bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-182 Bilateral Adrenal Hemorrhage with Clinically Preserved Adrenal Function Leading to the Diagnosis of Antiphospholipid Syndrome
Authors: Hurtado Carolina , Kim Sarah Sangnim Rhee , Grock Shira
Published: May 2020

Background: Spontaneous bilateral adrenal hemorrhage (BAH) is a rare complication of antiphospholipid syndrome (APS), which is the most common identifiable risk factor for BAH. Although adrenal dysfunction is generally irreversible, adrenal function might be preserved or even recover in rare cases1.

Clinical case: A 48 year-old man with history of hypertension and gout presented with right upper quadrant abdominal pain following trauma to his left leg. He was found to have a left lower extremity deep vein thrombosis and bilateral pulmonary emboli (PE) and was started on anticoagulation therapy. He continued to have abdominal pain and a CT abdomen revealed BAH. Three am cortisol level was 21 mcg/dL (8–25 mcg/dL), ACTH 37 pg/mL (6–59 pg/mL), aldosterone <3 ng/dL (4–31 ng/dL), renin 2.6 ng/mL/hr (0.2–1.6 ng/mL/hr), sodium 130 mmol/L (135–146 mmol/L) and potassium 4.3 mmol/L (3.6–5.3 mmol/L). Patient was hemodynamically stable and did not report symptoms of adrenal insufficiency. Hypercoagulable work-up was consistent with APS and Lupus. Despite normal cortisol levels, he was started on hydrocortisone in the setting of anticoagulation and recent hemorrhage. Given low aldosterone with slightly high renin he was also started on fludrocortisone. Six weeks after discharge, his morning cortisol was 6 mcg/dL and ACTH was elevated at 76 pg/mL which was concerning for adrenal insufficiency. However, 250 mcg IM ACTH stimulation test showed peak cortisol of 17 mcg/dL which is considered adequate. Aldosterone and renin levels normalized so fludrocortisone was discontinued.

Patient subsequently self-discontinued all medications for 1 month with no symptoms of adrenal insufficiency, and later restarted hydrocortisone on his own. Repeat ACTH stimulation test showed baseline ACTH 57 pg/mL with peak cortisol of 17 mcg/dL. Patient was tapered off hydrocortisone and displayed no subsequent symptoms of adrenal insufficiency.

Conclusion: This case highlights the need to consider APS in patients with spontaneous BAH. Additionally, patients with BAH may have relatively preserved adrenal function. There is limited data to guide when steroid replacement is necessary for patients without clear adrenal insufficiency. It may be reasonable to monitor these patients off hydrocortisone replacement with close monitoring.

1. Ramon I, Mathian A, Bachelot A, et al. Primary adrenal insufficiency due to bilateral adrenal hemorrhage-adrenal infarction in the antiphospholipid syndrome: long-term outcome of 16 patients. J Clin Endocrinol Metab. 2013;98(8):3179–3189.
SUN-626 Survival of Patients with Gastroenteropancreatic Neuroendocrine Tumors and Diabetes Mellitus in a Seer-Medicare Cohort
Authors: Thapi Sahityasri , Baeg Kiwoon , Kim Michelle K , Gallagher Emily Jane
Published: May 2020

Background: The incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NET) is increasing globally and has been associated with diabetes mellitus (DM). In this study we aimed to compare tumor characteristics, disease-specific survival (DSS) and overall survival (OS) of GEP-NET patients (pts) with and without DM. Methods: Using the Surveillance, Epidemiology, and End Results registry (SEER) linked to Medicare claims, we identified pts diagnosed with GEP-NET between January 1995 and December 2010, aged ≥65 years at the time of GEP-NET diagnosis. We included patients who were in exclusive Medicare coverage without healthcare management organizations and had Medicare Parts A and B coverage for ≥1year after GEP-NET diagnosis or until death. Within the pts with GEP-NET diagnosis, we identified those without a diagnosis of DM prior to the GEP-NET diagnosis. We compared baseline sociodemographics, co-morbidities, and GEP-NET location, stage, grade and treatment between pts with and without DM using χ 2 analysis. Kaplan Meier (KM) curves were used to compare OS and DSS up to 10 years between the DM and non-DM groups. We used Cox proportional hazards analysis to compare the DSS between the groups, adjusting for confounding variables. Results: We identified a cohort of 1,969 well-characterized GEP-NET patients with accurate tumor stage, grade, comorbidities, and treatment data. 478 (25.7%) had DM and 1,383 (74.3%) did not have DM. There were no statistically significant differences in gender or age at the time of GEP-NET diagnosis in the DM (mean age 74.7±SD 6.6 yrs) and non-DM (74.9±7.4 yrs) groups. Significant differences in race were found in the DM (80.6% white, 13.6% black, 1.3% hispanic) and non-DM (86.8% white, 8.2% black, 1.8% Hispanic) groups (p=0.002). Patients with DM had more gastric (14.7%), duodenal (10.9%) and pancreatic (21.0%), and less jejunal/ ileal (12.8%) NETs compared with the non-DM group (9.7%, 6.4%, 16.9%, 18.2%, respectively, p<0.0001). Patients with DM had earlier stage disease than those without DM (p=0.0012), but no difference in tumor grade or treatment was found. KM curves revealed no differences in OS and DSS in the GEP-NET patients with and without DM across all stages. Multivariate adjusted Cox proportional-hazards model found no significant difference in DSS between those with and without DM (HR=0.97, 95%CI: 0.76–1.24). Compared with pts with pancreatic NETs, pts with colon (HR=1.39, 95%CI: 1.04–1.86) had worse survival, while those with jejunal/ileal (HR = 0.59, 95%CI: 0.42–0.83) NETs had a better survival. Discussion: This is the first study to investigate the effect of DM on survival of pts GEP-NETs. We found a high prevalence of pre-existing DM in pts with GEP-NETs, but no difference in OS or DSS in pts with and without DM. Interestingly, pts with DM had more foregut GEP-NETs which may suggest mechanistic links between DM and GEP-NETs at these sites.
MON-442 Tall Cell Variant of Papillary Thyroid Carcinoma Presenting Acutely as a Right Thyroid Mass and Thyroiditis - an Unusual Presentation
Authors: Goyal Itivrita , Bhat Salman Zahoor , Batra Manav , Karunakaran Abhijana
Published: May 2020

