Pituitary Center Research

The pituitary and neuroendocrine clinical programs at Stanford bring together knowledge and expertise in both clinical research and teaching applications to treatment of neuroendocrine diseases. Our expert physicians and surgeons are also researchers, offering the latest clinical trials, and conducting cutting-edge research using state-of-the-art technologies.

Clinical Trials

Clinical trials are research studies that evaluate a new medical approach, device, drug, or other treatment. As a Stanford Health Care patient, you may have access to the latest, advanced clinical trials.

Open trials refer to studies currently accepting participants. Closed trials are not currently enrolling, but may open in the future.

Featured Trial

A Phase 3, Randomized, Open-Label, Active Controlled, Multicenter Study To Evaluate Maintenance Of Response, Safety and Patient Reported Outcomes in Acromegaly Patients Treated with Octreotide Capsules, and in Patients Treated with Standard of Care Parenteral Somatostatin Receptor Ligands Who Previously Tolerated and Demonstrated a Biochemical Control on Both Treatments

Status: Recruiting
PI: Laurence Katznelson, MD
NCT not available yet
Contact: Bharati Sanjanwala
bharatis@stanford.edu


Published Studies

Professor of Neurosurgery and, by courtesy, of Otolaryngology - Head & Neck Surgery (OHNS)

Publications

  • Resection of corticotroph microadenomas invading the medial wall of the cavernous sinus in two cases of a primary and recurrent case of Cushing's disease. Neurosurgical focus: Video Mohyeldin, A., Nunez, M. A., Xu, Y., Fernandez-Miranda, J. C. 2023; 9 (1): V2

    Abstract

    Emerging evidence from multiple highly specialized groups continues to support a role for resection of the medial wall of the cavernous sinus when it is invaded by functional pituitary adenomas, to offer durable biochemical remission. The authors present two cases of Cushing's disease that underscore the power of this surgical technique in achieving remission in microadenomas that ectopically present in the cavernous sinus or have invaded the medial wall of the sinus. This video demonstrates key steps in the safe removal of the medial wall of the cavernous sinus and successful resection of tumor burden in the cavernous sinus for sustained postoperative remission. The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2323.

    View details for DOI 10.3171/2023.4.FOCVID2323

    View details for PubMedID 37416808

  • Cytodifferentiation of pituitary tumors influences pathogenesis and cavernous sinus invasion. Journal of neurosurgery Asmaro, K., Zhang, M., Rodrigues, A. J., Mohyeldin, A., Vigo, V., Nernekli, K., Vogel, H., Born, D. E., Katznelson, L., Fernandez-Miranda, J. C. 2023: 1-9

    Abstract

    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.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.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.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.

    View details for DOI 10.3171/2023.3.JNS221949

    View details for PubMedID 37119095

  • The Pterygosphenoidal Triangle: Surgical Anatomy and Case Series in Endoscopic Endonasal Skull Base Surgery. Operative neurosurgery (Hagerstown, Md.) Xu, Y., Asmaro, K., Mohyeldin, A., Zhang, M., Nunez, M. A., Mao, Y., Cohen-Gadol, A. A., Fernandez-Miranda, J. C. 2023

    Abstract

    BACKGROUND: Safe exposure of the lacerum segment of the carotid artery remains a challenge in endoscopic endonasal surgery.OBJECTIVE: To introduce the pterygosphenoidal triangle as a novel and reliable landmark for facilitating access to the foramen lacerum.METHODS: Fifteen colored silicone-injected anatomic specimens were dissected using an endoscopic endonasal approach to the foramen lacerum region in a stepwise manner. Twelve dried skulls were studied and 30 high-resolution computed tomography scans were analyzed to measure the borders and angles of the pterygosphenoidal triangle. Surgical cases incorporating the foramen lacerum exposure between July 2018 and December 2021 were reviewed to provide surgical outcomes of the proposed surgical technique.RESULTS: The pterygosphenoidal triangle is delineated by the pterygosphenoidal fissure medially and the vidian nerve laterally. The palatovaginal artery is located at the base of the triangle anteriorly, while the apex is formed by the pterygoid tubercle posteriorly, which leads to the anterior wall of the foramen lacerum and lacerum internal carotid artery. In the reviewed surgical cases, 39 patients underwent 46 foramen lacerum approaches for resection of pituitary adenoma (12 patients), meningioma (6 patients), chondrosarcoma (5 patients), chordoma (5 patients), or other lesions (11 patients). There were no carotid injuries or ischemic events. Near-total resection was achieved in 33 (85%) of 39 patients (gross-total in 20 [51%]).CONCLUSION: This study details the pterygosphenoidal triangle as a novel and practical anatomic surgical landmark for safe and effective exposure of the foramen lacerum in endoscopic endonasal surgery.

