bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT347 Surprising Turn Of Events In A Patient With Weight Gain: Simultaneous Diagnosis Of Macroprolactinoma And Polycystic Ovary Syndrome
Authors: Keskinkilic Ayse Nur , Sistla Divya
Published: October 2023

Disclosure: A.N. Keskinkilic: None. D. Sistla: None.

Background: The differential diagnoses of excess weight gain are broad and endocrinopathies constitute a small proportion of these etiologies. A pattern of associated symptoms, classical exam findings and hormonal testing can signal some endocrine causes. However, diagnosis can still be challenging due to overlapping clinical and biochemical features and concurrent presentations of endocrine disorders. Here, we present a diagnostically challenging rare case of a young female with weight gain who had simultaneous diagnosis of macroprolactinoma and PCOS. Clinical Case: A 34-year-old healthy female presented with one year of weight gain despite lifestyle changes. She also reported headaches, acne, hirsutism, stretch marks, excessive sweating, and had 10 years of amenorrhea while on oral contraceptives (OCs). Labs revealed mildly low free T4 of 0.72 ng/dl (n: 0.70-1.48 ng/dl) and significantly elevated prolactin (PRL) of 259.8 ng/ml (n: 1.2-29.9 ng/ml); normal FSH, LH, GH, IGF, TSH, ACTH, 1 mg dexamethasone suppression test, and 24-hour urinary cortisol. HbA1c, lipid panel, plasma metanephrine and androgen levels were normal. MRI pituitary revealed a 2.1 x 1.9 x 1.5 cm macroadenoma with mild compression to the optic chiasm. A low dose levothyroxine and cabergoline 0.25 mg twice weekly was started with dose increment to 0.5 mg twice weekly. At 6-month follow-up, PRL decreased to 30 ng/ml. Repeat MRI showed a decrease in size of the pituitary adenoma (1.5 x 1.4 x 1.3 cm). However, she could not tolerate cabergoline due to persistent headaches and depression. Hence, she elected to undergo transsphenoidal pituitary resection. Tumor pathology showed sparsely granulated lactotroph adenoma. Post op PRL level normalized, and MRI showed radiological cure of the adenoma. Headaches improved but amenorrhea persisted despite discontinuation of OCs for 6 months. Progesterone challenge tests resulted in withdrawal bleed suggesting anovulation. Repeat work-up ruled out nonclassical CAH, Cushing’s, and androgen-secreting tumors. However, subsequent pelvic ultrasound confirmed polycystic ovarian morphology, suggesting PCOS. The patient preferred to avoid OCs and could not tolerate metformin. She elected progesterone IUD placement for endometrial protection in combination with lifestyle changes with notable improvement in her symptoms. Conclusion: PCOS is a diagnosis of exclusion. Thorough evaluation of symptoms like weight gain, amenorrhea, clinical hyperandrogenism is recommended to rule out serious pathology like prolactinoma. Dual diagnosis of PCOS and macroprolactinoma is rare and should be suspected if menstrual abnormalities persist even after treatment of hyperprolactinemia.

Presentation: Saturday, June 17, 2023
SAT588 Cushing’s Syndrome Due To Ectopic ACTH Secretion From Ovarian Teratomas
Authors: Kang Yu Mi , Gildenberg Melissa S , Quade Bradley J , Blair Rachel A
Published: October 2023

Disclosure: Y. Kang: None. M.S. Gildenberg: None. B.J. Quade: None. R.A. Blair: None.

Background: Approximately 9-18% of Cushing’s syndrome (CS) cases are secondary to ectopic ACTH secretion, most commonly from sources in the lung or mediastinum. However, ACTH-producing tumors are rarely found in distant organs, occasionally making the localization and management challenging. Clinical Case: A 32-year-old woman with class 3 obesity, hidradenitis suppurativa, anxiety, and depression experienced atraumatic pelvic and sacral fractures. DXA scan result showed Z-scores of -3.1 in the lumbar spine, -2.6 in the femur neck, and -0.5 in the total hip. She reported a steady weight-gain of 250 lbs over 7 years despite lifestyle modifications and liraglutide. On examination, she had a round face with plethora, acne, violaceous abdominal striae, and dorsocervical fat pad. Laboratory findings revealed elevated midnight salivary cortisol levels of 453 and 424 ng/dL (n: <100 ng/dL), elevated 24-hour urine cortisol levels of 254 and 741 (n: 3.5-45 mcg), and an abnormal 1 mg dexamethasone suppression test (DST) result at 15.1 ug/dL. AM plasma ACTH and cortisol levels were 190 pg/mL and 18.5 ug/dL, suggesting ACTH-dependent hypercortisolism. The plasma cortisol level after an 8 mg DST was unsuppressed at 13.1 ug/dL with a dexamethasone level of 3,380 ng/dL (n: >800 ng/dL). Abdominal CT and MRI scans showed large bilateral adnexal masses measuring up to 13.7 cm on the left and 9.3 cm on the right, with heterogeneous solid and cystic components, consistent with mature cystic ovarian teratomas. DOTATE-PET scan did not show any areas of increased uptake. The patient underwent a laparoscopic right cystectomy and left oophorectomy, with immediate drop in cortisol (1.6 ug/dL) and signs of adrenal insufficiency post-operatively, requiring hydrocortisone replacement. After holding hydrocortisone for 24 hours prior to laboratory assessment one week post-operatively, her ACTH and cortisol were undetectable, reflecting successful source removal. Pathology report showed neuroendocrine tumor with pituitary differentiation with positive ACTH immunohistochemical staining and Ki-67 proliferative index of 22.6% on the left adnexal mass, and a mature cystic teratoma on the right. Conclusion: Although rare, pituitary differentiation of ovarian teratomas should be considered as a possible source of ectopic ACTH secretion in CS patients without obvious sources identified in commonly involved organs.

