bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-917 Aggressive De Novo MEN1 Variant in a Child with Metastatic Pancreatic Acth and Crh Co-Secreting Neuroendocrine Tumor: Diagnosis and 10-Year Follow Up
Authors: Bompou Maria Eleni , Flippo Chelsi L , Zenno Anna , Keil Meg F , Stratakis Constantine A
Published: May 2020

Background:

In Multiple Endocrine Neoplasia type 1 (MEN1) only about 2% of pituitary adenomas are ACTH-secreting. Cushing Syndrome due to ectopic ACTH or CRH secretion from neuroendocrine tumors (NETs), carcinoid tumors, or pheochromocytomas is very rare, though patients with MEN1 are at increased risk for these three types of tumors, as well as autonomous adrenal secretion of cortisol. The 10-year follow up of a previously-reported case of a child with MEN1 and metastatic pancreatic ACTH/CRH-secreting NET is presented.

Clinical Case:

A previously-reported (J Clin Endocrinol Metab, 2015) now 21 yo female presented to the National Institutes of Health (NIH) at 11 yo with persistent hypercortisolemia despite transsphenoidal surgery for suspected Cushing Disease. However, the resected tissue revealed pituitary hyperplasia, and she remained hypercortisolemic. A CRH test was consistent with an ectopic source, and abdominal CT, PET scan, and Octreotide scan revealed a mass in the pancreatic tail. The patient underwent partial pancreatectomy at 11 yo with the resected tissue staining positive for ACTH and CRH. However, she remained hypercortisolemic, so bilateral adrenalectomy was performed. At 12 yo metastases were found, so Octreotide therapy was initiated. She continued to have elevated ACTH levels > 1000 pg/mL (5-46).

Additionally, a pituitary adenoma was noted at 12 yo, which has since increased in size. The patient also developed mild primary hyperparathyroidism, first noted at 19 yo. Sequencing of MEN1 for the patient and her parents revealed a de novo heterozygous c.1546dupC variant, consistent with sporadic MEN1. The patient also had a chromosome 8p23.2 duplication that was present in unaffected relatives.

Conclusion:

While 2% of patients with MEN1 may develop Cushing Syndrome due to an ACTH-secreting pituitary adenoma, it is also important to consider ectopic secretion of ACTH/CRH from MEN1-associated NETs, carcinoid tumors, or pheochromocytomas, as well as autonomous adrenal secretion of cortisol. Given the early age and severe presentation of MEN1 features in this patient, the c.1546dupC heterozygous variant of MEN1, which has been previously reported in multiple other cases of MEN1, may represent a higher-risk causative variant of MEN1. Alternatively, expression of this variant may have been affected by the concurrent presence of an otherwise apparently benign chromosomal variant.

References:

A. Karageorgiadis, G. Papadakis, J. Biro, M. Keil, C. Lyssikatos, M. Quezado, M. Merino, D. Schrump, E. Kebebew, N. Patronas, M. Hunter, M. Alwazeer, L. Karaviti, A. Balazs, M. Lodish, and C. Stratakis. Ectopic Adrenocorticotropic Hormone and Corticotropin-Releasing Hormone Co-Secreting Tumors in Children and Adolescents Causing Cushing Syndrome: A Diagnostic Dilemma and How to Solve It. Clin Endocrinol Metab, January 2015, 100(1):141–148
MON-440 Unusual Case of Metastatic Struma Ovarii Diagnosed at the Time of Hysterectomy
Authors: Merrill Jennifer , Ahmadi Sara , Perkins Jennifer
Published: May 2020

Introduction: Struma ovarii is rare ovarian teratoma composed of more than 50% mature thyroid tissue, which can rarely transform to malignancy. There are fewer than 200 cases reported and no established treatment approach. We present a case of metastatic malignant struma ovarii. Case Presentation: A 41 year old female was diagnosed with metastatic papillary thyroid carcinoma (PTC) after it was found on uterine histopathology. History was notable for remote left ovarian cystectomy of a mature teratoma with prominent thyroid component. She had no personal or family history of craniocervical radiation or thyroid cancer. Eight years later, she had a total hysterectomy for menorrhagia. Pathology showed subcentimeter serosal deposits of follicular variant PTC, staining positive for thyroglobulin, CK19, and HBME1. Endometrial and cervical pathology were normal; the myometrium had many leiomyomata. Post-hysterectomy TSH was 2.3 (0.34 - 5.66 µIU/mL), and thyroglobulin 44.3 (<=33.0 ng/mL). Thyroid ultrasound showed a 7 mm isoechoic nodule without lymphadenopathy. Whole body PET/CT showed multiple hypermetabolic masses in the pelvic peritoneum and liver. The right ovary had many cystic lesions and was enlarged to 5.3 x 4.5 cm. She underwent partial hepatectomy, oophorectomy, salpingectomy, and omental resection with no residual disease. Pathology showed follicular variant PTC in both ovaries, peritoneum, colonic mesentery, and omentum. Thyroglobulin fell to 6.9 ng/mL 3 weeks later. A 0.2 cm focus of follicular variant PTC with capsular invasion was found on pathology after total thyroidectomy. She underwent radioiodine ablation with 150 mCi. Postablative scan showed residual activity in the thyroid bed and right hemipelvis, but no new foci of activity. CT abdomen showed resolution of perihepatic lesions and thyroglobulin declined further to 0.5 ng/mL. Discussion: A low risk of recurrence (7.5%) has been reported in patients with malignant struma ovarii, with survival rates of 96.7% at 5 years and 84.9% at 20 years, despite a variety of surgical and adjuvant management strategies. Unilateral cystectomy, unilateral salpingo-oophorectomy, or total abdominal hysterectomy and bilateral salpingo-oophorectomy may be sufficient for patients with well differentiated thyroid cancer arising in struma ovarii without metastases. Thyroid ultrasound should be performed to exclude primary thyroid malignancy. Patients with distant metastases may benefit from aggressive treatment including resection of gross abdominal and pelvic disease and total thyroidectomy to facilitate radioactive iodine ablation and surveillance for recurrence. Conclusion: Due to its rarity, there is no consensus on optimal treatment of malignant struma ovarii. More research in this field is warranted.
SUN-251 The Effects of Unilateral Vagotomy in Female Rats with Blockade of the Muscarinic System of the Suprachiasmatic Nucleus on Ovulation and Estradiol Serum Levels
Authors: Vieyra-Valdez Elizabeth , Garcia-Tabla Julio Cesar , Zarco-Juarez Hugo Alberto , Calderon-Ramos Roberto , Morales-Ledesma Leticia , Dominguez Roberto
Published: May 2020