    View details for DOI 10.1227/ons.0000000000000627

    View details for PubMedID 37071748

  • Prospective intraoperative and histologic evaluation of cavernous sinus medial wall invasion by pituitary adenomas and its implications for acromegaly remission outcomes. Scientific reports Mohyeldin, A., Katznelson, L. J., Hoffman, A. R., Asmaro, K., Ahmadian, S. S., Eltobgy, M. M., Nayak, J. V., Patel, Z. M., Hwang, P. H., Fernandez-Miranda, J. C. 2022; 12 (1): 9919

    Abstract

    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.

    View details for DOI 10.1038/s41598-022-12980-1

    View details for PubMedID 35705579

  • Microsurgical anatomy of the dorsal clinoidal space: implications for endoscopic endonasal parasellar surgery. Journal of neurosurgery Xu, Y., Nunez, M. A., Mohyeldin, A., Vigo, V., Mao, Y., Cohen-Gadol, A. A., Fernandez-Miranda, J. C. 2022: 1-13

    Abstract

    OBJECTIVE: The clinoidal venous space dorsal to the internal carotid artery (ICA) has not been well studied given its inaccessibility due to obstruction by the ICA during transcranial surgery. The evolution of endoscopic endonasal surgery has provided a new perspective into the clinoidal space and a new route for paraclinoidal lesions. Understanding the dorsal clinoidal space (DCS) is vital in planning and performing endoscopic endonasal surgery in the parasellar region. A detailed and precise description of the DCS from the endonasal perspective has not yet been provided. The authors' goal in this study was to delineate the microsurgical anatomy of the DCS from an endoscopic endonasal perspective, emphasizing its surgical implications when treating invasive pituitary adenomas and other parasellar lesions.METHODS: An endoscopic endonasal transsellar approach was performed in 15 silicone-injected postmortem heads. Afterward, the sellar region was dissected through a transcranial approach using magnification *3 to *40 microscopy. The osseous, dural, and arterial relationships of the DCS and its architecture were investigated. The DCS's length, width, and depth were measured and its anatomical variations recorded.RESULTS: The DCS was identified in 90% of the specimens, and in most cases, its shape was a narrow rectangular pyramid, with its base oriented toward the sphenoid sinus and its apex toward the posterior clinoid process. It is delimited superiorly by the distal ring, inferiorly by the medial aspect of the proximal dural ring or caroticoclinoid ligament, laterally by the clinoidal ICA, and medially by the superior continuation of the medial wall of the cavernous sinus. The width, height, and length of the DCS were 4 ± 1, 4.5 ± 1.5, and 7 ± 2 mm, respectively. A fenestrated caroticoclinoid ligament is a potential route for tumor invasion from the cavernous sinus into the DCS.CONCLUSIONS: This report provides important anatomical descriptions of the DCS from endoscopic endonasal and transcranial perspectives that may facilitate the space's safe exposure for the removal of invasive adenomas, increasing total resection rates and minimizing the risk of injury to neurovascular structures.

    View details for DOI 10.3171/2021.12.JNS211974

    View details for PubMedID 35120312

  • Microsurgical anatomy and the importance of the petrosal process of the sphenoid bone in endonasal surgery JOURNAL OF NEUROSURGERY Doniz-Gonzalez, A., Vigo, V., Nunez, M., Xu, Y., Mohyeldin, A., Cohen-Gadol, A. A., Fernandez-Miranda, J. C. 2021; 137 (5): 1431-1442
  • Proximal Branches of the Anterior Cerebral Artery: Anatomic Study and Applications to Endoscopic Endonasal Surgery. Operative neurosurgery (Hagerstown, Md.) Najera, E., Truong, H. Q., Belo, J. T., Borghei-Razavi, H., Gardner, P. A., Fernandez-Miranda, J. 2019

