A proposed clinical classification for pituitary neoplasms to guide therapy and prognosis.

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.

Fertility issues in hypopituitarism.

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.

How Many Lives Will You Save? A Mixed Methods Evaluation of a Novel, Online Game for Patient Safety and Quality Improvement Education.

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.

Diagnosis and management of prolactin-secreting pituitary adenomas: a Pituitary Society international Consensus Statement.

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.

Patient handoffs and multi-specialty trainee perspectives across an institution: informing recommendations for health systems and an expanded conceptual framework for handoffs.

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.

Cytodifferentiation of pituitary tumors influences pathogenesis and cavernous sinus invasion.

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.

Optimizing Care Teams by Leveraging Advanced Practice Providers Through Strategic Workforce Planning.

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.

Socio-behavioral dysfunction in disorders of hypothalamic-pituitary involvement: The potential role of disease-induced oxytocin and vasopressin signaling deficits.

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.

Role of Radiation in the treatment of Cushing Disease.

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.

Prospective intraoperative and histologic evaluation of cavernous sinus medial wall invasion by pituitary adenomas and its implications for acromegaly remission outcomes.

Recurrence and biochemical remission rates vary widely among different histological subtypes of pituitary adenoma. In this prospective study, we evaluated 107 consecutive primary pituitary adenomas operated on by a single neurosurgeon including 28 corticotroph, 27 gonadotroph, 24 somatotroph, 17 lactotroph, 5 null-cell and 6 plurihormonal. In each case, we performed direct endoscopic intraoperative inspection of the medial wall of the cavernous sinus, which was surgically removed when invasion was visualized. This was performed irrespective of tumor functional status. Medial wall resection was performed in 47% of pituitary adenomas, and 39/50 walls confirmed pathologic evidence of invasion, rendering a positive predictive value of intraoperative evaluation of medial wall invasion of 78%. We show for the first-time dramatic disparities in the frequency of medial wall invasion among pathological subtypes. Somatotroph tumors invaded the medial wall much more often than other adenoma subtypes, 81% intraoperatively and 69% histologically, followed by plurihormonal tumors (40%) and gonadotroph cell tumors (33%), both with intraoperative positive predictive value of 100%. The least likely to invade were corticotroph adenomas, at a rate of 32% intraoperatively and 21% histologically, and null-cell adenomas at 0%. Removal of the cavernous sinus medial wall was not associated with permanent cranial nerve morbidity nor carotid artery injury, although 4 patients (all Knosp 3-4) experienced transient diplopia. Medial wall resection in acromegaly resulted in the highest potential for biochemical remission ever reported, with an average postoperative day 1 GH levels of 0.96 ug/L and surgical remission rates of 92% based on normalization of IGF-1 levels after surgery (mean = 15.56 months; range 3-30 months). Our findings suggest that tumor invasion of the medial wall of the cavernous sinus may explain the relatively low biochemical remission rates currently seen for acromegaly and illustrate the relevance of advanced intradural surgical approaches for successful and durable outcomes in endonasal pituitary surgery for functional adenomas.

The role of growth hormone for fertility in women with hypopituitarism.

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.

Italian Association of Clinical Endocrinologists (AME) and International Chapter of Clinical Endocrinology (ICCE). Position statement for clinical practice: prolactin-secreting tumors.

Prolactinomas are the most frequent pituitary adenomas. Prolactinoma may occur in different clinical settings and always require an individually tailored approach. This is the reason why a panel of Italian neuroendocrine experts was charged with the task to provide indications for the diagnostic and therapeutic approaches that can be easily applied in different contexts. The document provides 15 recommendations for diagnosis and 54 recommendations for treatment, issued according to the GRADE system. The level of agreement among panel members was formally evaluated by RAND-UCLA methodology. In the last century, prolactinomas represented the paradigm of pituitary tumors for which the development of highly effective drugs obtained the best results, allowing to avoid neurosurgery in most cases. The impressive improvement of neurosurgical endoscopic techniques allows a far better definition of the tumoral tissue during surgery and the remission of endocrine symptoms in many patients with pituitary tumors. Consequently, this refinement of neurosurgery is changing the therapeutic strategy in prolactinomas, allowing the definitive cure of some patients with permanent discontinuation of medical therapy.

