bluuebunny/crossref_metadata_2025 huggingface dataset:
LBMON299 Aldosterone Production Is Regulated By Gap Junctions In Human Adrenal Cells
Authors: Goodchild Emily , Aizan Elena , Wu Xilin , Drake William , Brown Morris
Published: November 2022

Aldosterone plays a critical role in blood pressure regulation via the renin-angiotensin-aldosterone system. Autonomous production of aldosterone, primary aldosteronism (PA), is the commonest curable cause of hypertension worldwide. Two cell types in the adrenal cortex produce aldosterone: zona glomerulosa (ZG) cells and aldosterone producing nodules (APN), and in cells of aldosterone producing adenomas (APA). Adrenal cortex cells undergo phenotypic metamorphosis as they migrate from the subcapsular region, centripetally, towards the corticomedullary junction, changing from aldosterone- to cortisol- producing cells as they go. Gap junctions (GJs) are specialised channels of cytoplasmic communication between cells, permitting the regulated transfer of substrates. Loss-of-function mutations in the CADM1 gene, which affects GJ protein CX43, have been found in APAs, implicating CX43 in aldosterone regulation. This study aims to demonstrate the dysregulation of aldosterone production by CX43 inhibition in human adrenal cell line, H295R, and elucidate GJ distribution in human adrenal cortex.

Methodology

H295R cells were treated with 1×10-8M angiotensin II and connexin mimetic GJ inhibitor, GAP27, at 0µM, 25µM, 83µM and 250µM. Immunofluorescence (IF) was used to identify the abundance of CX43 in different cell types of the adrenal cortex, performed on ex-vivo para-APA adrenal tissue, using antibodies against CX43 (GJA1), colocalised with markers of aldosterone-producing cells (aldosterone synthase, CYP11B2), cells of the zona glomerulosa (ZG) (VSNL1, and DAB2) and zona fasciculata (ZF) (CYP7A1).

Results

Inhibition of CX43 with Gap27 results in a dose-dependent increase in CYP11B2 mRNA expression and aldosterone production. At the highest concentration of 250µM GAP27, CYP11B2 mRNA expression increased by 133-fold (p=<0. 00001) and aldosterone production by 29-fold (p=0. 0006). IF studies demonstrate a crescendo gradient of CX43 in a centripetal direction from cells of APN to ZF. The abundance was lowest in aldosterone-producing APN cells, moderate in non-aldosterone-producing ZG cells and highest in cortisol-producing ZF cells. GJ distribution was pan-membranous in ZF, but, where present, mostly cytoplasmic in APN. Evidence of recent active communication, in the form of annular gap junctions (AJG), was present in all three cell types.

Conclusion

The CX43 inhibition-induced upregulation of CYP11B2 expression and aldosterone synthesis indicates that it has an important regulatory role in physiological aldosterone production via CYP11B2 expression. The distribution of CX43 in adrenal tissue suggests its transport substrate not only regulates aldosterone synthesis, but also in adrenal cortex cell phenotypic metamorphosis/migration. Future work will investigate the substrate of CX43 in adrenal cells and its possible effect on adrenal cell phenotype.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF03 | PMON300 Sex Hormones, Sex Hormone Binding Globulin, and Gonadotropins in Men with Inguinal Hernias
Authors: Zhao Hong , Liu Lijia , Chen Simeng , Potluri Tanvi , You Tianming , Halle Ariel W T , Coon V John , Bulun Serdar E
Published: November 2022

Background

More than 1 in 4 men will undergo inguinal hernia repair during their lifetime. Age is a significant risk factor for inguinal hernias in men with increased incidence in older age. Sex steroid hormone changes are observed with a higher ratio of serum estradiol (E2) to testosterone (T) as men age. We previously demonstrated that a shift from androgen to estrogen action caused inguinal hernia formation in a transgenic male mouse model with increased estrogen action in lower abdominal muscle tissues. However, age-related changes in serum E2 levels in men are conflicting, as some studies have reported increases but others have noted unchanged or even decreased E2 levels with advancing age.

Method: This study was performed on 212 men with inguinal hernias, aged 20 to 90 years, stratified at 10-year intervals of age (20-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90 years). We assessed total T (TT), total E2 (TE2), dehydroepiandrosterone (DHEA), sex hormone-binding globulin (SHBG), and gonadotropins (FSH and LH). Body mass index (BMI) was calculated using height and weight.

Results

The BMI distribution was balanced for men with inguinal hernias among all age groups. TE2 was low in 23.7%, normal in 65.8%, and high in 10.5% of men 50 years or younger. In contrast, the percentage of patients with high TE2 was increased 2.6-fold in men over the age of 50 (20.1% in low, 52.3% in normal, and 27.6% in high). TT was normal in all men 50 years and younger but was low in 3.5% and normal in 96.5% of men over the age of 50. We found that serum TE2 levels and the ratio of TE2/TT positively correlated with age (p=0.001). In addition, serum TE2 levels were significantly higher in the advanced age groups (71-80 and 81-90 years) than in the young age group (20-40 years). Serum TT levels decreased but did not reach significance in the advanced age groups compared to the young age group. Remarkably the ratio of E2/T was higher in the advanced age groups than in the young age group (20-30 years). Serum DHEA levels in men over the age of 50 were significantly higher than in men 50 years or younger. SHBG levels were higher in men over 70 years than men 50 years or younger (p< 0.01). Serum levels of FSH and LH in men over 60 years were 3-fold greater than in men 50 or younger (p<0.01).

Conclusions

Our findings suggest a correlation of increased estrogen action in the formation of inguinal hernias at an advanced age. This points to a potential utilization of inhibitors of estrogen synthetase or estrogen antagonists in a subset of elderly inguinal hernia patients with increased circulating estrogen as a non-surgical intervention.