    Abstract

    BACKGROUND: The endoscopic endonasal approach is a surgical alternative for midline anterior skull base tumors. A detailed understanding of the proximal anterior cerebral artery (ACA) branches' anatomy from an endonasal perspective is essential for avoiding vascular complications.OBJECTIVE: To evaluate, from an endonasal perspective, the anatomic variations of the ACA and its proximal branches, specifically the recurrent artery of Heubner (RAH), and the fronto-orbital (FOA) and frontopolar (FPA) arteries.METHODS: We study the origin, course, branching pattern, diameter, and relationship between the proximal ACA branches and the optic apparatus and olfactory tract in 25 head specimens.RESULTS: The RAH was present in all hemispheres and originated within 3±1.5 mm of the AcomA, with a 0.4±0.1 mm diameter. Based on its relationship with the A1 segment, we observed three RAH courses: anterior (40%), superior (22%), and posterior (38%). The FOA was present in all cases, a mean of 6±4 mm from the AcomA, with a 0.7±0.4 mm diameter. The FOA arose mainly from the A2 (70%), with three courses in relation to the olfactory tract: crossing its proximal third (54%), crossing its middle third (31%), and running parallel to it along the gyrus rectus (15%). The FPA was present in 92% of the hemispheres, a mean of 10±5 mm from the AcomA, always arising from the A2 and coursing anteriorly within the interhemispheric fissure towards the frontal pole.CONCLUSION: The RAH, FOA, and FPA can be differentiated by origin, course, and destination using the A1 segment, olfactory tract, and interhemispheric fissure, respectively, as surgical landmarks.

    View details for PubMedID 30649510

  • Proposal and Validation of a Simple Grading Scale (TRANSSPHER Grade) for Predicting Gross Total Resection of Nonfunctioning Pituitary Macroadenomas After Transsphenoidal Surgery. Operative neurosurgery (Hagerstown, Md.) Mooney, M. A., Sarris, C. E., Zhou, J. J., Barkhoudarian, G., Chicoine, M. R., Fernandez-Miranda, J. C., Gardner, P. A., Hardesty, D. A., Jahnke, H., Kelly, D. F., Liebelt, B. D., Mayberg, M. R., Prevedello, D. M., Sfondouris, J., Sheehy, J. P., Chandler, J. P., Yuen, K. C., White, W. L., Little, A. S., TRANSSPHER Study Group 2019

    Abstract

    BACKGROUND: A simple, reliable grading scale to better characterize nonfunctioning pituitary adenomas (NFPAs) preoperatively has potential for research and clinical applications.OBJECTIVE: To develop a grading scale from a prospective multicenter cohort of patients that accurately and reliably predicts the likelihood of gross total resection (GTR) after transsphenoidal NFPA surgery.METHODS: Extent-of-resection (EOR) data from a prospective multicenter study in transsphenoidal NFPA surgery were analyzed (TRANSSPHER study; ClinicalTrials.gov NCT02357498). Sixteen preoperative radiographic magnetic resonance imaging (MRI) tumor characteristics (eg, tumor size, invasion measures, tumor signal characteristics, and parameters impacting surgical access) were evaluated to determine EOR predictors, to calculate receiver-operating characteristic curves, and to develop a grading scale. A separate validation cohort (n=165) was examined to assess the scale's performance and inter-rater reliability.RESULTS: Data for 222 patients from 7 centers treated by 15 surgeons were analyzed. Approximately one-fifth of patients (18.5%; 41 of 222) underwent subtotal resection (STR). Maximum tumor diameter>40 mm; nodular tumor extension through the diaphragma into the frontal lobe, temporal lobe, posterior fossa, or ventricle; and Knosp grades 3 to 4 were identified as independent STR predictors. A grading scale (TRANSSPHER grade) based on a combination of these 3 features outperformed individual variables in predicting GTR (AUC, 0.732). In a validation cohort, the scale exhibited high sensitivity and specificity (AUC, 0.779) and strong inter-rater reliability (kappa coefficient, 0.617).CONCLUSION: This simple, reliable grading scale based on preoperative MRI characteristics can be used to better characterize NFPAs for clinical and research purposes and to predict the likelihood of achieving GTR.

