Bio

Bio


Laurence Katznelson, MD received his medical degree from the University of California, Los Angeles and performed his internship and residency in Internal Medicine at the Hospital of the University of Pennsylvania, Philadelphia. He then performed a fellowship in Endocrinology and Metabolism at the Massachusetts General Hospital, Boston. Dr. Katznelson is a Professor of Neurosurgery and Medicine (Endocrinology)at Stanford University School of Medicine. At Stanford University, he is the Associate Dean of Graduate Medical Education and the Chair of the GME Committee. Dr. Katznelson is the Medical Director of the Pituitary Center at Stanford Hospital and Clinics. In the Endocrine Society, Dr. Katznelson has served as Chair of the Special Programs Committee and Nominations Committees. He has served as Chair of the Task Forces for writing clinical guidelines for the approach to acromegaly for both The Endocrine Society and the American Association of Clinical Endocrinologists, and Chair, Pituitary Committee for the American Association of Clinical Endocrinologists. In endocrinology, Dr. Katznelson has a long standing clinical and research interest in the pathophysiology and treatment of pituitary disease.

Clinical Focus


  • Cancer > Neuro Oncology
  • Endocrine
  • Endocrine - Endocrinology
  • Endocrinology
  • Multiple Endocrine Neoplasias
  • Multiple Endocrine Neoplasias - Endocrinology
  • Neuroendocrine
  • Neuroendocrine - Endocrinology
  • Neuroendocrine - Medical Oncology
  • Parathyroid Disease
  • Parathyroid Disease - Endocrinology
  • Pituitary Adenomas
  • Pituitary Adenomas - Endocrinology
  • acromegaly
  • Cushing's
  • Cushing's Syndrome
  • Cushing Disease
  • Prolactinoma
  • Adrenal Gland Neoplasms
  • Adrenal Cortex Diseases
  • Growth Hormone-Secreting Pituitary Adenoma
  • Growth Hormone Deficiency Dwarfism
  • Hyperprolactinemia
  • Hypopituitarism
  • Diabetes and Metabolism

Academic Appointments


Administrative Appointments


  • Associate Dean of Graduate Medical Education, Stanford School of Medicine (2014 - Present)
  • Chair, Graduate Medical Education Committee, Stanford Healthcare (2014 - Present)
  • Medical Director, Pituitary Center, Stanford Healthcare (2004 - Present)
  • Director, Endocrinology Fellowship Training Program, Stanford Healthcare (2005 - 2014)
  • Chair, Special Programs Committee, Endocrine Society (2008 - 2011)

Honors & Awards


  • 2017 Laureate Award for Educator of the Year, The Endocrine Society (2017)
  • H. Jack Baskin, MD, Endocrine Teaching Award, American Association of Clinical Endocrinologists (2015)
  • Best Doctors in America, Best Doctors (2005-)

Professional Education


  • BS, U.C., Berkeley, Genetics (1981)
  • MD, UC, Los Angeles, Medicine (1985)
  • Internship: Hospital of the University of Pennsylvania (1986) PA
  • Residency: Hospital of the University of Pennsylvania (1989) PA
  • Fellowship, Massachusetts General Hospital, MA, Endocrinology and Metabolism` (1992)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (1988)
  • Board Certification: Endocrinology, Diabetes and Metabolism, American Board of Internal Medicine (1991)
  • Board Certification, Endocrinology, Diabetes and Metabolism, American Board of Internal Medicine (2013)
  • Fellowship: Massachusetts General Hospital (1992) MA

Research & Scholarship

Current Research and Scholarly Interests


My clinical and research interests in neuroendocrinology include the following programs:

1. Investigations into the effects of brain injury on pituitary function, with emphasis on the impact of hypopituitarism on rehabilitation

2. Research on the effects of neuroendocrine factors, including growth hormone and glucocorticoids, on neurocognitive function

3. Investigations into novel therapeutic modalities for acromegaly and hypopituitarism

Clinical Trials


  • Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies Recruiting

    The purpose of this study is to allow continued use of pasireotide in patients who are on pasireotide treatment in a Novartis-sponsored study and are benefiting from the treatment as judged by the investigator.

