Normal Serum Testosterone Levels Research Articles

Adult-type granulosa cell tumor associated with elevated luteinizing hormone: Two rare case reports.

Adult-type granulosa cell tumors (AGCTs), which account for 2% to 5% of all malignant ovarian tumors, are rare sex cord-stromal tumors that usually secrete excess estrogens, but they can also secrete androgens. We report 2 patients of childbearing age with AGCT who presented with the complaint of abnormal menstruation and elevated luteinizing hormone (LH), and mildly elevated testosterone. The ovarian tumors had hormonal activity. The 2 patients underwent laparoscopic left adnexectomy. The second patient underwent 4 cycles of chemotherapy with paclitaxel and carboplatin as adjuvant treatments. Their postoperative pathology confirmed AGCTs. Also, their menstrual cycle returned to normal, with normal serum LH and testosterone levels. There was no sign of recurrence. The cases suggest that elevated serum LH levels may be a sign of unknown tumors in cases of oligomenorrhea or secondary amenorrhea. It is useful to evaluate the serum levels of inhibin B and anti-Müllerian hormone to improve the early recognition of ovarian granulosa cell tumors.

Dehydroepiandrosterone-induced polycystic ovary syndrome mouse model requires continous treatments to maintain reproductive phenotypes

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrinopathy associated with infertility and metabolic disorder in women of reproductive age. Animal models have been developed and used as tools to unravel the pathogenesis of PCOS, among which most postnatal models employ continuing experimental manipulations. However, the persistence and stability of these animals after modeling is unknown. Dehydroepiandrosterone (DHEA)-induced PCOS mouse model is commonly used in PCOS studies. Thus the aim of the present study was to investigate the reproductive features of DHEA-induced PCOS mice fed a normal chow or an high-fat diet (HFD) with treatment withdrawal or consecutive treatments after PCOS mouse models were established.MethodsPrepubertal C57BL/6 J mice (age 25 days) were injected (s.c.) daily with DHEA on a normal chow or a 60% HFD for 20 consecutive days to induce PCOS mouse models. Mice injected with the vehicle sesame oil were used as controls. After 20 days, mice were divided into 2 groups, namely “Continue dosing group” and “Stop dosing group”. The animals were consecutively treated with DHEA or DHEA + HFD, or housed without any treatment for 2 or 4 weeks. Estrous cycles were evaluated during this period. At the end of the experiment, serum testosterone (T) levels were measured and the morphology of ovaries was evaluated.ResultsThe mice in Continue dosing groups maintained reproductive phenotypes of PCOS mouse models. In contrast, 2 or 4 weeks after PCOS models were established, the mice with treatment withdrawal in Stop dosing groups exhibited normal serum testosterone levels, regular estrous cycle, and relatively normal ovarian morphology. In addition, even with consecutive treatments, there was no marked difference in body weight between DHEA mice on the normal chow or an HFD in Continue dosing groups and the control animals 3 weeks after modeling.ConclusionsAfter PCOS mice were induced with DHEA or DHEA + HFD, the mice still need consecutive treatments to maintain reproductive phenotypes to be regarded as PCOS mice that meet the diagnostic criteria of PCOS defined by the 2003 Rotterdam criteria.

Dietary intervention in adult rats exposed to a high-sugar diet early in life permanently impairs sperm quality

Childhood obesity predicts the presence of adult obesity. Obesity is associated with poor sperm quality. We hypothesized that exposure to a high-sugar diet (HSD) in early life would cause permanent histomorphology damage to the testes, resulting in reduced sperm quality in adult life. Wistar rats (aged 21days) were divided into four groups (n=6). In the first experiment, the rats received tap water (control) and a 30% sucrose diet for two months (S30). In the second experiment, the control and 30% sucrose diets were fed for two months, followed by replacement with tap water for two months (IS30). Eating and drinking were monitored. Animals were then euthanized, visceral and gonadal fat tissue and testes were collected, and epididymal spermatozoa were excised. Testicular samples were used for morphological description by H&E staining and for quantifying triacylglycerol content, caspase activity, and oxidative stress. Serum testosterone concentration was evaluated. Spermatozoa were used to assess sperm quality. Our results show that sperm quality was impaired by consuming HSD and could not be restored by dietary intervention. HSD feeding induced hyperplasia of visceral adipose tissue, increased testicular weight, and serum testosterone levels. The dietary intervention increased visceral adipose tissue, serum, and testicular triacylglycerol levels and normalized serum testosterone levels. Overall, the HSD diet caused permanent changes in seminiferous tubule cross-sectional area, caspase activity, oxidative stress, and sperm quality. Therefore, a high-sugar diet in early life causes permanent damage to sperm quality in adulthood.

