Severe Hyperandrogenism Research Articles

7874 Management Of “Hyperandrogenism” Confounded By Dermatology Biotin Prescriptions

Abstract Disclosure: S.S. Sundar: None. S. Shankar: None. M.S. Vaishnav: None. L. Lekkala: None. S. Sathyanarayana: None. C. Siddlingappa: None. K. M: None. T.-. Kamala: None. R.B. V: None. V. Nath: None. M.D. Chitra: None. P. Ravikumar: None. Introduction: Immunoassay interferences include: Cross-reactions, heterophile antibodies, biotin and anti-analyte antibodies, with positive or negative bias, leading to difficulties in clinical decision-making (confounding diagnosis, unnecessary investigations or inappropriate treatments). The interfering substance may be exogenous (e.g., drug or substance absorbed by patient) or endogenous (e.g., antibodies produced by patient). Clinical Case 2023 Dec 1 Dermatology management for hyperandrogenism 28-year-old female evaluated for acne 3 years (increased 4 months), hair fall 6 months and hirsutism 3 years (threading) Total Testosterone 443 ng/dL (10-55) CLIA Free Testosterone 8.9 pg/mL (0.1-6.4) ELISA DHEAS 209 µg/dL (35-430) CLIA S Cortisol 8 am 6.9 µg/dL (2.6-10.5) CLIA LH 4.2 mIU/mL (1.9-12.5); FSH 5.3 mIU/mL (3.0-8.0) T3 133 ng/dL (80-200); T4 8.5 ug/dL (4.8-12.7), TSH 3.78 µIU/mL (0.5-5.3) HbA1c 5.0%; Glucose fasting 81 mg/dL; Insulin fasting 39.4 mU/L (3-25); HOMA-IR 5.2; HOMA%B 380; HOMA%S 19.2; T3 133 ng/dL (80-200) 2023 Dec 14 Endocrinology for “scaringly” very high testosterone levels Menstrual history: Menarche 11 years; Cycles regular. Unmarried Family history: Diabetes++; Hirsutism+; Infertility- Physical exam: Height 159 cm; Weight 55 kg; BMI 21.8 kg/m2; Ferriman Gallwey score 11; Pulse 75; BP 79/62; Thyroid: Grade 0. In view of total testosterone levels in “neoplastic androgen excess” range, further endocrinology evaluations (multiple labs and assays) were carried out. However, discordance between the mild clinical versus severe biochemical hyperandrogenism was noted. Review of the dermatology prescription indicated that patient had consumed only one 10 mg tablet of biotin 36 hours before the earlier blood draw obtained by dermatologist. Total Testosterone 22.3 and 33.8 ng/dL (6-82) ECLIA; 19.7 (15-70) LCMS Free Testosterone 0.69 pg/mL (< 2.85) (ELISA) DHEAS 101 µg/dL (45-380) LCMS Androstenedione 104 ng/dL (75-205) LCMS 17OH Progesterone 0.89 ng/mL (0.16-2.05) EIA; 0.40 (0.35-2.9) LCMS S Cortisol 5.92 ug/dl (6-18) ECLIA; 5.45 (5-23) LCMS FSH 2.74; LH 6.07; Prolactin 20.1 ng/mL (4.7-23.3) T3 114 ng/dL; T4 7.2 µg/dL; TSH 1.29 Diagnosis Falsely elevated total testosterone (and free testosterone) levels due to biotin immunoassay interference. Clinical Lessons: Very limited studies exist confirming the exact clinical indications for biotin (eg: improvement of hair quality or quantity, or nail growth). FDA warning highlights biotin’s interference (false elevations or reductions) with immunoassays relying on biotin-streptavidin technology. Physicians must ask patients about supplement usage, and discontinue biotin for 8 hours for patients taking 10 mg/day, 3 days for 100-300 mg/day, 7 days for children taking 2 and 15 mg/kg/daily, and inform laboratory if diagnostic test was performed while taking biotin. Presentation: 6/2/2024