INTRODUCTION

Aggressive malignant thyroid tumors (AMTT) can rarely present with signs and symptoms mimicking that of acute suppurative thyroiditis (AST). In its early course, correct diagnosis may be difficult but a prompt recognition is crucial. We report an interesting case of an aggressive papillary thyroid cancer with presenting acute symptoms masquerading as AST.

CLINICAL CASE

A 50-year-old Caucasian male was admitted for 2 day history of sore throat, odynophagia, low grade fever with a tender and enlarging right neck swelling, not improving with oral antibiotics. CT neck showed a 5.8 x 4.5cm mass in right thyroid lobe with shallow retropharyngeal effusion. Labs showed elevated WBC 10.7 x 109/L (4–10.5), ESR 20 mm/hr (0–12), CRP 92.93 mg/L (0.2–10), with negative rapid strep and IgM for viruses EBV and CMV. Thyroid function tests were normal. Ultrasound neck showed an ill-defined 6.5 cm hypoechoic mass with cystic component and increased vascularity and calcification, replacing the right thyroid lobe. Due to concern for thyroid abscess he underwent urgent aspiration. Fluid analysis and cultures were negative for bacterial source. FNA (fine needle aspiration) of one specimen was suspicious for follicular neoplasm with predominant hurtle cells and suspicious for thyroid neoplasm with papillary architecture in the other. Core biopsy was suspicious for papillary carcinoma but limited due to scant amount of tissue. Affirma unavailable due to insufficient RNA yield. Flow cytometry was negative for abnormal lymphocyte population. Repeat CT neck 3 weeks later was concerning for metastatic lymphadenopathy. He underwent total thyroidectomy with lymph node (LN) dissection and pathology showed papillary thyroid cancer, tall cell variant, tumor size 6 cm, predominantly hemorrhagic, extending to perithyroidal strap muscles and involving 5/6 LN in right trachea-esophageal groove. It was a stage I, pT3bN1aMx cancer. Subsequently, he underwent thyrogen stimulated I-131 ablation of residual thyroid carcinoma with pretherapy scan showing increased uptake in thyroid bed and a satellite lesion suspicious for LN metastasis. Post-ablative scan showed no other new lesions. He is now on levothyroxine suppressive therapy.

CONCLUSION

Early course of AMTT can rarely present as AST, both being progressive and fatal diseases. Our case had a typical presentation of AST, causing delay in diagnosis of his very aggressive form of thyroid cancer. Gross pathology showed predominantly hemorrhagic areas in the tumor with central necrosis, which was likely the cause of acute mass with systemic signs suspicious for infection. One should consider an alternative diagnosis in suspected cases of AST in the absence of positive cultures or lack of improvement with parenteral antibiotics. It is imperative to make a diagnosis without any delay as prognosis for either condition depends on prompt recognition and treatment.
SAT-248 Cushing’s Disease with Two ACTH-Producing Pituitary Tumors
Authors: Mathai Christine , Anolik Jonathan Robert
Published: May 2020

Objective: The objective of this case report is to discuss a case of Cushing’s disease with two ACTH-producing pituitary tumors and emphasize consideration of repeat surgery as a treatment modality for unsuccessful initial surgery.

Methods: We present a case of a patient with Cushing’s disease with two ACTH-producing pituitary tumors and a literature review.

Results: A 36 year-old female found to have left supraclavicular fossa swelling was screened for Cushing’s syndrome. Midnight salivary cortisol levels elevated at 0.636 ug/dL and 0.316 ug/dL (<0.010–0.090 ug/dL). 24-hour urine cortisol 162 ug/24 hr (0–50 ug/24 hr). 1-mg dexamethasone suppression test 14.0 ug/dL. Serum morning cortisol 26.4 ug/dL with corresponding ACTH 66.7 pg/mL (7.2–63.3 pg/mL). MRI brain with and without contrast showed a 7-mm relatively hypoenhancing lesion of the anterior pituitary gland. 8-mg dexamethasone suppression test 2.7 ug/dL. She underwent transsphenoidal surgery (TSS) and pathology was consistent with a pituitary adenoma staining positive for ACTH. No residual tumor was seen. Postoperative morning serum cortisol 17.0 ug/dL and ACTH 79 pg/mL (9–46 pg/mL). She had repeat TSS and the area of resection was clean with no residual tumor but a second adenoma was found that was not visualized on MRI and was distinct from the initial lesion. Postoperative morning cortisol 0.7 ug/dL and ACTH <9 pg/mL (9–46 pg/mL). Pathology was consistent with pituitary adenoma staining positive for ACTH. She is now on steroids for central adrenal insufficiency.

