Histologic analysis of gonadal tissue in patients with Turner syndrome and Y chromosome material.

This study investigates gonadal histology in individuals with Turner syndrome assigned female at birth and Y-chromosome material (TS+Y) who underwent prophylactic gonadectomy. Despite case reports suggesting spontaneous menarche and pregnancies in TS+Y, this research reveals the absence of germ cells, indicating low fertility likelihood. Germ cell neoplasia in-situ was present in some patients, emphasizing a non-negligible risk of cancer precursor. As no malignancies were found even in older individuals, the study challenges the immediate need for prophylactic gonadectomy upon TS+Y diagnosis. Limited fertility benefits are suggested, emphasizing the need for further research on optimal timing and criteria for the procedure.

Van Wyk-Grumbach Syndrome and Gonadectomy.

Van Wyk-Grumbach syndrome (VWGS) refers to the development of peripheral precocious puberty, long-standing hypothyroidism, and gonadal masses; when not diagnosed, an unnecessary gonadectomy may be performed. Herein, we present a case of a 10-year-old girl with Down's syndrome, short stature, and vitiligo who presented to our hospital with vaginal bleeding and a palpable pelvic mass. Upon ultrasound and topographical examination, bilateral ovarian masses with negative tumor markers were detected. After bilateral gonadectomy, endocrine studies revealed profound hypothyroidism and peripheral puberty that led to the VWGS syndrome diagnosis (TSH 367.3 mUI/mL, isolated menstruation, indetectable LH, and elevated estradiol). Levothyroxine treatment improved obesity and short stature, and sexual hormone replacement began at 13 years of age. The literature on Van Wyk-Grumbach syndrome shows that it presents most often in women, and classic hypothyroidism symptoms always precede the diagnosis. Approximately 11% of patients have Down's syndrome, sometimes tumor markers are elevated, and some develop severe symptoms (myopathy, short stature, mental delay, ascites, pericardial effusion, Cullen's sign, pituitary hyperplasia, and severe anemia) that respond to levothyroxine treatment. Conclusions: Children with peripheral precocious puberty and gonadal masses must be studied for hypothyroidism before any radical decision is made.

Mixed gonadal dysgenesis with gonadoblastoma diagnosed by prophylactic laparoscopic gonadectomy: A case report.

Mixed gonadal dysgenesis (MGD) is a disorder of sex development caused by mosaicism of the Y chromosome, represented by 45,X/46,XY. Prophylactic gonadectomy is recommended as soon as possible after its diagnosis, owing to a high risk of malignancy. In the present case, a 21-year-old woman presented with primary amenorrhea. Although the patient's external genitalia were female, the patient exhibited a hypoplastic uterus, wherein the ovaries were difficult to identify. The patient's height was 146 cm; they had cubitus valgus and webbing of the neck, leading to the consideration of a disorder of sex development. Chromosomal examination revealed 45,X/46,XY mosaicism. Thus, the patient was diagnosed with MGD. After thorough counseling, laparoscopic bilateral gonadectomy was performed. Pathological examination revealed a gonadoblastoma of the left gonad. Postoperatively, the patient had no recurrence and continued on Kaufmann therapy. In conclusion, prophylactic gonadectomy is recommended immediately following a diagnosis of MGD; however, the timing of the surgery should be carefully considered and adequate counseling should be conducted by a multidisciplinary team.

Seminoma in a 46, XY patient with 17α-hydroxylase deficiency.

Introduction: 17α-Hydroxylase deficiency is a very rare disease reported to be associated with a risk of gonadal malignancy. We herein report a rare case of seminoma in a 46, XY patient with 17α-hydroxylase deficiency. Case presentation: A 52-year-old woman presented with a 9-cm pelvic tumor. At age 14, she had been identified as having the XY karyotype and 17α-hydroxylase deficiency. However, she was not informed and did not consult the urology department. Laparoscopic gonadectomy was performed at the latest consultation, and seminoma was diagnosed. Conclusion: This is the third reported case of testicular tumor and the first of germ cell tumor in a 46, XY patient with 17α-hydroxylase deficiency. Given the rarity and the risk of gonadal malignancy associated with 17α-hydroxylase deficiency, the involvement of multidisciplinary specialists and prophylactic gonadectomy is considered crucial in its management.

Gonadal hormone deprivation regulates response to tibolone in neurodegenerative pathways.

