bluuebunny/crossref_metadata_2025 huggingface dataset:
FRI311 GnRH Agonist Induced Pituitary Apoplexy In A Patient With Gonadotropinoma
Authors: Madahar Inderpreet , Khan Salwa , Hergenroeder Laurel , Skaff Brianna , Haider Adnan
Published: October 2023

Disclosure: I. Madahar: None. S. Khan: None. L. Hergenroeder: None. B. Skaff: None. A. Haider: None.

Introduction: GnRH therapy is commonly employed in patients with advanced prostate cancer. It acts as an agonist that binds to pituitary GnRH receptors. It acts via desensitization, downregulating FSH and LH production, and ultimately decreasing testicular steroidogenesis. Initial administration leads to transient stimulation of the pituitary which leads to elevated FSH and LH levels and increased production of estrogen and testosterone with eventual downregulation of the overall pathway. Case description: 80-year-old male with a past history of atrial fibrillation and OA was diagnosed with prostate cancer. Prostate adenocarcinoma Gleason score 7 (4+3) grade 3 was diagnosed by needle core biopsy five months prior to presentation. CT chest, abdomen, pelvis, and bone scan did not show evidence of metastatic disease. A week prior to starting Lupron therapy he was started on bicalutamide therapy. He received a dose of leuprolide (Elligard) as part of his chemoradiation therapy for his cancer. The patient went golfing after the treatment and within four hours he started noticing headaches and retroorbital pain. Headaches were sharp in quality, intensity 9 out of 10, and associated with nausea and vomiting. He later developed right-sided ptosis and double vision which progressively worsened after the next few hours. An initial CT scan of the head showed an enlarging pituitary mass which was followed MRI of the brain with and without contrast showed an enlarged pituitary mass and right cavernous sinus effacement of the optic chiasm. Anterior pituitary hormone functions were ordered, and the patient was started on stress-dose steroids. Transsphenoidal pituitary resection was done which the patient tolerated well pathology showed pituitary adenoma with pituitary apoplexy and the immunoprofile was compatible with gonadotroph adenoma. The adenoma cells were positive for synaptophysin, cam 5.2, GATA3, and FSH. A repeat MRI of the Sella three months after surgery showed a 9 mm nodule in the right aspect of the Sella. Anterior pituitary hormone levels done prior to surgery showed an IGF- 1 level of 204 ng/ml (Z score 1.5 SD). TSH and free T4 were in the normal range. Hydrocortisone was tapered and stopped 6 weeks after transsphenoidal surgery. Discussion: Lupron levels reach maximum concentration four hours after intramuscular administration. Initial pituitary stimulation by leuprolide administration causes the increased metabolic activity of the underlying adenoma which outgrows its blood supply, thus developing ischemic necrosis and subsequent hemorrhage. The majority of pituitary apoplexy develops in patients with previous undiagnosed pituitary adenomas. Should patients get central imaging to screen for pituitary macroadenoma before Lupron treatments to prevent this potentially life-threatening complication?

Presentation: Friday, June 16, 2023
FRI350 Prolonged Transient Central Diabetes Insipidus Induced By Traumatic Brain Injury
Authors: Marques Renata , Sharma Sapna , Flores Chang Bessy Suyin , Sajan Alen
Published: October 2023

Disclosure: R. Marques: None. S. Sharma: None. B.S. Flores Chang: None. A. Sajan: None.

Introduction: Central diabetes insipidus (CDI) is a rare complication of traumatic brain injury (TBI). Most cases of CDI due to TBI are transient and resolve within 2-5 days. We report a patient with prolonged transient CDI which lasted for 35 days after sustaining a gunshot wound to the head. Case Description: A 17-year-old male with no past medical history presented after gunshot wound in the head. He had comminuted fractures of the right temporal bone, right zygomatic arch, greater and lesser rings of sphenoid bone, right maxillary sinus, right medial orbital wall, right orbital floor and bilateral frontal sinuses. A computerized tomography of head showed subarachnoid haemorrhage of the frontal lobes as well as subdural haemorrhage of right parietal lobe, right falx cerebri and left cerebral hemisphere. On hospital day 2, he had an intracranial pressure monitor placed which was unremarkable. He underwent right hemicraniectomy with debridement and washout on hospital day 3. Shortly afterwards, his urine output increased to >500 cc/hr with serum sodium of 172 mEq/L [135-145], serum osmolality 307 mOsmol/kg [270-295], and urine osmolality of 117 mOsm/kg [300-900]; consistent with CDI. He was acutely treated with intravenous desmopressin with resolution of hypernatremia. During the next five weeks of his 3-month hospitalization, he continued to have polyuria with specific gravity as low as 1.003 [1.005-1.030], and occasional hypernatremia, with a peak serum sodium of 150 mEq/L. Intranasal desmopressin as well as free water supplementation were given daily to alleviate his polyuria and hypernatremia. Evaluation of anterior pituitary function was normal except for decreased gonadotrophins. His polyuria resolved after five weeks, and labs showed urine osmolality of 530 mOsm/kg with serum sodium 138 mEq/L and urine specific gravity 1.010, consistent with resolution of CDI. Intranasal desmopressin was discontinued. His serum sodium remained stable without desmopressin for the next 7 weeks with serum sodium at discharge of 141 mEq/L. Discussion: The damage of the hypothalamic vasopressin-producing neurons, their axons or the posterior pituitary results in permanent post-TBI CDI. In cases of transient CDI, the pathogenesis is likely related to small vessel damage or inflammatory edema rather than direct neuronal damage. In our case, the patient initially developed hypernatremia and polyuria from acute CDI due to hemicraniectomy with debridement and washout. He continued to have prolonged transient CDI due to the extensive intracranial hemorrhage and edema. The CDI resolved with desmopressin (both intravenous and intranasal) and fluid replacement. Transient CDI is a rare complication intracranial haemorrhage. Our case highlights that the severity of TBI may correlate with the duration of transient CDI.