Presentation: Saturday, June 17, 2023
SAT600 Absent LH Signaling Rescues The Anxiety Phenotype In Aging Female Mice
Authors: Sims Steven , Barak Orly , Ryu Vitaly , Miyashita Sari , Kannangara Hasni Suhasha , Korkmaz Funda , Macdonald Anne , Gumerova Anisa , Goosens Ki , Zaidi Mone , Yuen Tony , Lizneva Daria , Frolinger Tal
Published: October 2023

Disclosure: S. Sims: None. O. Barak: None. V. Ryu: None. S. Miyashita: None. H.S. Kannangara: None. F. Korkmaz: None. A. Macdonald: None. A. Gumerova: None. K. Goosens: None. M. Zaidi: None. T. Yuen: None. D. Lizneva: None. T. Frolinger: None.

Clinical studies and experimental data together support a role for pituitary gonadotropins, including luteinizing hormone (LH), otherwise considered solely as a fertility hormones, in age-related cognitive decline. Furthermore, rising levels of LH in post-menopausal women have been implicated in the high prevalence of mood disorders. This study was designed to examine the effect of deficient LH signaling, using the global Lhcgr-/- mouse, on both cognitive and emotional behavior in 12-month-old mice. For this, we established and validated a battery of five tests, including Dark-Light Box (DLB), Y-Maze Spontaneous Alternation, Novel Object Recognition (NOR) and contextual and cued Fear Conditioning (FCT) tests. We found that 12-month-old female mice display a prominent anxiety phenotype on DLB and FCT. This phenotype was not seen in female Lhcgr-/- mice, indicating full phenotypic rescue. Furthermore, there was no effect of depleting LHCGRs on recognition memory or working spatial memory on NOR and Y-maze testing, respectively, in 12-month-old mice, notwithstanding the absence of a basal phenotype in wild type littermates. The latter data do not exclude an effect of LH on cognition documented in previous studies. Finally, male mice and 3-month-old male and female mice did not consistently display deficits on any test. The data collectively document, for the first time, that loss of LH signaling reverses age-related emotional disturbances, a prelude to future targeted therapies that block LH action.

Presentation: Saturday, June 17, 2023
SAT602 The Regulation Of Food Intake Via Gastrointestinal Receptors
Authors: Bethea Maigen Michelle , da Silva Teixeira Silvania , Cook Tyler M , Mommandi Marwa , Nault Genna , Sandoval Darleen
Published: October 2023

Disclosure: M.M. Bethea: None. S. da Silva Teixeira: None. T.M. Cook: None. M. Mommandi: None. G. Nault: None. D. Sandoval: None.

Obesity is a global pandemic characterized by excessive fat storage due to an imbalance in energy homeostasis. This metabolic imbalance is driven by increased energy intake relative to energy expenditure. The gut vagal afferent neurons play a critical role in energy homeostasis by sensing the various chemo- and mechano-signals resulting from ingested nutrients and initiating changes in feeding behavior. However, these neurons fail to respond adequately in the context of diet-induced obesity, leading to overeating and ultimately obesity. Bariatric surgeries, which modify the anatomy of the gut, are currently the most effective but also the most invasive treatments for obesity. The mechanism(s) by which bariatric surgery modulates metabolic processes is still not fully understood. The vertical sleeve gastrectomy (VSG) procedure, a bariatric surgery where 80% of the stomach is removed, alters feeding patterns and induces sustained weight loss. Our findings demonstrate that VSG induces alterations in the signals in the gut-brain-axis, resulting in increased activation of the nucleus of the solitary tract (NTS) - a brain region critical for integrating peripheral signals and regulating food intake. Importantly, emerging data demonstrate that neurons that sense intestinal distension play a critical role in the regulation of feeding. We hypothesized that diet induced obesity attenuates intestinal-stretch inhibition of food intake and that VSG restores it. Using non-nutritive substances such as methylcellulose and mannitol to differentiate stomach versus intestinal stretch respectively, we demonstrate that high-fat diet feeding ablates intestinal stretch-induced reductions in food intake while weight loss via dietary intervention, restores this response. More importantly, VSG restores intestinal stretch-induced food intake reduction, suggesting the reactivation of the peripheral neurons that detect intestinal stretch. Taken together, our data provide evidence that VSG alters the signals in the gut-brain-axis by creating an environment where intestinal distension is exaggerated. This effect likely contributes to the sustained weight loss and alterations in feeding patterns observed after VSG. Our findings have important implications for the development of less invasive therapies for obesity that target the gut-brain-axis and feeding behavior.

Presentation: Saturday, June 17, 2023
SAT606 Comparison Of Psychosocial And Immune/Inflammatory Stress On Luteinizing Hormone Pulsatile Secretion
Authors: Jang Jessica , Kreisman Michael J , Breen Church Kellie M
Published: October 2023

Disclosure: J. Jang: None. M.J. Kreisman: None. K.M. Breen Church: None.