Gonadal hormone deprivation (GHD) and decline such as menopause and bilateral oophorectomy are associated with an increased risk of neurodegeneration. Yet, hormone therapies (HTs) show varying efficacy, influenced by factors such as sex, drug type, and timing of treatment relative to hormone decline. We hypothesize that the molecular environment of the brain undergoes a transition following GHD, impacting the effectiveness of HTs. Using a GHD model in mice treated with Tibolone, we conducted proteomic analysis and identified a reprogrammed response to Tibolone, a compound that stimulates estrogenic, progestogenic, and androgenic pathways. Through a comprehensive network pharmacological workflow, we identified a reprogrammed response to Tibolone, particularly within "Pathways of Neurodegeneration", as well as interconnected pathways including "cellular respiration", "carbon metabolism", and "cellular homeostasis". Analysis revealed 23 proteins whose Tibolone response depended on GHD and/or sex, implicating critical processes like oxidative phosphorylation and calcium signalling. Our findings suggest the therapeutic efficacy of HTs may depend on these variables, suggesting a need for greater precision medicine considerations whilst highlighting the need to uncover underlying mechanisms.

Challenges in the management of Turner syndrome with Y chromosome material: a case report of prophylactic gonadectomy revealing dysgerminoma.

Turner syndrome (TS) patients with Y chromosome material face an increased risk of gonadal germ cell tumors (GCTs). This case report discusses the challenges in decision-making regarding prophylactic gonadectomy, considering the risk of malignancy and the desire to preserve fertility. We report a case of a 12-year-old female with mosaic TS and Y chromosome material who initially presented with short stature and obesity. Karyotype analysis showed a mixed cell line (45X and 46XY). Counseling about the increased risk of developing GCT and preservation of gonadal function was provided, and we decided to delay gonadectomy until the age of 12. Prophylactic bilateral gonadectomy revealed dysgerminoma associated with GB at the age of 12. Fortunately, the patient was asymptomatic, with no additional therapy required due to the early stage of the disease. The case highlights the dilemma in managing TS patients with Y chromosome material, where the risk of GCT varies depending on the type of difference in sex development and gonadal function. The decision to delay gonadectomy reflects the emphasis on preservation of ovarian, although it poses a risk of malignancy. This case underscores the importance of individualized care in TS patients with Y chromosome material, balancing the risk of malignancy against preservation of ovarian. It emphasizes the need for timely and personalized decision-making in prophylactic gonadectomy.

Identifying the target population and preventive strategies to combat feline obesity.

Feline obesity continues to be a priority health and welfare issue. Most research surrounding obesity currently focuses on obesity treatment. However, treatment for feline obesity is slow, often unsuccessful and not without consequences. Identifying high-risk populations for obesity onset is crucial for developing and implementing preventive strategies. This review identifies post-gonadectomy kittens aged 5-12 months as the primary target population for obesity prevention in domestic cats and highlights dietary and feeding management strategies to be implemented for obesity prevention.

DHEA Induces Sex-Associated Differential Patterns in Cytokine and Antibody Levels in Mice Infected with Plasmodium berghei ANKA.

Malaria is the most lethal parasitic disease worldwide; the severity of symptoms and mortality are higher in men than in women, exhibiting an evident sexual dimorphism in the immune response; therefore, the contribution of 17ß-estradiol and testosterone to this phenomenon has been studied. Both hormones differentially affect several aspects of innate and adaptive immunity. Dehydroepiandrosterone (DHEA) is the precursor of both hormones and is the sexual steroid in higher concentrations in humans, with immunomodulatory properties in different parasitic diseases; however, the involvement of DHEA in this sexual dimorphism has not been studied. In the case of malaria, the only information is that higher levels of DHEA are associated with reduced Plasmodium falciparum parasitemia. Therefore, this work aims to analyze the DHEA contribution to the sexual dimorphism of the immune response in malaria. We assessed the effect of modifying the concentration of DHEA on parasitemia, the number of immune cells in the spleen, cytokines, and antibody levels in plasma of CBA/Ca mice infected with Plasmodium berghei ANKA (P. berghei ANKA). DHEA differentially affected the immune response in males and females: it decreased IFN-γ, IL-2 and IL-4 concentrations only in females, whereas in gonadectomized males, it increased IgG2a and IgG3 antibodies. The results presented here show that DHEA modulates the immune response against Plasmodium differently in each sex, which helps to explain the sexual dimorphism present in malaria.