Performance Nutrition for Physician Trainees Working Overnight Shifts: A Randomized Controlled Trial.

PURPOSE: To compare acute effects of 2 dietary interventions with usual dietary habits on physician trainees' alertness during overnight shifts. METHOD: This registered, controlled, block randomized crossover trial (NCT03698123) was conducted between October 2018 and May 2019 at Stanford Medicine. Physician trainees working at least 3 overnight shifts during a 1-week period were recruited. During the first night, participants followed their usual dietary habits. During the intervention nights (low carbohydrate-to-protein ratio and high carbohydrate-to-protein ratio interventions), participants received healthy dinners, snacks, water, and, upon request, caffeinated beverages, at the beginning of their shifts and were instructed to eat meals before 10 pm. The sequence of interventions on the second and third nights were block randomized across study weeks. Outcome measures (a priori) were overnight changes in validated measures of specific neurobehavioral dimensions: psychomotor vigilance, sensory-motor speed, working memory, and risk decision making, as well as self-reported sleepiness and work exhaustion. RESULTS: Sixty-one physician trainees participated in this study. Compared with usual dietary habits, overnight changes in psychomotor vigilance scores (scale 0-1,000) improved by 51.02 points (95% CI: 12.08, 89.96) and sleepiness (scale 1-7) improved by 0.69 points (95% CI: 0.33, 1.05) under the low carbohydrate-to-protein ratio intervention. Compared with usual dietary habits, overnight changes in sleepiness (scale 1-7) improved by 0.61 points (95% CI: 0.25, 0.96) under the high carbohydrate-to-protein ratio intervention. Neither intervention had beneficial effects relative to usual dietary habits with respect to sensory-motor speed, working memory, risk decision making, or work exhaustion. There were no differences in outcomes between low carbohydrate-to-protein ratio and high carbohydrate-to-protein ratio interventions. CONCLUSIONS: Dietary interventions may mitigate negative effects of physician trainee sleep deprivation during overnight shifts. Future studies are warranted to further examine the effectiveness of nutritional strategies on physician alertness during overnight shifts.

Consensus on diagnosis and management of Cushing's disease: a guideline update.

Cushing's disease requires accurate diagnosis, careful treatment selection, and long-term management to optimise patient outcomes. The Pituitary Society convened a consensus workshop comprising more than 50 academic researchers and clinical experts to discuss the application of recent evidence to clinical practice. In advance of the virtual meeting, data from 2015 to present about screening and diagnosis; surgery, medical, and radiation therapy; and disease-related and treatment-related complications of Cushing's disease summarised in recorded lectures were reviewed by all participants. During the meeting, concise summaries of the recorded lectures were presented, followed by small group breakout discussions. Consensus opinions from each group were collated into a draft document, which was reviewed and approved by all participants. Recommendations regarding use of laboratory tests, imaging, and treatment options are presented, along with algorithms for diagnosis of Cushing's syndrome and management of Cushing's disease. Topics considered most important to address in future research are also identified.

A pilot, randomized controlled trial of telementorship: A useful tool during social distancing.

BACKGROUND: During social distancing, resident mentorship may be an unmet need. Telementorship, mentorship through video conferencing software, presents a unique approach to overcome these challenges. AIMS: This study evaluated whether telementorship through video conference increased access to mentorship encounters and decreased perceived barriers to access, factors that determine likelihood to maintain mentor relationships, and quality of mentorship. METHODS: A year-long randomized, prospective cohort study was conducted in 2016-2017 with pairs of resident mentors from seven different training programs and medical student mentees, randomized to telementorship or in-person mentorship. The number of quarterly encounters was monitored and demographic predictors of meeting were determined. Likert scale survey responses were analyzed with linear regression. RESULTS: Forty-three of 46 (93.5%) volunteer mentor-mentee pairs participated. Telementorship did not alter likelihood of meeting or attitudes toward mentorship barriers (time and distance). Mentee satisfaction increased from 42.5% to 65.4% (P<0.05) throughout the year. Operating room-based practice (P<0.05) and higher postgraduate level (P=0.02) decreased the likelihood of meeting. CONCLUSION: Telementorship provided an equal number of encounters compared to the pairs who were asked to meet in-person. Telementorship may serve as an adjunct modality for flexible communication. RELEVANCE FOR PATIENTS: Medical mentorship is a key component to medical education. Effective mentorship increases academic research productivity, job satisfaction, and advancement of clinical skills, which translate to improved patient care.

