bluuebunny/crossref_metadata_2025 huggingface dataset:
RF03 | PMON297 Connecting Fluctuations in Estrogen Production, Release, and Action with Hormone-Dependent Gene Expression in Breast Cancers
Authors: Kim Hyung Bum , Gupte Rebecca , Nagaria Anusha , Lee Kraus W
Published: November 2022

Estrogens are steroid hormones that play a key role in a wide range of physiological and pathological processes. Estrogen receptor-alpha, ERɑ, functions primarily as a nuclear transcription factor (TF) through ligand-dependent activation by 17β-estradiol (E2), the predominant naturally-occurring estrogen. This results in dimerization, DNA binding to cis-regulatory elements called enhancers, and gene regulatory function of ERɑ. In vivo, E2 production and action fluctuates during reproductive cycles and possibly even in a circadian manner. In tissues and cells, E2-regulated gene expression is dynamic, with rapid induction of enhancer formation and target gene expression (or repression), followed by enhancer "decommissioning" and cessation of the gene regulatory effects. The effects of sustained E2 production and signaling, fluctuations in E2 levels, and removal of E2 on estrogen-regulated gene expression are unknown. Classical experiments exploring the gene regulatory effects of E2 involve stimulation of cultured cells throughout the duration of the experiment with a continuous dose of hormone, with the cells harvested at the end of the stimulation period. While this has allowed us to understand the molecular underpinnings of signal-dependent transcription, it has not allowed analysis of physiological fluctuations in estrogen signaling involving periods of stimulation and non-stimulation. In our studies, we are applying a combination of next generation sequencing techniques and fluorescence microscopy to investigate signal-dependent responses to fluctuating E2 levels using ERɑ-positive MCF-7 human breast cancer cells after E2 treatment and removal. Our initial results suggest that different E2 target genes respond differently to E2 withdrawal. Moreover, for some E2 traget genes, sustained E2 treatment may not be required for a complete E2 transcriptional response. With these studies, we hope to connect physiological aspects of E2 production, release, and action with the molecular mechanisms of E2-dependent gene expression - an aspect of our understanding of estrogen signaling that has been lacking.

This work is supported by grants from the NIH/NIDDK (DK058110) and CPRIT (RP160319) to W.L.K.

Presentation: Saturday, June 11, 2022 1:12 p.m. - 1:17 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBODP101 Misleading FT4 Result In A Patient With Hashimoto's Thyroiditis
Authors: ALShehri Sara Mohammed , AlFadel Sultan , Ekhzaimy Aishah Ali , Hasanto Rana
Published: November 2022

Thyroid hormones and thyroid-stimulating hormone (TSH) laboratory tests are widely utilized worldwide, and their results have a significant impact on treatment decisions and subsequent diagnostic processes. In order to avoid misdiagnosis and inappropriate therapy, any differences between symptoms and laboratory findings should be thoroughly investigated. Many factors can cause discrepancies between thyroid function test and the patients’ clinical picture such as physiological changes, severe illness, drugs, or laboratory interference. Thyroid hormone autoantibodies, anti-streptavidin, and anti-ruthenium antibodies are the major thyroid function test interferers. Here, we present a case of a 70-year-old woman who is known to have hashimoto's thyroiditis maintained on Levothyroxine (LT4) for more than 10 years, but was stopped by her primary care physician due to abnormal thyroid panel results (high TSH and high fT4). She was referred to the endocrinology clinic for further evaluation. The patient complained of generalized fatigue and weakness. She had no hyperthyroid symptoms. She was not on any supplements. Testing thyroid hormones with the 2-step assay revealed severe hypothyroidism, so LT4 was resumed, and patient symptoms improved. This case aims to direct clinicians’ attention to the importance of considering the patient's clinical status in the diagnostic process and not replacing it with the laboratory diagnosis, given the possibility of many laboratories’ interference. Also, to underline the available methods to minimize false results and misleading diagnoses to avoid unnecessary investigations and interventions.

Presentation: No date and time listed
LBODP105 A Case of Significantly Increased Levothyroxine Requirement With Rifampin Therapy
Authors: Naher Kamrun , Samsuddoha Kazi , Karam Jocelyne Georges
Published: November 2022

Introduction

Rifampin has a wide range of drug interactions through increased hepatic microsomal enzyme activity. We are reporting a case of a patient with post-surgical hypothyroidism on stable thyroid hormone replacement therapy who required significantly higher doses of levothyroxine after starting rifampin.

Case Report

Patient is a 78-year-old woman with history of Papillary Thyroid Cancer (PTC) in remission status post thyroidectomy in 1994 and radioactive iodine therapy in 1997. Patient had been on a stable dose of Levothyroxine of 75-88mcg daily until a visit in January 2013 when her TSH was found to be 39 despite compliance with levothyroxine. Further history revealed that she was diagnosed with Mycobacterium Avium Intracellulare (MAI) infection of the lungs for which she was given rifampin therapy. Her Levothyroxine dose was progressively increased to 150mcg daily. She received rifampin therapy for 18 months, from August 2012 until April 2013. Her Levothyroxine dose was later changed to average 139 mcg /day based on TSH levels and continued to be the same through the rifampin course. In April 2014, and following discontinuation of rifampin, Levothyroxine was decreased to 100mcg daily and subsequently 75mcg daily. During a relapse of MAI in March 2016, her levothyroxine dosage was similarly again increased to 125mcg daily for TSH of 24.58. In June 2017, rifampin was discontinued after completion of second course of MAI treatment, and Levothyroxine dose decreased to 88 mcg daily, and subsequently 75 mcg in September 2017, and average daily 64mcg most recently given age and long-term remission with target mid normal TSH.