    View details for PubMedID 30649445

  • Left Pan-Hippocampal Low Grade Glioma-2-Stage Transsylvian Transventricular and Paramedian Supracerebellar Transtentorial Approaches: 2-Dimensional Operative Video. Operative neurosurgery (Hagerstown, Md.) Fernandez-Miranda, J. C. 2018

    Abstract

    The surgical goal for low-grade gliomas (LGGs) is to maximize resection while minimizing morbidity. Pan-hippocampal LGGs extend from the hippocampal head to the hippocampal tail, and involve the parahippocampal gyrus and uncus. Given their anteroposterior extension, they cannot be completely removed with 1 single approach, requiring a 2-stage front-to-back operation.In this video, we present the case of a 52-yr-old man with new onset of generalized seizures and a dominant-side, nonenhancing, pan-hippocampal infiltrative lesion compatible with a low-grade glioma. Preoperative high-definition fiber tractography (HDFT) showed the spatial relationship of the tumor with surrounding fiber tracts, such as the arcuate, inferior fronto-occipital, and middle longitudinal fascicles, and optic radiations.Surgical resection was planned in 2 separate stages. The first stage consisted of a transsylvian transinferior insular sulcus approach to the extra- and intraventricular aspects of the uncohippocampal region. The entire anterior and middle portions of the tumor were successfully removed with minimal morbidity, including transient naming difficulties and permanent superior quadrantanopia. Postoperative HDFT showed preservation of all fiber tracts, except for a portion of Meyer's loop and the inferior-most aspect of the inferior fronto-occipital fascicle. The second stage was completed 8 wk later and consisted of a paramedian supracerebellar-transtentorial approach on sitting position. The posterior portion of the tumor was entirely removed to achieve a complete macroscopic tumor resection. The final diagnosis was IDH1-positive LGG.Pan-hippocampal tumors remain a surgical challenge but accurate knowledge of surgical neuroanatomy and surgical approaches facilitates their safe and effective treatment.The patient signed an informed consent including the use of photographic and video material for educational or academic purposes.

    View details for PubMedID 30295907

  • Paramedian Supracerebellar Approach in Semi-Sitting Position for Endoscopic Resection of Pineal Cyst: 2-Dimensional Operative Video. Operative neurosurgery (Hagerstown, Md.) Fernandez-Miranda, J. C. 2018

    Abstract

    In this video, we present the case of a 41-yr-old female with new onset of recurrent syncopal episodes. She underwent extensive evaluations and diagnostic work-up by cardiology and neurology, excluding any other cause than a large pineal cyst that was found on magnetic resonance imaging.Surgical indications for pineal cyst resection are very limited as most pineal cyst can be treated conservatively. Recurrent drop-attacks (without loss of consciousness) or syncopal episodes (with brief loss of consciousness) have been associated with pineal cysts secondary to a possible ball valve effect with shift of position causing sudden obstruction of the ventricular system followed by rapid rising of intracranial pressure.Several approaches, different positions, and alternative surgical techniques (microscopic vs endoscopic) have been proposed for resection of pineal region lesions. The semi-sitting position provides excellent exposure of the pineal region secondary to gravity-based retraction of the cerebellum, and carries minimal risk of air venous embolism when head elevation is reduced to 30° and lower extremities are elevated. The paramedian supracerebellar approach is less invasive and faster than midline supracerebellar approach, because it requires exposure of just 1 transverse sinus (nondominant for centered lesions) and avoids exposure of the torcula. The endoscopic technique greatly improves the ergonomics of the approach when compared to the microscope based technique, and provides excellent visualization of all the neurovascular structures in the pineal region.Surgical resection was successfully performed with no complications and complete cyst resection. Patient was discharged on postoperative day 1 and remains free of syncopal episodes.The patient signed informed consent including the use of photographic and video material for educational or academic purposes.

    View details for PubMedID 30295900

Professor of Neurosurgery and of Medicine (Endocrinology)

Publications

  • Optimizing Care Teams by Leveraging Advanced Practice Providers Through Strategic Workforce Planning. The Journal of nursing administration Kuriakose, C., Stringer, M., Ziegler, A., Hsieh, C., Atashroo, M., Hendershott, J., Tippett, V., Shah, D., Cianfichi, L., Katznelson, L., Mahoney, M. 2022; 52 (9): 474-478

    Abstract

    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.

    View details for DOI 10.1097/NNA.0000000000001185

    View details for PubMedID 35994601

  • Prospective intraoperative and histologic evaluation of cavernous sinus medial wall invasion by pituitary adenomas and its implications for acromegaly remission outcomes. Scientific reports Mohyeldin, A., Katznelson, L. J., Hoffman, A. R., Asmaro, K., Ahmadian, S. S., Eltobgy, M. M., Nayak, J. V., Patel, Z. M., Hwang, P. H., Fernandez-Miranda, J. C. 2022; 12 (1): 9919

    Abstract

    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.