Several studies show that the suprachiasmatic nucleus (SCN) participates in the regulation of the functions of various endocrine organs through multisynaptic nerve pathways. Some of these pathways communicate the SCN with the dorsal motor nucleus of the vagus and the nucleus of the solitary tract, which are part of the origin of the vagus nerve (1). Previously we demonstrated that atropine (ATR) microinjection in the right SCN on the day of the proestrus, blocks ovulation, while the same treatment in the left SCN does it partially (2). In the present study we analyzed the possibility that the vagus nerve is one of the neural ways by which the SCN regulates the secretion of estradiol (E2) in the proestrus and subsequent ovulation. For this, cyclic rats were anesthetized with ketamine-xylazine at 09.00 of the day of the proestrus. The animals were randomly assigned to one of the following groups: rats with ATR (62.5 ng diluted in 0.3 µl of saline) microinjection in the right or left SCN, followed by ventral laparotomy or ipsilateral vagotomy to the microinjection side. The animals were sacrificed 5 h after surgery, and estradiol (E2) levels were measured. Other groups of animals with the same treatments were sacrificed 24 hours after surgery, and ovulation rate and number of ova shed were evaluated. The left vagus section did not modify the effects of ATR microinjection in the left SCN on ovulatory rate (2/5 vs. 4/7) and E2 secretion (46.6±9.0 vs. 51.3±9.0, pg/ml). In animals with ATR microinjection in the right SCN, the right vagus section increased the rate of ovulating animals (6/8 vs. 2/9, p <0.0001, Fisher’s exact probability test) and E2 levels (51.8±9.4 vs. 22.4 ± 4.0, p <0.05, two-way ANOVA, followed by Tukey’s multiple comparison test). Present results suggest that the right vagus nerve plays a role in the multisynaptic communication between the right SCN and the right ovary, while the left vagus does not. Reference: (1) Travagli, R. A. J. Physiol. 2007 Jul 15:582(Pt 2):471. (2) Vieyra et al., Reproductive Biology and Endocrinology. 2016 Jun 16 14(1):34, 1-11.Supported by CONACyT 236908; DGAPA-PAPIIT IN216519
SAT-501 Thyrotoxicosis with Pre-Ventricular Complexes Resulting in Thyroid Storm and Cardiac Arrest
Authors: Pham Nam D , Kermani Asra , Hussain Iram
Published: May 2020

Background: Ventricular arrythmias are a rare, often lethal complication of thyrotoxicosis. We describe a patient with uncontrolled hyperthyroidism and pre-ventricular complexes (PVCs) who presented with ventricular tachyarrhythmia cardiac arrest and was successfully resuscitated.

Clinical Case: A 64 year old woman was diagnosed with thyrotoxicosis secondary to Graves’ disease [TSH < 0.01 (0.40 – 4.5 mcIU/mL) and free T4 of 2.8 (0.8 – 1.8 ng/dL)] 1 year ago in the setting of a 6 month history of weight loss, palpitations, tremors, and a large goiter. She was started on methimazole and metoprolol XL and was intermittently compliant. During follow-up evaluation she complained of light headedness, developed agonal breathing, and became pulseless. Chest compressions were initiated. She regained spontaneous rhythm after receiving 1 shock with an Automated Electronic Defibrillator (AED). She was transferred to the Emergency Room (ER) and intubated for altered mental status.

Emergent CT Angiography and bedside echocardiogram showed no pulmonary embolism and normal biventricular function. Troponin T high sensitivity assay was negative and electrolytes were normal. Repeat thyroid function tests showed TSH <0.01, Free T4 of 5.6 and free T3 of 14.5 (2.0 – 4.4 pg/mL). She was started on propylthiouracil, glucocorticoids, potassium iodide and treated for thyroid storm. EKG in the ER showed sinus tachycardia with no ischemic ST changes but PVCs and fusion complexes were noted. These were also present on EKG at the time of her initial diagnosis of hyperthyroidism. EKGs prior to the diagnosis of hyperthyroidism showed normal sinus rhythm.

Cardiac arrest was attributed to thyrotoxicosis as there was no infectious nidus and no evidence of structural cardiac disease. The AED rhythm strips could not be obtained but she was presumed to have an appropriately shockable ventricular tachyarrhythmia such as ventricular tachycardia (VT) or ventricular fibrillation (VF).

Her thyroid hormone levels declined appropriately over the course of the hospitalization and PVCs were no longer noted on telemetry and daily EKGs. She was discharged on methimazole which she took consistently. She underwent RAI ablation several months after discharge.

Conclusion: Failure to achieve rapid euthyroidism in thyrotoxicosis is associated with increased cardiovascular morbidity and mortality (1). Most arrythmias associated with thyrotoxicosis are supraventricular and ventricular arrythmias are a rare sequela (2). This is one of the few cases reported of antecedent PVCs being noted on EKG. The PVCs resolved with anti-thyroid medications.

