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

Browse Trials

Published Studies

Juan Fernandez-Miranda
Surgical Director, Stanford Pituitary Center

Publications

  • 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 DOI 10.1093/ons/opy308

    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 DOI 10.1093/ons/opy401

    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 DOI 10.1093/ons/opy214

    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 DOI 10.1093/ons/opy216

    View details for PubMedID 30295900

  • The medial wall of the cavernous sinus. Part 1: Surgical anatomy, ligaments, and surgical technique for its mobilization and/or resection. Journal of neurosurgery Truong, H. Q., Lieber, S., Najera, E., Alves-Belo, J. T., Gardner, P. A., Fernandez-Miranda, J. C. 2018: 1–9

    Abstract

    OBJECTIVE The medial wall of the cavernous sinus (CS) is often invaded by pituitary adenomas. Surgical mobilization and/or removal of the medial wall remains a challenge. METHODS Endoscopic endonasal dissection was performed in 20 human cadaver heads. The configuration of the medial wall, its relationship to the internal carotid artery (ICA), and the ligamentous connections in between them were investigated in 40 CSs. RESULTS The medial wall of the CS was confirmed to be an intact single layer of dura that is distinct from the capsule of the pituitary gland and the periosteal layer that forms the anterior wall of the CS. In 32.5% of hemispheres, the medial wall was indented by and/or well adhered to the cavernous ICA. The authors identified multiple ligamentous fibers that anchored the medial wall to other walls of the CS and/or to specific ICA segments. These parasellar ligaments were classified into 4 groups: 1) caroticoclinoid ligament, spanning from the medial wall and the middle clinoid toward the clinoid ICA segment and anterior clinoid process; 2) superior parasellar ligament, connecting the medial wall to the horizontal cavernous ICA and/or lateral wall of the CS; 3) inferior parasellar ligament, bridging the medial wall to the anterior wall of the CS or anterior surface of the short vertical segment of the cavernous ICA; and 4) posterior parasellar ligament, which anchors the medial wall to the short vertical segment of the cavernous ICA and/or the posterior carotid sulcus. The caroticoclinoid ligament and inferior parasellar ligament were present in most CSs (97.7% and 95%, respectively), while the superior and posterior parasellar ligaments were identified in approximately half of the CSs (57.5% and 45%, respectively). The caroticoclinoid ligament was the strongest and largest ligament, and it was typically assembled as a group of ligaments with a fan-like arrangement. The inferior parasellar ligament was the first to be encountered after opening the anterior wall of the CS during an interdural transcavernous approach. CONCLUSIONS The authors introduce a classification of the parasellar ligaments and their role in anchoring the medial wall of the CS. These ligaments should be identified and transected to safely mobilize the medial wall away from the cavernous ICA during a transcavernous approach and for safe and complete resection of adenomas that selectively invade the medial wall.

    View details for DOI 10.3171/2018.3.JNS18596

    View details for PubMedID 30192192

  • Supratotal Resection of Residual Clival Chordoma With Combined Endoscopic Endonasal and Contralateral Transmaxillary Approaches: 2-Dimensional Operative Video. Operative neurosurgery (Hagerstown, Md.) Lavigne, P., Wang, E. W., Fernandez-Miranda, J. C. 2018

