Explore the vast range of titles available.

Abstract Disclosure: S. Waheed: None. Primary AmenorrheainanAdult :ACase of Septo-OpticDysplasia Background: Wepresent acaseof ayoung femalewith primary amenorrhea, absenceof secondary sexualcharacteristics, right-sidedvisionloss, andhypopituitarism. Clinical Case: A 32-year-oldfemalewith ahistory of generalizedseizures presentedfor evaluationof primaryamenorrhea. Shehadcongenital right visionloss. Shehadnever experiencedpuberty ordevelopedsecondary sexual characteristics. Shewas treatedwith Humanchorionicgonadotrophins (HCG), somatotropinandoral contraceptivepills (OCP)for short staturewhenshewas 15-years oldfor less thantwoyears. Shehadnever undergoneapelvic ultrasound.Shedeniedanosmiaor headaches. Shewas diagnosedwith hypothyroidism inchildhoodandhas beenonastabledoseof levothyroxine. Laboratory findings revealedFSH 1.6mIU/mL(normal: 2.5-9.1mIU/mL), LH 0.3mIU/mL (normal: 1.9-16.9mIU/mL), TSH 0.07mIU/mL(normal: 0.40-4.50mIU/mL), T42.2ng/dL (normal: 0.8-1.8ng/dL). Repeat labs showedTSH0.02mIU/mL, thyroidperoxidaseantibody >900IU/mL (normal: <9IU/mL), ACTH 14pg/mL(normal: 6-50pg/mL), IGF-1<10ng/mL (normal: 53-331ng/mL), DHEA-S 5mcg/dL (normal:19-237mcg/dL), prolactin4ng/mL (normal: 3-20ng/mL), cortisol 2.2mcg/dL (normal: 4-22mcg/dL), estradiol <2pg/mL (normal: 39-440pg/mL). AnMRI revealedanabnormal corpuscallosum with hypoplasia/dysplasiaof its anterior half, abnormal genu andasymmetric changesintheright cingulategyrus. A pelvic ultrasoundshowedahypoplastic uterus, andtheovariescouldnot beidentified.Twoor morefeatures of thetriadof optic nervehypoplasia,pituitaryhormonedeficiency andmidlinebraindefects (absenceof septum pellucidum and/or corpuscallosum)arerequiredfor thediagnosis of Septo-optic dysplasia(SOD)alsoknownas deMorsier syndrome. Our patient hadall thethreecomponents. Patient was startedonhydrocortisoneandlow doseestrogen/progesterone. Discussion: SOD is arareconditionwith prevalenceof 1in10,000livebirths. Most individuals with SODarediagnosedearlier inlife, oftenduring infancy or childhood. Interestingly, this patient wentundiagnosedintothe3rddecade. Severeadrenal insufficiency typically results inlife-threatening adrenal crises, yet thepatient has managedtoavoidtheseacutecomplications. Presentation: Sunday, July 13, 2025