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  • An Open-Labeled, Extended-Use of XERECEPT (hCRF) for Patients in Studies NTI 0302, 0303, or Other Designated Studies Not Recruiting

    The purpose of this study is to examine the long-term safety and tolerability of human corticotropin-releasing factor (hCRF), XERECEPT®, in patients requiring dexamethasone (Decadron) to treat peritumoral brain edema. This open-label, extended-use study is open to all patients who participate in either of the blinded studies, NTI 0302, NTI 0303, or other designated studies, including patients who may have discontinued blinded study medication early but completed the protocol-stipulated follow-up periods.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lynn Adler, (650) 725 - 8630.

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  • Pilot Study to Determine Radioiodide Accumulation and Dosimetry in Breast Cancers Using 124I PET/CT Not Recruiting

    This is a pilot imaging study for women whose tumors express NIS [Na+I- symporter, sodium iodide symporter]. Eligibility is limited to the presence of strong (3+) and/or plasma membrane staining in > 20% of cells as determined by immunohistochemical methods. A total of 10 patients will be imaged with 124I PET/CT (serial scans over 24 hour period) to determine radioiodide uptake and distribution in tumor tissue. Thyroid iodide uptake and retention will be blocked beginning one week prior to 124I PET/CT scan with thyroid hormone (T3) and methimazole (impedes organification). Tumor, organ and whole body dosimetry will be calculated in each patient.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • Safety and Efficacy of Pasireotide Long Acting Release (LAR) vs. Octreotide LAR in Patients With Active Acromegaly Not Recruiting

    The patients received either Pasireotide LAR or Octreotide LAR for one year of treatment. The objective of this study was to compare the proportion of patients with a reduction of mean GH level to <2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) between the two treatment groups (pasireotide LAR and octreotide LAR) at 12 months. Following one year of treatment patients could proceed into the study extension. Patients who did not respond to the treatment they were randomized to (based on month 12 assessment results) were switched to the other treatment arm at month 13.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jacob Petralia, (650) 721 - 2830.

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  • XERECEPT® (hCRF) for Patients Requiring Dexamethasone to Treat Edema Associated With Brain Tumors Not Recruiting

    The purpose of this study is to compare the safety and efficacy of XERECEPT® to dexamethasone (Decadron) a common treatment for symptoms of brain swelling (edema). This study is specifically aimed at patients who require chronic high doses of dexamethasone to manage symptoms.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lynn Adler, (650) 725 - 8630.

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Teaching

2019-20 Courses


Graduate and Fellowship Programs


Publications

All 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 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

  • Italian Association Of Clinical Endocrinologists (Ame) And Italian Aace Chapter Position Statement For Clinical Practice: Acromegaly - Part 2: Therapeutic Issues. Endocrine, metabolic & immune disorders drug targets Cozzi, R., Ambrosio, M. R., Attanasio, R., Bozzao, A., De Marinis, L., De Menis, E., Guastamacchia, E., Lania, A., Lasio, G., Logoluso, F., Maffei, P., Poggi, M., Toscano, V., Zini, M., Chanson, P., Katznelson, L. 2020

    Abstract

    Any newly diagnosed patient should be referred to a multidisciplinary team experienced in the treatment of pituitary adenomas. The therapeutic management of acromegaly always requires a personalized strategy. Normal age-matched IGF-I values are the treatment goal. Transsphenoidal surgery by an expert neurosurgeon is the primary treatment modality for most patients, especially if there are neurological complications. In patients with poor clinical conditions or who refuse surgery, primary medical treatment should be offered, firstly with somatostatin analogs (SSAs). In patients who do not reach hormonal targets with first generation depot SSAs, a second pharmacological option with pasireotide LAR or pegvisomant (alone or combined with SSA) should be offered. Irradiation could be proposed to patients with surgical remnants who would like to be free from long-term medical therapies or those with persistent disease activity or tumor growth despite surgery or medical therapy. Since the therapeutic tools available enable therapeutic targets to be achieved in most cases, the challenge is to focus more on the quality of life.

