bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI453 Genetic Heterogeneity of Hypothalamic Hypogonadism DIsorders
Authors: Bheeman Chandni , Astapova Olga 
Published: October 2023

Abstract
Disclosure: C. Bheeman: None. O. Astapova: None.
Title: Genetic Heterogeneity of Hypothalamic Hypogonadism disorders. Introduction: Hypothalamic hypogonadism (HH) can be defined as having inappropriately low serum concentrations of gonadotropins in the presence of low circulating concentrations of sex steroids. It represents a group of genetically and clinically heterogeneous disorders. Case A 32-year-old female who presented to the endocrine clinic for evaluation of infertility. Patient had menarche at age 12 but became amenorrhoeic at age 14. Her physical exam was notable for normal female secondary sexual characteristics and intact sense of smell. She had no history of bone fracture or menopausal symptoms. The patient had failed the progesterone withdrawal test twice, but had withdrawal bleeding with the birth control pill or with hormonal replacement therapy. She had failed ovulation induction with clomiphene citrate, but was able to conceive 3 pregnancies through in vitro fertilization. Patient’s labs off of hormonal replacement and birth control were: LH &lt;0.3. FSH 0.6, Estradiol &lt;5, Progesterone 0.4. Her prolactin level was within normal limits at 6.6 and her TSH was 1.08. MRI of the brain showed no abnormalities in the pituitary gland. Genetic testing showed that the patient was heterozygous for a duplication mutation in the ANOS1 gene. Conclusion The genotypic and phenotypic heterogeneity that can be seen in HH disorders is due to the numerous genes involved in hypothalamic hypogonadism and their intricate interactions. Mutations contributing to HH can be involved in either the neurodevelopmental or neuroendocrine pathways of the hypothalamic pituitary gonadal axis or in both. There are mutations that can be inactivating variants while some can play the role of the modifier genes. The later may be able to explain the incomplete penetrance and variable expressivity sometimes seen in HH. It is important to note that though &gt; 60 genes have been implicated in HH 50% of the cases remain genetically undiagnosed. This case is particularly interesting as this patient is a female with a heterozygous mutation on the ANOS1 gene, the primary gene associated with Kallmann syndrome. Kallmann syndrome is a X-linked recessive disorder and therefore the patient having phenotypical expression of the mutation is unexpected. Through the presentation of this case we aim to explore different modes of genetic expression and the different mechanisms that could have led to this patient hypothalamic hypogonadism.
Presentation Date: Friday, June 16, 2023
FRI170 Ultrasound-Based Evaluation Of Muscles And Tendons In Patients With Cushing Syndrome
Authors: Bolayir Basak , Gogus Feride , Demir Beril , Yalcin Mehmet Muhittin , Meray Jale , Altinova Alev , Toruner Fusun Saadet , Akturk Mujde Yasim 
Published: October 2023

Abstract
Disclosure: B. Bolayir: None. F. Gogus: None. B. Demir: None. M.M. Yalcin: None. J. Meray: None. A. Altinova: None. F.S. Toruner: None. M.Y. Akturk: None.
Background: Myopathy, being induced by antianabolic and catabolic effects of excess corticosteroids is one of the characteristic features of Cushing Syndrome (CS). Muscle thickness which has been shown to be correlated with muscle cross sectional area can be used as an indicator of muscle mass. Although many studies have demonstrated effects of corticosteroids on collagen metabolism and case reports documented rupture of tendons in patients with chronic exposure to corticosteroids, tendon changes of patients with endogenous hypercortisolism have not been studied. Ultrasound, although not studied well in this group of patients, can be an alternative imaging method that provides information about muscle and tendon thickness. The aim of this study was to investigate muscle, tendon thicknesses and serum levels of myostatin in patients with CS. Methods: Twenty-two patients with CS and nineteen healthy control subjects similar for age, sex, height and weight were enrolled. Lower extremity tendon and muscle groups’ thickness were evaluated by ultrasound. Serum myostatin levels were measured by ELISA. Results: Age, height, weight and body mass index were similar between groups (p&gt;0.05). The thicknesses of rectus femoris, vastus medialis, vastus lateralis, gastrocnemius medialis and gastrocnemius lateralis were lower in the CS group than control group (p≤0.001). However, thickness of soleus muscle was not significantly different between the groups (p &gt; 0.05). No significant difference was revealed between groups in terms of Achilles and patellar tendon thickness (p&gt;0.05). Median serum myostatin levels were found to be lower in the CS group than the control group (p&lt;0.001).Conclusions: Ultrasound based measurement of muscle thickness can be used to assess and monitor steroid-induced changes of muscle mass. The fact that the thickness of the proximal muscles of lower extremity was found to be lower by ultrasound in patients with CS in our study supports the proximal myopathy feature of CS. Besides that, it was shown that the gastrocnemius lateralis and medialis thicknesses, which are the distal muscles of the lower extremity, were also shown to be lower in the Cushing group. On the other hand, CS might not affect the thickness of the lower extremity tendons. Moreover, the mechanism of the decrease in the level of myostatin, the negative regulator of muscle growth, in patients with needs to be elucidated with CS further studies.
