Neuroendocrine Dysfunction Research Articles

Clinical Phenotypes of PCOS: a Cross-Sectional Study.

This cross-sectional study examines the Doi-Alshoumer PCOS clinical phenotype classification in relation to measured clinical and biochemical characteristics of women with polycystic ovary syndrome (PCOS). Two cohorts of women (Kuwait and Rotterdam) diagnosed with PCOS (FAI > 4.5%) were examined. These phenotypes were created using neuroendocrine dysfunction (IRMA LH/FSH ratio > 1 or LH > 6 IU/L) and menstrual cycle status (oligo/amenorrhea) to create three phenotypes: (A) neuroendocrine dysfunction and oligo/amenorrhea, (B) without neuroendocrine dysfunction but with oligo/amenorrhea, and (C) without neuroendocrine dysfunction and with regular cycles. These phenotypes were compared in terms of hormonal, biochemical, and anthropometric measures. The three suggested phenotypes (A, B, and C) were shown to be sufficiently distinct in terms of hormonal, biochemical, and anthropometric measures. Patients who were classified as phenotype A had neuroendocrine dysfunction, excess LH (and LH/FSH ratio), irregular cycles, excess A4, infertility, excess T, highest FAI and E2, and excess 17αOHPG when compared to the other phenotypes. Patients classified as phenotype B had irregular cycles, no neuroendocrine dysfunction, obesity, acanthosis nigricans, and insulin resistance. Lastly, patients classified as phenotype C had regular cycles, acne, hirsutism, excess P4, and the highest P4 to E2 molar ratio. The differences across phenotypes suggested distinct phenotypic expression of this syndrome, and the biochemical and clinical correlates of each phenotype are likely to be useful in the management of women with PCOS. These phenotypic criteria are distinct from criteria used for diagnosis.

Recognition and Management of the Long-term Effects of Cranial Radiation.

Cranial radiation is ubiquitous in the treatment of primary malignant and benign brain tumors as well as brain metastases. Improvement in radiotherapy targeting and delivery has led to prolongation of survival outcomes. As long-term survivorship improves, we also focus on prevention of permanent side effects of radiation and mitigating the impact when they do occur. Such chronic treatment-related morbidity is a major concern with significant negative impact on patient's and caregiver's respective quality of life. The actual mechanisms responsible for radiation-induced brain injury remain incompletely understood. Multiple interventions have been introduced to potentially prevent, minimize, or reverse the cognitive deterioration. Hippocampal-sparing intensity modulated radiotherapy and memantine represent effective interventions to avoid damage to regions of adult neurogenesis. Radiation necrosis frequently develops in the high radiation dose region encompassing the tumor and surrounding normal tissue. The radiographic findings in addition to the clinical course of the patients' symptoms are taken into consideration to differentiate between tissue necrosis and tumor recurrence. Radiation-induced neuroendocrine dysfunction becomes more pronounced when the hypothalamo-pituitary (HP) axis is included in the radiation treatment field. Baseline and post-treatment evaluation of hormonal profile is warranted. Radiation-induced injury of the cataract and optic system can develop when these structures receive an amount of radiation that exceeds their tolerance. Special attention should always be paid to avoid irradiation of these sensitive structures, if possible, or minimize their dose to the lowest limit.

Hypothalamic neuroglial plasticity is regulated by anti-Müllerian hormone and disrupted in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder affecting between 5 and 18% of women worldwide. An elevated frequency of pulsatile luteinizing hormone (LH) secretion and higher serum levels of anti-Müllerian hormone (AMH) are frequently observed in women with PCOS. The origin of these abnormalities is, however, not well understood. We studied brain structure and function in women with and without PCOS using proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging combined with fiber tractography. Then, using a mouse model of PCOS, we investigated by electron microscopy whether AMH played a role on the regulation of hypothalamic structural plasticity. Increased AMH serum levels are associated with increased hypothalamic activity/axonal-glial signalling in PCOS patients. Furthermore, we demonstrate that AMH promotes profound micro-structural changes in the murine hypothalamic median eminence (ME), creating a permissive environment for GnRH secretion. These include the retraction of the processes of specialized AMH-sensitive ependymo-glial cells called tanycytes, allowing more GnRH neuron terminals to approach ME blood capillaries both during the run-up to ovulation and in a mouse model of PCOS. We uncovered a central function for AMH in the regulation of fertility by remodeling GnRH terminals and their tanycytic sheaths, and provided insights into the pivotal role of the brain in the establishment and maintenance of neuroendocrine dysfunction in PCOS. INSERM (U1172), European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement n° 725149), CHU de Lille, France (Bonus H).