References: (1) Okosieme, O. E., et al. (2019) Primary therapy of Graves’ disease and cardiovascular morbidity and mortality: a linked-record cohort study. Lancet Diabetes Endocrinol 7, 278-287. (2) Marrakchi, S., et al. (2015) Arrhythmia and thyroid dysfunction. Herz 40 Suppl 2, 101-109.
MON-035 Does Androgen Exposure Result in Germline Transmission of PCOS-Like Phenotypes and Can It Be Reversed?
Authors: Lu Haojiang , Manti Maria , Risal Sanjiv , Lindgren Eva , Benrick Anna , Deng Qiaolin , Stener-Victorin Elisabet
Published: May 2020

Daughters of women with polycystic ovary syndrome (PCOS) are more likely to be diagnosed with PCOS, including reproductive and metabolic dysfunctions. Our recent research has demonstrated that dihydrotestosterone (DHT) exposure during late pregnancy results in transgenerational transmission of PCOS susceptibility to female offspring. But it remains unclear whether the transmission of the PCOS-like phenotypes is induced by in utero environment or via germ cell reprogramming, and whether treatment by exercise or androgen receptor blocker, flutamide, can prevent disease transmission. To model PCOS condition, donor mice were implanted with a continuous releasing DHT or vehicle pellet at 4 weeks of age. A subset of DHT exposed F0 donors had either free access to running wheels or were implanted with a slow-releasing flutamide pellet. Mice were exposed with or without treatment for either 6 weeks before IVF or 10 weeks prior to phenotypic testing. Here we present the phenotype of the F0 donors and the result of IVF to generate first (F1) and second (F2) generation offspring. Donors weigh more already after 2 weeks of DHT exposure and had more fat mass with larger adipocyte size, impaired glucose tolerance, and heavier kidney after 10 weeks of androgenization, which was reversed by both flutamide and exercise intervention. Moreover, DHT exposure increased circulating androgens and donors were completely acyclic. Simultaneous treatment with flutamide reversed the elevated androstenedione, testosterone, and restored estrus cyclicity, indicating that androgen receptor blocker can reverse hyperandrogenemia and reproductive dysfunction, whereas exercise failed to improve these phenotypes. After 6 weeks of exposure or treatment, donor oocytes were superovulated for IVF. Fewer oocytes per donor were found in androgenized + flutamide lineage, but no significant difference was observed in oocyte to two-cell embryo conversion rate after fertilization among all groups. Although the number of live offspring at weaning was similar among all groups, a trend of more F1 male than female offspring was found in both androgenized and androgenized + exercise lineage. Similar results were obtained in the F1 females when generating F2 offspring by IVF, which androgenized + flutamide lineage showed fewer oocytes per donor upon superovulation and more F2 male than female offspring was obtained in androgenized lineage at weaning. We here show that the androgenized donors develop clear PCOS-like phenotypes and give rise to more male than female F1 and F2 offspring. While blocking androgen receptor reverses both metabolic and reproductive disturbance in the donor, it also shows a negative impact on the donor and F1 female oocyte maturation process, although number of offspring via IVF is not affected. Excercise, however, only reverses the metabolic phenotypes in the F0 donor mice with no impact on IVF outcome.
MON-158 Rates of Illnesses in Patients with Congenital Adrenal Hyperplasia
Authors: Mallappa Ashwini , Sinaii Ninet , El-Maouche Diala , Veeraraghavan Padmasree , Joyal Elizabeth , Hargreaves Courtney J , Merke Deborah P
Published: May 2020

Background: Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most common cause of primary adrenal insufficiency during childhood and patients are at risk for life-threatening adrenal crisis. In a recent study from our group, we reported gastrointestinal and upper respiratory tract infections as the two most common precipitating events for adrenal crises and hospitalizations across all ages. We also reported 11 incidents of life-threatening hypoglycemic events in children, sometimes accompanied by seizures.

Objective: To evaluate the annual rates of illnesses in patients with CAH.

Methods: We retrospectively reviewed longitudinally collected data over 23 years from 156 CAH patients enrolled in our CAH natural history study (www.clinicaltrials.gov #NCT00250159). Incidence of illnesses and occurrence of stress-dose days were computed per person-years. Incidence rate ratio (IRR) with 95% confidence intervals (CI) were calculated for comparisons.

Results: A total of 2298 visits (1909 for children and 389 for adults) were available for evaluation among the 156 patients (21-OHD: 97.4%). A total of 1870 illness events (1664 in children) were observed in 143 patients (121 children) and 2710 stress-dose days (2460 in children) were observed in 141 patients (120 children) during the study period. The incidence rate of illnesses was higher in children than adults (1.5 vs. 0.5 illnesses/person-years, IRR = 3.1, 95% CI 2.7 - 3.6; P<.0001) with incidence highest in young patients: 2.5 illnesses/person-years in <3 year olds. Similarly, the stress-dose days were higher in children than adults (2.2 vs. 0.6 days/person-years, IRR = 3.8, 95% CI 3.3 - 4.3; P<.0001).

Conclusions: Patients with CAH do not appear to have higher rates of infectious illnesses than expected, but remain at risk for life-threatening adrenal crises. As expected, illness rates are higher during childhood than adulthood. Prevention of adrenal crisis is crucial and is best accomplished through repeated age-specific education of patients and caregivers.

Acknowledgement: This research was supported by the Intramural Research Program at the National Institutes of Health (NIH), Bethesda, Maryland.
OR04-01 MRAP2 Regulates Energy Homeostasis by Promoting Primary Cilia Localization of MC4R
Authors: Bernard Adelaide A , Naharros Irene Ojeda , Guglielmetti Florence Bourgain , Yue Xinyu , Vaisse Christian
Published: May 2020

Genetic studies in humans and mice have demonstrated that the Melanocortin 4 Receptor (MC4R) is essential for adequate regulation of food intake and body weight. MC4R is expressed in a small population of hypothalamic neurons and very little is known about its molecular and cellular dynamics in vivo. We have recently demonstrated that MC4R localizes to and functions at the primary cilia of select hypothalamic neurons to control energy homeostasis. The primary cilium is a solitary hair-like organelle that serves as an antenna sensing extracellular environment. Defective primary cilia lead to a series of conditions known as ciliopathies, that can manifest through a variety of clinical features, including hyperphagia and obesity.