Stress induces a physiological response in the body to return to the homeostatic state. It is recognized that many stress types impair reproduction, but the mechanisms conveying inhibition may be distinct and stressor-dependent. Our research aims to understand how stress inhibits the neuroendocrine mechanisms controlling the pulsatile release of luteinizing hormone (LH). This is especially important because pulsatile LH is pivotal to reproductive health in males and females. Immune/inflammatory stressors such as lipopolysaccharides (LPS) cause an inflammatory response, producing peripheral cytokines that can signal to the brain in distinct ways compared to the neural mechanisms employed in response to psychosocial stress. However, how LPS disrupts the neural mechanisms involved in gonadotropin pulsatility is still unknown. Here, we compared the alteration in LH pulses in response to psychosocial restraint stress or immune/inflammatory LPS stress and sought to understand stress-specific regulation of the upstream targets controlling LH synthesis and secretion. Our initial observations demonstrated, in ovariectomized (OVX) female mice, that restraint stress elicited suppression rapidly, within 30 minutes; yet, the response to LPS was delayed, occurring approximately 90 minutes from injection. Therefore, we investigated the prolonged response of the stressors on LH pulses, observing LH pulse profiles 90 minutes to 180 minutes after the initiation of stress. Restraint stress significantly suppressed mean LH, resulting from a suppression of pulse frequency. LPS injected intraperitoneal (IP, 1.5 ug/g) also significantly suppressed mean LH. In contrast to restraint stress, LPS induced a reduction in both frequency as well as LH pulse amplitude. We conducted two follow-up experiments to investigate the lowered LH pulse amplitude during immune/inflammatory stress. The first study assessed hypothalamic kisspeptin gene expression and pituitary LHβ and GnRH receptor expression, in LPS versus restraint animals, to test whether altered gene transcription in LPS animals resulted in lowered LH secretion. The results of this experiment are still pending. The second study tested the LH response to a single bolus of GnRH or kisspeptin. Interestingly, we found equivalent LH increases, to either agonist, in saline versus LPS-treated animals. Collectively, these data indicate that both restraint and immune/inflammatory stress inhibit LH pulse frequency. However, the endogenous LH pulse profiles suggest an additional stressor-specific mechanism that lowers pulsatile LH during immune/inflammatory stress via LPS. Identification of stress pathways that alter endocrine hormones is critical as it allows for the development of therapeutics and medications to treat endocrine disorders.

Presentation: Saturday, June 17, 2023
SAT627 Is Cyberknife Stereotactic Radiosurgery Effective For Treating Cushing’s Disease?
Authors: Wintermyer Gelareh , Villanueva Erika
Published: October 2023

Disclosure: G. Wintermyer: None. E. Villanueva: None.

Patients with pituitary adenoma can often present with endocrine abnormalities. Transsphenoidal surgery(TSS) is the “gold standard” treatment. In patients with recurrent or post-surgery remaining adenoma, stereotactic radiosurgery with CyberKnife (CKRS) has demonstrated to be a good adjuvant therapy. Occasionally patients develop hypopituitarism and adrenal insufficiency (AI) post CKRS. Here is a patient with ACTH-secreting pituitary adenoma with Cushing’s disease who developed remission afterCKRS:52-year-old-male with PMHx of T2DM, hypothyroidism, HTN presented to hospital complaining of fatigue, ataxia, 40-lbs weight loss over four months and mood changes. Due to ataxia, CT of the head was done which revealed an Empty Sella. During the workup, ACTH and cortisol were detected 131 pg/mL and 37.5 ug/dL respectively. After ruling out life-threatening medical conditions, he was discharged with endocrinology referral for Empty Sella syndrome (ESS) and elevated ACTH. During endocrinology evaluation, patient was sent for testosterone, LH, FSH, ACTH, AM cortisol, prolactin and DHEAS tests. Results were as follows: elevated ACTH (91 pg/mL) and Cortisol (33.5ug/dL), elevated DHEAS (401 ug/dL) and prolactin (15 NG/dL), low testosterone (72 NG/dL), within appropriately low LH and FSH. Later, PM Salivary cortisol level, Dexamethasone suppression test(DST), and urine free cortisol (UFC) level were tested. He had pituitary MRI concurrently. Salivary cortisol and UFC were high. There was no suppression of cortisol level after DST. Pituitary MRI demonstrated pituitary tumor. He was diagnosed with Cushing’s disease and was referred to neurosurgery for pituitary tumor TSS. Patient was started on Ketoconazole prior to surgery. Pathology confirmed ACTH-secreting pituitary adenoma. After surgery, Cortisol level normalized, and the patient regained his energy. Post-surgery MRI showed complete resection of adenoma. Ketoconazole was discontinued post-operatively. Two years later, during routine workup, there were elevations in 24-hour and PM salivary cortisol levels. The patient was asymptomatic. He failed his DST. Repeat pituitary MRI showed small hypo enhancement at the bottom of Sella suspicious for pituitary adenoma recurrence. The patient underwent CKRS. Cortisol level and pituitary axis activity remained normal since CKRS. No change was noted in the six-month and one-year surveillance MRI. Even though TSS is a “gold standard” treatment for pituitary adenoma, the likelihood of remaining residues or recurrence of the tumor is high. Frequent pituitary hormone checks can detect recurrence of adenoma before emerging symptoms. CKRS should be considered as a therapeutic option for recurrent adenoma. Clinicians should frequently check patients for hypopituitarism and AI post-CKRS. Clinicians should also recognize that ESS may contribute to MRI-negative Cushing’s disease.

Presentation: Saturday, June 17, 2023
OR2804 Endocrine And Vision Outcomes Following 90Yttrium Therapy For Cystic Sellar Lesions—A Prospective Cohort Study
Authors: MacLean Mark A , Ahmad Syed , Hebb Andrea L O , Tahir Anas , Greene Ryan , Clarke David B , Imran Syed Ali
Published: October 2023

Disclosure: M.A. MacLean: None. S. Ahmad: None. A.L. Hebb: None. A. Tahir: None. R. Greene: None. D.B. Clarke: None. S.A. Imran: None.