Developmental programming of the neuroendocrine axis by steroid hormones: Insights from the sheep model of PCOS.

The reproductive neuroendocrine system is a key target for the developmental programming effects of steroid hormones during early life. While gonadal steroids play an important role in controlling the physiological development of the neuroendocrine axis, human fetuses are susceptible to adverse programming due to exposure to endocrine disrupting chemicals with steroidal activity, inadvertent use of contraceptive pills during pregnancy, as well as from disease states that result in abnormal steroid production. Animal models provide an unparalleled resource to understand the effects of steroid hormones on the development of the neuroendocrine axis and their role on the developmental origins of health and disease. In female sheep, exposure to testosterone (T) excess during fetal development results in an array of reproductive disorders that recapitulate those seen in women with polycystic ovary syndrome (PCOS), including disrupted neuroendocrine feedback mechanisms, increased pituitary responsiveness to gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) hypersecretion, functional hyperandrogenism, multifollicular ovarian morphology, and premature reproductive failure. Similar to a large proportion of women with PCOS, these prenatally T-treated sheep also manifest insulin resistance and cardiovascular alterations, including hypertension. This review article focuses on the effects of prenatal androgens on the developmental programming of hypothalamic and pituitary alterations in the sheep model of PCOS phenotype, centering specifically on key neurons, neuropeptides, and regulatory pathways controlling GnRH and LH secretion. Insights obtained from the sheep model as well as other animal models of perinatal androgen excess can have important translational relevance to treat and prevent neuroendocrine dysfunction in women with PCOS and other fertility disorders.

Biomechanics of Traumatic Head and Neck Injuries on Women: A State-of-the-Art Review and Future Directions.

The biomechanics of traumatic injuries of the human body as a consequence of road crashes, falling, contact sports, and military environments have been studied for decades. In particular, traumatic brain injury (TBI), the so-called "silent epidemic", is the traumatic insult responsible for the greatest percentage of death and disability, justifying the relevance of this research topic. Despite its great importance, only recently have research groups started to seriously consider the sex differences regarding the morphology and physiology of women, which differs from men and may result in a specific outcome for a given traumatic event. This work aims to provide a summary of the contributions given in this field so far, from clinical reports to numerical models, covering not only the direct injuries from inertial loading scenarios but also the role sex plays in the conditions that precede an accident, and post-traumatic events, with an emphasis on neuroendocrine dysfunctions and chronic traumatic encephalopathy. A review on finite element head models and finite element neck models for the study of specific traumatic events is also performed, discussing whether sex was a factor in validating them. Based on the information collected, improvement perspectives and future directions are discussed.

Social isolation from early life induces anxiety-like behaviors in adult rats: Relation to neuroendocrine and neurochemical dysfunctions

Subjects suffering from psychosis frequently experience anxiety. However, mechanisms underlying this comorbidity remain still unclear. We investigated whether neurochemical and neuroendocrine dysfunctions were involved in the development of anxiety-like behavior in a rodent model of psychotic-like symptoms, obtained by exposing male rats to social isolation rearing from postnatal day 21 to postnatal day 70. In the elevated zero maze test, isolated rats showed a significant reduction in the time spent in the open arms, as well as an increase in the time spent in the closed arms, compared to controls. An increased grooming time in the open field test was also observed in isolated animals. Isolation-induced anxiety-like behavior was accompanied by a decrease of plasmatic oxytocin, prolactin, ghrelin and melatonin levels, whereas plasmatic amount of Neuropeptide S was not altered. Social isolation also caused a reduction of noradrenaline, serotonin and GABA levels, together with an increase of serotonin turnover and glutamate levels in the amygdala of isolated animals. No significant differences were found in noradrenaline and serotonin levels, as well as in serotonin turnover in hippocampus, while glutamate amount was increased and GABA levels were reduced in isolated rats. Furthermore, there was a reduction in plasmatic serotonin content, and an increase in plasmatic kynurenine levels following social isolation, while no significant changes in serotonin turnover were observed. Taken together, our data provide novel insights in the neurobiological alterations underlying the comorbidity between psychosis and anxiety, and open new perspectives for multi-target therapies acting on both neurochemical and neuroendocrine pathways. Data availability statementThe data presented in this study are available on request from the corresponding author.