    View details for DOI 10.1038/s41598-022-12980-1

    View details for PubMedID 35705579

  • Acromegaly: An Endocrine Society Clinical Practice Guideline JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Katznelson, L., Laws, E. R., Melmed, S., Molitch, M. E., Murad, M. H., Utz, A., Wass, J. A. 2014; 99 (11): 3933-3951

    Abstract

    The aim was to formulate clinical practice guidelines for acromegaly.The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), five experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This guideline is cosponsored by the European Society of Endocrinology.This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews.One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society and the European Society of Endocrinology reviewed drafts of the guidelines.Using an evidence-based approach, this acromegaly guideline addresses important clinical issues regarding the evaluation and management of acromegaly, including the appropriate biochemical assessment, a therapeutic algorithm, including use of medical monotherapy or combination therapy, and management during pregnancy.

    View details for DOI 10.1210/jc.2014-2700

    View details for Web of Science ID 000346743100001

    View details for PubMedID 25356808

  • Surgical Interventions and Medical Treatments in Treatment-Naive Patients With Acromegaly: Systematic Review and Meta-Analysis JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Abu Dabrh, A. M., Mohammed, K., Asi, N., Farah, W. H., Wang, Z., Farah, M. H., Prokop, L. J., Katznelson, L., Murad, M. H. 2014; 99 (11): 4003-4014

    Abstract

    Acromegaly is usually treated with surgery as a first-line treatment, although medical therapy has also been used as an alternative primary treatment.We conducted a systematic review and meta-analysis to synthesize the existing evidence comparing these two approaches in treatment-naïve patients with acromegaly.This study performed a comprehensive search in multiple databases, including Medline, EMBASE, and Scopus from early inception through April 2014.The study used original controlled and uncontrolled studies that enrolled patients with acromegaly to receive either surgical treatment or medical treatment as their first-line treatment.Reviewers extracted data independently and in duplicates. Because of the noncomparative nature of the available studies, we modified the Newcastle-Ottawa Scale to assess the quality of included studies. Outcomes evaluated were biochemical remission and change in IGF-1 or GH levels. We pooled outcomes using the random-effects model.The final search yielded 35 studies enrolling 2629 patients. Studies were noncomparative series with a follow-up range of 6-360 months. Compared with medical therapy, surgery was associated with a higher remission rate (67% vs 45%; P = .02). Surgery had higher remission rates at longer follow-up periods (≥ 24 mo) (66% vs 44%; P = .04) but not the shorter follow-up periods (≤ 6 mo) (53% vs 26%; P = .02). Surgery had higher remission rates in the follow-up levels of GH (65% vs 46%; P = .05). In one study, the IGF-1 level was reduced more with surgery compared with medical treatment (-731 μg/L vs -251 μg/L; P = .04). Studies in which surgery was performed by a single operator reported a higher remission rate than those with multiple operators (71% vs 47%; P = .002).Surgery may be associated with higher remission rate; however, the confidence in such evidence is very low due to the noncomparative nature of the studies, high heterogeneity, and imprecision.

    View details for DOI 10.1210/jc.2014-2900

    View details for Web of Science ID 000346743100013

    View details for PubMedID 25356809

  • Utility of Adrenocorticotropic Hormone in Assessing the Response to Transsphenoidal Surgery for Cushing's Disease. Endocrine practice Salmon, P. M., Loftus, P. D., Dodd, R. L., Harsh, G., Chu, O. S., Katznelson, L. 2014; 20 (11): 1159-1164