Discussion

Rifampin is used to treat active tuberculosis and MAI infection among other uses. It is a hepatic enzyme inducer which significantly interacts with other drugs. It has been reported previously to cause hypothyroidism in patients with underlying thyroid disorder and increased serum TSH while on levothyroxine, but its impact range on thyroid function has not been clearly described. Our patient was on stable levothyroxine dose following thyroidectomy, and required almost a 100% increase of levothyroxine dose when started on rifampin therapy, returning to baseline levothyroxine requirements off rifampin. This case highlights the severe hypothyroidism and significant impact on levothyroxine dose requirements following rifampin therapy, and the importance of close thyroid function monitoring in patients with hypothyroidism and on rifampin, especially in context of post-surgical hypothyroidism.

Presentation: No date and time listed
LBSAT314 Diagnosis And Management Of A Rare Case Of Marine-Lenhart Syndrome
Authors: Patel Janki , Karthikeyan Nishok
Published: November 2022

Introduction

Marine-Lenhart syndrome is defined as Graves’ disease with co-existing toxic thyroid nodules. Approximately 25% to 30% of patients with Graves’ disease have accompanying nodules. More than 95% of these nodules are hypoactive, and thus, only a tiny percentage are hyperactive. In these patients, Graves’ disease and toxic nodules both contribute to thyrotoxicosis11. Here we present a case that details this syndrome's diagnosis, management, and treatment complication.

Clinical Case

A 68-year-old female presented to the primary care physician's office with complaints of anxiety and heat intolerance. Three years before this visit, the patient was diagnosed with Graves’ disease. She had achieved remission after one year of methimazole therapy. During the office visit, the patient was in sinus tachycardia at 112 BPM. There were no signs of exophthalmos on examination, and the thyroid was not palpable. Further testing revealed thyrotoxicosis with suppressed TSH of <0. 01 mcIU/mL (0.36-3.74) and elevated free T4 of 2.49 ng/dL (0.76-1.46). Thyrotropin receptor antibody (TRAb) was positive at 2.60 IU/L (0. 00-1.75). The patient was started on atenolol. Although TRAb was positive, thyroid ultrasound and radioactive iodine uptake scan (RAIU) were ordered to look for alternative diagnoses. The thyroid ultrasound showed four nodules in the left lobe, the largest of which was 1.8×1.5×1.3 cm. RAIU showed increased 24-hour uptake of 45% and three areas of increased focal uptake in the left thyroid lobe consistent with toxic nodules. Definitive treatment was needed due to both toxic nodules and Graves’ disease. The patient agreed to radioiodine ablation therapy (RAI) and received a dose of 21 uCi. One month after receiving RAI, the patient complained of worsening anxiety and heat intolerance. On repeat testing, TSH was <0. 01mcIU/mL, and free T4 was 4.78 ng/dL. The patient developed radiation thyroiditis and was given methimazole 10mg daily for two weeks. Three weeks after the course of methimazole, the patient became hypothyroid and was managed with 88 mcg of levothyroxine daily with no symptoms.

Conclusion

Common causes of hyperthyroidism are Graves’ disease or autonomous functioning thyroid nodules per the American Thyroid Association12. However, in hyperthyroid patients, Marine-Lenhart syndrome should be considered, especially those with thyrotoxicosis recurrence. This diagnosis steers management away from antithyroid drugs and toward RAI or thyroidectomy. For patients treated with RAI, antithyroid medications should be included as an adjunct therapy to reduce post-radiation thyroiditis.

References

1 Cakir, Mehtap. "Marine-Lenhart Syndrome.," Journal of the National Medical Association 97, no. 7 (July 2005): 1036-38.12 Ross, Burch, et al., Thyroid. Oct 2016, 26(10): 1343-1421.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
ODP454 A Middle Aged Woman With a Thyroid Cyst: A Case of Squamous Cell Carcinoma of the Thyroid
Authors: Jiang Zhaozhi , LaRoe Matthew , Sultana Sanjeda
Published: November 2022

Background

Squamous cell carcinoma of the thyroid (SCCT) is a very rare malignant neoplasm of the thyroid with distinct squamous differentiation of tumor cells. Only 84 cases of primary SCCT were diagnosed worldwide up until 2012. The number has now increased to around 200. The incidence of SCCT is less than 1% out of all thyroid malignancies, but it has one of the fastest increasing incidences of cancer worldwide 1 . With no standard consensus to guide the management plan and 3 year survival rate of 43%, primary SCCT is challenging to treat 1 . Here we describe a case of primary SCCT.

Case Summary

A 65 year old white female with a medical history of longstanding Hashimoto's thyroiditis on Levothyroxine was initially evaluated for left neck enlargement and compressive symptoms. She had no significant risk factors for malignancy. TFTs were normal on Levothyroxine 100 mcg daily. CT neck showed a left thyroid cyst measuring 4.4×7 cm. Biopsy showed cystic material. Left hemithyroidectomy pathology showed moderately differentiated squamous cell carcinoma stage pT3aN0a, 4.5 cm without lymph node involvement. The cells stained positive for p40, Ck5/6, p63 and TTF1, but negative for thyroglobulin and calcitonin. Subsequently, completion thyroidectomy with central lymph node dissection resulted in benign pathology. Postoperative imaging was without evidence of residual neoplasm or pathologic cervical adenopathy. Levothyroxine was continued to maintain a TSH in the normal range. SCCT is not radioiodine avid and is therefore resistant to I-131 treatment. For this reason, the patient was referred to radiation-oncology and completed 6 weeks of XRT. Oncology recommended supportive care due to the aggressive nature of this tumor subtype.