Here we establish that the ciliary localization and the body weight regulating activity of MC4R is dependent on a single-pass transmembrane accessory protein: the Melanocortin Receptor Associated Protein 2 (MRAP2). Specifically, we show that deleting MRAP2 specifically from MC4R neurons (MC4RMRAP2-/-) leads to early onset obesity and hyperphagia. In vitro, co-expression of MRAP2 in ciliated IMCD3 cells increases MC4R localization to the primary cilium. We further demonstrate that MRAP2 and MC4R colocalize specifically at the primary cilium in vivo, and that MC4R fails to localize to the primary cilium when MRAP2 is deleted.

These findings highlight the role of the primary cilium in the control of energy homeostasis, and the importance of accessory proteins for the localization of GPCRs to the primary cilium where they exert their function, in this case being critical for the regulation of energy homeostasis.
MON-345 Hypercalcemia After Placement of Antibiotic-Loaded Calcium Sulfate Beads
Authors: Lane Kyrstin , Kim Sarah , Grock Shira , Freeby Matthew
Published: May 2020

Calcium sulfate beads are used to fill bone voids in bone loss and nonunion, as well as in the management of bone and joint infections.1 Specifically, Stimulan® is an absorbed form of antibiotic-loaded calcium sulfate beads which delivers high local antibiotic concentrations for treatment of infection, but has also been associated with hypercalcemia in 5.4% of cases.1 Despite the significant morbidity associated with hypercalcemia, there is little published literature describing this important complication.

In our institution, five patients hospitalized between March 2019 and September 2019 with normal baseline calcium levels developed hypercalcemia as a complication of Stimulan® placement. Typically, 10 to 60 cc of Stimulan® were inserted in each surgery, with the exception of 120cc in one surgery. Three patients required a second surgery with antibiotic bead placement, and hypercalcemia occurred with both initial and subsequent surgeries. The onset of hypercalcemia varied from post-operative day one to four. The peak corrected calcium was 10.7-16.1 mg/dL which corresponded to ionized calcium of 1.57 to >2.20 mmol/L (normal 1.09-1.29 mmol/L). The patient with the highest bead volume had the highest calcium. Calcium peaked on post-operative days three to five. Patients were treated with intravenous fluids, furosemide, calcitonin and anti-resorptives including denosumab and zoledronic acid. Four patients required hemodialysis. Three patients required dialysis for symptomatic hypercalcemia and in one patient the indication was multifactorial. Calcium typically normalized by post-operative day 14 to 21, but hypercalcemia duration was unknown in two patients (one died; one had hypercalcemia on hospital discharge).

As illustrated in our cases, patients who develop hypercalcemia after their initial antibiotic bead placement may be at risk for recurrent hypercalcemia if additional surgeries use antibiotic beads. Higher bead volume may be associated with more significant hypercalcemia.1 Although previous cases have reported milder hypercalcemia, our cases demonstrate that hypercalcemia can be more severe and prolonged, necessitating dialysis in addition to traditional therapies. 1-3

References:

1.Kallala R, Harris WE, Ibrahim M, Dipane M, McPherson E. Use of Stimulan absorbable calcium sulphate beads in revision lower limb arthroplasty: Safety profile and complication rates. Bone Joint Res. 2018 Nov 3;7(10):570-579.

2.Kallala R, Haddad FS. Hypercalcaemia following the use of antibiotic-eluting absorbable calcium sulphate beads in revision arthroplasty for infection. Bone Joint J. 2015 Sep;97-B(9):1237-41.

3.Carlson Jr. CR, Markulis E, Thompson E, Havill J. A novel case of hypercalcemia following the use of calcium sulfate beads. Nephrol Open J. 2015; 1(1): 17-19.
MON-058 Precocious Puberty and Hypothyroidism in a Pediatric Case
Authors: Sea Jessica L , Head Michael J , Chiu Harvey Kenn
Published: May 2020

Background: Hypothyroidism with secondary sellar/suprasellar mass is rarely associated with precocious puberty. Here we describe a rare case of pediatric hyperprolactinemia and precocious puberty secondary to hypothyroidism, marked TSH elevation, and pituitary hyperplasia.

Clinical Case: A 9-year-old female, with onset of thelarche and menses occurring at age 7 and 8 respectively, presented with primary hypothyroidism (Free T4 <0.11; n=4.9-11.4mcg/mL), elevated TSH (1620.0mU/mL; n=0.3-4.7mU/mL), hyperprolactinemia (108.6ng/mL; n=3.0-23.1ng/mL), and elevated serum estradiol (37.6pg/mL; n=10pg/mL). The patient had coarse scaly skin, diminished energy, and poor growth lasting 1 year. There were no associated gastrointestinal issues, temperature intolerance, nor visual impairments noted during this time.

Magnetic resonance imaging revealed a large mass (1.48cm) with suprasellar extension and a mass effect on the optic chiasm. The patient was then started on Levothyroxine and Cabergoline, to reduce serum prolactin levels. However, upon follow-up two months later, the patient had hypoprolactinemia (2.0ng/mL; n=3.0-23.1ng/mL). The patient was referred to neurosurgery for resection of the sellar mass. Endocrinology was also consulted, at which point Cabergoline was discontinued and Levothyroxine was gradually increased.

Follow up 4 months later showed prolactin levels had normalized to 11.4ng/mL (3.0-23.1ng/mL). Serum LH and FSH were within normal ranges (1.2mIU/mL and 4.2mIU/mL, respectively). TSH, though still elevated (47.35mU/mL; n=0.3-4.7mU/mL), was significantly reduced compared to the prior measurement (1620mU/mL). Serum levels of Free T4 increased to 1.06mcg/mL (n=4.9-11.4mcg/mL). Levothyroxine was titrated up and a repeated pituitary MRI demonstrated a significant decrease in the size of the mass with resolution of the suprasellar extension and mass effect on the optic chiasm. Further, the patient’s menses ceased and thelarche resolved upon correction of T4 and regression of the pituitary mass.

