bluuebunny/crossref_metadata_2025_split huggingface dataset:
PMON311 45,X/46,XY mixed gonadal dysgenesis: a case report from Saudi Arabia
Authors: Aljasser Abdullah , Alsaleh Norah 
Published: November 2022

Abstract

Introduction
Mixed gonadal dysgenesis is a sex developmental disorder where the gonads are abnormal from there being some cells with XY chromosomes and some with just asingle X, known as chromosome Y mosaicism. This results in a wide range of male/female genitalia that are not typically, or clearly, male or female
The case: 3 years old Saudi boy was born term to 35 year old G5P5 Normal anti natal and history of consanguinity. Birth weight 2 kilogram and found to have genital ambiguity in the form of short phallus structure and hypospiadius testis were felt at the right inguinal canal. his investigation showed abnormal chromosomes 45×46XY musiac . Mother chromosomes were 46XX normal female karyotype.
normal siblings and Wes WES: CNV DESCRIPTION*: seq[GRCh37] Yp11.31q11.23 (mosaic∼50% of the cells) SIZE (KB):
∼26Mb, GENE COUNT**: 116, INTERPRETATION***: Pathogenic.
RELATED DISORDER: 45,X/46,XY mixed gonadal dysgenesis
The radiological investigations showed small oval shaped mass over the right inguinal canal 0.8/0.6/0.8 cm in size .the left testis couldn't be seen . And Genetogram showed presence of vagina and small uterus.
his laboratory investigations showed at age of 2.5 years LH: less than o.3 and his Testosterone basal was less than 0.09 and Testosterone post HCG 8.29 which should excellent response to HCG.. the case was discussed with the paediatric urologist and the decision was as per the anatomical finding and results of the stimulated Testosterone to give Testosterone injections and asses the response. The child respond very well to the testosterone treatment which leads to improvement in the size and length of the phallus.

Discussion
mixed gonadal dysgenesis is one of the causes of DSD .45, X/ 46, XY mosaic: At birth around 90 per cent of babies with 45,X/46,XY have normal-appearing external male genitals, five per cent have normal-appearing female genitals and in five percent the external reproductive organs are neither fully male nor fully female. They may find one or two gonads that are very inadequate testes, possibly with some ovary-like tubules present. They may find one streak gonad and one immature, dysgenetic or normal testis. They may find an internal vagina, cervix and uterus, although these are usually quite small compared to a normal female. Some people with a 45,X/46,XY karyotype have reduced fertility and some are infertile. No judgment can be made about fertility until well after puberty in the apparently normal males. Children with a 45,X/46,XY karyotype can have any of the medical conditions that are more common among girls with Turner syndrome (who have a 45,X karyotype), which includes heart and disorders, autoimmune disorders and short stature.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF14 | PMON320 Ovarian Malignancy, Familial Multinodular Goiter Associated with DICER1 Mutation
Authors: Broussard Julia R 
Published: November 2022

Abstract

Background
DICER1 syndrome, a rare autosomal dominant disorder, places affected individuals at risk for benign and malignant tumors of multiple organs, including thyroid, ovaries, lungs, kidneys, CNS. These tumors occur in childhood and usually before 40 years of age.

Clinical Case
A 15-year old female presented with worsening abdominal pain and vomiting. She noted a "hard spot" on her abdomen and reported secondary amenorrhea with worsening acne and development of hirsutism over the previous 12 months. Imaging evaluation showed a 9 cm×19 cm×13 cm right ovarian mass with no enlarged lymph nodes. Initially, tumor markers and hormone levels were elevated: Alpha Fetoprotein 424 ng/mL [0-7], Testosterone 208 ng/dL [12-60], Free Testosterone 6.03 ng/dL [0.04-1.09], Inhibin A 129 pg/mL [97.5], Inhibin B 817 pg/mL [&lt; 136], LDH 742 unit/L [370-645]. Patient underwent right salpingo-oophorectomy, lymph node and omentum biopsy; pathologic exam showed Stage 1C Sertoli-Leydig tumor of the right ovary (intermediate to poorly differentiated). She received chemotherapy with Cisplatin, Etoposide, Bleomycin. Genetic analysis revealed that she is heterozygous for a likely pathogenic variant, c.343del (p.Thr115Leufs*13) in DICER1, consistent with a diagnosis of autosomal dominant DICER1-associated disease. After therapy ended, her tumor markers and hormone levels normalized. Patient was found to have a multinodular goiter with benign pathology; her thyroid function remained normal. A 2 mm right middle lobe pulmonary nodule, stable, has been present on chest CT. Family history is significant for an euthyroid multinodular goiter with benign nodules in her 2-year older brother who has the same DICER1 pathogenic variant. Their mother and maternal grandmother also had total thyroidectomy for multinodular goiter.