Evaluation of Neuroendocrine Dysfunction Following Acute Aneurysmal Subarachnoid Hemorrhage

Background and Aim: In the management of aneurysmal subarachnoid hemorrhage (aSAH), endocrine dysfunction is infrequently considered. Pituitary (neuroendocrine) dysfunction is highly prevalent after aSAH, leading to residual symptoms such as decreased cognition and quality of life. Although hypopituitarism following SAH may present with non-specific subtle symptoms, it can lead to potentially serious consequences if left undiagnosed. Methods and Materials/Patients: This study was performed to observe the incidence and pattern of neuroendocrine alterations in cases of acute aSAH. A total of 25 patients with acute SAH within 7 days of ictus were included in this prospective study, and an endocrine assessment was performed. The pituitary axes were evaluated for possible dysfunctions, including somatotropic, gonadotropic, corticotropic, and thyrotropic axes. Results: A total of 25 SAH cases (10 males and 15 females; mean age 55.24 years) were included in the study. Aneurysms were more commonly found in the anterior circulation (n=22) than in the posterior circulation (n=3). Most of the patients presented with the Hunt-Hess grade of 1, followed by grades 3, 2, and 4, respectively. Growth hormone deficiency (48%) was the most common pituitary dysfunction, followed by adrenocorticotrophic hormone (24%), gonadotropins (FSH/LH) (24%), and thyroid stimulating hormone (16%) deficiencies, respectively. Single pituitary axis neuroendocrine dysfunction was noted in 9 patients (36%) and multiple pituitary axes dysfunction was observed in 8 patients (32%). Overall, 17 patients (68%) had neuroendocrine dysfunction in single or multiple pituitary hormone axes. Conclusion: Neuroendocrine dysfunction in acute aSAH is 68%. Accordingly, 32% of the participants had single-axis pituitary dysfunction and 36% had multiple axes pituitary dysfunction. The most common endocrine dysfunction is growth hormone deficiency (48%), followed by adrenocorticotrophic hormone, gonadotropins (LH & FSH), and thyroid stimulating hormone. Therefore, it is suggested to include hormonal evaluation in the management of acute SAH for better clinical outcomes.

Meccanismi comuni tra diabete e declino cognitivo

The increased prevalence of diabetes (DM) constitutes a major public health problem, primarily due to its numerous comorbidity and complications. It is widely demonstrated that DM is a significant risk factor for the development of cognitive impairment. Metabolic diseases can influence cognitive functions through multiple interconnected mechanisms. Cerebral insulin resistance, oxidative stress, neuroinflammation, and neuroendocrine dysfunctions can further the development of neurodegeneration diseases. The identification of the molecular mechanisms involved represents the target for the founding of early potential markers and new therapeutic targets of neurodegenerative diseases.

The Role of Apoptosis and Autophagy in the Hypothalamic-Pituitary-Adrenal (HPA) Axis after Traumatic Brain Injury (TBI)

