ResearchPad - clinical-studies-in-female-reproduction-ii Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SUN-001 Identification of Dehydroepiandrosterone-s (DHEA-s) Elevation Due to Performance Enhancing Supplements]]> Background: Recreational athletes and individuals in certain occupations may utilize supplements with the goal of enhancing their physical performance and strength. These individuals may be reluctant to provide their supplement use history due to the stigma associated with performance enhancing drugs. We report a case of supplement use causing elevated dehydroepiandrosterone sulfate (DHEA-S) levels in a young woman presenting with alopecia. Clinical Case: A 29-year-old Caucasian woman presented for evaluation of progressive alopecia spanning 7 years. She was initially managed by dermatology with topical ketoconazole and clobetasol creams followed by intra-lesional triamcinolone injections. Despite treatment, she had minimal improvement. She reported menarche at age 15 with normal regular monthly menstrual cycles and normal breast development. She has no significant medical history. Physical exam was unremarkable other than localized alopecia and athletic build. She denied any medication use. Routine laboratory screening showed a DHEA-S of 624 ug/dL (ref. 35-430) with repeat DHEA-S at 602.2 ug/dL. Complete blood count, metabolic panel, thyroid function test, total/free testosterone, estradiol, 17-hydroxprogesterone, urinary 17-ketosteroids, prolactin, and iron panel were all within normal limits. Anabolic abuse screen was negative. Adrenal imaging was normal. After discussion on elevated DHEA-S results, patient revealed that she was taking a supplement that contained enobosarm (Ostarine). She was instructed to discontinue the supplement and repeat her labs but she was lost to follow up. Discussion: Developed in 1997, enobosarm is a selective androgen receptor modulator (SARMs) that is increasingly used as a performance-enhancing drug. SARMs have tissue specific androgenic receptor effect and patients on SARMs can present with a completely normal hypothalamic-pituitary gonadal axis without biochemical evidence of hyperandrogenism; which was the case in our patient. Conventional anabolic drug abuse screens do not detect SARMs. There have been multiple studies that have evaluated different performance enhancing supplements and nearly 25% of tested products contained compounds that were not correctly labeled. It is therefore uncertain what may have raised this patient’s DHEA-S levels, but the authors theorize the supplement may have contained exogenous DHEA rather than a direct effect of enobosarm. Unfortunately, there is paucity of data or literature on the effect of SARMs on androgen hormone synthesis and DHEA-S levels. A PubMed search for SARMs and DHEA-S levels led to zero returns. It is important for clinicians to recognize and identify the possibility of SARM or supplement use in order to guide diagnostic and management decisions. Further investigation is needed to understand the impact of SARMs on laboratory data and its long term effects.

<![CDATA[SUN-LB1 Atypical Presentation Of Myocardial Infarction In A Young Patient With Polycystic Ovarian Syndrome]]> Background: Polycystic ovarian syndrome (PCOS) is a very common and complex endocrine problem in women of childbearing age, with a prevalence of 4 to 12% globally. Myocardial infarction (MI) is the leading cause of death in women worldwide. PCOS increases the risk of MI because of chronic inflammation, endothelial dysfunction, impaired pulse wave velocity and its association with metabolic syndrome, and hormonal imbalance.

Clinical Case: A 36-year-old female with a history of PCOS, hirsutism, severe acne on spironolactone, presented to ER with a chief complaint of lower back pain for 10 days that started after lifting a 60-pounds printer. The pain was attributed to musculoskeletal type, one dose of ketorolac intramuscularly was given and she was discharged on cyclobenzaprine. The next morning, she presented with worsening back pain and new-onset vomiting. Physical exam was normal except for BMI 34.6kg/m2; vitals were stable. Lab work showed elevated troponin of 1.43 which rose to 10.6 ng/ml (normal 0.00-0.034), cholesterol 125 mg/dL (less than 200), HDL 33 mg/dL (normal 40-59), LDL 164 mg/dL (normal 100-129). Electrocardiogram showed sinus tachycardia with Q wave changes in leads III and V1 to V3. Echocardiogram showed hypokinesia of left ventricular wall in the mid to apical anterior septum. Computed tomography (CT) scan of the thoracic spine was negative for abscess or fracture. CT of abdomen and pelvis as well as CT angiography chest were negative. Urine drug screening was also negative.

