bluuebunny/crossref_metadata_2025 huggingface dataset:
ODP650 Impaired Cognition in Patients with Mild Autonomous Cortisol Secretion
Authors: Nathani Rohit , Thangamuthu Karthik , Singh Sumitabh , Zhang Catherine , Suresh Malavika , Ebbehøj Andreas , Bancos Irina
Published: November 2022

Background

Limited data describe cognitive deficits in patients with Cushing syndrome (CS). The impact of mild autonomous cortisol secretion (MACS) on cognition is unknown.

Objective

To determine the impact of MACS on cognitive function.

Methods

Single-center cross-sectional study of adults with MACS and age and sex-matched volunteers. MACS was defined as cortisol >1.8 mcg/dL following the dexamethasone suppression test (DST) in patients with an adrenal incidentaloma and no features of CS. We measured cognitive function through the NIH toolbox cognition battery (7 standardized tests of attention, episodic and working memory, language, executive function, and processing speed). T-scores corrected for age, sex, education, and race were used for analysis. All patients completed the SF-36 questionnaire. The frailty index was calculated as previously reported (Singh S. JCEM 2020).

Results

Participants included 50 patients with MACS (median age 61, range 54-68) and 50 volunteers (median age 60 years, range 54-68), with 60% women in both groups. In patients with MACS, median post-DST morning cortisol was 3.6 (range, 2.4-6.2), and median corticotropin was 8.5 (range, 5.9-13) pg/mL (normal 6-60). Patients with MACS had a higher median frailty index (median of 0.26 vs. 0. 05 in volunteers, p<0. 001) and lower quality of life scores on the SF-36 survey (median of 47 vs. 91, p<0. 001). Compared to volunteers, patients with MACS performed worse in the domains of attention and executive function (effective allocation of one's limited capabilities in an abundance of stimuli) (median T-score of 50 vs. 46, p=0. 03), cognitive flexibility (tested as the capacity to plan and monitor goal-directed activities) (median T-score of 61 vs. 55, p=0. 01). The fluid composite score (includes executive function, episodic memory, working memory, and processing speed) was lower in patients with MACS (mean of 53.2 vs. 48.9, p=0. 03). The total composite score was lower in patients with MACS when compared to volunteers (median T score of 50 vs. 54, p=0. 06). The total composite cognitive scores in patients of MACS were associated with the Frailty Index (R2 = 0.13, p = 0. 025) and SF-36 scores (R2 = 0. 08, p = 0. 05), but not post-DST cortisol.

Conclusion

Compared to volunteers, patients with MACS demonstrate cognitive impairment, particularly in the executive domain, which closely mimics changes observed with aging. These deficits do not correlate with the degree of cortisol excess.

Presentation: No date and time listed
OR09-1 Decoding Cancer Immunoediting of Tumor Microenvironment Provides Immunogenomic Marker for Thyroid Cancer Screening
Authors: Ali Sophia , Elsherif Ahmed , Jaume Juan , Kanzy Abed , Khogeer Feras , Madkhali Mohammed , Niaz Azra , Paparodis Rodis , Rafiqi Shafiya , Salim Nancy , Sarwar Haider , Tovar Yara , Zahid Zeeshan , Imam Shahnawaz
Published: November 2022

Thyroid cancer will become 4th most common cancer in women by 2030. Thyroid cancer is the most prevalent endocrine malignancy of women with an age-standardized rate of 10.1/100,000 while in men it is 3.1/100,000.

The microenvironment of thyroid cancer has a high degree of immune invasion, characterized by the presence of T effector (Teff, CD4, and CD8) cells. In our previous study based on 127 human FNA thyroid samples, we reported a dominant T cell species characterized by the deficiency of CD4 and CD8 expression (CD3+CD4-CD8-) Double Negative (DN) T cells, seem to have a regulatory function towards thyroid cancer immune tolerance (1-3).

Here, in another cohort study (46 patients), FNAs of thyroids showed that DN T-cells were significantly more abundant in lymphocytic infiltrates of thyroid cancer patients (post-operatively confirmed diagnosis by an academic pathologist), and if the DN T cell population exceeded our defined threshold (>9.14%), it indicated a high likelihood of cancer presence (96.6% sensitivity, 95% CI, 0.915 to 1.000). Conversely, DN T cells below the threshold (<9.14%) provide 100% specificity in predicting benignity of thyroid nodules. This study identifies DN T cell quantification as an accurate rule-out test. The high specificity of the test is promising since it abolishes false-positive diagnoses and unnecessary surgical procedures. Current molecular diagnostic testing, based on the identification of tumor gene mutations in FNA samples usually reduces the risk of cancer rather than guarantee the absence of cancer which leads to 70% of unnecessary thyroidectomies.

The present study proposes DN T cell quantification as a diagnostic signature for thyroid cancer. Its integration with RNA transcriptomics may provide a simplified technology for thyroid cancer screening and active surveillance.