Conclusion
A cluster of certain tumors in family members involving successive generations, should prompt evaluation for a genetic cause, as early diagnosis, management and appropriate surveillance improve patients’ quality of life.
Presentation: Sunday, June 12, 2022 12:54 p.m. - 12:59 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP537 A 1.6cm Androgen Secreting Ovarian Leydig Cell Tumor Evades Detection on Multiple Imaging Modalities
Authors: DeLorenzo Frank , Gruntmanis Ugis 
Published: November 2022

Abstract

A 1.6cm Androgen Secreting Ovarian Leydig Cell Tumor Evades Detection on Multiple Imaging Modalities Background: Leydig Cell Tumors can present with marked virilization and yet may evade detection with common imaging modalities. This is a case of a patient with hyperandrogenism due to a 1.6cm ovarian Leydig cell tumor that could not be detected on transvaginal ultrasound, contrast enhanced CT or MRI with contrast. Clinical Case: A 61-year woman presented with virilization. She had a history of a right-sided borderline serous ovarian tumor status post right oophorectomy 23 years prior to presentation and a hysterectomy 16 years prior to presentation. She followed up with gynecologic-oncology for several years but eventually stopped as her condition was stable. On re-presenting to establish care with a gynecologist she complained of increased hair growth on her face, abdomen and buttocks as well as hair loss on the front and top of her scalp. On exam, she was noted to have clitoromegaly with no palpable adnexal masses. Labs revealed total testosterone 398ng/dL (8-60ng/dL), free testosterone 9.15ng/dL (0. 06–0.87ng/dL), 17-hydroxyprogesterone 204ng/dL (&lt;51ng/dL) CA-125 of 6.2U/mL (&lt;=38.1U/mL) and DHEAS 23.1mcg/dL (18.9 – 205mcg/dL). Transvaginal ultrasound showed a left ovary of 3cc with no mass or abnormality. She was referred to endocrinology and a CT abdomen and pelvis with contrast was obtained that again showed no adnexal mass but was notable for a 7mm isoattenuating nodule in the left adrenal gland. Additional labs were obtained including 24 hour urinary cortisol and metanephrines, late night salivary cortisol and serum aldosterone and renin activity, all of which were within normal limits. Suspicion remained high for an ovarian source of the hyperandrogenism so a pelvic MRI with and without contrast was performed which showed a normal appearing left ovary measuring 2.3cm×4.2cm×1.8cm. She was referred to gynecologic-oncology and it was decided to proceed with a left oophorectomy. This was performed and the pathology revealed a 1.6cm Leydig cell tumor in the left ovary. Testosterone and 17-hydroxyprogesterone subsequently normalized when checked seven weeks post-op.

Conclusion
Leydig cell tumors are rare ovarian tumors often presenting with hyperandrogenism in postmenopausal patients and can be difficult to identify on imaging. A review of published case reports revealed 8 cases in which Leydig cell tumors ranging from 1.2cm to 4.6cm could be detected using one of the imaging modalities employed in this case. There were 9 reports of tumors ranging from 0.8cm to 2cm that evaded detection on imaging. When significant hyperandrogenism is present in a postmenopausal patient a strong suspicion for an ovarian source should be maintained even when imaging is apparently normal.
Presentation: No date and time listed
ODP642 Differences in hormonal profiles and vitamin D status depending on the insulin sensitivity status in women with polycystic ovary syndrome (PCOS).
Authors: Ozga-Piszczek Katarzyna , Krzyczkowska-Sendrakowska Magdalena , Piszczek Piotr , Ratajczak Maciej , Ratajczak Magdalena , Chaykivska-Agafonova Zlata 
Published: November 2022

Abstract

Background
Depending on metabolic profile, two different PCOS phenotypes may be distinguished- the metabolic phenotype related to insulin resistance (IR) and the reproductive one, with persistent insulin sensitivity. Hyperandrogenemia, the main feature of PCOS, leads to increased visceral fat and muscle masses and thus to lower insulin sensitivity. In turn, IR leads to metabolic consequences and hormonal imbalance. Moreover, vitamin D deficiency, which is common in PCOS patients, is also associated with insulin resistance.