Abstract Disclosure: L. Walfish: None. L. Feldman: None. O. Ajise: None. J.A. Rivera: None. Background: Adrenal tumors can be seen in inadequately treated patients with congenital adrenal hyperplasia (CAH), thought to result from chronic adrenocorticotrophic hormone (ACTH) overstimulation. In patients with CAH, a characteristic finding of poor control is elevated 17-hydroxyprogesterone (17-OHP). Similarly, it has been documented that some non-secreting adrenal adenomas can be 21-hydroxylase deficient and, therefore, also produce 17-OHP under ACTH stimulation. Scarce data exists describing autoimmune adrenalitis associated with adrenal masses and elevated 17-OHP. Case Presentation: A previously healthy 17-year-old female presented to her primary care physician for a 1-year history of secondary amenorrhea after discontinuing oral contraceptives. Progesterone challenges were negative. Notable laboratory investigations included an elevated 17-OHP at 117 nmol/L (ref. 0.6-8.0nmol/L). An abdominal pelvic ultrasound revealed a 2.7 cm right adrenal tumor. Upon presentation to endocrinology, history and physical examinations showed no signs or symptoms of adrenal hormone overproduction. Further biochemical assessment of adrenal hyperfunction was also negative. Other than an elevated renin at 464.8 ng/L (ref. 3.3-6.1) with a low normal aldosterone, the rest of her hormonal work up showed no abnormalities. Genetic analysis showed no mutation in a 12-genes CAH panel. On further questioning, the patient admitted to salt craving, morning nausea, fatigue, and spontaneous skin darkening in comparison to her twin sister. A morning cortisol resulted at 76 nmol/L (ref.120-535), ACTH > 440pmol/L (ref. 1.6-13.9), with presence of adrenal autoantibodies. She was diagnosed with autoimmune primary adrenal insufficiency (AI) and started on hydrocortisone and fludrocortisone replacement. An abdominal MRI demonstrated a 2.5x1.4x1.8cm right adrenal, well-circumscribed tumour, isointense in T2, hypointense in T1, with no loss of signal on the out-of-phase T1 sequences, in keeping with a lipid-poor lesion. A PET scan demonstrated the mass to be FDG avid at 19.4 SUV. The patient is currently waiting for laparoscopic right adrenalectomy. Conclusion: This case highlights a potential relationship between adrenal masses and primary autoimmune adrenalitis that has not been described before. Most reported cases of this type of co-occurrence have been related to adrenal lymphoma or CAH. The elevated plasma 17-OHP in our case is unusual and is suspected to originate from the adrenal tumor’s expected decreased 21-hydroxylase expression. Such deficiency would otherwise go unnoticed but has become evident under strong ACTH stimulation from the primary AI. The strong ACTH stimulation may also explain the high FDG uptake, contrasting with surrounding ongoing adrenalitis. Nevertheless, surgical removal is indicated given the lipid-poor nature of the lesion. Presentation: Monday, July 14, 2025

BACKGROUNDKisspeptin is a key regulator of hypothalamic gonadotropin-releasing hormone (GnRH) neurons and is essential for reproductive health. A specific kisspeptin receptor (KISS1R) agonist could significantly expand the potential clinical utility of therapeutics targeting the kisspeptin pathway. Herein, we investigate the effects of a KISS1R agonist, MVT-602, in healthy women and in women with reproductive disorders.METHODSWe conducted in vivo and in vitro studies to characterize the action of MVT-602 in comparison with native kisspeptin-54 (KP54). We determined the pharmacokinetic and pharmacodynamic properties of MVT-602 (doses 0.01 and 0.03 nmol/kg) versus KP54 (9.6 nmol/kg) in the follicular phase of healthy women (n = 9), and in women with polycystic ovary syndrome (PCOS; n = 6) or hypothalamic amenorrhea (HA; n = 6). Further, we investigated their effects on KISS1R-mediated inositol monophosphate (IP1) and Ca2+ signaling in cell lines and on action potential firing of GnRH neurons in brain slices.RESULTSIn healthy women, the amplitude of luteinizing hormone (LH) rise was similar to that after KP54, but peaked later (21.4 vs. 4.7 hours; P = 0.0002), with correspondingly increased AUC of LH exposure (169.0 vs. 38.5 IU∙h/L; P = 0.0058). LH increases following MVT-602 were similar in PCOS and healthy women, but advanced in HA (P = 0.004). In keeping with the clinical data, MVT-602 induced more potent signaling of KISS1R-mediated IP1 accumulation and a longer duration of GnRH neuron firing than KP54 (115 vs. 55 minutes; P = 0.0012).CONCLUSIONTaken together, these clinical and mechanistic data identify MVT-602 as having considerable therapeutic potential for the treatment of female reproductive disorders.TRIAL REGISTRATIONInternational Standard Randomised Controlled Trial Number (ISRCTN) Registry, ISRCTN21681316.FUNDINGNational Institute for Health Research and NIH.

Cosponsoring Associations:The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the Endocrine Society.Objective:To formulate clinical practice guidelines for the diagnosis and treatment of functional hypothalamic amenorrhea (FHA).Participants:The participants include an Endocrine Society–appointed task force of eight experts, a methodologist, and a medical writer.Evidence:This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies.Consensus Process:One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and cosponsoring organizations reviewed and commented on preliminary drafts of this guideline.Conclusions:FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation.FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof.

