Educating for adaptive expertise: case examples along the medical education continuum.

Adaptive expertise represents the combination of both efficient problem-solving for clinical encounters with known solutions, as well as the ability to learn and innovate when faced with a novel challenge. Fostering adaptive expertise requires careful approaches to instructional design to emphasize deeper, more effortful learning. These teaching strategies are time-intensive, effortful, and challenging to implement in health professions education curricula. The authors are educators whose missions encompass the medical education continuum, from undergraduate through to organizational learning. Each has grappled with how to promote adaptive expertise development in their context. They describe themes drawn from educational experiences at these various learner levels to illustrate strategies that may be used to cultivate adaptive expertise.At Vanderbilt University School of Medicine, a restructuring of the medical school curriculum provided multiple opportunities to use specific curricular strategies to foster adaptive expertise development. The advantage for students in terms of future learning had to be rationalized against assessments that are more short-term in nature. In a consortium of emergency medicine residency programs, a diversity of instructional approaches was deployed to foster adaptive expertise within complex clinical learning environments. Here the value of adaptive expertise approaches must be balanced with the efficiency imperative in clinical care. At Mayo Clinic, an existing continuous professional development program was used to orient the entire organization towards an adaptive expertise mindset, with each individual making a contribution to the shift.The different contexts illustrate both the flexibility of the adaptive expertise conceptualization and the need to customize the educational approach to the developmental stage of the learner. In particular, an important benefit of teaching to adaptive expertise is the opportunity to influence individual professional identity formation to ensure that clinicians of the future value deeper, more effortful learning strategies throughout their careers.

Establishing an expert consensus for the operational definitions of asthma-associated infectious and inflammatory multimorbidities for computational algorithms through a modified Delphi technique.

BACKGROUND: A subgroup of patients with asthma has been reported to have an increased risk for asthma-associated infectious and inflammatory multimorbidities (AIMs). To systematically investigate the association of asthma with AIMs using a large patient cohort, it is desired to leverage a broad range of electronic health record (EHR) data sources to automatically identify AIMs accurately and efficiently. METHODS: We established an expert consensus for an operational definition for each AIM from EHR through a modified Delphi technique. A series of questions about the operational definition of 19 AIMS (11 infectious diseases and 8 inflammatory diseases) was generated by a core team of experts who considered feasibility, balance between sensitivity and specificity, and generalizability. Eight internal and 5 external expert panelists were invited to individually complete a series of online questionnaires and provide judgement and feedback throughout three sequential internal rounds and two external rounds. Panelists' responses were collected, descriptive statistics tabulated, and results reported back to the entire group. Following each round the core team of experts made iterative edits to the operational definitions until a moderate (≥ 60%) or strong (≥ 80%) level of consensus among the panel was achieved. RESULTS: Response rates for each Delphi round were 100% in all 5 rounds with the achievement of the following consensus levels: (1) Internal panel consensus: 100% for 8 definitions, 88% for 10 definitions, and 75% for 1 definition, (2) External panel consensus: 100% for 12 definitions and 80% for 7 definitions. CONCLUSIONS: The final operational definitions of AIMs established through a modified Delphi technique can serve as a foundation for developing computational algorithms to automatically identify AIMs from EHRs to enable large scale research studies on patient's multimorbidities associated with asthma.

A novel variant of the cleidocervicalis muscle with clinical implications for nerve compression/entrapment.

PURPOSE: The cleidocervicalis muscle occurs in approximately 1-3 % of the population that may be confused with pathological neck masses. We describe a novel variant of the muscle and its clinical implications. METHODS: This is a case report of a cleidocervicalis muscle variant identified during routine cadaveric dissection. RESULTS: The muscle identified originated on the C5 vertebra and inserted on the clavicle medial to the trapezius muscle. Innervation was provided by a C6 spinal nerve branch. Notably, a branch of the supraclavicular nerve was closely associated with the muscle, raising the possibility of compression of this nerve. CONCLUSIONS: Presence of a cleidocervicalis muscle should be considered in cases of shoulder pain consistent with supraclavicular nerve entrapment or compression.

A Call to Action for Improving LGBTQIA2S+ Inclusive Policies and Practices in Educating Science and Medical Professionals.