References

1. Imam S, Paparodis R, Sharma D, et al. 2014 Lymphocytic profiling in thyroid cancer provides clues for failure of tumor immunity. EndocrRelat Cancer 21. 2. Imam S, Dar P, Paparodis R, et al. 2019 Nature of coexisting thyroid autoimmune disease determines success or failure of tumor immunity in thyroid cancer. J Immunother Cancer 7. 3. Imam S, Jaume J C 2021 Stratifying risk of malignancy in indeterminate thyroid nodules and immuno-genomic markers for early detection of thyroid cancer. International Application No. PCT/US2021/012057, Publication Number WO/2021/138661

Presentation: Saturday, June 11, 2022 11:30 a.m. - 11:45 a.m.
OR11-1 Thyroglobulin Structural Requirements in Protein Trafficking for Thyroid Hormonogenesis
Authors: Arvan Peter , Clarke Oliver , Kim Kookjoo , Citterio Cintia
Published: November 2022

In vertebrates, thyroglobulin (Tg) is secreted into the lumen of thyroid follicles to enable its iodination for the synthesis of thyroid hormone — defective Tg secretion causes hypothyroidism. A defining step in Tg secretion is export from the endoplasmic reticulum (ER), but Tg structural features needed to meet ER quality control requirements remain poorly defined. Tg primary structure is composed of Regions I, II, III, and ChEL, each engaged in intradomain disuflide bonding. Two major surprises that have recently emerged from the visualization of bovine Tg 3D-structure by cryoEM include the first identified long-range disulfide bond (C408-C608), which appears to tether a boundary separating two halves of region I, as well as the apparent absence of an evolutionarily conserved disulfide bond between C2444 and C2455 in the ChEL domain, which is known to support folding stability of region I. To understand the cell biological importance of these findings, we employed site-directed mutagenesis to determine the impact of these structural features in protein export of recombinant Tg expressed in cultured cells.

To our surprise, we found that mutation of either a single Cys residue or both cysteines that contribute to the C408-C608 disulfide bridge had no discernible impact on the efficiency of Tg export. These data strongly suggest that the proximity of the two-halves of region I in the final Tg structure may be achieved by protein folding of individual repeating units of region I that must take place independently of (and thus presumably prior to) the formation of this interesting long-range disulfide bond.

As ChEL supports Tg region I folding stability, we turned attention to the apparent absence of the C-2444-C2455 disulfide, which is one of the three disulfide bonds that had been thought to exist in every member of the large Cholinesterase-Like gene superfamily. Reported detection of this disulfide within human Tg, but lack of detection in bovine Tg, means either that this bond is 'structurally optional', or that this surface disulfide bond might have been broken by radiolysis under the X-ray beam used for cryoEM. Unequivocally, we found that mutagenesis of either C2444, C2455, or both, blocks Tg secretion and causes a pattern of intracellular misfolding consistent with incomplete Tg compaction indicative of lack of maturation of region I. Moreover, we found that disruption of these same residues causes misfolding and blocks secretion of an expressed isolated secretory ChEL domain, or acetylcholinesterase itself.

Loss of the C2444-C2455 disulfide bridge behaves similarly to the defective folding observed in the mutant Tg encoded within cog/cog mice and rdw/rdw rats, whereas no pathogenic mutations have been reported affecting the long-range disulfide in Tg region I. Together, these results highlight the importance of ChEL domain structure in the maturation and secretion of Tg.

Presentation: Sunday, June 12, 2022 11:00 a.m. - 11:15 a.m.
OR11-2 RNA Sequencing Reveals Unique Transcriptomic Signatures of the Thyroid in a Murine Lung Cancer Model Treated with PD-1 and PD-L1 Antibodies
Authors: Dresner-Pollak Rivka , Fridlender Zvi G , Gurt Irina , Kaisar-Iluz Naomi , Lishinsky Natan , Pollack Rena , Shaul Merav E , Stokar Joshua
Published: November 2022

Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy, however, are associated with immune-related adverse events (irAEs). Thyroid dysfunction is among the most common irAEs, yet its mechanism has not been fully elucidated. To further explore the molecular mechanism of ICI-induced thyroid dysfunction, we profiled changes in transcription induced by PD-1/PD-L1 antibody treatment in a non-small cell lung cancer murine model using RNA-seq. We used bioinformatic tools to compare transcriptional changes in our model to previously published transcription data sets of drug-induced thyroiditis. C57BL6/129SvJ mice harboring LKR-M (Lung cancer K-ras metastatic tumor) flank tumors were treated with PD-1 antibody, PD-L1 antibody, or vehicle every 3 days over a period of 7 days when mice were sacrificed, and thyroid glands were removed. The tumor volume increased in the control mice (1.38 ± 0.19) and decreased in the anti PD-1 treated (0.64 ± 0.15; P=0.0001) and PD-L1 treated mice (0.74 ± 0.11; P=0.004). RNA-seq was performed in the LKR-M tumor-bearing control mice and in the anti PD-1/PD-L1 treated mice (n=4 per group). A total of 952 differentially expressed genes (DEGs), including 265 upregulated and 688 downregulated, were identified with anti PD-1 treatment (fold-change ≥1.8, FDR ≤0.05). Only 35 genes were differentially expressed with anti PD-L1 treatment, and we therefore chose to focus on the anti PD-1 treated group alone. Using Ingenuity Pathway Analysis (IPA), we determined that of the DEGs in the PD-1 treatment group, 362 were associated with functions of cell death and survival, with a predicated activation of pathways for apoptosis and necrosis (Z=2.89 and 3.21, respectively) and negative activation of pathways for cell viability and cell survival (Z=-6.22 and -6.45, respectively). When compared to previously published datasets of interleukin-1β and interferon gamma-treated human thyroid cells, the apoptosis pathways were similarly activated. To our knowledge this is the first study to evaluate transcriptomic changes in thyroid tissue following ICI therapy. Our data suggest that there are unique changes in gene expression in the thyroid associated with anti PD-1 therapy. ICI-induced thyroid dysfunction may be mediated by increased tissue apoptosis resulting in destructive thyroiditis.

