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Background: Untreated Cushing disease historically has a high mortality rate, but the long-term survival of patients with Cushing disease after transsphenoidal surgery has not been reported.Objective: To determine long-term mortality rate in patients who are treated for Cushing disease with current management techniques.Design: Retrospective case series.Setting: Tertiary care center.Patients: 161 patients (32 men and 129 women; mean age, 38 years) who were treated for Cushing disease between 1978 and 1996.Intervention: Transsphenoidal adenomectomy and as-needed adjunctive therapy.Measurement: Record review with follow-up interview.Results: The cure rate for patients with microadenomas who had no previous therapy was 90% (123 of 137). No perioperative deaths occurred (0 of 193 procedures [95% CI, 0.0% to 1.9%]). Follow-up data (mean, 8.7 years) were obtained for 99% of patients (159 of 161). Six patients died. The 5- and 10-year survival rates were 99% (CI, 97% to 100%) and 93% (CI, 88% to 99%), respectively. Survival was similar to that seen in an age- and sex-matched sample that was based on U.S. population data (standardized mortality ratio, 0.98 [CI, 0.44 to 2.2]; P > 0.2).Conclusion: Survival of patients treated for Cushing disease with current management techniques between 1978 and 1996 was better than the poor survival historically associated with this disorder. [ABSTRACT FROM AUTHOR]

Abstract: Labor unions represent an increasing number of graduate medical education (GME) trainees in the United States. Most GME and other leaders at academic medical centers lack familiarity with resident/fellow unions, including what to expect, what decisions need to be made, and the processes involved in a unionization effort. It is important for designated institutional officials (DIOs), GME program directors, teaching faculty, and other institutional leaders to understand the drivers of resident/fellow unionization, the union organizing campaign and election process, and what follows a vote to unionize, including collective bargaining. Careful consideration of the role of educational and other institutional leaders during the unionization process is important to prevent any loss of trust between residents/fellows and those they view as their advocates. In this Commentary, the authors describe these considerations from their perspective as DIOs and GME leaders., (Copyright © 2024 the Association of American Medical Colleges.)

Context: Acromegaly, characterized by excessive growth hormone (GH) and insulin-like growth factor-1 (IGF-1), impacts quality of life (QoL) and mortality. Standard of care (SoC; octreotide long-acting repeatable or lanreotide autogel) treatment typically requires healthcare provider administration. CAM2029, a novel subcutaneous octreotide depot with increased bioavailability using FluidCrystal technology, enables self-administration and room-temperature storage., Objective: Assess superiority of CAM2029 versus placebo for biochemical control in patients with controlled acromegaly., Design: 24-week, multinational, randomized, double-blind, phase 3 trial (NCT04076462)., Setting: 45 sites; ten countries., Patients: 72 patients on SoC with biochemical control at screening (IGF-1 ≤upper limit of normal [ULN]; mean GH <2.5 μg/L)., Interventions: Patients were randomized 2:1 to once-monthly CAM2029 (n=48) or placebo (n=24)., Main Outcome Measures: Primary endpoint was proportion of patients with IGF-1 ≤ULN (Week 22/24 mean), with dose-reduced patients classified as non-responders; first key secondary endpoint was the same, including dose-reduced responders. Second key secondary endpoint was proportion of patients with IGF-1 ≤ULN (Week 22/24) and mean GH <2.5 μg/L (Week 24)., Results: At Week 22/24 (intention-to-treat analysis), CAM2029-treated patients demonstrated superior response rates versus placebo for IGF-1 (72.2% versus 37.5%; risk difference: 34.6, 95% confidence interval: 11.3, 57.9; p=0.0018), and combined IGF-1/GH (70.0% versus 37.5%; p=0.0035). CAM2029-treated patients had well-controlled symptoms, improved QoL and treatment satisfaction versus placebo and baseline. CAM2029 was well tolerated; safety was consistent with SoC., Conclusions: CAM2029 provides a convenient and effective treatment option for acromegaly, with superior biochemical control versus placebo. Symptom control, QoL and satisfaction were improved from baseline SoC., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Women with hypopituitarism have lower fertility rates and worse pregnancy outcomes than women with normal pituitary function. These disparities exist despite the use of assisted reproductive technologies and hormone replacement. In women with hypogonadotropic hypogonadism, administration of exogenous gonadotropins can be used to successfully induce ovulation. Growth hormone replacement in the setting of growth hormone deficiency has been suggested to potentiate reproductive function, but its routine use in hypopituitary women remains unclear and warrants further study. In this review, we will discuss the clinical approach to fertility in a woman with hypopituitarism., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