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

7452 A Diagnostically Challenging Case of Hyperandrogenism in Postmenopausal Woman

Abstract Disclosure: M.S. Hossain: None. S. Hossain: None. B. Gautam: None. H. liao: None. S.C. Kumar: None. D.S. Rosenthal: None. Background: The diagnosis of new-onset severe hyperandrogenism in postmenopausal women is rarely encountered, posing a unique challenge for clinicians. Ovarian hyperthecosis and androgen-secreting tumors are the usual suspects in post menopause. In our case ovarian hyperthecosis is the primary consideration but elevated 17-OH Progesterone (17-OHP) introduces the potential co-existence of Non classical congenial adrenal hyperplasia (NCCAH) or rare instances of Sertoli-Leydig Cell Tumor (SLCT). Case Presentation: A 70 years old female, with no past medical history, referred to the Endocrinology clinic for significantly elevated testosterone level. She reported excessive hair growth in various areas of her body since 2022, which required shaving almost every day. She also reported male pattern hair loss and weight loss of 15 lbs over the last three months. She denied headache, vision changes, deepening of voice, history of fertility problems and use of exogenous testosterone. Her vital sign were normal. On examination, she had clitoromegaly, terminal hair growth on her upper lip and chin, breast atrophy, male pattern baldness, but no cushingoid or acromegaly features. Blood tests showed significantly elevated total testosterone: 1422 ng/dl (2-45); free testosterone: 147.9 pg/ml (0.2-3.7) and Estradiol: 64 pg/ml (Postmenopausal <31) with low LH: 7.6 mIU/ml (Postmenopausal 10.0-54.7) and FSH: 22.2 mIU/mL (Postmenopausal 23-116). Her serum ACTH, DHEA Sulfate, 11-deoxycortisol, 17 OH pregnenolone, TSH, Free T4, prolactin, IGF-1 were normal while her 17-OHP: 396 ng/dl (<45 ng/dl) was significantly elevated. An ACTH stimulation test showed 17-OHP level of 734 ng/dl at 30 minutes and 901 ng/dl at 1 hour. Pelvic ultrasonography: right ovary of 2.3 x 1.6 x 1.9 cm and the left ovary of 3.1 x 1.8 x 3.0 cm. MRI showed normal adrenal glands but a prominent left ovary. Patient was referred to the Obstetrics department to undergo bilateral oophorectomy for the definitive diagnosis and treatment. Discussion: The current ACTH stimulation test for non-classical congenital adrenal hyperplasia is validated for premenopausal women but lacks standardization in post-menopausal state. In our case, distinguishing the source of elevated 17-OHP between adrenal (NCCAH) and ovarian (SLCT) was difficult. Unexpected asymmetry in ovarian size observed in our case further complicates the scenario, contrasting with the typical symmetrical enlargement seen in ovarian hyperthecosis. Pending surgical pathology will further guide the management. This case highlights the complexity of diagnosing hyperandrogenism in postmenopausal women, emphasizing the significance of thoroughly exploring differential diagnoses and meticulously analyzing laboratory results. Presentation: 6/2/2024

9274 Combined Ovarian and Adrenal Vein Sampling in Women Presenting with Severe Hyperandrogenism

9274 Combined Ovarian and Adrenal Vein Sampling in Women Presenting with Severe Hyperandrogenism

7417 Combined Ovarian and Adrenal Vein Sampling in Women Presenting with Severe Hyperandrogenism

7417 Combined Ovarian and Adrenal Vein Sampling in Women Presenting with Severe Hyperandrogenism

Case Report: Hyperandrogenism in Menopause.

Postmenopausal androgen excess often occurs due to the imbalance between the rapid decline in ovarian estrogen and a relatively gradual decline in androgen secretion. The rapid onset of hirsutism, alopecia, and acne, on the other hand, is a rare occurrence and requires further investigation in order to rule out an underlying neoplasm. A 54-year-old woman arrived at the endocrinology outpatient clinic for the appearance of hirsutism and defluvium capitis in the past 9 months. She had hypertrichosis of the face, trunk, and mammary areolae and reduced timbre of voice. Circulating androgens were higher than normal levels (testosterone: 7.7 ng/mL, DHEAS: 5437 mcg/L, 17-OH-progesterone: 3.1 nmol/L), gonadotropin and prolactin levels were normal, and Nugent test was negative. Abdominal CT scan was negative for adrenal lesions, while transvaginal ovarian ultrasonography revealed a left adnexal formation (19x18x24 mm) compatible with stromal neoplasm. A bilateral hysteroannessiectomy was performed. Histological examination was diagnostic for multiple ovarian Leydig cell tumors. The most frequent cause of postmenopausal hyperandrogenism is polycystic ovary syndrome. It is necessary to exclude the presence of neoplastic causes (ovarian or adrenal androgen- secreting tumors). In case of marked virilization and severe hyperandrogenism, it is useful to perform transvaginal ultrasonography to search for the presence of ovarian hypertrichosis or androgen-secreting ovarian tumors and a CT/RM scan to study the adrenal glands. The best treatment for hyperandrogenism of neoplastic origin is surgery. Patients who are not candidates for this approach are candidates for therapy with GnRH agonists.