    View details for DOI 10.2174/1871530320666200129113328

    View details for PubMedID 31995025

  • ITALIAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS (AME) and ITALIAN AACE CHAPTER POSITION STATEMENT FOR CLINICAL PRACTICE: ACROMEGALY - PART 1: DIAGNOSTIC AND CLINICAL ISSUES. Endocrine, metabolic & immune disorders drug targets Cozzi, R., Ambrosio, M. R., Attanasio, R., Bozzao, A., De Marinis, L., De Menis, E., Guastamacchia, E., Lania, A., Lasio, G., Logoluso, F., Maffei, P., Poggi, M., Toscano, V., Zini, M., Chanson, P., Katznelson, L. 2020

    Abstract

    Acromegaly is a rare disease. Improvements in lifespan in these patients have recently been reported due to transsphenoidal surgery (TSS), advances in medical therapy, and tighter criteria for defining disease remission. This document reports the opinions of a group of Italian experts who have gathered together their prolonged clinical experience in the diagnostic and therapeutic challenges of acromegaly patients. Both GH and IGF-I (only IGF-I in those treated with Pegvisomant - PegV) are needed in the diagnosis and follow-up. Comorbidities (cardio-cerebrovascular disease, sleep apnea, metabolic derangement, neoplasms, and bone/joint disease) should be specifically addressed. Any newly diagnosed patient should be referred to a multidisciplinary team experienced in the treatment of pituitary adenomas.

    View details for DOI 10.2174/1871530320666200127103320

    View details for PubMedID 31985386

  • A Consensus on the Diagnosis and Treatment of Acromegaly Comorbidities: An Update. The Journal of clinical endocrinology and metabolism Giustina, A., Barkan, A., Beckers, A., Biermasz, N., Biller, B. M., Boguszewski, C., Bolanowski, M., Bonert, V., Bronstein, M. D., Casanueva, F. F., Clemmons, D., Colao, A., Ferone, D., Fleseriu, M., Frara, S., Gadelha, M. R., Ghigo, E., Gurnell, M., Heaney, A. P., Ho, K., Ioachimescu, A., Katznelson, L., Kelestimur, F., Kopchick, J., Krsek, M., Lamberts, S., Losa, M., Luger, A., Maffei, P., Marazuela, M., Mazziotti, G., Mercado, M., Mortini, P., Neggers, S., Pereira, A. M., Petersenn, S., Puig-Domingo, M., Salvatori, R., Shimon, I., Strasburger, C., Tsagarakis, S., van der Lely, A. J., Wass, J., Zatelli, M. C., Melmed, S. 2019

    Abstract

    OBJECTIVE: The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013.PARTICIPANTS: The Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration.EVIDENCE: This evidence-based Consensus 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 following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities.CONSENSUS PROCESS: Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system.CONCLUSIONS: Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality.

    View details for DOI 10.1210/clinem/dgz096

    View details for PubMedID 31606735

  • Beyond duty hours: leveraging large-scale paging data to monitor resident workload NPJ DIGITAL MEDICINE Kaushal, A., Katznelson, L., Harrington, R. A. 2019; 2: 87

    Abstract

    Monitoring and managing resident workload is a cornerstone of policy in graduate medical education, and the duty hours metric is the backbone of current regulations. While the duty hours metric measures hours worked, it does not capture differences in intensity of work completed during those hours, which may independently contribute to fatigue and burnout. Few such metrics exist. Digital data streams generated during the usual course of hospital operations can serve as a novel source of insight into workload intensity by providing high-resolution, minute-by-minute data at the individual level; however, study and use of these data streams for workload monitoring has been limited to date. Paging data is one such data stream. In this work, we analyze over 500,000 pages-two full years of pages in an academic internal medicine residency program-to characterize paging patterns among housestaff. We demonstrate technical feasibility, validity, and utility of paging burden as a metric to provide insight into resident workload beyond duty hours alone, and illustrate a general framework for evaluation and incorporation of novel digital data streams into resident workload monitoring.

    View details for DOI 10.1038/s41746-019-0165-2

    View details for Web of Science ID 000484610000001

    View details for PubMedID 31531394

    View details for PubMedCentralID PMC6733865

  • A protected time policy to improve dental health among resident physicians JOURNAL OF THE AMERICAN DENTAL ASSOCIATION Jun, T., Liebert, C., Esquivel, M., Cox, J., Trockel, M., Katznelson, L. 2019; 150 (5): 362-+

    Abstract

    Resident physicians underuse preventive dental health services. The authors assessed the barriers to and need for oral health care among residents and piloted a program to enhance dental health care among house staff.Participants from 5 residency programs received 2 hours of protected time during business hours for visits to a nearby dental office. The authors surveyed participating residents before and after the visits about barriers to seeking oral health care and their experiences with the program. The authors recorded dental findings for each participant.A total of 35 of 243 eligible residents (14.4%) participated in the study; 71.4% reported delaying or skipping preventive dental examinations during residency. Lack of time and norms and peer perceptions were important barriers; 28.6% of residents had dental findings requiring further management.Residents neglect preventive oral health care because of work obligations. More than one-quarter of residents had clinically significant dental findings. Providing protected time addressed common barriers and was well received.Resident physicians have unmet oral health care needs. Collaborations between residency programs and dental practices to provide protected time for residents to seek oral health care could address common barriers to care.