As her presentation was attributed to MI, patient was started on heparin drip, aspirin, atorvastatin, and metoprolol. She underwent cardiac catheterization that showed 99% ostial left anterior descending artery stenosis; a drug-eluting stent was successfully placed. After intervention her back pain resolved. She was discharged on dual antiplatelet therapy (aspirin and Prasugrel) along with atorvastatin, metoprolol and nitroglycerin.

Conclusion: This case suggests an association of PCOS with MI. A meta-analysis has shown a two-fold increase in risk of coronary artery disease in patients with PCOS (1). Future studies are need to examine opportunities for cardiovascular disease risk reduction in PCOS patients.

Reference:1. de Groot PCM, Dekkers OM, Romijn JA, Dieben SWM, Helmerhorst FM. PCOS, coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysis. Human Reproduction Update 2011. 17 495-500.

<![CDATA[SUN-009 Variable Presentation of Two Patients with Gestational Trophoblastic Disease and Hyperthyroidism]]> Background: Gestational trophoblastic disease (GTD) represents a group of tumours caused by abnormal proliferation of trophoblastic cells, including molar pregnancy. Elevated β-hCG levels are an established marker for the presence of the disease and useful for monitoring. Due to the shared structural homology of β-hCG and TSH, hyperthyroidism can occur.

Clinical Cases: We present two patients with GTD associated with hyperthyroidisim. Case 1, a 20 year old female (G1P0) presented to the emergency department complaining of vaginal bleeding associated with abdominal pain. She was estimated to be 13 weeks. Laboratory evaluation were β-hCG 648 324 IU/L, TSH 0.06 (0.35 - 4.94 mIU/L, free T4 23.2 (9.0 - 19.0 pmol/L, Hb 8.0 (11.6 - 16.4 g/dL). Ultrasound revealed molar pregnancy. She underwent uterine evacuation, thereafter complicated with thyroid storm (Burch Wartofsky score = 45). Post- operative vitals were BP 192/112, pulse rate 120 bpm and temperature 360C. She was managed in high care on labetolol, carbimazole, lugol’s iodine and hydrocortisone.

She was subsequently referred to Medical Oncology for further management. Histology sample obtained in theatre confirmed complete molar pregnancy.

Her staging CT scan indicated the presence of small lung nodules, suggesting metastatic disease. The patient’s FIGO/WHO score was III: 2. At the time of preparing this study, she had already received 7 weeks of methotrexate intramuscularly and still had detectable β-hCG levels.

Case 2 was a 31 year old female presented similarly. This was her second pregnancy (G2P1), 12 weeks by dates. Her vitals were BP 141/74, pulse rate 110 bpm and temperature 36oC. The Ultrasound revealed larger for gestational age uterus with cystic structures in utero. Her quantitative β-hCG was significantly elevated (> 1 500 000 IU/L) she was thyrotoxic [TSH (<0.1 (0.34 - 4.94 mIU/L) free T4 (47.2 (9.0 - 19.0 pmol/L)], however did not develop thyroid storm (Burch Wartofsky score = 20). This patient also underwent uterine evacuation and did well post operatively. She was treated for her thyrotoxicosis with carbimazole, propranolol and thiamine. Further management was by Medical Oncology. Histological examination was in keeping with a partial mole.

Her staging CT scan showed no metastasis, and had a FIGO/WHO score of 1: 4 due to her pre-treatment hCG of >1.5 million IU/L. She received 7 cycles of intramuscular methotrexate from which she achieved and maintained suppressed β-hCG levels (<1 IU/L).

Conclusions: This study has demonstrated that the β-hCG levels may not always correlate with disease severity and prognosis.