    Abstract

    To compare adrenocorticotrophic hormone (ACTH) and cortisol dynamics in subjects with Cushing's disease (CD) following transsphenoidal surgery (TSS) and to determine the value of early postoperative ACTH levels in predicting subsequent hypocortisolemia.Following TSS for CD, serum cortisol and plasma ACTH were measured every 6 hours in the absence of empiric glucocorticoid coverage.A total of 26 subjects (25 female) underwent 28 operations. Hypocortisolemia was achieved in 21 (81%) subjects after the initial TSS. Repeat TSS was performed in 2 subjects, resulting in hypocortisolemia in 1. Subjects who achieved hypocortisolemia had significantly lower ACTH levels by 19 hours postoperatively (P = .007). Plasma ACTH fell to <30 pg/mL in 86% and <20 pg/mL in 82% of subjects who subsequently achieved hypocortisolemia. Plasma ACTH declined to <30 pg/mL by a mean of 10 hours and to <20 pg/mL by 13 hours prior to hypocortisolemia. Follow-up data were available on 25 patients for a median of 23 months. Three subjects who achieved initial surgical remission had disease recurrence at 19, 24, and 36 months; all of these subjects had a postoperative nadir serum cortisol levels <3 μg/dL and plasma ACTH <20 pg/mL.Following TSS for CD, plasma ACTH declined prior to achievement of hypocortisolemia in most subjects. In the majority, the ACTH level reached a nadir of <20 pg/mL. Low early postoperative ACTH levels predict early hypocortisolemia but may not accurately predict long-term remission.

    View details for DOI 10.4158/EP14140.OR

    View details for PubMedID 24936567

  • Global clinical response in Cushing's syndrome patients treated with mifepristone. Clinical endocrinology Katznelson, L., Loriaux, D. L., Feldman, D., Braunstein, G. D., Schteingart, D. E., Gross, C. 2014; 80 (4): 562-569

    Abstract

    Mifepristone, a glucocorticoid receptor antagonist, improves clinical status in patients with Cushing's syndrome (CS). We examined the pattern, reliability and correlates of global clinical response (GCR) assessments during a 6-month clinical trial of mifepristone in CS.Post hoc analysis of secondary end-point data from a 24-week multicentre, open-label trial of mifepristone (300-1200 mg daily) in CS. Intraclass correlation coefficient (ICC) was used to examine rater concordance, and drivers of clinical improvement were determined by multivariate regression analysis.Forty-six adult patients with refractory CS along with diabetes mellitus type 2 or impaired glucose tolerance, and/or a diagnosis of hypertension.Global clinical assessment made by three independent reviewers using a three-point ordinal scale (+1 = improvement; 0 = no change; -1 = worsening) based on eight broad clinical categories including glucose control, lipids, blood pressure, body composition, clinical appearance, strength, psychiatric/cognitive symptoms and quality of life at Weeks 6, 10, 16, and 24.Positive GCR increased progressively over time with 88% of patients having improved at Week 24 (P < 0·001). The full concordance among reviewers occurred in 76·6% of evaluations resulting in an ICC of 0·652 (P < 0·001). Changes in body weight (P < 0·0001), diastolic blood pressure (P < 0·0001), two-hour postoral glucose challenge glucose concentration (P = 0·0003), and Cushingoid appearance (P = 0·022) were strong correlates of GCR.Mifepristone treatment for CS results in progressive clinical improvement. Overall agreement among clinical reviewers was substantial and determinants of positive GCR included change in weight, blood pressure, glucose levels and appearance.

    View details for DOI 10.1111/cen.12332

    View details for PubMedID 24102404

  • Clinical characteristics, timing of peak responses and safety aspects of two dosing regimens of the glucagon stimulation test in evaluating growth hormone and cortisol secretion in adults PITUITARY Yuen, K. C., Biller, B. M., Katznelson, L., Rhoads, S. A., Gurel, M. H., Chu, O., Corazzini, V., Spiller, K., Gordon, M. B., Salvatori, R., Cook, D. M. 2013; 16 (2): 220-230

    Abstract

    Weight-based (WB: 0.03 mg/kg) and fixed dose (FD: 1-1.5 mg) regimens of the glucagon stimulation test (GST) have been used to evaluate GH and cortisol secretion in children and adults, respectively. However, experience of the WB regimen in assessing GH and cortisol secretion in adults are limited. We describe a multicenter experience using WB and FD regimens in evaluating GH and cortisol secretion in adults suspected of GH deficiency and central adrenal insufficiency. Retrospective case series of GSTs (n = 515) performed at five tertiary centers. Peak and nadir glucose, and peak GH and peak cortisol responses occurred later with WB (mean dose: 2.77 mg) compared to FD (mean dose: 1.20 mg) regimens. Main side-effects were nausea and vomiting, particularly in younger females. Nausea was comparable but vomiting was more frequent in the WB regimen (WB: 10.0 % vs FD: 2.4 %; P < 0.05). Peak and nadir glucose, ΔGH, and peak and Δcortisol were higher in the WB regimen. In both regimens, age correlated negatively with peak cortisol levels, and body mass index (BMI), fasting, peak and nadir glucose correlated negatively with peak GH levels. WB and FD regimens can induce adult GH and cortisol secretion, but peak responses occur later in the WB regimen. Both regimens are relatively safe, and vomiting was more prevalent in the WB regimen. As age, BMI, and glucose tolerance negatively correlated with peak GH and cortisol levels, the WB regimen may be more effective than the FD regimen in older overweight glucose intolerant patients.

