bluuebunny/crossref_metadata_2025_split huggingface dataset:
7850 Developmental ZNHIT3 expression in mice embryos in Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome related organs
Authors: Kira Dina , Eroglu Binnur , Hawkins Zoe , Chorich Lynn P , Brakta Soumia , Layman Lawrence C 
Published: October 2024

Abstract
Disclosure: D. Kira: None. B. Eroglu, MS, PhD: None. Z. Hawkins: None. L.P. Chorich: None. S. Brakta: None. L.C. Layman: None.
Introduction: MRKH is a severe form of the Mullerian duct (MD) anomaly where the upper 2/3 of the vagina and the uterus fail to develop. Individuals with MRKH still have normally functioning ovaries and normal chromosomes. MRKH may be isolated Mullerian aplasia (type 1) or associated with renal, skeletal, cardiac, and/or auditory dysfunction (type 2). The etiology of MRKH syndrome remains unknown for most probands, although a genetic contribution is likely. Most evidence suggests autosomal dominant inheritance with incomplete penetrance. WNT4 and HNF1B pathogenic variants have been identified in some MRKH individuals. Recently, our lab identified heterozygous (HTZ) ZNHIT3 loss of function variants in persons with MRKH, Both variants predict functional changes in the ZNHIT3 C-terminus and impair protein expression in vitro. Previously, other investigators found biallelic variants in the N-terminus of ZNHIT3 in individuals with PEHO syndrome, a severe autosomal recessive neurodevelopmental disorder characterized by extreme cerebellar atrophy. We are currently characterizing a novel Znhit3 knockout (KO) mouse model, in which homozygous KO mice exhibit embryonic lethality. We have demonstrated ZNHIT3 RNA expression in the human uterus, heart, kidney, and skeleton, but developmental expression of ZNHIT3 in wild type (WT) animals has not been studied. In the WT mouse embryo, the kidney forms between E8.0 and E11, while the MDs form through invagination of epithelium ∼E11.5 and extend along the Wolffian duct until reaching the cloaca at ∼E13.5. Hypothesis: We hypothesize that ZNHIT3 is involved in MD development and expressed in the urogenital system and MRKH-related organs during embryonic development of WT mice. Method: Timed mating of WT mice produced embryos for analysis. Embryos were dissected out at E11.5, 12.5 and 13.5, fixed in 4% PFA, embedded in paraffin, and sectioned sagittally at 5mm thickness. H&E staining was done to identify sections showing kidney, genital tubercle, skeleton and cerebellum. Immunohistochemistry was also done using a ZNHIT3 antirabbit antibody and DAPI as nuclear counter stain. Imaging was performed using the Keyence fluorescence microscope (BZ-X800) at 10x and 40x magnification. Results: At all 3 time points, ZNHIT3 protein expression was observed in the developing urogenital organs including kidneys and bipotential gonads, as well as in vertebral bones and cerebellum. Heart protein expression studies are ongoing. Conclusion: ZNHIT3 protein expression is seen as early as E11.5 and is present in MRKH-related organs, suggesting it may play a role in the development of urogenital and MRKH-related organs. These findings provide the basis to compare expression in the Znhit3 KO mouse, a mouse model for MRKH.
Presentation: 6/2/2024
7275 Diverse Reasons for Discontinuing Gender Affirming Hormone Therapy
Authors: Jain A , Irwig M S 
Published: October 2024

Abstract
Disclosure: A. Jain: None. M.S. Irwig: None.