(074) Association of Androgen Receptor Signaling in Human Corpus Cavernosum with Serum Testosterone Levels

Abstract Introduction Testosterone (T) plays an important role in properly developing and maintaining male reproductive tissues. The normal serum testosterone levels can vary between 300 to 1000 ng/dL or 10.4 to 34.7 nmol/L. However, it is unclear whether androgen receptor signaling can vary based on serum T levels or the half-life of testosterone therapy. What remains unknown is whether there is a uniform serum T level above which androgen receptor signaling within the tissue remains similar (saturation hypothesis). Objective We first evaluated whether varying serum levels of T alter androgen receptor (AR) signaling in human penile tissue. Then, we evaluated and compared AR signaling in corpus cavernosum tissue of men treated with short-acting vs. long-acting testosterone. We hypothesized that we would find similar AR signaling in the penile tissue of both eugonadal and hypogonadal men as well as those men receiving short and long-acting testosterone. Methods We obtained human corpus cavernosum (hCC) tissue biopsies during penile surgery (for erectile dysfunction) from 14 men. We recorded their serum T levels on week prior to surgery before 10AM. We used western blot to evaluate adrenergic receptor (AR) and VEGF protein levels. Men without erectile dysfunction undergoing penile surgery for Peyronie's disease were used as controls. Results The median age of participants was 61 (IQR 12) and the median T level was 325ng/dL (IQR 201.45). The results of western blot showed expression of similar levels of VEGF in hCC samples from men with T >200ng/dL. However, men with serum T levels lower than 200 ng/dL had decreased expression of VEGF and AR. Conclusions This finding is significant because it demonstrates that serum testosterone beyond a certain threshold may have a minimal impact on erectile function. If a serum testosterone threshold is identified, this threshold could be a valuable target for future studies on the effects of testosterone on ED. It may alter the treatment threshold for men who have ED as their primary symptom of hypogonadism. This data also suggests the saturation value for penile androgen receptors. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus Pharmaceuticals, Boston Scientific, Coloplast, Endo Pharmaceuticals, Empower Pharmacy, Nestle Health, Olympus, Hims, Inc

MP27-05 ANDROGEN RECEPTOR SIGNALING IN THE HUMAN PENIS IS SIMILAR REGARDLESS OF SERUM TESTOSTERONE LEVEL

You have accessJournal of UrologyCME1 Apr 2023MP27-05 ANDROGEN RECEPTOR SIGNALING IN THE HUMAN PENIS IS SIMILAR REGARDLESS OF SERUM TESTOSTERONE LEVEL Katherine Campbell, Alexandra Dullea, Braian Ledesma, Kajal Khodamoradi, Himanshu Arora, and Ranjith Ramasamy Katherine CampbellKatherine Campbell More articles by this author , Alexandra DulleaAlexandra Dullea More articles by this author , Braian LedesmaBraian Ledesma More articles by this author , Kajal KhodamoradiKajal Khodamoradi More articles by this author , Himanshu AroraHimanshu Arora More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003255.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone (T) plays an important role in the proper development and maintenance of male reproductive tissues. The normal serum testosterone levels can vary between 300 to 1000 ng/dL. However, it is unclear whether androgen receptor (AR) signaling varies based on serum T levels. The aim of this study was to assess the impact of varied serum testosterone levels on AR signaling in Human Corpus Cavernosum tissue. Based on our previous work on the Androgen Saturation hypothesis, we hypothesized that above 200 ng/dL, AR signaling would not vary. METHODS: We obtained corpus spongiosum biopsies from men undergoing inflatable penile prosthesis placement for high grade erectile dysfunction. After mechanical dispersion of tissue with a homogenizer, the total protein was extracted using RIPA buffer. Quantitative detection of VEGF (Vascular endothelial growth factor), an androgen receptor marker, and AR (Androgen Receptor) expression was evaluated by western blot. The density of the bands in all the blots was quantified using densitometry analysis with ImageJ software. RESULTS: The median age of participants was 60.7 (57.6, 65.9) years. The median serum testosterone level was 378 (257, 419) ng/dl. The western blot results (Figure 1) showed no association in the expression level of VEGF or AR regardless of the serum testosterone level. CONCLUSIONS: Even with a wide range of serum testosterone levels (209-1478 ng/dl), androgen receptor signaling was similar in penile tissue. The results of this study support our previous work to demonstrate that AR signaling may be similar regardless of T level above 200 ng/dL. This suggests that serum testosterone levels might not reflect downstream androgen receptor signaling within the penile tissue. Understanding the AR saturation hypothesis provides important context necessary for appropriate prescribing of exogenous testosterone replacement therapy to optimize patient outcomes. Markers of androgen receptor signaling in tissue could be similar regardless of serum testosterone levels. Therefore, the utility of only serum testosterone levels in considering the effect of testosterone therapy needs to be re-evaluated. Source of Funding: This work was supported by: NIH Grant R01 DK130991 and Clinician Scientist Development Grant from the ACS to Ranjith Ramasamy, SMSNA Sexual Medicine Grant to Kajal Khodamoradi © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e363 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Katherine Campbell More articles by this author Alexandra Dullea More articles by this author Braian Ledesma More articles by this author Kajal Khodamoradi More articles by this author Himanshu Arora More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...

