bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

Case presentation
A 60-year-old female with Bipolar disorder (discontinued Lithium &gt; 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 &lt; 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

Abstract

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&lt;0. 0001), decreased mitochondrial mass (p&lt;0. 0001), and decreased density (p=0. 03) of cholesterol lipid droplets as well as cortisol (p&lt;0,0001) and aldosterone (p=0. 006) secretion. Reexpression of NNT in an NNT-deficient cell clone restored the ROS levels (p&lt;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&lt;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

Abstract

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

Abstract

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 &lt;12) and 28 pg/ml (N &lt;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

Abstract
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

Abstract
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

Abstract
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

Abstract

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.