O-257 Comparing the accuracy of the novel clustering model versus phenotype classification in predicting live birth in polycystic ovary syndrome women undergoing In-Vitro fertilization

Abstract Study question Is the clustering model more accurate than phenotype classification in predicting live birth in polycystic ovary syndrome (PCOS) women undergoing in vitro fertilization (IVF)? Summary answer Novel PCOS clusters, identified by patients’ endocrine and metabolic profiles, more accurately predict live birth rates in women undergoing IVF than the traditional phenotype classification What is known already PCOS is a heterogeneous condition that affects fertility and IVF success. It is classified based on three factors: hyperandrogenism (HA), ovulatory dysfunction (OD), and polycystic ovaries (PCOM). The ESHRE/ASRM classification system identifies four phenotypes: A (including all three factors), B (HA and OD), C (HA and PCOM), and D (OD and PCOM). Although this classification is widely used, its focus solely on clinical signs and symptoms, while neglecting underlying endocrine and metabolic factors, may limit its effectiveness in predicting fertility outcomes in PCOS patients. Therefore, classifying PCOS patients may require a more comprehensive and inclusive assessment approach. Study design, size, duration This prospective cohort study was conducted from June 2020 to August 2022 at a tertiary IVF center in Ho Chi Minh City, Vietnam. Clustering models were built based on the endocrine and metabolic profiles of 731 PCOS patients. Patients were grouped into novel clusters based on their endocrine and metabolic profiles and compared with traditional phenotypes classification. The primary outcome measured was the live birth rate. Participants/materials, setting, methods Patients aged 18–45, diagnosed with PCOS according to the Rotterdam 2003 criteria, and undergoing IVF treatment were included in the study. Patients with hypothyroidism, Cushing’s syndrome, congenital adrenal hyperplasia, or contraindications to hormonal treatment were excluded. We employed Gaussian Mixture Models for clustering, using endocrine and metabolic data as the key features. We then compared the accuracy of the clustering model with phenotype classification in predicting IVF outcomes using a logistic regression model. Main results and the role of chance We identified three distinct clusters among polycystic ovary syndrome (PCOS) patients. Cluster 0 (n = 298) was characterized by significant insulin resistance and dyslipidemia. Cluster 1 (n = 219) displayed the lean PCOS phenotype, and Cluster 2 (n = 214) had moderate insulin resistance with severe hyperandrogenism. Our findings indicated that Clusters 1 and 2 had a higher cumulative live birth rate (CLBR) (39.7% and 37.9% versus 28.5% in Cluster 0, p = 0.015) and lower gestational diabetes rates (8.68% and 6.07%, respectively) compared to Cluster 0 (12.4%, p = 0.048). Additionally, the prevalence of hypertensive disorders during pregnancy showed differences across clusters (3.69% in Cluster 1, 0.46% in Cluster 2, and 2.8% in Cluster 0, p = 0.059). In contrast, the traditional phenotype classification did not demonstrate significant differences in CLBR, gestational diabetes, and hypertensive disorders. The cluster-based method provided a more accurate prediction of CLBR using logistic regression, with an AUC of 0.67 (95% CI: 0.57-0.76) compared to 0.49 (95% CI: 0.41-0.59) for traditional classifications (p = 0.001) Limitations, reasons for caution This is a single-center study conducted on Vietnamese patients. Therefore, the generalizability may be limited. The novel clustering’s predictive value for IVF outcomes in PCOS patients requires further validation in prospective studies. Wider implications of the findings This study suggests a potential shift towards personalized IVF treatment strategies for PCOS, using machine learning-based PCOS clustering identified by patients’ endocrine and metabolic profiles. Trial registration number NCT04364087