EVALUATION OF ANDROGEN SATURATION IN HUMAN CORPUS CAVERNOSUM

Testosterone (T) plays an essential role in properly developing and maintaining male reproductive tissues (1). The normal serum testosterone levels can vary between 300 to 1000 ng/dL. However, it is unclear whether androgen receptor signaling can vary based on serum T levels. What remains unknown is whether there is a consistent serum T level above which androgen receptor signaling within the tissue remains similar. Therefore, we evaluated whether varying serum levels of T alter androgen receptor (AR) signaling in human penile tissue.

MP38-18 ANDROGEN RECEPTOR SIGNALING IN CORPUS CAVERNOSUM IS SIMILAR IN MEN WITH SERUM TESTOSTERONE LEVELS ABOVE 200 ng/dL

You have accessJournal of UrologyCME1 May 2022MP38-18 ANDROGEN RECEPTOR SIGNALING IN CORPUS CAVERNOSUM IS SIMILAR IN MEN WITH SERUM TESTOSTERONE LEVELS ABOVE 200 ng/dL Kajal Khodamoradi, Alexandra Dullea, Roei Golan, Jesse Ory, Himanshu Arora, and Ranjith Ramasamy Kajal KhodamoradiKajal Khodamoradi More articles by this author , Alexandra DulleaAlexandra Dullea More articles by this author , Roei GolanRoei Golan More articles by this author , Jesse OryJesse Ory More articles by this author , Himanshu AroraHimanshu Arora More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002592.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone (T) plays an important role in the proper development and maintenance of male reproductive tissues. The normal serum testosterone levels can vary between 300 to 1000 ng/dL. However, it is unclear whether androgen receptor signaling can vary based on serum T levels. What remains unknown is also whether there is a uniform serum T level above which androgen receptor signaling within the tissue remains similar (saturation hypothesis). Therefore, we evaluated whether varying serum levels of T alters androgen receptor (AR) signaling in human penile tissue. METHODS: We obtained human corpus cavernosum (CC) tissue biopsies during penile surgery (either for erectile dysfunction or Peyronie’s disease). We recorded their serum T levels one week prior to surgery. After mechanical dispersion of CC tissue with a homogenizer, the total protein was extracted using RIPA buffer, and quantitative detection of vascular endothelial growth factor (VEGF) was evaluated by western blot. RESULTS: The mean age of participants was 64±10 and the mean T level was 487.46ng/dL±377.20. The results of western blot showed that all corpus cavernosum samples in men with T >200ng/dL expressed similar levels of VEGF in men. However, men with a low serum T level (<200 ng/dL) had decreased expression of VEGF. The VEGF expression from men undergoing penile surgery for Peyronie's disease without erectile dysfunction was used as controls. CONCLUSIONS: Despite a wide range of serum T levels (200-1594 ng/dl), androgen receptor signaling was similar in penile tissue. This data suggests that the saturation value for penile androgen receptors appears to be around approximately 200ng/dL. Understanding androgen receptor saturation hypothesis provides important context necessary for appropriate prescribing of exogenous T to optimize patient outcomes. Source of Funding: This work was supported by Acerus Pharmaceuticals, National Institutes of Health Grant R01 DK130991 and Clinician Scientist Development Grant from the American Cancer Society to RR © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e625 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kajal Khodamoradi More articles by this author Alexandra Dullea More articles by this author Roei Golan More articles by this author Jesse Ory More articles by this author Himanshu Arora More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF DownloadLoading ...

