bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract
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

Abstract
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

Abstract

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

Abstract

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 &lt; 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

Abstract
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 &lt;0. 0015 mcunit/mL, free thyroxine of 3.43 ng/dL, total T3 of 463 ng/dL, TSI &gt;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

Abstract
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&lt;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

Abstract
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.