Discussion: First-line treatment for Cushing’s disease is surgical resection of the primary lesion (Nieman LK, Biller BMK, et al. Treatment of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015; 100(8):2807–2831). Remission rates are 73–76% for selectively resected microadenomas but 43% for macroadenomas (Nieman et al. 2015). For patients who undergo a noncurative surgery, second-line therapies include repeat TSS, radiotherapy, medical therapy, and bilateral adrenalectomy. Repeat TSS is recommended particularly in patients who had evidence of incomplete resection or a pituitary lesion on imaging although this was not the case with our patient. Repeat TSS is cited to be successful in about 50–60% of cases (Patil CG, Veeravagu A, et al. Outcomes after repeat transsphenoidal surgery for recurrent Cushing’s disease. Neurosurgery. 2008;63(2):266–270) but carries an increased risk of hypopituitarism and lower likelihood of remission compared to initial surgery. Remission can be achieved more rapidly compared to other second-line treatments.

Conclusion: In Cushing’s Disease with unsuccessful initial surgery, consideration for repeat TSS may be considered when there is access to an expert pituitary surgeon.
OR32-05 Lower Oxytocin Levels Are Associated with Lower Bone Mineral Density and Less Favorable Hip Geometry in Hypopituitary Men
Authors: Maso Ana Aulinas , Guarda Francisco J , Yu Elaine Wei-Yin , Haines Melanie S , Asanza Elisa , Silva Lisseth , Tritos Nicholas A , Verbalis Joseph G , Miller Karen Klahr , Lawson Elizabeth Austen
Published: May 2020

Introduction: Hypopituitary patients are at risk for bone loss. Oxytocin (OT) and vasopressin (VP) are hypothalamic-posterior pituitary hormones with opposing actions on bone (anabolic and catabolic, respectively). Whether OT and/or VP contribute to impaired bone homeostasis in hypopituitarism is unknown.

Hypothesis: We hypothesized that lower plasma OT and higher VP levels would be associated with lower bone mineral density (BMD) and less favorable hip geometry and estimated strength in men with hypopituitarism.

Design: We performed a cross-sectional study of 37 men with hypopituitarism ages 20–60 (mean±SEM 45.8±1.9) years: 20 with anterior pituitary deficiencies only (APD) and 17 with central diabetes insipidus (CDI; marker of posterior pituitary dysfunction), of similar age, body mass index and number of adenohypophyseal deficiencies, on stable hormone replacement. Main outcome measures were fasting plasma OT and VP levels, and dual X-ray absorptiometry-derived BMD (lumbar spine, total hip, femoral neck, distal radius and subtotal body) and hip structural analysis (HSA; cortical thickness, section modulus, and buckling ratio at narrow neck, intertrochanteric region and femoral shaft). All analyses were adjusted for multiple comparisons using Holm-Bonferroni correction.

Results: Mean BMD Z-scores were lower at all sites and all HSA parameters at the intertrochanteric region as well as cortical thickness at the femoral shaft were less favorable in those participants who had fasting OT levels below the median than in those with higher levels (P≤0.022). There were no differences in any bone variables at any skeletal site in those with fasting VP levels below vs. above the median (P≥0.232). Lower fasting OT levels were positively associated with (1) lower BMD Z-scores at the lumbar spine, femoral neck, total hip and subtotal body (P≤0.02) and (2) less favorable hip geometry and strength variables (lower cortical thickness, lower section modulus and higher buckling ratio) at the intertrochanteric region in CDI (P≤0.018), but not APD participants (P≥0.458 and P≥0.429, respectively). The associations between OT and bone variables remained significant after adjusting for key determinants of BMD including lean body mass and IGF-1 levels. There were no relationships between plasma VP levels and bone variables in CDI or ADP groups (P≥0.173).

Conclusions: OT, but not VP levels, are positively associated with BMD at multiple sites as well as favorable hip geometry and estimated strength in men with hypopituitarism and CDI. Future studies will be important to determine whether OT could be used therapeutically to optimize bone health in patients with hypopituitarism.
MON-106 Prevalence and Incidence of Obesity in Children and Young Adults in Korea: The Kangwha Study
Authors: Suh Junghwan , Song Kyungchul , Choi Han Saem , Kwon Ah Reum , Chae Hyun-wook , Kim Ho-Seong
Published: May 2020

Childhood obesity is a major global concern, arousing a variety of health problems and high social costs. The prevalence of childhood obesity has increased, but plateaued during the first decade of the 21th century in developed countries. Many previous studies reported cross-sectional data with prevalence of obesity, but researches about incidence of obesity based on longitudinal data is insufficient, especially in Korean population. In this study, we analyzed prevalence and incidence of overweight and obesity in Korean children and young adults from a prospective cohort study. We analyzed data from the Kangwha study, which is a community-based prospective cohort study began in 1986 with 6-year-old, first-grade elementary school students in Kangwha county, South Korea. The Kangwha study is a dynamic cohort, which the number of participants was expanded several times during the follow-up period. The study was started with 482 children, which expanded to total 1,223 participants. The participants were examined annually until 1997, which is 17 years of age. Four adulthood follow-up studies were performed in 1999, 2005, 2010, and 2015. The data includes a 30-year period (1986–2015), with total 16 observations conducted. We used the 2007 Korean National Growth Charts to determine cutoffs for normal weight, overweight, and obesity in children. In adulthood, Asia-Pacific classification of obesity from World Health organization (WHO) recommendation was applied to define overweight and obesity. When the children were in their first-grade of elementary school, prevalence of overweight was 1.04% and obesity was 0.62%. Prevalence of overweight and obesity increased since age 10 (fifth-grade in elementary school) (overweight 4.44%, obesity 1.18%), reaching 7.34% and 3.39% in age 12 (first-grade in middle school), and 9.5% and 5.37% in age 17 (third-grade in high school). Prevalence of overweight and obesity in girls were higher than in boys throughout childhood. Annual incidence of obesity showed small peak at entering middle school (2.1%, age 12), and another peak at third-grade in high school (2.33%, age 17). Also, a positive correlation was found between body mass index (BMI) in younger ages and follow-up BMI. Prevalence of overweight and obesity increased since senior years of elementary school, and more prominent in girls. Detailed study design and larger population would be required for subsequent investigations.
MON-688 Emphysematous Gastritis and Diabetes
Authors: Singh Abhilasha , German Massiell , Grotzke Marissa Paige
Published: May 2020