Many Transgender and Gender Diverse (TGD) individuals take Gender Affirming Hormone Therapy (GAHT). A study that included 264 adults [67% assigned male at birth (AMAB)] in Georgia found that 2% (n=5) discontinued GAHT over a follow-up period of 64 months. Reasons identified were change in gender identity (n=2), financial barriers (n=2) and venous thrombosis (n=1). Discontinuation was temporary for 2 and permanent for 2. Here we describe the reasons why four TGD individuals discontinued GAHT. Case Descriptions: Patient 1, AMAB, came out as gay as a teenager. In his mid 30s he became unhappy which he attributed to a conflict between religion and his sexual orientation and failed relationships. He thought that changing his sex would solve his problems. He took injectable estrogen for 3-4 years. He subsequently underwent multiple gender-affirmation surgeries including facial feminization surgery, breast implants, an orchiectomy and vaginoplasty. Immediately following the breast implant surgery he had regrets and wanted them removed. He also regretted the vaginoplasty. He stopped estrogen following the bottom surgery. In his 40s he stated that he would like to detransition as he sees himself "as a fake" when looking in the mirror. Patient 2 was assigned female at birth. Puberty was associated with discomfort from having a large chest. In his late 20s he began injectable testosterone which he took for three years. He then decided to take a two year break as he was frustrated that he had not achieved the desired results and because he was still not able to pass as a man. He resumed testosterone two years ago and underwent top surgery. Patient 3, AMAB, knew from a young age that he was transgender. He took estrogen and an antiandrogen for &gt; 5 years and underwent an orchiectomy and vaginoplasty. He was pleased with the results from the GAHT and surgeries. He presented as a woman for many years. A few years ago, however, he awoke one day with the thought that God wanted him to be a man. He decided to detransition and presented to the endocrinology clinic to start testosterone therapy. Patient 4, AMAB, began GAHT in her late 30s. She discontinued GAHT 4 years later due to lack of results (feminization, larger breasts, wider hips and a more curvy figure). She presented to the endocrinology clinic 2 years later, wanting to resume GAHT. Conclusion: In addition to the reasons identified by Gupta et al for discontinuation of GAHT, we also identified unrealistic expectations, not achieving the desired results and perceived conflict between religion and gender identity. Endocrinologists should be aware of the possibility of discontinuation of GAHT and know how to manage any potential complications such as hypogonadism that may arise. Reference: Gupta P et al. J Clin Endocrinol Metab. 2023.
Presentation: 6/2/2024
7472 Estrogen Monotherapy for Testosterone Suppression in Gender Diverse Patients
Authors: Zhou C , Jones Q , Kokosa S , Kelley C 
Published: October 2024

Abstract
Disclosure: C. Zhou: None. Q. Jones: None. S. Kokosa: None. C. Kelley: None.
Background: For gender diverse individuals assigned male at birth (AMAB), gender-affirming hormone therapy consists of estrogen in combination with anti-androgen medications. Exogenous estrogen use results in the development of feminine secondary sex characteristics while indirectly decreasing testosterone. Anti-androgens such as spironolactone, leuprolide, finasteride, or dutasteride work to further suppress testosterone with successful suppression levels &lt;50ng/dL. However, use of these agents increases the risk of adverse side effects like hyperkalemia, polyuria, and orthostatic hypotension, thus is not suitable for everyone. Anecdotally, estrogen monotherapy has been sufficient in reducing testosterone levels to goal in some patients, however at this time there are no known studies which evaluate estrogen monotherapy and suppression of testosterone. The purpose of this study is to retrospectively review estrogen formulations and dosages in patients who have adequate testosterone suppression in the absence of anti-androgen medications. Methods: The study was a retrospective chart review of adult patients ages 18- 84.99 AMAB receiving gender-affirming estrogen between 9/2020 and 12/2023 seen within an endocrine clinic at a single academic institution. Patients younger than 18, those receiving anti-androgen medications, and those with history of orchiectomy were excluded from the study. Charts were reviewed for estrogen formulations and dosages and total serum testosterone levels. Retrospective chart review will continue with additional data expected in 2024. Results: Ten patients between the ages of 19-81 met the inclusion criteria. Of these, 7 patients identified as transfeminine and 3 identified as nonbinary. The 3 patients who identified as non-binary were not included in analysis as their treatment goals may not align with full feminization or testosterone suppression (total serum testosterone &lt;50ng/dL). Testosterone suppression from estrogen monotherapy was achieved in 100% (n=7) of the transfeminine patients when serum estradiol was &gt;100pg/mL. In those who achieved testosterone suppression, 5 used injectable formulations (estradiol valerate 4-6mg weekly) and 2 used transdermal patches (range of estradiol from 0.2mg twice weekly to 0.3mg three times weekly). Conclusions: Estrogen monotherapy may be effective in suppressing testosterone without the need for anti-androgen medications. So far, this was noted most commonly with use of injectable estrogen formulations. A limitation of the study is the small sample size, however ongoing data collection is anticipated. Additional research evaluating estrogen monotherapy and testosterone suppression is needed and has potentially significant implications for simplified treatment protocols for transfeminine patients.