Presentation: Saturday, June 11, 2022 1:42 p.m. - 1:47 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBODP064 A Rare Case Of Paraneoplastic Cushing Syndrome Associated With Pulmonary Carcinoid Tumor
Authors: Mandal Gaurav , Happel Aja , Felder Jill , Iyer Pritish , Murty Preethi , Lale Ajit , Greco Rick
Published: November 2022

A 67-year-old female with a history of primary pulmonary carcinoid tumor with metastasis to the liver presented with shortness of breath and generalized weakness. On presentation, her vital signs were BP 170/100 mm Hg, pulse 99/min, RR 18/min, O2 saturation 85% on room air. Physical exam was significant for diffuse rhonchi in bilateral lungs. Initial labs showed marked hypokalemia with K+ 2.5 and HCO3- 42. CT scans showed increased numbers of nodules and sizes in the lungs and numerous large liver masses. The adrenal glands and aldosterone-to-renin ratio were within normal limits. A random cortisol level was 113.14 ug/dL (2.50-12.50) with a concomitant elevated ACTH level of 353.6 pg/mL (7.2-63.3), while brain MRI was negative for pituitary or metastatic lesion. A liver mass biopsy revealed a transformation into a high-grade neuroendocrine tumor with a Ki-67 of 32%. A low dose dexamethasone suppression test showed a cortisol level of 66. 08. Interpreting this result and the imaging studies, it was determined that hypercortisolism was secondary to ectopic ACTH production. This clinical presentation and findings supported her cancer transformation to a functional metastatic neuroendocrine cancer with a paraneoplastic syndrome previously unknown. She was started on spironolactone as a potassium-sparing diuretic, itraconazole to inhibit cortisol synthesis based on inpatient formulary at that time, and combination chemotherapy with cisplatin and etoposide. Over the next few weeks, she developed signs of Cushing syndrome with leg swelling, facial puffiness, proximal muscle weakness, muscle loss, easy bruising, abdominal striae, coccydynia, glucose intolerance, and acid reflux. She had complications of peptic ulcer disease with bleeding, Clostridium difficile colitis, bacterial pneumonia, persistent hypokalemia, hypomagnesemia, and chemotherapy-induced anemia and severe thrombocytopenia. A repeat cortisol level was >150. 00 ug/dL despite the uptritation of itraconazole, suggesting not so much success. With insurance approval, she was started on ketoconazole, on which the cortisol levels on Days 5, 12, and 19 were 114.74 ug/dL, 126.84 ug/dL, and 118.42 ug/dL, respectively. Given uncontrolled hypercortisolism, a novel cortisol synthesis inhibitor, osilodrostat, was ordered and approved. However, two days later, the patient required another hospitalization for respiratory failure and severe sepsis from Coronavirus Disease 2019 pneumonia and Acinetobacter radioresistens bacteremia, and she passed away. This case highlights the therapeutic challenge of managing a late presentation of Cushing syndrome from ectopic ACTH production secondary to the progression of metastatic lung cancer. As such, clinicians should periodically consider screening for the subclinical-Cushing syndrome to diagnose such cases early, preventing such consequences of overt Cushing syndrome.

Presentation: No date and time listed
LBODP069 Parathyroid Crisis And Recalcitrant Hypercalcemia From Double Parathyroid Adenomas
Authors: Parihar Aisha , Iyer Karishma , Patel Amani , Patel Alpa
Published: November 2022

Parathyroid crisis is a rare and life-threatening manifestation of hyperparathyroidism. Patients present with severe hypercalcemia and associated symptoms of bone disease, nephrolithiasis, abdominal pain, and fatigue. Multi-organ dysfunction in the form of encephalopathy, cardiac dysrhythmias, and renal failure is often present. There have also been reports of bleeding duodenal ulcers secondary to marked elevated parathyroid hormone. The most common etiology is a single parathyroid adenoma (85%) followed by hyperplasia (10%), double adenomas (4%), and carcinoma (1%). Parathyroid crisis requires immediate medical management of hypercalcemia and in recalcitrant cases, urgent parathyroidectomy. A 67-year-old female presented to the hospital with weakness and intermittent hematochezia. She was found to have acute renal failure, new onset anemia, and profound hypercalcemia of 17.1 mg/dl. On exam, she was slow to respond and exhibited diffuse muscle weakness. EKG showed sinus tachycardia, a right bundle branch block, and normal QTc. She received aggressive intravenous fluids and calcitonin. Bisphosphonate was not given due to renal failure. Due to refractory hypercalcemia, she was initiated on cinacalcet. She ultimately required hemodialysis due to failure of medical therapy. Further work-up showed a PTH of 2627 pg/ml. Vitamin D levels, TSH, and serum and urine protein electrophoresis were unremarkable. Renal ultrasound did not show nephrolithiasis. Given hematochezia and anemia in the setting of parathyroid crisis, endoscopy was done and was unrevealing of ulcers. A parathyroid ultrasound and nuclear medicine CT scan showed bilateral parathyroid adenomas. She underwent left superior and right inferior parathyroidectomy with biopsies revealing hypercellular parathyroid tissue with no features of malignancy. Following surgery, calcium levels gradually normalized. However, she remained dialysis dependent. This case exhibits a rare presentation of parathyroid crisis from double adenomas, requiring urgent double parathyroidectomy due to refractory hypercalcemia. This patient had an astoundingly elevated PTH level of 2627 pg/dl, one of the highest values documented in literature, which may attribute to the recalcitrant nature of hypercalcemia. Prompt diagnosis and treatment of parathyroid crisis is critical in preventing life-threatening complications.