Presentation: Friday, June 16, 2023
SAT353 Relevance of Ovarian Morphology Among Adolescents With Polycystic Ovary Syndrome (PCOS)
Authors: Christ Jacob P , Shinkai Kanade , Corley Jamie , Pasch Lauri , Cedars Marcelle Ivonne , Huddleston Heather 
Published: October 2023

Abstract
Disclosure: J.P. Christ: None. K. Shinkai: None. J. Corley: None. L. Pasch: None. M.I. Cedars: None. H. Huddleston: None.
Background: The 2018 international guidelines for the assessment and management of PCOS exclude ovarian morphology from the diagnosis of PCOS in adolescents due to limited data regarding normative values in this population. Adolescents with oligo-amenorrhea (OA) or hyperandrogenism (HA) alone are thus excluded from diagnosis and ultrasonography has been removed from clinical use without an assessment of its utility in this population. Objective: To characterize ovarian morphology among adolescents with PCOS and evaluate the relevance of PCOM among those currently excluded from diagnosis. Methods: A cross-sectional analysis of patients that underwent a standardized evaluation for PCOS at a single tertiary center from 2006 to 2022 was completed. Participants were included if they were within 8 years of menarche or were &lt;20 years of age at screening and had data on ovarian morphology. Follicle number per ovary (FNPO) and ovarian volume (OV) were assessed by transvaginal ultrasound, or if not tolerated, transabdominal (in which case FNPO was omitted) or transrectal approach. PCOM was defined as a FNPO of &gt;20 follicles or an OV &gt;10cc in either ovary. Maximum FNPO and OV in either ovary was used for analyses. Age based criteria were used to define irregular menstrual cycles and were characterized among those &gt;1 year post menarche. Patients were grouped into those with OA and HA (PCOS-NIH), with OA or HA as well as PCOM (PCOS-Rotterdam), and with one or no features (non-PCOS). Results: Of the 133 subjects included, 95 met PCOS-NIH criteria, 22 met PCOS-Rotterdam criteria and 16 met non-PCOS criteria. Prevalence of PCOM among PCOS-NIH was 82.1%. Significant differences were seen between Non-PCOS, PCOS-Rotterdam, and PCOS-NIH for FNPO (15.5±8.7 vs 30.9±12.5 vs 31.8±14.6), OV (6.1±4 vs 10.8±4.5 vs 11.4±6.4), waist:hip ratio (WHR) (0.7±0.1 vs 0.8±0.1 vs 0.8±0.1), 2-hour glucose (99.5±17.1 vs 84.8±18.9 vs 105.6±41 uIU/mL), QUICKI (0.4±0 vs 0.4±0.1 vs 0.3±0.1), and HOMA-IR (1.9±1.2 vs 2.4±2.1 vs 4.7±5.7) (p&lt;0.05 for overall comparisons between groups). Among PCOS-Rotterdam and Non-PCOS, in multivariable models controlling for WHR, systolic blood pressure (β=0.5, p=0.09) and free testosterone (β=0.03, p=0.03) associated with FNPO and QUICKI (β=69.1, p=0.003) associated with OV. Conclusion: Adolescents meeting NIH criteria appear to be at greatest metabolic risk. Ovarian morphology, however, may reflect degree of hyperandrogenism and metabolic dysfunction among adolescents currently excluded from diagnosis of PCOS (i.e. PCOS-Rotterdam and non-PCOS groups). The inclusion of ultrasound assessment may thus be able to aid in risk stratification and phenotyping among those without a definitive PCOS diagnosis.