Background: Emphysematous gastritis (EG) is a rare and severe form of gastritis of infectious origin. Diabetes is an important underlying risk factor as it leads to a systemic predisposition to infections. Other risk factors include long term steroid use, nonsteroidal anti-inflammatory (NSAID) use, alcohol use, corrosive ingestion, and pancreatitis, all of which disrupt gastric mucosa. First described in the 1800s, it is characterized by the presence of air in the stomach wall and differentials for these cases include gastric emphysema and cystic pneumatosis both of which are non-infectious in origin.

Clinical Case: A 57-year-old male with type 2 diabetes presented with a one-day history of abdominal pain, non-bloody diarrhea, and vomiting. One day prior to presentation, he developed diarrhea which was followed by episodes of projectile vomiting reported as orange-tinged with mucus. On the day of admission, he was afebrile, tachycardic in 120s with stable blood pressure. Laboratory evaluation was significant for leukocytosis at 18.8 k/uL (4.3–11.3 k/uL) and lactic acidosis 2.37 mmol/L (0.7–2.1 mmol/L). Abdominal examination was notable for soft abdomen with diffuse tenderness to deep palpation without rebound or guarding. Further workup with Computed Tomography (CT) was concerning for emphysematous gastritis with air in the gastric vein, splenic vein, and portal vein. Given hemodynamic stability and benign abdominal examination, medical management was initiated. He was started on ceftriaxone and metronidazole which were continued for a total of 10 days with clinical improvement. Discussion: EG results from disruption in gastric mucosa which facilitates translocation of gas-producing bacteria commonly Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa, and Enterobacter subspecies. Immunosuppression with diabetes is an important underlying factor and patients are at risk even with controlled diabetes. Additionally, patients with diabetic complications like gastroparesis with frequent retching are at increased risk. Considering variable and non-specific symptoms of presentation, a high index of clinical suspicion is required for recognition as it may have a fulminant course with high mortality risk. CT scan is the imaging of choice for diagnosis. Management primarily consists of bowel rest, antibiotics and monitoring for signs of peritonitis. In the absence of complications including rupture or stricture formation, surgery is not recommended. In our case, possible gastroenteritis with subsequent vomiting and retching in the setting of underlying diabetes predisposed to the development of emphysematous gastritis. Although air in the portal venous system is associated with higher mortality, our patient was successfully managed conservatively. As the diagnosis carries a high mortality risk, early recognition is imperative for a successful outcome.
SUN-308 Central Adrenal Insufficiency Is Rare in Adults with Prader-Willi Syndrome
Authors: Rosenberg Anna G W , Pellikaan Karlijn , Poitou Christine , Goldstone Anthony P , Hoybye Charlotte , Markovic Tania , Grugni Graziano , Crinò Antonino , Caixàs Assumpta , Coupaye Muriel , van den Berg Sjoerd A A , van der Lely Aart Jan , de Graaff-Herder Laura C G
Published: May 2020

Introduction: Prader-Willi syndrome (PWS) is associated with several hypothalamic-pituitary hormone deficiencies. There is no agreement on the prevalence of central adrenal insufficiency (CAI) in adults with PWS. This is partly due to the variable results of the synacthen test, compared with the more robust metyrapone test (MTP) and insulin tolerance test (ITT). In some countries, patients with PWS receive stress-dose corticosteroids during physical or psychological stress. Side effects of frequent corticosteroids use are weight gain, osteoporosis, diabetes mellitus and hypertension, already major problems in adults with PWS. However, undertreatment of CAI can cause significant morbidity or even mortality. To prevent over- and undertreatment with corticosteroids, we assessed the prevalence of CAI in a large international cohort of adults with this rare disorder.

Methods: The hypothalamic-pituitary-adrenal axis was tested in 81 adult subjects (55 Dutch, 10 British, 10 French, 6 Swedish) with genetically confirmed PWS. For multiple-dose MTP, 11-deoxycortisol >230 nmol/L (7.6 g/dL) was considered sufficient. For Dutch, French and Swedish patients who underwent ITT, cortisol >500 nmol/L (18.1 μg/dL) was considered sufficient. For British patients cortisol >450 nmol/L (16.3 μg/dL) was considered sufficient, as this center used a different assay. Additionally, we reviewed medical files of 645 adults with PWS from Italy (240), France (110), the Netherlands (110), Australia (60), Spain (45), Sweden (38) and the United Kingdom (42) for symptoms of hypocortisolism/adrenal crisis during surgery.

Results: Data on 81 adult subjects (46 males and 35 females), median age (range) 25.2 yr (18.0 – 55.5), median BMI (range) 29.1 kg/m2 (20.0 – 62.0), with genetically confirmed PWS were collected. 33 subjects (41%) were using GH treatment since childhood. Multiple-dose MTP was performed in 45 subjects and ITT in 36 subjects. Both tests were well tolerated by all individuals. CAI was excluded in 80 of 81 patients. One patient with a peak cortisol level of 494 nmol/L (just below cut-off level of 500 nmol/L) was prescribed hydrocortisone for use during physical stress. There was no relation between baseline cortisol and ITT/multiple-dose MTP results. Even patients with a low baseline cortisol level (lowest: 102.0 nmol/L) had normal responses. Among the 645 patients whose medical files were reviewed, 200 had undergone surgery without perioperative corticosteroids treatment. None of them displayed any features of hypocortisolism/adrenal crisis.

