bluuebunny/crossref_metadata_2025_split huggingface dataset:
LBMON272 Chromatoid Bodies In The Regulation Of Spermatogenesis: Novel Role Of Grth
Authors: Anbazhagan Rajakumar , Kavarthapu Raghuveer , Dufau Maria L 
Published: November 2022

Abstract
More than 5 million couples in US are affected by infertility. Male infertility is a major cause (&gt;30%), and understanding spermatogenesis is important to address the problem. During early spermatogenesis, mRNAs are actively transcribed, transported and stored transiently in chromatoid bodies (CBs). CBs are membrane-less perinuclear organelles which serve as storehouses of mRNAs until later stages of spermatogenesis. Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) plays critical role in spermatogenesis. In addition to its inherent helicase activity, GRTH transports mRNAs from nucleus to cytoplasm and from there to CBs for storage until translation. In Germ cells, there are two species of GRTH, the 56 kDa non-phospho and 61 kDa phospho (pGRTH) forms. Our early studies revealed a missense mutation (R242H) of GRTH in Japanese azoospermic men which resulted in the lack of pGRTH in in vitro studies. GRTH knock-in (KI) mice with the human mutant GRTH gene (R242H), show loss of the phospho-species from cytoplasm and CBs with preservation of the non-phospho form in the cytoplasm, Nucleus and CBs. GRTH-KI mice are sterile, lack elongated spermatids and spermatozoa with spermatogenic arrest at step 8 of round spermatids (RS). CBs isolated from GRTH KI mice are smaller, highly condensed, lack pGRTH and RNA-Seq analysis of isolated mRNA (from CBs) revealed differential abundance of mRNAs related to spermatid differentiation. Integrative analysis of small RNA and mRNA expression will provide cohesive outlook of molecular mechanisms of gene regulation during spermatogenesis. Hence, we proceeded with small RNAseq analysis which reveal differential expression (Padj&lt;0. 05) of piRNAs and miRNAs. In total 226706 piRNAs upregulated and 166567 piRNAs downregulated in the round spermatids. Several miRNAs like miR32, miR7, miR184, miR335, miR140, miR141, miR1981, miR202, miR880, miR669c were downregulated. These are involved in the positive regulation of spermatid differentiation, sperm motility, mRNA processing and decay. The miRNAs, miR150, miR196a-2, miR7b, miR652, miR146, miR10b, miR379, miR122a, miR27a, miR127 and miR328 were upregulated, which negatively regulate the spermatid differentiation. Gene ontology analysis revealed that the majority of downregulated miRNAs belong to regulation of gene expression. Majority of upregulated miRNAs belong to miRNA mediated suppression of translation mostly associated with spermiogenesis and CBs. The identified miRNAs regulate essential genes like Tnp2, TSSK6, Pabpc1, Ppp1cc and UPF2 etc. These indicates that the CBs mediate highly specialized mRNA metabolism process and serve as a processing center of essential mRNAs. These results demonstrate the importance of GRTH and phospho-GRTH in the regulation of CB and their role in mRNA storage and stability of germ cell specific mRNAs during spermiogenesis and healthy sperm formation.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBODP090 The Addition Of Anastrozole To Standard Testosterone Enanthate Treatment Significantly Improves Penile Size In Adolescent Boys With Micropenis
Authors: Papadimitriou Dimitrios T , Dermitzaki Eleni , Papagianni Maria , Papadimitriou Anastasios , Vlahos Nikos F , Mastorakos George 
Published: November 2022

Abstract

Background
Micropenis is treated preferably in infancy (≤ 2 yrs) or at the onset οf puberty, usually with 3 (2-4) monthly testosterone enanthate I. M. injections at the dose of 100 mg/m2. This short-term therapy may temporarily advance bone maturation but with a concomitant increase in height velocity and no apparent change in predicted adult height. Bone maturation depends on locally produced estrogens by aromatization. Third generation aromatase inhibitors (AIs) are used as an off-label treatment to improve predicted adult height (PAH) in boys as well as in girls, either as monotherapy or in combination with growth hormone and/or puberty inhibition. They induce reverse binding inhibiting the activity of aromatase (a cytochrome P450 enzyme), which catalyzes the conversion of androstenedione and testosterone to estrone and estradiol, respectively, resulting in a substantial increase of the circulating testosterone concentrations.