Use of selective adrenal and ovarian venous sampling in postmenopausal women with severe hyperandrogenism: Report of 3 cases

Use of selective adrenal and ovarian venous sampling in postmenopausal women with severe hyperandrogenism: Report of 3 cases

SAT364 A Rare Cause of Hyperandrogenism in a Premenopausal Woman

Abstract Disclosure: L. El Musa Penna: None. W. Medina-Torres: None. L.R. Sepulveda-Garcia: None. L.N. Madera Marin: None. A. Rosado-Burgos: None. M.A. Ortiz-Rivera: None. B. Torres Rivera: None. M. Alvarado: None. M. Ramirez: None. L.A. Gonzalez-Rodriguez: None. M. Marcos Martínez: None. M. Correa Rivas: None. N. Bracero, MD: None. Hyperandrogenism in premenopausal women is most commonly associated to polycystic ovarian syndrome (PCOS). Approximately 10% of females in reproductive age present with clinical and/or biochemical findings of androgen excess, such as hirsutism, acne, alopecia, oligo-amenorrhea or if hyperandrogenism is severe it can lead to extreme virilization. Androgen excess can also contribute to insulin resistance. In this case we discuss a patient with severe hyperandrogenism, extreme insulin resistance and a rare cause of androgen excess in a woman of childbearing age. 34-year-old female patient G0P0 with type 2 diabetes mellitus (T2DM) on continuous insulin infusion system (CIIS), familial partial lipodystrophy, PCOS and severe hyperandrogenism, who was referred to our clinics for management of uncontrolled T2DM. Patient was on CIIS with regular insulin U-500 using a total daily dose of 95 units. She referred amenorrhea for the past 12 years and significant progression of hirsutism, alopecia and acanthosis nigricans in the past two years. Patient had clinical findings of hyperandrogenism such as hirsutism evaluated with modified Ferriman-Gallwey scale with a score of 32, alopecia Ludwig class 3 and marked acanthosis nigricans in neck and abdomen.Pre-operative laboratories: hemoglobin (Hgb) level 15.13 g/dL, hematocrit (Ht) 44.59 %, total testosterone level 525 ng/dL (13-53 ng/dL) and DHEAS 113 ug/dL (95.8-511.7 ug/dL), suggesting an ovarian source of androgen excess. Transvaginal ovarian ultrasound showed at the posteromedial edge of right ovary a hyperechoic structure measuring 1.5 cm long x 1.0 cm AP representing a lesion of unknown etiology. After discussion with patient a decision for oophorectomy was made. Pathology report described the ovary negative for neoplasia with findings consistent with hyperthecosis. Laboratories two weeks post-operative showed significant decrease in total testosterone to 81 ng/dL and in Hgb/ Ht (12.50 g/dL and 37.8% respectively). Insulin requirement decreased and she was able to be transitioned to U-100 insulin lispro with a total daily dose of 100. Four weeks after surgery patient had her menstrual period. Ovarian hyperthecosis is a disorder where there is an increased tissue with luteinized theca cells in the ovarian stroma; these cells are ovarian interstitial cells that differentiate into steroidogenically active cells. It is most commonly observed in post-menopausal women, but it has been described in women of childbearing age presenting with worsening hirsutism, virilization and insulin resistance. Monitoring patterns and progression of androgen excess is important in premenopausal women with a diagnosis of PCOS. Severe biochemical or clinical presentation, as well as progression of hyperandrogenism should increase suspicion of additional pathological entities as it will improve patient’s quality of life with the appropriate management. Presentation Date: Saturday, June 17, 2023

SAT383 Case Study: Impact of Weight Reduction and Oral Contraceptive Pills on Hyperandrogenism