Conclusions: CAI is rare (1.2%) in adults with PWS. Based on these results, we recommend against routinely prescribing corticosteroids stress-doses in adults with PWS.

Funding: CZ foundation.
SUN-069 A 14 Year Old Female with Primary Amenorrhea
Authors: Chakravarthy Varshini , Ejaz Sehar
Published: May 2020

Background: Swyer Syndrome is an extremely rare disorder of sexual development. These patients often present with primary amenorrhea during adolescence and are phenotypically female with 46 XY chromosomes. Given the association of invasive gonadal malignancies with this disorder, suspicion should be high in patients who present with a stagnant or decreased rate of pubertal progression. We present a case of Swyer Syndrome in a 14-year-old female with primary amenorrhea in the setting of decreased pubertal progression. Case: A 14-year-old female presents with a chief complaint of primary amenorrhea. She first noticed breast budding 2 years prior but reports no significant increase in breast tissue over the last 2 years. She does not appreciate any other signs of puberty. She denies any acne, body odor, hirsutism, hair loss, or abdominal/pelvic pain. She denies any changes in her diet or physical activity and is not on any medication. No history of cancer, surgeries, or radiation exposure. There is no family history of infertility or delayed puberty. Her vitals on presentation are within normal limits. Her growth parameters are the following: weight-69.9 kilos, height-163 cm, and BMI-26.3. Physical exam shows a well-appearing adolescent with grossly female external genitalia and the breast exam is SMR II. No pubic or axillary hair appreciated on the exam. Although our patient did not meet the traditional definition of primary amenorrhea, a workup was started due to the slow progression of puberty. Initial blood testing shows normal blood count, electrolytes and thyroid levels. DHEA-S androstenedione, free and total testosterone were all within normal limits. Further results such as LH (25.4 uIU/mL), FSH (56.5 mIU/mL) and estradiol (22 pg/mL) along with low levels of AMH (0.52 ng/mL) and inhibin A (1pg/mL) confirms suspicion for ovarian insufficiency. Chromosomal analysis and pelvic ultrasound findings of a small uterus and ovaries led to our diagnosis of Swyer syndrome. Our patient had surgical resection of both ovaries and fallopian tubes and the ovarian pathology showed gonadoblastoma with invasive dysgerminoma in both gonads. She was started on hormone replacement after gonadectomy. Conclusion: Although Swyer syndrome is uncommon with an incidence of 1 in 80,000, this case illustrates that suspicion for Swyer Syndrome should be high in patients with slow progression of puberty and primary amenorrhea (1). Early diagnosis is critical, as patients with gonadal dysgenesis are at great risk for germ cell cancers. Though most of these patients have an identifiable genetic mutation, we were unable to elicit the exact mutation in our patient despite whole-genome sequencing. References: Jaideep Khare, Prasun Deb, Prachi Srivastava & Babul H. Reddy (2017) Swyer syndrome: The gender swayer?, Alexandria Journal of Medicine, 53:2, 197–200, DOI: 10.1016/j.ajme.2016.05.006 Varshini Chakravarthy, Sehar Ejaz. A 16-Year-Old With Amenorrhea and Delayed Breast Development - Medscape - Jan 14, 2020
SUN-922 An Indolent Recurrent Parathyroid Carcinoma - A Case Report
Authors: Murthi Swetha , Abdulla Maha B , Har-El Gady , Opher-Iosifescu Elana , Merker Edward
Published: May 2020

Introduction

Parathyroid carcinoma is a rare endocrine malignancy with reported incidence from 0.5 to 5% of primary hyperparathyroidism (1). Etiologies include prior neck irradiation, adenoma or hyperplastic parathyroid gland. Molecular pathogenesis includes RB gene overexpression, low P53, loss of APC and especially HRPT2 tumor suppressor gene. It has low malignant potential, but tends to recur locally or spread to contiguous areas. Here, we present a case of a recurrent parathyroid carcinoma that recurred after 17 years.

Clinical Case

The patient is a 56 YO female with Stage 1 breast cancer status post bilateral mastectomy who had underwent resection of a 2.5cm low-grade left lower parathyroid carcinoma in 1997 after 10 years of primary hyperparathyroidism. At that time of resection, iPTH was 2500 pg/ml and calcium level greater than 15 mg/dl. She presented with hypercalcemia (Calcium 11.5 mg/dl, PTH 67.1 pg/ml) again after 17 years. Work-up showed a 2.3 cm suspected parathyroid lesion in the left neck. She underwent removal of the left upper parathyroid gland along with a right enlarged parathyroid gland, as intra-operative PTH did not decline. Pathology confirmed parathyroid carcinoma with capsular invasion and muscle infiltration of the left gland and adenoma of the right gland. Repeat imaging in a month showed persistent parathyroid activity in the left neck. She had removal of the left upper parathyroid and a left paratracheal mass excision with pathology confirming recurrent parathyroid carcinoma. After 4 years, her PTH and calcium levels rose. Sestamibi imaging showed abnormal activity in a 1.1 cm soft tissue mass near the sternal notch. The patient underwent complete excision of the left suprasternal mass and the left sternohyoid muscle with pathology confirming recurrent parathyroid carcinoma with lympho-vascular and perineural invasion. Follow-up Sestamibi imaging after a month showed no abnormal activity with recent labs of calcium level 10mg/dl and PTH 25 pg/ml.

