Symptoms Of Hyperandrogenism Research Articles

Clinical Manifestations and Challenges in Adolescent and Adult Females With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.

Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is a rare genetic condition that results in cortisol deficiency and excess production of adrenal androgens. While the introduction of newborn screening for CAH has reduced morbidity and mortality, management of CAH remains challenging. Lifelong treatment with glucocorticoids is required to replace the endogenous cortisol deficiency and reduce excess adrenal androgens. Undertreatment or overtreatment with glucocorticoids can lead to multiple disease- and treatment-related comorbidities, including impaired growth and compromised final height, menstrual irregularities and reduced fertility in females, and long-term cardiometabolic complications. In addition to avoiding adrenal crisis and sudden death, treatment goals in adolescent females with CAH are to obtain normal growth and bone maturation and normal timing of puberty. Management of adolescents is particularly challenging due to changes in growth and sex hormone levels that can lead to inadequate suppression of adrenal androgens and increasing independence that can affect treatment adherence. During the transition to adult care, treatment goals focus on preventing symptoms of hyperandrogenism, preserving menstrual regularity and fertility, and providing education and support for issues related to sexuality, atypical genitalia, and/or complications from previous surgical treatment. In addition, patients must be monitored continuously to prevent long-term complications such as decreased bone mineral density, obesity, diabetes, and hypertension. In this review, we discuss the challenges faced by adolescent and adult females with CAH and provide guidance to health-care professionals to help patients to navigate these challenges.

12405 A Severe Case Of Virilization Of Premenopausal Woman Secondary To A Rare Testosterone Producing Sertoli Cell Tumor

Abstract Disclosure: S. Waheed: None. N.J. Vernetti: None. S. Nakhle: None. Introduction: We present a case of a premenopausal woman with elevated testosterone who was diagnosed with an aggressive Sertoli cell tumor of the ovary. Case Description: A 49-year-old multiparous female presented to the clinic with hirsutism and markedly elevated testosterone levels. Her symptoms started a year before the presentation with diffuse alopecia, acne, and increased muscle mass. Last menstrual periods were 3 years, prior to the presentation.Denies any exposure to testosterone herself or indirectly through family. On physical exam, blood pressure 170/122 coarse features, oily skin, and muscular build. She had terminal hair loss and increased hair growth on face and arms. Laboratory data revealed testosterone levels of 9280 ng/dl (reference range premenopausal 18-55 ng/dl), free testosterone > 50 ng/dl (premenopausal0-4.2 ng/dl), LH <0.3 mIU/mL (2.4-12.6 mIU/mL), FSH <0.3 mIU/mL (3.6-12.5 mIU/mL), 17-OHP 2270 ng/dl (15-70 ng/dl), DHEA-S 71 ug/dl (<229 ug/dl), LDL 128 mg/dl, Creatinine 1.29 and hematocrit 56% (34-44.6%). CT abdomen/pelvis showed 10 cm ovarian mass. She underwent Total Abdominal Hysterectomy-Bilateral Salpingo Oophorectomy (TAH-BSO). After the surgery, her testosterone levels normalized and features of hyperandrogenism resolved. Pathology report revealed sex cord stromal tumor Not otherwise specified (NOS) with cellular atypia and possible aggressive behavior. Discussion: Androgen-producing tumors in women are rare neoplasms that can cause secondary virilizing characteristics. Of patients presenting with symptoms of hyperandrogenism, these tumors are found in ∼0.2% of cases. Androgen-producing tumors can arise from the ovary or the adrenal gland. Those arising from the ovary are rare, accounting for <5% of all ovarian tumors. Few cases of steroid cell tumors, not otherwise specified, have been reported in the literature.Testosterone elevation of more than 2 times upper normal limit increases the suspicion for cancer. In our patient, testosterone was 180 times above the normal range for women and 15 times above the normal range for men. With rapid virilization and significant elevation in testosterone, an androgen producing ovarian tumors should be considered. Presentation: 6/2/2024