Based on Nature's novel sex and gender guidelines, we share a call to action to enact policy changes in medical and scientific education. We conducted a literature search of current policies and practices affecting sex and gender minorities. Our work indicated a scarcity of guidelines and curricula dedicated to standardizing LGBTQIA2S+ topics. Educational policies must be enacted to ensure that sex and gender guidelines are implemented across all institutions as it impacts the future of healthcare and science. It is essential that sex and gender considerations be mandated topics in both medical and scientific education.

Online interactive medical neuroimaging exercise to identify human brain structures.

A persisting need remains for developing methods for inspiring and teaching undergraduate medical students to quickly learn to identify the hundreds of human brain structures, tracts and spaces that are clinically relevant (viewed as three-dimensional volumes or two-dimensional neuroimages), and to accomplish this with the option of virtual on-line methods. This notably includes teaching the essentials of recommended diagnostic radiology to allow students to be familiar with patient neuroimages routinely acquired using magnetic resonance imaging (MRI) and computed tomography (CT). The present article includes a brief example video plus details a clinically oriented interactive neuroimaging exercise for first year medical students (MS1s) in small groups, conducted with instructors either in-person or as an entirely online virtual event. This "find-the-brain-structure" (FBS) event included teaching students to identify brain structures and other regions of interest in the central nervous system (and potentially in head and neck gross anatomy), which are traditionally taught using brain anatomy atlases and anatomical specimens. The interactive, small group exercise can be conducted in person or virtually on-line in as little as 30 min depending on the scope of objectives being covered. The learning exercise involves coordinated interaction between MS1s with one or several non-clinical faculty and may include one or several physicians (clinical faculty and/or qualified residents). It further allows for varying degrees of instructor interaction online and is easy to convey to instructors who do not have expertise in neuroimaging. Anonymous pre-event survey (n = 113, 100% response rate) versus post-event surveys (n = 92, 81% response rate) were attained from a cohort of MS1s in a neurobiology course. Results showed multiple statistically significant group-level shifts in response to several of the questions, showing an increase in MS1 confidence with reading MRI images (12% increase shift in mean, p < 0.001), confidence in their approaching physicians for medical training (9%, p < 0.01), and comfort levels in working online with virtual team-based peers and with team-based faculty (6%, p < 0.05). Qualitative student feedback revealed highly positive comments regarding the experience overall, encouraging this virtual medium as a desirable educational approach.

Reimagining Faculty Development Deployment: A Multipronged, Pragmatic Approach to Improve Engagement.

PROBLEM: Faculty at academic health centers have many competing demands on their time, leading to high work stress, burnout, and limited capacity to meaningfully improve their teaching, evaluation, feedback, and other education-related skills. Faculty development provides a useful mechanism to assist faculty in enhancing their knowledge and skills in these areas, but engaging faculty can be a challenge. APPROACH: To promote engagement, the authors developed a multipronged, pragmatic approach to faculty development. They created: (1) brief videos leveraging micro-learning strategies; (2) prepackaged workshops for use during existing faculty meetings; (3) a newsletter to raise awareness of faculty development opportunities; (4) a searchable, web-based catalog to facilitate rapid retrieval of faculty development content; and (5) an academy to acknowledge engagement of individual faculty members, provide certificates, and promote a culture that prioritizes our education mission. OUTCOMES: Since they launched the new approach in 2017, they have developed 41 microlearning videos, 15 prepackaged workshops, and 24 issues of the newsletter. Between January 2017 and May 2021, the videos generated more than 150,055 views; the workshops were downloaded 2,850 times; and the issues of the newsletter, emailed bimonthly to 3,500 members of the faculty, had an open rate that increased from 30% in 2017 to 70% in 2021. The Academy of Educational Excellence, which was launched in 2018, grew to more than 490 members. Preliminary feedback suggests faculty and education leaders are highly satisfied with the faculty development resources and approaches to engagement. NEXT STEPS: Next steps include obtaining more user satisfaction data and evaluating whether education-related knowledge and skills have improved among faculty participants.

Reimagining Learning Spaces of the Future: An Interprofessional, Virtual Workshop Utilizing Rapid Idea Generation and Lean Startup Methodologies.