Presentation: No date and time listed
LBSAT367 Association Of Thyroid Functioning With Depression: A Population-based Historical Cohort Study
Authors: Liu Junting , Akcan Tugce , Gabor Rachel , Delgoffe Brooke , Sharma Shivy , Singh Balwinder , Parsaik Ajay K
Published: November 2022

Background

Despite the abundance of literature, the relationship between hypothyroidism and depression is not clearly defined. We conducted this study to investigate the association of thyroid functioning [measured by serum Thyroid Stimulating Hormone (TSH) level] with depression [measured by Patient Health Questionnaire-9 (PHQ-9)] in a population-based study. Method: This is a cross-sectional and longitudinal study, which included all adult patient who received care at the Marshfield Clinical Health System from 2015 through 2020 and had one or more TSH and PHQ-9 measurement pair within 6 months. Logistic regression was used to estimate the effect of TSH level on depression in patients without or with thyroid diseases (untreated thyroid disease- not on any thyroid medications and treated thyroid disease - on thyroid medications). Candidate models included depression regressed on (1) TSH, (2) log-transformed TSH, (3) TSH level: normal (0.5-4.9), elevated (5. 0-9.9), very elevated (≥10), and model fit statistics were used to select the TSH-level model. Patient characteristics that were significantly associated with TSH level were included as covariates including Charlson Score.

Results

127,587 unique patients with 236,799 pairs of PHQ-9 and TSH were identified from Electronic Medical Record (EMR) data base. The average age was 53.6 (19.1) years, 90.4% were Caucasians, and 66.2% were females. 87.8% had no depression, 4.4% had minimal depression, and 3.6% had moderate depression, while rest had severe depression. 5.4% had low TSH, 85.8% had normal TSH, 6.8% had elevated and 2. 0% had very elevated TSH. 38.6% had thyroid disease, off which 32.6% were treated In adjusted model, patients without thyroid disorder did not have an increased risk of depression with elevated and very elevated TSH. However, patients with untreated thyroid disorder had increased risk of depression with very elevated TSH (OR=2. 08, 95% CI: 1.39-3.12), while patients with treated thyroid disorder had increased risk of depression with elevated (OR=1.15, 95% CI: 1. 03-1.27) and very elevated TSH (OR=1.26, 95% CI: 1.11-1.42) Conclusions: This large cohort study suggests that there is no association between TSH and depression in patients without any thyroid disorders. However patients with thyroid disorders do have higher risk of depression with elevated TSH level.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
ODP584 Corticosteroid-binding Globulin Deficiency Independently Predicts Mortality and is Associated with Norepinephrine Requirements in Septic Shock.
Authors: Chapman Marianne , Davies Michael , Nenke Marni , Rankin Wayne , Rushworth Rosemary , Torpy David , Meyer Emily
Published: November 2022

Context: Hydrocortisone administration in septic shock remains controversial. Corticosteroid-binding globulin (CBG) transports cortisol to inflammatory sites and is depleted in septic shock.

Objective

To determine if severely deficient plasma CBG <200 nmol/L (Ref range 269-641 nmol/L) independently predicts septic shock mortality.

Methods

A prospective observational study in patients with septic shock. Patients were categorised into two groups: mean plasma CBG concentrations <200 nmol/L and ≥200 nmol/L (day 1/2), with additional categorisation by nadir CBG. Primary outcome was Intensive Care Unit (ICU) mortality. Secondary outcomes were 28- and 90-day mortality, norepinephrine requirements, renal-replacement therapy, and clinician-instituted hydrocortisone.

Results

135 patients were included. Mortality rates in ICU were higher in the CBG <200 nmol/L vs the CBG ≥200 nmol/L group: 32.4% vs 13.9%; Odds ratio (OR), 2.97, (95% confidence intervals (CI) 1.19,7.41); P=0. 02: 28-days; OR 2.25 (95% CI 0.99,5.11): 90-days; OR 2.21 (95% CI 0.99,4.91). Multivariate analysis revealed 4 factors independently associated with ICU mortality: CBG <200 nmol/L (OR 3.23, 95% CI 1. 06,9.88), Acute Physiology and Chronic Health Evaluation (APACHE) II >25 (OR 3.58, 95% CI 1.20,10.68); Sequential [Sepsis-related] Organ Failure Assessment (SOFA) liver score (OR 1.98, 95% CI 1. 04,3.72); and renal-replacement therapy (OR 6.59, 95% CI 2.17,20. 01). Nadir CBG levels were associated with higher SOFA cardiovascular scores, norepinephrine total dose (ug) P<0. 01 and duration (days) P<0. 01. Plasma cortisol concentrations and hydrocortisone administration did not relate to ICU mortality.

Conclusion

Septic shock patients with CBG <200 nmol/L had higher norepinephrine requirements and 3.2-fold higher ICU mortality. CBG concentration was the only directly reversible independent mortality risk factor.

Presentation: No date and time listed
ODP452 A Case of Thymic Hyperplasia in Graves’ Disease
Authors: Ahmed Ammar , Buckley Lisa , Maradana Jhansi , Nuvvula Sri , Tan Zi , Thompson Michael J , Zainal Abir
Published: November 2022

Introduction

We report a case of a patient with Graves’ Disease (GD) associated with thymic hyperplasia (TH) which regressed with treatment of GD. The association between these two conditions is under recognized. The causative mechanisms between TH associated with GD are still under investigation.