Conclusions: While rare, primary hypothyroidism and TSH-driven pituitary hyperplasia can result in a large mass effect with suprasellar extension, causing secondary hyperprolactinemia by a mass effect and central precocious puberty. This case highlights the benefits for evaluating underlying hypothyroidism as a cause for hyperprolactinemia and sellar/suprasellar mass.
SUN-040 Hormone Replacement Therapy in Transgender Unmasks Testicular Tumor
Authors: Tran Kelvin , Elshimy Ghada , Correa Ricardo Rafael , Harman Sherman Mitchell
Published: May 2020

Introduction In transwomen, hormonal replacement therapy typically usually consists of anti-androgen and/or estrogens. Per Endocrine Society 2017 guidelines, patients should be evaluated every 3 months in the first year for appropriate signs of feminization and adverse reactions. This includes measuring serum testosterone every 3 months initially and the testosterone level should be < 50 ng/dL. We describe a case of a transwoman patient diagnosed with testicular seminoma during surveillance of hormonal replacement therapy (HRT). Case presentation A 31-year-old male-to-female transgender presents to the endocrine clinic for HRT. She previously had seen another provider for HRT and was started on estradiol valerate 5 mg weekly and leuprolide 3.75 mg every month. After 5 months of therapy, she reported that her testosterone level remained elevated, so spironolactone 100 mg BID was subsequently added. Despite adherence, she was dismayed at how little physical changes she achieved after 1.5 years of HRT. She denies taking exogenous substances or OTC mediation containing androgens. Her examination reveals a male habitus and musculature with male voice, male diamond pubic hair pattern, adult penis size and scrotum measuring 20 cc’s bilaterally. Initial labs revealed total testosterone 131 ng/dl, free testosterone 30.8 ng/dl, bioavailable testosterone 64.6 ng/dl, SHBG 12 nmol/L, LH < 0.07 IU/L, FSH < 0.1 IU/L, and estradiol 146 pg/ml. Due to non-suppressed testosterone level despite undetectable gonadotropins, adrenal androgen labs were obtained which was normal. However, her HCG-beta tumor marker was elevated, 12 IU/L (0-3). This prompted a scrotal ultrasound which revealed 3.2 cm right testis mass. Follow-up PET/CT revealed increased activity localized to the right testis without findings of metastasis. Patient underwent right orchiectomy with pathology revealing seminoma stage 1A pT1bMx. At 2 months postop, her total testosterone is now 8 ng/dl, and she reports that her breast tissue has increased and skin softened. Conclusion Hyperandrogenism can be easily diagnosed in females given more obvious clinical features; however, except for precocious puberty, there are typically no obvious features of exogenous testosterone production in males. Thus, typically no workup is undertaken in males to look for underlying cause, including testicular cancer. While presence of scrotal mass is the most common initial presentation, patients can be asymptomatic until tumor burden is high and there is metastasis. Transwomen should be monitored by obtaining estradiol and testosterone levels following the Endocrine Society guidelines. If patient is on GnRH agonist, her testosterone level should be almost completely suppressed (T <50). A testosterone level > 50 ng/dL while on GnRH therapy should warrant workup for exogenous sources, including testicular cancer and adrenal abnormalities.
SUN-132 KLF5 Is a Poor Prognostic Marker and Therapeutic Target for Middle Eastern Papillary Thyroid Carcinoma
Authors: Al-Kuraya Khawla S , Siraj Abdul K , Poyil Pratheeshkumar , Padmaja Divya , Parvathareddy Sandeep Kumar , Al-Dayel Fouad
Published: May 2020

Thyroid cancer is the second most common malignancy among females in Saudi Arabia, with Papillary thyroid carcinoma (PTC) accounting for 80-90%. The Kruppel-like factor 5 (Klf5) is a transcription factor that play a critical role in cell transformation, proliferation and oncogenesis. Immunohistochemical analysis of KLF5 was performed in 1219 PTC cases. KLF5 over-expression was noted in 65.1% (793/1219) of PTCs, and was significantly associated with tall-cell variant (p <0.0001), extrathyroidal extension (p = 0.0003), lymph node metastasis (p < 0.0001) and stage IV tumors (p < 0.0001). Significant association was also noted with HIF-1α over-expression (p = 0.0492). Interestingly, KLF5 over-expressing tumors showed poor disease-free survival (p = 0.0066). Functional studies in PTC cell lines showed that KLF5 co-immunoprecipitated with HIF-1α. Knockdown of KLF5 decreased the expression of HIF-1α while KLF5 was not affected by HIF-1α inhibition, suggesting that KLF5 is a functional upstream of HIF-1α. Down-regulation of KLF5 using specific inhibitor, ML264 or siRNA inhibited cell invasion and migration. In addition, treatment of PTC cell lines with ML264 resulted in inhibition of proliferation and induction of apoptosis in a dose-dependent manner. Furthermore, silencing of KLF5 significantly decreased the self-renewal ability of spheroids generated from PTC cells. Our findings confer that KLF5 may be a potential therapeutic target for the treatment of papillary thyroid cancer.
SUN-001 Identification of Dehydroepiandrosterone-s (DHEA-s) Elevation Due to Performance Enhancing Supplements
Authors: Shin Terry , Plunkett Mary T , Hoang Thanh Duc , Mai Vinh Q , Shakir Mohamed K M
Published: May 2020