Traumatic brain injury (TBI) is a major health problem affecting millions of people worldwide and leading to death or permanent damage. TBI affects the hypothalamic-pituitary-adrenal (HPA) axis either by primary injury to the hypothalamic-hypophyseal region or by secondary vascular damage, brain, and/or pituitary edema, vasospasm, and inflammation. Neuroendocrine dysfunctions after TBI have been clinically described in all hypothalamic-pituitary axes. We established a mild TBI (mTBI) in rats by using the controlled cortical impact (CCI) model. The hypothalamus, pituitary, and adrenals were collected in the acute (24 h) and chronic (30 days) groups after TBI, and we investigated transcripts and protein-related autophagy (Lc3, Bcln1, P150, Ulk, and Atg5) and apoptosis (pro-caspase-3, cleaved caspase-3). Transcripts related to autophagy were reduced in the hypothalamus, pituitary, and adrenals after TBI, however, this was not reflected in autophagy-related protein levels. In contrast, protein markers related to apoptosis increased in the adrenals during the acute phase and in the pituitary during the chronic phase. TBI stresses induce a variation of autophagy-related transcripts without modifying the levels of their proteins in the HPA axis. In contrast, protein markers related to apoptosis are increased in the acute phase in the adrenals, which could lead to impaired communication via the hypothalamus, pituitary, and adrenals. This may then explain the permanent pituitary damage with increased apoptosis and inflammation in the chronic phase. These results contribute to the elucidation of the mechanisms underlying endocrine dysfunctions such as pituitary and adrenal insufficiency that occur after TBI. Although the adrenals are not directly affected by TBI, we suggest that the role of the adrenals along with the hypothalamus and pituitary should not be ignored in the acute phase after TBI.

Application of Antipsychotic Medication: Gender Differences in Tolerance and Medication Response

This paper covers the role of gender factor in the efficacy and tolerance of antipsychotic therapy in patients with schizophrenic spectrum disorders. The author describes phenomenology of definitions that characterizes differences between male and female sexes. The authors give the data on biological basis of gender differences, frequency of occurrence and clinical features of neuroendocrine dysfunctions (NED) in patients with schizophrenic spectrum disorders during the therapy by first and second generations antipsychotics. It is shown that female patients are more “vulnerable” for some NED. It is emphasized that the problem of tolerance is now more relevant and significant in comparison with the efficacy of antipsychotics, because intolerance or poor tolerance are one of the most common reasons for non-adherence to therapy up to the complete abandonment of it.

LBMON237 Predictors Of Postmenarchal Progression Of Pcos Phenotypes In At-risk Girls

Abstract Physiologic and genetic analyses implicate hyperandrogenemia (HA) as a core causal pathway in PCOS. Both daughters of women with PCOS (PCOS-d) and overweight/obese girls (OW-g) have HA beginning in childhood suggesting that they are at increased risk for PCOS. Accordingly, we performed a prospective study of girls in the early postmenarchal transition until the diagnosis of PCOS can be established according to clinical guidelines at 2 or more yrs after menarche. | PCOS-d, OW-g and lean control girls (LC), ages 11-16 yrs at baseline, were studied within 0.2-1.2 yrs of menarche and returned after 1-3 years. Two PCOS-d, 2 OW-g, and 4 LC could not be assessed at follow up because they were taking hormonal contraception, which was most often prescribed for irregular menses. Baseline and follow up sample sizes were: PCOS-d 16, 12; OW-g 13, 9; LC 18, 14. A fasting morning blood sample was obtained. | Age was similar but BMI differed by design. The change in BMI from baseline to follow up did not differ between the groups. At baseline, DHEAS levels were increased (P=0. 009) and SHBG levels decreased (P<0. 001) in PCOS-d and OW-g. In contrast, LH levels were higher only in PCOS-d (P=0. 03), whereas insulin levels were increased only in OW-g (P=0. 01). At baseline, the prevalence of HA (T, fT or DHEAS > LC mean + 1 SD) was increased (χ2 P=0. 04) in PCOS-d (69%) compared to OW-g (62%) and LC (28%). The prevalence of ovulatory dysfunction (OD, menses >45 d or <21 d) was also increased (χ2 P=0. 04) in PCOS-d (63%) compared with OW-g (15%) and LC (18%). All PCOS-d and 75% OW-g and LC had persistent HA at follow-up. Thirty-eight percent of PCOS-d had persistent OD, while 1 of 2 LC had persistent OD. Neither OW-g with OD at baseline returned for follow up. Two PCOS-d, 2 OW-g and 1 LC fulfilled PCOS criteria at follow up. One of these PCOS-d also had HA and OD at baseline, one OW-g developed both HA and OD. A model that included BMI, SHBG, fasting insulin and LH levels at baseline predicted PCOS diagnosis after 2-yrs of follow up with a Receiver-Operator-Curve area-under-the-curve of 0.98. | There was an increased prevalence of HA in PCOS-d and OW-g early postmenarche that persisted after 2-yrs postmenarche. PCOS-d also had an increased prevalence of OD early postmenarche, which aligns with their increased LH levels at baseline. These findings suggest neuroendocrine dysfunction in PCOS-d, which appears to improve with pubertal maturation, since in the majority of PCOS-d, OD resolved. In contrast, OW-g were hyperinsulinemic. There were no significant differences in the prevalence of PCOS at follow up, although there may have been bias because of preferential exclusion of girls with OD due to hormonal contraception. A model of biomarkers in early postmenarchal girls, that included both reproductive and metabolic parameters, was highly predictive of PCOS diagnosis at follow up. Girls with HA should still be considered at risk for PCOS and require ongoing monitoring. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Patterns of Failure in Pediatric Craniopharyngioma with Surgery Alone