INTRODUCTION: The needs and expectations of health professional educators and learners are evolving. Therefore, physical and virtual learning environments will look and function differently in the future. Understanding desirable, feasible options for educators and learners, including online, in-person, hybrid, and extended realities, is critical. We designed and facilitated a faculty development workshop that adapted Lean Startup methodologies and role-modeled effective virtual teaching skills to engage stakeholders in generating ideas to inform future development of learning spaces within one national academic medical center. METHODS: We facilitated the 3-hour workshop with an interprofessional group of health professional educators, learners, and administrative staff. The workshop included asynchronous prework and synchronous microlectures, small-group activities, and large-group report-outs. We employed Lean Startup methodologies to promote divergent thinking. Each small group had a dedicated convener and scribe. A designated chat moderator, social media facilitator, and several audiovisual staff provided support during the workshop. RESULTS: More than 4,000 ideas were generated by the 350 participants. Participants reported that prework, microlectures, and small-group activities were successful in preparing them to engage in rapid idea generation and propose potential solutions for future learning spaces within health professions education. DISCUSSION: The workshop, which utilized a rapid idea generation and Lean Startup methodologies format, was successful in producing an abundance of original ideas and potential solutions for future learning spaces within health professions education. As reported through postsession evaluation, participants valued the opportunity to contribute ideas and co-create potential solutions to guide future planning and feasibility studies.

Got 15? Try Faculty Development on the Fly: A Snippets Workshop for Microlearning.

Introduction: Faculty development (FD) is an element critical to the professional growth of medical educators and a necessary component in developing effective educators. FD offerings are prevalent across academic institutions; however, faculty report they are unable to participate in these initiatives due to time limitations and competing priorities. The snippet FD approach can address these concerns but requires training for FD providers to be effectively used. Methods: This snippet train-the-trainer workshop was presented to approximately 310 physician and nonphysician medical educators at a national medical education conference. The session incorporated multiple teaching modalities (e.g., lecture, demonstrations, structured small-group snippet development groups, and large-group debriefs). A 14-item Likert-scale survey was used to obtain participant evaluations. Narrative feedback was collected using constructed response items. Results: Ninety-five percent of respondents (125 of 132) planned to use snippets as an FD strategy at least once per year, with 38% (50 of 132) noting they planned to use snippets at least four times per year. Respondents indicated that FD snippets could positively impact educational practices (94%) and that the session was a valuable use of their time (94%), as well as expressing interest in a snippet repository (90%). Discussion: A brief FD train-the-trainer workshop for snippets can successfully prepare FD providers to create and use this approach.

Individual and team competencies in translational teams.

Translational scientists create, advance, and translate knowledge as a result of research, learning, and application. Translational teams are composed of dynamic and diverse interprofessional and cross-disciplinary members that generate new knowledge to address a shared translational objective. The objective involves advancing an interventional product, behavioral intervention, or evidence-based approach to improve human health. This paper focuses on identifying individual and team competencies using a modified Delphi method to reach a consensus on the competencies needed by translational teams (TTs).

Working Toward Consensus on Sporadic Vestibular Schwannoma Care: A Modified Delphi Study.

OBJECTIVE: To address variance in clinical care surrounding sporadic vestibular schwannoma, a modified Delphi study was performed to establish a general framework to approach vestibular schwannoma care. A multidisciplinary panel of experts was established with deliberate representation from key stakeholder societies. External validity of the final statements was assessed through an online survey of registered attendees of the 8th Quadrennial International Conference on Vestibular Schwannoma. STUDY DESIGN: Modified Delphi method. METHODS: The panel consisted of 16 vestibular schwannoma experts (8 neurotology and 8 neurosurgery) and included delegates representing the AAOHNSF, AANS/CNS tumor section, ISRS, and NASBS. The modified Delphi method encompassed a four-step process, comprised of one prevoting round to establish a list of focus areas and three subsequent voting rounds to successively refine individual statements and establish levels of consensus. Thresholds for achieving moderate consensus, at ≥67% agreement, and strong consensus, at ≥80% agreement, were determined a priori. All voting was performed anonymously via the Qualtrics online survey tool and full participation from all panel members was required before procession to the next voting round. RESULTS: Through the Delphi process, 103 items were developed encompassing hearing preservation (N = 49), tumor control and imaging surveillance (N = 20), preferred treatment (N = 24), operative considerations (N = 4), and complications (N = 6). As a result of item refinement, moderate (4%) or strong (96%) consensus was achieved in all 103 final statements. Seventy-nine conference registrants participated in the online survey to assess external validity. Among these survey respondents, moderate (N = 21, 20%) or strong (N = 73, 71%) consensus was achieved in 94 of 103 (91%) statements, and no consensus was reached in 9 (9%). Of the four items with moderate consensus by the expert panel, one had moderate consensus by the conference participants and three had no consensus. CONCLUSION: This modified Delphi study on sporadic vestibular schwannoma codifies 100% consensus within a multidisciplinary expert panel and is further supported by 91% consensus among an external group of clinicians who regularly provide care for patients with vestibular schwannoma. These final 103 statements address clinically pragmatic items that have direct application to everyday patient care. This document is not intended to define standard of care or drive insurance reimbursement, but rather to provide a general framework to approach vestibular schwannoma care for providers and patients.