7696 Ovarian Steroid Cell Tumor Presenting as Non-classical Adrenal Hyperplasia

Abstract Disclosure: V. Reddy: None. A. Gowda: None. V. Vattipally: None. D. Kunduru: None. IntroductionSteroid cell tumors(SCT) of the ovary make up less than 0.1% of all ovarian tumors. The three subtypes are stromal luteoma, Leydig cell tumor, and steroid cell tumor-not otherwise specified (NOS) which is the commonest subtype. Androgen excess is seen in 75% tumors and presents with virilization. Tumors are usually benign but maybe malignant in 25-43% cases. Factors predicting malignancy include size >7 cm, mitotic activity, necrosis, hemorrhage, and nuclear atypia. Case ReportA 29 y/o Caucasian female presented with secondary amenorrhea and hirsutism. History includes DM2,hypothyroidism,depression and morbid obesity. She reported early pubarche by age 8,menarche at age 13 and developed hirsutism and irregular menstrual cycles from age 15. No workup due to poor follow up until she saw PCP at age 21.She was diagnosed with PCOS and started on Metformin. Eventually referred to endocrinology at age 27, since amenorrhea and hirsutism persisted. On exam she had significant male pattern hair loss and hirsutism over face and body.She reported three first trimester miscarriages.Labs showed testosterone 370 ng/dl, 17 OHP 808 ng/dl, DHEAS 47 ng/dl, Estradiol 117 pg/ml, FSH 2.2 mIU/ml, LH 2.5 mIU/ml, androstenedione 319 ng/dl.Transvaginal US was unremarkable. She was diagnosed with non classical adrenal hyperplasia (NCAH) and started on treatment with prednisone 5 mg daily, drospirenone and spironolactone 100 mg daily.3 months later, labs showed 50% lowering of testosterone to 199 ng/dl and 17 OHP to 407 ng/dl.There was continued biochemical and clinical improvement at the next visit with 17 OHP 73 ng/dl and testosterone 55 ng/dl. Labs done 21 months after initial presentation, showed sudden dramatic rise in 17 OHP to 1148 ng/dl and testosterone to 639 ng/dl. Normal AFP, HCG, CEA, CA125, CA19-9, Inhibin A. CT showed 10.4 cm solid right ovarian mass and underwent right salpingo-oophorectomy. Pathology showed steroid cell tumor, NOS. Labs 1 month postoperatively showed complete normalization of testosterone to <3 ng/dl, 17 OHP to 11 ng/dl and DHEAS 0.66 ng/dl. Steroid therapy was tapered and discontinued. DiscussionWe present the case of a patient with ovarian SCT presenting as NCAH.SCTs are very rare accounting for only 0.1% of all ovarian tumors. Since they commonly secrete androgens, they present similarly to CAH or PCOS and may rarely even co-exist with CAH. Differentiating between NCAH and SCT is difficult especially when there is initial response to steroid therapy and imaging is unremarkable as with our patient. It is important to consider SCT in patients with hyperandrogenism even in the setting of elevated 17 OHP levels. Care should be taken to follow up both clinical and metabolic metrics closely and investigate if any change is noticed. Early diagnosis can prevent irreversible symptoms of hyperandrogenism. Presentation: 6/1/2024

8661 A case of post-menopausal female with virilization due to Sertoli-Leydig cell ovarian tumor recurring in contralateral ovary 8 years later

Abstract Disclosure: M.S. Maharaul: None. J.L. Miller: None. Introduction: Sertoli-Leydig cell tumors (SLCTs) are rare androgen-secreting tumors of the ovaries, accounting for less than 0.5% of all ovarian tumors. Their incidence peaks in the second to third decade of life. New onset of severe hyperandrogenism with virilization in postmenopausal women is exceedingly rare, and the three most frequent causes are ovarian tumors, ovarian hyperthecosis and adrenal androgen producing tumors. We report one such case of ovarian androgen producing tumor which was further complicated by recurrence in the contralateral ovary. Case: A 66-year-old woman presented for evaluation of hyperandrogenism. Physical examination revealed evidence of virilization and clitoromegaly. Laboratory workup was remarkable for total serum testosterone level of 367 ng/dL with normal dehydroepiandrosterone sulfate and cortisol levels. A computerized scan of abdomen did not show any adrenal masses. Transvaginal ultrasound revealed uterine myomas but did not show any ovarian pathology. She underwent selective vein catheterization of her adrenal glands as well as ovaries and was noted to have right ovary secreting 3,982 ng/dL of testosterone whereas all other samples had total testosterone levels < 200 ng/dL. She underwent right salpingo-oophorectomy. Histopathologic examination revealed a 2.2 cm well differentiated Sertoli-Leydig cell tumor confined to the ovary; the fallopian tube was negative for tumor. Six weeks later, her serum total testosterone level was 18 ng/dL. 8 years later, she returns with recurrent symptoms of hyperandrogenism. Repeat workup revealed a total testosterone level of 662 ng/dL. A computerized scan of abdomen and transvaginal ultrasound revealed an unremarkable uterus and left ovary. Magnetic resonance imaging of the pelvis was done that showed a 1.2 cm enhancing mass in the left ovary. She then underwent left salpingo-oophorectomy and supracervical hysterectomy. Histopathologic examination revealed a 1.5 cm Sertoli-Leydig-cell tumor of the left ovary, the fallopian tube was negative for tumor. Six weeks later, her serum total testosterone level was 24 ng/dL and she felt significant improvement in her symptoms. Conclusion: We present an interesting case of virilization in a post-menopausal female due to Sertoli-Leydig cell tumor that resolved after unilateral oophorectomy but recurred 8 years later in the contralateral ovary with resolution after completion oophorectomy. Presentation: 6/2/2024