Changes in gut microbiota and short-chain fatty acids are involved in the process of canine obesity after neutering.

Neutering is a significant risk factor for obesity in dogs. Changes in gut microbiota and its metabolites have been identified as a key player during obesity progression. However, the mechanisms that promote neuter-associated weight gain are not well understood. Therefore, in this study, sixteen clinically healthy Beagle dogs (6 male and 10 female, mean age = 8.22 ±â€…0.25 mo old) were neutered. Body weight (BW) and body condition score (BCS) were recorded at 1 d before neutering, 3, 6, 10, 16, and 21 mo after neutering. Dogs were grouped based on their BCS as ideal weight group (IW, n = 4, mean BW = 13.22 ±â€…1.30 kg, mean BCS = 5.00 ±â€…0.41) and obese group (OB, n = 12, mean BW = 18.57 ±â€…1.08 kg, mean BCS = 7.92 ±â€…0.82) at 21 mo after neutering. Serum lipid profile, glucose, and hormones and fecal microbiota and short-chain fatty acids (SCFAs) were measured. Our results showed that OB dogs had greater (P < 0.0001) BW (18.57 vs. 13.22 kg), BCS (7.92 vs. 5.00), and average daily gain (12.27 vs. 5.69 g/d) than IW dogs at 21 mo after neutering, and the obesity rate was up to 60%. In addition, significant increases (P < 0.05) in serum triglyceride (TG, 1.10 vs. 0.56 mmol/L) and high-density lipoprotein cholesterol (HDL-C, 6.96 vs. 5.40 mmol/L) levels and a significant decrease (P < 0.05) in serum adiponectin (APN, 54.06 vs. 58.39 µg/L) level were observed in OB dogs; serum total cholesterol (4.83 vs. 3.75 mmol/L) (P = 0.075) and leptin (LEP, 2.82 vs. 2.53 µg/L) (P = 0.065) levels tended to be greater in OB dogs; there was a trend towards a lower (P = 0.092) APN/LEP (19.32 vs. 21.81) in OB dogs. Results of fecal microbial alpha-diversity showed that Observed_species and Chao1 indices tended to be lower (P = 0.069) in OB dogs. The STAMP and LEfSe analyses revealed that OB dogs had a greater (P < 0.05 and LDA > 2) reduction in relative abundances of Bacteroides, Prevotella_9, and Megamonas than IW dogs. In addition, OB dogs also had greater (P < 0.05) reduction in fecal acetate, propionate, and butyrate concentrations than IW dogs. Moreover, clear negative correlations (|r| > 0.5 and P < 0.05) were found between SCFAs-producing bacteria and BW, TG, and HDL-C. The functional predictions of microbial communities based on PICRUSt2 analysis revealed that lipid metabolism and endocrine system were significantly disturbed in obese dogs after neutering. Thus, intervention with SCFAs-producing bacteria might represent a new target for the prevention or treatment of canine obesity after neutering. Moreover, weight control before neutering may also contribute to the prevention of canine obesity after neutering.

Neutering contributes to canine obesity risk. In this study, obesity rate of 60% at 21 mo after neutering was observed. Obese dogs had greater serum triglyceride, total cholesterol, high-density lipoprotein cholesterol, and leptin levels and lower adiponectin level than ideal weight dogs. In addition, fecal microbiota analysis found a decreasing microbial diversity in obese dogs, and decreasing SCFAs-producing bacteria Megamonas, Bacteroides, and Prevotella_9 in obese dogs resulted in lower production of fecal acetate, propionate, and butyrate. Importantly, strong negative correlations between SCFAs-producing bacteria and body weight, TG, and HDL-C revealed that SCFAs-producing bacteria are involved in the process of canine obesity after neutering. Thus, intervention with SCFAs-producing bacteria may be a target for the prevention or treatment of canine obesity after neutering. Moreover, weight control before neutering may also contribute to the prevention of canine obesity after neutering.

Dietary Progesterone Contributes to Intratissue Levels of Progesterone in Male Mice.