Case Description

A 39-year-old male patient presented with hemoptysis, dyspnea, palpitations, tremors and unintentional weight loss. His TSH was suppressed to < 0. 005 and free T4 was elevated to 5.51. As part of his work up a CT scan was performed which revealed a prominent anterior mediastinal mass. He was started on Methimazole and Atenolol. Lab work confirming positive TSI and TRAB antibodies consistent with Graves’ disease. At follow up, he opted for radioactive iodine ablation therapy with 20mCi. He had failure of therapy and was resumed on Methimazole. He ultimately underwent total thyroidectomy with subsequent thyroid hormone replacement with Levothyroxine 150mcg daily. His thyroid function tests normalized, and his symptoms resolved. A repeat CT thorax was performed which showed complete resolution of his mediastinal mass, consistent with GD associated TH.

Conclusions

GD associated TH was first described in 1914. Data supports TSH receptor antibody mediated thymic enlargement1. TH can be classified in two morphological types, lymphoid hyperplasia unassociated with thymic enlargement and true TH in which an increase in thymic volume is evident 2. Thymic cortical tissue expansion seems to be due to a hyperthyroid state involving increased levels of thymulin, a protein involved in lymphocyte differentiation whereas lymphoid hyperplasia correlates with the immune process in GD 2. Antithyroid drug therapy reduces circulating thyroid hormone levels causing a generalized immunosuppressive effect. This reduces hyperplasia of lymphatic organs including the thymus 3. There are no current guidelines for the management and surveillance of thymic hyperplasia in GD as the course and timeline of regression of TH can vary widely. Thymic biopsies are performed frequently to rule out malignancy, however, it is important to raise awareness that GD associated TH has a benign course and generally resolves with management of the underlying GD 3. It is imperative to avoid unnecessary invasive procedures and their subsequent complications in such GD patients. References: 1] Dalla Costa M (2014) Thymic hyperplasia in patients with Graves’ disease. J Endocrinol invest 37: 1175-1179. 2] Nakamura S (2012) Thymic enlargement in two cases of Graves’ disease. Internal Med 51: 673-674.3] Nakamura T et al (2004) A case of thymic enlargement in hyperthyroidism in a young woman. Thyroid 14: 307-310.

Presentation: No date and time listed
ODP456 A rare case of massive goiter with overlapping features of Riedel's thyroiditis and Fibrous Variant of Hashimoto's thyroiditis
Authors: Fernandez Yeset Cervelo , Khan Areej
Published: November 2022

Background

Hashimoto's thyroiditis is the most common autoimmune disorder of the thyroid gland associated with hypothyroidism. It is distinguished by painless inflammation and elevated titers of TPO antibodies. Fibrous Variant of Hashimoto's Thyroiditis is a rare condition occurring in about 10% of cases, mainly middle-aged individuals, and characterized by an extensive fibrous proliferation without extension into the surrounding structures. Riedel's thyroiditis is a rare generalized autoimmune disorder involving B lymphocytes and IgG4-secreting plasma cells, clinically characterized by extension of the fibrous process to surrounding tissues in the neck, as well as compression symptoms like dysphagia and dyspnea. It is usually associated with mediastinal and retroperitoneal fibrosis. There is significant clinical, pathological, and laboratory test overlap between these two entities that makes the differential diagnosis difficult.

Case report

A 54-year-old male diagnosed with hypothyroidism on Levothyroxine, and a large goiter seen with new onset of compressive symptoms including dyspnea and dysphagia since March/April 2021. He complains of having pressure on his neck, difficulty swallowing, and worse symptoms when lying flat on a bed. His thyroid is noted to be extremely large and firm, without evident nodularity on examination. Laboratory exams were significant for TSH 3.21 (0.36-3.74), T4 0.94 (0.76-1.46), vitamin D level 13 (30-100), TPO > 9000 (0-9), IgG4 81.9 (4. 0-86. 0), and a negative ANA screen. Thyroid ultrasound showed an enlarged heterogeneous thyroid gland with no discrete nodules. Given the compressing symptoms the patient presented, he was referred to surgery for total thyroidectomy. Surgery could not be completed due to the inability to safely mobilize the gland and adherence to surrounding tissues. He then underwent a right thyroid lobule core biopsy, showing an inflammatory infiltrate composed primarily of lymphocytes and plasma cells. Atrophic thyroid follicles with prominent fibrosis were noted. IgG4 immunostaining highlights <5 positive plasma cells/HPF and IgG4/IgG <30%, excluding IgG4-related fibrosing disease in this core biopsy material. There was no evidence of malignancy. Considering the prominent fibrosis, very high TPO Ab titer, and a seeming lack of extrathyroidal involvement, Fibrous Variant of Hashimoto's Thyroiditis seems more likely, but Riedel Thyroiditis cannot be completely ruled out. He was placed on Prednisone 40 mg daily, with modest improvement of symptoms. Tamoxifen 20mg daily was later added given literature reports of additional improvement in symptoms associated with its use. Referral to a tertiary center for possible isthmusectomy may be considered if symptoms worsen.

Presentation: No date and time listed
ODP484 Hyperthyroidism During Prostaglandin I2 Treatment in Pulmonary Hypertension and Its Molecular Mechanism
Authors: Ishida Emi , Yoshikawa Masashi , Hiraga Haruna , Nishikido Ayaka , Toki Akiko , Horiguchi Kazuhiko , Matsumoto Shunichi , Yoshino Satoshi , Ozawa Atsushi , Yamada Masanobu
Published: November 2022