Conclusion

Recurrent parathyroid carcinoma remains a challenge. Complete resection of the lesion along with care to avoid capsule rupture to prevent local seeding remains the treatment strategy. The main cause of morbidity and mortality is the sequelae of uncontrolled hypercalcemia rather than tumor burden. Management of hypercalcemia includes hydration, bisphosphonates and cinacalcet. Even though it is not radiosensitive, neck radiation after surgery may be helpful in preventing tumor regrowth. Clinical trials using nivolumab and ipilimumab are being conducted to treat parathyroid carcinoma (2).

Reference

1. Givi, B., & Shah, J. P. (2010). Parathyroid carcinoma. Clinical oncology, 22(6), 498–507

2. Long, K. L., & Sippel, R. S. (2018). Current and future treatments for parathyroid carcinoma. International Journal of Endocrine Oncology, 5(01), IJE06
OR19-04 Glucocorticoid Production in the Nervous and Immune Systems: Evidence for a Local HPA Axis Homolog
Authors: Salehzadeh Melody , Hamden Jordan Edward , Li Michael X , Bajaj Hitasha , Ma Cathy , Soma Kiran K
Published: May 2020

Glucocorticoid Production in the Nervous and Immune Systems: Evidence for a Local HPA Axis Homolog

The hypothalamic-pituitary-adrenal (HPA) axis is a critical stress response system in vertebrates. The hypothalamus secretes corticotropin-releasing hormone (CRH), which binds its receptor (CRH-R1) in the anterior pituitary. The anterior pituitary then secretes adrenocorticotropic hormone (ACTH), which binds its receptor (MC2R) in the adrenal glands and stimulates secretion of glucocorticoids into the bloodstream. Glucocorticoids are critical modulators of neural and immune system development. During early development (postnatal day (PND) 2 to 12), mice show decreased adrenal glucocorticoid secretion at baseline and in response to stressors, termed the stress hyporesponsive period (SHRP) (1). Traditionally, glucocorticoids have been thought to be synthesized only in the adrenal glands. However, recent evidence demonstrates that glucocorticoids are also produced in extra-adrenal tissues, such as the brain and lymphoid organs (2). This may be of particular importance during the SHRP, as local production allows glucocorticoid modulation of specific tissues and cells, without general effects throughout the organism. Importantly, the factors that regulate local glucocorticoid production remain unknown. To study the regulation of local glucocorticoid production, we examined whether mediators of the HPA axis are locally expressed at baseline and in response to an immune stressor. We assessed systemic and local glucocorticoid levels in neonatal (PND5) C57BL/6J mice 4hr after an immune challenge with lipopolysaccharide (50µg/kg i.p.) or vehicle control. We examined blood, microdissected brain regions (prefrontal cortex, hippocampus, hypothalamus), and lymphoid organs (thymus, spleen, bone marrow). A panel of 7 steroids was measured via liquid chromatography tandem mass spectrometry (LC-MS/MS). Gene expression of Crh, Crh-R1, Pomc, and Mc2r was quantified via qPCR. Preliminary data indicate that corticosterone was 2-fold higher in tissues than in blood after an immune stressor. The thymus expressed all genes of interest, supporting the existence of a local HPA axis “homolog” in the thymus. Brain, spleen and bone marrow expressed a subset of the genes of interest. These exciting data demonstrate that all the mediators of the HPA axis are locally expressed within the thymus, likely to regulate thymocyte development and reactivity. Greater understanding of local glucocorticoid production will provide crucial insight into neural and immune development and function. Reference: (1) Sapolsky et al., Brain Res Rev. 1986 11(1):65–76. (2) Taves et al., Endocrinology. 2015 156(2):511–522.
SAT-422 Evaluation of the Siemens Thyroid Stimulating Immunoglobulin (TSI) Assay for Diagnosis and Prognosis of Graves’ Disease
Authors: Paul Heather , Moledina Nadia , Robinson Jason , Chin Alex , Kline Gregory A , Sadrzadeh Hossein
Published: May 2020

Background: Hyperthyroidism due to Graves’ disease (GD) is an autoimmune condition caused by thyroid stimulating hormone receptor (TSHR) autoantibodies. Autoantibodies to the TSHR can stimulate or block thyroid hormone production, therefore testing specifically for stimulating antibodies would be beneficial for diagnosis of GD.

Objectives: The primary objective of the first phase of this trial is to assess the diagnostic capability of the Siemens Thyroid Stimulating Immunoglobulin (TSI) immunoassay in diagnosing GD and to compare it with the Roche TSH Receptor Antibody (TRAb) assay.

Design and Methods: Two hundred patients with suspected GD are being enrolled in this single-center multiphase prospective cohort study. Consenting patients undergo biochemical testing including thyroid stimulating hormone (TSH), free T3 (FT3) and T4 (FT4), TRAb and TSI measurements. GD diagnosis was confirmed by endocrinologists that were blinded to TSI results.

Results: To date, 85 patients were included in the analysis, of which 66 were diagnosed with GD. For the primary analysis, all patients taking anti-thyroid drugs (ATD) at time of sample collection (n=14) were removed. The respective sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for TSI was 98, 84, 94 and 94%, which were comparable to those generated by TRAb (98, 95, 95, and 98%). In patients with clinical findings of GD (ie. orbitopathy or goiter, n=33), both the TSI and TRAb assays had identical sensitivity and specificity at 96% and 80% respectively. In patients without orbitopathy or goiter (n=38), the TSI assay had perfect sensitivity and excellent specificity of 100% and 86% respectively (TRAb had 100% sensitivity and specificity). Sensitivity, specificity, NPV, and PPV were slightly lower for both TSI and TRAb in patients treated with ATDs compared to patients without treatment (TSI: 85, 84, 62, 95%; TRAb: 91, 95, 75, 98%). Of ten patients with GD and false negative TSI results, nine were on ATDs. Of this subset, four patients had discordant results between TSI (negative) and TRAb (positive). Notably, one of these patients had normalization of their FT3 and FT4 on the day of sample collection.