    Abstract

    The optimal treatment for skull base chordomas is gross total resection followed by radiotherapy and not radiation of partially resected tumors. Supratotal resection, defined as removal beyond all involved bone and dura, is ideal but difficult to achieve.In this video, we present the case of a 37-yr-old man with new onset of progressive cranial nerve sixth palsy and a skull base lesion compatible with clival chordoma. He underwent partial surgical resection at an outside institution via transcranial approach, with significant tumor residual at the clivus, dorsum sella, posterior clinoids, and petrous apex, extensive dural invasion, and intradural extension with attachment to the basilar artery and its long perforating branches.Supratotal surgical resection was achieved using an endoscopic endonasal transclival approach, ipsilateral transpteryoid approach to the foramen lacerum for carotid artery mobilization, bilateral interdural transcavernous approach with posterior clinoidectomies, and con-tralateral transmaxillary approach to the petrous apex. Reconstruction was performed in a multilayer fashion with fascia lata and fat grafts, extended nasoseptal flap, a lumbar drainage for 3 d. No cerebrospinal fluid leak occurred, and the abducens nerve palsy significantly improved at 3-mo follow-up. Proton therapy is planned.Recent advances in endoscopic endonasal surgery allow for very high rates of complete and even supratotal resection despite the challenging location. A long learning curve to acquire the technical skills and complex surgical anatomy is required to decrease complication rates and achieve maximal resection in chordomas. Reoperations are more challenging and risky; therefore, first attempt should have curative intent.The patient signed informed consent including the use of photographic and video material for educational or academic purposes.

    View details for DOI 10.1093/ons/opy220

    View details for PubMedID 30189024

  • Bilateral coagulation of inferior hypophyseal artery and pituitary transposition during endoscopic endonasal interdural posterior clinoidectomy: do they affect pituitary function? Journal of neurosurgery Truong, H. Q., Borghei-Razavi, H., Najera, E., Igami Nakassa, A. C., Wang, E. W., Snyderman, C. H., Gardner, P. A., Fernandez-Miranda, J. C. 2018: 1–6

    Abstract

    OBJECTIVE The endoscopic endonasal transcavernous approach with interdural pituitary transposition provides surgical access to the posterior clinoids and interpeduncular cistern. Prior to posterior clinoidectomy, selective coagulation and transection of the inferior hypophyseal artery (IHA) is recommended to prevent uncontrolled tearing of the artery and its avulsion from the wall of the cavernous carotid artery. The authors' preliminary experience has shown that unilateral sacrifice of the IHA caused no permanent endocrine dysfunction. In this study, they investigated the pituitary function in the setting of bilateral sacrifice of IHAs and pituitary transposition. METHODS All patients with normal preoperative pituitary function who underwent endoscopic endonasal bilateral posterior clinoidectomy with bilateral IHA sacrifice between March 2010 and December 2016 were included and retrospectively evaluated. All data regarding pituitary function were collected. The degree of pituitary gland manipulation was estimated based on tumor size on preoperative MRI. An angle between a line from the point where the gland meets the floor of the sella to the highest point of the tumor and the horizontal plane of the sellar floor, or access angle, was also measured. Posterior pituitary bright spots on pre- and postoperative T1-weighted MRI were also reported. RESULTS Twenty patients had bilateral transcavernous posterior clinoidectomies with coagulation of both IHAs. There were 13 chordomas, 3 epidermoid cysts, 2 chondrosarcomas, 1 meningioma, and 1 hemangiopericytoma. The mean follow-up was 19 months (range 13-84 months). Two patients experienced transient diabetes insipidus (DI) requiring desmopressin, which resolved before hospital discharge. One patient (with chordoma) developed delayed permanent DI, and a second patient (with hemangiopericytoma) developed permanent DI and panhypopituitarism. The access angle was higher in the group with pituitary dysfunction (47.25° compared to 33.81°; p = 0.07). Posterior pituitary bright spots were preserved in 75% of cases with normal postoperative endocrine function. CONCLUSIONS The endoscopic endonasal transcavernous approach to the interpeduncular cistern with pituitary transposition and bilateral sacrifice of the IHAs does not cause pituitary dysfunction in a majority of patients. When endocrine deficit occurs, it appears to be more likely to have been caused by surgical manipulation than loss of blood supply. This finding confirms clinically the crucial concept of interarterial anastomosis of pituitary vasculature proposed by anatomists.

