bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODP063 Development and Validation of Model for Sparing Adrenal Venous Sampling in Diagnosing Unilateral Primary Aldosteronism
Authors: Hu Jinbo , Song Ying , Li Qifu , Yang Shumin 
Published: November 2022

Abstract

Context
Current guidelines recommend adrenal venous sampling (AVS) to identify unilateral primary aldosteronism (UPA) before offering adrenalectomy. However, AVS is costly and technically challenging, limiting its use to expert centres.

Objective
To establish a model to predict UPA and therefore bypass the need for AVS prior to surgery. Design and Setting: The model was developed in a Chinese cohort and validated in an Australian cohort. Previously published prediction models of UPA were also tested. Participants: PA patients with a definite subtyping diagnosis based on AVS and/or surgery. Main Outcome Measure: Diagnostic value of the model.

Results
In the development cohort (268 UPA and 88 bilateral PA), combinations of different levels of low serum potassium (≤3. 0 or 3.5mmol/L), high PAC (≥15-30ng/dL), low PRC (≤2.5-10μIU/mL) and presence of unilateral nodule on adrenal CT (&gt;8-15mm in diameter) showedspecificity of 1. 00 and sensitivity of 0.16-0.52. The model of serum potassium≤3.5mmol/l, PAC≥20 ng/dL, PRC≤5μIU/mL plus a unilateral nodule≥10mmhad the highest sensitivity of 0.52(0.45-0.58) and specificity of 1. 00(0.96-1. 00). In the validation cohort (84 UPA and 117 bilateral PA), the sensitivity and specificity of the model were 0.13(0. 07-0.22) and 1. 00(0.97-1. 00), respectively. Ten previous models were tested, and only one had a specificity of 1. 00 in our cohorts, but with a very low sensitivity [0. 07(0. 04-0.10) and 0. 01(0. 00-0. 06) in our development and validation cohorts, respectively].

Conclusions
A combination of high PAC, low PRC, low serum potassium and unilateral adrenal nodule could accurately determine PA subtype in 13-52% of patients with UPA and obviate the need for AVS before surgery.
Presentation: No date and time listed
PMON268 A Multicenter, Open Label, Variable Dose, Two-Arm, Pilot Paediatric Phase 1 Pk Study To Evaluate 4.5% Testosterone Nasal Gel In Hypogonadal Boys
Authors: Lucas-Herald Angela , Hawcutt Daniel , Thankamony Ajay , Faisal Ahmed S 
Published: November 2022

Abstract

Introduction
Testosterone treatment is regularly required by adolescent boys with hypogonadism.

Aim
To evaluate the pharmacokinetics of a nasal testosterone gel, which is available for adult men with hypogonadism, in adolescents.

Methods
Open-label, variable-dose, non-randomized, 3-treatment crossover study of testosterone nasal gel 4.5% w/w (Natesto™). Subjects were hypogonadal adolescent boys between the ages of 12.0–17.9 years. Biochemical analyses were performed by Acerus Pharma.

Summary and Conclusions
Testosterone nasal gel 4.5% w/w (Natesto™) represents a safe and acceptable method of administering testosterone to hypogonadal adolescents. Based on feedback from both patients and investigators, the nasal gel was well tolerated by patients, and it was felt that children would be able to administer this independently.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF03 | PMON288 Determining Mechanisms of Farnesoid×Receptor Regulation of Heme Biosynthesis and Ductular Reaction
Authors: Dean Angela , Jungwirth Emilian , Bailey Keith , Panzitt Katrin , Wagner Martin , Anakk Sayeepriyadarshini 
Published: November 2022

Abstract
Bile acids are increasingly becoming recognized as hormones, and their main endogenous receptor is the farnesoid X receptor (FXR). In order to investigate whether FXR is necessary to maintain proliferation of the bile ducts in response to injury, we challenged male and female wild-type (WT) and Fxr knockout (FxrKO) mice with 0.1% 1,4 dihydro 2,4,6 trimethyl 3,5 pyridinediacarboxylic acid diethyl ester (DDC) in the diet for two weeks. DDC is an inhibitor of ferrochelatase, the final enzyme of heme biosynthesis, resulting in a buildup of bile plugs in the liver causing an inflammatory response called ductular reaction. We found that deletion of Fxr led to a dramatic reduction in the ductular reaction independent of the sex. Then we tested if the inhibition of ferrochelatase was compensated for in FxrKO mice by analyzing the expression of genes in the heme biosynthesis pathway. Although we find a decrease in basal Alad gene expression in FxrKO mice in both sexes, upon DDC treatment, expression does not decrease as much as seen in the WT mice. Intriguingly, we also noted sex-specific changes. Cpox expression was increased in male FxrKO mice, but FxrKO mice showed reduced suppression of Cpox expression when treated with DDC. Conversely, Ppox expression was reduced in male FxrKO mice compared to WT mice, and both male WT and FxrKO mice had a comparable reduction in Ppox expression upon DDC treatment. Female FxrKO mice showed a significant decrease in Fech expression basally that did not change with DDC treatment. These results suggest that FXR may contribute towards regulating expression of genes in the heme biosynthesis pathway. However, these observations do not explain the lack of ductular reaction. Since PGC1α was previously shown to control heme biosynthesis through its downstream targets, FOXO1 and NRF1, we examined their transcript expression in our study to determine if the pathway is playing a role in our observations. We examined this pathway and observed a significant decrease in Foxo1 expression in both sexes of WT and FxrKO mice basally but only a reduction in Nrf1 expression upon DDC treatment. We are currently investigating other potential regulators of heme biosynthesis and ductular reaction, such as Klf1 which regulates erythropoiesis and plays a role in ductular reaction and the nuclear receptors Rev-Erbα/β that use heme as a ligand, to determine how FXR is regulating heme biosynthesis.
Presentation: Saturday, June 11, 2022 1:24 p.m. - 1:29 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
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

Abstract
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

Abstract
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

Abstract

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

Abstract

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 &lt;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 &lt;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

Abstract

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

Abstract

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