Background: Untreated cystic sellar lesions can cause vision loss, endocrine dysfunction, and obstructive hydrocephalus related to growth and mass effect. Microsurgical resection, stereotactic aspiration, and radiation treatment strategies are limited by significant complications and high risk of recurrence. Stereotactic intracavitary irradiation with the beta-emitting isotope 90Yttrium (90Yt) has been proposed as an alternative to mitigate these challenges. Long term-efficacy data is lacking. Here, our objective was to prospectively assess the effect of 90Yt on cyst volume, endocrine, and vision outcomes. Methods: We conducted a Health Canada approved, single-centre, prospective cohort study. Clinical outcome measures included cyst volume measured on magnetic resonance imaging, formal visual field (VF) testing, and hypothalamic-pituitary (HP) hormonal function. All patients provided informed consent and underwent right frontal stereotactic insertion of 90Yt colloid (200 Gy cyst wall). Results: Twenty-two patients (55% females) received 90Yt therapy. Mean age was 63.5 (SD 15.4) years with no difference between genders (p = 0.055). Mean duration of follow-up was 52 months (range 5-113). Cystic lesions included: craniopharyngioma (86%), Rathke’s cleft cyst (9%) and cystic prolactinoma (5%). Mean tumor cyst volumes were reduced by 77% at 12-month follow-up (pre-operative: 5.2, SD 4.5 cc; 12 months post-operative: 1.2, SD 1.5 cc; p = 0.002). Males had larger tumor volumes at baseline (7.7, SD 5.0 cc vs. 3.2, SD 2.8; p = 0.02) and 3 months (4.7, SD 3.4 vs. 1.8, SD 2.0; p = 0.04) but these differences had resolved by 9-month follow-up. Pre-operative clinical features included: VF deficit (36%), VF deficit plus headache (36%), headache alone (9%), hydrocephalus (5%), and 14% were asymptomatic. HP hormone dysfunction was observed in 59% of patients pre-operatively (27% complete; 73% partial) and 68% post-operatively (p = 0.50); specifically, no differences were found pre- and post-operatively for secondary hypogonadism (50% vs. 55%), hypothyroidism (45% vs. 59%), hypoadrenalism (36% vs. 27%), growth hormone deficiency (27% vs. 23%), diabetes insipidus (23% vs. 27%), and hyperprolactinemia (36% vs. 36%) (all p > 0.05). Pre-operative VF deficits were found in 68% of patients, of which 32% normalized and 36% remained stable (p = 0.180). Worsened vision was detected in 9% of patients post-operatively. Treatment failure requiring conventional surgery occurred in 18% of patients. Conclusions:90Yt therapy significantly reduced tumor cyst size and stabilized both endocrine function and vision in patients with cystic lesions of the sellar region.

Presentation: Sunday, June 18, 2023
SAT026 Melanocortin Receptors In The Earliest Chordates?
Authors: Ji Ren-Lei , Jiang Shanshan , Kleinau Gunnar , Scheerer Patrick , Tao Ya-Xiong
Published: October 2023

Disclosure: R. Ji: None. S. Jiang: None. G. Kleinau: None. P. Scheerer: None. Y. Tao: None.

Melanocortin receptors (MCRs) genes have been identified to be functional in the genome of early chordates, e.g. the cyclostomata, around 360 million years ago. Whether it appears in the most ancient chordates, such as cephalochordate and urochordata (500 million years ago), however, remained unknown until now. Herein, therefore, we studied experimentally four putative, sequence based predicted melanocortin-4 receptor (mc4r) like receptors and one putative MC1R-like receptor from urochordata and cephalochordate (from NCBI database), including Styela clava (sc), Ciona intestinalis (ci), Branchiostoma floridae (fl), and Branchiostoma belcheri (bb). No genes coding the endogenous MCR ligands were observed in these species. We further expressed these putative receptor plasmids in HEK293T cells and stimulated with α-melanocyte stimulating hormone (α-MSH) and synthetic MCR ligands to verify whether these receptors are functional MCRs. Our results showed that four receptors (so far named flMC4R, bbMC4R-1, bbMC4R-2, and ciMC1R) had high cell surface expression in HEK293T cells, whereas scMC4R had low cell surface expression. Four receptors (except scMC4R) showed high basal cAMP signaling, suggesting that these receptors are likely coupled to the stimulatory Gs protein. However, no specific binding to the superpotent α-MSH analog, NDP-MSH, were observed at these five receptors, and in accordance they had no α-MSH-induced cAMP signaling coupled to Gs stimulation. Additionally, all five receptors had low basal and no α-MSH-stimulated ERK1/2 signaling. Four human MC4R inverse agonists, including Agouti-related protein and three small molecular compounds (Ipsen5i, MCL0020, and ML00253764), had no effect on cAMP and ERK1/2 signaling of the four predicted MC4R-like receptors. In summary, our results suggested that the four predicted MCR-like receptors (except scMC4R) in ancient chordates are indeed functional receptors, with high constitutive activity, but they are all not MCR-like receptors based on our experimental data with common endogenous and synthetic MCR ligands. We hypothesize that these receptors might be MCR-like receptors, in that receptors might appear earlier than appearance of endogenous ligands; or these receptors might be other ancient G protein-coupled receptors (GPCRs) with other unidentified ligands. However, further studies are needed to identify the ancient GPCR system, which may include studies on the appearance of ligands or precursors.

Presentation: Saturday, June 17, 2023
THU214 Exploratory Study Of The Association Of Genetic Factors With Recovery Of Hypothalamic-Pituitary-Adrenal Axis In Cushing Disease
Authors: Nguyen Matthew H , Zhang Wei , Pankratz Nathan , Lane John , Chittiboina Prashant , Faucz Fabio R , Liu Aiyi , Mills James L , Stratakis Constantine A , Tatsi Christina
Published: October 2023

Disclosure: M.H. Nguyen: None. W. Zhang: None. N. Pankratz: None. J. Lane: None. P. Chittiboina: None. F.R. Faucz: None. A. Liu: None. J.L. Mills: None. C.A. Stratakis: None. C. Tatsi: None.