Presentation Date: Saturday, June 17, 2023
SAT362 Low-dose DHT’s Effects On Gluconeogenesis And Energy Metabolism Are Ameliorated By Central Nervous System Knockout Of The Androgen Receptor
Authors: Ubba Vaibhave , Joseph Serene , Akbar Razeen , Dsilva Milan , Wu Sheng 
Published: October 2023

Abstract
Disclosure: V. Ubba: None. S. joseph: None. R. Akbar: None. M. Dsilva: None. S. Wu: None.
Polycystic ovarian syndrome (PCOS) is a leading cause of infertility in women of reproductive age. Mostly, the level of androgens are deviated from their physiological values in females, resulting in hyperandrogenemia. Androgen manifests its function in the cells via the Androgen Receptor (AR), making it a prime factor for studying PCOS pathophysiology. We generated central nervous system (CNS) specific AR knockout mouse (SynARKO), using synapsin promoter driven cre, to examine its role under normal and hyperandrogenemic conditions in female mice. Assessment of reproductive parameters under physiological levels of androgens, revealed no differences in the cyclicity and fertility of SynARKO mice when compared to Control (Con-veh) mice. These parameters were altered under hyperandrogenemia (induced using DHT) in Control mice (Con-DHT) mice and were not rescued in the SynARKO- DHT mice, suggesting CNS AR is dispensable to reproductive features in females. Evaluation of metabolic functions by Glucose tolerance test, we observed alleviated glucose intolerance in SynARKO-DHT (4 months). Energy expenditure and food intake were increased in Con-DHT mice compared to Con-veh, while showing no further differences in SynARKO-DHT mice compared to SynARKO-veh. At the molecular level, DHT treatment showed increased phosphorylated Akt in hypothalamus of control mice. Interestingly, it was restored in synARKO upon DHT treatment. Further, the inflammation marker, phosphorylated NF-kB p-65, was increased in the hypothalamus of Con-DHT mice. Additionally, IBA, a marker of macrophage activation was also increased upon DHT treatment in control mice. Taken together, our results suggest that while the reproductive functions are not mediated by the CNS AR, metabolic effects caused by hyperandrogenemia, is regulated by the central nervous system AR.
Presentation Date: Saturday, June 17, 2023
SAT485 Knockout Of TLR4 Alters Reproductive And Metabolic Outcomes In Mouse Model Of Polycystic Ovary Syndrome
Authors: Dominique Wiggins Kiara , De Robles Gabriela , De La Torre Jamie-Jean , Nicholas Dequina 
Published: October 2023

Abstract
Disclosure: K.D. Wiggins: None. G. De Robles: None. J. De La Torre: None. D. Nicholas: None.
Title: Knockout of TLR4 Alters Reproductive and Metabolic Outcomes in Mouse Model of Polycystic Ovary Syndrome. Polycystic Ovarian Syndrome (PCOS) is a heterogeneous endocrine disorder often characterized by reproductive and metabolic dysfunction. Prior literature has found a correlation between PCOS and chronic low-grade inflammation. However, it remains unknown if inflammation plays a causal role in the pathology of PCOS. In women with PCOS, serum levels of Lipopolysaccharides (LPS), a ligand for Toll-like receptor 4 (TLR4), are elevated. The binding of LPS to TLR4 leads to the production of pro-inflammatory cytokines, which can result in low-grade inflammation and metabolic syndrome, a prominent feature of PCOS. Given the role of TLR4, we hypothesize that the induced inflammatory environment mediates the development and pathogenesis of PCOS. To test this hypothesis, we subcutaneously implanted a nonsteroidal aromatase inhibitor, Letrozole, in TLR4 knockout mice (TLR4KO) and C57BL/6J (wild type) mice. Following five weeks of letrozole treatment, wild type mice failed to cycle, whereas TLR4KO mice were able to enter each estrous cycle phase. Furthermore, in contrast to wild type mice, TLR4KO mice display normalized Luteinizing Hormone (LH) levels with increased levels of Follicle Stimulating Hormone (FSH). We also characterized how inflammation influences the metabolic phenotypes of PCOS. Our results reveal that the deletion of TLR4 reduces weight gain and improves glucose intolerance. Moreover, we show that the development of insulin resistance in letrozole-treated TLR4KO mice was independent of other metabolic outcomes. Our study demonstrates that disruption of this pro-inflammatory pathway mediates the development of reproductive and metabolic phenotypes. Thus, research on the modulation of chronic low-grade inflammation may lead to the development of new therapeutics for PCOS patients.