Progesterone serum levels have been identified as a potential predictor for treatment effect in men with advanced prostate cancer, which is an androgen-driven disease. Although progesterone is the most abundant sex steroid in orchiectomized (ORX) male mice, the origins of progesterone in males are unclear. To determine the origins of progesterone and androgens, we first determined the effect of ORX, adrenalectomy (ADX), or both (ORX + ADX) on progesterone levels in multiple male mouse tissues. As expected, intratissue androgen levels were mainly testicular derived. Interestingly, progesterone levels remained high after ORX and ORX + ADX with the highest levels in white adipose tissue and in the gastrointestinal tract. High progesterone levels were observed in mouse chow and exceptionally high progesterone levels were observed in food items such as dairy, eggs, and beef, all derived from female animals of reproductive age. To determine if orally ingested progesterone contributes to tissue levels of progesterone in males, we treated ORX + ADX and sham mice with isotope-labeled progesterone or vehicle by oral gavage. We observed a significant uptake of labeled progesterone in white adipose tissue and prostate, suggesting that dietary progesterone may contribute to tissue levels of progesterone. In conclusion, although adrenal-derived progesterone contributes to intratissue progesterone levels in males, nonadrenal progesterone sources also contribute. We propose that dietary progesterone is absorbed and contributes to intratissue progesterone levels in male mice. We speculate that food with high progesterone content could be a significant source of progesterone in males, possibly with consequences for men undergoing androgen deprivation therapy for prostate cancer.

A Case Report on Ambiguous Genitalia: A Diagnostic, Therapeutic, and Cosmetic Challenge.

Ambiguous genitalia is a matter of concern and needs thorough evaluation and treatment. Gonadectomy becomes a potentially lifesaving procedure in patients with partial androgen insensitivity due to the increased risk of malignancy if left undiagnosed. We present a case report of two patients in their late 20s and 30s, raised as girls, who came with complaints of primary amenorrhea with ambiguous genitalia. Both patients had features of masculinization. Her MRI revealed an absent uterus, cervix, upper 2/3 of the vagina, and ovaries, with the presence of bilateral testicles. She was diagnosed with partial androgen insensitivity syndrome. The first patient underwent bilateral gonadectomy with hernia repair and nerve-sparing reduction clitoroplasty with labioplasty. She is under close follow-up with a further plan for augmentation mammoplasty. The second patient, however, refused clitoroplasty and underwent bilateral gonadectomy. Androgen insensitivity syndrome is an X-linked inheritance with a mutation in the AR gene. It consists of a spectrum of conditions ranging from complete insensitivity to less insensitivity towards testosterone, which results in a complete, partial, and mild form of androgen insensitivity syndrome. Studies have been done on cosmetic outcomes after genitoplasty in children with genital atypicalities, which showed significant improvement (p<0.001) and no difference in ratings by parents and surgeons. Surgeries done on patients with partial androgen insensitivity syndrome are not only lifesaving procedures, but with reasonable reassurance, these aesthetic surgeries help people live a life that otherwise would have been genetically compromised.

Chronic testosterone deficiency increases late inward sodium current and promotes triggered activity in ventricular myocytes from aging male mice.

Clinical studies suggest low testosterone levels are associated with cardiac arrhythmias, especially in later life. We investigated whether chronic exposure to low circulating testosterone promoted maladaptive electrical remodeling in ventricular myocytes from aging male mice and determined the role of late inward sodium current (INa,L) in this remodeling. C57BL/6 mice had a gonadectomy (GDX) or sham surgery (1 mo) and were aged to 22-28 mo. Ventricular myocytes were isolated; transmembrane voltage and currents were recorded (37°C). Action potential duration at 70 and 90% repolarization (APD70 and APD90) was prolonged in GDX compared with sham myocytes (APD90, 96.9 ± 3.2 vs. 55.4 ± 2.0 ms; P < 0.001). INa,L was also larger in GDX than sham (-2.4 ± 0.4 vs. -1.2 ± 0.2 pA/pF; P = 0.002). When cells were exposed to the INa,L antagonist ranolazine (10 µM), INa,L declined in GDX cells (-1.9 ± 0.5 vs. -0.4 ± 0.2 pA/pF; P < 0.001) and APD90 was reduced (96.3 ± 14.8 vs. 49.2 ± 9.4 ms; P = 0.001). GDX cells had more triggered activity (early/delayed afterdepolarizations, EADs/DADs) and spontaneous activity than sham. EADs were inhibited by ranolazine in GDX cells. The selective NaV1.8 blocker A-803467 (30 nM) also reduced INa,L, decreased APD and abolished triggered activity in GDX cells. Scn5a (NaV1.5) and Scn10a (NaV1.8) mRNA was increased in GDX ventricles, but only NaV1.8 protein abundance was increased in GDX compared with sham. In vivo studies showed QT prolongation and more arrhythmias in GDX mice. Thus, triggered activity in ventricular myocytes from aging male mice with long-term testosterone deficiency arises from APD prolongation mediated by larger NaV1.8- and NaV1.5-associated currents, which may explain the increase in arrhythmias.NEW & NOTEWORTHY Older men with low testosterone levels are at increased risk of developing cardiac arrhythmias. We found aged mice chronically exposed to low testosterone had more arrhythmias and ventricular myocytes had prolonged repolarization, abnormal electrical activity, larger late sodium currents, and increased expression of NaV1.8 sodium channels. Drugs that inhibit late sodium current or NaV1.8 channels abolished abnormal electrical activity and shortened repolarization. This suggests the late sodium current may be a novel target to treat arrhythmias in older testosterone-deficient men.