Evidence that gamma-aminobutyric acid is part of the neural circuit mediating estradiol negative feedback in anestrous ewes.

Seasonal anestrus in ewes is driven by an increase in response to estradiol (E2) negative feedback. Compelling evidence indicates that inhibitory A15 dopaminergic (DA) neurons mediate the increased inhibitory actions of E2 in anestrus, but these neurons do not contain estrogen receptors. Therefore, we have proposed that estrogen-responsive afferents to A15 neurons are part of the neural circuit mediating E2 negative feedback in anestrus. This study examined the possible role of afferents containing gamma-aminobutyric acid (GABA) and nitric oxide (NO) in modulating the activity of A15 neurons. Local administration of NO synthase inhibitors to the A15 had no effect on LH, but GABA receptor ligands produced dramatic changes. Administration of either a GABA A or GABA B receptor agonist to the A15 increased LH secretion in ovary-intact ewes, suggesting that GABA inhibits A15 neural activity. In ovariectomized anestrous ewes, the same doses of GABA receptor agonist had no effect, but combined administration of a GABA A and GABA B receptor antagonist to the A15 inhibited LH secretion. These data are consistent with the hypothesis that endogenous GABA release within the A15 is low in ovary-intact anestrous ewes and elevated after ovariectomy. Using dual immunocytochemistry, we observed that GABAergic varicosities make close contacts on to A15 neurons and that A15 neurons contain both the GABA A-alpha1 and the GABA B-R1 receptor subunits. Based on these data, we propose that in anestrous ewes, E2 inhibits release of GABA from afferents to A15 DA neurons, increasing the activity of these DA neurons and thus suppressing episodic secretion of GnRH and LH.

Impact of Doximity Residency Navigator on Graduate Medical Education Recruitment.

OBJECTIVE: To assess residency applicants' use and perceptions of Doximity Residency Navigator (DRN) and to analyze the impact of Doximity reputation rankings on application, interview acceptance, and match list ranking decisions. PARTICIPANTS AND METHODS: We developed and distributed a survey seeking feedback from residency applicants to describe their use of DRN during the 2017 residency recruitment and match process. The dates of the study were March 1, 2017, through May 8, 2017. RESULTS: We received responses from 2152 of 12,617 applicants (17%) across 24 graduate medical education programs. Sixty-two percent of respondents (n=1339) used DRN during the residency application, interview, and match list process. Doximity reputation rankings were noted to be valuable or very valuable to 78% of respondents (958 of 1233). Overall, 79% of respondents (977 of 1241) reported that Doximity reputation rankings influenced their application, interview acceptance, or match list ranking decisions. When asked about the accuracy of Doximity reputation rankings, 56% of respondents (699 of 1240) believed that rankings were slightly accurate or not accurate. The most commonly used resources to research potential residency programs were residency program websites, American Medical Association resources, and DRN. CONCLUSION: Most survey respondents used DRN during the application, interview, and match ranking process. Doximity reputation rankings were found to be the most valuable resource in DRN, although more than 50% of responders had doubts about the accuracy of reputation rankings.

Development of a self-directed, online-learning curriculum to increase community-engaged research in clinical and translational science.

BACKGROUND: Medical research strives to improve health; community-engaged research (CEnR) supports translation to the community. METHODS: This article describes the use of andragogical theory to develop asynchronous CEnR training. RESULTS: A total of 43 researchers and community members completed at least one module. The majority (67%-100%) stated that training met their educational needs and noted a desire for more information. CONCLUSION: The curriculum reinforced CEnR principles to enhance medical research.

Endocrine basis for disruptive effects of cortisol on preovulatory events.