Conclusion

SCCT is a very rare cancer of the thyroid with a mortality rate of 57% at 3 years. Overall survival rate, although poor, is dependent on the extent of the tumor resection and adjuvant radiotherapy/chemotherapy. Experts predict a 6 month average life expectancy with SCCT. At the time of this abstract, there is no evidence of recurrence or metastasis for our patient. There are no official guidelines on the diagnosis and treatment of SCCT, and more research is needed to better manage this rare cancer. Reference: 1. Primary Squamous Cell Carcinoma of the Thyroid Gland. Mohd-Irman-Shah Ibrahim et al. Iranian Journal of Otorhinolaryngology 2018 Jan; 30(96): 65–68

Presentation: No date and time listed
ODP457 A Single-center Retrospective Study of Thyroid Nodules 4 cm or Larger
Authors: Nalla Raveena , Izquierdo Roberto , Khurana Kamal , Wang Dongliang
Published: November 2022

Background

There is conflicting data and no clear consensus regarding the management of thyroid nodules 4 cm or larger. Diagnostic accuracy of fine needle aspiration (FNA) cytology of these nodules has been variable. Few studies have reported higher false negative rates suggesting surgery as reasonable option whereas other studies reported low false negative rates with no significant difference between small and large nodules. The goal of our study was to evaluate the reliability of FNA cytology in excluding malignancy in thyroid nodules 4 cm or larger in our patient population and to investigate the association between malignancy and any patient specific risk factors or ultrasound features.

Methods

We conducted a retrospective review of 380 patients with thyroid nodules who underwent thyroid surgery between 2014 and 2021 at our institution. Patient demographics such as age, gender and ethnicity, number and size of thyroid nodules, TSH level, FNA cytology, type of surgery and final surgical pathology results were recorded for patients with nodules 4 cm or larger and nodules between 2-4 cm. False negative rate of FNA cytology was compared between these two groups. Accessible ultrasound images for nodules 4 cm or larger were reviewed. Patient specific and nodule characteristics were compared between malignant and benign nodules. Fisher exact tests and multivariate logistic regression were used for data analysis.

Results

A total of 81 patients with thyroid nodules 4 cm or larger were studied, of which 22 patients (27.1%) had thyroid cancer. Mean age in patients with malignant nodules was 48.1 +/- 18.3 years versus 51.7 +/- 14.5 years in patients with benign nodules. The adjusted odds of malignancy for males was 20 times (95% CI: 3.3-125; p=0. 001) the odds for females. The adjusted odds of malignancy for nodules with both peripheral and internal vascularity on doppler ultrasound was 9.9 times (95% CI: 1.36-71.70; p=0. 024) that of nodules with only peripheral vascularity. Other nodule characteristics like composition, echogenicity, margins, halo, echogenic foci and taller than wide shape were not significantly different between malignant and benign nodules. False negative rate of FNA cytology for nodules 4 cm or larger was 8.7% (4/46 patients) as compared to 10% (4/40 patients) for nodules between 2-4 cm. This was not statistically significant (p=1. 0).

Conclusion

In our study, the false negative rate of FNA cytology in thyroid nodules 4 cm or larger was similar to that of nodules between 2-4 cm. This indicates that patients with thyroid nodules 4 cm or larger and benign cytology can be managed conservatively with appropriate clinical follow up. Male gender and nodules with peripheral and internal vascularity on doppler ultrasound were associated with thyroid malignancy in our review.

Presentation: No date and time listed
ODP460 Age- and sex- specific reference ranges for serum thyrotropin (TSH), free T4 and free T3 levels: Significant effects on the definition of subclinical dysfunction
Authors: Yamada Sayaka , Horiguchi Kazuhiko , Akuzawa Masako , Sakamaki Koji , Masamura Yasuhiro , Shimomura Yohnosuke , Kobayashi Isao , Andou Yoshitaka , Yamada Masanobu
Published: November 2022

Introduction

Consistent reference ranges of serum TSH, FT4 and FT3 levels without consideration of age and sex have been used to evaluate thyroid function. However, based on the recent development of highly sensitive assays of these hormones, subtle differences significantly affect the diagnosis, especially when diagnosing subclinical dysfunction, which affects more than 5% of the population. In the present study, we investigated the age- and sex- differences in these hormone levels using two different kits.

Methods

A total of 14,860 subjects for the Siemens kit and 6,604 subjects for the Abbot kit who underwent annual health check-ups at Takasaki Hidaka Hospital were included. Exclusion criteria comprised a history of thyroid disease, steroid use, renal failure or liver cirrhosis. All samples were measured at 8–9: 00 AM after overnight fasting.

Results

Regarding serum TSH levels in men, the median of subjects in their 30's was 1.4 mIU/L, the 2.5th percentile was 0.4, and the 97.5th percentile was 3.7 with the Siemens kit. These values in subjects in their 60's were 1.6, 0.5, and 5.7, respectively. They gradually but significantly increased with age based on both kits. Similarly in women, the serum TSH levels gradually increased, particularly with the Siemens kit, and the levels in women were higher than those in men. The median serum FT4 level in men in their 30's was 1.3 ng/dL (1. 0-1.7) and that in those in their 60's was 1.2 (1. 0-1.6) with the Siemens kit. The levels in men gradually but significantly decreased with age, but those in women were lower than those in men and remained consistent with age. Regarding serum FT3 levels in men, they were significantly higher than those in similarly aged women, and also gradually but significantly decreased with age; men in their 30's: 3.37 pg/mL (2.68-3.99), 60's: 3.15 (2.46-3.76) with the Abbot kit.