Continuous intravenous infusion of prostaglandin I2 (PGI2) analog, epoprostenol, has improved the survival rate for severe pulmonary hypertension, but longer treatment with PGI2 sometimes occurs hyperthyroidism. For the hyperthyroidism during PGI2 treatment, two molecular mechanisms are speculated; the direct effect of PGI2 on thyroid follicular cells via PGI2 receptor which is coupled with G-protein alpha subunit like TSH receptor, and the indirect effect of PGI2 on activated T helper 17 cells which are associated with autoimmune disease (1). Here, we experienced three different cases of hyperthyroidism during PGI2 treatment in pulmonary hypertension. In case 1, epoprostenol had been administered intravenously for about ten months before the onset of hyperthyroidism. TSAb became positive (591%) and technetium uptake was elevated (4.7%), which were similar to the typical observations in Grave's disease. Total thyroidectomy was needed to control the thyroid function in case 1. In case 2, no thyroid antibody was detected and technetium uptake was almost vanished, as in the destructive thyroiditis. The thyroid function eventually normalized without any intervention. In case 3, hyperthyroidism occurred during oral PGI2 analog selexipag administration, but no evidence of Grave's disease or destructive thyroiditis was observed. Hyperthyroidism was declined when the dose of selexipag was reduced. To investigate the molecular mechanism underlying each case, we added the drugs which were used in each case on a thyroid follicular cell line, FRTL5. The thyroid tissue which was resected in case 1 and FRTL5 cells expressed PGI2 receptors in immunohistochemistry and immunofluorescence study. Human thyrotropin alpha (TSH) and epoprostenol elevated the intracellular cyclic AMP (cAMP) in FRTL5 (1.33 fold and 1.20 fold each, P<0. 05, n=3), but the other PGI2 analogs and the other drugs for pulmonary hypertension didn't change the cAMP in FRTL5. The gene expression level of Na/I symporter was up-regulated only by TSH (2.39 fold, P=0. 02, n=3), but not by PGI2 analogs in qPCR study. It is suggested that PGI2 increases the intracellular cAMP in thyroid follicular cells, but does not cause the same genetic changes as TSH. In conclusion, PGI2 analog may not directly affect the thyroid hormone synthesis in follicular cells, but further analysis is needed to elucidate the molecular mechanism underlying hyperthyroidism during PGI2 analog treatment. Reference: (1) Satoh et al.,Endocrine Journal 2017,64(12),1173-1180

Presentation: No date and time listed
ODP507 PREVALENCE OF CARDIOVASCULAR DISEASE IN PATIENTS WITH SUBCLINICAL HYPOTHYROISIM
Authors: Park Kyeeun , Konindala Navya , Konindala Navya , Aung Pyi Phyo , Enriquez Leidy Plaza
Published: November 2022

Introduction

Thyroid hormones play an essential role in maintaining cardiovascular homeostasis. Experimental studies have revealed that subtle changes in thyroid hormone levels, as observed in subclinical hypothyroidism, have adverse effects on the cardiovascular system due to predisposition to endothelial dysfunction, dyslipidemia and direct effects of thyroid hormones on the myocardium. We conducted a retrospective cohort study to elicit the role of subclinical hypothyroidism as an independent risk factor for cardiovascular diseases.

Methods

We conducted a retrospective analysis of 3 years of the National Inpatient Sample (NIS) database, 2016 to 2018. Study populations were selected using ICD-10 diagnosis code. Discharge-level weight analysis was used to produce a national estimate. We conducted multivariate regression analysis to calculate odds ratio with STATA 17.

Results

During the study period, 106,970,745 study population met the inclusion criteria and 37,215 of subclinical hypothyroidism (SCH) patients were discharged. SCH patients tended to be more female (63.48% v 56.40%), older (mean age 58.22± 0.25 v 49.48 ± 0. 01), diabetic (24.84% v 21.47%) and obese (18.63% v 13.54%). Prevalence of hyperlipidemia and hypertension were similar in both SCH and non-SCH groups (3.75% v 3.24% and 29. 09% v 29.35% each). Caucasian patients were predominant in both groups with similar ethnicity distribution (62.26% v 64.96%). 3.56% of SCH patient had acute coronary artery syndromes (ACS), whereas 2.78% of non-SCH patients developed the ACS. For the patients without history of heart failure (HF), 2.54% of SCH patients developed new onset of HF, whereas 1.11% of non-SCH patients developed HF. After adjusting for age, sex, race and comorbid burden, SCH is not associated with ACS (p = 0.375) or Afib (p= 0.74) but associated with elevated risk for new onset of HF (OR 1.88, 1.62–2.18, p < 0. 0001).

Conclusion

Our study shows that subclinical hypothyroidism is not associated with higher rates of ACS or Atrial fibrillation, however it is associated with statistically significant higher risk of new onset HF. Further research needs to be done to determine subclinical hyperthyroidism as a potential risk factor for HF and assess the benefit of lower threshold for treating subclinical hypothyroidism in preventing or delaying the onset of HF in patients with associated cardiac risk factors.

Presentation: No date and time listed
ODP510 Pseudolymphoma of the Thyroid Gland in Association with Hashimoto's Thyroiditis: A Benign Lesion in Whitish Thyroid Gland
Authors: Chatchomchuan Waralee , Thewjitcharoen Yotsapon , Krittiyawong Sirinate , Nakasatien Soontaree , Veerasomboonsin Veekij , Kanchanapituk Auchai , Junyangdikul Pairoj , Himathongkam Thep
Published: November 2022

Background

Pseudolymphoma or reactive lymphoid hyperplasia is a benign localized tumor-forming lymphoid hyperplasia found in various organs. Its occurrence in the thyroid gland is rare and could mimic malignant lesion. Here, we present a case of pseudolymphoma of the thyroid in a patient with Hashimoto's Thyroiditis.