Presentation: Sunday, June 12, 2022 11:15 a.m. - 11:30 a.m.
OR11-5 Outcomes and Predictors of 30-day Readmission for Hyperthyroidism: A Nationwide Study
Authors: Adeoti Oluwatomi , Salim Michael , Kichloo Asim , Shaka Hafeez
Published: November 2022

This retrospective cohort study examines the 30-day readmission rate for patients with hyperthyroidism. Analysis of data from the 2018 Nationwide Readmissions Database exposed factors that affect this rate and described key healthcare quality indices that are associated with these readmissions. Understanding these will help identify areas for improving patient outcomes.

Presentation: Sunday, June 12, 2022 12:00 p.m. - 12:15 p.m.
OR19-4 A Minimal Human Physiologically Based Kinetics Model of Thyroid Hormones and Effects of Endocrine-Disrupting Chemicals
Authors: Zhang Qiang , Bagga Anish
Published: November 2022

Thyroid hormones (THs) thyroxine (T4) and triiodothyronine (T3) are under homeostatic and circadian control by the hypothalamic-pituitary-thyroid axis while their free plasma concentrations are strongly buffered by three TH binding proteins (THBPs): thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB). The THBPs are crucial to the even delivery of THs from the blood to tissues, but their relative contributions and spatial kinetics within tissues are unclear. Many endocrine-disrupting chemicals (EDCs) can interfere with the regulation and actions of THs, some of which are structurally similar to THs with comparable or even higher binding affinities for THBPs. It has been suspected that by disrupting the binding of THs with THBPs, EDCs may alter the plasma TH concentrations and the delivery to tissues. Given that the majority of the binding sites on THBPs are unoccupied—thus available for EDC binding—it is uncertain whether TH homeostasis can be tangibly perturbed by EDC exposure. To answer these questions, we constructed a spatial multi-compartment human physiologically based kinetic (PBK) model of TH production, distribution, and metabolism. The model contains the thyroid, liver, and rest-of-body compartments with explicit descriptions of the reversible binding kinetics between THs and THBPs in the blood. The model was parameterized and validated extensively based on literature data. Here we reported several novel findings: (1) The contribution to TH tissue delivery by each THBP is not spatially constant across a tissue: ALB always contributes more THs to the arterial side of the tissue while TBG contributes more to the venous side. (2) THBPs are essential for a uniform TH tissue delivery but are cross-compensatory in this role. (3) Contrary to the long-held assumption that ALB is the dominant contributor, TBG contributes more of the THs delivered to a tissue overall than ALB and TTR. (4) Bode plot analysis using control theory suggests that a circadian signal driving T4-to-T3 conversion in the extra-thyroidal tissue is crucial to establish the distinct phase and amplitude profiles of circulating T3 and T4 in humans. (5) Displacement of THs from THBPs by high-affinity EDCs has a negligible effect on free plasma THs even under high exposures. (6) Daily exposure to THBP-binding EDCs does not affect the circadian variations in tissue delivery of THs. The PBK model can be further elaborated in the future to make tissue-specific predictions of TH kinetics.

Presentation: Monday, June 13, 2022 11:45 p.m. - 12:00 p.m.
OR29-5 Phase 3 PaTHway Trial: Participants Treated With TransCon PTH Achieved Independence From Conventional Therapy While Maintaining Normal Serum Calcium
Authors: Khan Aliya
Published: November 2022

Background

Adults with chronic hypoparathyroidism managed with conventional therapy (calcitriol, alfacalcidol, and oral calcium) generally report a reduced quality of life (QoL) and remain at risk for long-term complications from abnormal calcium and phosphate metabolism. The PaTHway trial assessed the efficacy and safety of TransCon PTH at Week 26.

Methods

PaTHway was a double-blind, placebo-controlled 26-week trial with 3: 1 randomization to TransCon PTH 18 mcg/d or placebo, co-administered with conventional therapy. The composite primary efficacy endpoint was the proportion of participants at Week 26 who achieved: serum calcium levels in the normal range (8.3–10.6 mg/dL), independence from conventional therapy defined as requiring no active vitamin D and ≤600 mg/day of calcium supplementation, and no increase in prescribed study drug over 4 weeks prior to Week 26. Key secondary endpoints included Hypoparathyroidism Patient Experience Scale (HPES) domain scores and 36-Item Short Form Survey (SF-36) subscale scores.

Results

82 participants were dosed (78% female, mean age 49 years). 79 completed treatment through Week 26. 79% (48/61) of participants randomized to TransCon PTH met the composite primary efficacy endpoint, compared to 5% (1/21) in the placebo group (p <0.0001). 93% (57/61) participants treated with TransCon PTH achieved independence from conventional therapy. At baseline, mean serum calcium was 8.8 and 8.7 mg/dL for TransCon PTH and placebo respectively; 8.9 mg/dL and 8.2 mg/dL at Week 26, respectively. For TransCon PTH, mean urine calcium decreased significantly from 390 mg/24-hour at baseline to 220 mg/24-hour (normal range <250 mg/24-hour) at Week 26 compared to 329 mg/24-hour at baseline to 292 mg/24-hour at Week 26 for placebo. TransCon PTH therapy demonstrated a significant improvement in HPES-Symptom domain scores − Physical (p = 0.0038) and Cognitive (p = 0.0055), HPES-Impact domain scores − Physical Functioning (p = 0.0046) and Daily Life (p = 0.0061), and SF-36 Physical Functioning subscale score (p = 0.0347) compared to placebo. Overall, TransCon PTH was well-tolerated. The majority of adverse events (AE) were mild or moderate in severity. The most commonly reported study drug-related AEs were injection site reactions, hypercalcemia, and headaches. No study drug-related AEs led to withdrawal from the study.