The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.

Hypogonadism in Adult Males with Prader-Willi Syndrome-Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion.

Prader-Willi syndrome (PWS) is a complex genetic syndrome characterized by hyperphagia, intellectual disability, hypotonia and hypothalamic dysfunction. Adults with PWS often have hormone deficiencies, hypogonadism being the most common. Untreated male hypogonadism can aggravate PWS-related health issues including muscle weakness, obesity, osteoporosis, and fatigue. Therefore, timely diagnosis and treatment of male hypogonadism is important. In this article, we share our experience with hypogonadism and its treatment in adult males with PWS and present a review of the literature. In order to report the prevalence and type of hypogonadism, treatment regimen and behavioral issues, we retrospectively collected data on medical interviews, physical examinations, biochemical measurements and testosterone replacement therapy (TRT) in 57 Dutch men with PWS. Fifty-six (98%) of the patients had either primary, central or combined hypogonadism. Untreated hypogonadism was associated with higher body mass index and lower hemoglobin concentrations. TRT was complicated by behavioral challenges in one third of the patients. Undertreatment was common and normal serum testosterone levels were achieved in only 30% of the patients. Based on the Dutch cohort data, review of the literature and an international expert panel discussion, we provide a practical algorithm for TRT in adult males with PWS in order to prevent undertreatment and related adverse health outcomes.

Serum concentrations of dihydrotestosterone are associated with symptoms of hypogonadism in biochemically eugonadal men

PurposeSymptoms of hypogonadism are often reported by subjects with normal serum testosterone (T) levels. We aimed to assess the association between clinical symptoms in andrological outpatients and sex steroids levels.MethodsThis is a retrospective cross-sectional cohort study in an Academic clinic and research unit. International Index of Erectile Function (IIEF, EF domain) and Aging Males Symptoms scale (AMS) questionnaires were completed by 635 and 574 men, respectively (mean age: 47.3 ± 13.9 and 47.4 ± 13.8 years, p = 0.829), free of interfering medications with complaints possibly related to hypogonadism.ResultsSerum total/free T as well as dihydro-T (DHT) was associated with IIEF-EF and AMS scores in the overall population using univariate analyses. Multivariate approaches revealed DHT concentrations in subjects with normal T levels (n = 416, Total T > 12 nmol/L) to be significant predictors of AMS scores. A 0.1 nmol/l serum DHT increase within the eugonadal range was associated with a 4.67% decrease in odds of having worse symptoms (p = 0.011). In men with biochemical hypogonadism (Total T < 12 nmol/L), total and free T rather than DHT were associated with AMS results. This association was not found for IIEF-EF scores. Indirect effects of age and BMI were seen for relations with hormone concentrations but not questionnaire scores.ConclusionDHT can be associated with symptoms of hypogonadism in biochemically eugonadal men. Serum DHT measurement might be helpful once the diagnosis of hypogonadism has been ruled out but should not be routinely included in the primary diagnostic process.

Maintenance of muscle mass in adult male mice is independent of testosterone.

Testosterone is considered a potent anabolic agent in skeletal muscle with a well-established role in adolescent growth and development in males. However, the role of testosterone in the regulation of skeletal muscle mass and function throughout the lifespan has yet to be fully established. While some studies suggest that testosterone is important for the maintenance of skeletal muscle mass, an understanding of the role this hormone plays in young, adult, and old males with normal and low serum testosterone levels is lacking. We investigated the role testosterone plays in the maintenance of muscle mass by examining the effect of orchiectomy-induced testosterone depletion in C57Bl6 male mice at ages ranging from early postnatal through old age (1.5-, 5-, 12-, and 24-month old mice). Following 28 days of testosterone depletion, we assessed mass and fiber cross-sectional-area (CSA) of the tibialis anterior, gastrocnemius, and quadriceps muscles. In addition, we measured global rates of protein synthesis and degradation using the SuNSET method, western blots, and enzyme activity assays. Twenty-eight days of testosterone depletion resulted in reduced muscle mass in the two youngest cohorts, but had no effect in the two oldest cohorts. Mean CSA decreased only in the youngest cohort and only in the tibialis anterior muscle. Testosterone depletion resulted in a general increase in proteasome activity at all ages. No change in protein synthesis was detected at the terminal time point. These data suggest that within physiological serum concentrations, testosterone may not be critical for the maintenance of muscle mass in mature male mice; however, in young mice testosterone is crucial for normal growth.