Effect of gonadectomy on pain assessment in dogs undergoing orthopaedic stifle surgery.

OBJECTIVE: To compare pain perception between gonadectomized and intact dogs. STUDY DESIGN: Blinded, prospective, cohort study. ANIMALS: A group of 74 client-owned dogs. METHODS: Dogs were divided into four groups: group 1-female/neutered (F/N), group 2-female/intact (F/I), group 3-male/neutered (M/N) and group 4-male/intact (M/I). Premedication consisted of intramuscularly administered acepromazine (0.05 mg kg-1) and morphine (0.2 mg kg-1), and subcutaneously administered carprofen (4 mg kg-1). Anaesthesia was induced with propofol (1 mg kg-1 intravenously and supplementary doses to effect) and maintained with isoflurane in 100% oxygen. Intraoperative analgesia was achieved with fentanyl infusion (0.1 µg kg-1 minute-1). Pain assessments [using the University of Melbourne Pain Scale (UMPS) and an algometer at the incision site (IS), parallel to the incision site (NIS), and on the contralateral healthy limb] were performed preoperatively, and at 1, 2, 4, 6, 9 and 20 hours after extubation. The time-standardised area under the curve (AUCst) for measurements was calculated and compared by performing a one-way multivariate analysis of variance (manova). Statistical significance was set at p < 0.05. RESULTS: Postoperatively, F/N exhibited higher pain than F/I, with estimated marginal means (95% confidence intervals) AUCstISGroup1 909 (672-1146) versus AUCstISGroup2 1385 (1094-1675) (p = 0.014), AUCstNISGroup1 1122 (823-1420) versus AUCstNISGroup2 1668 (1302-2033) (p = 0.024) and AUCstUMPSGroup1 5.30 (4.58-6.02) versus AUCstUMPSGroup2 4.1 (3.2-5.0) (p = 0.041). Similarly, M/N showed higher pain than M/I with AUCstISGroup3 686 (384-987) versus AUCstISGroup4 1107 (871-1345) (p = 0.031) and AUCstNISGroup3 856 (476-1235) versus AUCstNISGroup4 1407 (1109-1706) (p = 0.026), and AUCstUMPSGroup3 6.0 (5.1-6.9) versus AUCstUMPSGroup4 4.4 (3.7-5.2) (p = 0.008). CONCLUSIONS AND CLINICAL RELEVANCE: Gonadectomy affects pain sensitivity in dogs undergoing stifle surgery. Neutering status should be taken into consideration when planning individualized anaesthetic/analgesic protocols.

Gonadal tumors in a contemporary cohort of patients with differences in sex development undergoing surgery - A multi-site study from the Pediatric Urologic Oncology Working Group of the societies for pediatric urology.

