published: November 2022

Background

Thyroglossal duct cysts (TGDC) are common congenital neck anomalies. They persist through adulthood in 7% of the general population. Associated malignancy is rare, occurring in <1% of cases. Over 90% of such malignancies are papillary thyroid carcinoma (PTC). Twenty to 60% of patients with TGDC malignancies are found to have concomitant cancer in the thyroid. The rarity of TGDC malignancy make its management particularly challenging, given limited long term outcome data. We describe a case of a 4cm TGDC PTC.

Case

A 49-year-old female with a history of autoimmune thyroid disease presented for evaluation of a goiter. She reported 6 months of painful midline neck swelling. No family history of thyroid cancer and she had no history of radiation to her head or neck. She denied swallowing, dyspnea, or hoarseness. Physical exam was notable for a mildly tender, firm 2.5 cm submental midline neck mass overlying the hyoid. TSH was normal and thyroid peroxidase antibody was >1000 (n: <5 IU/mL). Neck ultrasound showed a 3.7×2.5×1.6 cm mixed solid/cystic midline neck mass and a mildly enlarged, heterogeneous, and vascular thyroid without discrete intrathyroidal nodules. A neck CT with contrast indicated that the midline mass was heterogeneously enhancing with tiny internal cystic spaces. The differential diagnosis included an infected thyroglossal duct cyst versus malignant transformation. Fine needle aspiration of the mass was suggestive of PTC. The patient underwent the Sistrunk procedure, with excision of the thyroglossal duct cyst, the middle of the hyoid bone, and the tissue surrounding the thyroglossal tract. Final pathology was consistent with a 4 cm PTC, classical type, without lymphatic, vascular or perineural invasion. Surgical margins were negative for malignancy. Two months postoperatively, TSH remained normal, and the thyroglobulin (TG) level was 78 with negative TG antibodies. She declined a thyroidectomy.

Conclusion

To date, there is no consensus guideline regarding optimal management for malignancy involving TGDC. Studies suggest that surgical decision making be based on patient risk stratification. High risk factors include age older than 45 years, tumor >4 cm in size, extension of tumor to adjacent soft tissue, and/or the presence of nodal or distant metastases. In high-risk patients, treatment with Sistrunk procedure combined with thyroidectomy, neck dissection and radioactive iodine therapy have shown excellent results. In younger than 45 years with tumor size <1.5 cm, without extension beyond cyst wall and normal thyroid ultrasound Sistrunk procedure alone might be sufficient. Despite low risk factors patients should still be advised to have thyroidectomy as there could be a 20% risk of coexisting thyroid cancer. Additional longitudinal studies are needed to confirm that this approach leads to optimal long-term outcomes for patients with TGDC-associated malignancy.

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