Presentation: Friday, June 16, 2023
FRI361 Insulinoma Presenting With Complete Heart Block
Authors: Campbell Ruth , Lawless Sarah Jean , MacNeill Briain , Brosnan Elizabeth , Bell Marcia J
Published: October 2023

Disclosure: R. Campbell: None. S.J. Lawless: None. B. MacNeill: None. E. Brosnan: None. M.J. Bell: None.

Background: Insulinomas are a rare functioning pancreatic neoplasm, causing hypoglycaemia, typically during the fasting state (1). The non-specific and varied presentations of this condition make it quite the elusive diagnosis. Clinical Case: A 32 year old female with multiple presentations to the hospital with loss of consciousness and fatigue was subsequently noted to have complete heart block with a 4.4 second pause due to ventricular standstill in the early morning on a holter monitor. She had a background history of temporal lobe epilepsy from the age of 17 and was on regular anti-epileptics. Following discussion with the electrophysiology team, a dual chamber pacemaker (PPM) was inserted. Two months following PPM insertion she was re-admitted with another collapse, however on this occasion a blood glucose level (BGL) was 1.7mmol/L, promoting investigation for a possible insulinoma. A 72hr fast provided biochemical evidence of same with a BGL of 1.6mmol/L within 24hrs, insulin level 72.7pmol/L and c-peptide 621pmol/L. She was commenced on Octreotide and Diazoxide while awaiting further work-up. A CT pancreas was normal, and she subsequently underwent an endoscopic ultrasound, which visualised an isoechoic lesion in the pancreatic mid-body. One year following her initial presentation she underwent enucleation of the pancreatic lesion and pathology confirmed an insulinoma. Her symptoms resolved and her pacemaker was subsequently removed after multidisciplinary discussion and a period of close observation with the device function turned off. Conclusion: To date there are no published case reports of an insulinoma presenting as complete heart block, however the phenomenon has been studied in animal models. Key learning points are the ambiguous nature of this diagnosis and the need to keep an open mind, particularly when other factors muddy the water, which in this case were cardiac arrhythmias and seizure disorder. Reference: (1) Okabayashi T, Shima Y, Sumiyoshi T, Kozuki A, Ito S, Ogawa Y, et al. Diagnosis and management of insulinoma. World journal of gastroenterology: WJG. 2013;19(6):829.

Presentation: Friday, June 16, 2023
THU171 Reference Intervals For Bioavailable IGF-I Values In Dutch Healthy Children, Adolescents And Young Adults
Authors: Pellikaan Karlijn , Elizabeth Melitza , Hokken-Koelega Anita C S , van den Berg Sjoerd Adrianus Antonius , de Graaff-Herder Laura
Published: October 2023

Disclosure: K. Pellikaan: None. M. Elizabeth: None. A.C. Hokken-Koelega: None. S.A. van den Berg: None. L. de Graaff-Herder: None.

Background: Immunoreactive ‘total’ IGF-I is the main biochemical marker for titration of growth hormone (GH) treatment. However, in several endocrine disorders like Prader-Willi syndrome (PWS) and Silver-Russell syndrome, total IGF-I levels are often higher than expected based on GH dose and clinical effects. When patients reach total IGF-I concentrations above +2SDS, fear of negative long-term effects makes clinicians reduce GH dose. This dose reduction often leads to a deterioration in body composition, growth (in children) and quality of life, which suggests that bioavailability of IGF-I is reduced in patients with these disorders. Measurement of bioavailable IGF-I could improve GH dose titration. However, use of bioavailable IGF-I assays has been hindered by the lack of proper reference intervals. We report reference intervals of bioavailable IGF-I in a large group of healthy children, adolescents and adults. Methods: Serum was collected of 260 Dutch healthy controls aged 1-21 years. Total IGF-I and unbound, bioavailable IGF-I were measured manually using Ansh Labs total and free IGF-I assays. We calculated male and female age-related reference intervals for total and bioavailable IGF-I. Results: We present male and female age-related reference intervals. Both total and bioavailable IGF-I increased with age and were significantly higher in females than in males (p < 0.001). Conclusions: the reported reference intervals for bioavailable IGF-I concentrations will facilitate the use of bioavailable IGF-I levels as an alternative marker for GH dose titration in patients with disorders in which total IGF-I levels are unreliable.

Presentation: Thursday, June 15, 2023
FRI385 Influence Of Maternal Dietary Protein Precursor On Reproductive Endocrinology Of Neonatal Bovine Offspring
Authors: Thorson Jennifer F , Prezotto Ligia D
Published: October 2023

Disclosure: J.F. Thorson: None. L.D. Prezotto: None.

Bovine oogenesis and follicular maturation are initiated during in utero development, a process that is stringently orchestrated by the endocrine milieu. Of paramount importance are the three major biologically active estrogens: estron, estradiol, and estriol that are involved in the development and maintenance of germ cells. Previous work using the current model have revealed that maternal urea (protein precursor) supplementation reduces the ovarian follicular reserve without compromising the number of secondary and tertiary follicles. Therefore, we did not anticipate an influence of dietary treatment on biologically active estrogens. However, as the ovarian reserve is positively associated with circulating concentrations of anti-Mullerian hormone (AMH) we hypothesized that offspring from dams supplemented urea would have reduced circulating concentrations of AMH at birth. To characterize the effects of maternal urea supplementation, multiparous cows pregnant with female calves were individually-fed isocaloric dietary treatments consisting of chopped forage top-dressed with a control (0 g urea/animal/d) or urea (80 g urea/animal/d) pelleted supplement. Diets met or exceeded dietary requirements throughout gestation. Blood samples were collected from offspring at birth for the collection of plasma. Plasma was analyzed for concentration of estradiol, estrone, unconjugated estriol, and AMH using commercially available ELISA kits. The effect of maternal dietary treatment on concentration of hormones in offspring were evaluated by ANOVA. As expected, maternal dietary treatment did not influence circulating concentrations of estradiol (P = 0.41), estrone (P = 0.35), or unconjugated estriol (P = 0.31). However, it was not anticipated that maternal dietary treatment would have no effect on circulating concentrations of AMH (P = 0.97) as offspring of urea-supplemented dams had fewer primordial and primary follicles than offspring from control dams. From these results we infer that maternal urea supplementation induces precocious follicular activation and/or increases the number of follicles recruited during maturation through an AMH-independent mechanism. Moreover, these data illustrate that while offspring of dams offered urea throughout pregnancy have a reduction in primordial and primary follicles, the steroidogenic competence of secondary and tertiary follicles is no different than dams offered the control diet.