Low serum testosterone and prostate cancer behaviour - any correlation

Background and Objective: Prostate cancer is one amongst the most common medical diseases affecting elderly men. Carcinoma of the prostate is being the most common non-cutaneous cancer diagnosed. The lifetime risk of prostatic carcinoma is 16.7 % and the risk of death during the entire lifetime is around 2.6% for men but the overall lifetime risk of death due to prostate malignancy is low in comparison to lifetime risk of diagnosis. Prostate cancer is a hormone dependant cancer and the clinical course of prostate cancer varies with individual and again it varies within the individual in relationship to serum testosterone levels. The present study is to find out the role of low serum testosterone level in predicting prostate cancer behaviour in comparison with normal serum testosterone level patients and to find out the relationship between low serum testosterone level and serum PSA levels in TRUS biopsy proven cancer prostate patients. The primary aim and objective of our study is to determine the association of low serum testosterone and prostate cancer behaviour and with a Secondary objective to determine the relationship of serum PSA level in cancer prostate patients with low serum testosterone. Methodology: Informed consent was obtained from all patients. All TRUS biopsy proven caner prostate patients were enrolled to a maximum number of 100. All details were recorded. Blood investigations like serum PSA, serum testosterone and other baseline investigations were obtained. The serum determinations of Testosterone obtained between 7 – 9.30 am. The serum Testosterone levels measured by appropriate standard protocols. Patients were divided into two groups based on the serum testosterone levels. Patients with low serum testosterone levels ( 250 ng/dl) were categorized as Group B and the findings between two groups will be compared. Results: Total of 106 patients with cancer prostate were taken into our study of which 5 patients on 5 alpha reductase inhibitors and 1 patient on testosterone replacement therapy were excluded from our study and finally 100 patients were enrolled in our study of which patients with low testosterone level ( 250 ng/dl) were categorized as group B. The majority (74%) of patients in low testosterone group has got a serum PSA of more than 20 values compared with only 34% of patients in the corresponding group. P value is found to be statistically significant. Most of the patients (82.6%) in low testosterone group had a higher Gleason grade (8-10) compared to the normal testosterone group. P value is found statistically significant. Conclusion: Low total serum testosterone is associated with higher proportion of predominant Gleason pattern 4, an indicator of aggressive prostate cancer. Patients with low serum testosterone levels were associated with an increased serum PSA levels compared with patients in normal serum testosterone levels. Patients with low testosterone who were managed by radical prostatectomy had a higher proportion of positive surgical margin, extra capsular extension and seminal Vesical invasion suggesting an aggressive prostate cancer behaviour. Preoperative total testosterone should be routinely added to serum prostate specific antigen estimation to improve prostate cancer management.

Testosterone treatment longer than 1 year shows more effects on functional hypogonadism and related metabolic, vascular, diabetic and obesity parameters (results of the 2-year clinical trial)

Objective We evaluated long-term effects of testosterone undecanoate on glycemic control, metabolic syndrome, vascular function and morphology in obese men with functional hypogonadism (FH) and type 2 diabetes (T2D) in a 2-year prospective clinical trial. Methods A total of 55 participants were enrolled in this study; group P (n = 27) received placebo during first and testosterone therapy (TTh) during second year, group T (n = 28) received TTh both years. We pooled results after 1 year of TTh to obtain more statistical power. Results for group T after 2 years of TTh are also presented. We evaluated wide assortment of biochemical (fasting plasma glucose—FPG, glycated hemoglobin—HbA1c and lipid profile), hormonal, vascular (flow-mediated dilatation—FMD and intima-media thickness—IMT), anthropometrical and derived parameters (BMI, HOMA-IR, non-HDL cholesterol, bioavailable and calculated free testosterone). Quality of life was assessed using Aging Males’ Symptoms (AMS) questionnaire. Results FPG, HbA1c, HOMA-IR and IMT decreased, FMD increased, lipid profile and AMS sexual sub-score improved, and testosterone levels fully normalized after 2 years of TTh. Conclusions Two-year of TTh resulted in normalized serum testosterone levels, improved glycemia, endothelial function, lipids and insulin sensitivity, and quelled the symptoms of hypogonadism, potentially reducing cardiovascular risk in obese men with FH and T2D.