    View details for DOI 10.1016/j.adaj.2018.12.016

    View details for Web of Science ID 000465431400024

    View details for PubMedID 31029211

  • Authors' response. Journal of the American Dental Association (1939) Jun, T. W., Liebert, C. A., Esquivel, M., Cox, J. A., Trockel, M., Katznelson, L. 2019; 150 (7): 568–69

    View details for DOI 10.1016/j.adaj.2019.05.010

    View details for PubMedID 31248480

  • 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 PubMedID 30400048

  • Natural history of Rathke's cleft cysts: A retrospective analysis of a two centres experience CLINICAL ENDOCRINOLOGY Sala, E., Moore, J. M., Amorin, A., Carosi, G., Martinez, H., Harsh, G. R., Arosio, M., Mantovani, G., Katznelson, L. 2018; 89 (2): 178–86

    Abstract

    Rathke's cleft cyst (RCC) is a common sellar lesion which may cause visual impairment, hypopituitarism and headaches from mass effect. The natural history of these lesions is currently unclear. We investigated the natural history of RCCs and compared surgically treated patients with those treated conservatively.We performed a retrospective cohort study of patients diagnosed with a RCC between 1996 and 2016 at Stanford University and Ospedale Maggiore Policlinico di Milano.Patients were divided into 2 cohorts: Group A, 72 subjects who underwent surgical resection of a symptomatic RCC, and Group B, 62 subjects managed conservatively. Compared to Group B, Group A subjects had larger RCCs (79% vs 22% had a largest diameter >10 mm, P < .001) and were more likely (41.5% vs 16%, P < .001) to present with hypopituitarism and diabetes insipidus (DI) (18% vs 1.6%, P = .002). In Group A, after a mean follow-up of 53.7 months, 12.5% of patients had recurrence and a second surgery. After surgery, 35% of patients recovered pituitary function. Hyperprolactinemia (26.6%) and hypogonadism (66.6%) resolved more commonly that did DI (20.1%). New pituitary deficits appeared in 16.6% of patients after surgery. In Group B, with a mean follow-up of 41 months, only 6.4% had cyst enlargement, none underwent surgery, and none developed a pituitary deficit.Our data offer guidance in decision-making regarding the management of RCC patients and confirm the safety of conservative treatment in asymptomatic patients.

    View details for PubMedID 29781512

  • Clinical and Immunohistochemical Analysis of Clinically Non-functional Pituitary Neuroendocrine Tumors Lavezo, J., Frankel, M., Balliu, B., Pan, J., Hoffman, A., Dodd, R., Harsh, G., Katznelson, L., Vogel, H. OXFORD UNIV PRESS INC. 2018: 518
  • CyberKnife robotic radiosurgery in the multimodal management of acromegaly patients with invasive macroadenoma: a single center's experience JOURNAL OF NEURO-ONCOLOGY Sala, E., Moore, J. M., Amorin, A., Martinez, H., Bhowmik, A. C., Lamsam, L., Chang, S., Soltys, S. G., Katznelson, L., Harsh, G. R. 2018; 138 (2): 291–98