Presentation: Friday, June 16, 2023
FRI389 Granulosa Cell-specific Knockout Of Scnn1a Disturbs Estrus Cycle And Impairs Estrogen Production In Mice
Authors: Ma Xiyang , Xu Ruiyao , Que Yanting , Chen Junjiang , Ruan Ye Chun
Published: October 2023

Disclosure: X. Ma: None. R. Xu: None. Y. Que: None. J. Chen: None. Y. Ruan: None.

Estrogens are produced primarily by ovarian granulosa cells in females, the homeostasis of which is not only a prerequisite for female reproduction but also essential to the overall health. Studies suggested Na+ environment/intake in relation to ovarian functions, although the underlying mechanism remains unclear. In the present study, we explored possible expression and function of the epithelial Na+ channel (ENaC) in granulosa cells. We analyzed an available single-cell RNA sequencing database of human ovarian cells, mouse ovarian tissues as well as a human granulosa cell line (KGN), which showed ENaC expression and its channel activities (measured by patch-clamp) in granulosa cells. Since ENaCα (Scnn1a) is the rate-limiting subunit for ENaC to function, we established a granulosa cell-specific Scnn1a knockout mouse model (Scnn1afl/fl, Cyp19a1-Cre). In such a conditional knockout (cKO) model, the estrus cycle of the female mice at reproductive ages of 8 to 10-week-old was found to be disturbed with the ratio of proestrus/estrus versus metestrus/diestrus significantly higher (t-test, p < 0.001) in cKO (1.8 ± 0.1, n = 8) compared to that of the Cre-negative control (Scnn1afl/fl, 1.0 ± 0.1, n = 8) mice. Histological analysis of the ovarian tissues showed a fewer (t-test, p < 0.05) number of corpus luteum in cKO mice (1.9 ± 0.8 per ovary, n = 8) than that of the control mice (6.2 ± 1.5 per ovary, n = 6). We next isolated the granulosa cells from the mouse model and tested their responses to gonadotropins in vitro. In granulosa cells from the control mice, the estradiol level in the culture medium (measured by ELISA) was significantly increased by the treatment of FSH (100 ng/ml, 48 hours) and subsequent LH (100 ng/ml, 18 hours) as compared to that of cells without FSH/LH treatment (33.0 ± 12.3 vs. 5.1 ± 0.9 ng/ml, t-test, p < 0.05, n = 6). Whereas, in cKO granulosa cells, no such elevation of estradiol level in response to FSH/LH was detected (7.6 ± 1.8 vs. 6.5 ± 1.3 ng/ml, t-test, p > 0.05, n = 6), suggesting impaired estrogen production with ENaCα knockout. Consistently, quantitative PCR results showed significant downregulation of Cyp19a1 (-96.1 ± 0.9%), Lhcgr (-99.5 ± 0.1%) and Fshr (- 67.9 ± 7.2%), three key steroidogenic genes, in FSH/LH-treated cKO cells, as compared to that of FSH/LH-treated control cells (n = 6, t-test, p < 0.05). Taken together, these results have suggested a previously undefined role of ENaC in granulosa cells for estrogen production in response to gonadotrophins maintaining female cycle homeostasis. This work was supported by National Natural Science Foundation of China (82071599).

Presentation: Friday, June 16, 2023
FRI390 The Effects Of Chronic Asprosin Administration On Ovarian Tissue
Authors: Kelestimur Haluk , Oz Zeynep Dila , Ozdede Mehmet Ridvan , Serhatlioglu Ihsan , Tektemur Nalan Kaya , Kacar Emine
Published: October 2023

Disclosure: H. Kelestimur: None. Z. Oz: None. M. Ozdede: None. I. Serhatlioglu: None. N. Kaya Tektemur: None. E. Kacar: None.

Purpose: Asprosin is a novel glucogenic and orexigenic hormone produced by the fibrillin 1 (FBN1) gene that is secreted by white adipose tissue during fasting. Fibrillins (FBNs) are structural and signalling proteins found mainly in the ovarian stroma, tunica albuginea and theca layers. The aim of this study was to determine the effects of asprosin on ovarian tissue in the female rats. Materials and methods: Twenty-four female Sprague-Dawley rats were randomly divided into 2 groups (n=12) as control and asprosin. Asprosin and control groups were given intraperitoneal saline at doses of 500 ng/kg and 1 ml/kg, respectively, at 14.00 every day for eight weeks. After the application, decapitation was performed, and the rapidly removed ovarian tissues were placed in a 10% formaldehyde solution for fixation. Formalin-fixed ovaries were dehydrated in a graded alcohol series and graded ethanol, respectively After that, all tissues were embedded in paraffin wax. The ovaries were cut into 5-µm sections and stained with hematoxylin and eosin (H&E) and also Masson trichrome staining. Ovarian follicular reserve and fibrosis were evaluated by light microscopy. The follicles were histologically classified as primordial, primary, secondary, and Graaf and all follicular structures were counted in each section. The fibrosis was evaluated with Masson’s trichrome staining and scored from 0 to 3 semi-quantitatively (0 = no fibrosis, 1 = low fibrosis, 2 = intermediate fibrosis, 3 = severe fibrosis). Results: In the asprosin group, unlike the control group, occasional congestion was observed in the vessels located in the ovarian medulla. Apart from this, no histopathological changes were found. An increase in fibrosis was detected in the ovarian sections of the asprosin group when compared to the control group (p = 0,035). In the light microscopic evaluation of the ovarian sections of the rats in the asprosin group, the primary and secondary follicle numbers were significantly higher than those in the control group (p = 0,008 and p = 0,047 respectively). However, the difference between the control and asprosin groups in terms of the primordial follicle, Graafian follicle and corpus luteum numbers were not statistically significant. Conclusion: Our results have shown that chronic asprosin administration causes an increase in the number of primary and secondary follicles, suggesting that changes in ovarian steroidogenesis and folliculogenesis depending on the application may lead to positive effects on female fertility.