Conclusions

In the PaTHway phase 3 trial, 79% of participants on TransCon PTH therapy (versus 5% on placebo) were able to achieve independence from conventional therapy while maintaining normocalcemia at Week 26. Uniquely, TransCon PTH therapy decreased and normalized 24-hour urine calcium excretion and significantly improved QoL (symptom burden and impact) from baseline compared to placebo. These data suggest the potential for TransCon PTH to improve clinical outcomes and QoL compared to current conventional therapy.

Presentation: Tuesday, June 14, 2022 10:45 a.m. - 11:00 a.m.
PSAT239 Pregnant Patient With a History of Methimazole-Induced Agranulocytosis Presenting With Hyperthyroidism: A Case Report
Authors: Abduraup Abdusattar , Barrera Jerome
Published: November 2022

Background

Pregnancy has a profound impact on the thyroid gland and its function. Severe thyrotoxicosis can lead to many complications and endanger the mother or fetus. Antithyroid drug (ATD), at its lowest possible dose, should be given. However, one of the complications of treatment include agranulocytosis which is a rare but serious allergic event with a prevalence of 0.1 to 0.5 percent. Thus, alternative treatment should be prescribed because a cross-reaction between ATDs was observed in 15.2% of patients in a study. Insufficient data is available regarding the use of these medications in pregnant patients with history of drug-induced adverse reactions. There are other feasible alternative treatments but are contraindicated in pregnancy.

Case

We report a 29-year old patient gravida 5 para 4 at 10 weeks age of gestation at the time of consult presenting with palpitations. She is a known case of Graves’ disease for 7 years and maintained on Methimazole. She was admitted a year prior consult as a case of impending thyroid storm; Methimazole-induced agranulocytosis. Initially, maintained on Lithium but shifted back to Methimazole without a physician's advice and later on, discontinued the medication upon knowledge of pregnancy. She presented on her first trimester of pregnancy with palpitations and elevated free thyroxine (T4) at 71.29 pM (normal range: 11-24 pM). She was started on Propylthiouracil 50 mg/tablet 1 tablet three times a day. On her second trimester, no reported symptoms of hyperthyroidism and/or agranulocytosis such as fever or sore throat. Thyroidectomy was offered at this time explaining the risks and benefits but she strongly refused. Free T4 was then maintained at a value slightly above the upper normal limit. Propylthiouracil was also shifted to Methimazole 5 mg/tablet 1 tablet once daily and revised to 1 tablet every other day on the third trimester of pregnancy. Delivery was uneventful and the newborn was evaluated by a pediatrician with unremarkable findings. Four weeks postpartum, no noted symptoms of hyperthyroidism and/or agranulocytosis. Free T4 was noted within the normal range at 18.84 pM. Alternative treatment was offered due to the risk of ATD-induced agranulocytosis.

Conclusion

Hyperthyroidism in pregnancy is associated with a variety of complications for the mother and fetus. Three effective treatment options include ATD, thyroidectomy or RAI therapy. But, not all are relatively safe for pregnancy. In initiating ATD, cross-reaction between medications should be considered especially for patients with history of adverse reaction, such as agranulocytosis, which can be life-threatening. However, there are limited studies in the management of this specific case. Treating physician and patient should discuss each of the options, including the benefits, drawbacks and side effects.

Keywords: Hyperthyroidism, Graves’ disease, Pregnancy, Agranulocytosis

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT251 Examination of TRH test in Central Hypothyroidism due to Non-Functional Pituitary Adenoma
Authors: Buyandalai Battsetseg , Takamizawa Tetsuya , Horiguchi Kazuhiko , Yoshioka Masayuki , Nishikido Ayaka , Toki Akiko , Ishida Emi , Yoshino Satoshi , Matsumoto Shunichi , Yamada Eijiro , Ozawa Atsushi , Yamaguchi Rei , Tosaka Masahiko , Yamada Shozo , Yamada Masanobu
Published: November 2022

Objectives

There is a little evidence for the TRH test criteria in the diagnosis of Central Hypothyroidism (CeH). Therefore, we investigated the significance of the TRH test for Central Hypothyroidism due to Non-Functional Pituitary Adenoma.

Methods

107 cases of Non-functional pituitary adenoma (NFPA) in Gunma University Hospital Neurosurgery and Toranomon Hospital Intercerebral Pituitary Surgery, between 2007 to 2020 are studied. Subjects divided into CeH group (n = 19) with FT4 below the reference value and a normal group (n = 88). Serum TSH level was determined before (basal-TSH value) and 30, 60, 120 minutes after TRH administration. Peak-TSH value, delayed and prolonged responses were analyzed. A peak-TSH occurring at 60 minutes or later was considered as a delayed response. If 120-minutes TSH value to peak-TSH value ratio is equal to or higher than 0.6 was considered as a prolonged response.