7696 Ovarian Steroid Cell Tumor Presenting As Non-classical Adrenal Hyperplasia

Abstract Disclosure: V. Reddy: None. A. Gowda: None. V. Vattipally: None. D. Kunduru: None. Ovarian Steroid Cell Tumor Presenting as Non-classical Adrenal Hyperplasia IntroductionSteroid cell tumors(SCT) of the ovary make up less than 0.1% of all ovarian tumors. The three subtypes are stromal luteoma, Leydig cell tumor, and steroid cell tumor-not otherwise specified (NOS) which is the commonest subtype. Androgen excess is seen in 75% tumors and presents with virilization. Tumors are usually benign but maybe malignant in 25-43% cases. Factors predicting malignancy include size >7 cm, mitotic activity, necrosis, hemorrhage, and nuclear atypia. Case ReportA 29 y/o Caucasian female presented with secondary amenorrhea and hirsutism. History includes DM2,hypothyroidism,depression and morbid obesity. She reported early pubarche by age 8,menarche at age 13 and developed hirsutism and irregular menstrual cycles from age 15. No workup due to poor follow up until she saw PCP at age 21.She was diagnosed with PCOS and started on Metformin. Eventually referred to endocrinology at age 27, since amenorrhea and hirsutism persisted. On exam she had significant male pattern hair loss and hirsutism over face and body.She reported three first trimester miscarriages.Labs showed testosterone 370 ng/dl, 17 OHP 808 ng/dl, DHEAS 47 ng/dl, Estradiol 117 pg/ml, FSH 2.2 mIU/ml, LH 2.5 mIU/ml, androstenedione 319 ng/dl.Transvaginal US was unremarkable. She was diagnosed with non classical adrenal hyperplasia (NCAH) and started on treatment with prednisone 5 mg daily, drospirenone and spironolactone 100 mg daily.3 months later, labs showed 50% lowering of testosterone to 199 ng/dl and 17 OHP to 407 ng/dl.There was continued biochemical and clinical improvement at the next visit with 17 OHP 73 ng/dl and testosterone 55 ng/dl. Labs done 21 months after initial presentation, showed sudden dramatic rise in 17 OHP to 1148 ng/dl and testosterone to 639 ng/dl. Normal AFP, HCG, CEA, CA125, CA19-9, Inhibin A. CT showed 10.4 cm solid right ovarian mass and underwent right salpingo-oophorectomy. Pathology showed steroid cell tumor, NOS. Labs 1 month postoperatively showed complete normalization of testosterone to <3 ng/dl, 17 OHP to 11 ng/dl and DHEAS 0.66 ng/dl. Steroid therapy was tapered and discontinued. DiscussionWe present the case of a patient with ovarian SCT presenting as NCAH.SCTs are very rare accounting for only 0.1% of all ovarian tumors. Since they commonly secrete androgens, they present similarly to CAH or PCOS and may rarely even co-exist with CAH. Differentiating between NCAH and SCT is difficult especially when there is initial response to steroid therapy and imaging is unremarkable as with our patient. It is important to consider SCT in patients with hyperandrogenism even in the setting of elevated 17 OHP levels. Care should be taken to follow up both clinical and metabolic metrics closely and investigate if any change is noticed. Early diagnosis can prevent irreversible symptoms of hyperandrogenism. Presentation: 6/1/2024

Effect of Myo-Inositol in Treating Polycystic Ovary Syndrome (PCOS): A Review

Introduction: Background: Women of reproductive age are often affected by Polycystic Ovary Syndrome (PCOS), a condition that can cause infertility and metabolic problems. Hormonal changes contribute to PCOS's mechanism. It involves three interrelated symptoms, namely ovulation disorders, androgen excesses, and Polycystic Ovarian Morphology (PCOM), which should all be treated appropriately. Inositol therapy has been shown to play a significant role in PCOS in several studies. Despite this, there is no comprehensive discussion of Myo-Inositol (MI) and D-Chiro-Inositol (DCI) in relation to particular symptoms. Aim: The purpose of this review is to demonstrate how well Myo-inositol treats PCOS symptoms. Additionally, the study emphasises on evaluating inositol consumption while considering their physiological characteristics and the process by which certain PCOS symptoms arise. Methods: Using the databases PubMed and Google Scholar, a review of the literature was carried out using one of the following keywords: PCOS, myo-inositol, and insulin resistance. Results: Multiple research studies have shown that the treatment of MI improved the function of ovaries and fertility in patients with Polycystic Ovarian Syndrome (PCOS), reduced symptoms of hyperandrogenism, including acne and hirsutism, beneficially affected metabolic aspects, and regulated a number of hormonal factors that are deeply connected to the function of the reproductive system and ovulation. Thus, using MI as a treatment has become a breakthrough approach to enhance spontaneous ovulation, stimulate ovulation, or minimise PCOS symptoms. Conclusion: A physiological ratio of 40:1 between MI and DCI could prove to be advantageous for addressing the metabolic, hormonal, and reproductive components of PCOS, according to the existing clinical evidence.

Prevalence and Impact of Poly cystic Ovary Syndrome and Its Associated Irritable Bowel Syndrome among the Students: A Cross Sectional Study

To determine the prevalence and impact of poly cystic ovary syndrome (PCOS) and its associated irritable bowel syndrome (IBS) among college students. Materials and Methods: A cross-sectional study involving 280 female college students aged 17 to 28 years was conducted. Data collection was carried out using a structured questionnaire administered through Google Forms. The questionnaire gathered information on the following aspects: Demographic characteristics: Age at menarche. PCOS status: Presence or absence of PCOS diagnosis, family history of PCOS or infertility. Menstrual cycle characteristics: Duration of Menstrual bleeding, flow of menstrual bleeding, severity of menstrual pain. Hyper androgenic symptoms : Acne score, hirsutism score. IBS symptoms: Abdominal pain, cramping, diarrhoea, constipation, and psychological distress. Statistical analysis: The collected data was analyzed using descriptive statistics, including frequencies and percentages. Chi-square tests were used to assess the association between PCOS and IBSsymptoms.