Background: Recreational athletes and individuals in certain occupations may utilize supplements with the goal of enhancing their physical performance and strength. These individuals may be reluctant to provide their supplement use history due to the stigma associated with performance enhancing drugs. We report a case of supplement use causing elevated dehydroepiandrosterone sulfate (DHEA-S) levels in a young woman presenting with alopecia. Clinical Case: A 29-year-old Caucasian woman presented for evaluation of progressive alopecia spanning 7 years. She was initially managed by dermatology with topical ketoconazole and clobetasol creams followed by intra-lesional triamcinolone injections. Despite treatment, she had minimal improvement. She reported menarche at age 15 with normal regular monthly menstrual cycles and normal breast development. She has no significant medical history. Physical exam was unremarkable other than localized alopecia and athletic build. She denied any medication use. Routine laboratory screening showed a DHEA-S of 624 ug/dL (ref. 35-430) with repeat DHEA-S at 602.2 ug/dL. Complete blood count, metabolic panel, thyroid function test, total/free testosterone, estradiol, 17-hydroxprogesterone, urinary 17-ketosteroids, prolactin, and iron panel were all within normal limits. Anabolic abuse screen was negative. Adrenal imaging was normal. After discussion on elevated DHEA-S results, patient revealed that she was taking a supplement that contained enobosarm (Ostarine). She was instructed to discontinue the supplement and repeat her labs but she was lost to follow up. Discussion: Developed in 1997, enobosarm is a selective androgen receptor modulator (SARMs) that is increasingly used as a performance-enhancing drug. SARMs have tissue specific androgenic receptor effect and patients on SARMs can present with a completely normal hypothalamic-pituitary gonadal axis without biochemical evidence of hyperandrogenism; which was the case in our patient. Conventional anabolic drug abuse screens do not detect SARMs. There have been multiple studies that have evaluated different performance enhancing supplements and nearly 25% of tested products contained compounds that were not correctly labeled. It is therefore uncertain what may have raised this patient’s DHEA-S levels, but the authors theorize the supplement may have contained exogenous DHEA rather than a direct effect of enobosarm. Unfortunately, there is paucity of data or literature on the effect of SARMs on androgen hormone synthesis and DHEA-S levels. A PubMed search for SARMs and DHEA-S levels led to zero returns. It is important for clinicians to recognize and identify the possibility of SARM or supplement use in order to guide diagnostic and management decisions. Further investigation is needed to understand the impact of SARMs on laboratory data and its long term effects.
SAT-171 Adrenocortical Carcinoma in Thailand: A 10-Year Retrospective Review in a Single Tertiary Center
Authors: Gomutput Patrawon , Parksook Wasita Warachit , Sunthornyothin Sarat
Published: May 2020

Background: Adrenocortical carcinoma (ACC) is a rare and fatal endocrine malignancy. This retrospective review aims to investigate treatment outcomes and clinical characteristics of 18 patients diagnosed with ACC at King Chulalongkorn Memorial Hospital from 2009 to 2018. Methods: We reviewed medical records regarding the presenting symptoms, hormonal investigations, imaging results, staging, modalities of treatment and outcomes. Results: Of the 18 patients, 14 patients were female (77%). The median age at diagnosis was 47.5 years [interquartile range (IQR) 39.5-58.2]. Mass effects and/or hormonal hypersecretion were the most common presentation, documented in 7 (38%) and 6 (33%) patients respectively. Autonomous adrenal hormone excess was found in 10 patients (56%). Cushing’s syndrome and elevated dehydroepiandrosterone sulphate (DHEAS) were documented in 9 (50%) and 7 patients (41%) respectively. Mineralocorticoid excess was found in 1 patient (6%). At initial staging, 9 patients (50%) were in advance or metastatic stage. Surgery was performed in 17 patients (94%) and 13 patients (76%) were in remission. However, recurrence was observed in 6 patients (33%), with the median disease-free interval of 13.5 months (IQR 12.0-25.0 months). In patients with stage 2 disease, open surgery resulted in longer disease-free interval despite larger tumor size, compared with laparoscopic surgery. Final outcomes revealed that 8 patients (44%) had remission, 2 patients (11%) had persistent disease and 6 patients (33%) died. Combination therapy (adrenalectomy, radiation, medications and local control such as metastatectomy, radiofrequency ablation and transarterial chemoembolization) was documented in 11 patients (61%). All patients with remission received complete tumor resection and presented at early stages of cancer, with the majority of them having non-functioning tumors. The median follow-up time was 34 months (IQR 9-73). Conclusions: ACC is a rare and fatal disease with high mortality rates. Diagnosis is time-sensitive and requires multimodality approach.
MON-102 Serum Concentrations of FT4 and TSH in the First Six Months of L-Thyroxine Treatment in Infants with Congenital Hypothyroidism: Target Attainment Rates Should Be Improved
Authors: Leroux Stéphanie , Pascal Gächter , Gilbert Koch , Konrad Daniel , l’Allemand Dagmar , Welzel Tatjana , Pfister Marc , Szinnai Gabor
Published: May 2020

Levo-Thyroxine (L-T4) is the medication of choice for treating congenital hypothyroidism (CH). Adequate L-T4 treatment is essential for early neurodevelopment in affected patients. Both under- and overtreatment with L-T4 were associated with long-term adverse neurological outcomes. Based on clinical experience, initial L-T4 dosing does not always result in optimal TSH and FT4 concentrations in all CH patients. The purposes of this study were 1) to quantify FT4 and TSH target attainment rates (TAR) in the first six months of L-T4 treatment in infants with CH, 2) to compare characteristics of patients with FT4 concentrations “OUT of” versus “IN” the target range at first time of monitoring.

A multicenter retrospective analysis was conducted in infants born between 1995 and 2018. TSH and FT4 TARs were defined according to the most recent guidelines of the European Society for Paediatric Endocrinology (ESPE), as the percentage of concentrations “in” and “in the upper half” of the corresponding laboratory age-specific reference range for TSH and FT4, respectively.