    View details for DOI 10.3171/2018.2.JNS173126

    View details for PubMedID 30074461

  • Contralateral transmaxillary corridor: an augmented endoscopic approach to the petrous apex JOURNAL OF NEUROSURGERY Patel, C. R., Wang, E. W., Fernandez-Miranda, J. C., Gardner, P. A., Snyderman, C. H. 2018; 129 (1): 211–19

    Abstract

    OBJECTIVE The endoscopic endonasal approach (EEA) has been shown to be an effective means of accessing lesions of the petrous apex. Lesions that are lateral to the paraclival segment of the internal carotid artery (ICA) require lateralization of the paraclival segment of the ICA or a transpterygoid infrapetrous approach. In this study the authors studied the feasibility of adding a contralateral transmaxillary (CTM) corridor to provide greater access to the petrous apex with decreased need for manipulation of the ICA. METHODS Using image guidance, EEA and CTM extension were performed bilaterally on 5 cadavers. The anterior wall of the sphenoid sinus and rostrum were removed. The angle of the surgical approach from the axis of the petrous segment of the ICA was measured. Five illustrative clinical cases are presented. RESULTS The CTM corridor required a partial medial maxillectomy. When measured from the axis of the petrous ICA, the CTM corridor decreased the angle from 44.8° ± 2.78° to 20.1° ± 4.31°, a decrease of 24.7° ± 2.58°. Drilling through the CTM corridor allowed the drill to reach lateral aspects of the petrous apex that would have required lateralization of the ICA or would not have been accessible via EEA. The CTM corridor allowed us to achieve gross-total resection of the petrous apex region in 5 clinical cases with significant paraclival extension. CONCLUSIONS The CTM corridor is a feasible extension to the standard EEA to the petrous apex that offers a more lateral trajectory with improved access. This approach may reduce the risk and morbidity associated with manipulation of the paraclival ICA.

    View details for DOI 10.3171/2017.4.JNS162483

    View details for Web of Science ID 000440655000027

    View details for PubMedID 29053078

  • Cavernous sinus compartments from the endoscopic endonasal approach: anatomical considerations and surgical relevance to adenoma surgery. Journal of neurosurgery Fernandez-Miranda, J. C., Zwagerman, N. T., Abhinav, K., Lieber, S., Wang, E. W., Snyderman, C. H., Gardner, P. A. 2017: 1–12

    Abstract

    OBJECTIVE Tumors with cavernous sinus (CS) invasion represent a neurosurgical challenge. Increasing application of the endoscopic endonasal approach (EEA) requires a thorough understanding of the CS anatomy from an endonasal perspective. In this study, the authors aimed to develop a surgical anatomy-based classification of the CS and establish its utility for preoperative surgical planning and intraoperative guidance in adenoma surgery. METHODS Twenty-five colored silicon-injected human head specimens were used for endonasal and transcranial dissections of the CS. Pre- and postoperative MRI studies of 98 patients with pituitary adenoma with intraoperatively confirmed CS invasion were analyzed. RESULTS Four CS compartments are described based on their spatial relationship with the cavernous ICA: superior, posterior, inferior, and lateral. Each compartment has distinct boundaries and dural and neurovascular relationships: the superior compartment relates to the interclinoidal ligament and oculomotor nerve, the posterior compartment bears the gulfar segment of the abducens nerve and inferior hypophyseal artery, the inferior compartment contains the sympathetic nerve and distal cavernous abducens nerve, and the lateral compartment includes all cavernous cranial nerves and the inferolateral arterial trunk. Twenty-nine patients had a single compartment invaded, and 69 had multiple compartments involved. The most commonly invaded compartment was the superior (79 patients), followed by the posterior (n = 64), inferior (n = 45), and lateral (n = 23) compartments. Residual tumor rates by compartment were 79% in lateral, 17% in posterior, 14% in superior, and 11% in inferior. CONCLUSIONS The anatomy-based classification presented here complements current imaging-based classifications and may help to identify involved compartments both preoperatively and intraoperatively.