No comprehensive classification system that guides prognosis and therapy of pituitary adenomas exists. The 2022 WHO histopathology-based classification system can only be applied to lesions that are resected, which represent few clinically significant pituitary adenomas. Many factors independent of histopathology provide mechanistic insight into causation and influence prognosis and treatment of pituitary adenomas. We propose a new approach to guide prognosis and therapy of pituitary adenomas by integrating clinical, genetic, biochemical, radiological, pathological, and molecular information for all adenomas arising from anterior pituitary cell lineages. The system uses an evidence-based scoring of risk factors to yield a cumulative score that reflects disease severity and can be used at the bedside to guide pituitary adenoma management. Once validated in prospective studies, this simple manageable classification system could provide a standardised platform for assessing disease severity, prognosis, and effects of therapy on pituitary adenomas., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This Consensus Statement from an international, multidisciplinary workshop sponsored by the Pituitary Society offers evidence-based graded consensus recommendations and key summary points for clinical practice on the diagnosis and management of prolactinomas. Epidemiology and pathogenesis, clinical presentation of disordered pituitary hormone secretion, assessment of hyperprolactinaemia and biochemical evaluation, optimal use of imaging strategies and disease-related complications are addressed. In-depth discussions present the latest evidence on treatment of prolactinoma, including efficacy, adverse effects and options for withdrawal of dopamine agonist therapy, as well as indications for surgery, preoperative medical therapy and radiation therapy. Management of prolactinoma in special situations is discussed, including cystic lesions, mixed growth hormone-secreting and prolactin-secreting adenomas and giant and aggressive prolactinomas. Furthermore, considerations for pregnancy and fertility are outlined, as well as management of prolactinomas in children and adolescents, patients with an underlying psychiatric disorder, postmenopausal women, transgender individuals and patients with chronic kidney disease. The workshop concluded that, although treatment resistance is rare, there is a need for additional therapeutic options to address clinical challenges in treating these patients and a need to facilitate international registries to enable risk stratification and optimization of therapeutic strategies., (© 2023. Springer Nature Limited.)

Medical trainees have limited knowledge of quality improvement and patient safety concepts. The authors developed a free quality improvement/patient safety educational game entitled Safety Quest (SQ). However, 1803 undergraduate medical trainees, graduate medical trainees, and continuing medical education learners globally completed at least 1 level of SQ. Pre- and post-SQ knowledge and satisfaction were assessed among continuing medical education learners. Thematic analysis of feedback given by trainees was conducted. Among graduate medical trainees, SQ outranked other learning modalities. Three content areas emerged from feedback: engagement, ease of use, and effectiveness; 87% of comments addressing engagement were positive. After completing SQ, 98.6% of learners passed the post-test, versus 59.2% for the pretest ( P < 0.0001). Ninety-three percent of learners agreed that SQ was engaging and interactive, and 92% believed it contributed to their professional growth. With an increased need for educational curricula to be delivered virtually, gamification emerges as a unique strategy that learners praise as engaging and effective., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Medical Quality.)

Background: Safe and effective physician-to-physician patient handoffs are integral to patient safety. Unfortunately, poor handoffs continue to be a major cause of medical errors. Developing a better understanding of challenges faced by health care providers is critical to address this continued patient safety threat. This study addresses the gap in the literature exploring broad, cross-specialty trainee perspectives around handoffs and provides a set of trainee-informed recommendations for both training programs and institutions., Methods: Using a constructivist paradigm, the authors conducted a concurrent/embedded mixed method study to investigate trainees' experiences with patient handoffs across Stanford University Hospital, a large academic medical center. The authors designed and administered a survey instrument including Likert-style and open-ended questions to solicit information about trainee experiences from multiple specialties. The authors performed a thematic analysis of open-ended responses., Results: 687/1138 (60.4%) of residents and fellows responded to the survey, representing 46 training programs and over 30 specialties. There was wide variability in handoff content and process, most notably code status not being consistently mentioned a third of the time for patients who were not full code. Supervision and feedback about handoffs were inconsistently provided. Trainees identified multiple health-systems level issues that complicated handoffs and suggested solutions to these threats. Our thematic analysis identified five important aspects of handoffs: (1) handoff elements, (2) health-systems-level factors, (3) impact of the handoff, (4) agency (duty), and (5) blame and shame., Conclusions: Health systems, interpersonal, and intrapersonal issues affect handoff communication. The authors propose an expanded theoretical framework for effective patient handoffs and provide a set of trainee-informed recommendations for training programs and sponsoring institutions. Cultural and health-systems issues must be prioritized and addressed, as an undercurrent of blame and shame permeates the clinical environment., (© 2023. The Author(s).)