Discussion and Conclusion: Based on our preliminary results, TSI is an excellent marker for diagnosing GD, particularly in untreated GD patients. The performance of the TSI assay has been comparable to the TRAb assay and correlates well with clinical findings. Discordant false negative results were only seen in patients on ATD. One potential explanation is that the TSI assay is detecting a decrease in stimulating autoantibodies when there is normalization of FT3 and FT4. Importantly, all discordant samples will be tested by a TSI bioassay to confirm diagnosis. Further patient enrollment is occurring, and prognostic assessment of these assays will soon be possible.
SAT-484 Presyncope as Initial Presentation of Massive Pericardial Effusion with Tamponade in a Patient with Primary Hypothyroidism
Authors: Garcia Susan , Tin Su Lei
Published: May 2020

Presyncope as initial presentation of massive pericardial effusion with tamponade in a patient with primary hypothyroidism

Background: Hypothyroidism is an endocrinologic disorder that affects multiple systems ranging from cardiovascular, central nervous system, musculoskeletal, etc. One of the possible cardiovascular complications of hypothyroidism is pericardial effusion which is only rarely associated with tamponade. In this case report we have a 49 years old woman who presented with impending pericardial tamponade secondary to chronic primary hypothyroidism. Clinical case: A 49 years old woman with history of hypothyroidism presented to the hospital on account of headache, dizziness with presyncope episode, generalized weakness and shortness of breath for 7 days, physical exam showed normal vital signs, distant heart sounds, laboratory tests showed TSH:29.5 uIU/mL (normal range 0.270- 0.4200 uIU/mL), fT4: <0.1ng/dL (normal range 0.9–1.8 ng/dL), fT3: 1.68 pg/mL (normal range 1.80–4.60 pg/mL. Electrocardiogram showed low voltage QRS, chest CT showed large pericardial effusion with findings suggestive of right heart failure, Echocardiogram showed left ventricular dysfunction and large pericardial effusion. The patient was taken to the operating room for emergent pericardial window creation with pericardiectomy and was admitted to the Cardiac Care Unit for management of tamponade status post pericardial window. Levothyroxine 150 mcg, Liothyronine 25 mcg and Hydrocortisone 50 mg were started, the steroid was discontinued after adrenal insufficiency was ruled out. The pericardial drain was removed after 8 days and repeated tests showed TSH: 13.1 uIU/mL, fT3: 3.37 pg/mL, fT4: 0.5 ng/dL, studies of pericardial fluid only showed polymorphonuclear cells. The patient’s symptoms resolved and she was discharged on Levothyroxine 150 mcg and Liothyronine 25 mcg. During follow up visits the thyroid function tests were normal, Liothyronine was discontinued and a repeated Echocardiogram showed normal systolic function. Conclusions: Pericardial effusion can be found in 3–30% of patients with hypothyroidism but only in very rare cases (less than 3%) is associated with cardiac tamponade and occurs when there is a severe underlying condition like myxedema coma or prolonged untreated hypothyroidism (1). It is important not to miss that dizziness and presyncope in a patient with hypothyroidism may be a manifestation of cardiac tamponade. Once the diagnosis of hypothyroidism is made it is imperative to start treatment early as untreated hypothyroidism can cause severe cardiovascular complications but even when such are present, they can be reversible with thyroid replacement therapy. Reference: (1) Kahaly, G. and Dillmann, W. (2005). Thyroid Hormone Action in the Heart. Available at: https://academic.oup.com/edrv/article/26/5/704/2355198 [Accessed July 12 2019].
MON-025 Activin a Increases Human Trophoblast Invasion by Up-Regulating Integrinb1 Through ALK4
Authors: Zhu Shiqin , Leung Peter C , Ma Jinlong , Li Yan
Published: May 2020

Activin A Increases Human Trophoblast Invasion by Up-regulating Integrin β1 Through ALK4

Following implantation, extravillous trophoblast cells (EVTs) derived from trophectoderm invade into the maternal decidua to a certain extent, which is tightly regulated by a variety of factors. Activin A, a member of the TGF-β superfamily, has been shown to stimulate the invasion of human trophoblasts (1). Integrin β1 has been implicated in cancer cell invasion and is consistently expressed in human preimplantation embryos (2). However, whether integrin β1 is integrated in activin A signaling and mediates activin A increased-human trophoblast invasion remain unknown. The objective of our study was to investigate the possible mediation role of integrin β1 in the pro-invasive effect of activin A on trophoblasts and illustrate the underlying molecular mechanisms. Primary and immortalized (HTR8/SVneo) cultures of human trophoblast cells were employed as study models. Real-time qPCR, Western blot, and small interfering RNA (siRNA)-mediated knockdown approaches were used to investigate the molecular determinants of activin A-mediated functions. The integrin β1 protein levels in poorly invasive BeWo,JAR and JEG-3 human choriocarcinoma cells were lower than that in highly invasive HTR8/SVneo cells and primary human EVTs, suggesting the possible essential role of integrin β1 in mediating human trophoblast invasion. The expression levels of integrin β1 were up-regulated in a time-dependent manner after activin A treatment in HTR8/SVneo cells. Importantly, siRNA-mediated down-regulation of integrin β1 significantly attenuated both basal and activin A-induced cell invasion in HTR8/SVneo cells as measured by transwell invasion assay. Interestingly, the TGF-β type I receptors (ALK4/5/7) inhibitor SB431542 abolished activin A-induced activation of SMAD2/SMAD3 as well as activin

A-up-regulated integrin 1 expression. Moreover, siRNA-mediated down-regulation of ALK4 or SMAD4 attenuated activin A-up-regulated integrin β1 in both HTR8/SVneo cells and human primary EVT cells. These results reveal that activin A promotes human trophoblast cell invasion by up-regulating integrin β1 expression through ALK4-activated SMAD2/3-SMAD4 signaling pathway.