Abstract Disclosure: A. Syeda: None. T.L. Anderson: None. D. Millar: None. P. Madhavan: None. Introduction: Polycystic ovarian syndrome (PCOS) is a commonly encountered cause of hyperandrogenism which could interfere with fertility. Typical therapeutic options for hyperandrogenism including hormonal contraceptives and anti-androgen medication are contraindicated when planning pregnancy. This case highlights the profound impact of weightloss and oral contraception use to treat severe hyperandrogenism in select cases. Case: A 31-year-old female presented for initial evaluation of hyperandrogenism noted during evaluation for infertility. Laboratory investigations revealed a free testosterone level of 172 ng/dL (n:9-55 ng/dl), SHBG of 17 nmol/L (25-122 nmol/L), DHEAS of 306 ug/dL (n:99-340 ug/dL), TSH of 1.79 uIU/mL (n:0.35-4.96 uIU/mL), ACTH of 12.1 (n:7.2-63.3 pg/mL), cortisol of 9.6 ug/dL (7-23 ug/dL), prolactin of 7.85 ng/mL (3.34-26.72 ng/mL). The patient reported hirsutism, increasing body hair, darkening of skin and significant weight gain over the past 4 years. Menstrual cycles have been reported as being irregular since menarche. Vital signs were stable with a blood pressure of 112/84 mm Hg. Physical examination was remarkable for generalized obesity, hirsutism, and acanthosis nigricans, no abnormal abdominal striae were appreciated. Considering significant elevation in testosterone levels despite low SHBG, an MRI of abdomen and pelvis was obtained which demonstrated ovarian cysts with no concern for ovarian malignancy. CT of the abdomen without contrast was negative for adrenal mass. The overall clinical picture was suggestive of a diagnosis of PCOS. As the patient was planning pregnancy, oral contraceptive agents and spironolactone were deferred initially. The patient was encouraged to lose weight with lifestyle modifications and was started on up titrating dose of Metformin as tolerated. The patient complied with the recommendations and over the course of two years her weight decreased from 171 lbs. to 158 lbs. In the interim, she was placed on oral contraceptive pills for 2 months to undergo hysteroscopy. Subsequently, the testosterone levels normalized to 17 ng/dL. Conclusion: Although previous research has demonstrated the significance of weight loss, for reducing symptoms in patients with PCOS, this role has not been well elucidated in cases of severe hyperandrogenism without a neoplastic cause. The mechanism of interaction between weight loss, oral contraceptive pills and decreased androgens is based on the reduction in insulin resistance which causes a decrease in theca cell androgen synthesis and an increased SHBG. Additionally, a decrease in adiposity reduces the conversion of Δ4-androstenedione to testosterone. Notably, in this case there is potentially a causal relationship between the patient's weight loss of 13 pounds (7.6% of her body weight), OCP use and her return to normal testosterone levels. Presentation Date: Saturday, June 17, 2023

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

Severe hyperandrogenism following DHEA supplementation in menopausal woman: a case report

Severe hyperandrogenism following DHEA supplementation in menopausal woman: a case report

Severe hyperandrogenism due to ovarian hyperthecosis in a young woman

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1406879: Not Always PCOS: A Case of Virilizing Steroid Cell Ovarian Tumor

Ovarian steroid cell tumors (SCTs) are a rare type of sex-cord stromal tumors that account for 0.1% of all ovarian tumors. These tumors can occur at any age and typically secrete hormones such as androstenedione and testosterone. We report a young woman with known microprolactinoma who presented with secondary amenorrhea and virilization and was found to have a steroid secreting ovarian SCT. A 32-year-old nulligravid woman with history of infertility presented for evaluation for amenorrhea. Three years ago, she developed oligomenorrhea and was subsequently found to have hyperprolactinemia and an 8mm pituitary microadenoma. Thyroid function tests and IGF-1 at the time were normal, no other workup was obtained. She was started on cabergoline, though after developing full body hives was switched to bromocriptine. Despite prolactin normalization from 69.9 to 14.7 ng/mL and shrinkage of pituitary adenoma to 7mm after 1 year of therapy, she developed amenorrhea, acne, and new facial hair. Her testosterone was found elevated 212ng/dL and she states was then diagnosed with PCOS. In light of no clinical improvement and mental health issues, she self-discontinued her bromocriptine and was lost to follow up. Upon current presentation she reported last menstrual period 24 months ago, continued acne and facial hair, and now temporal hair loss and deepening voice. Ferriman-Gallwey score was 20/36. She did not have clinical signs of Cushing’s syndrome. Repeat prolactin was 195ng/mL, pituitary MRI showed 3mm microadenoma, and bromocriptine was resumed. Workup for her hyperandrogenism revealed testosterone of 137ng/dL (ref 8-60), androstenedione 972 ng/dL (41-262), DHEA-S 284 mcg/dL (84.8-378), 17-OH-progesterone 23ng/dL, and hCG <0.5mIU/mL. Late night salivary cortisol levels were elevated to 0.213, 0.429, and 0.552mcg/dL (<0.090) with ACTH 27.3pg/mL (9.72-63.3). CT scan showed normal adrenal glands. A pelvic ultrasound revealed a 2.2cm left ovarian vascular mass. She underwent left salpingo-oophorectomy and pathology confirmed a 2.4cm benign steroid cell tumor. Follow up after surgery is currently ongoing. Amenorrhea despite prolactin normalization and signs of severe hyperandrogenism such as testosterone >150ng/dL, male pattern baldness, and vocal deepening should prompt physicians to consider androgen-secreting tumors. Our patient was found to have a rare ovarian SCT—these tumors can lead to precocious puberty in adolescents, virilization in adults, Cushing’s syndrome, and infertility. Our patient reports significant clinical improvement postoperatively.