Results

The basal-TSH was higher in the CeH group than in the normal group (median 2.7 vs. 1.5μIU/mL) (p <0.01). There was no difference between two groups, in both 30-minute value and the peak value. Delayed response occurred in 10/19 (53%) in the CeH group, and 18/88 (20%) in the normal group (p < 0.01). Prolonged response occurred at a higher rate of 15/19 (79%) in the CeH group, while in 23/88 (26%) in the normal group (p <0.01). AUC was maximum when prolonged response (120-minute value to peak value ratio) is equal to or lower than 0.65.

Conclusion

In central hypothyroidism due to Non-Functional Pituitary Adenoma, the basal-TSH value does not usually decrease, but rather be higher value within the reference range. 30-minute value or peak value was not useful in diagnosis, yet the prolonged response was more significant. Central Hypothyroidism in Non-Functional Pituitary Adenoma, can be diagnosed with sensitivity of 79% and specificity of 78% when the 120-minute value to peak value ratio is equal to or lower than 0.65.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT295 Low Grade B-CELL Lymphoma and Follicular Cancer in a Patient with Hashimoto's Thyroiditis Presenting as Two Different Thyroid Nodules
Authors: Puchalski Adam , Hodge Marybeth
Published: November 2022

We present an 88 year old female with a history of hypothyroidism due to Hashimoto's thyroiditis who noted a lump in the left side of her neck. Thyroid ultrasound revealed multiple nodules throughout the thyroid gland. The right lobe contained a 4.3 cm solid, dominant nodule and the left lobe contained a 4.2 cm lobulated hyperechoic nodule.

Ultrasound-guided fine-needle aspiration biopsy of the 4.3 cm right thyroid nodule revealed follicular lesion of undetermined significance with predominantly Hurthle cells. Thyroseq was positive for aTERT and EIF1AX mutations. Ultrasound-guided fine-needle aspiration biopsy of the 4.2 cm left thyroid nodule revealed malignant cells consistent with a low-grade B-cell lymphoma.

She underwent a total thyroidectomy. The final pathology report revealed both a 5.5 cm follicular carcinoma in the right lobe and a low-grade B-cell lymphoma most compatible with extra nodal marginal zone lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma) involving predominantly the left lobe of the thyroid.

She is beginning radiation treatment for the lymphoma. Three months after radiation treatment is completed, she will undergo radioactive iodine treatment for the follicular carcinoma.

Thyroid cancer is the most common endocrine malignancy. However, the thyroid is an uncommon site of cancer overall, accounting for only 1.5% to 4.7% of new cancer cases in the general population of the United States. Malignant lymphoma presenting as a primary neoplasm in the thyroid is even more uncommon and represents only 1 to 5% of all thyroid malignancies. Hashimoto's thyroiditis is a known risk factor for MALT lymphoma. However, there is no known association between Hashimoto's thyroiditis and follicular carcinoma. There are several reports of patients with presence of both papillary thyroid cancer and MALT lymphoma. One case was reported of simultaneous MALT lymphoma and medullary thyroid cancer. This is the first case of a patient with both follicular thyroid cancer and MALT lymphoma in the thyroid gland.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT317 An Impending Thyroid Storm Caused by COVID-19 Infection
Authors: Ahmed Ammar , Biswas Suman , Tan Zi
Published: November 2022

Background

Thyroid storm is an acute, potentially fatal complication of hyperthyroidism, usually manifested with tachycardia, hyperthermia, and altered mental status. Despite medical advancements, the mortality associated with thyroid storms remained 5% to 25%. Previously, cases of thyroiditis following COVID-19 infection have been reported. But the manifestation of COVID-19 infection as a thyroid storm is infrequent, and less than 5 cases have been reported to date.

Case

A 72-year-old female with a remote history of breast cancer status post-mastectomy presented to the emergency department with the chief complaint of shortness of breath. She was found to have a history of fever eight days before the presentation; she was also complaining of non-productive cough, non-bloody, and non- bilious vomiting, myalgia, and fatigue. Home Covid Test was positive. On the day of the presentation, she received Regeneron infusion (casirivimab and imdevimab) and was discharged home. After a few hours, she represented to the hospital with chills and worsening of shortness of breath. She was found to be hypoxic on the presentation, was started on O2 supply, and transferred to the ICU. She received IV dexamethasone 6 mg and IV Remdesivir 200 mg on the first day, followed by 100mg for the next four days. On the fourth day following admission, she developed Atrial Fibrillation with a rapid ventricular response. The patient was somnolent and had loose bowel movements. Thyroid function tests were ordered; TSH was 0.02 and free T4 of 2.9. She stated she was never diagnosed with a thyroid disorder in the past. Thyroid function tests were ordered, which are mentioned in the table below. A thyroid-stimulating antibody assay was ordered to rule out Graves thyrotoxicosis, which turned out to be normal. Ultrasound of the thyroid gland didn't reveal any abnormalities.