Presentation: 6/2/2024
7745 Hirsutism in young girls, Beyond PCOS
Authors: Mishra Ipsita , Baliarsinha A K 
Published: October 2024

Abstract
Disclosure: I. Mishra: None. A. Baliarsinha: None.
Hirsutism is excessive terminal hair that appears in a male pattern in women.Though obesity,insulin resistance and PCOS are common cause of hirsutism in young girls,suspicion of other etiologies must be made on a background of overlapping features.We describe 3 cases of young females presenting with hirsutism with varied etiologies. Case 1.16 year 11months old female presented with oligomenorrhea -3years,excessive hair growth over face -2 years.On examination,BMI was 25.2 kg/m2,Grade 2 acanthosis,A3P5B5,modified FG- 16/36,clitoral length-1.3cm and clitoral index - 70 mm2.Biochemical evaluation revealed normal thyroid function tests,s.prolactin- 23.65 ng/ml,ONDST- 1.2 mcg/dl,LH - 1.49 IU/ml,FSH- 7.44IU/ml,serum testosterone- 70ng/dl,17OHP- 7.03 ng/ml,DHEAS- 553mcg/dl and post synacthen 17OHP- 36.89 ng/ml respectively. USG abdomen & pelvis was normal.HOMA-IR was 4.1. Diagnosis was LOCAH Case 2.19 year old female presented with hair growth in androgen dependent areas-5years, regular predictable menstrual cycles and was treated as a case of PCOS for 5 years with no changes in hair growth pattern.She was off therapy since 1 year prior presenting to us.On examination,BMI was 24 kg/m2,acanthosis absent,A3P5B5,modified FG- 18/36, clitoral length- 6 mm,clitoral index - 25mm2.Biochemical evaluation revealed normal thyroid function tests,s.prolactin- 22.9 ng/ml,ONDST- 0.508 mcg/dl,LH - 5.98 IU/ml,FSH- 5.29 IU/ml, serum testosterone- 23.4 ng/dl,17OHP- 1.01 ng/ml and DHEAS- 298 mcg/dl respectivelyUSG Abdomen & pelvis;RO - 5.7cc,LO - 5.6 cc with B/L PCOM.Review TVS was normal.In view of discordant results DHT and luteal phase serum progesterone were done which were 80.5 pg/ml and 2.1ng/ml respectively.HOMA IR was 1.9.Diagnosis was IDIOPATHIC HIRSUTISM. Case 3.12 year old female child presented with excessive hair growth over face,chest,back and abdomen- 1yr,hoarseness of voice - 1 yr,onset of breast enlargement apprx 8 to 9yrs with non-attainment of menarche.On examination BMI was 30 kg/m2,Grade 3 acanthosis, A3P5B3,modified FG- 15/36,clitoral length- 2.8 cm & clitoral index - 120 mm2. Biochemical evaluation revealed normal thyroid function tests,LH - 15.3 IU/ml,FSH- 6 IU/ml,s.prolactin- 11.2 ng/ml,ONDST- 0.38 mcg/dl,DHEAS- 161 mcg/dl,serum testosterone- 140 ng/dl,17OHP- 3.9 ng/ml and post synacthen 17OHP- 4.10 ng/ml respectively.USG abdomen-s/o PCOS with normal adrenals. In view of discordant results short DAST was done which was Testosterone(ng/dl)baseline-125;4hr-91.1, DHEAS (mcg/dl) baseline-180;4hr-188 cortisol (mcg/dl) baseline-7.04;4hr-0.95.HOMA-IR was 5.4. Diagnosis was PCOS(OVARIAN THECOSIS).Varied presentations of hyperandrogenic disorders occurs in young females.A need to revise the diagnosis must be made if no response is obtained with initial drug regimes.