Reference: (1) Bearfield et al., Eur J Endocrinol 2005;152:909–16. (2) Campbell et al., Hum Reprod 1995;10:1571–8.
MON-085 The Clinical and Endocrinologic Manifestations of Germinoma in Taiwanese Pediatric Population: One Medical Center Experience
Authors: Chang Hsin-Yuan , Lo Fu-Sung
Published: May 2020

Background:Intracranial germ cell tumors are rare extragonadal neoplasms. These patients may present with headache, visual impairment and endocrine disorder, depending on the size and location of the tumor. The aim of this study is to assess the clinical features of patients with germinomas in our hospital. Methods:We performed a retrospective chart review of 58 children diagnosed with intracranial germ cell tumors from January, 1990 to December, 2018. The initial clinical presentation, tumor markers (beta-hCG and alpha-fetoprotein, etc.), pituitary function, and brain images were reviewed and further analyzed. Results:Total 58 patients (45 boys and 13 girls) were included in the study. The mean age at diagnosis was 13.44 ± 2.64 years, ranging from 6.51 to 17.92 years. The initial complaints were weakness (n= 30, 51.7%), eye manifestation (n=27, 46.6%), polyuria (n=27, 46.6%), headache (n= 22, 27.9%), nausea or vomiting (n=16, 27.6%), dizziness or vertigo (n=16, 27.6%), and short stature (n= 8, 15.7%), respectively. Laboratory data showed central hypothyroidism (n = 14, 42.4%), central diabetes insipidus (n=14, 66.7%), hypogonadotropic hypogonadism (n= 4, 40%), and growth hormone deficiency (n=14, 73.7%). Conclusions:Germinomas may present with neurologic signs such as weakness, visual impairment, headache, nausea or vomiting. Some patiens presented short stature or polyuria due to central hypothyroidism, diabetes insipidus and growth hormone deficiency. Some atypical manifestations were also noted, such as psychological presentations and incontinence.
SUN-204 Case of Non-Classic Congenital Adrenal Hyperplasia with Compound CYP21A2 Mutations Combined with CYP11B1 Mutation
Authors: Salameh Rami , Prater Janna
Published: May 2020

Introduction:

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder, caused by a deficiency in one of the enzymes involved in adrenal steroid synthesis. Homozygotes usually have a severe classical CAH phenotype. Heterozygotes, carrying only one abnormal copy of the gene, are thought to be generally asymptomatic, although could be associated with hyperandrogenism, decreased fertility, adrenal incidentalomas.

21-hydroxylase deficiency (21OHD) accounts for 90% of all CAH cases, while 11 β-hydroxylase deficiency (11OHD) accounts for 4–8% of CAH cases.

The nature and mechanism of a combined enzymatic defect are unknown. The coincidental presence of gene mutation for both 21OHD and 11OHD CAH in a single individual is very unlikely to occur.

Clinical case:

A 22-year old female with no significant past medical history presented to endocrinologist for evaluation of facial hirsutism.

Patient had menarche at age 11, and menstrual cycle was regular since. No concerns for virilization of external genitalia. She was not sexually active, no pregnancies. No Family history of infertility or genetic conditions. Patient’s father was Jewish, and mother was Slavic.

Physical examination revealed female phenotype, normal Blood pressure and BMI, acne on the back and upper arm, Ferriman-Gallwey hirsutism score 5.

Labs: AM cortisol, CMP, CBC and TSH were normal. Total testosterone 68 ng/dL (2–45), free testosterone 7 pg/mL (0.1 - 6.4), FSH 5.7 mIU/mL (2.5–10.2), LH 10.6 mIU/mL (1.9–12.5), Progesterone 2.1 ng/mL (<1), Estradiol 51 pg/mL (19–144), 17-OH Progesterone 6728 ng/dL (45–285), Androstenedione 710 ng/dL (35–250), DHEA 1216 ng/dL (102 - 1185), 11-Deoxycortisol 204 ng/dL (<107), Pregnenolone 661 ng/dL(22–237), DHEAS 435 ng/dL (18–391).

Elevated 11-Deoxycortisol level raised a suspicion for 11-OHD CAH, or adrenal vs ovarian hormone-producing mass.

Abdominal CT and pelvic US were negative for adrenal or ovarian masses.

3-day dexamethasone suppression test completely normalized all biochemical abnormalities the patient had.

Genetic testing showed: CYP21A2 c.844G>T (non-classic 21OHD CAH mutation), CYP21A2 c.923dupT (classic 21OHD CAH mutation), CYP11B1 c.953C>G mutation.

Thus diagnosis of non-classic 21OHD CAH, and carrier status of 11OHD CAH was made. She was started on oral Dexamethasone 0.25 mg every other day.

11-Deoxycortisol elevation could not be explained by 21OHD alone. Her carrier state of the CYP11B1 mutation also cannot cause elevated 11-Deoxycortisol level.

We hypothesize that 11-Deoxycortisol was elevated either from extra adrenal conversion of 17-hydroprogesterone to 11-Deoxycortisol, or from 11 β-hydroxylase inhibition by excess intra-adrenal androgens.

Conclusion: Our case reports a rare finding of both CYP21A2 and CYP11B1 mutations in the same individual, which has implications for relatives, family planning and partner genetic screening.