Successful treatment of endogenous Cushing syndrome (CS) is often followed by a period of adrenal insufficiency of variable duration. Recovery of the hypothalamic-pituitary-adrenal (HPA) axis may range from 6 months to more than 2 years. Previous studies have investigated potential clinical and biochemical factors involved in this process with variable results. We performed an exploratory study on genetic factors potentially involved in HPA axis recovery in patients with Cushing disease (CD). Ninety (90) patients with CD, who were treated with transsphenoidal surgery (TSS), had initial remission, and a follow up of at least 3 months postoperatively, were included in the study. Recovery of the HPA axis was defined as morning cortisol level or peak cortisol during a standard dose (250 mcg) IV corticotropin stimulation test of >18mcg/dL. Genetic data was obtained by whole exome sequencing (WES). Variants 1) in genes potentially involved in the HPA axis, 2) rare in the general population and 3) predicted as possibly or probably damaging in silico, were selected from WES. Statistical analysis was performed for each variant or for each gene (calculating all variants present in the same gene) using a Cox proportional hazard model. Correction for multiple comparisons was assessed with the false discovery rate (FDR) method.We identified 97 variants in 47 genes of interest that met the above criteria. Although five variants showed a trend toward association with shorter duration of postsurgical adrenal insufficiency (AI), no significant association was noted after correction for multiple comparisons. Furthermore, each variant was present in only one patient. At the gene-level, the BAG1 gene showed significant correlation with shorter postsurgical duration of AI (Hazard ratio: 28.7, 95% Confidence Interval: 5.4-151.1, FDR q-value=0.004), but both patients with a BAG1 variant later experienced recurrent disease, which could suggest an independent predictor of shorter recovery time. When we excluded patients with recurrence, no significant association was reported on the gene-level. In this exploratory study, we did not identify a significant genetic modifier of HPA recovery time. Other factors, clinical or surgical, may play a more important role in the recovery process or larger cohort studies may be required.

Presentation: Thursday, June 15, 2023
THU217 Vision-related Quality Of Life In Patients With Childhood-onset Craniopharyngioma - Results Of Hit-Endo And Kraniopharyngeom 2000/2007
Authors: Sowithayasakul Panjarat , Boekhoff Svenja , Beckhaus Julia , Friedrich Carsten , Muller Hermann Lothar
Published: October 2023

Disclosure: P. Sowithayasakul: None. S. Boekhoff: None. J. Beckhaus: None. C. Friedrich: None. H.L. Muller: None.

Quality of life (QoL) has become a critical component of therapeutic outcomes in the survivors of childhood-onset craniopharyngioma (CP). Visual deficiency adversely affects daily functioning and QoL in childhood CP. This cohort study aimed to report the vision-related QoL in CP patients. The primary outcome measure was pediatric QoL (PEDQOL score) in patients with and without visual impairment from presentation at the time of CP diagnosis to three-year follow-up. The risk factors associated with visual impairment were also analyzed. A total of 120 patients were included in this study, with a median age at diagnosis of 10 years (ranging from 1.3 to 16.8 years). The most common presenting symptoms at the time of CP diagnosis were headache (42%), visual impairment (20%), and growth retardation (12%). Visual impairment was found in 87 patients (70%). Ophthalmologic examination and PEDQOL scores, which were grouped into seven domains: physical functioning, cognition, social functioning friends, social functioning family, and body image, were evaluated at the third month, first-year, and third-year after diagnosis. Parents of children with visual impairment report worse social functioning in their families than parents of children without visual impairment, one (p=0.017) and three years (p=0.011) after diagnosis. After three years, children with visual impairment were found to have worse quality of life in the autonomy domain of self- (p=0.029) and parental assessment (p=0.048). High tumor volume (>21 cm³), radiation therapy and extrasellar tumor location were identified as potential risk factors for visual impairment. We conclude that visual impairment has a negative impact on QoL after CP. Early detection of visual impairment, regular QoL assessment, and risk-appropriate follow-up care are recommended.

Presentation: Thursday, June 15, 2023
FRI589 MicroRNAs In Maternal Plasma At 15 Weeks Gestation As Biomarkers For Later Preterm Birth: Evidence For Dysregulated Mirna Biogenesis And Implications For Pregnancy-related Endocrine Signaling Pathways
Authors: Ramzan Farha , Rong Jing , Roberts Claire , O'Sullivan Justin , Perry Jo Kate , Taylor Rennae , McCowan Lesley , Vickers Mark Hedley
Published: October 2023

Disclosure: F. Ramzan: None. J. Rong: None. C. Roberts: None. J. O'Sullivan: None. J.K. Perry: None. R. Taylor: None. L. McCowan: None. M.H. Vickers: None.

Introduction: Preterm birth (PTB) is a leading cause of morbidity and mortality in infants, with rates of PTB increasing globally over the last 20 years. MicroRNAs (miRNAs) have been reported to have widespread involvement in the development of and protection from many diseases, there is increasing interest in their potential role in the aetiology of a range of pregnancy-related disorders, including PTB. Objectives: To investigate differential miRNA abundances in mid-pregnancy plasma samples between mothers with term infants compared with moderate to late preterm infants (spontaneous PTB) and replication across independent cohorts. Method: The Auckland and Adelaide arms of the Screening for Pregnancy Endpoints (SCOPE) study were utilised. miRNAs in plasma at 15 weeks gestation from mothers of term and moderate to late preterm infants (n=54 per group) were quantified using the NanoString nCounter human v2 miRNA expression panel. Gene expression of key mediators of miRNA biogenesis, including Drosha, Dicer and Argonaut were quantified via RT-qPCR. In-silico analysis was performed to investigate the biological pathways associated with the dysregulated miRNAs. Results: Of the 800 miRNAs examined, the top four miRNAs identified were conserved across both cohorts and were significantly downregulated in the plasma of mothers who later experienced a PTB. The gene pathways associated with the top candidate miRNAs were linked to inflammatory processes, mitochondrial biogenesis, apoptosis and regulation of key pregnancy-related hormonal signaling pathways. Moreover, miRNAs were consistently downregulated in the PTB group concomitant with reduced gene expression of key miRNA biogenesis markers. Conclusions: We identified miRNAs in maternal plasma in mid-pregnancy that were highly predictive of later spontaneous PTB and, importantly, were conserved across two independent cohorts. Moreover, in addition to identifying potential early biomarkers for subsequent PTB, we provide evidence for persistent downregulation of miRNAs in those mothers who later delivered preterm, which is likely to have widespread effects on endocrine signaling pathways during pregnancy.