An occult ovarian androgen-secreting steroid cell tumor in a postmenopausal woman with severe clinical and laboratory hyperandrogenism

An occult ovarian androgen-secreting steroid cell tumor in a postmenopausal woman with severe clinical and laboratory hyperandrogenism

Abstract #1307599: Successful Treatment of a Case of Congenital Lipodystrophy With 1 mg Subcutaneous Semaglutide

Lipodystrophy is a group of rare metabolic disorders characterized by generalized or partial lack of adipose tissue that leads to severe metabolic derangements including insulin resistance, severe hypertriglyceridemia, ectopic fat deposition, and hyperandrogenism. The available treatment is replacement of metroleptin which is costly and not available in my country. We review a case of generalized lipodystrophy presented with severely uncontrolled diabetes, severe hypertriglyceridemia, and severe hyperandrogenism treated successfully by insulin sensitizers and semaglutide 1 mg.

PMON228 The Hidden Source of Testosterone Hypersecretion in a Female - a Thirty-Year Journey

Abstract A Sertoli-Leydig cell tumor (SLCT) is a rare solid ovarian tumor that over-secretes testosterone or its precursor, androstenedione, that causes rapidly progressing severe androgen excess in females. A SLCT is usually large when patients seek medical assistance for hyperandrogenism. Testosterone production of a SLCT may be suppressed by GnRH agonists, making it unreliable to differentiate SLCT from another functional state. Ultrasound, CT, and MRI are usually used to visualize the ovarian tumor. We present a case of a female with severe hyperandrogenism from a SLCT taking three decades to confirm and resolve since conventional imaging could not detect the tumor. A 58-year-old female was seen for unresolved hyperandrogenism. She first noted amenorrhea at the age of 30. Subsequently, she developed hirsutism with baldness, clitoromegaly, deepened voice, and masculinity over the next decade. The patient reported normal puberty and a history of regular menses. The patient achieved spontaneous pregnancies, which she carried to the term for the first two and had an ectopic pregnancy for the third. She reported a history of left salpingo-oophorectomy at 24, resulting from the ectopic pregnancy. Initial evaluation showed testosterone 370 ng/dL (15-70 ng/dL) with low LH. ACTH, cortisol, androstenedione, and 17-hydroxyprogesterone were normal. The initial pelvic ultrasound did not visualize ovarian or adnexal masses, nor did the abdominal and pelvic CT scan show any tumor. The patient underwent right salpingo-oophorectomy in 2005 to treat persistent hyperandrogenemia, which revealed normal pathology without resolution of her problem. A following transvaginal US showed an absence of ovaries bilaterally. She was treated with GnRH analog for an unclear period. Since establishing care in our endocrinology clinic two years ago due to changing insurance, her testosterone ranged 292-346 ng/dL and FSH and LH remained low. Her ACTH, cortisol, DHEA, DHEA-S, androstenedione, estradiol, and SHBG were normal. The repeat abdominal and pelvic CT scan was unremarkable. An abdominal MRI showed no adrenal lesions. The 48-hour low-dose dexamethasone suppression test suggested extra-adrenal hypertestosteronism. Finally, a PET-CT scan showed hypermetabolic activities in the left adnexal area. The patient eventually underwent removal of the left adnexal mass detected in the PET scan. The pathology showed a Leydig cell tumor. Postoperative total testosterone level dropped to 5 ng/dL. Our patient presented with severe hyperandrogenism in her early 30s. Despite all biochemical evaluations suggesting SLTC, the conventional imaging studies failed to identify the tumor, and prior bilateral salpingo-oophorectomy failed to resolve her problem. Finally, PET/CT scan demonstrated an area of hypermetabolic activity in the left adnexal area, which was found to be a Leydig cell tumor after resection. While US, CT, and MRI remain the primary diagnostic tools for ovarian cancer, PET-CT should be considered when the lesion is not readily seen on conventional imaging studies. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

PMON227 Rare ovarian luteinized fibrothecoma as cause of severe hyperandrogenism in a pre-menopausal woman.