Keywords: Reproduction, Inflammation, Polycystic Ovary Syndrome,
Presentation Date: Saturday, June 17, 2023
THU578 Concept: Role Of Spiral Steroids (SS) During Pregnancy
Authors: Chasalow Fred I 
Published: October 2023

Abstract
Disclosure: F.I. Chasalow: None.
Background: Earlier, my laboratory reported 3 novel endogenous steroids (SS) that cross react with digoxin-specific antibodies (DLM). The SS are readily distinguished from all other steroids by 3 characteristics: [1] each is a phosphocholine diester, [2] each has more than 21 carbon atoms in the steroid fragment and [3] the extra carbons form an E-ring with a cyclic lactone. The discovery included a biosynthetic scheme with known enzymes and no need for a ‘magic’ step. Function: NaK-ATPase has 3 subunits, designated FXYD, α, and β. Affinity for Na+ and K+ ions is regulated by FXYD proteins. Each SS matches a tissue-specific α-subunit. Each α-subunit has 2 different binding sites for steroids. One site binds a SS; the ligand of the other site is unknown. For example, Ionotropin is specific for the α subunit present in cardiac and renal tissue. Kaleotropin is isolated from gonads, but the α subunit which matches each specific ovarian cell type is unknown. Galotropin (G-trop): One of the SS, G-trop, was detected as a DLM in human breast cyst fluids, specifically cysts with high K+ ion levels. Solubility properties distinguished it from previously known cardiac glycosides and, like other DLM, it inhibited NaK-ATPase. G-trop was also detected in milk from cows, sheep and goats. Ions derived from Ionotropin (m/z=341 Da) or Kaleotropin (m/z=369 Da) were not present in milk extracts. On LC-MS, G-trop fragmented to an ion at m/z= 381 Da. Trial and error analysis suggests C25O4H34. No other formula is consistent with m/z=381 Da. G-trop: G-trop wasn’t present in serum from children. At 22-26 weeks of gestation, whether or not a pregnant woman had pre-eclampsia, serum had low levels of G-trop. Maternal G-trop increases during the 3rd trimester, coincidentally with initiation of milk production; simultaneously, K+ ion levels in milk increased. Pre-eclampsia. In a pilot study, 65% of patients (n=20) with pre-eclampsia had elevated levels of Ionotropin precursor and 30% had elevated levels of Kaleotropin precursor. 25% of patients with pre-eclampsia develop life-threatening hypertension or seizures, typical of the expected response to elevated Ionotropin levels. Therapy includes immediate delivery of the infant at 30-36 weeks of gestation. Maternal G-trop synthesis has not yet begun and mother’s milk has low K+ ion levels. Elevated maternal Kaleotropin is not the cause of maternal hypertension, suggesting a specific gestational maternal α-subunit is its target. Kaleotropin from placenta may be the signal to respond to maternal hypokalemia. Necrotizing enterocolitis (NEC):In utero the fetus does not absorb K+ from the GI tract because fetal need for K+ ion is provided via the placenta. Concept: After premature delivery, without G-trop in milk, the infant can’t absorb K+ from the GI tract; the GI tract fails to grow and tight junctions do not form. As a result, infants are at high risk for developing NEC.
Presentation Date: Thursday, June 15, 2023
FRI159 Syndrome of Apparent Mineralocorticoid Excess (AME) from Licorice Tea
Authors: Clark Lambert Peter 
Published: October 2023

Abstract
Disclosure: P.C. Lambert: None.