Keywords: Asprosin, adipokine, ovarian follicle. Acknowledgement: This study was supported by TUBITAK (Project: 220S744).

Presentation: Friday, June 16, 2023
FRI401 Co-creating Patient-facing Materials For Primary Ovarian Insufficiency
Authors: McDonald Isabella R , Blocker Elizabeth S , Weyman Elizabeth A , Welt Corrine K , Dwyer Andrew A
Published: October 2023

Disclosure: I.R. McDonald: None. E.S. Blocker: None. E.A. Weyman: None. C.K. Welt: None. A.A. Dwyer: None.

Evidence suggests people with POI have unmet health and information needs that contribute to impaired health-related quality of life (HR-QoL). Co-creation can produce high-quality patient-facing educational materials that respond to patient-identified needs and overcome healthcare disparities. Our goal was to co-create patient-facing materials that respond to unmet health and informational needs, mitigate health disparities, and improve HR-QoL for people with POI. The project had three sequential steps. First, we synthesized the state of the science on HR-QoL, care, and management of POI. Next, we conducted a systematic scoping review to identify “best practices” for co-creating patient-facing materials. Last, we employed co-creation best practices, patient engagement, and an iterative “design thinking” process to co-create and evaluate patient-facing POI materials. The HR-QoL scoping review identified three inter-related themes related to impaired HR-QoL in POI (diagnostic odyssey, isolation & stigma, and ego integrity) along with sub-themes of decreased sexual function, altered body image, psychological vulnerability and catastrophizing. The co-creation scoping review identified 6 best practices for co-creation: (1) begin with a review of the literature, (2) utilize a framework to inform the process, (3) involve clinical and patient experts from the beginning, (4) engage diverse perspectives, (5) ensure patients have the final decision, and (6) employ validated evaluation tools. Informed by the synthesis of care and management of POI, we partnered with patients to create concise patient-facing materials responding to unmet health and informational needs of people with POI. Patients engaged in co-creation using the “design thinking” process: empathize, define the question, ideate/brainstorm, iterate prototypes (n=4), and testing using the “gold standard” Patient Education Materials Assessment Tool (PEMAT). The final 2-page patient-facing materials were evaluated using 7 readability algorithms revealing a consensus reading level of 7th grade (i.e., fairly easy to read for an 11-13 year-old). The patient partners rated the materials as highly acceptable and actionable. The online PEMAT evaluation is underway in collaboration with POI patient organizations. We envision such co-creation will produce understandable and actionable materials (i.e., all PEMAT domain scores >80%). This project may serve as a roadmap for healthcare organizations and patients to collaborate and surmount health disparities and improve care for other health conditions.

Presentation: Friday, June 16, 2023
SAT385 Pituitary Immune Cells Regulate Gonadotrope Hormone Secretion
Authors: Del Mundo Zena Marie , Nguyen Thu , Ujagar Naveena , Nicholas Dequina
Published: October 2023

Disclosure: Z. Del Mundo: None. T. Nguyen: None. N. Ujagar: None. D. Nicholas: None.

Polycystic ovary syndrome (PCOS) is one of the most common causes of female infertility in the US and is associated with a combination of reproductive neuroendocrine physiological changes. Previous studies have shown that PCOS patients have elevated serum C reactive peptide and lipopolysaccharide (LPS), which indicates chronic low-grade inflammation. However, it is unknown how inflammation or immune cells impact reproductive outcomes. In this project, I study how inflammation affects gonadotrope regulation of sex hormone secretion. I show that in vitro depletion of immune cells from dispersed primary mouse pituitary increases the luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio. In contrast, immune activation through chronic LPS exposure in mice results in decreased serum LH to FSH ratio. Using single-cell RNA sequencing data from immune cell-enriched mouse pituitaries, I identified specific resident immune cell populations. These cell populations include macrophages with higher RNA expression of heat shock proteins in male mice compared to female mice suggesting inflammatory protection in males. Ongoing experiments include chronic LPS exposure in mice, where pituitary cells are immunophenotyped, sex hormone serum levels measured, and ovulation monitored. Ultimately this work will allow us to understand the contribution of inflammation to PCOS, with the hope of designing immunotherapy for PCOS.

Presentation Date: Saturday, June 17, 2023
SAT387 Impact Of Genetic Background On Chronic Inflammation In A Letrozole-induced Mouse Model Of PCOS
Authors: Ujagar Naveena , De Robles Gabriela , Velez Leandro , Seldin Marcus , Nicholas Dequina
Published: October 2023

Disclosure: N. Ujagar: None. G. De Robles: None. L. Velez: None. M. Seldin: None. D. Nicholas: None.