Glucocorticoid use in patients with adrenal insufficiency following administration of the COVID-19 vaccine: a pituitary society statement.

PURPOSE: Side effects of the coronavirus disease 2019 (COVID-19) vaccines include pain at the injection site, fatigue, headache, myalgias, arthralgias, chills, and fever, all of which can be early indicators of an increased need for glucocorticoid replacement in patients with adrenal insufficiency. The Pituitary Society surveyed its membership to understand planned approaches to glucocorticoid management in patients with adrenal insufficiency who will receive a COVID-19 vaccine. METHODS: Members were asked to complete up to 3 questions regarding their planned approach for use of glucocorticoid replacement in patients with proven adrenal insufficiency. RESULTS: Surveys were sent to 273 members and 103 responded. Thirty-six percent plan to recommend that patients automatically increase glucocorticoid dosage with administration of the first vaccine injection. Of these, 84% plan to increase glucocorticoid dose on the day of vaccination, and 49% plan to increase glucocorticoid dose prior to vaccination. Of the 64% who do not plan to recommend automatic glucocorticoid dose increase with vaccine administration, 88% plan to increase the dose if the patient develops a fever, and 47% plan to increase the dose if myalgias and arthralgias occur. CONCLUSIONS: Most clinicians plan to maintain the current glucocorticoid dose with vaccine administration. The vast majority plan and to increase glucocorticoid dose in case of fever, and just under half in case of arthralgias and myalgias. These survey results offer suggested management guidance for glucocorticoid management in patients with adrenal insufficiency.

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

The WHO Classification of Endocrine Tumours designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.

A Pituitary Society update to acromegaly management guidelines.

Guidelines and consensus statements ensure that physicians managing acromegaly patients have access to current information on evidence-based treatments to optimize outcomes. Given significant novel recent advances in understanding acromegaly natural history and individualized therapies, the Pituitary Society invited acromegaly experts to critically review the current literature in the context of Endocrine Society guidelines and Acromegaly Consensus Group statements. This update focuses on how recent key advances affect treatment decision-making and outcomes, and also highlights the likely role of recently FDA-approved therapies as well as novel combination therapies within the treatment armamentarium.

Managing complications of endoscopic transsphenoidal surgery in pituitary adenomas.

INTRODUCTION: Over the last two decades there has been a gradual shift from the traditional microscopic approach toward the use of endoscopic endonasal approach for resection of pituitary adenomas. Multiple medical and surgical complications can occur following endoscopic transsphenoidal resection of adenomas. AREAS COVERED: We discuss the evolution of the surgical practice from the use of the 'microscope' to the 'endoscope' in the resection of pituitary adenomas. We present a comprehensive review of the medical and surgical complications following surgery with particular emphasis on both the prevention and management of electrolyte disturbance, cerebrospinal fluid leak and the rare but dreaded complication of internal carotid injury (ICA). We also searched the PubMed database to identify relevant literature between 1984 and 2019. EXPERT OPINION: Use of endoscope compared with microscope may be associated with better preservation of pituitary gland function with similar extent of resection. Overall medical and surgical complications can be safely managed in high volume centers in association with endocrinologists and skull base trained otolaryngologists. Understanding of anatomico-technical nuances and meticulous surgical technique are important toward preventing ICA injury. Ongoing surgical and technical developments coupled with imaging advances will likely lead to better future outcomes for patients with functioning and nonfunctioning adenomas.