BACKGROUND: Disturbances in gonadal development lead to increased risk of gonadal malignancy in some but not all patients with differences in sex development (DSD). However, the natural history of these tumors is poorly described, and the literature remains sparse. OBJECTIVE: The objective of this study was to describe the incidence of germ cell neoplasia in situ (GCNIS) and germ cell tumor (GCT) in a contemporary cohort of patients with DSD undergoing surgery and to provide long-term oncologic outcomes for these patients. STUDY DESIGN: Patients with DSD who have undergone gonadectomy or gonadal biopsy were identified at four institutions. Clinical characteristics, pathology, and treatment details were obtained retrospectively. Patients were stratified into risk categories based on DSD diagnosis. Oncologic treatment and outcomes were recorded. Descriptive statistics are reported using parametric methods. RESULTS: 83 patients were identified. Distribution of diagnoses is summarized in the summary table. 14 (16.9%) patients underwent gonadal biopsy, and 71 (85.5%) patients underwent gonadectomy (50/71 gonadectomies were bilateral). 8/83 (9.6%) patients had GCNIS or GCT (7 GCNIS, 1 GCT). Median age at surgery was 2.95 years (y) (interquartile range [IQR] 0.6-12.2) and 14y (IQR 0.85-16.9) in patients without and with GCNIS/GCT, respectively. All 8 patients with GCNIS/GCT had high or intermediate risk DSD diagnoses (4 mixed gonadal dysgenesis, 3 Turner with Y, 1 partial gonadal dysgenesis). Of the patients with high-risk diagnoses, 8/54 (15%) had GCNIS/GCT. No patient received adjuvant therapy, no patient had a recurrence, and all patients were living with mean follow up 6.4y. DISCUSSION: The risk of gonadal malignancy is heterogeneous in the DSD population and can vary based on DSD diagnosis as well as maturation, testicularization, and location of the gonads. The most recent consensus recommendations on gonadal management emphasize risk stratification and consideration of gonadal surveillance based on gender of rearing, but supporting literature remains sparse. In this contemporary cohort of DSD patients who underwent gonadal surgery, most patients did not have evidence of adverse pathology, all patients with malignant or premalignant pathology had a high/intermediate risk DSD diagnosis, and all patients with GCNIS/GCT were treated with surgery alone without recurrence. CONCLUSIONS: The distribution of patients with premalignant and malignant gonadal pathology and DSD in this cohort aligns with prior literature, and oncologic outcomes were excellent. These data add valuable information to the current literature and highlight the necessity to develop appropriate screening regimens for retained gonads.

Retrospective comparison of the effects of laryngeal mask and endotracheal tube on some cardio-respiratory variables in pet rabbits undergoing anaesthesia for elective gonadectomy.

BACKGROUND: Endotracheal intubation in rabbits is challenging and supraglottic airway devices, such as laryngeal masks (LMA), represent an alternative as they are easy to insert, and do not stimulate the larynx requiring therefore a lighter plane of anaesthesia for their insertion and positioning than the endotracheal tubes. We investigated whether, compared to an endotracheal tube, the LMA can reduce the negative effects of general anaesthetics on some cardiovascular and respiratory parameters routinely monitored in rabbits anaesthetized for elective gonadectomy. The records of 21 adult mixed breed pet rabbits were collected retrospectively. Rabbits were divided in two groups based on the type of airway device used. A laryngeal mask secured the airway in group LMA (n = 11), and in group ETT (n = 10) an endotracheal tube was used. The amount of propofol used before successful insertion of the airway device was recorded. A pitot-based spirometer was connected and ventilatory variables were measured immediately after insertion. Pulse rate, non-invasive arterial blood pressure, haemoglobin oxygen saturation, respiratory rate, end-tidal carbon dioxide and volatile anaesthetic consumption were also monitored during the surgical procedure; extubation time was noted as well. RESULTS: The use of LMA required significantly less propofol (0.8 to 4 mg/kg) for insertion than the ETT (1.2 to 5.6 mg/kg), and the difference was statistically significant (P < 0.01). No differences were observed in ventilatory variables measured immediately after airway positioning. Intraoperatively, there were no differences between groups for respiratory and cardiovascular variables, and amount of isoflurane administered. In all rabbits mean and diastolic blood pressure progressively decreased during surgery. Mean extubation time was shorter in group LMA (6 ± 2 min) than group ETT (8 ± 3 min, P < 0.01). CONCLUSION: The airway device did not clinically affect the cardiovascular and respiratory variables during anaesthesia. Intraoperative hypoventilation was observed in most rabbits regardless of the device being used; therefore ventilatory support may be required. Rabbits with the laryngeal masks were extubated earlier.

Deferring gonadectomy in patients with turner syndrome with a genetic Y component is not a safe practice.