Presentation: Friday, June 16, 2023
FRI591 Association Of TSH Levels And NAFLD Severity In Children And Adolescents
Authors: Untalan Matthew , Crimmins Nancy Abigail , Mencin Ali , Yates Katherine , Stavra Xanthakos , Thaker Vidhu
Published: October 2023

Disclosure: M. Untalan: None. N.A. Crimmins: None. A. Mencin: None. K. Yates: None. X. Stavra: None. V. Thaker: None.

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation and is now the most common form of chronic liver disease in children and adolescents. Recent studies have indicated an association between subclinical hypothyroidism (SH) and NAFLD. An underactive thyroid gland produces insufficient T3 and T4 involved in hepatic fat metabolism that could contribute to NAFLD. While increased TSH has been documented in individuals with NAFLD, its independent role with NAFLD disease severity is yet to be clarified. Objective: To study the relationship of TSH levels and the severity of NAFLD/NASH, as well as determine whether changes in TSH levels are associated with changes in NAFLD/NASH among children. Methods: This retrospective study used data from two cohorts within the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). TSH, free and total T4, total T3, TPO antibodies and thyroglobulin (TBG) levels were assessed in samples obtained first at baseline and then at 52-96 weeks. Individuals with overt hypothyroidism, abnormal TPO antibody levels, and those receiving thyroid treatment were excluded from analysis. SH was defined as TSH > 4.4 mIU/L. Linear and multinomial regression models were used to identify the association between TSH, SH and NAFLD severity measured by NAFLD activity score (NAS), fibrosis stage, steatosis level, lobular and portal inflammation and ballooning while adjusting for potential confounders (sex, age, race, BMI-z, HOMA-IR and non-HDL levels). Longitudinal analysis was conducted by mixed-effects model. Analyses were performed with SAS and R statistical software. Results: 218 individuals and 421 observations were included in the cross-sectional and longitudinal analyses, respectively. Children with more severe grades of steatosis were more likely to be younger (p = 0.03) and male (p = 0.02). At baseline, TSH was not significantly associated with any NAFLD histological measures. Longitudinal analyses revealed a positive association of change in TSH and steatosis level after adjusting for covariates, and follow-up time (p = 0.03). Change in SH was associated with change in fibrosis stage (p = 0.01). Adding HOMA-IR and non-HDL levels to the models did not change this relationship. The positive relationship of total T3 and T4 with NAS was explained by TBG. Conclusion: In a large cohort of pediatric patients with biopsy-confirmed NAFLD, high TSH levels correlated with increasing steatosis grade and NAS, and SH with increased liver fibrosis. Markers of impaired thyroid function may help predict disease severity in pediatric patients with NAFLD.

Presentation: Friday, June 16, 2023
THU620 Metastatic Adrenocortical Carcinoma Arising From A Testicular Rest Tumor
Authors: Chozet Luis Edmundo , Bruder Jan M , Flores Raina , Hackman Sarah , Highes Kenneth , Vasquez Libia , Le Guillaume , Cortez Tiffany , Escobar Vasco Maria Adelaida
Published: October 2023

Disclosure: L.E. Chozet: None. J.M. Bruder: None. R. Flores: None. S. Hackman: None. K. highes: None. L. Vasquez: None. G. Le: None. T. cortez: None. M.A. Escobar Vasco: None.

Background: Congenital adrenal hyperplasia (CAH) involves a range of autosomal recessive disorders characterized by abnormalities in the adrenal biosynthesis pathway. Testicular adrenal rest tumors (TARTs) are a complication mostly seen in male patients with congenital adrenal hyperplasia which can lead to infertility. These tumors are known to have benign characteristics. We present a unique case of a male patient with CAH diagnosed with metastatic adrenocortical carcinoma arising from a TART. Clinical Case: A 40-year-old man with poorly controlled congenital adrenal hyperplasia from 21-hydroxylase deficiency and bilateral testicular adrenal rest tumors presented with syncope and worsening left testicular pain for 2 months. Scrotal ultrasound showed enlarged bilateral scrotal masses (left bigger than right). Initial evaluation for his syncopal event included CTA chest which showed an incidental finding of innumerable bilateral solid pulmonary nodules. 17-hydroxyprogesterone levels were elevated at 5273 ng/dL (normal less than 138 ng/dL). Additional biochemical workup of the testicular mass was unremarkable. The patient underwent left radical orchiectomy with pathology showing high-grade carcinoma with adrenocortical differentiation. A right upper lobe lung biopsy was done which demonstrated metastatic carcinoma with adrenocortical differentiation, morphologically similar to the testicular tumor. The initial patient presentation of progressively worsening left testicular pain in the setting of testicular adrenal rest tumors (TARTs) led to the diagnosis of adrenal carcinoma. Conclusion: This case presents a unique presentation of adrenal carcinoma in a patient with congenital adrenal hyperplasia arising in the setting of testicular adrenal rest tumors (TARTs). This case demonstrates a unique presentation of adrenal carcinoma, as malignant degeneration has not been described in patients with TARTs. It also highlights the importance of close monitoring even if these tumors are thought to be of benign origin.