Case description

A 24-year-old woman without underlying disease presented with incidentally found thyroid nodule. Ultrasound revealed mild thyroid enlargement with diffuse heterogeneous parenchymal echotexture. A 5×7×8.5-mm hypoechoic solid nodule with irregular margin was found in the left upper pole. No microcalcification was detected. Multiple subcentimeter lymph nodes at bilateral cervical group VI and left cervical group IV were also detected, measuring up to 5 mm in short axis. Fine-needle aspiration was performed and suggested malignancy (Bethesda class V). Laboratory testing showed euthyroid state with positive anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies. The blood test and ultrasound findings suggested the underlying of Hashimoto's thyroiditis. The patient underwent total thyroidectomy and lymph node dissection without postoperative complication. Gross examination of the thyroid showed multiple well-demarcated whitish nodular lesions, ranging from 2-10 mm, in the upper pole of both thyroid lobe and a well-circumscribed area of a 7-mm greyish nodule in left thyroid lobe. Microscopically, the whitish lesion in both lobe composed of hyperplastic lymphoid tissues with many follicular centers on the background of lymphocytic thyroiditis. The immunohistochemistry study revealed a polyclonal nature of the plasma cell infiltrates. No abnormal staining with AE1/AE3 or cyclin D1 was found. Pseudolymphoma was diagnosed based on these findings. Papillary thyroid microcarcinoma (6 mm) without capsular invasion was also diagnosed in the lesion of left mid lobe. The cervical lymph nodes showed metastatic papillary thyroid carcinoma (1.5 mm) in level III cervical lymph nodes. No perinodal extension was found. Postoperative course was unremarkable and the patient was in stable condition at 18 months after the operation.

Conclusion

Although primary thyroid lymphoma is often considered in patients with Hashimoto's thyroiditis. The possibility of pseudolymphoma characterized by the presence of well-demarcated pearly white nodules and polyclonal cell populations should also be considered.

Presentation: No date and time listed
ODP513 Rhabdomyolysis: A Rare Presentation Of Central hypothyroidism
Authors: Humphries Derrek , Haddad Joseph , Mahase Anesia , Quaries Jake , Aleem Abdul
Published: November 2022

Background

Hypothyroidism is one of the most common endocrine disorders affecting approximately 5 percent of Americans aged 12 and older. The most common cause of hypothyroidism globally is iodine deficiency whereas in the United States, Hashimoto's thyroiditis is the most prevalent. Less frequently, hypothyroidism can be caused by central hypothyroidism. In uncontrolled states, this entity can lead to an array of complications with rhabdomyolysis being among the latest manifestations. We present a case when the patient was admitted to the hospital for significant rhabdomyolysis, and after workup, was found to be related to new onset central hypothyroidism.

Clinical Case

A 34-year-old African American male presented to our facility with proximal muscle weakness and pain in the bilateral hips and right shoulder for three days. During the interview, the patient was acutely debilitated demonstrating slow body movements and grimaces on passive and active range of motion. Motor strength and sensation was preserved in bilateral extremities. The patient denied any recent injury, compression, extensive exercise, seizure, or durg use. The patient, however, reported a family history of rheumatological and endocrine conditions. Labs were obtained and revealed a creatinine kinase level of 10,5000 U/L; creatinine kinase- MB 53.5 ng/mL; creatinine 1. 0 mg/dL; AST 146 U/L; ALT 72 U/L; CRP 8.6 mg/L. The patient was stabilized with appropriate fluid and steroid therapy. On further investigation, TSH and T4 levels were 0.30 µlU/mL and 0.55 ng/dL, respectively. MRI with and without contrast did not show any intracranial pituitary abnormality or mass. The patient was started on levothyroxine and instructed to remain on the drug as an outpatient to prevent future occurrences. He was subsequently discharged after CK levels normalized and proximal muscle weakness improved. The patient was instructed to have a repeat thyroid function test and T4 levels in 6 weeks with appropriate follow up.

Conclusion

Idiopathic central hypothyroidism is a rare cause of hypothyroidism estimated to occur in 1: 20,000-80,000 in the general public. The lack of a pituitary mass lesion on MRI added to the rarity of this presentation. Hypothyroid myopathy causing rhabdomyolysis is a known but rare consequence of untreated hypothyroidism, which may present with muscle weakness, pain, and elevated serum muscle enzyme. Prompt workup to rule out a multitude of other causes is required, and the patient should be closely monitored for electrolyte and kidney function changes. Levothyroxine remains the treatment of choice for correction of central hypothyroidism with dose adjustments based on patient symptoms and serum free T4 values.

Presentation: No date and time listed
ODP515 Severe thyrotoxicosis caused by subacute thyroiditis
Authors: Guo Rong R , Panday Deepika
Published: November 2022

Background

Subacute thyroiditis, also named giant cell thyroiditis, painful thyroiditis, and de Quervain's thyroiditis, usually presents with neck pain or discomfort, a tender diffuse goiter and mild or moderate elevation of serum free T4 and T3 levels. Here we report a case of subacute thyroiditis patient presenting with severe thyrotoxicosis. Clinical case: A 27-year-old woman with no significant past medical history presents to the emergency room with palpitations and abnormal EKG with heart rate at 160 beats per minute. She developed a sore throat 3 days prior to the presentation, but she did not have neck pain or fever. She reports a 3-month history of hair loss, headaches and weight gain. Labs showed significantly elevated free T4 greater than 7.7 ng/dl (0.8-1.7) and free T3 level at 20.7 pg/ml (2. 0-4.8), and suppressed TSH less than 0. 01 uIU/ml (0.45-4.5) and normal ESR at 15 mm/hour. Her TPO antibody was greater than 1300 u/ml. Thyroid stimulating immunoglobulin (TSI) and TSH receptor antibody (TRab) were obtained but results were pending when she was discharged from the hospital. She has no typical clinical features of subacute thyroiditis with normal ESR and her free T3 and free T4 levels were significantly elevated. She was discharged on Methimazole and Propranolol and to do neck ultrasound as outpatient and follow-up TSI and TRab results and repeat free T4 and T3 in 1 week. Her neck ultrasound revealed mild hypervascularity but no Graves’ features. Her TSI and TRab were negative and free T4 level had no improvement even on significant dose of Methimazole. All the findings argue against Graves’ disease, but support subacute thyroiditis. Then Methimazole was discontinued and Prednisone was started at 20 mg daily and quickly taper to 5 mg daily in 2 weeks then stopped. After on Prednisone for 3 weeks, her free T4 was close to normal at 2. 0 ng/dl, T3 normal at 120 ng/dl, although TSH is suppressed. After stopped Prednisone for 2 weeks, her free T4, T3 and TSH were all back to normal. She is currently euthyroid without any medication at 5 months after her initial presentation.