Aim
To compare the hormonal profiles and vitamin D status in women with PCOS depending on insulin sensitivity status.

Materials and methods
One thousand three hundred women with PCOS, aged 18 to 40, were recruited. The patients were divided into two groups depending on their insulin sensitivity status. Metabolic and hormonal parameters were assessed in subjects from each group. Blood samples were collected between the second and the sixth day of the menstrual cycle (follicular phase)for the quantification of hormonal parameters using the electrochemiluminescence immunoassay (ECLIA) methods or colorimetry.

Results
Patients with insulin resistance have a significantly higher concentration of DHEAS and TSH, higher Free Androgen Index, and significantly lower vitamin D concentration. Moreover, cortisol and estradiol concentrations are higher and prolactin is lower in patients with IR, but the differences are not statistically significant. There are no significant differences in the prevalence of Hashimoto disease between patients with IR and patients with persistent insulin sensitivity.

Conclusions
Metabolic phenotype of PCOS is associated with higher androgen concentration and higher TSH concentration compared to reproductive phenotype. Moreover, patients with PCOS and IR often have vitamin D deficiency compared to patients with persistent insulin sensitivity. Therefore the supplementation of vitamin D and regular TSH measurements are important in patients with metabolic PCOS phenotype.
Presentation: No date and time listed
PMON210 Ovariectomy of Middle-Aged Female Mice Leads to Decreased Fat Oxidation and Energy Expenditure Accompanied by Weight Gain and Dysregulated Blood Glucose
Authors: Stokar Joshua , Gurt Irina , Lishinsky Natan , Offir Neta , Dresner-Pollak Rivka 
Published: November 2022

Abstract

Introduction
In humans, menopause brings upon total body weight gain with increased visceral adiposity and a resulting increase in cardiometabolic risk profile. Although well described, the specific sequence and underlying mechanisms for this remain elusive. Rodent ovariectomy (OVX) is routinely used as an animal model for the study of human menopause but is often performed in young reproducing specimen, failing to replicate the complex interaction of concomitant chronological aging with the loss of sex hormones observed in humans. In this study we used middle-aged ovariectomized mice to explore the effect of concomitant estrogen deficiency with chronological aging on key aspects of cardiometabolic health and energy expenditure.

Methods
10-month-old C57BLj/6 female mice, were subjected to a SHAM or OVX procedure and followed for 6 weeks post-surgery (n=5 per group). Non-fasting blood glucose (BG) and body weight were measured weekly. Prior to sacrifice mice were observed in metabolic cages using the Promethion Metabolic Phenotyping System (Sable Systems International). Body composition including total body fat and lean mass were evaluated by EchoMRI. A Reduction in uterine weight was used to confirm successful OVX.

Results
Relative to baseline weight, OVX mice weighed 13% more than SHAM mice 6-weeks after surgery (p= 0.04; t-test) with no significant change in body composition. Non-fasting BG was consistently higher throughout the study period in OVX vs SHAM mice (p&lt;0.01; ANOVA). OVX mice exhibited an increased respiratory quotient (0.84 vs 0.81; p&lt;0.01; t-test) driven by a reduction in fat oxidation (24 vs 34 g/d/kgeff. mass p&lt;0.000; t-test). OVX mice showed a 17% percent decrease in total energy expenditure in both the light and dark phases (p&lt;0.01), driven by a 38% percent decrease in ambulatory activity (p=0.04) and close to a 3-fold decrease in wheel running (p&lt;0.001). No significant change was observed in overall food or water intake between the groups.