Objective: Pituitary tumors (PTs) continue to present unique challenges given their proximity to the cavernous sinus, whereby invasive behavior can limit the extent of resection and surgical outcome, especially in functional tumors. The aim of this study was to elucidate patterns of cavernoinvasive behavior by PT subtype., Methods: A total of 169 consecutive first-time surgeries for PTs were analyzed; 45% of the tumors were functional. There were 64 pituitary transcription factor-1 (PIT-1)-expressing, 62 steroidogenic factor-1 (SF-1)-expressing, 38 T-box transcription factor (TPIT)-expressing, and 5 nonstaining PTs. The gold standard for cavernous sinus invasion (CSI) was based on histopathological examination of the cavernous sinus medial wall and intraoperative exploration., Results: Cavernous sinus disease was present in 33% of patients. Of the Knosp grade 3 and 4 tumors, 12 (19%) expressed PIT-1, 7 (11%) expressed SF-1, 8 (21%) expressed TPIT, and 2 (40%), were nonstaining (p = 0.36). PIT-1 tumors had a significantly higher predilection for CSI: 53% versus 24% and 18% for TPIT and SF-1 tumors, respectively (OR 6.08, 95% CI 2.86-13.55; p < 0.001). Microscopic CSI-defined as Knosp grade 0-2 tumors with confirmed invasion-was present in 44% of PIT-1 tumors compared with 7% and 13% of TPIT and SF-1 tumors, respectively (OR 11.72, 95% CI 4.35-35.50; p < 0.001). Using the transcavernous approach to excise cavernous sinus disease, surgical biochemical remission rates for patients with acromegaly, prolactinoma, and Cushing disease were 88%, 87%, and 100%, respectively. The granule density of PIT-1 tumors and corticotroph functional status did not influence CSI., Conclusions: The likelihood of CSI differed by transcription factor expression; PIT-1-expressing tumors had a higher predilection for invading the cavernous sinus, particularly microscopically, compared with the other tumor subtypes. This elucidates a unique cavernoinvasive behavior absent in cells from other lineages. Innovative surgical techniques, however, can mitigate tumor behavior and achieve robust, reproducible biochemical remission and gross-total resection rates. These findings can have considerable implications on the surgical management and study of PT biology and behavior.

In Cushing disease (CD), radiation therapy (RT) is mostly used in the adjuvant setting in patients who have failed transsphenoidal surgery or have recurrent CD. Stereotactic radiotherapy (SRT) is administered as either single or several sessions, and the most commonly used modalities include photon source (Gamma Knife, CyberKnife, and LINAC) or heavy particles (protons). In multicenter studies, Gamma Knife SRT can lead to biochemical control in 80%, with medial time to remission approximately 15 mos, and 70% recurrence free at 10 years. Conventional RT (CRT) consists of administration of small daily fractions over six weeks, with cumulative dose of 45-50 Gy. Biochemical control is achieved in up to 64% of patients with CRT. Choice of radiation modality includes convenience for patients (SRT is more convenient) and proximity to critical structures. Both forms of RT can result in hypopituitarism. RT remains an important modality for the treatment of patients with CD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Disorders involving hypothalamic and pituitary (HPIT) structures-including craniopharyngioma, Langerhans cell histiocytosis, and intracranial germ cell tumors-can disrupt brain and endocrine function. An area of emerging clinical concern in patients with these disorders is the co-occurring socio-behavioral dysfunction that persists after standard hormone replacement therapy. Although the two neuropeptides most implicated in mammalian social functioning (oxytocin and arginine vasopressin) are of hypothalamic origin, little is known about how disease-induced damage to HPIT structures may disrupt neuropeptide signaling and, in turn, impact patients' socio-behavioral functioning. Here we provide a clinical primer on disorders of HPIT involvement and a review of neuropeptide signaling and socio-behavioral functioning in relevant animal models and patient populations. This collective evidence suggests that neuropeptide signaling disruptions contribute to socio-behavioral deficits experienced by patients with disorders of HPIT involvement. A better understanding of the biological underpinnings of patients' socio-behavioral symptoms is now needed to enable the development of the first targeted pharmacological strategies by which to manage patients' socio-behavioral dysfunction., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Advanced practice providers (APPs) are integral members of the healthcare delivery team. However, there has been a lack of standardization and uniformity in how they are utilized across inpatient, ambulatory, and procedural settings., Methods: A multidisciplinary workforce planning committee was formed in March 2021 to evaluate all new and replacement full-time equivalent APP positions at Stanford Health Care (SHC), an academic medical center of more than 600 APPs, to optimize and standardize the role of APPs as per national benchmarks., Results: Six months since the launch of the committee, there has been a 10% increase in the number of visits and procedures performed by APPs providing better access for patients. In addition, there has been a 38.7% improvement in ambulatory APPs meeting their productivity target, 19.4% improvement in ambulatory APPs meeting utilization targets, and 36.8% improvement in ambulatory APPs meeting the 50th percentile and above as per the relative value unit benchmark published by the Medical Group Management Association for Academic Medical Centers. For inpatient APPs, there has been a 38.8% improvement in APPs meeting the average daily census target., Discussion: APP utilization is an important topic that has not been consistently addressed in the literature. Inappropriate utilization and lack of top of licensure practice have been associated with increased turnover, decreased job satisfaction, and professional development. By developing a multidisciplinary workforce planning committee, full-time employee positions are evaluated with a goal of optimizing and standardizing the role of APPs at SHC., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Growth hormone (GH) is an important regulator of the female reproductive system. In vitro and non-human in vivo studies demonstrate a role of GH in steroidogenesis, folliculogenesis, and post-fertilization development. Given its ability to modulate the reproductive system and potentiate the effects of gonadotropins, a beneficial role of GH replacement therapy to optimize fertility has been suggested. Women with hypopituitarism have lower pregnancy and live birth rates. Limited data suggest a role of GH in enhancing fertility management in women with hypopituitarism. GH replacement therapy may be especially relevant in women with hypopituitarism as well as in women considered poor ovarian responders and require assisted reproductive techniques., (Copyright © 2022 Elsevier Ltd. All rights reserved.)