Effect of Unilateral Iatrogenic Testicular Torsion on the Contralateral Testis in Rats: Prepubertal and Postpubertal.

The present study was conducted to investigate the influence of hemicastration and age at hemicastration on the contralateral testis weight and function/testosterone production. 64 Wistar-derived male rats were divided randomly into 4 groups. Group 1 was named immature intervention, group 2 immaturecontrol, group 3 mature intervention, and group 4mature control. In group 1, rats were hemicastrated at 30 days of age (prepubertal). In group 2, sham surgery (midscrotal incision) was per-formed atthe same age. In group 3, rats were hemicastrated at 70 days of age (postpubertal) and in group 4,sham surgery was done at the same age. Twenty days after the first surgery, contralateral orchiectomy wasperformed in intervention groups and controls underwent random orchiectomy (left or right). Blood sampling for evaluation of serum testosterone was performed just before second surgery. The mean testis weight (1692 ± 26.7 in group 1 versus 1375 ± 39.7 in group 2; P < .001 and 1760 ± 26.6 in group 3 versus 1425 ± 44.9 in Group 4; P < .001) and the mean testicular weight (mg) per 100 g of body weight (735.8 ± 82.3 in group 1 versus 634.8 ± 84.8 in group 2; P = .005 and 652.4 ± 61.4 in group 3 versus 572.6 ± 97.7 in group 4; P = .03) were significantly greater in hemicastrated rats as to their controls. Also, these parameters was greater in prepubertal group than postpubertalhemicastrated rats. There was no appreciable difference in serum testosterone levels across the 4 groups (P = .77). Our research demonstrated that hemicastration results in compensatory hypertrophy of the remaining testis and it decreases as the animals age. Hemicastration does not lead to reduction in serum testosterone levels and the remaining testis can retrieve a normal serum testosterone level.

MON-LB065 A Norepinephrine-Only Secreting Pheochromocytoma in the Absence of an Identifiable Genetic Defect

Introduction - Pheochromocytoma is a rare catecholamine-secreting tumor with an incidence as low as 0.8 per 100,000 individuals. Despite the rarity of pheochromocytoma, the availability of definitive treatment makes early diagnosis crucial to avoid life-threatening hypertension. The objective of this report is to describe a case of norepinephrine-only-secreting pheochromocytoma. Case Description - A 33-year-old female with a medical history of hypertension presented with complaints of acute, left-sided chest pain and palpitation. She also reported intermittent dizziness and headache for previous one week. Vital signs pertinent for blood pressure 160/80mmHg and physical exam was unremarkable. Initial evaluation with chest radiograph showed an 8.8x8.3cm peripherally calcified mass in the left upper quadrant. Subsequent computed tomography of the abdomen revealed a 10cm heterogeneous left adrenal mass, size concerning for malignancy, with central necrosis and calcification. Hormonal workup for adrenal mass resulted with normal serum testosterone, DHEA-S, morning cortisol, ACTH, aldosterone, plasma epinephrine, and dopamine levels, but profoundly elevated plasma norepinephrine 4124 (80-520) pg/mL. Her 24-hour urinary metanephrine levels were normal but with elevated normetanephrine 24,364 (88-444) ug/24hr, confirming a pheochromocytoma. The normal metanephrine level in the setting of profoundly elevated normetanephrine raised concern for Von Hippel Lindau (VHL). Ultrasound-neck showed benign, bilateral cystic nodules and her thyroid function tests, serum calcitonin were unremarkable. Oncologic workup showed confinement of tumor to the left adrenal. She was started on high salt and high fluid diet. After adequate alpha blockage, the beta-blocking drug was initiated and she underwent robotic laparoscopic removal of the left adrenal gland. The surgical pathology report confirmed benign, 9.8cm pheochromocytoma confined to left adrenal. She was started on corticosteroid postoperatively given relative adrenal insufficiency, but with anticipation of eventual steroid wean. The patient had complete resolution of symptoms and remains clinically stable. Conclusion - Pheochromocytomas arise from chromaffin cells of the adrenal medulla. Although commonly sporadic in nature, a myriad of familial syndromes are associated with pheochromocytoma. The characteristic feature of VHL-associated pheochromocytoma is almost exclusive secretion of normetanephrine and high normetanephrine to metanephrine ratio as seen in this case. Gene testing and confirmation helps with appropriate surveillance and follow up. This case is unique due to the benign pathology despite the large size and negative paraganglioma-pheochromocytoma genetic panel, despite the presence of characteristic features of VHL-associated pheochromocytoma. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Functional Hypogonadotropic Hypogonadism in Men: Underlying Neuroendocrine Mechanisms and Natural History.