Aims
To compare the traditional treatment of isolated - idiopathic - relative micropenis in boys with testosterone enanthate monotherapy to its combination with anastrozole 1 mg×1 p. o.

Methods
164 boys with micropenis (stretched penile length ≤ -2 SD) received testosterone enanthate 100 mg/m2 I. M. /month either as monotherapy (n=63, mean age 10.8 yrs, group A) or in combination with anastrozole 1 mg/day (n=101, mean age 11 yrs, group B) for 3 months. Stretched penile length, bone maturation and auxological data were analyzed. All measurements were performed by the same examiner. The choice of therapeutic intervention was made randomly. Groups A and B did not differ in terms of age at intervention onset, bone age, target height or predicted adult height. They underwent a 6-month follow-up that included clinical examination, bone age X-ray evaluated by BoneXpert ver. 3.2. 0 (Visiana, Denmark), and laboratory tests at 8: 00hrs (LH, FSH, testosterone, estradiol, estrone), prior and under treatment.

Results
In both groups penile length normalized: for group A gain was +1.9 cm (+2. 08 SD) and for group B +2.24 cm (+2.3 SD), with group B attaining a greater length by +18% (p=0. 004) due to the higher testosterone concentrations attained by at least 50%. Group A presented a slight acceleration of height velocity with parallel advancement of their bone age maturation while group B with unchanged or lower estradiol and estrone concentrations maintained their height velocity with parallel movement of their bone age maturation.

Conclusions
Addition of anastrozole 1 mg/day p. o. in testosterone enanthate treatment for idiopathic-isolated-relative micropenis at the beginning of puberty significantly improves penile length by almost 20% while the tempo of height velocity and bone maturation continue their previous track.
Presentation: No date and time listed
ODP401 A new FGFR1 mutation causing Idiopathic Hypogonadotropic Hypogonadism and Polydactyly
Authors: Espinosa Luis Borges , Ayala Alejandro , Dicenso Daniela 
Published: November 2022

Abstract

Introduction
Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a heterogeneous condition with unknown genetic basis in approximately 30% of patients. We describe a case with normosmic IHH and an unreported FGFR1 mutation.

Case Report
A 23-year-old hispanic man, with a history of polydactyly presented to our clinic for evaluation of delayed puberty. He had no facial hair and minimal pubic and axillary hair. He reported fatigue, low libido and scant ejaculation. He denied anosmia, eating disorders, learning disability, urological malformations, obesity, galactorrhea, testicular trauma, mumps, or use of androgenic steroids. Family history was significant for polydactyly in his mother. Physical exam findings showed normal vitals, height 185 cm, BMI 24 kg/m2, eunuchoid body habitus, bilateral gynecomastia, no facial hair, scant axillary and pubic hair, prepubertal 2 ml testicles within the scrotum and a micro-penis. Serum total testosterone was 7 ng/dl (250-1100 ng/dl), free testosterone 0.9 pg/ml (9.3-26.5 pg/ml), FSH 2.2 mIU/ml (1.6-8. 0 mIU/ml), LH 0.8 mIU/ml (1.5-9.3 mIU/ml), Prolactin 4.1 ng/ml (4-15.2 ng/ml), TSH 1.68 mIU/ml (0.4-5.5 mIU/ml), free t4 1.2 ng/dl (0.8-1.7 ng/dl), growth hormone 0.3 ng/ml (0. 0-10 ng/ml), IGF-1 175 ng/ml (155-432 ng/ml), ACTH 14.6 pg/ml (7.2-63 pg/ml), cortisol (not am) 3. 0 ug/dl (6.2-19.4 ug/dl). Pituitary MRI revealed no focal sellar/suprasellar lesions with normal enhancement of the pituitary gland . DXA scan showed a low bone density for his age with Z-scores below -2. 0 in all regions. Chromosome analysis revealed a normal male 46, XY karyotype. Genetic testing of both patient and mother, using Invitae test kit, revealed an heterozygous mutation in FGFR1 gene, exon 9, variant c.1231C&gt;A (p. Gln411Lys), not described in medical literature. A diagnosis of normosmic idiopathic hypogonadotropic hypogonadism (nIHH) was made. Testosterone cypionate IM 100 mg once weekly was initiated and after 6 months he experienced improvement in energy, libido, muscle mass, facial and body hair, and virilization of his voice.