Hypothalamic amenorrhea may be accompanied by low leptin levels. These investigators administered recombinant human leptin to eight women with hypothalamic amenorrhea. Six additional untreated subjects served as historical controls. Treatment with recombinant leptin increased mean luteinizing hormone levels and pulse frequency, improved ovarian variables, and resulted in ovulation in three women and in withdrawal bleeding in two. Leptin administration may improve reproductive, thyroid, and growth hormone function. Hypothalamic amenorrhea, either organic or functional, 1 is characterized by the absence of menstrual cycles, low estrogen levels, and low or normal levels of gonadotropins. It accounts for over 30 percent of cases of amenorrhea in women of reproductive age 2 and may lead to infertility and bone loss. 3 Functional hypothalamic amenorrhea occurs when a relative energy deficit (owing to weight loss, excessive exercise, or eating disorders) disrupts the secretion of hypothalamic gonadotropin-releasing hormone (GnRH) and other neuroendocrine axes. 4 – 7 However, the precise signal or signals indicating the availability of energy remain unknown. Leptin, a hormone secreted by adipocytes that regulates energy . . .

Purpose The aim of our study was to evaluate changes in the retinal and choriocapillaris circulations in patients with hypothalamic amenorrhea. Methods Prospective, cross-sectional observational study on 25 patients (50 eyes) diagnosed with hypothalamic amenorrhea and 25 age-matched healthy women. Optical coherence tomography angiography (OCTA) was used to evaluate the vessel density (VD) of superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris VD layers in whole 6.4 × 6.4-mm image and in fovea grid-based image. In patients’ group, systemic parameters were collected: body mass index (BMI), endometrial rhyme thickness, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, insulin, and cortisol. Results SCP and DCP did not show any statistical difference when comparing patients and controls (all p > 0.05). Differently, choriocapillaris VD in the whole region showed a non-significant tendency toward higher values in the patients group in both eyes ( p = 0.038 for right eye [RE], p = 0.044 for left eye [LE]). Foveal choriocapillaris VD was higher in hypothalamic amenorrhea women vs. healthy controls (66.0 ± 2.4 vs. 63.7 ± 6.6%, p = 0.136 for RE; 65.0 ± 2.4 vs. 61.6 ± 7.0%, p = 0.005 for LE). Focusing on correlation with systemic parameters, SCP and DCP foveal density had a medium/high effect size with endometrial rhyme, along with DCP in the fovea area vs. cortisol and SCP in the whole area vs. FSH. Conclusion When comparing hypothalamic amenorrhea patients to healthy subjects, OCTA detected changes in the choriocapillaris layer, showing increased VD in the early stage of the systemic pathology, suggesting that microvascular “compaction” could be a first phase of hypoestrogenism adaptation.

Objectives To determine metabolic and hormonal profiles in women with functional hypothalamic amenorrhea (FHA) with normal body mass index (BMI). Methods In FHA ( n  = 69) and controls ( n  = 69), matched for age and BMI lipid, fasting plasma glucose (FPG) and insulin (Ins) levels along with hormonal profile were determined. Results FHA showed slightly lower FPG (− 8.2%, p  = 0.001) contrary to the controls with no differences in lipid profile. In the FHA group, BMI was positively correlated with Ins ( r  = 0.57, p  < 0.001) and negatively with high-density lipoprotein cholesterol (HDL-C; r  = − 0.58, p  < 0.001). Regarding hormonal profile, FHA showed higher prolactin (PRL; + 61.6%) and thyroid-stimulating hormone (TSH; + 4.0%) levels compared to the controls (all p  < 0.05). FHA had higher androgen levels reflected by higher total testosterone (TT; + 22.2%) and 17-hydroxyprogesterone (17-OHP; + 88.9%) levels (all p  < 0.05) in contrary to the remainder. Conclusion FHA women with normal BMI present unfavorably altered hormonal profile reflected by hyperandrogenemia and slightly lower, but significant, FPG level. The findings confirm the importance of assessing both metabolic and hormonal panels in FHA women despite normal BMI.