Conclusion

Although most patients remain euthyroid during COVID-19 infection, some may have shown transient thyroid derangements during the illness, which later turns out to be normal. Our case shows that a clinician should not take the thyroid derangements in COVID-19 lightly, as they can be the early signs of an impending thyroid storm. Our case guides the clinician to evaluate the thyroid function as soon as possible in any signs of overt hyperthyroidism. Due to the high mortality associated with thyroid storm, a clinician should have a high index of suspicion to diagnose the storm, such as in our case where other signs of hyperthyroidism are absent. Early treatment of thyroid storms becomes necessary to mitigate the mortality in such cases.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT347 New Onset of Graves’ Disease after COVID-19 Vaccination
Authors: Anto Antony Mc , Joglekar Mansi , Kurian Roshini , Kant Ravi , Verma Vipin , Chandra Lakshya
Published: November 2022

Introduction

Adjuvants are substances that are commonly found in vaccines. They can enhance the efficacy and potency of a vaccine via an immunological response. However, in some susceptible individuals, these adjuvants can lead to a serious autoimmune response known as autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This can lead to the onset of autoimmune disorders following vaccination. There are many case reports of the onset of autoimmune disorders following COVID-19 vaccination. However, new onset of Graves’ disease within one day after COVID-19 vaccination, is of rare occurrence.

Clinical Case

We present the case of a 33-year-old Caucasian male who presented to his primary care physician with chief complaints of fever ranging between 99.2F to 101.3F, palpitations and hand tremors which started one day after he received his first dose of COVID-19 vaccine. Initial laboratory evaluation included a negative throat swab for Group A Streptococcus, a negative nasal swab for Influenza A & Influenza B and a negative nasopharyngeal swab for SARS-COV-2 RNA. On physical examination, he was afebrile, pulse rate 101/min, blood pressure 125/74 mm Hg and oxygen saturation 98%. Due to persistence of tachycardia, an EKG was done which showed a normal sinus rhythm with no other abnormalities. Further laboratory testing was remarkable for a suppressed TSH 0.005 (0.300-4.00 uUI/ml), elevated FT4 2.36 (0.80-1.80 ng/dl) and an elevated TSH receptor Antibody (TRAb) 8.67 (0.00-1.75 IU/L), which confirmed the diagnosis of Graves’ disease. Subsequently, patient established care at our endocrinology clinic. Labs were repeated which showed persistence of hyperthyroidism with TSH <0.005, high normal FT4 1.56 and an elevated FT3 5.36 (2.00-4.40 pg/ml). Thyroid ultrasound was remarkable for mild thyromegaly with increased vascularity and no discrete nodules. Patient was initiated on Methimazole 10 mg daily and propranolol 10 mg twice daily. During the first follow-up visit, the dose of Methimazole was reduced to 5 mg daily based on improved labs. However, it had to be increased back to 10 mg daily due to subsequent worsening of labs. Since then, patient has been maintained on a stable dose of Methimazole 10 mg once daily and the beta-blocker has been discontinued. It has been almost 1 year since the diagnosis and the Graves’ disease specific Thyroid Stimulating Immunoglobulin (TSI) antibody is still elevated at 1.31 (0.00-0.55 IU/L).

Conclusion

Graves’ disease should be considered high in the differential diagnosis in a patient presenting with fever and tachycardia following COVID-19 vaccination. Our unique case supports the current literature available on the various autoimmune conditions caused by the autoimmune/inflammatory syndrome induced by adjuvants, also known as ASIA.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSAT350 Autoimmune Polyglandular Syndrome Type II Presenting with Hashimoto's Thyroiditis, Diabetes Mellitus Type I and Addison's Disease: A Case Report
Authors: Barjose Angelie Rose , Barrera Jerome , Yumol Daniel Mark , Caluscusin Ivan Rommel
Published: November 2022

A. BACKGROUND/SIGNIFICANCE Autoimmune polyglandular syndrome Type II (APS-II) is a rare polyendocrinopathy with a prevalence of 1 to 2 in 100,000, instigated by immune-mediated destruction of several organs. Knowledge of APS-II is crucial, especially in the early detection of polyglandular disorder among patients with endocrine autoimmunity.

B. CASE This case is of a 40-year-old male who initially presented with Grave's disease after showing signs and symptoms of hyperthyroidism, as supported by low thyrotropin (<0.05 uIU/mL; nv: 0.35-4.94) and high free thyroxine levels (2.05 ng/dL, nv: 0.71-1.85). He was maintained on methimazole.

Five months following diagnosis, he developed symptoms of Diabetes Mellitus Type 1 (T1DM) as confirmed by high capillary blood glucose, undetectable C-peptide, and positive anti-Glutamic acid decarboxylase. Insulin and rosuvastatin were added on his maintenance medications. Ten months later, he discontinued methimazole and became lost to follow-up. One month after discontinuation, he sought consult again after experiencing symptoms of fatigue, muscle cramps, cold intolerance, forgetfulness, abdominal pain, diarrhea, and episodes of hypoglycemia at home. On examination, he was noted to have hypotension of 80/60 mmHg and skin hyperpigmentation. His random blood sugar was 408 mg/dL. High thyrotropin (57.8777 uIU/Ml, nv: 0.35-4.94), low free thyroxine (0.57 ng/dL, nv: 0.71-1.85), and positive antithyroid peroxidase antibody levels revealed Hashimoto's thyroiditis. Low fasting 8 am serum cortisol (81 nmol/L, nv: 138-635) and low serum cortisol 30 mins (403.85 nmol/L) and 1 hour (542.31 nmol/L, normal response: >550 nmol/L) after adrenocorticotropic hormone stimulation test in addition to the clinical manifestations, supported the diagnosis of Addison's disease.

With the combination of Addison's disease, Autoimmune thyroid disease, and T1DM, a diagnosis of APS Type II was made. Management included insulin, prednisone, and levothyroxine. These resulted in significant improvement in the patient's symptoms. He is now clinically well and compliant to regular follow-up.