Conclusion

Treatment of patients with subacute thyroiditis is pain relief with NSAID or Prednisone when NSAID is not effective. Anti-thyroid medications are rarely effective even in subacute thyroiditis patient with thyroid storm. Our case illustrated the role of corticosteroids in the treatment of subacute thyroiditis patient with severe thyrotoxicosis. Neck ultrasound and thyroid antibodies including TSI and TRab are critical to make a correct diagnosis in subacute thyroiditis patient with severe thyrotoxicosis.

Presentation: No date and time listed
ODP519 Thyroid Cyst Grows E. coli
Authors: Hayes Clarissa , Stezzi Mark , Skutnik Emily , Scheckelhoff Trevor , Lam Henry , Wright Jeffrey , Egeler David , Perilli Gretchen
Published: November 2022

Background

Thyroid abscesses are extremely rare, representing less than 1% of all thyroiddiseases. The thyroid gland is very robust against infections due to its vastlymphatic drainage, dual blood supply, encapsulation, and iodine concentration. Immunocompromised patients are at greater risk of developing thyroid abscesses. 1 Case: A 51-year-old female presented to her primary care provider with acute onset ofpainful right neck mass with associated cough, hoarseness, fever, and fatigue. She was seen by an Otolaryngologist who aspirated 6 cc of brown purulentmaterial from a suspected thyroid mass. The thyroid fluid was sent for culture,and she was empirically started on Augmentin. CT neck demonstrated a cysticlesion of the right thyroid gland, retropharyngeal edema, and mass effect withleftward deviation of the larynx and trachea without airway obstruction. Due tothese findings, the patient was admitted to the hospital where initial two setsof blood cultures were negative but repeat blood cultures revealed 2 of 2positive for E. coli. Thyroid cyst fluid also grew E. coli. Urine culture hadno growth. She was found to have a suppressed TSH of 0.24 uIU/mL, elevated free T4 of 1.80 ng/dL, and suppressed total T3 of 0.52 ng/mL. Previous TSH was within normal limits, 0.82 uIU/mL. The suppressed TSH and suppressed T3 were thought to be secondary to euthyroid sick syndrome. She was maintained onCeftriaxone while admitted and discharged on Ciprofloxacin. Pathology from theright thyroid cyst revealed acute inflammatory cells only consistent with anabscess, negative for malignancy. The patient elected to undergo a righthemithyroidectomy with isthmusectomy.

Discussion

Thyroiditis is defined as inflammation of the thyroid gland and has a variety ofetiologies. Suppurative thyroiditis, which includes thyroid abscess as in thiscase we have described, is an infrequent cause of thyroiditis. It is usuallycaused by hematogenous spread or direct inoculation of a pathogen. Treatmentincludes systemic antibiotics targeting the causative organism; although thegold standard remains surgical drainage. Surgical management is the mainstay ofmanaging patients with thyroid abscesses. 2 References: 1 Sharma, R., McManus, C., Kuo, J. (2020). MON-485 Thyroid Abscess in a Healthy 22 Year Old Female. Journal of the Endocrine Society, 4(1), A792-A793. https://academic.oup.com/jes/article/4/Supplement_1/MON-485/5832886 2 Singh, G., Jaiswal R., Gulati, N.,Granieri, E. (2019). A case of idiopathic thyroid abscess caused by Escherichia coli. Journal of Community Hospital Internal Medicine Perspectives. 9(2): 159-161. https://europepmc.org/article/MED/31044048

Presentation: No date and time listed
OR04-2 WNT2B Deficiency Results in Hyperreninemic Hypoaldosteronism in Humans and Mice
Authors: Azova Svetlana , Basham Kaitlin , Breault David , Hammer Gary , LaPensee Christopher , O’Connell Amy , Ribeiro Claudio , Silva Borges Kleiton , Turcu Adina , Little III Donald
Published: November 2022

Proper development and zonation of the adrenal cortex is intimately connected with its lifelong capacity to produce steroid hormones. Both adrenocortical development and homeostasis are mediated in part by paracrine WNT/β-catenin signaling, an essential pathway for zonal maintenance and aldosterone production. Patients harboring homozygous or compound heterozygous loss-of-function (LOF) mutations in the WNT ligand WNT2B present with congenital diarrhea and require parenteral nutrition. Despite evidence for euvolemia, WNT2B-null patients exhibit markedly elevated plasma renin levels with no corresponding increase in aldosterone, suggesting a primary adrenal defect in aldosterone synthesis. To test this hypothesis, we generated both global and conditional Wnt2b knockout mouse models. In the mouse adrenal, Wnt2b is expressed exclusively in the capsule, the outer compartment of mesenchymal cells that overlay and signal to the subcapsular zona glomerulosa (zG), the adrenocortical zone that harbors aldosterone-producing cells and critical long-term progenitor cells. Global loss of Wnt2b from early mouse development results in a near-complete absence of the histological zG. Moreover, Wnt2b-null mice exhibit significantly increased plasma renin but normal aldosterone levels compared to wild-type controls. These data suggest that WNT2B-null patients indeed have an adrenocortical phenotype caused by apparent zG hypofunction. To further define the mechanism(s) by which Wnt2b LOF leads to zG hypofunction, we temporally deleted Wnt2b in the adrenal capsule of adult mice. Wnt2b conditional knockout (cKO) adrenals exhibit a zG-restricted decrease in Wnt/β-catenin signaling as determined by decreased β-catenin activity and target gene expression. Moreover, Wnt2b cKO mice demonstrated a disorganized zG and disrupted adrenocortical zonation. To determine the contribution of WNT2B to aldosterone production, we administered a sodium-deficient diet to control and Wnt2b cKO mice to activate the renin-angiotensin-aldosterone system. Indeed, while control mice exhibited the expected increase in both plasma renin and aldosterone, Wnt2b cKO mice showed marked elevation of renin despite normal aldosterone compared to controls, consistent with hyperreninemic hypoaldosteronism. Together, our work supports a WNT2B-dependent mechanism for adrenal zG development and maintenance in mice and humans and provides relevant models to study the consequences of WNT2B deficiency within the zG.