After completion of puberty a subset of men experience functional hypogonadotropic hypogonadism (FHH) secondary to excessive exercise or weight loss. This phenomenon is akin to hypothalamic amenorrhea (HA) in women, yet little is known about FHH in men. To investigate the neuroendocrine mechanisms, genetics, and natural history underlying FHH. Retrospective study in an academic medical center. Healthy postpubertal men presenting with symptoms of hypogonadism in the setting of excessive exercise (>10 hours/week) or weight loss (>10% of body weight). Healthy age-matched men served as controls. Clinical assessment, biochemical and neuroendocrine profiling, body composition, semen analysis, and genetic evaluation of genes known to cause isolated GnRH deficiency. Reproductive hormone levels, endogenous GnRH-induced LH pulse patterns, and rare genetic variants. Ten men with FHH were compared with 18 age-matched controls. Patients had significantly lower body mass index, testosterone, LH, and mean LH pulse amplitudes yet normal LH pulse frequency, serum FSH, and sperm counts. Some patients exhibited nocturnal, sleep-entrained LH pulses characteristic of early puberty, and one FHH subject showed a completely apulsatile LH secretion. After decreased exercise and weight gain, five men with men had normalized serum testosterone levels, and symptoms resolved. Rare missense variants in NSMF (n = 1) and CHD7 (n = 1) were identified in two men with FHH. FHH is a rare, reversible form of male GnRH deficiency. LH pulse patterns in male FHH are similar to those observed in women with HA. This study expands the spectrum of GnRH deficiency disorders in men.

Androgen Receptor in Neurons Slows Age-Related Cortical Thinning in Male Mice.

Androgens via the androgen receptor (AR) are required for optimal male bone health. The target cell(s) for the effects of androgens on cortical bone remain(s) incompletely understood. In females, estrogen receptor alpha in neurons is a negative regulator of cortical and trabecular bone. Whether neuronal AR regulates bone mass in males remains unexplored. Here, we inactivated AR in neurons using a tamoxifen-inducible CreERT2 under the control of the neuronal promoter Thy1. Tamoxifen induced a 70% to 80% reduction of AR mRNA levels in Thy1-CreERT2-positive brain regions cerebral cortex and brainstem as well as in the peripheral nervous tissue of male neuronal AR knockout (N-ARKO) mice. Hypothalamic AR mRNA levels were only marginally reduced and the hypothalamic-pituitary-gonadal axis remained unaffected, as determined by normal levels of serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). In contrast to orchidectomy, deletion of neuronal AR did not alter body weight, body composition, hindlimb muscle mass, grip strength, or wheel running. MicroCT analysis of the femur revealed no changes in bone accrual during growth in N-ARKO mice. However, 36- and 46-week-old N-ARKO mice displayed an accelerated age-related cortical involution, namely a more pronounced loss of cortical thickness and strength, which occurred in the setting of androgen sufficiency. Neuronal AR inactivation decreased the cancellous bone volume fraction in L5 vertebra but not in the appendicular skeleton of aging mice. MicroCT findings were corroborated in the tibia and after normalization of hormonal levels. Serum markers of bone turnover and histomorphometry parameters were comparable between genotypes, except for a 30% increase in osteoclast surface in the trabecular compartment of 36-week-old N-ARKO mice. Cortical bone loss in N-ARKO mice was associated with an upregulation of Ucp1 expression in brown adipose tissue, a widely used readout for sympathetic tone. We conclude that androgens preserve cortical integrity in aging male mice via AR in neurons. © 2018 American Society for Bone and Mineral Research.