Presentation: Thursday, June 15, 2023
FRI596 Randomized Clinical Trial Of Theophylline For Treatment Of Pseudohypoparathyroidism Type 1a
Authors: Shoemaker Ashley Hall , Tamaroff Jaclyn , Jueppner Harald
Published: October 2023

Disclosure: A.H. Shoemaker: None. J. Tamaroff: None. H. Jueppner: None.

Background: Pseudohypoparathyroidism type 1A (PHP1A) is a rare, genetic disorder caused by heterozygous inactivating mutations involving the maternal GNAS allele, the gene that encodes the stimulatory G protein (Gsα). Due to tissue specific reduced paternal Gsα expression, several tissues, particularly proximal renal tubules and thyroid, show decreased Gsα-coupled receptor function. Resultant hormone resistances can be treated, but other aspects of PHP1A such as early-onset obesity and short stature are without effective treatment options. Gsα-coupled receptor signaling cascade begins with agonist-stimulated increase in cAMP, the second messenger which is rapidly degraded by phosphodiesterase (PDE). Given that PHP1A patients have reduced, but not completely absent, cAMP production, this clinical trial will test the hypothesis that the non-selective PDE inhibitor theophylline will improve Gsα-coupled receptor signaling. We describe the study design and baseline characteristics of PHP1A patients enrolled in a double-blind, randomized, placebo-controlled clinical trial of theophylline. Methods: A single center will enroll 34 patients. Inclusion criteria: age >=2 years old, diagnosis of PHP1A and obesity. Exclusion criteria include seizure disorder, uncontrolled hormone resistance, pregnancy, and other significant medical problems. Enrollment starts with the oldest age group (>=13 years) and safety/efficacy is reviewed by the DSMB after each block of 6 patients before opening to the next age block (7-12 and 2-6 years). Patients are randomized to theophylline vs. placebo using a permuted-block randomization (2:1) stratified by age and gender. Theophylline levels guide dosing with a goal level of 10-19 mcg/mL. Unblinded study staff review theophylline levels and the dosing protocol includes sham placebo dose adjustments. The primary outcome is change in BMI, expressed as % of the 95th %ile (BMI95), to account for age and gender. Secondary endpoints include changes in glucose tolerance and insulin secretion (insulinogenic index), rate of epiphyseal closure and hormone replacement doses. Results: To date we have screened 27 and enrolled 24 patients. Enrollment in the youngest age block (2-6 years) opened in December 2022. Enrolled patients range from 4 to 55 years old (mean 16.0 ± 10.4 years, 18 pediatric patients), 92% are female, 100% are white and 13% are Hispanic. All patients were obese with a mean BMI95 130.8 ± 23.8%. Three adult patients withdrew due to headaches, nausea/difficulty swallowing pills or travel difficulties. The most common adverse event related to study drug was transient nausea/vomiting. Conclusion: This randomized clinical trial designed to test safety and efficacy of theophylline for PHP1A is ongoing. Thus far the study drug and procedures have been safe and well tolerated.

Presentation: Friday, June 16, 2023
THU624 Opioid Induced Adrenal Insufficiency (OIAI) Presenting With Altered Mental Status
Authors: Bondarenko Darya , Ahmad Mobeen , McGrath Glenn Alan
Published: October 2023

Disclosure: D. Bondarenko: None. M. Ahmad: None. G.A. McGrath: None.

Background: Opioid suppression of the hypothalamic-pituitary-adrenal (HPA) axis via inhibition of corticotropin releasing hormone secretion leading to secondary adrenal insufficiency (AI) has been described in literature. Biochemical secondary AI is evident in 6-50% of patients on chronic opioids; fewer cases are reported presenting with clinical AI.1 We present a rare case of symptomatic opioid-induced AI (OIAI) with clinical improvement on initiation of hydrocortisone. Clinical Case: A 49-year-old female on daily buprenorphine (20 mg) and naltrexone (5 mg) presented to the hospital with syncope and hypotension (79/49 mmHg). AM cortisol was 6.2 mcg/dL, a cosyntropin stimulation test was performed, but there was technical difficulty with the results. She was started on midodrine 2.5 mg three times daily and referred to outpatient endocrinology for follow up. Weeks later, outpatient cosyntropin stimulation test showed baseline cortisol of 18 mcg/dL with increase to 26 mcg/dL. Simultaneous adrenocorticotrophic hormone (ACTH) was 16.9 pg/mL. AI was ruled out. Seven years later she presented with acute lethargy, confusion, and memory loss over several days. AM cortisol was 1.6 mcg/dL and cosyntropin stimulation test increased cortisol to 15.1 mcg/dL (normal response being 18 mcg/dL or greater). ACTH was 24 pg/mL. The abnormal cosyntropin stimulation test results are consistent with AI, and lack of elevation of morning ACTH is consistent with secondary AI.2 Hydrocortisone therapy was started and midodrine was held due to elevated blood pressure after initiation of steroids. She was discharged on hydrocortisone 15 mg each morning and 5 mg each afternoon. Within 10 days of initiation of glucocorticoid replacement therapy her neurologic symptoms improved and midodrine discontinued. Prescription Drug Monitoring Program (PDMP) review shows reduction of buprenorphine (16 mg) and naltrexone (4 mg). Conclusion: Data on management of OIAI and recovery of the HPA axis with or without cessation of opioid therapy is limited. This case highlights that opioids should be considered as a potential cause of secondary AI. Further follow-up of this case and other OIAI cases would provide insight into management of opioid therapy, continuation of glucocorticoid therapy, and recovery of HPA axis. This data could provide basis for OIAI management recommendations. Reference: (1) Fountas, A., Prof, S.V.U., Karavitaki, N. Opioid-induced endocrinopathies. Lancet Diabetes Endocrinol. 2020;8(1);68-80. (2) Bornstein, S.R., Allolio, B., Arlt, W., et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocr. 2016;101(2);364-389.