Excessive caffeine intake inhibits steroidogenesis, folliculogenesis and disrupts utero-ovarian tissue histomorphology integrity in experimental rats, and precipitates polycystic ovary syndrome in Sprague-Dawley rats

Polycystic ovarian syndrome (PCOS) is characterized by anovulation and hyperandrogenism symptoms. Caffeine is popularly consumed and it is a legal psychoactive substance. This study evaluated the effect of excessive caffeine intake on utero-ovarian tissue in polycystic ovary syndrome rats. Twenty-four female rats randomized into group A control received 2 ml of normal saline. Group B received 4 mg/kg body weight (bwt) i.p of estradiol valerate (EV) on the first day, Group C received 100 mg/kg bwt of caffeine orally, and Group D received i.p 4 mg/kg bwt EV and 100 mg/kg bwt of caffeine orally. The experiment lasted 30 days. Histology of the ovary and uterus, oxidative and antioxidant, reproductive hormone, lipid profile, inflammatory markers, and apoptosis markers were evaluated.The ovarian histoarchitecture revealed degeneration of the theca cells, granulosa, and corpus luteum, and loss of mucin granules in the uterine tissues in PCOS, CAF, and PCO+CAF. The estrous cycle became irregular, with prolonged diestrous and proestrus phases. Marked rise in oxidative markers and decline in the activities of ovarian enzymatic antioxidants, inflammatory response, caspase-dependent apoptosis, and hormonal imbalance.Excessive caffeine consumption, therefore impaired utero-ovarian integrity, hormones, inflammatory indicators, oxidant and antioxidant parameters, apoptotic markers, and the estrous cycle.

THE RELATIONSHIP OF VITAMIN D TOPOLYCYSTIC OVARY SYNDROME (PCOS) TEENAGERS AT KOTO TANGAH PADANG DISTRICT HIGH SCHOOL IN 2022

PCOS is characterized by increased ovarian and adrenal androgen secretion,hyperandrogenic symptoms such as hirsutism, acne and/or alopecia, menstrual irregularities,and polycystic ovaries. The prevalence of PCOS in 2016 was 6−21% of reproductive ageworldwide. PCOS is the most common female endocrine disorder with a prevalence of around4-6% in women of reproductive age in Indonesia. Vitamin D deficiency can increase PCOSsymptoms. The research design was cross-sectional. The study was conducted at SMA N 7,SMA N 8 and SMA N 13 Padang in Koto Tangah District in May-August 2022. The researchsample was high school students who experienced menstrual cycle disorders and were willingto agree to informed consent for the study with a sample size of 59 respondents. Vitamin Dlevels were examined using the 25-Hydroxyvitamin D ELISA Kit. Data were analyzed by chi-square test. The results showed that 86.4% of respondents experienced vitamin D deficiency.Statistically there was a relationship between PCOS in adolescents accompanied byhyperandrogens and vitamin D levels, there was a relationship between PCOS in adolescentsaccompanied by obesity and vitamin D levels, there was no relationship between PCOS inadolescents accompanied by acanthosis nigrican and vitamin D levels, and there was norelationship between PCOS in adolescents accompanied by hyperandrogens, obesity andacanthosis nigrican with vitamin D levels in SMA Koto Tangah District Padang in 2022. Theconclusion of this study is that there is a relationship between PCOS in adolescentsaccompanied by hyperandrogens and vitamin D levels and there is a relationship betweenPCOS in adolescents accompanied by obesity and vitamin D levels. .

Reference intervals for serum 11-oxygenated androgens in children.

Classic androgens such as dehydroepiandrosterone, androstenedione, and testosterone are generally measured for diagnosis and treatment monitoring in children and adolescents with hyperandrogenism, as can occur in congenital adrenal hyperplasia, premature pubarche, or polycystic ovarian syndrome. However, adrenally-derived 11-oxygenated androgens also contribute to the androgen pool and should therefore be considered in clinical management. Nevertheless, paediatric reference intervals are lacking. Therefore, we developed a serum assay to establish reference intervals for four 11-oxygenated androgens in addition to four classic androgens. Reference interval study for serum 11-oxygenated androgens in children. We developed and validated a sensitive LC-MS/MS assay and quantified eight serum androgens, including four 11-oxygenated androgens, in serum of 256 healthy children (aged 0-17 years old). An age-dependency for all androgens was observed, and therefore we divided the cohort based on age (prepubertal (n=133; 94 boys, 39 girls) and pubertal (n=123; 52 boys, 71 girls)) to compute reference intervals (2.5th - 97.5th percentiles). In the prepubertal group, there was no significant sex-difference for any of the measured androgens. In the pubertal group, androstenedione, testosterone, and dihydrotestosterone showed a significant difference between boys and girls. In contrast, adrenal androgens dehydroepiandrosterone, 11-hydroxyandrostenedione, 11-ketoandrostenedione, 11-hydroxytestosterone, and 11-ketotestosterone did not. We developed and validated an assay for 11-oxygenated androgens, in addition to four classic androgens and established reference intervals. This enables a comprehensive evaluation of serum androgen status in children with clinical symptoms of hyperandrogenism.

