bluuebunny/crossref_metadata_2025_split 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

Abstract

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=&lt;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

Abstract

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&lt; 0.01). Serum levels of FSH and LH in men over 60 years were 3-fold greater than in men 50 or younger (p&lt;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

Abstract
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 &gt;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

Abstract
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

Abstract

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

Abstract

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 &lt;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 &lt;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 &lt;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 &lt;200 nmol/L (OR 3.23, 95% CI 1. 06,9.88), Acute Physiology and Chronic Health Evaluation (APACHE) II &gt;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&lt;0. 01 and duration (days) P&lt;0. 01. Plasma cortisol concentrations and hydrocortisone administration did not relate to ICU mortality.

Conclusion
Septic shock patients with CBG &lt;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

Abstract

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 &lt; 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

Abstract

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 &gt; 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 &lt;5 positive plasma cells/HPF and IgG4/IgG &lt;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