Presentation: Thursday, June 15, 2023
FRI428 VTE And Testosterone Therapy: What Is The Risk?
Authors: Cheatham Callie , Colburn Jeffrey , Kemm Matthew
Published: October 2023

Disclosure: C. Cheatham: None. J. Colburn: None. M. Kemm: None.

Testosterone replacement therapy (TRT) to treat hypogonadism from a variety of underlying etiologies remains increasingly prevalent within the United States. While VTE is a known potential risk, the prevalence, underlying mechanism, and associated risk factors remain incompletely understood. Men initiating TRT for hypogonadism often do not receive adequate pre-treatment evaluation or have therapy initiated despite normal testosterone levels. While a 2021 meta-analysis 1 did not demonstrate significantly increased VTE risk associated with TRT, the wide confidence interval, reported low quality of evidence, and lack of studies examining VTE as a primary outcome with data obtained via adverse event reporting demonstrates the importance of further investigation.

Case 1: 55-year-old male with unilateral orchiectomy and associated primary hypogonadism started on TRT 10years prior presented to the hospital with acute onset chest pain and shortness of breath. CT angiography demonstrated right lower lobe segmental pulmonary emboli with parenchymal infarction. At the time of presentation, he was on IM testosterone cypionate 200mg weekly and anastrozole with total testosterone970 ng/dL, free testosterone 298 pg/mL, undetectable estradiol, and hematocrit 41.5%. His testosterone and anastrozole were discontinued at discharge, and he had a negative hypercoagulability workup by a hematologist.

Case 2: 61-year-old male with history of OSA, obesity, and TRT initiated 8 months prior for erectile dysfunction presented to the hospital with dyspnea. CT angiography demonstrated large bilateral pulmonary artery emboli with right heart strain consistent with submassive PE. Review of clinical records preceding TRT initiation indicate normal testosterone values of 533 ng/dL with free testosterone 60.6 pg/dL. At the timeof presentation, his total testosterone was 685 ng/dL, free testosterone 139 pg/mL, and hematocrit of 54%with history of polycythemia since TRT initiation and no documented intervention. He was treated withIR thrombectomy and anticoagulation, and TRT was discontinued at discharge. His hematocrit normalized at follow-up and, after negative hypercoagulability evaluation by a hematologist, TRT was felt to be the most likely etiology of his VTE.

These reported cases of VTE in men of different ages, underlying pathology, testosterone levels at time of event, presence of polycythemia, and time since testosterone initiation highlights the importance of further investigation on the true risk of thrombotic events in TRT patients and necessity of increased patient counseling of potential adverse outcomes.

1. Ayele HT, Brunetti VC, Renoux C, Tagalakis V, Filion KB. Testosterone replacement therapy and the risk of venous thromboembolism: A systematic review and meta-analysis of randomized controlled trials. Thromb Res. 2021;199:123-131. doi:10.1016/j.thromres.2020.12.029

Presentation: Friday, June 16, 2023
SAT351 Utilization of Emergency Services by Transgender People in the United States, 2006-2018
Authors: Stroumsa Daphna , Marsh Erica Elizabeth , Pfeiffer Paul N , Jiang Charley , Vrolijk Aaron , Moravek Molly Bennette
Published: October 2023

Disclosure: D. Stroumsa: None. E.E. Marsh: None. P.N. Pfeiffer: None. C. Jiang: None. A. Vrolijk: None. M.B. Moravek: None.

Bridging the Gap: Utilization of Emergency Services by Transgender People in the United States, 2006-2018Introduction: Transgender or nonbinary (Trans) people face significant health disparities, including in access to primary and preventive care. These disparities are driven by structural, interpersonal, and individual stigma, which lead to barriers accessing care and avoidance of primary care, and to increased reliance on emergency care. We aimed to characterize ED use by Trans patients, and changes in such use over time. Methods: Data was obtained from the Nationwide Emergency Department Sample (NEDS) , which is a weighted stratified sample of hospital-based ED visits. Using gender-dysphoria related ICD-9 and ICD-10 diagnostic codes, we compared visits among trans people to those without such a diagnosis, adjusting for age, region, urbanicity, primary payer, and income quartile. We evaluated rates of chronic condition and mental health conditions as primary diagnosis at presentation and at admission. Presence of chronic conditions was assessed using the ICD-9 Chronic Condition Indicator for 2006-2014. Results: There was a rapid temporal increase in the proportion of visits with a trans-related diagnosis, from 0.001% of visits in 2006 to 0.016% in 2018. There were significant demographic differences between trans people and others. Trans people were significantly more likely to be admitted, adjusting for payment, age group, region, income and mental health condition (overall 52.4% vs. 17.3%, adjusted OR= 7.368 95% CI (6.771, 8.017)). A large proportion of ED visits by trans individuals was associated with a mental health diagnosis (28.7%, compared with 3.9% for others, p<0.001; adjusted OR =2.01, 95% CI 1.91-2.11) and/or with a chronic condition (58.2% vs. 19.2%, p<0.001; adjusted OR =3.65, 95% CI 3.61-3.69). Similarly, hospital admission among trans people was much more likely to be linked to a mental health condition (37.2% vs. 5.3% , p<0.001; adjusted OR = 2.78, 95% CI 2.44-3.16) or chronic condition (67.3% vs 41.3%, p<0.001; adjusted OR = 2.21, 95% CI 1.78-2.75) Discussion: The high admission rates, and high proportion of trans people with a chronic condition or with mental illness, may represent worse overall health due lack of primary care, or a delay in seeking emergency care among Trans people. Lastly, these findings could be a manifestation of a higher likelihood of a trans-related diagnostic code being charted among trans people at admission, or bias towards higher likelihood of trans people receiving a mental-health related diagnosis. There is a need for increasing access to affirming primary and mental health care among trans people, and increased training of emergency clinicians.

Presentation Date: Saturday, June 17, 2023