Reduction in the Free Androgen Index in Overweight Women After Sixty Days of a Low Glycemic Diet.

Hyperandrogenism is among the most common endocrine disorders in women. Clinically, it manifests as hirsutism, acne, and alopecia. A healthy lifestyle, including nutritious dietary patterns and physical activity, may influence the clinical manifestation of the disease. This study determined the effect of a low-glycemic index anti-inflammatory diet on testosterone levels and sex hormone-binding globulin (SHBG) and clinical symptoms in hyperandrogenic women at their reproductive age. The study included 44 overweight and obese women diagnosed with hyperandrogenism. The anthropometrics (weight, height, body mass index, waist circumference, hip circumference), physical activity, and dietary habits were assessed using valid questionnaires, scales, stadiometer, and tape meter. The significant p-value was <0.001. Serum testosterone and SHBG levels were measured using automated immunoassay instruments. The intervention based on a low-glycemic index diet with anti-inflammatory elements and slight energy deficit decreased total testosterone levels (p<0.003), increased SHBG levels (p<0.001), and decreased the free androgen index (FAI; p<0.001). Post-intervention, overall well-being was much higher than in the pre-intervention period (p<0.001), and stress was diminished (p<0.001). Western nutritional patterns positively correlate with clinical hyperandrogenism progression, whereas several factors of the low-glycemic index diet with anti-inflammatory elements and slight energy deficit positively associate with reduced clinical hyperandrogenism symptoms. In overweight and obese women, proper selection of diet, introduction of moderate physical activity, and reduction in weight, stress factors, and alcohol consumption translate into several positive effects, including reduced FAI and symptoms such as acne, hirsutism, menstrual disorders, and infertility.

Congenital dysfunction of the adrenal cortex on the background of 11β-hydroxylase deficiency

Congenital adrenal dysfunction (CHD) is a variant of hereditary fermentopathies that lead to a violation of the synthesis of cortisol in the adrenal cortex. Late diagnosis of this pathology significantly impairs the quality of life of patients, and in some cases can lead to fatal consequences. The most common form of CHD, occurring in more than 90% of cases, is due to a deficiency of 21-hydroxylase, which is responsible for the synthesis of deoxycorticosterone and 11-deoxycortisol. The prevalence of this form is 1:10,000 to 1:20,000 newborns in the world, in Russia — 1:9500. In second place is the deficiency of 11β-hydroxylase (hypertonic form of HCHD), which affects the synthesis of cortisol. This form of the disease occurs in about 1:100,000 newborns in the world, and in Russia the prevalence of this form is unknown [1].The cause of any form of CHD is mutations in the genes responsible for the synthesis of enzymes or transport proteins involved in the synthesis of cortisol. 11β-hydroxylase is synthesized in the zona fasciculata of the adrenal cortex and is regulated by adrenocorticotropic hormone by a negative feedback mechanism. 11β-hydroxylase deficiency (hypertonic form of HCHD) develops as a result of mutations in the CYP11B gene located on chromosome 8. This mutation blocks the enzymatic conversion of 11-deoxycortisol to cortisol, as well as deoxycorticosterone (DOC) to corticosterone, leading to the accumulation of DOC, which has mineralocorticoid activity. It is the excess of deoxycorticosterone that causes an increase.In 21-hydroxylase deficiency, the clinical picture is primary adrenal insufficiency (deficiency of glucoand mineralocorticoids). The clinical picture of mineralocorticoid deficiency includes salt loss syndrome: arterial hypotension, tachycardia, adynamia, fibrillary muscle twitching, dryness and decreased skin turgor, cyanosis and marbling of the skin. Glucocorticoid deficiency is manifested by muscle weakness, fatigue, hyperpigmentation of the skin. With a deficiency of 11β-hydroxylase, due to an increase in the level of deoxycorticosterone, there is no deficiency of mineralocorticoid activity, on the contrary, against the background of clinical signs of glucocorticoid insufficiency, an increase in blood pressure may be observed. Hyperandrogenism is characteristic of both forms of CHD. Symptoms of hyperandrogenism in females: virilization of the external genitalia, amenorrhea, severe alopecia and hirsutism. In undiagnosed cases of CHD, patients with a female karyotype have a male phenotype.

SAT368 Severe Hyperandrogenism in a Young Woman with Elevated BMI: A Case Study of The Role of Weight Loss in The Management of PCOS