INTRODUCTION: Patients with Turner syndrome who harbor Y chromosome material are known to be at increased risk of developing germ cell neoplasms. The optimal timing to perform gonadectomy to reduce the risk of cancer development in these patients is not well defined. We present outcomes of Turner with a Y component (TSY) patients who underwent gonadectomy at our institution. HYPOTHESIS/OBJECTIVE: We hypothesized that tumors could occur in a significant portion of TSY patients at any age and gonadectomy can be safely performed at diagnosis rather than deferred. STUDY DESIGN: We performed an IRB-approved retrospective single center study in which we queried our institutions electronic health record to identify all patients with TSY who underwent gonadectomy at our institution from 2012 to 2021. RESULTS: In our series of 18 consecutive TSY patients, a tumor was identified in 6 patients (33.3%): 4 (22.2%) with dysgerminoma (DG) [Fig. 1] and 2 (11.1%) with gonadoblastoma (GB). DISCUSSION: Our cohort of 18 consecutive TSY who underwent gonadectomy over a 9-year period is the largest published single site cohort to date. Additionally, our patient who was found to have GB at 40 days is to our knowledge the youngest TSY patient to be diagnosed with GB in the literature. This patient's remarkably early incidence of tumor occurrence illustrates the urgency of protective gonadectomy. Given the high incidence of tumor formation in this population and the minimal morbidity associated with gonadectomy, we do not recommend delaying gonadectomy in this population for any reason. Our study is vulnerable to selection bias and confounding innate to any retrospective study. There was variation with respect to the frequency and timing of pre-operative imaging as a strict preoperative imaging protocol with sequential studies was not in place at our institution. Additionally, we do not have a comparison cohort of patients who are being followed without operative intervention as all TSY patients at our institution have undergone gonadectomy. CONCLUSION: TSY patients cannot be safely observed for tumor formation based on clinical factors such as imaging or age. Gonadectomy is safe with a low complication rate and without tumor recurrence during three-year follow-up. We continue to recommend bilateral gonadectomy in this patient population at the time of diagnosis.

Behavior of the renal kallikrein in spontaneously hypertensive rats: Influence of sexual hormones and aldosterone-sensitive distal nephron ion channels.

The renal kallikrein-kinin system (RKKS) has been related to blood pressure control and sodium and water balance. We have previously shown that female spontaneously hypertensive rats (SHR) have high urinary kallikrein activity (UKa) and lower blood pressure (BP) than males whereas ovariectomy stimulates UKa and diminishes BP. We also showed that high K+ intake and prepuberal gonadectomy (Gx) diminish BP with a concomitant increase in UKa and plasma aldosterone levels. Since kallikrein co-localize in the same distal nephron segments of aldosterone effectors, we explored the effect of pharmacological blockage of aldosterone receptor, epithelial Na+ (ENaC) and the rectifying outer medulla K+ (ROMK) channels in different gonad contexts on the gene expression, renal tissue content and urine release of kallikrein. Klk1 gene expression was determined by real-time PCR and enzymatic activity of kallikrein by the amidolytic method. We found that the inhibition of the aldosterone receptor by spironolactone increases kallikrein renal tissue storage and decreases its urinary activity, especially in Gx rats. Moreover, ENaC blockade by benzamil increases the renal content of kallikrein without affecting synthesis or excretion, especially in females and Gx animals, while the inhibition of ROMK by glibenclamide increases the synthesis and renal content of kallikrein only in intact male animals. We concluded that RKKS regulation showed sexual dimorphism and seemed to be modulated by sex hormones throughout a process involving aldosterone and the aldosterone-sensitive ion channels..

Sex differences in adrenal cortex beta-catenin immunolocalisation of the Saharan gerbil, Libyan jird (Meriones libycus, Lichtenstein, 1823).