Discussion
It is difficult to detangle the complex web of causes and effects relating to the deranged metabolic phenotype induced by menopause. Here we show that even without additional insults such as a high-fat-diet or genetic manipulation, the combination of chronological aging at middle-age with the sex hormone deficiency resulting from OVX, led to an increase in total body weight, a dysregulated glucose profile and a deranged energy expenditure pattern. Additional studies are warranted using similar animal models to tease out cause and effect as well explore novel therapeutics and biomarkers for the rapidly increasing population of post-menopausal women at risk for cardiometabolic disease.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON211 Energy metabolism hormones irisin and leptin affect steroidogenesis in human granulosa cells: in vitro studies
Authors: Avtanski Dimiter , Poretsky Leonid , Singer Tomer , Stojchevski Radoslav , Ziskovich Karina 
Published: November 2022

Abstract
Energy metabolism and reproduction are closely linked; however, the role of the individual energy metabolism hormones in this association is still poorly understood. Irisin is a hormone produced mostly by skeletal muscle cells during exercise or shivering, and leptin is a satiety adipokine synthesized by the white adipose tissue. The aim of this study was to investigate the in vitro effects of irisin and leptin on steroidogenesis in cultured human granulosa cells. The cells were purified from follicular fluid samples from patients undergoing in vitro fertilization (IVF). Primary cell cultures were treated with increasing concentrations of irisin (0, 125, 250, 500, 1,000, and 2,000 ng/ml) or leptin (0, 25, 50, 100, 200, and 400 ng/ml) for 24 hours and subjected to qRT-PCR analysis for the expression of key steroidogenic enzymes (CYP11A1, CYP19A1, CYP21A1, HSD3B1, and HSD17B3). Concentrations of progesterone, testosterone and estradiol in the conditioned cell culture medium were measured using ELISA. Results demonstrated that both irisin and leptin significantly upregulated CYP19A1 mRNA expression. Leptin also increased the expression of HSD3B1 mRNA levels. Although not statistically significant, leptin produced a trend of increasing estradiol production after 24 hours of treatment. Taken together, these data support the hypothesis that irisin and leptin may affect steroid hormone metabolism in the ovary by modulating the expression of key steroidogenic enzymes.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON244 Alterations in Nonesterified Free Fatty Acids (NEFA) Trafficking Rather Than Hyperandrogenism Contribute to Variations in Insulin Sensitivity Among Obese Women with Polycystic Ovary Syndrome
Authors: Azziz Ricardo , Chen Ida Y , Ezeh Uche 
Published: November 2022

Abstract

Objectives
To compare the metabolic and hormonal features of metabolically unhealthy obese PCOS women (MU-PCOS) vs. metabolically healthy obese PCOS women (MH-PCOS) and determine whether alterations in non-esterified free fatty acids (NEFA) response to hyperinsulinemia contribute to variations in insulin sensitivity between MU-PCOS and MH-PCOS.

Design
Prospective cross-sectional study.

Setting
Tertiary-care academic center.

Methods
Insulin resistance (IR) in the basal state was assessed by HOMA-IR in 125 consecutive obese oligo-ovulatory PCOS women (BMI≥ 30 kg/m2; NIH 1990 or Rotterdam 2003 Phenotype A/B) undergoing an oral glucose tolerance test (oGTT); and IR in the dynamic state assessed by the modified frequently sampled intravenous glucose tolerance test (mFSIVGTT) in a subgroup of 16 non-diabetic obese PCOS women.
Main Outcome Measures: Primary outcome measures were: 1) IR in AT was assessed in the basal state by the Adipose Insulin Resistance Index [Adipo-IR]) and dynamically by the mFSIVGTT-derived indices of insulin-mediated NEFA suppression [NEFAnadir, TIMEnadir, and %NEFAsupp]); 2) peak lipolysis rate [SNEFA]; and 3) peak NEFA uptake rate [KNEFA]. Secondary outcome measures were levels of insulin and glucose during oGTT, HOMA-β%, and degree of hyperandrogenism (i.e. mF-G score, free testosterone [T], total T, DHEAS).