Abstract Disclosure: S. Rodriguez Ortega: None. I.R. Bass: None. Background: Increased adiposity enhances the phenotypic expression and severity of hyperandrogenism in women with Polycystic Ovarian Syndrome (PCOS). Weight loss has been associated with improved endocrine features in women with PCOS and elevated Body Mass Index (BMI). Bariatric surgery can be an effective means of significant weight loss and restoration of the hypothalamic pituitary axis. Case Presentation: A 21-year-old Hispanic nulligravid woman presented with history of oligomenorrhea, weight gain and hirsutism. Her symptoms started after menarche at 15 years old with irregular periods, hair growth on her face and neck, and rapid weight gain. She was evaluated by an endocrinologist and was found to have an elevated total testosterone level by LC/MS on several different occasions: 309ng/dl, 259ng/dl and 229 ng/dl, as well as elevated androstenedione 346 ng/dl (41-262ng/dl). She was treated with metformin and oral contraceptive pill for two years and then referred for second opinion. On our physical exam, she had a BMI of 44.60 kg/ m2, a deep voice, Ferriman Gallwey score of 12 and acanthosis nigricans. OCPs were held for three months for accurate testing and work up revealed total testosterone 164.7 ng/dl (10.0-55.0 ng/dl), sex hormone binding globulin 25.4 nmol/L (24.6-112.0 nmol/L), bioavailable testosterone 84.3ng/dL (51.4%), DHEAs 375 µg/dl (110-431.7 µg/dl), and androstenedione 264 ng/dl (41-262 ng/dl). Other causes of hyperandrogenism such as hyperprolactinemia, hypothyroidism and congenital adrenal hyperplasia were ruled out. MRI pituitary from outside facility was reviewed and was normal. MRI abdomen and pelvis with/without contrast was performed, which demonstrated normal adrenal glands and an 8.1 cm midline pelvic cyst, containing a 0.7 cm enhancing solid nodule. She was referred for surgery for concern for possible virilizing tumor. The cyst was surgically removed and intra-operative ovarian exploration and cytopathology from pelvic washing were negative. She was referred for bariatric surgery and underwent a sleeve gastrectomy. After 6 weeks, she lost 30lbs, BMI improved to 37.1 kg/ m2 and her menses resumed. Repeat labs showed improvement in her androgens: total testosterone 64.8ng/dl, SHBG 104nmol/L, androstenedione 127ng/dl. After 8 months, she lost 110lbs and has dramatic improvement in her hirsutism and clearance of her acanthosis nigricans. Conclusion: Sustained lifestyle changes and weight loss are a mainstay in the treatment of patients with PCOS and obesity. Bariatric surgery results in durable weight loss and restores the normal physiological balance of sex hormones and improves signs and symptoms of hyperandrogenism. Presentation Date: Saturday, June 17, 2023

THU643 Hyperandrogenism Caused By A Steroid Cell Tumor Of The Ovary In A Postmenopausal Woman

Abstract Disclosure: M.S. Myint: None. A. Pinero-Pilona: None. Introduction Steroid cell tumor-not otherwise specified (SCT-NOS) is a subtype of steroid cell tumors which, in turn, is a subtype of sex cord-stroma tumors of the ovary. SCTs are exceedingly rare, account for less than 0.1% of all ovarian tumors, can secrete androstenedione, α-hydroxyprogesterone, and testosterone, and cause hyperandrogenism. We present a case of SCT-NOS, which was revealed postoperatively and was associated with breast cancer. Clinical Case A 74-year-old postmenopausal woman presented approximately a year after the onset of hirsutism, frontal alopecia and an elevated serum total testosterone (TTST) 341 ng/dl (reference range 3 to 41 ng/dL) and free testosterone (FRTST) 10.5 pg/mL (reference range 0.0 to 4.2 pg/mL). She has no clitoromegaly, acne, striae, or changes in voice and no history of infertility or PCOS. Physical examination was significant for cushingoid appearance, frontal alopecia, and hirsutism on the face. Her estradiol level was 213 pg/mL (reference range 0 to 30 pg/mL), FSH and LH levels were in the postmenopausal range, 17-hydroxyprogesterone, DHEA-sulfate, androstenedione, and morning cortisol were normal. Pelvic ultrasonography and CT of the abdomen and pelvis did not reveal an adrenal or ovarian abnormality. We suspected an ovarian source and thus recommended bilateral oophorectomy due to the markedly elevated testosterone level and postmenopausal status. We also started spironolactone. Before setting up for surgery, she was diagnosed with invasive lobular left breast cancer and underwent surgery and radiotherapy. Then, she had bilateral salpingo-oophorectomy. After surgery, TTST dropped to 4 ng/dL and FRTST to 2 pg/mL. Her hyperandrogenic symptoms significantly subsided. Pathology revealed a 1.5 cm red-brown nodule within the left ovary. The nodule contains polygonal cells with vacuolated cytoplasm arranged in nests, cords, and sheets. Cells were positive in calretinin and inhibin and negative in Reinke crystal. A steroid cell tumor, NOS was confirmed. Pathologic features associated with aggressive clinical behavior were not present. Conclusion The incidence of SCT-NOS is highest in women of childbearing age but rare in postmenopausal women. There were only a few case reports of SCT-NOS, most of which are relatively larger and revealed on imaging. In our case, the imaging did not localize the tumor. Sex cord-stromal tumors are often not visualized on imaging. Failure to identify a tumor on imaging does not rule out the presence of a tumor. One should always rule out androgen-secreting tumors in cases of significantly high testosterone. When imaging fails to reveal a tumor, bilateral oophorectomy should be considered in postmenopausal women and an ovarian and adrenal venous sampling in women of childbearing age. It is worth doing so because hyperandrogenism is associated with an increased risk of endometrial and breast cancer. Presentation: Thursday, June 15, 2023

THU187 Genotype-Phenotype Correlation, Clinical Presentation And Feminizing Surgery In Children With Congenital Adrenal Hyperplasia Due To 21-Hydroxylase Deficiency: A Nationwide Multi-Center Study