When comparing the two patients Case 1 had lower levels of β-hCG and of free T4 than Case 2, however was clinically more unwell, developed thyroid storm and had metastatic disease. Case 2 had hCG levels almost double those of Case 1, wsa stable and her levels decreased much quicker reaching undetectable levels

<![CDATA[SUN-007 Elevated Levothyroxine Requirements Post-Partum as Initial Presentation of Placenta Accreta]]> Introduction: It is well known that estrogen plays an important role in thyroid regulation. We report an unusual case of post-partum placenta accreta causing pathologic estrogen secretion leading to increased levothyroxine (LT4) requirements and inability to lactate.

Case: A 36-year-old woman with history of Hashimoto’s hypothyroidism presented post-partum day 11 after a normal vaginal delivery with inability to produce breast milk and mildly elevated TSH levels. Prior to her pregnancy, she required an equivalent dose of 142 mcg of LT4 supplementation daily, which increased appropriately to 171 mcg during pregnancy. After delivery, LT4 was decreased to 150mcg in anticipation of normalization of levothyroxine requirements to pre-pregnancy level. However, she had difficulty lactating and was found to have elevated prolactin, estradiol, and TSH levels. The following day, she presented to her obstetrician for persistent vaginal bleeding and was found to have placenta accreta requiring dilation and curettage (D&C). Her LT4 requirements eventually dropped to 125 mcg with decreasing beta-HCG and estrogen levels after successful D&C treatment. She was also then able to produce sufficient breast milk for lactation.

Discussion: This case highlights the effect of estrogen on LT4 requirements during physiologic pregnancy and postpartum with placenta accreta. It is expected that hypothyroid patients have approximately 25-50% increased thyroid replacement requirements during pregnancy, which normalizes soon after delivery.1 Estrogen increases thyroxine-binding globulin and lowers circulating free thyroxine2,, which causes higher thyroid replacement requirements. Estrogen is also known to inhibit lactation. Our patient demonstrates that this holds true even in a pathologically high estrogen state from placenta accreta. Our case uniquely demonstrates a temporal association between estrogen levels and LT4 requirements in the post-partum hypothyroid patient. Patients with inappropriately high TSH levels after delivery should prompt investigation into pathologic causes of elevated estrogen-states, as levothyroxine requirements are expected to normalize immediately post-partum.


1. Bungard TJ, Hurlburt M. Management of hypothyroidism during pregnancy. CMAJ. 2007;176(8):1077-8.

2. Alexander EK, Marqusee E, Lawrence J, Jarolim P, Fischer GA, Larsen PR. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. N Engl J Med. 2004 Jul 15;351(3):241-9.