Stress activates the hypothalamo-pituitary-adrenal axis leading to enhanced glucocorticoid secretion and concurrently inhibits gonadotropin secretion and disrupts ovarian cyclicity. Here we tested the hypothesis that stress-like concentrations of cortisol interfere with follicular phase endocrine events of the ewe by suppressing pulsatile LH secretion, which is essential for subsequent steps in the preovulatory sequence. Cortisol was infused during the early to midfollicular phase, elevating plasma cortisol concentrations to one third, one half, or the maximal value induced by isolation, a commonly used model of psychosocial stress. All cortisol treatments compromised at least some aspect of reproductive hormone secretion in follicular phase ewes. First, cortisol significantly suppressed LH pulse frequency by as much as 35%, thus attenuating the high frequency LH pulses typical of the preovulatory period. Second, cortisol interfered with timely generation of the follicular phase estradiol rise, either preventing it or delaying the estradiol peak by as much as 20 h. Third, cortisol delayed or blocked the preovulatory LH and FSH surges. Collectively, our findings support the hypothesis that stress-like increments in plasma cortisol interfere with the follicular phase by suppressing the development of high frequency LH pulses, which compromises timely expression of the preovulatory estradiol rise and LH and FSH surges. Moreover, the suppression of LH pulse frequency provides indirect evidence that cortisol acts centrally to suppress pulsatile GnRH secretion in follicular-phase ewes.

The suprachiasmatic nucleus: a clock of multiple components.

Although impressive progress has been made in understanding the molecular basis of pacemaker function in the suprachiasmatic nucleus (SCN), fundamental questions about cellular and regional heterogeneity within the SCN, and how this heterogeneity might contribute to SCN pacemaker function at a tissue level, have remained unresolved. To reexamine cellular and regional heterogeneity within the SCN, the authors have focused on two key questions: which SCN cells are endogenously rhythmic and/or directly light responsive? Observations of endogenous rhythms of electrical activity, gene/protein expression, and protein phosphorylation suggest that the SCN in mammals examined to date is composed of anatomically distinct rhythmic and nonrhythmic components. Endogenously rhythmic neurons are primarily found in rostral, dorsomedial, and ventromedial portions of the nucleus; at mid and caudal levels, the distribution of endogenously rhythmic cells in the SCN has the appearance of a "shell." The majority of nonrhythmic cells, by contrast, are located in a central "core" region of the SCN, which is complementary to the shell. The location of light-responsive cells, defined by direct retinohypothalamic input and light-induced gene expression, largely overlaps the location of nonrhythmic cells in the SCN core, although, in hamsters and mice light-responsive cells are also present in the ventral portion of the rhythmic shell. While the relative positions of rhythmic and light-responsive components of the SCN are similar between species, the precise boundaries of these components, and neurochemical phenotype of cells within them, are variable. Intercellular communication between these components may be a key feature responsible for the unique pacemaker properties of the SCN observed at a tissue and whole animal level.

Endotoxin inhibits the surge secretion of gonadotropin-releasing hormone via a prostaglandin-independent pathway.

Immune/inflammatory challenges, such as bacterial endotoxin, disrupt gonadotropin secretion and ovarian cyclicity. We previously determined that endotoxin can block the estradiol-induced LH surge in the ewe. Here, we investigated mechanisms underlying this suppression. First, we tested the hypothesis that endotoxin blocks the estradiol-induced LH surge centrally, by preventing the GnRH surge. Artificial follicular phases were created in ovariectomized ewes, and either endotoxin or vehicle was administered together with a surge-inducing estradiol stimulus. In each ewe in which endotoxin blocked the LH surge, the GnRH surge was also blocked. Given this evidence that endotoxin blocks the estradiol-induced LH surge at the hypothalamic level, we began to assess underlying central mechanisms. Specifically, in view of the prior demonstration that prostaglandins mediate endotoxin-induced suppression of pulsatile GnRH secretion in ewes, we tested the hypothesis that prostaglandins also mediate endotoxin-induced blockade of the surge. The prostaglandin synthesis inhibitor flurbiprofen was delivered together with endotoxin and the estradiol stimulus. Although flurbiprofen abolished endotoxin-induced fever, which is a centrally generated, prostaglandin-mediated response, it failed to reverse blockade of the LH surge. Collectively, these results indicate endotoxin blocks the LH surge centrally, suppressing GnRH secretion via a mechanism not requiring prostaglandins. This contrasts with the suppressive effect of endotoxin on GnRH pulses, which requires prostaglandins as intermediates.

Evidence that thyroid hormones act in the ventromedial preoptic area and the premammillary region of the brain to allow the termination of the breeding season in the ewe.