Abstract Disclosure: M. Lind-Holst: None. A. Berglund: None. M. Duno: None. G. Hvistendahl: None. M. Fossum: None. A. Juul: None. N. Jørgensen: None. K.M. Main: None. C.H. Gravholt: None. D. Hansen: None. Background: Congenital adrenal hyperplasia (CAH) due to 21 hydroxylase deficiency (21OHD) is a common autosomal recessive disorder caused by pathogenic variants in CYP21A2. Genotype cannot always predict severity and clinical consequences, and genotype-phenotype is only well correlated in the most severe clinical cases of CAH. Furthermore, non-classical CAH suffers from non-diagnosis, especially in males. Objective: Describe the genotype-phenotype correlation in Danish children with 21OHD and identify the most frequent pathogenic CYP21A2 variants. We describe the clinical manifestations at time of diagnosis and present data on virilization and feminizing surgery of females, stratified by genotype group during 20 years. Method: A national population-based study of all Danish children diagnosed with 21OHD, combining health registries and medical record data. We identified pathogenic variants in CYP21A2 and genotype-phenotype correlation. Clinical presentation at diagnosis and feminizing surgery in females was stratified by genotype group: Null, A, B, C and D, reflecting the preserved 21-hydroxylase activity in increasing order. Results: Variants frequency of 494 unique alleles: Deletion (31.8%) followed by I2G, Q318X, I172N, V281L, P30L, Cluster-E6, R356W and insT by 25.9%, 9.1%, 8.6%, 8.7%, 6.5%, 1.4%, 1.4% and 0.6%, respectively. Genotype-phenotype correlations: Null: 98%, A: 94%, B: 50%, C: 76%. Overall, 62 of the 159 children (67%) had evidence of pseudo-precocious puberty at time of diagnosis which was the most frequent group of symptoms in genotype group B: 8.2%, C: 23.3% and D: 3.8%. Bone age advancement was significantly more advanced at the time of diagnosis in males compared to females (p=0.0009). The most frequently reported symptom at diagnosis in the genotype group null (n=20) and A (n=31) were: clitoral hypertrophy in females: 62.7%, failure to thrive: 29% and salt-wasting crisis: 22%. Clitoral hypertrophy was also present in genotype group B, C and D and feminizing surgery was performed in 85% of prenatally virilized females and overall in 40% of females at a median age of 0.9 years [IQR 0.5-1.6]. Conclusion: Genotype groups only predict phenotype with high certainty in the null and A genotype groups. In a national cohort evidence of virilization in females and feminizing surgery were observed in every genotype group. Delayed or non-diagnosis in children with SV and NC CAH was substantial, especially in males. We suggest that children with even mild hyperandrogenic symptoms and normal biochemical markers for 21OHD may benefit from genetic testing for CAH to establish a diagnosis. Presentation: Thursday, June 15, 2023

Successful Pregnancy in a Patient with Polycystic Ovary Syndrome Following Lifestyle Modification and Pharmacological Intervention: A Case Report

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age, often associated with obesity and fertility problems. This case report documents the management of a 32-year-old female patient diagnosed with Polycystic Ovary Syndrome (PCOS), who sought to conceive. Despite having normal hormonal levels, the patient exhibited insulin resistance, a common feature in PCOS. Intervention strategies included pharmacotherapy (metformin, spironolactone, and phentermine) and lifestyle modifications leading to significant weight loss (10.5% of total body weight). The treatments led to an improvement in the patient's metabolic profile, menstrual regularity, and reduction in hyperandrogenic symptoms. By December 2021, the patient had maintained her weight loss and improved metabolic parameters. She successfully conceived in January 2022 and delivered a healthy baby at term in August 2022. This case underscores the importance of weight management and metabolic control in improving fertility outcomes in patients with PCOS.

Study of women's knowledge of the role of androgens and their excess in women - research article

Introduction: excess androgens is one of the most common endocrine disorder in women. The ovaries and/or adrenal glands are responsible for the excess of androgens. The most common cause is polycystic ovary syndrome.&#x0D; The aim of the study: was to show the level of knowledge of the women surveyed about the role of androgens and to find out the degree of their awareness of androgen excess in women. Last but not least, it was important to find out which symptoms the respondents think are characteristic of androgen excess in women, whether they know the concept of hirsutism and what androgenetic alopecia looks like.&#x0D; Material and method: wykorzystano ankietę własnego autorstwa. Przebadano 172 kobiety. Dokonano porównania odpowiedzi na pytania pomiędzy podgrupami. Oparto się na aktualnej literaturze medycznej oraz artykułach oryginalnych i badawczych znalezionych w PubMed.&#x0D; Results: slightly more than half of those surveyed know that testosterone is produced by the ovaries and adrenal cortex. Only 35.5% of the women surveyed can name other hormones belonging to the androgens besides testosterone. 60.7% of women know the characteristic symptoms of hyperandrogenism. 51.7% know the term hirsutism and 32% correctly identify the most common cause.&#x0D; Conclusions: given the prevalence of endocrine disorders in women, it is important to expand and disseminate information on the symptoms and causes of androgen excess in women, especially among women without medical education.