Abstract Ovarian fibromas and fibrothecomas constitute up to 4.7% of ovarian sex cord stromal tumors (OSCSTs). Luteinized fibrothecomas (LFs) are a histological subvariant of OSCSTs. Typically benign and rare, LFs are mostly diagnosed in post-menopausal women with only 30% in women &amp;lt;30. Only 11% of LFs present with androgen excess (AE). We describe a case of severe hyperandrogenism from an ovarian LF in a young woman with primary amenorrhea and infertility.A 23-year-old woman presented for evaluation of hyperandrogenism. Iatrogenic menarche occurred at age 22, induced by letrozole and medroxyprogesterone (MP). BP was 133/86 mm Hg and BMI was 52 kg/m2. Exam revealed diffuse obesity, severe hirsutism (Ferriman Gallwey score 29), and severe acanthosis nigricans, but no scalp alopecia, deep voice, violaceous striae or bruising. Total testosterone (TT) was 108 ng/dl (2-45), free testosterone (FT) 24.7 pg/ml (0.1-6.4 dialysis), prolactin 13.2 ng/ml (&amp;lt;30), DHEAS 2308 ng/ml (240-4330), and TSH 1.29 µIU/mL (0.45-5.33). FSH, LH and estradiol could not be interpreted due to unclear timing in cycle. 17-hydroxyprogesterone after MP challenge was 73 ng/dl (&amp;lt;200). Pelvic ultrasound (US) gave normal endometrial stripe of 3.82 mm. Pelvic US and MRI showed polycystic ovarian morphology without masses. CT abdomen showed normal adrenal glands. Ovarian and adrenal vein sampling (OAVS) lateralized AE to the left ovary (LO). LO TT was 5743 ng/dl with associated IVC sample of 139 ng/dl, ratio of 41, and right ovarian TT was 381 ng/dl with associated IVC sample of 32 ng/dl, ratio of 1.18. Just prior to left oophorectomy, preoperative TT was 103 ng/dl, FT 27.8 pg/ml (0.1-6.4 dialysis), and androstenedione (A4) 212 ng/dl (mid-follicular 51-213). Two days post-operatively, TT dropped to 55 ng/dl, FT 11 pg/ml (0.2-5), and A4 105 ng/dl. Pathology revealed a 3.8 cm LF. Six weeks post-operatively, TT and FT normalized to 18 and 3.6 (0.2-5), respectively.Features atypical for PCOS, including presentation outside age 15-25, rapid progression, TT &amp;gt;2× upper limit of normal (ULN), and free androgen index &amp;gt;4× ULN should prompt thorough evaluation. Adherence to guidelines for TT threshold &amp;gt;150 in a pre-menopausal woman and focus on PCO morphology would have provided false reassurance. Maintaining a high degree of suspicion for an androgen-secreting tumor (AST) is paramount when clinical presentation is atypical. OAVS is usually performed when imaging fails to reveal an abnormality, as small ovarian tumors cannot be excluded. Our patient presented with symptoms atypical for PCOS including severe hirsutism and TT &amp;gt;2× ULN, raising concern for an AST. OAVS lateralized AE to her LO. Resection resulted in testosterone normalization and finding of a rare LF. Identifying the source of AE is especially important in women of reproductive age to restore normal reproductive function. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP420 Ovarian Venous Sampling and the Diagnostic Challenges Associated with Identifying the Source of Severe Hyperandrogenism in an Adolescent Female