Presentation: 6/3/2024
7838 Improvement of Cognition and Memory Scores in Transgender Individuals Within One Year of Initiating Gender-Affirming Hormone Therapy
Authors: Godar Cassandra M , De La Torre Sebastian C , Bonsu Osei , Shakir Mohamed K M , Hoang Thanh D 
Published: October 2024

Abstract
Disclosure: C.M. Godar: None. S.C. De La Torre: None. O. Bonsu: None. M.K. Shakir: None. T.D. Hoang: None.
Introduction: The use of gender-affirming hormone therapy (GAHT) in transgender individuals is known to provide many beneficial health effects to reduce gender dysphoria, reduce depressive symptoms, and increase overall quality of life. Cognitive function and memory ability are known to be influenced by sex hormone levels in studies of hormone replacement therapy in post-menopausal women, but studies of GAHT’s effects on cognition and memory in transgender patients have been scarcely reported. We discuss a study of cognitive testing in transgender individuals before and after 12 months of gender-affirming feminizing or masculinizing hormone therapy using a validated cognitive assessment tool. Methods: A prospective study of 32 transgender patients aged 18-45 years was approved by IRB at an academic medical center. The Wechsler Memory Scale 4th edition (WMS®-IV, Pearson) was administered to 19 transgender females and 13 transgender males prior to initiation of GAHT and again after one year of GAHT use. Mean scores were analyzed and reported for five categories of cognitive and memory function: auditory memory (AMI), visual memory (VMI), visual working memory (VWMI), immediate memory (IMI), and delayed memory (DMI). Mean scores for baseline and 12-month data were analyzed for total population and male and female subgroups. Results: Baseline mean WMS-IV values for the total study population were: AMI 105 points, VMI 78 points, VWMI 107 points, IMI 88 points, DMI 91 points. Mean values after 12 months of GAHT were: AMI 120 points, VMI 81 points, VWMI 110 points, IMI 99 points, DMI 102 points. Mean percent change from baseline to 12 months was as follows: AMI 13.4%, VMI 8.9%, VWMI 2.6%, IMI 12.8%, DMI 13%. Similar patterns were noted for both gender subgroups. Discussion: It is well-known that transgender individuals are subject to higher rates of depression, anxiety, and suicidality compared to the general population. Decreased cognitive function and memory are known effects of untreated depression. Our study demonstrated that treatment of gender dysphoria with GAHT provided a tangible cognitive and memory benefit. The long-term impact of GAHT on cognition and memory is not known and deserves additional study. Limitations of this study included the absence of a cis-gender control group and inability to stratify data based on age, which may provide additional significance.
Presentation: 6/2/2024
7955 Increased occurrence of psychiatric disorders and use of psychiatric-related medication in patients with congenital adrenal hyperplasia
Authors: Lind-Holst Marie , Hansen Dorte , Main Katharina Maria , Juul Anders , Andersen Marianne , Dunø Morten , Rasmussen Åse K , Jørgensen Niels , Gravholt Claus Hojbjerg , Berglund Agnethe 
Published: October 2024

Abstract
Disclosure: M. Lind-Holst: None. D. Hansen: None. K.M. Main: None. A. Juul: None. M. Andersen: None. M. Dunø: None. Å.K. Rasmussen: None. N. Jørgensen: None. C.H. Gravholt: None. A. Berglund: None.