<h3>Purpose/Objective(s)</h3> Though pathologically benign, craniopharyngiomas are frequently recurrent even with complete surgical resection. Thus, postoperative adjuvant radiation therapy (RT) is often employed for durable local control, with conventional irradiation to the surgical bed of both cystic and solid components of the initial tumor. However, this carries risk of high morbidity in the form of late effects, including learning disabilities, neuroendocrine dysfunction, and secondary malignancy. There exists a potential opportunity to reduce radiotherapy-induced toxicity if radiotherapy can be constrained to the initial solid tumor bed and a minimal cystic component within the sellar region. Motivated by this, we sought to characterize the pattern of recurrence in craniopharyngiomas managed surgically without adjuvant therapy. <h3>Materials/Methods</h3> Medical records of 81 patients with craniopharyngioma diagnosed between 1979 and 2021 were reviewed. We identified a subset of patients treated with surgical resection alone who subsequently experienced local recurrence on surveillance MRI. Patients with unavailable pre-operative or recurrent imaging were excluded. Contours of both cystic and solid components of the initial tumor were created utilizing pre-operative MRI, and the recurrent tumor MRI was fused with these contours using deformable image registration. <h3>Results</h3> Fourteen patients who had received surgical resection without adjuvant RT were identified, with a median age of 10.1 years old. An endoscopic surgical approach was used in 8 (57.1%) patients, while open microsurgical approach was used in 6 (42.9%) patients; 3 (21.4%) resections were gross total resections, while 11 (78.6%) were considered near-total or subtotal resections. Median interval from date of initial surgery to first radiographic evidence of recurrence was 1.55 years. Local recurrence occurred purely in the initial cystic component of the tumor extent in 2 (14.3%) patients, was predominantly cystic and extending inferiorly to the initial solid component in 2 (14.3%) patients, and arising from the solid tumor resection bed in 10 (71.4%) patients. <h3>Conclusion</h3> A significant proportion of craniopharyngiomas recur within the cystic component of the initial tumor without adjuvant therapy, supporting continued incorporation of both solid and cystic components of the pre-surgical tumor extent in radiation therapy treatment plans.

CRISPR-Cas9 for treatment of bipolar disorder caused by gene mutation

Bipolar disorder is a highly debilitating psychiatric illness that is associated with great morbidity and extreme mood changes inducing emotional highs（mania) and lows (depression). Scientists have found that bipolar is a kind of complicated mental illness and difficult to fully heal. Bipolar is caused by three main factors, environmental, biological, and genetic factors. Adverse life events and environmental stress events can induce the onset of affective disorder. This bipolar disorder is one of our most heritable psychiatric disorders. It's second only to autism. The patient has abnormal central neurotransmitter metabolism and corresponding receptor function changes, neuroendocrine dysfunction, mainly the hypothalamic-pituitary-adrenal cortex axis, and hypothalamic-pituitary-thyroid axis dysfunction. Based on researches, the gene mutation is one of the pathogenic factors for bipolar disorder, and there is no therapy has been confirmed that can cure bipolar disorder so far. Thanks to the development of biotechnology, microbiologists developed a new technology. Nowadays, we try to cure bipolar disorder by CRISPR. CRISPR is a new microbiology technology by correcting mutation gene and re-editing it to reduce bipolar disorder incidence. Thus, our study provides a basis for studying gene mutation, therapy of bipolar disorder, and CRISPR technology in the future.