We analyzed a total of 208 TSH and 186 FT4 serum concentrations from 60 patients during the first 6 months of L-T4 treatment. The pretreatment FT4 and TSH serum concentrations (mean±SD) were 8.3±5.7 pmol/L and 338±248 mU/L, respectively. CH severity according to ESPE guidelines was severe, moderate and mild for 32%, 27% and 32% of the patients. Postnatal age (PNA) (mean±SD) at start of treatment was 10±12 days. Starting dose of L-T4 (mean±SD) for severe, moderate and mild CH were 10±4, 10±3, and 7±4 µg/kg/day, respectively. Over the study period, TSH TARs of 63% did not further improve between the first monitoring (mean at 17 days of treatment) and fourth monitoring (mean at 4 months of treatment), while FT4 TARs increased from 22% to 45% paralleled with a decrease of too high FT4 values from 55% to 21%.

Comparing patients with FT4 concentrations “OUT of” versus “IN” the target range at first time monitoring (16 versus 18 days after starting treatment; p=0.45), they did not differ in pretreatment FT4 concentrations (p=0.2). In contrast, patients who had FT4 concentrations “OUT of” versus “IN” the target range received first dose of L-T4 at an earlier median PNA (7 versus 16 days; p=0.008), had higher pretreatment mean TSH concentrations (364 versus 181 mU/L; p=0.02) and received a higher mean initial L-T4 dose (10.3 versus 7.1 µg/kg/day; p=0.01).

First, our results show that FT4 and TSH target ranges were not reached in all patients in the first six months of treatment. Second, our data suggest that TARs could be improved by individualizing initial L-T4 dosing not only according to pretreatment FT4 but also to pretreatment TSH concentrations. L-T4 dosing optimization is needed in this population.
OR03-04 The Study of Cell Senescence in Cortisol-Producing Adrenocortical Adenomas
Authors: Gao Xin , Yamazaki Yuto , Pieroni Jacopo , Tezuka Yuta , Omata Kei , Ono Yoshikiyo , Morimoto Ryo , Nakamura Yasuhiro , Satoh Fumitoshi , Sasano Hironobu
Published: May 2020

Introduction Aging is associated with the pathogenesis of many endocrine disorders such as cardiovascular diseases and diabetes. Cell senescence has been reported as one of their mechanisms. In addition, stress responsiveness has been reported to be associated with cell senescence. In addition, some genetic abnormalities such as mitochondrial DNA (mtDNA) damages or telomere shortening, have been detected in some endocrine disorders. Cortisol is a well-known stress-induced hormone and closely associated with aging. We previously reported that cortisol-producing adenoma (CPA) more abundantly expressed cell senescent markers such as p16 and p21 than other hormone-producing adrenocortical adenomas. However, the detailed pathophysiology of cell senescence and its association with histological features in CPAs have remained virtually unknown. Therefore, we analyzed cell senescent markers (telomere length, mtDNA copy number, mtDNA deletion and p16 and p21 immunoreactivity) and analyzed their correlation with clinicopathological factors in CPA patients.

Methods & Materials Forty CPA cases was immunohistochemically evaluated. Twenty CPA, ten adjacent ZF and six non-functional adenoma (NFA) were examined for mtDNA abnormalities. mtDNA deletion was evaluated by nested-PCR and mtDNA copy number and telomere length were measured using real-time PCR.

Results p21 immunoreactivity was significantly higher in CPA than that of adjacent ZF (P=0.0001) and significantly inversely correlated with tumor size (P=0.0004). Telomere length was much longer in CPA than that in adjacent ZF(P=0.0038), and NFA (P=0.0018). mtDNA copy number of NFA was significantly higher than that of CPA and adjacent ZF (P=0.0038). mtDNA copy number of compact cells was significantly higher than that of clear cells (P=0.0432). mtDNA copy number of compact cells was positively correlated with urinary free cortisol (UFC) (P=0.0428) and plasma cortisol (F) (P=0.0609). mtDNA copy number of clear cells were inversely correlated with F (0.0497). 4977 bp mtDNA deletion was more frequently detected in CPA (54%) and in adjacent ZF (50%) than in NFA (17%).

Discussion Results of our present study did reveal that CPA harbored more senescent phenotype as demonstrated by abundant p16 and p21, marked telomere shortening, frequent mtDNA 4977bp deletion and relatively low mtDNA copy number, possibly caused by long-term exposure of excessive cortisol in situ compared to NFA. In addition, clear tumor cells could represent more senescent histological phenotype because of their lower mtDNA copy numbers. This is the first study to demonstrate that compact tumor cells were biologically more active than clear tumor cells and could reflect clinical cortisol biosynthesis, resulting in marked functional intratumoral heterogeneity in CPAs.
MON-262 A Case of the Suprasellar Atypical Teratoid Rhabdoid Tumor (ATRT) Presenting in an Adult Treated with Intrathecal Chemotherapy
Authors: Oraibi Omar , Mau Christine , Daggubati Lekhaj , Khormi Yahya , Manni Andrea , Zacharia Brad
Published: May 2020