Background: Clinical studies on psychiatric morbidity, quality of life and cognition in patients with congenital adrenal hyperplasia (CAH) imply impaired mental health. Epidemiological studies on psychiatric morbidity in CAH are, however, scarce. Methods: A registry study of hospital diagnoses and prescribed medication related to psychiatric disorders in a national cohort of patients (n=462) diagnosed with CAH from 1943 to 2018 compared to 100 randomly selected sex- and age-matched controls (n=44,527) from the general population. Psychiatric hospital diagnoses were available for in-patient contacts from 1968 and out-patient contacts from 1994. Medication data were available from 1995. Outcomes: CAH was associated with an increased risk of hospital contacts related to any psychiatric diagnosis (incidence rate ratio (IRR)=2.73, 95% CI 1.85-4.04), and this applied to both males (IRR=2.48, 95% CI 1.57-3.91) and females (IRR=3.20, 95% CI 1.58-6.50). Psychiatric disorders due to psychoactive substance use were more common among CAH males (IRR=3.55, 95% CI 1.58-7.96) and females (IRR=3.81, 95% CI 1.71-8.48). Males with CAH also had an increased risk of suicidal behaviour (IRR=10.66, 95% CI 3.74-30.42). By the age of 30 years, 23% of CAH females and 21% of CAH males had at least one diagnosis related to a psychiatric disorder while this was the case in 14% of female controls and 15% of male controls. Stratifying by sex and CAH phenotype there were important differences among groups. Prescription of medication related to psychiatric disorders was increased for CAH overall (HR=1.73, 95% CI 1.48-2.03) and males (HR=1.80, 95% CI 1.35-2.38) and females (HR=1.70, 95% CI1.36-2.38), separately. Age at the first prescription of any psychiatry-related medication was significantly earlier for patients than for controls (HR males=1.67, 95% CI 1.2-2.3; HR females=1.48, 95% CI 1.2-1.8). Thirty-five per cent (157/448) of CAH patients and 24% of controls had at least one prescription related to a psychiatric disorder within the study period. Interpretation: An increased risk of psychiatric morbidity, psychoactive substance use and use of medication related to poor mental health was seen in both males and females with CAH. The risk of suicidal behaviour was increased for patients with CAH, yet only significantly in CAH males. The study underlines the need for more attention and extension of psychological care and support for patients with CAH.
Presentation: 6/1/2024
7117 Cushings Conundrum: Taming The Hormone Hurricane
Authors: Syed Shakera , Poloju Alekya , Krueger Abigail , Swe Khine , Kaeding Sylwia , Shariff Julia , O’connor Clare 
Published: October 2024

Abstract
Disclosure: S. Syed: None. A. Poloju: None. A. Krueger: None. C. O'connor: None.
Ectopic ACTH syndrome is a rare disease that presents with severe hypercortisolism that can be challenging to treat. This case reviews a patient with high- grade metastatic neuroendocrine tumor causing ectopic ACTH-related Cushing's syndrome and describes navigating these treatment challenges with an evidence-based and patient centered strategy to try to optimize care.Clinical case: This 32-year-old male, with a history of metastatic pancreatic neuroendocrine tumor and liver metastases, initially presented with dyspnea, hyperglycemia, and metabolic derangements. Agitated, with a systolic blood pressure of 190mm Hg, he exhibited notable hypokalemia (2.5mmol/L), hyperglycemia (508mg/dL), and elevated beta-hydroxybutyrate (3.60mmol/L). Random cortisol was 85.9ug/dL and ACTH 472pg/ml. Urgent cortisol control prompted etomidate infusion, lowering cortisol to 27ug/dL in 24 hours. Ketoconazole was initiated but discontinued later due to rising liver enzymes, Metyrapone and spironolactone were initiated and etomidate infusion titrated off. Hemorrhagic shock, DKA, and mental status changes complicated his course.Interventional radiology-guided hepatic artery embolization was performed. Post-procedure cortisol levels improved, metyrapone and spironolactone were stopped. Dexamethasone was initiated given concern for relative adrenal insufficiency during this time and was later switched to hydrocortisone, and eventually discontinued with normalizing cortisol levels. Octreotide and later lanreotide maintained stability for a year. He was readmitted with uncontrolled diabetes, hypertension, and vertebral compression fractures, requiring rapid control with etomidate infusion again. Metyrapone was reintroduced, facilitating etomidate tapering. Spironolactone was re-initiated. Bilateral adrenalectomy was discussed as definitive treatment for the ectopic ACTH syndrome (neuroendocrine cancer was deemed incurable, however he was considered elevated risk for surgery given other co-morbidities. Even with normalization of cortisol, he intermittently refused cares/medications. Conclusion: Managing ACTH-producing neuroendocrine tumors necessitates a multidisciplinary approach. In severe Cushing’s syndrome, etomidate infusion quickly normalizes cortisol but requires intensive care due to sedation risks. Ketoconazole and levoketoconazole carry a hepatotoxicity risk. Metyrapone and mitotane are alternatives but supply challenges exist. Osilodrostat, studied for short-term use, has limited data in ectopic ACTH syndromes. Bilateral adrenalectomy is an option if surgical risks are acceptable. Patient history influences therapeutic decisions, highlighting the need for a patient-centered approach.