We report a patient who had Syndrome of Apparent Mineralocorticoid Excess (AME) from licorice tea. Pt is a 65 y/o man with past medical history of HLD, HTN who presented to clinic for routine follow up. BMP was normal. Six months later patient reported diarrhea, bloating and gas after visiting family. To alleviate symptoms, he tried apple cider vinegar, herbal teas and stopped coffee and caffeinated drinks. His BP was 162/92. BMP showed Na 145, K 3.1, CO 37 and 20 meq of potassium daily was started. Follow up in 5/2020 found persistent elevated BP of 160/102 with elevated BP on home monitor and leg edema. Lisinopril-HCTZ was changed to amlodipine 5 mg. BMP showed Na 146, K 2.2, CO 44. Potassium was increased to 40 meq bid. Two weeks later BP was 160/90. Amlodipine was increased to 10 mg daily. He reported resolution of his edema. BMP showed Na 131, K 3.1, CO 33. At this point, the renin/aldosterone axis was tested with aldosterone &lt;1.0 ng/dL and PRA &lt;0.167 ng/mL/hr. On subsequent discussion it was found pt was taking black licorice tea. After cessation, pt’s BP improved and pt was gradually titrated off potassium supplements and blood pressure meds entirely. Repeat lab testing on 6/2020 found aldosterone 2.4 ng/dL, PRA 0.455 ng/mL/hr, Na 142, K 4.8, CO 31. On return to clinic on 8/2020 BP was 124/72 off medication. His labs were Na 143, K 4.1, CO 30. Syndrome of Apparent Mineralocorticoid Excess (AME) is caused by a deficiency in the 11-beta-hydroxysteroid dehydrogenase enzyme type 2 isoform (11-beta-HSD2). The enzyme converts cortisol to cortisone which cannot bind to the mineralocorticoid receptor. Deficiency of this enzyme will lead to more cortisol binding to the mineralocorticoid receptor which binds just as avidly as aldosterone. This leads to increased mineralocorticoid activity without increased aldosterone. Causes of AME can be genetic or induced by the steroid glycyrrhetinic acid, in licorice, that inhibits 11-beta-HSD2. Licorice candy in the USA generally does not have licorice root. It can be found in many sources including chewing tobacco and flavored chewing gum besides tea. Pt can take as low as 50 g daily of confectionery licorice for two weeks to produce elevated blood pressure. Patients will present with hypokalemia hypertension, metabolic alkalosis, low plasma renin activity and low plasma aldosterone levels. Urinary free cortisone and cortisol levels can assist with diagnosis but as in this case review of history was enough to diagnose and treat the patient.
Presentation Date: Friday, June 16, 2023
FRI444 Testosterone Therapy in Men with Classical vs Functional Hypogonadism: Results from a Controlled 9-year, Real-world Registry Study
Authors: Zitzmann Michael 
Published: October 2023

Abstract
Disclosure: M. Zitzmann: None.
Background and Significance: Long-term data on Testosterone therapy (TTh) in hypogonadal men are limited and the clinical value, especially in men with functional hypogonadism (FH) is debated. A long-term, real-world registry study comprising groups of patients with hypogonadism of various etiologies provides a suitable and novel approach to this clinical issue. Methods: A registry spanning 9 years comprising 650 patients with hypogonadism included 188 patients with FH (mean age 42.3±11.3 years) and 462 men with classical hypogonadism (CH). Of these, 266 men had primary hypogonadism (PH, mean age 34.0±11.7 years) and 196 secondary hypogonadism (SH, mean age 31.9±12.0 years). All men uniformly received intramuscular T undecanoate (1000 mg). Effects of TTh on anthropometric parameters, as well as metabolic and safety parameters were compared. Results: The registry contained metabolic and safety parameters in individual duration of TTh spanning 1 to 9 years. Serum T concentrations increased from 6.6±2.4 nmol/L to 19.3±2.9 nmol/L in all patients (duration-of-treatment-dependent averages, mixed linear model for repeated measurements with the fixed variable “time x visit interaction”: p&lt;0.001). In both categories of hypogonadism, TTh was associated with significant weight loss and decrease in waist circumference (WC, both p&lt;0.001). Cox regression and Kaplan-Meier models revealed differences of inter-individual check-points: men with FH were more likely to lose &gt;10% weight and &gt;5% of WC than men with CH (hazard ratio 1.3 [1.1-1.4], p=0.008 and hazard ratio 1.4 [1.3-1.5], p=0.001). There was no difference between groups for the overall marked increase in hematocrit. Changes in PSA levels were more likely to occur in FH (hazard ratio 1.3 [1.1-1.6], p=0.003). During TTh, patients with FH exhibited significantly more pronounced changes of favourable nature in metabolic parameters than patients with CH (total cholesterol, triglycerides, LDL- and HDL-cholesterol and fasting glucose). The same applied to scores of AMS and IIEF-EF questionnaires. Effects on most parameters, especially hematocrit, were significantly modulated by age and baseline values for weight, WC und T. Conclusions: Findings regarding effects and safety of TTh in different groups of hypogonadal men are provided. Effects on factors associated with cardiovascular health are modulated by diagnosis and age. Patients with FH seem to benefit to a larger extent from TTh, most likely attributable to their more pronounced risk factor profile at baseline.
Presentation Date: Friday, June 16, 2023