Cancer risk in polycystic ovary syndrome patients: Common treatments and future perspectives

In women of childbearing age, polycystic ovarian syndrome (PCOS) is the most common endocrine and metabolic condition. Ovulatory dysfunction, clinical symptoms of hyperandrogenism, and multiple cystic ovaries are the hallmarks of PCOS. Women who have PCOS may have irregular insulin activity in addition to other difficulties such as pattern hair loss, acne, obesity, infertility, and hirsutism. An unhealthy lifestyle, hereditary causes, androgen exposures, and neuroendocrine factors are frequently the causes of PCOS. This results in an unbalanced hormonal state, hyperandrogenism, high insulin, and inflammation. Due to the overlapping metabolic and endocrine issues, PCOS patients' cancer risk has been the subject of debate for decades.This review article examines the relationship between PCOS and various types of reproductive cancers, focusing on the possible reasons for cancer in PCOS patients.

Serum 21-Deoxycortisol for Diagnosis of Nonclassic Congenital Adrenal Hyperplasia in Women With Androgen Excess.

Nonclassic congenital adrenal hyperplasia (NCCAH) requires exclusion before diagnosing polycystic ovary syndrome (PCOS). Increasing use of liquid chromatography and tandem mass spectrometry (LC-MS/MS) necessitates revision of immunoassay-based criteria for NCCAH. Measurement of 21-deoxycortisol (21DF) may simplify the diagnosis of heterozygosity (HTZ), the presence of 1 affected CYP21A2 allele, which currently relies on complex molecular studies. We aimed to determine LC-MS/MS-specific criteria for NCCAH and HTZ and compare the diagnostic accuracy of 21DF and 17-hydroxyprogesterone (17OHP). A cross-sectional study involving 99 hyperandrogenic females was performed. We identified females who had undergone both a synacthen stimulation test (SST) and CYP21A2 genotyping from 2010 to 2017, and prospectively recruited females referred for an SST to investigate hyperandrogenic symptoms from 2017 to 2021. Steroids were compared between genetically confirmed NCCAH, HTZ, and PCOS. Optimal 17OHP and 21DF thresholds for HTZ and NCCAH were determined by receiver operating characteristic analysis. Basal 17OHP, stimulated 17OHP, and 21DF were measured in 99, 85, and 42 participants, respectively. Optimal thresholds for NCCAH were 3.0 nmol/L and 20.7 nmol/L for basal and stimulated 17OHP, respectively. Basal and stimulated 21DF thresholds of 0.31 nmol/L and 13.3 nmol/L provided 100% sensitivity with specificities of 96.8% and 100% for NCCAH, respectively. Diagnostic thresholds for HTZ of 8.0 nmol/L, 1.0 nmol/L, and 13.6 for stimulated 17OHP, 21DF, and the ratio (21DF + 17OHP)/cortisol each provided 100% sensitivity with specificities of 80.4%, 90.5%, and 85.0%, respectively. LC-MS/MS-specific 17OHP thresholds for NCCAH are lower than those based on immunoassay. LC-MS/MS-quantified 17OHP and 21DF accurately discriminate HTZ and NCCAH from PCOS.

O-095 Different phenotypes of PCOS: Implications to clinical practice

Abstract Polycystic ovary syndrome (PCOS) is a very common, heterogeneous syndrome which presents with a spectrum of clinical and biochemical features. It is associated with both reproductive and metabolic dysfunction and has a negative impact on long term health, including mental health. Although there appears to be a common genetic background to PCOS, regardless of presentation, environmental factors, including diet, play an important part in determining the phenotype. The most commonly used diagnostic criteria, the Rotterdam criteria, takes account of the heterogenous nature of the syndrome but the spectrum of presentation can be categorised as four clinical and biochemical subtypes which comprise (A) ovulatory dysfunction, hyperandrogenism, polycystic ovaries (PCO), (B) ovulatory dysfunction, hyperandrogenism but without PCO, (C) hyperandrogenism without ovulatory dysfunction but with PCO and (D) ovulatory dysfunction with PCO but without hyperandrogenism. These are not rigid categories since some women may go from one to another, for example weight gain may lead to anovulation in a woman who previously had hirsutism but regular cycles. Nevertheless, the diagnostic sub-category has a significance influence on clinical management. Women who have both hyperandrogenism and ovulatory dysfunction (A&amp;B) are at higher risk of metabolic dysfunction which is exacerbated by obesity (and carries a high long-term risk of diabetes and cardiovascular disease) and so merit thorough investigation which includes assessment of glucose tolerance and lipids. Those who have predominantly ovulatory problems may require fertility treatment or regulation of menses but some who simply have irregular menses may need no specific treatment. Symptoms of hyperandrogenism (hirsutism, acne, alopecia) can be particularly distressing and may be best managed in collaboration with a dermatologist. The negative impact of PCOS on mental health is a very common problem, the high prevalence of which has only recently been appreciated. Not surprisingly, it is particularly relevant in those women who have moderate to severe symptoms of hyperandrogenism. In summary, PCOS is a syndrome characterised by a variety of symptoms and endocrine abnormalities and it is important to tailor treatment individually, according to the need for symptom relief and with regard to concerns about long-term health.