Thyroid hormones are permissive for various species to enter seasonal anestrus. In the ewe they act centrally to permit the onset of potent estradiol-negative feedback responsible for anestrus, but the specific sites of action are unknown. Therefore, we tested whether T(4) replacement via chronic microimplants in any of five brain areas could reverse the reproductive effects of thyroidectomy. Diffusion of (125)I-T(4) from the microimplant was largely (>98%) limited to a 1.2-mm radius. A marked decline in LH concentration in ovariectomized, estradiol-treated ewes was used as an index for anestrus. In experiment 1, all thyroidectomized (THX) ewes with microimplants in the medial preoptic area, A15 area, and medial basal hypothalamus failed to enter anestrus; instead, LH levels remained elevated, similar to those in untreated THX controls. In ventromedial preoptic area (vmPOA)-microimplanted ewes, only the two animals with the most caudal microimplants entered anestrus, as did thyroid-intact controls and THX ewes receiving icv or sc T(4) replacement. In experiment 2, all vmPOA-treated ewes with similar placements to those effective in experiment 1 along with all ewes microimplanted in the premammillary region entered neuroendocrine anestrus. Thus, the premammillary region and vmPOA are brain sites in which thyroid hormones act to permit the onset of seasonal anestrus.

Temporal requirements of thyroid hormones for seasonal changes in LH secretion.

The transition between breeding and anestrous seasons in ewes is driven by an endogenous rhythm in responsiveness to estradiol negative feedback. One stage of this rhythm, the transition to anestrus, requires the presence of thyroid hormone during a window of responsiveness that opens in the late breeding season. The primary goal of this study was to assess when ewes lose responsiveness to thyroid hormone (i.e. when the window closes). In addition, we investigated whether thyroid hormone influences aspects of seasonality other than the transition to anestrus. Ovariectomized ewes maintained in a simulated natural photoperiod were implanted with estradiol, thyroidectomized, and treated with T(4) for 100 d beginning at progressively later dates during the anestrous season. Onset of neuroendocrine anestrus (decrease in LH), latency to anestrus, and time of onset of the subsequent neuroendocrine breeding season (rise in LH) were determined. Ewes gradually lost responsiveness to T(4) during the latter half of the anestrous season, as judged by increasing latency to the decrease in LH and, eventually, failure to exhibit a decrease in LH. Progressively later T(4) replacements also caused progressive delays in the subsequent breeding season. In contrast, the annual PRL cycle was not significantly affected by thyroidectomy or T(4) replacement. These findings indicate that 1) responsiveness to T(4) is lost gradually during the mid to late anestrous season; 2) thyroid hormones can influence the timing of the breeding season and thus may be required for the maintenance or entrainment of the endogenous reproductive rhythm; 3) thyroid hormones are not required for all seasonal neuroendocrine cycles.

Does cortisol mediate endotoxin-induced inhibition of pulsatile luteinizing hormone and gonadotropin-releasing hormone secretion?

Bacterial endotoxin (lipopolysaccharide), a commonly used model of immune/inflammatory stress, inhibits reproductive neuroendocrine activity and concurrently induces a profound stimulation of the hypothalamo-pituitary-adrenal axis. We employed two approaches to test the hypothesis that enhanced secretion of cortisol mediates endotoxin-induced suppression of pulsatile GnRH and LH secretion in the ovariectomized ewe. First, we mimicked the endotoxin-induced increase in circulating cortisol by delivering the glucocorticoid in the absence of the endotoxin challenge. Within 1-2 h, experimentally produced increments in circulating cortisol suppressed pulsatile LH secretion in a dose-dependent fashion. Second, we blocked the endotoxin-induced stimulation of cortisol secretion using the drug metyrapone, which inhibits the 11-beta hydroxylase enzyme necessary for cortisol biosynthesis. In the absence of a marked stimulation of cortisol secretion, endotoxin still profoundly inhibited pulsatile GnRH and LH secretion. We conclude that, although enhanced cortisol secretion may contribute to endotoxin-induced suppression of reproductive neuroendocrine activity, the marked stimulation of the glucocorticoid is not necessary for this response. Our findings are consistent with the hypothesis that immune/inflammatory stress inhibits reproductive neuroendocrine activity via more than one inhibitory pathway, one involving enhanced secretion of cortisol and the other(s) being independent of this glucocorticoid.