Conclusions
The heterogeneity in phenotypic presentation of IHH makes its diagnosis a challenge. Furthermore, the genetic basis for these multiple phenotypes are still not fully described. We report a new FGFR1 mutation causing hypogonadism. Reference: Ferreira Gontijo, L., Latronico, A. Approach to the Patient With Hypogonadotropic Hypogonadism. JES, Vol. 98, Issue 5, 1 May 2013, P. 1781–1788.
Presentation: No date and time listed
ODP412 High Frequency of Erythrocytosis in Hypogonadal Men on Testosterone Replacement Therapy
Authors: Pérez-Luis Jesús , Adolewska Patrycja Dagmara 
Published: November 2022

Abstract

Introduction
Erythrocytosis is a frequent side effect of testosterone replacement therapy (TRT) in hypogonadal males and can be deleterious by increasing blood viscosity, which can lead to headaches, hypertension, and thromboembolic complications. Main causes of erythrocytosis are short-acting testosterone injections, smoking habit and obesity.

Aim
Study the frequency of erythrocytosis induced by TRT and its predictive factors in hypogonadal men in our setting. Subjects and methods: A retrospective study in hypogonadal males on TRT for at least 3 months was conducted. Age, age at treatment onset, months on treatment, initial hematocrit (IHt), highest hematocrit during follow-up (MaxHt), hematocrit on last visit (FHt), hematocrit increase (HtIn), maximum hematocrit increase (HtMaxIn), anthropometric measures, sex hormones and biochemical parameters on the last visit were recorded. In addition, testosterone formulation, smoking status, dyslipidemia, hypertension, diabetes, type of hypogonadism and presence of cardiovascular disease (CVD) were also documented. A hematocrit ≥ 50% (Ht≥50) was considered erythrocytosis and one ≥ 53% was indication for phlebotomy (Ht≥53).

Results
108 patients were included, age 54 ± 19 years, age at THT onset 44 ± 18 years, BMI 30 ± 5 Kg/m 2 . On the last visit, 29% had FHt≥50 and 11% had FHt≥53, while during follow-up 58% had MaxHt≥50 and 35% had MaxHt≥53. Moreover, 18% were smokers, 61% had dyslipidemia, 48% had hypertension, 36% were diabetic, 59% were on short acting IM testosterone injections (cypionate), 25% were on extended-release IM testosterone injections (undecanoate) and 16% were on transdermal testosterone. On the other hand, 13% had CVD at onset and 6% developed CVD during follow-up. None of the hematocrit or hematocrit increase values was related to the type of testosterone formulation, smoking habit or appearance of CVD during follow-up. They also did not correlate with serum total testosterone, other sexual hormones and lipids levels or BMI. Interestingly, there was no difference in total testosterone levels between the three testosterone preparations groups. FHt (44 vs 48%, p=0,018) and HtIn values (1.86 vs 5.31%, p=0,036) were lower in those with previous CVD disease. This fact cannot be explained by BMI since there was no difference between patients with and without CVD. Although it could be due to a lower percentage of smokers in the group of patients with CVD, that could not be demonstrated.

Discussion
The occurrence of erythrocytosis secondary to TRT in hypogonadal men in our setting was very common and higher than reported previously: 58% of patients during follow-up and 35% required phlebotomy. Hematocrit and hematocrit increase values were independent of BMI, smoking status, type of testosterone formulation and presence of CVD. This lack of association could be due in part to the small number of individuals in some of the subgroups.
Presentation: No date and time listed
ODP058 Topiramate causing elevation of urinary cortisol assay
Authors: Grissett Bryan , Sosa-Pagan Max , Iqbal Qasim Zafar 
Published: November 2022