<![CDATA[SUN-005 Hirsutism Due to Bilateral Leydig Cell Tumors]]> Severe hyperandrogenism in post-menopausal women is rare. It may be caused by either benign or malignant neoplasms of the adrenal or ovary. We report a rare case of a post-menopausal woman with hirsutism associated with virilization due to Leydig cell tumors (LCT) of both ovaries. Case report 61 yo female presented for evaluation of hirsutism. She had also been experiencing increased facial hair growth, deepening of voice, clitoromegaly, alopecia, and acne. Physical examination: normal vital signs. Patient had signs of virilization, including coarse hair along her upper lip, chin, lower abdomen and inner thigh with Ferriman-Gallwey score of 8, acne, and clitoromegaly. She had no signs of acanthosis nigricans or Cushing syndrome. Base line labs: Hemoglobin 16.2 gm/dL (ref 12.0 to 15.5), total testosterone 803 ng/dL (ref 3–41), free testosterone 20.2 pg/mL (ref 0.0–4.2), estradiol 77 pg/mL (<6.0−54.7), estrone 148 pg/mL (ref 7–40), FSH 11.5 mIU/mL (ref 25.8 - 134.8), LH 6.90 mIU/mL (ref 7.7 - 58.5), androstenedione 28 ng/dL (ref 17–99), DHEAS 99.9 mcg/dL (ref 19–205), dehydroepiandrosterone 512 ng/dL (ref 31–701), inhibin A 2.3 pg/mL (ref <5), inhibin B <7.0 pg/mL (ref 00-16.9), 17-alpha hydroxyprogesterone 187 ng/dl (ref <51). Her other serum markers such as anti -Mullerian hormone, alpha-fetoprotein, and hCG were normal. A CT scan of adrenals: normal. Similarly a transvaginal US did not show any ovarian pathology, however MRI of the pelvis showed homogeneous ovarian enhancement bilaterally and based on this information a diagnosis of ovarian hyperthecosis was considered and patient underwent laparoscopic bilateral oophorectomy. Pathology confirmed: LCT in both ovaries. Laboratory values performed 3 months later showed the following values: hemoglobin 14.2 gm/dL, total testosterone 13 ng/dL, free testosterone 1.4 pg/mL, LH 124 mIU/mL, FSH 99mIU/mL, estradiol <5.0 pg/mL. In 6 months she had significant improvement in hirsutism and virilization. Discussion Hyperandrogenism, especially serum testosterone in the male range with rapidly progressive hirsutism or virilization signs in a female indicates tumor etiology. Androgen-secreting ovarian tumors are usually small and often embedded in the ovary. Transvaginal US is useful in the diagnosis of ovarian tumors. However, in our case, transvaginal US failed while MRI scan showed bilaterally enlarged ovaries and with this information patient underwent bilateral oophorectomy. Although 5 cases of bilateral LCT are reported in the literature, LCT is unilateral 95% of the time, the pathogenesis of Leydig cell proliferation and LCT is unclear. In conclusion, androgen secreting tumors should be considered in women (especially in post-menopausal state) with hyperandrogenism and hirsutism. In fact, diffuse stromal Leydig cell hyperplasia and small Leydig cell tumors may be missed on imaging and in some cases only pathology can confirm the result.

<![CDATA[SUN-002 Hormonal Profile of Ovarian Sertoli-Leydig Cell Tumor]]> Background: Sertoli-Leydig cell tumors account for less than 1% of ovarian tumors, and information about their biochemical markers has been lacking. Objective: The objective was to characterize the hormonal profile of Sertoli-Leydig cell tumor, which should be helpful in recognizing this rare condition in the future. Methods: We reviewed test results including serum total and free testosterone, steroid hormone precursors, and inhibin B levels in a 17-year-old adolescent girl with ovarian Sertoli-Leydig cell tumor who developed secondary amenorrhea for 6 months, deepening of the voice, acne, and severe hirsutism. Results: Our patient had serum testosterone 641 ng/dL (expected 20 - 38), dihydrotestosterone 42.5 ng/dL (expected 3 - 18), 17-OH progesterone 659 ng/dL (expected 20 - 265), androstenedione 869 ng/dL (expected 50 - 224), 17-OH pregnenolone 760 ng/dL (expected 53 - 357), DHEA 1250 ng/dL (expected 4 - 491), and DHEA-S of 366 mcg/dL (expected 44 - 248). Inhibin B level was 321 pg/mL (expected <136); inhibin A was normal. Anti-mullerian hormone, a-fetoprotein, carcinoembryonic antigen, and CA-125 tumor markers were not elevated. Karyotype was female 46,XX. Dexamethasone 0.5 mg QID PO for 4 days resulted in plasma ACTH <5.0 pg/mL and serum cortisol <1.0 mcg/dL, total testosterone 611 ng/dL, free testosterone 25.1 ng/dL (expected <0.04 - 1.09 ng/dL), and 17-OH progesterone 887 ng/dL. Abdomen and pelvis MRI demonstrated a right ovarian mass primarily solid with high cellularity, measured 4.4 x 3.9 cm; there was at least moderate diffuse enhancement of the mass after contrast administration; adrenal glands were normal. Surgical pathology of the resected right ovary revealed moderately to poorly differentiated Sertoli-Leydig cell tumor. Single antibody immunostain procedures with appropriate controls showed a staining pattern supportive of this rare diagnosis: WT-1 showed moderate nuclear staining, calretinin showed a strong positive stain, and CK showed a patchy moderate staining pattern; immunostains for myogenin, desmin, and EMA were negative. Genetic testing revealed a germline heterozygous mutation in DICER1 gene, c3737del, p.Asn1246Metfs*12, establishing the diagnosis of DICER1 syndrome, an autosomal dominant disorder predisposing to cancer. Menses resumed one month after tumor resection. Conclusions: High serum 17-OH progesterone, androstenedione, 17-OH pregnenolone, and DHEA levels used as indicators of adrenocortical function could be markers of an ovarian tumor. If serum 17-OH progesterone and testosterone remain high when cortisol and plasma ACTH are suppressed on Dexamethasone test, a source of 17-OH progesterone and testosterone is other than ACTH-dependent adrenal one. High serum inhibin B level may be sign of an ovarian tumor. Patients with Sertoli-Leydig cell tumor should be screened for DICER1 gene syndrome to assess risk for other rare neoplasms.