C. LEARNING POINTS/CONCLUSION It is crucial in APS-II management to identify and manage the associated autoimmune disorders to prevent significant morbidity and mortality. Therefore, in the presence of any autoimmune disorder, a high index of suspicion for APS-II is essential. There should be regular follow-up and observation of patients with autoimmune endocrine disorders to ensure early detection of APS-II. Patient health education must include identifying symptoms of the disorders for which they are at high risk.

Keywords: APS Type 2, Addison's Disease, DM Type 1, Hashimoto's Thyroiditis

Sources of Support: None

Conflicts of Interest: None

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT353 Can Generalized Granuloma Annulare occur in patients with Graves’ disease?
Authors: Elshimy Ghada , Raj Rishi
Published: November 2022

Introduction

Granuloma annulare (GA) is a benign self-limiting dermatosis, typically characterized by an annular arrangement of erythematous or flesh-colored papules, affecting patients of all ages. An association between GA and autoimmune diseases (including autoimmune thyroiditis) has been reported in the literature thus suggesting that GA belongs to the spectrum of autoimmune diseases. However, only a few case reports described the unusual association of localized GA with hyperthyroidism. The definitive correlation between thyroid disease and GA hasn't been established. It was suggested that there is a common immunogenic predisposition or that both diseases share a common pathway. We present a rare case of generalized granuloma annulare in a patient with Graves’ disease.

Case report

A 52-year-old African American female with a past medical history of Graves’ disease with mild Graves’ ophthalmopathy was referred to the endocrinology clinic. She was diagnosed with Graves’ disease seven years ago and was medically managed ever since. Initially, she was treated with a high dose of methimazole however, for the past six years, she was on a stable dose of methimazole 5 mg daily. Two years following diagnosis of Graves’ disease, she developed serpiginous non-pruritic erythematous skin papules and patches in the right upper arm which slowly progressed over the course of years to involve bilateral inner thighs and under the breasts. She was evaluated by dermatology at that time and was empirically treated with a topical antifungal agent without any significant improvements. After establishing care with us, there was suspicion of methimazole-induced ANCA vasculitis or other autoimmune diseases. Extensive rheumatological workup including ANCA level was performed with negative results. Since her thyroid function tests (TSH and free T4) were normal on a low dose of methimazole for an extended period, we discontinued methimazole, however, skin rash didn't improve. The patient was then evaluated by dermatology and was diagnosed with GA based on clinical judgment. She was subsequently treated with an extended course of triple antibiotics therapy using rifampin, ofloxacin, and minocycline for 5 months with significant improvement of the skin rash. Currently, the patient has been off methimazole for 12 months and off triple antibiotic for 4 months with no recurrence of symptoms.

Conclusion

Although rare, generalized granuloma annulare can be seen in patients with autoimmune thyroid disease including Graves’ disease. Hence, endocrinologists should be aware of the different skin manifestations which can be seen in patients with autoimmune thyroid disease. Further studies are necessary to clarify the association of GA with autoimmune thyroid disease.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT357 Preventing Progression of Ophthalmopathy Using a 'Block-Replace' Treatment Strategy in Labile Graves’ Disease
Authors: Bauer Jessica , Riordan Marianne , Panvelker Samir
Published: November 2022

Introduction

Graves’ disease is an autoimmune disorder that most commonly causes hyperthyroidism. Pathogenesis usually involves the stimulation of TSH receptors by antibodies, but in rare cases can alternate between hyper- and hypothyroidism. In this case report, we describe a patient who had labile thyroid function with persistent ophthalmopathy, requiring a temporizing "block and replace" strategy for treatment.

Case Description

A 53-year-old woman with a history of GERD and fibroids presented to her primary care physician with a month-long history of hand and leg tremors, weakness, heat intolerance, palpitations and worsened anxiety. She also developed eye irritation and enlargement. Thyromegaly was noted on examination. Thyroid function tests showed that TSH was <0.01 (0.45-5.33 uIU/mL) and Free T4 was 2.48 (0.61-1.12 ng/dL). TRab was 21.2 (<1.75 IU/L). Thyroid ultrasound revealed heterogeneous enlargement with increased vascularity representing thyroiditis. CT orbit revealed mild bilateral ocular proptosis with normal extraocular muscle. She was diagnosed with Graves’ disease complicated by ophthalmopathy and she was started on methimazole and metoprolol. Repeat labs six weeks later improved to TSH of 0.01 and total T4 of 6.5 (4.50-11.70 ug/dL). Unfortunately, follow up labs 2 months later revealed overt hypothyroidism, with TSH of 134 with total T4 0.9. Methimazole and metoprolol were discontinued and 75mcg of levothyroxine was started. One month later, TSH was suppressed again to 0.11 and Total T4 was 17.8, so methimazole was again added with the intent of suppressing hyperthyroidism while simultaneously replacing levothyroxine to avoid hypothyroidism. Given the difficulty of maintaining a euthyroid state and ongoing symptomatic ophthalmopathy, she eventually underwent total thyroidectomy and started levothyroxine post operatively. Pathology of the thyroid gland was consistent with Graves’ disease.