Presentation: Saturday, June 11, 2022 11:45 a.m. - 12:00 p.m.
PSAT294 Black Thyroid – Is It a Benign or a Malignant Finding?: A Case Report and Review of the Literature
Authors: Cordero-Garate Juana , Naranjo Eddy P Lincango , Dominguez Carla M , Godoy Richard , Jacome Carolina Polanco , Pérez Carla Rocha , Solis-Pazmino Paola , Soto Jacome Cristian , Cevallos Belen , García-Bautista Andrea , Dy Benzon , Kawkgi Omar E , Garcia Cristhian
Published: November 2022

Background

Black thyroid is a rare condition with fewer than 70 cases reported around the globe. Black thyroid is seen almost exclusively in patients upon minocycline ingestion, and the process has previously been thought to be generally benign. Despite the favorable impact of this drug on thyroid function, several studies have reported an association between black thyroid and thyroid cancer. Herein, we report a black thyroid associated with papillary thyroid cancer.

Clinical Case

A 30-year-old woman with no significant medical history and no risk factors for thyroid cancer, but with a history of acne treated with minocycline for 2 months 10 years ago, came to the office for a thyroid nodule found during a routine healthcare visit. The patient was asymptomatic and euthyroid. Physical examination was unremarkable. The thyroid ultrasonography showed a 1.4 × 1.0 cm hypoechogenic solid nodule with irregular borders and microcalcifications located in the right lobe. No cervical lymph nodules were found. Fine-needle aspiration of the nodule displayed a Bethesda VI category. Total thyroidectomy was performed. No lymph node dissection was implemented. During surgery, the thyroid parenchyma was diffusely black in color, increased in size, and multinodular. The patient was uneventfully discharged on postoperative day 1. Histopathology revealed a diffuse black discoloration of the specimen with a well-defined 1.2×0.8×0.6 cm nodule in the right upper lobe with features of classic papillary thyroid carcinoma. Recently the patient was seen at his 3-month follow-up, and there were no signs or symptoms of recurrence or metastasis.

Clinical lessons: Although several studies describe a higher incidence of malignancy (being papillary thyroid carcinoma the most frequently associated) in black thyroid compared to non-black thyroid glands, a causal relationship has never been proven. Perhaps in this case the thyroid ultrasonography screening triggered the overdiagnosis and subsequently the overtreatment. Finally, having a "black organ" can be distressing for patients. Therefore, we should be meticulous in explaining "this disturbing fact".

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT303 Fecal Impaction as a Gastrointestinal Prodrome of Myxedema Coma in an Elderly Woman with Multiple Co-morbidities
Authors: Ahmad Mobeen , Song Rui , Elrod Sarah , Tejada Luis Arzeno
Published: November 2022

Introduction

Fecal impaction is a common occurrence in the elderly, with the most common risk factor being chronic constipation. A common cause of chronic constipation that can be overlooked in the elderly is hypothyroidism. If left untreated, hypothyroidism can have life-threatening manifestations including myxedema coma. In this case report, we describe a rare case of myxedema coma with prodromal fecal impaction.

Case description

An 87-year-old female with a past medical history of colon cancer status post partial colectomy, stroke, and end stage renal failure (ESRD) requiring hemodialysis, presented to the emergency department with extreme rectal pain. She was found to have fecal impaction on abdominal x-ray and was manually disimpacted and discharged home. Five days later, she presented with altered mental status in the setting of a new active herpes zoster infection and possible pneumonia. She was hypothermic (95F) and hypoxic, needing supplemental oxygen (2 L nasal cannula). Her labs showed hyponatremia (133 mg/dL), hypoglycemia (43 mg/dL), an elevated TSH level (100.0 mIU/ml) and decreased free T4 level (0.9 ng/L). Her EKG showed first-degree AV block with low voltage QRS complexes and her chest x-ray demonstrated bilateral pleural effusions. A CT scan of her head did not show hemorrhage or stroke. Given her classic clinical presentation and lab work findings, myxedema coma was diagnosed and the patient was treated with levothyroxine and hydrocortisone, though she was later transitioned to hospice as per her wishes.

Discussion

Chronic constipation is a known etiology of fecal impaction and can be caused by many chronic conditions in the elderly including ESRD, immobility, and hypothyroidism. Fecal impaction is easily identified but the investigation for the etiology is often overlooked. In this case, we argue that patients with an initial presentation of fecal impaction or with severe and unexplained constipation may warrant screening for hypothyroidism as a manageable risk factor for fecal impaction. By doing so, early recognition and treatment of hypothyroidism may prevent potentially fatal patient outcomes such as myxedema coma.

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