    View details for DOI 10.3171/2017.2.JNS162214

    View details for PubMedID 28862552

  • Extended Middle Fossa Approach With Anterior Petrosectomy and Anterior Clinoidectomy for Resection of Spheno-Cavernous-Tentorial Meningioma: The Hakuba-Kawase-Dolenc Approach: 3-Dimensional Operative Video OPERATIVE NEUROSURGERY Fernandez-Miranda, J. C. 2017; 13 (2): 281

    View details for Web of Science ID 000404126300037

    View details for PubMedID 28927221

Laurence Katznelson
Medical Director, Stanford Pituitary Center

Publications

  • 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 Web of Science ID 000319295500013

    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

  • Fatigue after TBI: Association with neuroendocrine abnormalities BRAIN INJURY Bushnik, T., Englander, J., Katznelson, L. 2007; 21 (6): 559-566

    Abstract

    Evaluate the association between neuroendocrine findings and fatigue after traumatic brain injury (TBI) Research design: Prospective, observational.Sixty-four individuals at least 1 year post-TBI underwent neuroendocrine testing including thyroid, adrenal, gonadal axes and growth hormone (GH) after glucagon stimulation with assessment of fatigue using the Global Fatigue Index (GFI) and the Fatigue Severity Scale (FSS).GFI and FSS scores were significantly higher within this sample compared to published control data. At least one pituitary axis was abnormal in 90% of participants. Higher GH levels were significantly associated with higher FSS scores. There was a noted trend between lower basal cortisol and higher scores on both the FSS and GFI.The association between higher GH levels and greater fatigue contradicted the prevailing hypothesis that post-acute TBI fatigue is associated with GH deficiency. The association between lower basal cortisol and greater fatigue was in the expected direction. While no other trends were noted, the fatigue derived from neuroendocrine abnormalities alone may be masked by fatigue induced by other factors commonly experienced following TBI. Given the high prevalence of pituitary abnormalities, screening for hypopituitarism after TBI is a reasonable recommendation. The contribution of GH deficiency to diminished quality of life post-TBI remains unclear.

    View details for DOI 10.1080/02699050701426915

    View details for Web of Science ID 000248204100002

    View details for PubMedID 17577706

  • Psychological effects of Dopamine Agonist Treatment in Patients with Hyperprolactinemia and Prolactin Secreting Adenomas. European journal of endocrinology Ioachimescu, A. G., Fleseriu, M., Hoffman, A. R., Vaughan Iii, T. B., Katznelson, L. 2018

    Abstract

    BACKGROUND: Dopamine agonists (DAs) are the main treatment for patients with hyperprolactinemia and prolactinomas. Recently, an increasing number of reports emphasized DAs' psychological side effects, either de- novo or as exacerbations of prior psychiatric disease.METHODS: Review of prospective and retrospective studies (PubMed 1976- September 2018) evaluating the psychological profile of DAs-treated patients with hyperprolactinemia and prolactinomas. Case -series and case reports of psychiatric complications were also reviewed.RESULTS: Most studies were cross-sectional and had a control group of healthy volunteers or patients with nonfunctioning pituitary adenomas. There were few prospective studies, with/without control group, that included small numbers of patients. Compared with controls, patients with hyperprolactinemia generally had worse quality of life, anxiety, depression and certain personality traits. Patients receiving DAs had higher impulsivity scores than normoprolactinemic controls. Impulse control disorders (ICDs) were reported in both genders, with hypersexuality mostly in men. Multiple ICDs were sometimes reported in the same patient, usually reversible after DA discontinuation. In case reports, DA therapy was temporally associated with severe depression, manic episodes or psychosis, which improved after discontinuation and administration of psychiatric medications. Gender type of DA, dose and duration of therapy didn't correlate with occurrence of psychiatric pathology.CONCLUSION: Patients with hyperprolactinemia receiving DAs may develop changes in mood and behavior regardless of prior psychiatric history. Increased awareness for ICDs, depression, mania and other types of psychosis is needed by all physicians who prescribe DAs. Larger prospective controlled clinical studies are needed to delineate prevalence, risk stratification and management.

    View details for DOI 10.1530/EJE-18-0682

    View details for PubMedID 30400048

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