    View details for DOI 10.1007/s11102-012-0407-7

    View details for PubMedID 22806554

  • AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND TREATMENT OF ACROMEGALY-2011 UPDATE: EXECUTIVE SUMMARY ENDOCRINE PRACTICE Katznelson, L., Atkinson, J. L., Cook, D. M., Ezzat, S. Z., Hamrahian, A. H., Miller, K. K. 2011; 17 (4): 636-646

    View details for Web of Science ID 000294276000014

    View details for PubMedID 21846619

  • Pituitary Incidentaloma: An Endocrine Society Clinical Practice Guideline JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Freda, P. U., Beckers, A. M., Katznelson, L., Molitch, M. E., Montori, V. M., Post, K. D., Vance, M. L. 2011; 96 (4): 894-904

    Abstract

    The aim was to formulate practice guidelines for endocrine evaluation and treatment of pituitary incidentalomas.Consensus was guided by systematic reviews of evidence and discussions through a series of conference calls and e-mails and one in-person meeting.We recommend that patients with a pituitary incidentaloma undergo a complete history and physical examination, laboratory evaluations screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm. We recommend that patients with incidentalomas not meeting criteria for surgical removal be followed with clinical assessments, neuroimaging (magnetic resonance imaging at 6 months for macroincidentalomas, 1 yr for a microincidentaloma, and thereafter progressively less frequently if unchanged in size), visual field examinations for incidentalomas that abut or compress the optic nerve and chiasm (6 months and yearly), and endocrine testing for macroincidentalomas (6 months and yearly) after the initial evaluations. We recommend that patients with a pituitary incidentaloma be referred for surgery if they have a visual field deficit; signs of compression by the tumor leading to other visual abnormalities, such as ophthalmoplegia, or neurological compromise due to compression by the lesion; a lesion abutting the optic nerves or chiasm; pituitary apoplexy with visual disturbance; or if the incidentaloma is a hypersecreting tumor other than a prolactinoma.

    View details for DOI 10.1210/jc.2010-1048

    View details for Web of Science ID 000289242800027

    View details for PubMedID 21474686

  • Fatigue after traumatic brain injury: Association with neuroendocrine, sleep, depression and other factors BRAIN INJURY Englander, J., Bushnik, T., Oggins, J., Katznelson, L. 2010; 24 (12): 1379-1388

    Abstract

    Define associations between post-traumatic brain injury (TBI) fatigue and abnormalities in neuroendocrine axes, sleep, mood, cognition and physical functioning.Survey.Large community hospital-based rehabilitation centre.Convenience sample of 119 individuals at least 1 year post-TBI.Multidimensional Assessment of Fatigue (MAF); Fatigue Severity Scale (FSS); neuroendocrine assessments-growth hormone (GH) reserve, thyroid, cortisol and testosterone levels; visual analogue pain rating; Pittsburgh Sleep Quality Index; Beck Depression Inventory-II; Disability Rating Scale; Craig Handicap Assessment and Reporting Technique; Neurobehavioural Functioning Inventory.Fifty-three per cent reported fatigue on the MAF and one-third on the FSS; 65% were found to have moderate/severe GH deficiency; 64% had adrenal insufficiency (low fasting cortisol); 12% had central hypothyroidism; and 15% of men had testosterone deficiency. Pituitary dysfunction did not correlate with fatigue or other symptoms. Predictors of MAF total scores were female gender, depression, pain and self-assessed memory deficits. Predictors of FSS scores were depression, self-assessed motor deficits and anti-depressant usage.Robust correlates of fatigue were gender, depression, pain and memory and motor dysfunction. Investigation of post-TBI fatigue should include screening for depression, pain and sleep disturbance. There was no correlation between pituitary dysfunction and fatigue; however, the relatively high prevalence of hypothyroidism and adrenal dysfunction suggests screening for these hormone deficiencies.

    View details for DOI 10.3109/02699052.2010.523041

    View details for Web of Science ID 000283200800001

    View details for PubMedID 20961172