The etiology behind polycystic ovary syndrome (PCOS) is elusive due to the heterogeneity of its symptoms and varying severity in patients. There are a wide variety of factors associated with PCOS, like hyperinsulinemia, hyperandrogenism, endotoxemia and chronic inflammation that have been implicated as causal factors in the condition. However mechanisms of cause and effect are difficult to establish in human cohorts. Endotoxemia, observed in humans and mouse models of PCOS, is known to trigger chronic inflammation by activating immune cells. Although correlation of chronic inflammation with PCOS has been established, the type of inflammation in PCOS patients has not been defined, in part due to the genetic variance from person to person. Using a systems immunology approach to mimic human genetic diversity, combined with a letrozole-induced PCOS mouse model, we aim to distinguish the types of inflammation present in PCOS. We analyzed the immune cells from lymph nodes and spleens of 21 different strains of PCOS induced and control mice (130 mice in total), and found that based on genetic background the reproductive and metabolic phenotypes differed- similar to how PCOS presents clinically. Splenocytes from these control and PCOS mice were activated in vitro to trigger T cell and myeloid cell cytokine secretion, which was measured via luminex. Clustering analysis of these multi-analyte cytokine measurements together with flow cytometry of the immune cells allowed us to identify T-helper 17 (Th17) cells as the prominent immune cell driving inflammation in letrozole-induce mouse model of PCOS independent of genetic background. This systems immunology approach has allowed us to define PCOS associated inflammation and will be the basis for integrating human inflammation in PCOS with mouse models that appropriately recapitulate disease. The discovery of Th17 cells as key inflammatory mediators provide targets for understanding the mechanisms linking chronic inflammation to reproductive and metabolic outcomes in PCOS, and will assist in future development of anti-inflammatory therapies.

Presentation Date: Saturday, June 17, 2023
SAT389 Reproductive And Metabolic Characterization of Mice Overexpressing CYP17 in Ovarian Theca Cells
Authors: Joseph Serene , Ubba Vaibhave , DSilva Milan K , Wu Sheng
Published: October 2023

Disclosure: S. Joseph: None. V. Ubba: None. M. K DSilva: None. S. Wu: None.

Androgens, in physiological levels are important to normal ovarian function. However, excess androgens are detrimental to ovarian function, and is seen in PCOS, Congenital Adrenal Hyperplasia and Transgender Males undergoing testosterone therapy. Current models of androgen excess in females, mostly involve external administration of the causative agent. Hence, we developed an endogenous model of excess testosterone in female mice. To achieve this, a Triple mutant (TM) mouse was developed using the doxycycline inducible tet- on system, which involved RTTA, Cyp17 Cre and teto operator specifically inserted into CYP17 gene (purpose- double secure CYP17 specifically expressed in theca cells). These mice were fed with Doxycycline 625 mg/kg at 2 months of age. The TM mice showed significantly increased testosterone levels and Cyp17 protein expression in the ovaries. Estradiol, progesterone was unchanged. Reproductive characterization of the mice showed impaired estrous cyclicity and reduced fertility (number of pups and litters). Ovarian histology showed increased number of atretic follicles, with no changes in the number of developmental follicles and corpus leuteum. In the pituitary, mRNA expression of LHβ was significantly decreased, while GnRHR and FSHβ was unchanged. GnRH stimulation showed a decrease in LH levels in the TM mice. Immunoblotting showed increased expression of Androgen Receptor (Ar). Although increased androgens in females is associated with metabolic dysfunction, we did not observe any changes in Glucose, pyruvate and insulin tolerance in TM mice. Comprehensive Laboratory Animal Monitoring System (CLAMS) did not show any changes in the Respiratory Exchange Ratio, heat production and ambulatory movement. These studies show a unique strategy to develop an endogenous excess testosterone producing transgenic mice with decreased fertility.

Presentation Date: Saturday, June 17, 2023
FRI503 HCG-induced And Autoimmune Hyperthyroidism In A Male Patient With HCG Secreting Germ Cell Tumor
Authors: Mohamed Abubakr H B , Basina Marina
Published: October 2023

Disclosure: A.H. Mohamed: None. M. Basina: None.

Background: While Graves’ disease is the most common cause of hyperthyroidism, other rare causes include HCG secreting germ cell tumors. We describe a hyperthyroidism case with metastatic HCG secreting germ tumor and Graves’ disease. Case: 34 years old smoker male presented in 2016 with weakness and hypokalemia 2.7 mmol/L with concerns of paroxysmal periodic paralysis and was found to have hyperthyroidism consistent with Graves’ disease per work up (suppressed TSH <0.01- uIU/ml (ref 0.27-4.2 uIU/ml), elevated FT4 4.08 ng/dl (ref 0.93-1.7 ng/dl), elevated Free T3 15.0 (ref 2.3 - 4.0 pg/ml), and (thyroid stimulating immunoglobulin (TSI) 354 (ref 0 - 139 %). He was started on methimazole 20 mg that he did not use and lost follow up. In May 2022, he presented with expressive aphasia and seizures along with 4 months of right scrotal swelling, generalized lymphadenopathy, and hemoptysis episodes. He had intermittent palpitations, 30 Ibs weight loss and eye bulging. On exam he was tachycardic 120 bpm, enlarged thyroid, brisk reflexes and mild tremors. His eye exam was significant for stare, lid lag, proptosis and bilateral lid edema. His labs were remarkable for suppressed TSH <0.01 uIU/ml, FT4 >7.7 ng/dl , Total T3 394 ng/dl (80 - 200 ng/dl)Thyrotropin receptor antibodies (TRAb) 29 IU/L (ref 0-1.75 IU/L), TSI 4.8 (ref <1.3 index), Thyroglobulin Ab 5.8 IU/ml (ref <4IU/ml), TPO-Ab >900 (ref <9.0) and HCG >1,000,000 (ref <2mIU/ml). Thyroid US showed diffuse heterogeneous enlargement of the thyroid with increased vascularity and without a discrete well-defined nodule. His lymphadenopathy work revealed high grade stage III C non-seminomatous mixed germ tumors (60% teratoma and 40% choriocarcinoma) with metastasis to brain, lungs, liver, spine, iliac and sacral bones. He was started on methimazole (MMI) 20 mg TID, propranolol 40 mg TID, dexamethasone 2 mg q6hrs and chemotherapy. His thyroid labs improved in 3 days to FT4 2.83 ng/dl and TT3 93 ng/dl while TSH and HCG were unchanged. He was discharged on MMI 25 mg daily. Over 3 months, he subsequently underwent right orchiectomy, cyber knife radiation of the brain metastatic lesions and 4 chemotherapy cycles. His HCG levels fluctuated (1,000,000->3980-> 120,181) as well thyroid function test (TSH <0.01-> 5.1->0.01 uIU/ml, FT4 1.02->0.65->5.7 ng/dl and TSI 6.4 ). He required multiple methimazole adjustments. Discussion: Co-occurrence of HCG secreting germ tumors and Graves’ hyperthyroidism is rare. HCG can bind TSH receptors and in high levels has thyrotropic effects. The interplay between HCG thyrotropic effects and thyroid autoimmunity can be challenging and use of both binding and functional bioassays maybe helpful. Close thyroid function monitoring and frequent adjustment of thioamides are needed as patients undergo treatment of the primary HCG source as well as long term follow up.