Results
Eighty-five obese PCOS participants undergoing oGTT had a HOMA-IR index of ≥2.5 (MU-PCOS) and 40 had a HOMA-IR of &lt;2.5 (MH-PCOS). MU-PCOS had higher mean HOMA-β%, levels of fasting, 1-hr and 2-hr. glucose and insulin, and peak insulin during the oGTT, and higher prevalence of prediabetes and elevated 1-hr. glucose and a trend towards higher prevalence of type 2 diabetes mellitus (T2DM), than MH-PCOS. Alternatively, measures of HA were similar between the groups. Assessing IR dynamically, subjects were subdivided into MU-PCOS by an insulin sensitivity index [Si] ≤1.7 [mU/L]−1·min−1 (n=8) or MH-PCOS by an Si ≥5.6 [mU/L]−1·min−1 (n=8), matched for age and BMI. MU-PCOS had lower Si and KNEFA, smaller %NEFAsupp, longer TIMEnidar, and higher NEFAnidar and Adipo-IR than MH-PCOS, although fasting plasma NEFA levels and SNEFA were similar. In bivalent analysis, Si correlated strongly and negatively with NEFAnadir, weakly and negatively with TIMEnadir, and positively and strongly with KNEFA and NEFAsupp, in MUO-PCOS only.

Conclusion
Independent of age and BMI, metabolically unhealthy obese PCOS women, compared with metabolically healthy obese PCOS women, had lower rates of NEFA uptake and altered insulin-mediated plasma NEFA suppression in response to mFSIVGTT-determined endogenous insulin secretion, rather than disparities in HA and rate of lipolysis, mechanism that may contribute to variations in insulin sensitivity among obese PCOS women.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON248 Predictive value of markers of hyperandrogenism in 1610 women with PCOS
Authors: VanHise Katherine , Wertheimer Sahar , Handelsman Roy , Clark Ekaterina , Buttle Rae , Chan Jessica , Wang Erica , Azziz Ricardo , Pisarska Margareta 
Published: November 2022

Abstract
Polycystic ovary syndrome (PCOS), an endocrine disorder that affects 10% of women worldwide. In 1990, the NIH established the first consensus on diagnostic criteria for PCOS which included chronic anovulation with clinical and/or biochemical hyperandrogenism, after the exclusion of related disorders. Traditionally the assessment of hyperandrogenism included serum studies of total testosterone (TT), free testosterone (FT), and dehydroepiandrosterone sulfate (DHEA-S), and physical exam assessing hirsutism using the modified Ferriman-Gallwey (mFG) score. The most recent 2018 International Guidelines suggest the measurement of DHEA-S can be considered if TT or FT are not elevated, but probably provide limited diagnostic value. We evaluated the diagnostic utility of TT, FT, DHEA-S and hirsutism in a large prospective cohort of PCOS women.
Subjects presented to tertiary-care specialty clinics with symptoms of androgen excess in Birmingham, Alabama and Los Angeles, California from 1987-2010. Clinical hyperandrogenism was assessed using the mFG score, and hirsutism was defined as mFG &gt;4. Participants underwent serum studies to assess for hyperandrogenemia and exclude other causes of hyperandrogenism. Fasting blood samples were obtained on cycle days 3 through 8 of a spontaneous or progesterone-induced vaginal bleed for measurement of TT, FT and DHEA-S. Elevated serum androgens were defined as values exceeding the laboratory reference range or greater than the 95th percentile of reported values. Subjects were considered to have oligomenorrhea if they reported &gt;35 day cycles, &lt;10 bleeds per year or reported being eumenorrheic but were confirmed non-ovulatory with a luteal phase progesterone &lt;4 ng/mL. One thousand six hundred and ten women and adolescents (n=1610), aged &gt; 14 years, were diagnosed with PCOS by NIH Criteria and included.
Of these 1610 subjects, 39.3% (n=643) were diagnosed with PCOS based upon an elevated TT and FT with oligomenorrhea; 23.9% (n=384) based upon an elevated TT, normal FT and oligomenorrhea; 11.3% (n=182) based upon an elevated FT, normal TT and oligomenorrhea; 1.1% (n=17) based upon oligomenorrhea with normal TT, normal FT and elevated DHEA-S; and 23.9% (n=384) based upon normal serum androgens, oligomenorrhea, and hirsutism (mFG&gt;4).
Results suggest that the diagnosis of PCOS is rarely made based upon elevated DHEA-S in the setting of normal TT and FT. Most women had elevated TT and/or FT values, but still a significant proportion (23.9%) of women were diagnosed with PCOS based upon hirsutism in the context of normal serum androgens. Thus, an assessment of hirsutism, which is both timely and inexpensive, is a strong predictor and valuable tool in diagnosing PCOS, reserving DHEAS when better measures of hyperandrogenism are not diagnostic.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.