Discussion

Graves’ disease is typically treated with anti-thyroid medical therapy (thioamides such as methimazole), which is titrated to a euthyroid state. In our case, the patient's thyroid function varied widely on methimazole, potentially representing variable stimulating and blocking functions of TRab. As periods of hypothyroidism can worsen ophthalmopathy, a "block and replace" treatment strategy was adopted, which involves a thioamide and levothyroxine concurrently to achieve a biochemically euthyroid state. While a Cochrane review has suggested there is no improvement in relevant outcomes using this approach, it was useful in our case as a bridge to surgical management1.

References

[1] Abraham P, Avenell A, McGeoch SC, Clark LF, Bevan JS. Antithyroid drug regimen for treating Graves’ hyperthyroidism. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD003420. DOI: 10.1002/14651858.CD003420.pub4

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT362 Hypothyroidism Associated Colonic Rupture
Authors: Seetharaman Karthik , Mandava Sri , Wilson Mark
Published: November 2022

A 59 year old female with history of thyroid cancer status post thyroidectomy presented with sudden onset severe and diffuse abdominal pain. CT Abdomen Pelvis with contrast showed extensive pneumoperitoneum suggestive of perforated viscus. The patient was taken to emergent diagnostic laparoscopy showing sigmoid perforation with fecal contamination and multiple large stool balls. Sigmoidectomy and end colostomy was performed for perforated sigmoid diverticulitis with feculent peritonitis. On admission, tests evaluating for thyroid function were consistent with hypothyroidism (TSH 39.700, n 0.400 - 4.500 uIU/mL). Over the previous two years, thyroid function studies were variable with both elevated and low TSH values (range 0.221-117 uIU/ml), although TSH values over the prior 12 months were not elevated. The patient reported adherence to taking levothyroxine 137 mcg daily in the outpatient setting. Furthermore, she endorsed appropriate administration of levothyroxine prior to food and was not taking the medication with any offending vitamins or minerals. Review of systems was negative for alternative causes of colonic rupture including trauma or chronic constipation. A thorough literature review was performed and revealed only 10 cases between 2004-2007 of spontaneous perforation of the colon in the absence of tumors, diverticulosis, or external injury.1 Only two reports were found linking spontaneous perforation of the colon with hypothyroidism, and proposed the causative mechanism as intestinal motility dysfunction causing chronic constipation, megacolon, or even pseudo-obstruction eventually leading to stercoral perforation.[2-3] Hypothyroid status was addressed by increasing levothyroxine dosage to 150 mcg daily. The patient recovered from septic shock and performed a 2 week course of inpatient rehabilitation from which she was discharged home with good functional status. Follow up labs evaluating thyroid status will be performed 4-6 weeks after initial testing and are still pending.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT378 Hashimoto's Thyroiditis and Differentiated Thyroid Cancer Aggressiveness
Authors: Mushref Malek , Bridges Matthew , Chandran Keshav , Mukherjee Rupak , Javid Mahsa
Published: November 2022

Background

Hashimoto's thyroiditis (HT) is associated with a 1.5-fold increased risk of differentiated thyroid cancer (DTC). It is postulated that the inflammatory milieu in HT may damage thyrocytes, increasing the risk of cancer. However, it is not precisely known how the presence of thyroiditis affects aggressiveness of DTC and if a causal relationship exists. It has been suggested HT may correlate with a less aggressive phenotype with smaller tumor size, lower rate of aggressive variants, less frequent radioactive-iodine administration, and higher rates of clinical remission. The aim of this study was to investigate the pathological features of DTC in patients with HT and whether length of time with HT affects tumor aggression.

Method

Charts of 367 consecutive patients with DTC undergoing thyroidectomy were reviewed. Clinical and pathological factors were analyzed. A composite score of tumor aggressiveness was calculated using the presence of multifocality, angioinvasion, lymphatic invasion, extrathyroidal extension, central and lateral lymph node (LLN) involvement. This score and tumor size were compared in patients with clinical (elevated thyroid peroxidase or anti-thyroglobulin antibodies) or pathological (presence of inflammation on pathology) HT. Time to surgery from diagnosis of HT was also evaluated.

Results

In 367 patients with DTC (343 papillary, 29 follicular, 5 both), mean size of the largest tumor was 1.5±1.7cm, mean composite score was 1.3±1.6cm. Seventy-three (19.9%) and 156 (42.5%) patients had clinical or pathological HT, respectively; 92 (25.1%) had preoperative hypothyroidism.

Patients with clinical HT alone, or in addition to pathological HT, had a reduced risk of LLN disease (Odds Ratio: 0.21 p<0.005, and OR: 0.43 p=0.01, respectively); those with pathological HT alone had a trend towards lower risk (p=0.06). Neither the overall score for tumor aggressiveness nor tumor size correlated with clinical or pathological HT.

Length of time from diagnosis of clinical HT to surgery was not associated with tumor size, aggressiveness or presence of inflammation on pathology.

Conclusion

Clinical HT is associated with reduced risk for LLN metastasis, supporting the suggestion that presence of HT confers a better prognosis in DTC. Length of time with HT does not alter the risk for aggressive features of DTC indicating lack of an escalating causal relationship.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT388 A Rapidly progressive papillary thyroid carcinoma presenting 22 years after RAI therapy
Authors: Norwich Diana , Kotla Nishitha , Kirkeby Kjersti
Published: November 2022

The risk of thyroid cancer following RAI therapy remains controversial. We report a case of an aggressive papillary thyroid carcinoma presenting over twenty years after RAI therapy for Graves’ disease.

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