Multidisciplinary approach in the management of neurotrauma and its sequelae

It is well known that traumatic brain injury (TBI) can long-term consequences of major public health concern. It can be said that wide spectrum and distinct lesions resulting in variable clinical consequences make the process of post-TBI rehabilitation challenging. A patient who sustains TBI can have variable outcome ranging from complete recovery to persistent vegetative state. Between these two there is a spectrum of TBI related sequel which may be disturbed levels of consciousness, post-traumatic agitation, post-traumatic paroxysmal sympathetic hyperactivity, posttraumatic hydrocephalus, and posttraumatic neuroendocrine dysfunctions all these requiring different rehabilitation programmes and rehabilitation approaches.

IMG-08. Response assessment for pediatric craniopharyngioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group

Abstract INTRODUCTION: Craniopharyngioma (CP) is a histologically benign tumor of the pituitary stalk that accounts for 4% of pediatric central nervous system (CNS) tumors. Given its location, CP often causes neuro-endocrine, hypothalamic, and vision dysfunction. Standard therapy consists of maximally safe resection +/- radiation therapy (RT). Medical management, including intra-cystic therapy, may have utility in certain contexts. Survival after CP is excellent, but quality of life is often poor secondary to functional deficits from the tumor and/or treatment. Few prospective CP trials have been performed, and response assessment has not been standardized. METHODS: The Response Assessment in Pediatric Neuro-Oncology (RAPNO) committee, formed of international experts in relevant subspecialties, devised consensus guidelines from published literature and/or expert opinion to assess CP response in prospective clinical trials. RESULTS: Magnetic resonance imaging (MRI) is the recommended radiological modality for baseline and follow-up CP assessment. Computed tomography can be useful for identification of calcification in the initial diagnostic work-up. The committee defined specific standard MRI-based sequences focused on comprehensive evaluation of the suprasellar space. Radiologic CP response is defined by two-dimensional measurements of both solid and cystic tumor components. Three-dimensional measurements are also encouraged in prospective trials. In certain clinical contexts, response of solid and cystic disease may be differentially considered based on their unique natural histories and responses to treatment (including transient cyst growth during or after RT). Importantly, the committee incorporated functional endpoints related to neuro-endocrine and visual assessments into CP response definitions. In most circumstances, cystic disease should be considered progressive only if growth is associated with acute, new-onset or progressive functional impairment. CONCLUSION: CP is a common pediatric CNS tumor for which standardized response parameters have not been defined. A RAPNO committee devised guidelines for baseline and longitudinal assessments of CP to uniformly define response in future prospective trials.

Peer victimization and associated alcohol and substance use: Prospective pathways for negative outcomes

A considerable number of studies have documented associations between peer victimization and concurrent and prospective increase in alcohol and substance use. Only a handful have investigated the psychological (e.g., internalizing behavior) and biological (e.g., neural systems) factors that contribute to this relation. Emerging studies provide clues as to mechanisms that may underlie increased risk for alcohol and substance use and associated problems in peer victimized youth, which may serve as potential targets for intervention. This review proposes a conceptual framework of increased alcohol/substance use in peer victimized youth as sequelae of alterations in the structure and/or function of neural regions broadly implicated in cognitive control and emotion processing/regulation. Studies are outlined linking peer victimization with alcohol/substance use, associations with internalizing symptoms, and differential structure and function in, and connectivity among, neural regions implicated in alcohol/substance use disorders. Further, the role(s) of neuroendocrine dysfunction, comorbid mental illness, and genetics are discussed as risk factors for substance use following peer victimization. This review concludes with the identification of gaps in the literature and suggestions for further investigation, such as the need for more studies examining the neural correlates of peer victimization, including cyberbullying, and greater consistency in how peer victimization and alcohol/substance use are operationalized and measured across studies. Prospective investigations of biological and psychosocial factors that contribute to alcohol and substance use and development of alcohol/substance use problems are needed to inform novel intervention and prevention strategies in typically developing youth and in populations with high rates of peer victimization, such as individuals with comorbid mental illness and those at high risk for psychiatric disorders.