<![CDATA[SUN-006 Light and Exercise Therapy Improves Depression in Women with Premenstrual Syndrome]]> <![CDATA[SUN-004 Case Study: A 17-year-old Girl with HAIR-AN Syndrome, T2DM and Primary Amenorrhea]]> <![CDATA[SUN-011 Beyond PCOS - Ovarian Neoplasms Presenting with Hirsutism and Virilization]]> 250ng/dl) is another “red flag” finding. Persistent radiologic search for such lesions should continue as they may not be immediately apparent on routine abdominopelvic imaging. ]]> <![CDATA[SUN-003 Very Restricted Carbohydrate (Ketogenic) Diet: A Rare Cause of a Recurrent Hypoglycemic-Euglycemic Diabetic Ketoacidosis in the Pregnancy]]> <![CDATA[SUN-008 Loss of Antimullerian Hormone Immunoreactivity Due to a Homozygous AMH Gene Mutation Rs10417628 in a Woman with Classical Polycystic Ovary Syndrome]]> T, p.(Ala515Val)) was identified in the index PCOS woman. PCOS women with detectable AMH had higher serum AMH (10.82 [6.74–13.40] ng/mL, Median [IQR]), total/free testosterone (T) (total T: 55.5 [49.5–62.5] ng/dL; fT: 5.65 [4.75–6.6] pg/mL) levels and greater total antral follicle numbers (AFNs) (46 [39–59] follicles) than controls (AMH: 4.03 [2.47–6.11] ng/ml; total T: 30 [24.5–34.5] ng/dL; fT: 2.2 [1.8–2.45] pg/mL; AFNs 16 [14.5–21.5] follicles, P<0.05, all values), along with a trend toward LH hypersecretion (P=0.06). The index PCOS woman with the lowest AMH levels (0.1 ng/ml) did not have the highest serum total T/fT (total T: 89 ng/dL; fT: 7 pg/mL,) or LH levels nor the greatest AFN (43 follicles). In vitro analysis of cells expressing hAMH-515Val or hAMH-515Ala showed that hAMH515-Val, in contrast to hAMH515-Ala, was undetectable and severely reduced in the pico-AMH assay in cell lysates and supernatants, respectively. AMH protein processing and AMH-induced luciferase activity, however, did not differ between hAMH515Val and hAMH515Ala. Thus, homozygous AMH mutation rs10417628 in a PCOS woman can impair serum AMH immunoreactivity without affecting AMH bioactivity, perhaps because of conformational changes from the mutation that only interfere with its immunodetection but not its function. References: 1. Teixeira J, et al. Endocrinology 1999;140:4732 2. Gorsic LK et al. JCEM 2019;104:2855 3. Broekmans FJ, et al. Trends Endocrinol Metab 2008;19:340 ]]> <![CDATA[SUN-LB2 Undescended Testicle and Short Stature as Manifestation of Pituitary Stalk Interruption Syndrome a Report From Saudi Arabia]]> <![CDATA[SUN-010 Efficacy of High Intensity Intermittent Training for Improving Cardio-Metabolic Health in Women with Polycystic Ovary Syndrome: A Pilot Study]]>