    Abstract

    Surgery is the primary treatment for acromegaly. However, surgery may not be curative of some tumors, particularly invasive macroadenomas. Adjuvant radiation, specifically robotic stereotactic radiosurgery (rSRS), may improve the endocrine outcome. We retrospectively reviewed hormonal and radiological data of 22 acromegalic patients with invasive macroadenomas treated with rSRS at Stanford University Medical Center between 2000 and 2016. Prior to treatment, the tumor's median maximal diameter was 19 mm (2.5-50 mm). Cavernous sinus invasion occurred in 19 patients (86.3%) and compression of the optic chiasm in 2 (9.0%). At last follow up, with an average follow up of 43.2 months, all patients had a reduction in their IGF-1 levels (median IGF-1% upper limit of normal (ULN) baseline: 136% vs last follow up: 97%; p = 0.05); 9 patients (40.9%) were cured, and 4 (18.1%) others demonstrated biochemical control of acromegaly. The median time to cure was 50 months and the mean interval to cure or biochemical control was 30.3 months (± 24 months, range 6-84 months). Hypopituitarism was present in 8 patients (36.3%) and new pituitary deficits occurred in 6 patients with a median latency of 31.6 ± 14.5 months. At final radiologic follow-up, 3 tumors (13.6%) were smaller and 19 were stable in size. The mean biologically effective dose (BED) was higher in subjects cured compared to those with persistent disease, 163 Gy3 (± 47) versus 111 Gy3 (± 43), respectively (p = 0.01). No patient suffered visual deterioration. Robotic SRS is a safe and effective treatment for acromegaly: radiation-induced visual complications and hypopituitarism is rare.

    View details for PubMedID 29429125

  • Nurse Telephonic Triage Service for After-hour Patient Calls in Neurosurgery. Annals of surgery Escobedo-Wu, E. L., Dhebar, F., Harsh, G., Steinberg, G., Vyas, A., Katznelson, L., Ho, A. L., Pendharkar, A. V., Sussman, E. S., Rohatgi, N. 2018; 267 (4): e67–e68

    Abstract

    OBJECTIVE: The aim of this study was to report the utilization and experience of the nurse telephonic triage service for after-hour patient calls in Neurosurgery.BACKGROUND: It is challenging for patients to reach their clinicians after-hours in a timely manner. This may result in worse health outcomes for the patients, or inappropriate utilization of emergency rooms and urgent care facilities. Physicians continue to remain overwhelmed with frequent after-hours calls in addition to other clinical responsibilities while on-call.METHODS: In August 2015, our institution launched the Clinical Advice Service (CAS) to provide a patient-centric, nurse-run telephone triage service for after-hour calls from Neurosurgery patients. Clinical protocols were created for use by CAS staff by Neurosurgery clinicians.RESULTS: Between July 2016 and June 2017, CAS has accepted 1021 after-hours calls from Neurosurgery patients. A total of 71.4% of these calls were clinical, and the remaining nonclinical (directions, appointments, general information). CAS escalated 37.3% of the calls to the on-call Neurosurgery physician; 4.8% Neurosurgery patients were triaged to the emergency room by CAS.CONCLUSION: CAS has been able to provide well-coordinated care to Neurosurgery patients while reducing physician workload.

    View details for PubMedID 29064895

  • Adrenal Axis Insufficiency After Endoscopic Transsphenoidal Resection of Pituitary Adenomas WORLD NEUROSURGERY Ajlan, A., Almufawez, K. A., Albakr, A., Katznelson, L., Harsh, G. R. 2018; 112: E869–E875

    Abstract

    Hormonal insufficiency of 1 or more pituitary axes can appear after pituitary surgery. Adrenal axis impairment after surgery can lead to serious consequences if not identified and treated.Assess early and late postoperative adrenal insufficiency (AI) and identify the risk factors predicting their occurrence after endoscopic transsphenoidal resection of pituitary adenomas.Retrospective review identified 176 pituitary adenomas resected using an endoscopic transsphenoidal approach. Patients taking steroids preoperatively, Cushing disease patients, and patients with incomplete records were excluded. Sixty-nine patients were excluded according to our exclusion criteria.The study group thus included 107 patients (total of 111 operations). The median age was 50 years (range, 18-89 years). The median duration of follow-up was 30 months (range, 6-74 months). Eighty-three patients (74.7%) had macroadenomas, and 89 (59.3%) had nonfunctional adenomas. Of the 111 procedures, 61 patients (55%) had early AI. Of the 61 patients, 48 patients (79%) were not taking steroids in long-term follow-up, and only 13 (21%) required long-term replacement. Sixteen of the patients undergoing 111 procedures (14.4%) had AI on long-term follow-up. Of those 16 patients, 13 were already taking steroids and 3 had new diagnoses of AI. Age, male gender, and cerebrospinal fluid (CSF) leaks were associated with persistent postoperative AI (P = 0.018, P = 0.001, P = 0.007, respectively).Hypothalamic pituitary adrenal axis insufficiency is common after endoscopic transsphenoidal surgery. Male gender, age greater than 50 years, visual impairment, and intraoperative CSF leak were correlated with late postoperative AI. More than two thirds of patients in whom early AI developed did not require steroids in the long term.