A randomized clinical trial demonstrating cell type specific effects of hyperlipidemia and hyperinsulinemia on pituitary function.

IntroductionObesity is characterized by elevated lipids, insulin resistance and relative hypogonadotropic hypogonadism, reducing fertility and increasing risk of pregnancy complications and birth defects. We termed this phenotype ‘Reprometabolic Syndrome’ and showed that it can be recapitulated by acute infusions of lipid/insulin into healthy, normal weight, eumenorrheic women. Herein, we examined the broader impact of hyperlipidemia and euglycemic hyperinsulinemia on anterior pituitary trophic hormones and their targets.MethodsSerum FSH, LH, TSH, growth hormone (GH), prolactin (PRL), thyroid hormones (free T4, total T3), cortisol, IGF-1, adiponectin, leptin and creatinine were measured in a secondary analysis of an interventional crossover study of 12 normal weight cycling women who underwent saline and heparin (control) infusion, or a euglycemic insulin infusion with heparin and Intralipid® (lipid/insulin), between days 2–5 in sequential menstrual cycles.ResultsIn contrast to the decrease in gonadotropins, FSH and LH, infusion of lipid/insulin had no significant effects on other trophic hormones; TSH, PRL or GH. Thyroid hormones (fT4 and total T3), cortisol, IGF-1, adiponectin and creatinine also did not differ between saline or lipid/insulin infusion conditions. Leptin increased in response to lipid/insulin (p<0.02).ConclusionAcute hyperlipidemia and hyperinsulinemia exerted differential, cell type specific effects on the hypothalamic-pituitary-gonadal, adrenal and thyroid axes. Elucidation of mechanisms underlying the selective modulation of pituitary trophic hormones, in response to changes in diet and metabolism, may facilitate therapeutic intervention in obesity-related neuroendocrine and reproductive dysfunction.

Evaluation of neuroendocrine dysfunction in the diagnosis of depressive and non-depressive alcohol-dependent persons

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

Abstract #1185035: Panhypopituitarism Secondary to Neurosarcoidosis with Superimposed Mycobacterium Nebraskense Meningitis

Neurosarcoidosis (NS) is a severe manifestation in 5-15% of sarcoidosis cases. Complications can involve both the central and peripheral nervous system. The most common manifestations are cranial neuropathy and aseptic meningitis. In the setting of hypothalamic or pituitary involvement, patients may present with neuroendocrine dysfunction. In this case report we describe a patient who presented with panhypopituitarism in the setting of neurosarcoidosis as well as superimposed Mycobacterium nebraskense infection.

The neuroendocrine stress response impairs hippocampal vascular function and memory in male and female rats

Chronic psychological stress affects brain regions involved in memory such as the hippocampus and accelerates age-related cognitive decline, including in Alzheimer's disease and vascular dementia. However, little is known about how chronic stress impacts hippocampal vascular function that is critically involved in maintaining neurocognitive health that could contribute to stress-related memory dysfunction. Here, we used a novel experimental rat model that mimics the neuroendocrine and cardiovascular aspects of chronic stress to determine how the neuroendocrine components of the stress response affect hippocampal function. We studied both male and female rats to determine potential sex differences in the susceptibility of the hippocampus and its vasculature to neuroendocrine stress-induced dysfunction. We show that activation of neuroendocrine stress pathways impaired the vasoreactivity of hippocampal arterioles to mediators involved in coupling neuronal activity with local blood flow that was associated with impaired memory function. Interestingly, we found more hippocampal arteriolar dysfunction and scarcer hippocampal microvasculature in male compared to female rats that was associated with greater memory impairment, suggesting the male sex may be at increased risk of neuroendocrine-derived hippocampal dysfunction during chronic stress. Overall, this study revealed the therapeutic potential of targeting hippocampal arterioles to prevent or slow memory decline in the setting of prolonged and/or unavoidable stress.