Presentation: Friday, June 16, 2023
FRI190 Catching A Chimera: A Case Of Suspected Glucocorticoid Remediable Aldosteronism
Authors: Khan Aysha , Ramchandani Bhanvi , Aftab Hassaan B
Published: October 2023

Disclosure: A. Khan: None. B. Ramchandani: None. H.B. Aftab: None.

Introduction: Familial hyperaldosteronism type 1 (FH-I), also known as glucocorticoid remediable aldosteronism (GRA) is responsible for 1% of cases of primary aldosteronism (PA). It is caused by a chimeric fusion of the CYP11B2 and CYP11B1 genes resulting in ACTH-sensitive aldosterone production. We describe a case of suspected GRA and outline the diagnosis of this rare condition. Case. A 52-year-old female with history of type 2 diabetes mellitus, obesity, sleep apnea, SVT with ablation presented with long-standing history of resistant hypertension (HTN). HTN was diagnosed in her late twenties. She was previously trialed on eight different classes of antihypertensive medications excluding mineralocorticoid antagonists or potassium-sparing diuretics but HTN remained uncontrolled. Current regimen included hydralazine, nebivolol, and furosemide. Her sister had HTN diagnosed in her forties, a nephew with HTN diagnosed in his early twenties and mother with HTN with unclear age of diagnosis. Her systolic and diastolic BP averaged 150 mmHg and 90 mmHg, respectively, on both home and clinic monitoring. Physical examination was significant for mild cushingoid appearance. Screening tests for pheochromocytoma and hypercortisolism were normal. Plasma aldosterone concentration (PAC) was noted to be at 14.4 ng/dl (<39.2) with a plasma renin activity (PRA) of <0.6 ng/mL/h (2.9 - 10.8), with aldosterone to renin ratio (ARR) of 24. Repeat testing showed PAC of 15.1 ng/dl, PRA<0.6 ng/ml/hr (ARR: 25.1) with potassium of 3.3 mmol/L (3.5 -5.1). PAC levels remained unsuppressed above 10 ng/dL following four-hour, seated, 2 L IV saline suppression test with serum potassium of 3.5 mmol/L. CT abdomen showed normal appearance of the adrenal glands. Given early age of onset of HTN and strong family history, 3-day dexamethasone test was performed using 1 mg oral dexamethasone every 12 hours following which PAC suppressed to <1 ng/dl. Patient was started on spironolactone 25 mg twice daily and at the time of writing is awaiting genetic testing to confirm the diagnosis of GRA. Discussion: GRA is a rare subtype of PA which has an increased risk of cardiovascular and cerebrovascular complications. Our case highlights the importance of screening for GRA in patients who have a personal and/or family history of early onset HTN who have screened positive for PA. Genetic testing for chimeric CYP11B1/B2 gene is the confirmatory step of diagnosis, however, a 3-day dexamethasone suppression test can be used to screen for GRA with a high sensitivity. Elevated levels of urine 18-hydroxycortisol and 18-oxocortisol are also noted but these are not widely available tests. Treatment of GRA is with medical management only; since surgical intervention is not required; proper diagnosis can also save the patient from unnecessary and invasive tests such as adrenal vein sampling.

Presentation: Friday, June 16, 2023
FRI509 A Girl With Trisomy 21 Presents With Van Wyk-Grumbach Syndrome
Authors: Hayes Dorado Juan Pablo , Calla Ayala Marco Antonio , Arias Andrea Colque , Gaite Karem Lanuza , Lopez Marco Rossell , Frias Eid Daniela
Published: October 2023

Disclosure: J. Hayes dorado: None. M. Calla Ayala: None. A. Colque Arias: None. K. Lanuza Gaite: None. M. Rossell Lopez: None. D. Frias Eid: None.

Van Wyc-Grumbach syndrome (VWGS) is a rare presentation of long standing prepubertal hypothyroidism characterized by bilateral multicystic enlarged ovaries, vaginal bleeding and delayed bone age. It appeared that high TSH could produce FSH and LH like activity leading to multiple ovarian cysts. A 7-year-old girl with trisomy 21, presented with vaginal bleeding for 2 days prior to admission. Physical exam revealed bradycardia (68 bbm), apathy, sluggishness, as well as dry skin and eyelid oedema. She had no breast development nor pubic hair.Causes of vaginal bleeding such as trauma, possible abuse, foreign body insertion and urethral prolapse were excluded. There was no purpura or bleeding from other sites.The abdominal sonogram revealed bilateral ovarian cystic masses (V:17.29 cm3 and 16.48 cm3, right and left, respectively). Bone age was delayed almost 3 years behind her chronological age. Laboratory tests revealed TSH 860 μIU/mL, T4 0.71 μg/dL, FSH 8.12 mIU/mL, LH < 0.1 mIU/mL, estradiol 193 pg/mL, thyroid peroxidase Abs 184 IU/mL, thyroglobulin Abs 212 IU/mL, Β-hCG < 0.1mU/mL, confirming severe hypothyroidism. The girl was diagnosed with VWGS due to unrecognized chronic lymphocytic thyroiditis and LT4 treatment (75mug/OD) was initiated. The patient responded with complete remission of symptoms and regression of the ovarian cysts one month after initiation of treatment. It is very important to think of VWGS and investigate for thyroid status during the evaluation of ovarian cysts or isolated premature menarche. Early recognition can eliminate unnecessary surgery to remove ovarian cysts, as appropriate treatment with levothyroxine leads to complete remission of symptoms. Even when the diagnosis of VWGS is confirmed, practitioners must be watchful to consider surgical intervention in the presence of uncontrolled vaginal bleeding, hemodynamic instability, or failure of regression of ovarian cysts with exogenous thyroid hormone replacement.