Abstract

69-year-old female with pituitary adenoma status-post transsphenoidal resection 6 years prior and isolated growth hormone deficiency [on somatropin 0.2 mg daily], migraines [on topiramate 25 mg daily], left lipid-rich adrenal incidentaloma, primary hypothyroidism [on levothyroxine 75 mcg daily], and secondary hyperparathyroidism from vitamin-D deficiency [on ergocalciferol 50000 IU weekly] and hydrochlorothiazide 25 mg daily presented for follow-up. Physical exam: afebrile, blood pressure hypertensive at 163/71 mmHg, heart rate 91 beats per minute, respiratory rate 18 breaths per minute, saturating 100% on room air and patient weighed 105 kg. Patient appeared obese but did not exhibit cervicodorsal fat pads, abdominal striae, or other cushingoid features. Neck was supple and did not demonstrate palpable nodules or lymphadenopathy. Labs ordered at clinic visit demonstrated normal TSH 1.28 with normal free T4 1.21, elevated PTH 232 with corrected calcium 9.7 (on hydrochlorothiazide) and normal vitamin-D, 25 level 43, normal ACTH 21, and normal IGF-1 level 75. Given adrenal incidentaloma and prior pituitary adenoma, the integrity of the hypothalamus-pituitary-adrenal axis was also tested. A subsequent 8: 00 a. m. cortisol was insufficiently suppressed at 5.2 after 1 mg dexamethasone suppression test which raised concern for hypercortisolism from pituitary adenoma or adrenal adenoma. Accordingly, ACTH as well as DHEA-S and 24 hour urine cortisol as well as midnight salivary cortisol level was ordered to assess pituitary versus adrenal origin, respectively. Interestingly, while midnight salivary cortisol was found to be normal at less than 50, the 24 hour urine cortisol measurement was elevated at 878 despite otherwise normal cortisol findings. ACTH and DHEA-S levels are still pending. Plan was made to check two additional midnight cortisol levels and await ACTH and DHEA-S levels. In an effort to explain the urinary cortisol elevation, the patient's medications were reviewed and subsequent literature search revealed that topiramate may interfere with urinary cortisol measurement by causing a dose-dependent increase in the measured urinary cortisol, presumably due to its action on the kidney during renal excretion. Patient had been on topiramate for approximately 6 months prior to this assay.
Presentation: No date and time listed
ODP415 Inclusion Health Clinic: Gender-Affirming Hormone Therapy & Surgery Booklet and Review of Efficacy in Patient-Provider Encounters
Authors: Pulsiano Sune Wolf , Sarvaideo Jenna 
Published: November 2022

Abstract
While gender-inclusive health has been a growing field, comprehensive information on the topic has lacked for both patients and providers. The "Inclusion Health Clinic (IHC) Gender-Affirming Hormone Therapy & Surgery" booklet, modelled after other Froedtert Health resources and created using guidelines from Endocrine Society, University of California, San Francisco, and World Professional Association for Transgender Health (WPATH), was introduced to IHC on April 28, 2021. Its goal was to facilitate patient-provider relationships through sharing clinical knowledge and practice preferences with patients as well as to assist providers in communicating concepts to individuals seeking advice and care. Booklet efficacy was analyzed through anonymous surveys self-selected among transgender and gender-nonconforming patients seen at Inclusion Health Clinic. Regardless of gender identity or new patient status, 100% of survey respondents found the booklet useful in generating a productive conversation. For numerical questions, averages for all data sets were above 4. 0/5. 0: ease of navigation was rated highest (4.75 +/- .24), followed by scope of care (4.25 +/- .34), and lastly the booklet's utility in explaining concepts (4.15 +/- .36). For qualitative responses, respondents found the most value in pages related to hormone therapy and surgery. Data from the survey was primarily used to improve the booklet; this revision is projected to be distributed to IHC in Spring 2022. The aspiration is for the booklet to evolve as care for the LGBTQ+ population advances, and that it will continue to serve as a relevant and useful source of information on gender-affirming health needs.
Presentation: No date and time listed
ODP419 Measurement of Free Testosterone in Serum using Equilibrium Dialysis Coupled with ID-UHPLC-MS/MS: in Comparison to Calculated FT
Authors: Zhou Hui , Ribera Ashley , Danilenko Uliana , Sugahara Otoe , Vesper Hubert 
Published: November 2022