Discussion

The serum TSH level is highly sensitive to slight changes in the serum level of thyroid hormones even within the normal ranges; therefore, we diagnose subclinical hypothyroidism and hyperthyroidism using serum TSH levels. Many investigators have discussed the effects of subclinical dysfunction on lipid metabolism, osteoporosis, and cognitive mental diseases, and medications to normalize thyroid hormone levels. As there are significant differences in serum TSH, FT4, and FT3 levels according to age and sex, the age- and sex- dependent normal ranges should be used to precisely evaluate thyroid function and decide clinical therapies.

Presentation: No date and time listed
ODP483 Histone deacetylase 3 plays an important role in cerebellar developmental defects induced by hypothyroidism
Authors: Ishii Sumiyasu , Susetyo Alvin , Amano Izuki , Koibuchi Noriyuki
Published: November 2022

Background

Properly organized transcriptional regulation is responsible for the organogenesis of central nervous system including the cerebellum. Perinatal hypothyroidism impairs cerebellar organogenesis and results in motor coordination defects. In the absence of ligand, thyroid hormone receptor binds to co-repressor complexes which contain histone deacetylase (HDAC) 3, and acts as a transcriptional repressor. Although histone acetylation status is highly correlated with transcriptional regulation, the role of histone acetylation and deacetylation in cerebellar development in vivo remains largely unknown. In this study, we aim to study the role of HDAC3 in the cerebellar developmental defects induced by hypothyroidism.

Methods

Perinatal hypothyroidism and cerebellar defects were induced by an anti-thyroid agent propylthiouracil in mice. The mice were further treated with a specific HDAC3 inhibitor, RGFP966. Motor coordination was analyzed by three behavioral tests. Cerebellums are subjected to RT-PCR and chromatin immunoprecipitation for acetylated histone H3.

Results

Treatment with HDAC3 inhibitor significantly alleviated motor coordination defects in perinatally hypothyroid mice, suggesting that the enzymatic activity of HDAC3 contributes to motor coordination defects in these mice. These findings were associated with a partial rescue of small cerebellar size in hypothyroidism. In addition, HDAC3 inhibitor increased mRNA levels of cerebellar thyroid hormone responsive genes. The increase in mRNA levels was correlated with an increase in histone acetylation status at these gene loci.

Conclusion

HDAC3 plays an important role in cerebellar developmental defects induced by hypothyroidism, at least partly by histone deacetylation and transcriptional repression of thyroid hormone-target genes.

Presentation: No date and time listed
ODP488 Incidental papillary thyroid cancer found after hemi-thyroidectomy in man with MUTYH-associated polyposis
Authors: Yuen Alexa , Greenberg Pietra , Saul Shira
Published: November 2022

MUTYH-associated polyposis (MAP) is an autosomal recessive syndrome caused by a mutation to the MUTYH gene, a base excision repair gene that repairs oxidative damage to DNA. Mutations to both allelic copies of this gene typically manifest as multiple colonic polyps, which develop by middle age. Individuals with MAP are also at higher risk for developing non-gastrointestinal (GI) cancers including those affecting the ovary, bladder, breast, endometrium, and possibly thyroid. A 66-year-old man with a history of MAP complicated by colonic polyposis requiring subtotal colectomy, an esophageal adenocarcinoma resected by esophagectomy, and a gastrointestinal stromal tumor also resected was referred to endocrinology clinic for an incidental thyroid nodule found on routine surveillance. The patient denied prior neck radiation but reported having a daughter and cousin with thyroid cancer. Ultrasound showed a left 3.3 by 2.8 by 1.6 cm thyroid nodule with multiple lobulations. Although a fine needle aspiration (FNA) of the nodule was benign, a repeat ultrasound several months later noted an increase in size to 3.5 by 3.5 by 2. 0 cm. Given the nodule's significant growth, the patient's history of MAP, and family history of thyroid cancer, the patient underwent a left hemi-thyroidectomy. Pathology revealed that the nodule was a follicular adenoma, however also identified two papillary microcarcinomas, measuring 1 and 2 mm. The patient was started on levothyroxine 50 mcg with a goal TSH below 0.5 mU/L and was monitored with ultrasounds which were unremarkable. In 2021, the national cancer institute estimated approximately 150,000 cases of colorectal cancer (CRC) with a 65% 5-year survival, compared to 44,000 cases of thyroid cancer with a 98% 5-year survival. Although the incidence of CRC in patients with MAP is high, approximately 43-63% by age 60, the risks of several associated non-GI malignancies are not as well defined. The national comprehensive cancer network (NCCN) and the American College of Gastroenterology (ACG) both published guidelines regarding appropriate screening for both GI and associated non-GI malignancies. In regards to thyroid cancer, both advise screening in patients with familiar adenomatous polyposis (FAP), another familial condition, due to the increased risk of papillary thyroid cancer (PTC) of approximately 1-2%. The evidence concerning MUTYH is not as strong, with the ACG recommending annual thyroid cancer screening, although the quality of evidence is low. Since a thyroid ultrasound is both low-cost and non-invasive and the overall survival of patients with PTC is high, we agree that patients with MAP be screened with thyroid ultrasounds. This case highlights the possibility that thyroid cancer is a manifestation of MAP, and a lower threshold to send for surgery may be warranted for those with other risk factors such as a family history or prior neck radiation.