BACKGROUND: The adrenal cortex provides adequate steroidogenic responses to environmental changes. However, in desert rodents, the adrenocortical activity varies according to several factors especially sex, age, and seasonal variations. Herein, we examined the sex differences in the adrenal cortex activity and explored the involvement of sex hormones in the regulation of this function in Libyan jird Meriones libycus. MATERIALS AND METHODS: Twenty-four adult male and female animals weighing 109-110 g were captured in the breeding season and equally assigned into control and gonadectomised groups. Animal euthanasia was performed 50 days after the gonadectomy. Adrenal gland was processed for structural and immunohistochemistry study of b-catenin, whereas plasma was used for cortisol assay. RESULTS: The results showed that female adrenal gland weight was heavier than male and gonadectomy reduced this dimorphism. The adrenal cortex thickness was greater in the female than in the male, mainly due to significant development of the zona fasciculata. Females presented higher cell density in fasciculata and reticularis zones. The plasma cortisol was higher in females than in males. The immunolocalisation of beta-catenin showed that the expression was particularly glomerular in both sexes. However, in the female, the immunostaining was present in the zona reticularis while it was absent in the control male. Orchiectomy reduced zona glomerulosa cell density and induced hypertrophy of zona reticularis characterised by strong beta-catenin immunoreactivity. CONCLUSIONS: Results indicated that sex hormones had a major role in the regulation of the Saharan gerbil's adrenal homeostasis by modulating beta-catenin signalling. Androgens seem to inhibit the Wnt-beta-catenin pathway and oestrogens are activators of the adrenal inner zones.

Changes in Serum Testosterone and Adrenal Androgen Levels in Transgender Women With and Without Gonadectomy.

BACKGROUND: Initiating feminizing gender-affirming hormone therapy (GAHT) in transgender women causes a steep decline in serum testosterone. It is unknown if testosterone concentrations change further and whether adrenal androgen levels change during feminizing GAHT and after gonadectomy. This limits clinical decision making in transgender women with symptoms attributed to GAHT or gonadectomy. METHODS: Transgender women (n = 275) initiating estradiol and cyproterone acetate (CPA) were included at baseline, and had follow-up visits after 3 months, 12 months, and 2 to 4 years. During follow-up, 49.5% of transgender women underwent a gonadectomy. Total testosterone (TT), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and androstenedione (A4) were measured using liquid chromatography tandem mass spectrometry. RESULTS: After 3 months of GAHT, mean TT, calculated free testosterone (cFT), and A4 decreased by 18.4 nmol/L (95% CI, -19.4 to -17.4, P < 0.001 [ie, -97.1%]), 383 pmol/L (95% CI, -405 to -362, P < 0.001 [ie, -98.3%]), and 1.2 nmol/L (95% CI, -1.4 to -1.0, P < 0.001 [ie, -36.5%]), respectively, and remained stable thereafter. DHEA and DHEAS decreased by 7.4 nmol/L (95% CI, -9.7 to -5.1 [ie, -28.0%]) and 1.8 µmol/L (95% CI, -2.2 to -1.4 [ie, -20.1%]), respectively, after 1 year and did not change thereafter. After gonadectomy, CPA therapy is stopped, which induced no further change in TT, cFT, DHEA, DHEAS, and A4 compared with those who did not undergo gonadectomy. CONCLUSIONS: Our findings confirm that after an initial drop, testosterone levels in transgender women remain stable. Adrenal androgens decrease in the first year of CPA and estrogen supplementation and remain unchanged after gonadectomy. Androgens did not change after gonadectomy and cessation of CPA. Correlates with clinical symptoms remain to be elucidated.

Successful in Vitro Fertilization Pregnancy and Delivery by an Infertile Woman with Ovotesticular Disorder of Sex Development: A Case Report.

On the basis of postoperative histopathological findings, a 29-year-old nulliparous woman was diagnosed as having ovotesticular disorder of sex development (DSD). She had undergone unilateral gonadectomy at age 6 years and vulvoplasty and vaginoplasty at age 8 years. Her karyotype was 46, XX. She had dyspareunia because of a narrow vagina, but her uterus and left gonad were normal. Spontaneous ovulation was confirmed, but sexual intercourse was impossible because of dyspareunia, despite vaginal self-dilatation with a vaginal dilator. Artificial insemination was initiated; however, five cycles failed to yield a viable pregnancy. We decided to perform in vitro fertilization (IVF), which resulted in conception. During IVF we administered intravenous anesthesia before oocyte collection to reduce her distress due to insufficient lumen expansion after vaginoplasty. The patient delivered a healthy male infant weighing 2,558 g at 37 weeks of gestation via cesarean section, which was performed because of gestational hypertension. This is the eighth report of a viable neonate born from a patient with ovotesticular DSD after gonadectomy and the first such pregnancy achieved by IVF. Therefore, IVF may be an effective option for infertile patients with ovotesticular DSD. Additionally, to prevent dyspareunia, self-management of the plastic vagina is important during the peri- and postoperative periods of early vaginoplasty.