Presentation: 6/3/2024
8314 Masculinizing Hormone Therapy and Gynecological Neoplasm: a Single Institution Cohort
Authors: Korpaisarn Sira , Ngaothepphurktharam Teerit , Tingthanatikul Yada 
Published: October 2024

Abstract
Disclosure: S. Korpaisarn: None. T. Ngaothepphurktharam: None. Y. Tingthanatikul: None.
Background: Gynecological neoplasm/malignancy is one of the concerned areas among transgender men on masculinizing hormone therapy (MHT). Long-term MHT and gynecological neoplasm/malignancy remain unclear. Methods: A retrospective cohort chart review was done on all transgender men (TM) who underwent hysterectomy with or without oophorectomy between January 2014 and October 2022. Intraoperative findings and pathological results of genital organs, including the cervix, endometrium, myometrium, and fallopian tubes, were extracted. The pathological results were classified as benign, precancerous, and malignant. Descriptive statistical analysis was used to demonstrate the prevalence of gynecological neoplasm and malignancy. Results: A total of 30 TM underwent hysterectomy with oophorectomy. Twenty-eight (93%) had bilateral oophorectomy, and 7% had unilateral oophorectomy due to gynecological conditions. The mean age when TM underwent surgery was 32.1 ± 5.1 years, and the mean age of gender-affirming hormone initiation was 28.7± 5.1 years. The median duration of MHT before gynecological surgery was 32 months (IQR 22-59). Most TM (73%) used testosterone enanthate, 17% testosterone undecanoate, and 2 transgender men did not start MHT before genital surgery. All TM who used GHT became amenorrheic before surgery. The median preoperative testosterone level was 561.5 ng/dL (IQR 776-1189). Intraoperative findings revealed that most TM (86.7%) had unremarkable uterus size, and 13% showed enlarged uterus size. In the latter, all were from myoma uteri. Most intraoperative findings of ovaries showed 93% unremarkable. One TM had intraoperative polycystic ovarian morphology, and one showed a unilateral ovarian cyst. Cervical pathological reports showed unremarkable results in 67%. Five TM (17%) had chronic cervical inflammation. There was 1 TM (3%) who showed low-grade squamous intraepithelial lesion (LSIL) with squamous metaplasia. Regarding endometrial pathology, the mean endometrial thickness was 0.13 ± 0.08 cm. Most endometrial reports (66%) were in a proliferative phase, 27% were in an atrophic or inactive endometrium, and 7% were in the secretory phase. Regarding pathological reports of ovaries, 80% had cystic ovaries. None of the TM showed precancerous or malignant conditions of endometrium, ovaries, and fallopian tubes. PAP smear was available in 27 TM; all were negative for intraepithelial lesions or malignancy. Conclusion: Among a cohort of TM who received MHT for 32 months, there is no evidence of precancerous or malignant pathology of the endometrium, ovaries, and fallopian tubes. Most of them had thin endometrium with cystic ovaries. One TM showed LSIL with squamous metaplasia of the cervix. Healthcare providers should follow local gynecological cancer screening guidelines developed for cisgender women in their clinical practice.
Presentation: 6/2/2024