Presentation: No date and time listed
ODP506 Posterior Staphyloma misdiagnosed as unilateral Grave's ophthalmopathy
Authors: Houri Muhammad
Published: November 2022

21 year old female presented to our clinic for management of "grave's disease" She was given diagnosis of Graves’ disease three years before presentation to our institution She was treated with PTU for 2-3 months then it was stopped On physical exam On physical exam she has a small diffused goiter Left eye was prominent without chemosis or lid lag Right eye was normal Decreased vision in the left eye, counting fingers only Thyroid function was normal Thyroid receptor antibody was negative Because of decline of vision and unilateral protrusion of Left eye she was referred to ophthalmology for further evaluation. MRI of the Orbits was ordered MRI revealed findings consistent with Staphyloma Staphyloma is a chronic eye condition which results from poor vision if left untreated and causes increase in AP diameter of eye which results in protrusion of eye which might be confused with grave's ophthalmopathy This diagnosis should be considered when patients present with unilateral ophthalmopathy, especially if there is significant decline in vision in the effected eye. Since she presented late in adulthood there is no treatment to improve her vision at this point From the thyroid standpoint she had negative thyroid antibodies and normal thyroid function Ultrasound of thyroid showed thyroid to be diffusely enlarged with homogenous texture Complete eye exam by ophthalmology is indicated in evaluation of ophthalmopathy especially in case of red flags like decreased vison or unilateral presentation With unilateral Ophthalmopathy MRI of the orbits should be part of the workup to exclude other etiologies such as retro-orbital tumors which may be confused with grave's ophthalmopathy. As evident in this case MRI revealed different diagnosis.

Presentation: No date and time listed
ODP512 Renal Cell Carcinoma Metastatic to Thyroid: A Case Report
Authors: XU Shiming , Tabatabaie Vafa
Published: November 2022

Introduction

The thyroid gland is an uncommon site (0.7%) among all distant metastasis from renal cell carcinoma (RCC). Here we report a case of metastasis from RCC to the thyroid gland, diagnosed 15 years after treatment.

Clinical Case

A 63-year-old female, was referred to endocrine for evaluation of neck mass of several months’ duration. Thyroid function test revealed mildly low TSH and normal free T4. Recent thyroid ultrasound showed multinodular thyroid, the largest nodule was in mid to upper left thyroid lobe and measured 6cm in max diameter. Biopsy of 4 thyroid nodules was performed. Three nodules were benign (Bethesda 2), but the left mid to upper 6cm thyroid nodule showed Atypia of Undetermined Significance (Bethesda 3). Due to concern of large size, potential for further growth and gradual development of local compressive symptoms, total thyroidectomy was recommended. Patient was initially hesitant, however, within several months, she developed dysphagia and progressive neck swelling, and eventually had total thyroidectomy. Surgical pathology revealed metastatic RCC involved left thyroid lobe (8.4cm in greatest dimension) and right thyroid lobe (0.3cm in greatest dimension). Immunohistochemical stain were positive for CA9, CD10, PAX8, while negative for CKIT, CK7, TFT-1, thyroglobulin, synaptophysin, chromogranin, calcitonin, and PTH. Patient reported a history of right nephrectomy in 2005 and did not require adjuvant therapy at that time. Post-operative workup including CT neck/chest/abdomen/pelvis revealed a 2.4cm left superior mediastinum mass suspicious for metastasis. Patient was evaluated by genitourinary oncology and the decision was to continue surveillance with CT every three months. A new gallbladder lesion was detected after six months, laparoscopic cholecystectomy was performed, and pathology showed metastatic RCC.

Conclusion

This is an unusual case of metastatic RCC to thyroid gland, diagnosed 15 years after initial presentation with RCC that required only a nephrectomy. The cytology – pathology discrepancy in our case highlights the limitation of FNA in diagnosing rare thyroid masses of extra-thyroidal origin. A study has showed thyroid cytology was only diagnostic in 29.4% of population with RCC metastatsis(1). Especially when rapid growth is seen, surgery needs to be considered regardless of FNA results. Reference: 1. Khaddour K, Marernych N, Ward WL, Liu J, Pappa T. Characteristics of clear cell renal cell carcinoma metastases to the thyroid gland: A systematic review. World J Clin Cases. 2019 Nov 6;7(21): 3474-3485. doi: 10.12998/wjcc. v7. i21.3474. PMID: 31750330; PMCID: PMC6854394.

Presentation: No date and time listed
ODP639 The Occurrence and Predictors of Postoperative Adrenal Insufficiency for Patients With Subclinical Cushing's Syndrome
Authors: Da-long Zhu , Huan Chen , Meng-si Liu , Ping Li , Yang-jie Zeng , Yi-jie Wang , Yuan Lou , Zhao-yang Tian , Yuan Lou
Published: November 2022

Objective

To identify the occurrence and predictive factors of postoperative adrenal insufficiency in patients with subclinical Cushing's syndrome (SCS), and try to provide evidence for decision-making in SCS management.

Methods

The present retrospective analysis included 77 patients who underwent unilateral laparoscopic adrenalectomy for SCS between December 2011 and April 2021. Among them, 59 patients with complete follow-up data were included. We compared clinical characteristics of patients with and without postoperative adrenal insufficiency. The logistic regression model was used to find the potential risk factors in predicting the occurrence of postoperative adrenal insufficiency. The receiver operating characteristic (ROC) curve was used to evaluate the predictive values.