Presentation: Friday, June 16, 2023
FRI513 Pathological Bone Fracture In An Adolescent With Graves’ Disease
Authors: Hayes Dorado Juan Pablo , Calla Ayala Marco Antonio , Sejas Daniela Vargas , Tapia Emilene Coca , Vargas Gerben Justiniano , Arze Francisco Leon
Published: October 2023

Disclosure: J. Hayes dorado: None. M. Calla Ayala: None. D. Vargas Sejas: None. E. Coca Tapia: None. G. Justiniano Vargas: None. F. Leon Arze: None.

Graves’ disease is the most common pediatric cause of hyperthyroidism. Although hyperthyroidism has been reported to cause a decrease in bone mineral density (BMD), its association with bone fractures is rare. A 12-year-old female patient presented to emergency with left arm pain that started after collision with an electricity pole. Her medical history included fractured right femur one year previously. Her heart rate 128 beats/min, blood pressure 120/70 mm Hg, weight 44 kg, height 156 cm (75th percentile) and BMI 18 kg/m2(50th percentile). Family history was unremarkable. He had prominent thyromegaly with diffuse enlargement and soft consistency on palpation. X-ray revealed a fracture of left humerus. Demineralization of bone was detected. Blood Tests: calcium 8.9 mg/dL (8.5-10.5); phosphate 4.36 mg/dL (3.7-5.6); alkaline phosphatase 239 U/L (42-362); PTH 23 pg/mL (12-88); 25-OHD 22.8 ng/mL (20-80); TSH <0.01 μIU/mL (0.38-5.33); fT3 29 pg/mL (2.6-4.37); and fT4 5.13 ng/dL (0.61-1.2). Auto-antibodies were positive: thyroid peroxidase Abs 42 IU/mL (0-9), thyroglobulin Abs 21 IU/mL (0-4) and TSH Receptor Abs 7.33 IU/L (0-0.1). Complete blood count, liver, kidney function tests were normal. Thyroid ultrasonography showed a significant increase in thyroid gland volume and vascularization. A diagnosis of Graves’ disease was confirmed. Methimazole, propranolol, calcium and vitamin D therapies were started. Pre-treatment bone densitometry showed significantly low BMD: lumbar BMD (L1-L4) was 0.701 g/cm2 (Z-score - 2) and femoral BMD was 0.639 g/cm2 (Z-score -2). Euthyroidism was achieved after ten weeks of treatment and clinical signs of hyperthyroidism had improved. At six months follow up there were no clinical signs of hyperthyroidism and the patient remained euthyroid. Bone densitometry investigation one year after diagnosis showed marked improvement: lumbar BMD (L1-L4) was 0.898 g/cm2 (Z-score -0.5) and femoral BMD was 0.799 g/cm2 (Z-score -0.4). Untreated adolescents with Graves’ disease may present with fractures. It highlights the importance of considering hyperthyroidism as a possible diagnosis among the differential diagnoses of pathological bone fractures.

Presentation: Friday, June 16, 2023
FRI559 An Uncommon Association Of Two Common Etiologies Of Hyperthyroidism
Authors: Kian Chew Chee
Published: October 2023

Disclosure: C. Chew: None.

Introduction: Subacute thyroiditis and Graves’ disease are two common etiologies of hyperthyroidism. Association of these two diseases in patient presented with recurrent hyperthyroidism has rarely been reported. Case Report: A 35 years old women, with no known medical illness, was referred to Endocrine Clinic for painful anterior neck swelling associated with palpitation for 2 weeks. The symptoms were preceded by 3 days history of sore throat and mild fever She denied other symptoms of hyperthyroidism. Her last menses was 3 weeks prior. On physical examination, she was tachycardic with heart rate of 115 beats per minute. Her blood pressure was 135/90 mmHg and she was afebrile. There was a tender and diffusely enlarged goiter. However, there were no signs of thyroid eye disease and other signs of hyperthyroidism. Examinations of her throat, lung, abdomen, cardiovascular system and neurological system were unremarkable. There was also absence of lymphadenopathy. She denied family history of thyroid disease. Results of laboratory investigations were suggestive of hyperthyroidism secondary to subacute thyroiditis: Free T4 52 pmol/L (8-16), TSH <0.01 mIU/L (0.45-4.50), TRAb 0.8 IU/L (0-1.0) and ESR 108 mm/hr (1-10). The technetium scan showed mildly enlarged gland with decreased uptake of Tc-99m tracer suggestive of thyroiditis. She was treated with Ibuprofen and Propranolol, and her symptoms improved. At 6 weeks follow up, her thyroid function normalized with Free T4 of 13 pmol/L (8-16), TSH of 1.28 mIU/L (0.45-4.50). However, she complained of weight loss and palpitation at 6 months follow up. Examination revealed a small painless diffuse goiter and she was tachycardic with heart rate of 115 beats per minute. Thyroid function test confirmed recurrence of hyperthyroidism: free T4 45.8 pmol/L (8-16) and TSH <0.01 mIU/L (0.45-4.50). Elevated TSH receptor antibody (TRAb) level at 16.8 IU/L confirmed the diagnosis of Graves’ disease. Carbimazole was then started. Discussion: Subacute thyroiditis and Graves’ disease are two common etiologies of hyperthyroidism. The incidence of association of these two diseases had been reported to be rare at 0.15% in patients with Graves’ disease and 0.76% in patients with subacute thyroiditis (1). The postulated mechanism of the association is that the release of thyroid antigens and corresponding activation of the immune system due to viral invasion of the thyroid gland in subacute thyroiditis may cause the subsequent Graves’ disease (1,2). Conclusion: Graves’ disease should be suspected in patient with persistent or recurrent hyperthyroidism after an episode of subacute thyroiditis although it is rare. Reference:

1. Nakano Y et al. Graves’ disease following subacute thyroiditis. Tohoku J. Exp. Med. 2011; 225:301-309.

2. Bartalena L et al. Graves’ disease occurring after subacute thyroiditis. Report of a case and review of the literature. Thyroid. 1996; 4:345-348.

Presentation: Friday, June 16, 2023
FRI560 A Rare Case Of Hashimoto Encephalopathy
Authors: Nokhbehzaeim Mahrokh , Keane Driscoll Henry , Sanati Milad
Published: October 2023

Disclosure: M. Nokhbehzaeim: None. H.K. Driscoll: None. M. Sanati: None.

Background: Hashimoto encephalopathy is a rare syndrome associated with Hashimoto’s thyroiditis. It presents as an encephalopathy without central nervous system infection or tumor. It is also described as steroid-responsive encephalopathy. It is characterized by high titers of antithyroid peroxidase antibodies. Case: 60-year-old female, with known Hashimoto thyroiditis on levothyroxine 200 mcg daily was admitted to the hospital with generalized weakness and lethargy. On admission, her TSH level was 0.085 with a Free T4 of 2.15. Subsequently, the Levothyroxine dose was decreased to 175 mcg and then was held for a few days. During her hospital stay her mental status deteriorated, and she became altered. As a part of the work-up, an MRI of the brain was done. It showed nonspecific left-sided dural thickening with enhancement, consistent with meningitis, but no signs of brain metastasis. She also developed persistent plantar flexion of both ankles and staring forward. MRI of Cervical, Thoracic, and Lumbar spine was done and leptomeningeal carcinomatosis was ruled out. She underwent a lumbar puncture; however, the CSF meningitis panel was negative. She was started on a trial of Dexamethasone 4 mg PO q 12 hours for 5 days. Her repeat thyroid function test revealed TSH: 54.4 and normal Free T4: 1.1. Levothyroxine 150 mcg was restarted, and the dose of Levothyroxine was increased to 175 mcg daily. She underwent a brain biopsy, which was unremarkable. Paraneoplastic panel and GAD 65 antibody were not detected. She was started on a trial of methylprednisolone and IVIG, and she showed significant improvement. Discussion: Hashimoto encephalopathy may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms, and myoclonus. Thyroid function is usually clinically and biochemically normal. It is characterized by high titers of antithyroid peroxidase antibodies. The other causes of encephalopathy such as toxic, metabolic, and infectious should be excluded with neuroimaging and CSF examination. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. It is a rare disorder but it is responsive to treatment with corticosteroids. Clinical improvements are also observed with IV immunoglobulin and plasmapheresis.

Presentation: Friday, June 16, 2023
SAT558 Papillary Thyroid Carcinoma With Anaplastic Transformation in a Filipino Male Treated With Radioactive Iodine and Radiotherapy: A Case Report
Authors: Apa-Ap Archimedes Almasol , Abarquez Paolo Patrick , Sedurante Myrna Buenaluz , Ongbit Ann Marie , Miguel Perez Carlos , Acenas Francis Dale , Gacula John Kenneth , Lee Vannah Marjolaine , Estreller Sachiko
Published: October 2023

Disclosure: A.A. Apa-ap: None. P. Abarquez: None. M.B. Sedurante: None. A. Ongbit: None. P. Carlos Miguel: None. F. Acenas: None. J. Gacula: None. V. Lee: None. S. Estreller: None.

INTRODUCTION. Papillary thyroid carcinoma (PTC) is an epithelial malignancy showing follicular differentiation and distinctive nuclear features, with a generally excellent prognosis. On the other hand, anaplastic thyroid cancer (ATC) is rare and highly lethal, with an incidence of only 0.7% in the Philippines. CASE DESCRIPTION. This paper describes a 43year old Filipino male with a 3-year history of anterior neck mass with an initial fine needle aspiration biopsy read as probable PTC. He underwent total thyroidectomy and bilateral radical lymph node dissection and histopathology revealed conventional PTC, solid variant with 5% focal anaplastic transformation. Metastatic workup revealed multiple sub-centimeter pulmonary nodules and a tiny hypodense nodule on left adrenal gland on CT scan. Bone scintigraphy showed increased tracer uptake in the posterior 10th rib and the sphenoid's greater wing. While the multidisciplinary team wanted to proceed with Radiation therapy (RT) first to address the more aggressive histology, this was not possible logistically and thus RAI was performed first. This slight deviation from guidelines was deemed acceptable by Nuclear Medicine due to the possible decrease in iodine absorption from post radiation fibrosis. After a dose of 150 mci, 4 weeks after surgery, patient then completed 33 fractions of RT. Surveillance revealed stable pulmonary nodules and adrenal mass but increasing TSH-stimulated thyroglobulin and antithyroglobulin. Patient underwent another cycle RAI and is currently stable on his 16th month from diagnosis, 15th month post initial RAI, and 13th month post-RT. DISCUSSION. In several case series, patients with minor anaplastic component had 1- and 2-year survival rates of 88% and 43%, respectively with a median survival of 17 months. The overall prognosis of patients with PTC with minor ATC component points to the value of active surveillance compared to more aggressive treatment modalities in the setting of conventional ATC.

Presentation Date: Saturday, June 17, 2023