Background: Atypical teratoid rhabdoid tumors (ATRTs) are highly malignant tumors that usually present as a posterior fossa mass in children less than 3 years old. Only 38 cases have been reported in adults. They are also typically located in the supratentorial region. In none of the reported cases of suprasellar ATRT in the adult, intrathecal chemotherapy (via ommaya) has been used. Clinical case: A 70-year-old woman presented with a severe headache and magnetic resonance imaging (MRI) revealed a suprasellar mass measuring 2.9 x 2.1 x 3.0 cm. Shortly after her presentation, she developed an acute 3rd nerve palsy, and repeat MRI found dramatic interval growth. A transsphenoidal approach for biopsy/resection was attempted, but the lesion was not accessible via this corridor. She then underwent a right frontotemporal craniotomy and subsequently developed panhypopituitarism, including diabetes insipidus. Pathology revealed poorly differentiated malignant cells. Immunohistochemistry was positive for synaptophysin, Epithelial Membrane Antigen (EMA), Tumor protein p53, and negative for integrase interactor 1 (INI-1 antibody) with loss of expression in tumor nuclei with positive internal control in endothelial cells. These findings confirmed the diagnosis of ATRT. The Ki-67 index was 60% consistent with a highly proliferative tumor. One month later, she developed acute mental status change. Repeat computed tomography, and MRI showed recurrence of the tumor at the same location with new leptomeningeal enhancement involving the left facial nerve. Multimodal treatment was instituted, consisting of intraventricular/intrathecal chemotherapy with etoposide and topotecan plus fractionated external beam cranial irradiation (30 Gy in 10 fractions). She continued to deteriorate, and following consultation with her family, she was transferred to hospice care and died six months following her initial surgery. Conclusion: This is the first case of adult suprasellar ATRT that has been treated with intrathecal chemotherapy. There is no consensus on the best combination of chemotherapy, and often the St. Jude’s protocol used in the treatment of pediatric ATRT is used. In line with the biological behavior reported for this tumor in children and adults in different locations, the tumor was very aggressive, resulting in the patient’s death only after 6 months from the diagnosis despite aggressive surgical and medical treatment. Reference: 1. Athale, U. H., J. Duckworth, I. Odame, and R. Barr. 2009. Childhood atypical teratoid rhabdoid tumor of the central nervous system: a meta-analysis of observational studies. J. Pediatr. Hematol. Oncol. 31:651-663. 2. Shonka N, Armstrong T (2011) Atypical teratoid/rhabdoid tumors in adults: A case report and treatment-focused review. J Clin Med Res 3: 85-92.
SAT-216 Retroperitoneal Paraganglioma: Case Report
Authors: Silva Eugénia Morado , Ferreira Rute , Cunha Clara , Boligo Sofia , Branco Cláudia , Araújo Ana Virgínia , Oliveira Manuela , Duarte Sequeira
Published: May 2020

Introduction: Paraganglioma (PGL) is a rare type of neuroendocrine neoplasm able to secrete neuropeptide and catecholamines. It can occur in any location between the neck and the pelvis. Most of the PGLs are diagnosed in the third to fifth decades and clinical presentation is variable and depends upon catecholamine secretion and tumor location. PGLs occur in the abdomen in 85% of cases. There are no unique imaging characteristics specific for PGLs, consequently, these tumors can be mistaken with other primary abdominal tumors.

Clinical-Case: We present the case of a 65-year-old woman with history of hypertension (diagnosis at 40 years) and dyslipidemia. She denied family history of hypertension. In the context of a recent diagnosis of type 2 Diabetes Mellitus, she underwent abdominal ultrasound which revealed a large, heterogeneous nodular formation with partial liquid content, measuring 12x15 cm, adjacent to the left hepatic border. Abdominal CT scan revealed an intra-abdominal mass, with 14cm (largest diameter), showing intimate contact, with no cleavage plan with the posterior wall of the gastric fundus, suggesting Gastrointestinal Stromal Tumor. A left adrenal nodule with 3.3 cm was also present, rounded, hypoechogenic, with regular margins and homogeneous. Echoendoscopy with biopsy of the retro-gastric mass showed a neuroendocrine neoplasia. At this point she was sent to an endocrinologist. When questioned she referred headache, diaphoresis and anxiety complaints for 3 years. At examination, a painless abdominal mass in the epigastrium and left hypochondrium was found. Laboratory evaluation revealed urinary metanephrines 11738 (64-302) ug/day, urinary normetanephrines 5832 (162-527) ug/day, renin 15.5 (1-8.2) pg/mL, aldosterone 28.6 (10-160)ng/dL, cortisol after 1 mg dexamethason 1,18 µg / dl (less than 1,8ug/dl) and chromogranin A 36.6 nmol / L (less than 3nmol/l). MIBG scintigraphy revealed fixation only in the large known retroperitoneal mass. The patient underwent excision of the retroperitoneal mass and of the left adrenal gland without complications. The histological diagnosis revealed, respectively, paraganglioma and adrenal cortical adenoma. Four weeks after surgery laboratory results were normal (urinary metanephrines 202 ug/24h and normetanephrines 382.0 ug /day; Chromogranin A 2.60 nmol/l). The results of the genetic tests including SDHB, SDHD, SDHC, VHL and MAX were negative.

Conclusion: This report emphasizes the necessity to include paraganglioma in the differential diagnosis and management of retroperitoneal tumors avoiding the risk of the biopsy in this kind of tumors.
SAT-124 Optimization of Experimental Conditions for Mimicking Hypoxia in Cultured Breast Cancer Cells by Using Cobalt(II) Chloride (CoCl2)
Authors: Chen Karin , Satlof Leo , Kothapalli Udithi , Ziluck Noah , Lema Maribel , Poretsky Leonid , Avtanski Dimiter
Published: May 2020

Hypoxia is a common phenomenon in solid tumor development caused by a decrease in either oxygen concentration or oxygen pressure as a result of rapid tumor cell growth. Hypoxia is characterized by stabilization of the alpha subunit of the hypoxia-inducible factor (HIF-1α) and its nuclear translocation and heterodimerization with HIF-1β. Activation of this signaling pathway involves multiple downstream effectors including carbonic anhydrase 9 (CA9, s. CAIX). A reliable method to mimic hypoxia utilizes cobalt(II) chloride (CoCl2), which directly induces the expression of HIF-1α. The aim of this study was to optimize the experimental conditions for CoCl2 treatment of breast cancer cells in vitro using three human breast cancer cell lines (MDA-MB-231, T-47D, and MCF-7 cells). We performed time- and concentration-response experiments, using various concentrations of CoCl2 (50, 100, 200, and 300 μM) for 24 and 48 hours, and measured the expression of HIF-1α and CA9 by qRT-PCR and Western blot analyses. Results demonstrated that CoCl2 downregulated HIF-1α mRNA levels but upregulated CA9 mRNA levels in a concentration- and time-dependent manner. Concomitantly, CoCl2 treatment resulted in a significant induction of HIF-1α protein levels. We further investigated the effect of the CoCl2 concentrations listed above on cell apoptosis using an in situ apoptosis detection kit. The results demonstrated that concentrations of CoCl2 up to 100 μM had no significant effect on cell apoptosis.