Results

We included 59 patients, of whom the incidence of postoperative adrenal insufficiency is 42.37%. The circadian rhythms of adrenocorticotropic hormone (ACTH) and cortisol disappeared in both two groups. Compared patients without postoperative adrenal insufficiency, patients with postoperative adrenal insufficiency were characterized by suppressed plasma ACTH level [1.11(1.11, 1.83) pmol/L vs 2.56(1.16, 4.63) pmol/L], elevated midnight cortisol level [268. 00(164. 00, 347.50) nmol/L vs 181.50(156.32, 227. 00) nmol/L] and increased cortisol level after 1 mg overnight dexamethasone suppression test (DST) [281. 00(241. 00, 396.64) nmol/L vs 172.50(144. 05, 215.25) nmol/L] (all P < 0. 05). Multivariate logistic regression analysis showed that the serum cortisol after a 1 mg-DST was the only independent predictive factor for the occurrence of postoperative adrenal insufficiency. The ROC curve showed that the best cut-off value of the serum cortisol after a 1 mg-DST was 233 nmol/L, with a sensitivity of 80. 00% and a specificity of 82.35%. The combination of the serum cortisol after a 1 mg-DST, plasma ACTH and midnight cortisol had the highest predictive accuracy (83. 05%).

Conclusion

Patients who underwent unilateral laparoscopic adrenalectomy for SCS had a risk of postoperative adrenal insufficiency. The pre-surgical assessment of the serum cortisol after a 1 mg-DST plus elevated midnight cortisol and suppressed plasma ACTH had predictive value for the occurrence of postoperative adrenal insufficiency.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:00 p.m. - 1:05 p.m.
ODP525 Thyrotoxic Periodic Paralysis
Authors: Anderson Karolina , Wellons Melissa
Published: November 2022

Thyrotoxic periodic paralysis manifests with painless muscle weakness, mostly in the proximal lower extremities. It is often precipitated byexercise, high carbohydrate meals, and occasionally fasting. Though most cases are hereditary, and affect Asian men disproportionately, some cases may occur sporadically. This thyrotoxicosis is most often attributable to Graves disease and patients typically have symptoms of thyrotoxicosis for months leading up to the episodes of paralysis. This is an 18-year-old Asian man with a history of Autism Spectrum Disorder who presents for evaluation of lower extremity weakness. He was seen two weeks prior for similar complaints. At that time, he had hypokalemia, hypomagnesemia, hypophosphatemia and was repleted and discharged home. The day prior to admission, he had pain in his bilateral posterior legs. On the morning of presentation, he could no longer ambulate which led him to present to the emergency room. Per his collateral, he had lost forty-five pounds in the last 6 months. He has not been tolerating oral food well with early satiety. He denies any diarrhea or constipation, fever/chills, or recent illness. He denies any family history of muscle disorders, thyroid disease, or any other autoimmune disease. He does not smoke tobacco, drink alcohol, or use any illicit substances. On physical exam, he is notably tachycardic to 120 bpm. He has thyromegaly but no palpable nodules. He has no exophthalmos on eye exam. On his neurologic exam, patient has 2/5 strength in his bilateral lower extremities. On laboratory evaluation, patient has fully suppressed TSH <0. 0015 mcunit/mL, free thyroxine of 3.43 ng/dL, total T3 of 463 ng/dL, TSI >40 IU/L, and TSH Receptor Antibody 31 IU/L. His potassium is low at 2.8 with a magnesium of 1.7. His thyroid ultrasound is without evidence of any nodules, has a homogenous parenchymal pattern, with increased vascularity diffusely. Patient is started on methimazole 20mg daily which is then increased to 20mg twice daily as well as propranolol 120mg daily, with plans for definitive therapy in the future. Though mechanism by which thyrotoxicosis can produce electrolyte abnormalities including hypokalemia leading to periodic paralysis is poorly understood, it is thought that thyroid hormone may increase tissue responsiveness to B-adrenergic stimulation like exercise or stress. This may lead to hyperpolarization of the muscle membrane and relative excitability. A variety of other factors play a role in the pathogenesis of thyrotoxic paralysis including insulin and testosterone through activation of the sodium potassium ATPase. Treatment for TPP includes aggressive electrolyte repletion, correction of the underlying cause with methimazole and propranolol-taking advantage of its beta adrenergic blocking ability, and often times planning for definitive therapy.

Presentation: No date and time listed
ODP598 Liquid levothyroxine (L-T4) maintains more stable TSH levels in hypothyroid patients, than tablet L-T4
Authors: Antonelli Alessandro , Balestri Eugenia , Botrini Chiara , Elia Giusy , Ferrari Silvia Martina , Mazzi Valeria , Paparo Sabrina Rosaria , Patrizio Armando , Ragusa Francesca , Fallahi Poupak
Published: November 2022

Hypothyroidism affects approximately 5% of the population, mostly women and people over 60 years of age. The standard therapy used for the treatment of hypothyroidism is tablet levothyroxine (L-T4). Thyroid-stimulating hormone (TSH) is monitored, and L-T4 is adjusted as necessary to reach euthyroidism. Upon the stabilization of TSH levels in the normal range, it is recommended to perform an annual testing in treated patients to warrant suitable replacement. Large population studies showed an increased mortality in people with TSH in the hypothyroid range, demonstrating the importance of maintaining a stable TSH level in the normal range.

We evaluated the stability of circulating TSH in hypothyroid patients treated with liquid L-T4, with respect to those treated with tablet L-T4. We enrolled patients with normal circulating TSH levels at the basal evaluation, not reporting any malabsorption or drug interference issues, who were in treatment with liquid or tablet L-T4.Six hundred and fifty six hypothyroid patients treated with liquid L-T4 were compared to 328 hypothyroid subjects receiving tablet L-T4 (both groups were matched by age and gender).Patients were followed for two years, and serum TSH, FT3, FT4 levels were assessed after one and two years.

At the first abnormal TSH value, the evaluated parameters were: age, gender, body mass index, history of chronic autoimmune thyroiditis, initial TSH, and L-T4 dosage. At the time of initial normal TSH, these parameters were not associated significantly with time to abnormal TSH values. After 1 year, normal TSH values were registered in 86% of the patients who received L-T4 liquid formulation, but only in 81% of patients treated with tablet L-T4. After 2 years, normal TSH values were registered in 84% of patients receiving L-T4 liquid formulation, while only in 74% of those with tablet L-T4 (p<0.05).