Abstract
Assessment of free testosterone (FT) has been recommended in recent clinical practice guidelines as a biomarker for diagnosis and management of testosterone related disorders such as male testosterone deficiency due to hypogonadism and female androgen excess due to polycystic ovary syndrome (PCOS). FT is currently measured using direct commercial immunoassays, assays using equilibrium dialysis (ED) or other separation techniques, or estimated by calculating free testosterone (cFT) using different formulas. The most widely used formula was developed by Vermeulen et al and uses total testosterone and sex hormone binding globulin (SHBG) concentrations. The ED approach is recognized as the gold standard; however, it is technically challenging for routine clinical use. CDC's Clinical Standardization Program (CDC CSP) has developed a high throughput method using ED coupled with isotope dilution ultra-high-performance liquid chromatography tandem mass spectrometry. The study to evaluate the agreement of this ED-based method to the cFT using different algorithms is being conducted. Serum samples are dialyzed in a custom-designed multi-well plate against a protein-free HEPES buffer (pH 7.4) at 37 °C until equilibrium. After isolating endogenous FT from protein-bound testosterone by ED, isotope-labeled internal standard (13C3-testosterone) was added to the resulting dialysate for quantification. Certified pure primary reference material (National Measurement Institute-M914) was used to prepare calibrators, enabling traceable quantitation and ensuring measurement trueness. FT was further isolated from the dialysate matrix using supported liquid extraction and a chromatographic separation from interfering compounds and quantitation by tandem MS. The assay allowed detection of 2.9 pg/mL FT, with the bias within ± 5% and precision less than 10% CV. A total of 45 samples with a wide range of TT (21-912 ng/dL) and SHBG (11-129 nmol/L) were analyzed. The obtained FT values were compared to the cFT values obtained with the Vermeulen algorithm. The mean difference of 34.1% (95% CI 29.1% to 39.9%) between the measured and calculated FT were observed, with majority of the calculated values overestimating FT concentrations. The described high throughput method for FT allows for sufficiently accurate and precise measurement and can provide more reliable FT measurements compared to cFT (that can lead to overestimation of FT) for routine applications including large epidemiologic studies.
Presentation: No date and time listed
PMON226 Primary Ovarian Insufficiency: A Case of a Missed Puberty
Authors: Lin Jack , Suarez Maria Gabriella 
Published: November 2022

Abstract
Premature Ovarian Insufficiency (POI) is a loss of ovarian function in women less than 40 years old. We present a case of a female with primary amenorrhea due to autoimmune primary ovarian insufficiency (APOI), in which diagnosis was delayed as she had normal breast and pubic/axillary hair development.
A 18-year-old female presented to endocrine clinic for evaluation of primary amenorrhea and hypoplastic uterus and ovaries. During her regular follow ups with her pediatrician it was noted that she had not undergone menarche but since her breast development was normal, further evaluation was not pursued. She had a complicated social history and missed several of her follow up appointments. However, further evaluation was done after she presented with severe pain during intercourse. During her physical exam, it was found she had a vaginal opening of 4 cm with an unpalpable cervix. She did however have pubic/axillary hair and breast development consistent with Tanner stage V. Pelvic MRI showed hypoplastic uterus/ovaries. Her lab work revealed she had a total testosterone of 28ng/dL, prolactin 11.1ng/mL, TSH 1.68iIU/mL, LH 42.2mIU/mL, FSH99.77 mIU/mL, estradiol29.36 pg/ML, AMH 3.1ng/mL. Her karyotype was 46XX. Testing for Fragile×Syndrome and 21 hydroxylase antibodies were negative. Anti-ovarian antibody (AOA) was obtained and found to be positive (1: 160). She was diagnosed with APOI and started on estrogen with a goal to increase to adult doses over 1.5-2 years. Progestins are planned to be introduced once she reaches adult doses of estrogen or develops breakthrough bleeding.
Typical presentation of patients with POI is primary amenorrhea and lack of breast development during puberty. However, it is important to remember that there can be a broad spectrum of presenting symptoms with variable breast, uterine, and ovarian development as not all patients have the same degree of estrogen deficiency. This is a case of a patient with POI with hypoplastic uterus and ovaries who had Tanner V breast development. Given this patients ovarian atrophy it is likely that the majority of estrogen production originated from adrenal glands and fat cells, which contributed to the normal development of secondary sexual characteristics delaying her diagnosis. Therefore, identification of abnormal menstrual patterns in adolescence should always raise concern for POI even in the setting of normal breast and pubic/axillary hair development.
POI is due to premature deprivation of estrogen with subsequent amenorrhea and compensatory elevations in FSH/LH. Early diagnosis of this condition can prevent potential health complications in such as decreased bone mineral density, psychological complications, and extremely painful intercourse as our patient had. It is important to note that fertility in patients with POI is also unpredictable, however earlier diagnosis/treatment can improve fertility preservation, especially in women with normal AMH levels such as this patient.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.