PurposeChemotherapy-related amenorrhea (CRA) is a surrogate for ovarian toxicity and associated risk of infertility and premature menopause. Here, we compare CRA rate with paclitaxel (T)-trastuzumab (H) to that with ado-trastuzumab emtansine (T-DM1).MethodsPatients with T1N0 HER2 + early-stage breast cancer (eBC) enrolled on the ATEMPT trial and were randomized 3:1 to T-DM1 3.6 mg/kg IV every (q) 3 weeks (w) × 17 vs. T 80 mg/m2 with H IV qw × 12 (4 mg/kg load → 2 mg/kg), followed by H (6 mg/kg IV q3w × 13). Enrollees who self-reported as premenopausal were asked to complete menstrual surveys at baseline and every 6–12 months for 60 months. 18-month CRA (no periods reported during prior 6 months on 18-month survey) was the primary endpoint of this analysis.ResultsOf 512 ATEMPT enrollees, 123 who began protocol therapy and answered baseline and at least one follow-up menstrual survey were premenopausal at enrollment. 76 had menstrual data available at 18 months without having received a gonadotropin-releasing hormone agonist or undergone hysterectomy and/or oophorectomy. Median age was 45 (range 23–53) among 18 who had received TH and 46 (range 34–54) among 58 who had received T-DM1. The 18-month rate of CRA was 50% after TH and 24% after T-DM1 (p = 0.045).ConclusionAmenorrhea at 18 months was less likely in recipients of adjuvant T-DM1 than TH. Future studies are needed to understand how T-DM1 impacts risk of infertility and permanent menopause, and to assess amenorrhea rates when T-DM1 is administered after standard HER2-directed chemotherapy regimens.

Hypothalamic amenorrhea (HA) is associated with dysfunction of the hypothalamic-pituitary-peripheral endocrine axes, leading to infertility and bone loss, and usually is caused by chronic energy deficiency secondary to strenuous exercise and/or decreased food intake. Energy deficiency also leads to hypoleptinemia, which has been proposed, on the basis of observational studies as well as an open-label study, to mediate the neuroendocrine abnormalities associated with this condition. To prove definitively a causal role of leptin in the pathogenesis of HA, we performed a randomized, double-blinded, placebo-controlled trial of human recombinant leptin (metreleptin) in replacement doses over 36 wk in women with HA. We assessed its effects on reproductive outcomes, neuroendocrine function, and bone metabolism. Leptin replacement resulted in recovery of menstruation and corrected the abnormalities in the gonadal, thyroid, growth hormone, and adrenal axes. We also demonstrated changes in markers of bone metabolism suggestive of bone formation, but no changes in bone mineral density were detected over the short duration of this study. If these data are confirmed, metreleptin administration in replacement doses to normalize circulating leptin levels may prove to be a safe and effective therapy for women with HA.

Background The resumption of menses is an important indicator of recovery in anorexia nervosa (AN). Patients with early-onset AN are at particularly great risk of suffering from the long-term physical and psychological consequences of persistent gonadal dysfunction. However, the clinical variables that predict the recovery of menstrual function during weight gain in AN remain poorly understood. The aim of this study was to investigate the impact of several clinical parameters on the resumption of menses in first-onset adolescent AN in a large, well-characterized, homogenous sample that was followed-up for 12 months. Methods A total of 172 female adolescent patients with first-onset AN according to DSM-IV criteria were recruited for inclusion in a randomized, multi-center, German clinical trial. Menstrual status and clinical variables (i.e., premorbid body mass index (BMI), age at onset, duration of illness, duration of hospital treatment, achievement of target weight at discharge, and BMI) were assessed at the time of admission to or discharge from hospital treatment and at a 12-month follow-up. Based on German reference data, we calculated the percentage of expected body weight (%EBW), BMI percentile, and BMI standard deviation score (BMI-SDS) for all time points to investigate the relationship between different weight measurements and resumption of menses. Results Forty-seven percent of the patients spontaneously began menstruating during the follow-up period. %EBW at the 12-month follow-up was strongly correlated with the resumption of menses. The absence of menarche before admission, a higher premorbid BMI, discharge below target weight, and a longer duration of hospital treatment were the most relevant prognostic factors for continued amenorrhea. Conclusions The recovery of menstrual function in adolescent patients with AN should be a major treatment goal to prevent severe long-term physical and psychological sequelae. Patients with premenarchal onset of AN are at particular risk for protracted amenorrhea despite weight rehabilitation. Reaching and maintaining a target weight between the 15 th and 20 th BMI percentile is favorable for the resumption of menses within 12 months. Whether patients with a higher premorbid BMI may benefit from a higher target weight needs to be investigated in further studies.