To sum up, the obtained data suggest that liquid L-T4 maintains more efficiently (than tablet L-T4) normal TSH levels in hypothyroid patients in the long term follow-up.

Presentation: No date and time listed
OR09-2 The RCAN 1.4 Metastasis Progression Suppressor Gene is Hypermethylated at Intron 1 and Downregulated in Papillary Thyroid Cancer
Authors: Li Wei , Liyanarachchi Sandya , Rajan Neel , Ringel Matthew , Khanal Tilak
Published: November 2022

Progressive metastasis is the proximate cause of cancer-related mortality for the majority of patients with solid tumors. Identifying both drivers, and gatekeepers of late stage progression (metastasis progression suppressors; MPS) is crucial to improve biomarkers and treatments. We previously identified Regulator of Calcineurin 1.4 (RCAN1.4) as a MPS gene in thyroid cancer that functions in part through overexpression of the cap-n-collar transcription factor NFE2L3 (NRF3). However, the mechanisms for RCAN1.4 loss in thyroid cancer, and whether or not this is reversible, had not be addressed. Because the RCAN 1.4 promoter contains CG rich regions reported to be hypermethyalated in other tissues, we hypothesized that RCAN 1.4 downregulation in thyroid cancer was similarly regulated. Studies were performed in both cell lines and de-identified human papillary thyroid cancer (PTC) tumor and normal tissue pairs from our Endocrine Neoplasia Repository tumor bank. Five thyroid cancer cell lines (TPC1, FTC133, BCPAP, C643, and 8505C) with different genetic drivers were selected based on low expression of RCAN 1.4. To determine if lines display methylation-regulated expression of RCAN 1.4, cells were treated with 1-10uM decitabine, a DNA methyl transferase inhibitor. In all cell lines, RCAN1.4 mRNA and protein levels increased with decitabine treatment, consistent with hypermethylation. Analysis of the literature and in silico analysis of the RCAN 1.4 gene identified CG rich regions as putative methylation targets in the proximal promoter and in intron 1. Using two different methods; 1) isolation of MseI-digestion DNA fragments using CpG MethylQuest beads followed by qPCR and 2) methylation-specific PCR (MSP) of bisulfite-modified DNA, hypermethylation of the intron 1 CG rich region was identified. There was no evidence of hypermethylation of the CG rich region of the proximal promoter. Methylation of the two regions also was assessed on 18 pairs PTC and adjacent normal tissues. Similar to the cell lines, hypermethylation was identified at intron 1 of RCAN 1.4 in PTC versus normal tissues. QRT-PCR results confirmed lower levels of RCAN1-4 mRNA in the PTC vs normal tissue. These samples also demonstrated increased NRF3 expression versus normal tissue. Taken together, these data demonstrate that RCAN 1.4 is downregulated in thyroid cancer cells and human PTCs by hypermethylation of CG rich regions in intron 1 and that this effect is reversible using demethylating agents.

Presentation: Saturday, June 11, 2022 11:45 a.m. - 12:00 p.m.
PSAT334 An Unusual Case of Thyroid Storm in a Patient with Schizophrenia-A Diagnostic Dilemma
Authors: Markovic Nikolina , Umar Rehan , Raghuwanshi Maya
Published: November 2022

Introduction

Thyroid storm represents life threatening endocrine disorder that requires early recognition and treatment due to significant mortality rates. Case reports in which diagnosis of thyroid storm was delayed secondary to acute psychotic symptoms mainly consisting of auditory hallucinations, delusions, and violent behavior have been published. This case serves to illustrates that even in patients with schizophrenia acute psychiatric disorder can be early manifestation of life-threatening endocrine disorder.

Clinical case

We present a case of 25-year-old male with history of schizophrenia who was brought to hospital after he was found down, disoriented, with auditory hallucinations. Associated symptoms included diarrhea and abdominal pain. On physical exam patient was found to have altered mental status, proptosis, tachycardia, diaphoresis, and warm and moist skin. Due to suspicion for worsening schizophrenia patient was evaluated by psychiatry and was found to have active suicidal ideation. Thyroid function tests (TFTs) was significant of elevated fT4 and T3 (fT4 > 5.0 ng/dl, T3 6.5 ng/dl) and suppressed TSH (0.020 µIU/ml). Burch-Wartofsky Point Scale was suggestive of impending thyroid storm and endocrinology was consulted after which treatment with methimazole, dexamethasone, propranolol, and potassium iodide (Lugol's solution) was started. On second day of treatment patient had significant improvement in mental status with resolution of auditory hallucination, suicidal ideation, and tachycardia with complete return to his baseline mental status on the third day of hospital stay. At the end of hospital course TFTs also showed decrease in fT4 and T3 and patient was discharged on methimazole and propranolol as well as paliperidone for treatment of schizophrenia. When patient was seen during outpatient follow-up, he was free of any psychiatric symptoms.

Conclusion

Mental status changes due to thyroid storm versus acute worsening of schizophrenia is hard to differentiate. Our case shows that even in the patients with prior psychiatric history, thyroid storm should be highly on differential diagnosis especially when patients are presenting with acute worsening of symptoms. In this case high suspicion for thyroid storm and early treatment in first 24h of the presentation lead to favorable outcome of this life-threatening condition. As thyroid storm is clinical diagnosis, high suspicion, use of Burch-Wartofsky Point Scale and early measurement of TFTs can help physicians distinguish thyroid storm from primary neuropsychiatric presentation.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF11 | PSAT234 Deep learning analysis of thyroid nodule ultrasound images has high sensitivity and negative predictive value to rule-out thyroid cancer
Authors: Clark Toshimasa , Cohen Trevor , Haugen Bryan R , Subramanian Devika , Pozdeyev Nikita , Dighe Manjiri , Barrio Martin , Leu Michael G
Published: November 2022

Purpose

To evaluate deep learning analysis of thyroid nodule ultrasound images as a rule-out test for thyroid malignancy.