Abstract Background Polycystic ovarian syndrome (PCOS) accounts for most cases of hyperandrogenism in adolescent females. Rarely, evaluation reveals testosterone concentrations (&amp;gt; 200 ng/dL). In those instances, imaging is recommended to evaluate for an ovarian or adrenal neoplasm. Recommendations are lacking for when imaging is nondiagnostic, yet testosterone levels continue to rise on standard treatment. Ovarian venous sampling may be considered as a diagnostic tool to locate the source of hyperandrogenism. A 12-year-old female was referred for evaluation of secondary amenorrhea, weight gain, and possible PCOS. Thelarche was at age 10 years and menarche at age 11 years. Eighteen months post-menarche she developed amenorrhea, acne, and hirsutism. She had no clitoromegaly. Her height was 50th percentile, weight &amp;gt;99 th percentile, and BMI 130th of the 95th percentile. She had no family history of PCOS. Initial lab evaluation showed mild hyperandrogenism: total testosterone of 52ng/dL (17-75), free testosterone of 1.3ng/dL (&amp;lt;0. 04-0.84), and DHEA of 423ng/dL (&amp;lt;202). OGTT done with only glucoses was normal. HbA1c was 5.6%. DHEAS, androstenedione, 17-OH progesterone, prolactin and TSH were normal. LH was 3.5mIU/mL, FSH 4.8mIU/mL, and estradiol 45pg/mL. Pelvic ultrasound showed enlarged right (25mL) and left ovaries (15.6mL). The follicular distribution was normal and bilateral simple cysts were noted. PCOS was suspected and she started on metformin and oral contraceptive pills. Her testosterone levels increased during subsequent visits with a peak total and free testosterone of 344ng/dL and 7.83ng/dL. HbA1c rose to 5.9%. She had fasting and postprandial insulin levels of 74.3 and 260mcIU/mL, respectively. Further evaluation revealed a normal AMH level of 6.4ng/mL (0.49-6.9), SHBG of 22.9nmol/L (7.7-108), a negative screen for anabolic steroid use, and 46,XX karyotype. Imaging over 8 months (multiple transabdominal ultrasounds, MRI of abdomen/pelvis and brain) was negative for neoplasm. The potential next steps discussed with the patient were continued serial imaging, GnRH agonist, or ovarian venous sampling with possible oophorectomy. Due to concern for neoplasm, the patient opted for venous sampling which showed a 10-fold gradient in total testosterone between right and left gonadal veins (2300ng/dL vs. 203ng/dL). She underwent right oophorectomy and switched from OCP to transdermal hormone therapy. Three months later, her total testosterone was normal (26ng/dL), she had lost 5kg and menstrual cycles returned. Pathology resulted as PCOS, with no evidence of neoplasm. Conclusions Localization of the source of severe hyperandrogenism can be a challenge. In our case, ovarian venous sampling results prompted unilateral oophorectomy, yet pathology showed no ovarian neoplasm. While ovarian venous sampling is a potential diagnostic tool, there is no data guiding when it should be used and interpretation of results, specifically if/when oophorectomy should be pursued. This is particularly relevant in the management of young, premenopausal females. Presentation: No date and time listed

Unilateral or bilateral adrenalectomy in PPNAD: six cases from a single family followed up over 40 years

The most frequent endocrine Carney complex manifestation is a bilateral primary pigmented nodular adrenocortical disease and bilateral adrenalectomy (BA) is therefore its main treatment. In this study, a 40 years follow-up of six members of the same family with heterozygous PRKAR1A germline mutation, is reported over two generations. The first cases, two sisters with severe hyperandrogenism and Cushing syndrome (CS) diagnosed in 1972 at age 14 and 25, were successfully treated with unilateral adrenalectomy (UA). Their two brothers were then diagnosed, one with a CS-related severe osteoporosis treated with BA and the other with CS treated with UA. The second generation was diagnosed with CS signs at 7 and 21 years of age and were treated with BA and UA respectively. Out of the four patients treated with UA, the only event possibly related to CS was spontaneous episode of pulmonary embolism, 30 years after surgery. Hormonal evaluation revealed either eucortisolism in one patient or partial adrenal deficiency in two and mild hypercortisolism in one patient. For the two patients with BA, one of them accidentally died. The second one, surprisingly, recovered progressively normal cortisol secretion and circadian variation. Steroid substitution was stopped 6 years after her surgery and we demonstrated by iodocholesterol scintigraphy the presence of bilateral adrenal remnants. In conclusion, our results of long term evolution of PPNAD patients show that UA in this subset of patients could be considered to treat CS.