Regulation of anti-Müllerian hormone (AMH) in males and the associations of serum AMH with the disorders of male fertility.

Anti-Müllerian hormone (AMH) is a functional marker of fetal Sertoli cells. The germ cell number in adults depends on the number of Sertoli cells produced during perinatal development. Recently, AMH has received increasing attention in research of disorders related to male fertility. This paper reviews and summarizes the articles on the regulation of AMH in males and the serum levels of AMH in male fertility-related disorders. We have determined that follicle-stimulating hormone (FSH) promotes AMH transcription in the absence of androgen signaling. Testosterone inhibits the transcriptional activation of AMH. The undetectable levels of serum AMH and testosterone levels indicate a lack of functional testicular tissue, for example, that in patients with anorchia or severe Klinefelter syndrome suffering from impaired spermatogenesis. The normal serum testosterone level and undetectable AMH are highly suggestive of persistent Müllerian duct syndrome (PMDS), combined with clinical manifestations. The levels of both AMH and testosterone are always subnormal in patients with mixed disorders of sex development (DSD). Mixed DSD is an early-onset complete type of disorder with fetal hypogonadism resulting from the dysfunction of both Leydig and Sertoli cells. Serum AMH levels are varying in patients with male fertility-related disorders, including pubertal delay, severe congenital hypogonadotropic hypogonadism, nonobstructive azoospermia, Klinefelter syndrome, varicocele, McCune-Albright syndrome, and male senescence.

The impact of testosterone replacement therapy on glycemic control, vascular function, and components of the metabolic syndrome in obese hypogonadal men with type 2 diabetes

Objective: This study set out to assess effects of testosterone replacement therapy (TRT) on parameters of metabolic syndrome and vascular function in obese hypogonadal males with type 2 diabetes mellitus (DM2).Study design: Fifty-five obese hypogonadal diabetic males on oral hypoglycemic treatment were enrolled into this one-year, double-blind, randomized, placebo-controlled clinical study. Group T (n = 28) was treated with testosterone undecanoate (1000 mg i.m. every 10 weeks) while group P (n = 27) received placebo.Methods: Anthropometrical and vascular measurements – flow-mediated dilatation (FMD) and intima media thickness (IMT) – biochemical and hormonal blood sample analyses were performed at the start of the study and after one year. Derived parameters (BMI, HOMA-IR, calculated free testosterone (cFT) and bioavailable testosterone (BT)) were calculated.Results: TRT resulted in reduction of HOMA-IR by 4.64 ± 4.25 (p < .001), HbA1c by 0.94 ± 0.88% points (p < .001), and an increase in FMD by 2.40 ± 4.16% points (p = .005).Conclusion: TRT normalized serum testosterone levels, improved glycemic control and endothelial function while exerting no ill effects on the study population.

Salivary testosterone may not serve as a screening test in the diagnosis of biochemical hyperandrogenism.

The diagnosis of biochemical hyperandrogenism is still challenging because a set of appropriate, recommended diagnostic tests has not been established. In our study, we aimed to answer the question of whether salivary testosterone is a reliable test to establish the diagnosis of biochemical hyperandrogenism as compared to serum total testosterone (TT) measured either by liquid chromatography-tandem mass spectrometry (LC-MS/MS) or immunoassay and to assess which set of biochemical tests would be the most appropriate for the identification of biochemical hyperandrogenism. A total of 39 women, aged 18-45 years, with clinical or biochemical hyperandrogenism and 41 healthy individuals, aged 19-45 years, were enrolled in the study. Salivary testosterone was measured using the Salimetrics test. Serum TT was measured either using the LC-MS/MS method or immunoassay, and dehydroepiandrosterone sulphate (DHEA-S) and androstenedione were measured using LC-MS/MS. In 15 of 17 (88%) patients with elevated serum TT measured by LC-MS/MS and in 14 of 16 (87%) measured with immunoassay, salivary testosterone showed normal levels. In 11 of 39 women (28%) with normal serum testosterone levels, DHEA-S was elevated. All patients with elevated androstenedione presented with an elevated concentration of either serum testosterone or DHEA-S. Salivary testosterone measurement may lead to the underdiagnosis of biochemical hyperandrogenism. Both serum testosterone and DHEA-S should be measured in the endocrine work-up toward biochemical hyperandrogenism.