Methods

Supervised deep learning (DL) classifier of thyroid nodules was trained on 32,545 thyroid US images from 621 nodules representing all major benign and malignant types of thyroid lesions and tested on an independent set of 145 nodules collected at a different healthcare system in the United States. The Big Transfer BiT-M ResNet-50×1 convolutional neural net architecture was modified to contain 3, 4, 6 and 3 PreActBottleneck units per block 1 through 4. Weights pretrained on the ImageNet-21k dataset were loaded and weights for blocks 3 and 4 were fine-tuned for the binary classification task of distinguishing benign and malignant thyroid nodules.

Results

The deep learning thyroid nodule classifier achieved an area under receiver operating characteristic curve (AUROC) of 0.889 on five-fold cross-validation. The AUROC improved when images were scaled by nodule size and six randomly selected cine clip frames were added to the training set per epoch. GradCAM class activation heatmaps revealed that microcalcifications and spongiform appearance were reliably recognized by the classifier as malignant and benign features, respectively. Spongiform nodules were found to be benign even when microcystic spaces constituted less than 50% of nodule volume.

To investigate the clinical relevance of the benign vs. malignant classifier, the binary classification threshold for the probability of malignancy generated by model was set at 7% to achieve sensitivity and negative predictive value (NPV) comparable to that of the fine needle aspiration biopsy (FNA). At this threshold, cross-validated deep-learning model achieved a sensitivity of 90%, specificity of 63%, positive predictive value (PPV) of 46% and negative predictive value of 94%. When tested on an independent image set that includes 18 classic papillary thyroid cancers (PTC), 5 follicular variant PTC, 4 medullary thyroid cancers, 3 follicular thyroid cancers (FTC), and 1 Hurthle cell thyroid cancer, the DL classifier achieved AUROC of 0.88, sensitivity of 97%, specificity of 61%, PPV of 40% and NPV of 99%. A single minimally-invasive FTC that had no suspicious features on thyroid ultrasound was incorrectly classified as benign.

Conclusions

This study demonstrates that the ultrasound-based deep-learning classifier of thyroid nodules achieves sensitivity and negative predictive value comparable to that of thyroid fine needle aspiration (FNA). Clinicians may use this tool to augment clinical judgment when determining whether to perform FNA procedures.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:06 p.m. - 1:11 p.m.
RF35 | PSAT262 Comparative Study of Hertel Exophthalmometer and Luedde Exophthalmometer Versus Computed Tomography for Measurement of Proptosis in Normal Subjects
Authors: Traiwanatham Sirinapa , Sirinvaravong Sirinart , Plengvidhya Nattachet , Wongsripuemtet Jitsupa , Lertlam Supassa
Published: November 2022

Background

Clinical evaluation of proptosis is measured by an exophthalmometer. Hertel exophthalmometer has long been considered a standard instrument for measurement of eye protrusion. The reading may be subject to error while the examiners read through the integral reflection mirrors. Luedde exophthalmometer, which is a ruler correcting for parallax, is easier to use and less expensive than Hertel exophthalmometer. Since CT scan of orbits or brain provides the most objective assessment of proptosis measurements, we aim to study the correlation between Luedde and Hertel exophthalmometers in comparison with the CT scan for the evaluation of proptosis in normal subjects.

Methods

This prospective study was carried out between November 2020 and January 2021. Sixty-three patients were enrolled from a single tertiary hospital. All patients underwent CT scan of brain for medical reasons. On the same day, proptosis was measured with Hertel and Dual Luedde exophthalmometer by two independent examiners. Measurement of proptosis from CT scan was performed by one experienced neuroradiologist, using 2 reference measurement techniques. Correlation coefficients between proptosis values measured by each exophthalmometer and CT scan were compared.

Results

The mean age of the participants was 63 years old and 54% were female. For the right eye, mean proptosis measurement was 14.9+/-1.6 mm by Hertel exophthalmometer, 14.1+/-2.3mm by Luedde exophthalmometer, 16.6+/-2.3 mm by first CT technique, and 13.1 +/- 2.2 mm by second CT technique. For the left eye, mean proptosis measurement was 15.5 +/-1.5mm by Hertel exophthalmometer, 13.7+/-2.3 mm by Luedde exophthalmometer, 16.6+/-2.3 mm by first CT technique and 13.1 +/- 2.2 mm by second CT technique. The Intraclass correlation coefficient (ICC) of Hertel exophthalmometer for proptosis measurement compared to first CT technique and second CT technique were 0.63 and 0.60 for right eye; 0.61 and 0.55 for left eye, respectively. The ICC of Luedde exophthalmometer for proptosis measurement compared to first CT technique and second CT technique were 0.78 and 0.74 for right eye; 0.77 and 0.74 for left eye, respectively.

Conclusion

There is a good correlation between Hertel and Luedde exophthalmometers in evaluation of proptosis. However, proptosis measured by Luedde exophthalmometer shows superior correlation with CT scan. The result suggests that Luedde exophthalmometer can be routinely used for measurement of proptosis in place of Hertel exophthalmometer, given the simplicity and the inexpensiveness of the instrument.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:30 p.m. - 12:35 p.m.