    View details for PubMedID 29421453

  • Diabetes Insipidus following Endoscopic Transsphenoidal Surgery for Pituitary Adenoma JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE Ajlan, A. M., Bin Abdulqader, S., Achrol, A. S., Aljamaan, Y., Feroze, A. H., Katznelson, L., Harsh, G. R. 2018; 79 (2): 117–22

    Abstract

    Objectives  Pituitary adenoma (PA), among the most commonly encountered sellar pathologies, accounts for 10% of primary intracranial tumors. The reported incidence of postoperative diabetes insipidus (DI) is highly variable. In this study, we report our experience with DI following endoscopic transsphenoidal surgery (TSS) for PAs, elucidating the risk factors of postoperative DI, the likelihood of long-term DI, and the impact of DI on the length of stay (LOS). Methods  The study included 178 patients who underwent endoscopic resection of PAs. Early DI was defined as that occurring within the first postoperative week. The mean follow-up was 36 months. Long-term DI was considered as DI apparent in the last follow-up visit. Results  Of the 178 patients included in the study, 77% of the tumors were macroadenomas. Forty-seven patients (26%) developed early DI. Long-term DI was observed in 18 (10.1%) of the full cohort. Age younger than 50 years was significantly associated with a higher incidence of long-term DI ( p  = 0.02). Macroadenoma and gross total resection were significantly associated with higher incidence of early DI ( p  = 0.05 and p  = 0.04, respectively). The mean LOS was 4 days for patients with early postoperative DI and 3 days for those without it. Conclusion  The reported incidence of postoperative DI is significantly variable. We identified age younger than 50 years a risk factor for developing long-term postoperative DI. Gross total surgical resection and tumor size (> 1 cm) were associated with development of early DI. Early DI increased the LOS on average by 1 day.

    View details for PubMedID 29868315

    View details for PubMedCentralID PMC5978855

  • CyberKnife Radiosurgery in the Multimodal Management of Patients with Cushing Disease WORLD NEUROSURGERY Moore, J. M., Sala, E., Amorin, A., Martinez, H., Bhowmik, A. C., Chang, S. D., Soltys, S. G., Harsh, G. R., Katznelson, L. 2018; 112: E425–E430

    Abstract

    Surgery is the primary treatment for Cushing disease. When surgery is unsuccessful in normalizing hypercortisolism, adjuvant radiation, such as stereotactic radiosurgery, may be useful to improve biochemical control.This retrospective study included a cohort of consecutive patients treated with CyberKnife (CK) radiosurgery for active Cushing disease at Stanford Hospital and Clinics.As first-line treatment, all patients underwent transsphenoidal surgery with histologic demonstration of an adrenocorticotropic hormone-producing pituitary adenoma. CK was performed as adjuvant therapy for persistent or recurrent disease. The median time between surgery and CK was 14 ± 34 months. Before CK, median maximal diameter of tumors was 9 mm (range, 7-32 mm), with cavernous sinus invasion in all patients (100%) and abutment of the optic chiasm in 1 patient (14.2%). With an average follow-up of 55.4 months, normalization of hypercortisolism was achieved in 4 patients (57.1%): 2 patients (28.5%) achieved normalization of the hypothalamic-pituitary-adrenal axis without glucocorticoid replacement, and 2 patients developed hypoadrenalism (28.5%). The median time to biochemical remission was 12.5 months. Hypopituitarism occurred in only 1 patient (14.2%), and no patients had visual complications. Time between surgery and radiotherapy of <14 months was associated with a significantly improved biochemical remission rate (P = 0.02).In a cohort of patients with Cushing disease, we demonstrate that CK is an effective treatment with rare complications.

    View details for PubMedID 29355797

  • Utility of Pit-1 Immunostaining in Distinguishing Pituitary Adenomas of Primitive Differentiation from Null Cell Adenomas ENDOCRINE PATHOLOGY Lee, J. C., Pekmezci, M., Lavezo, J. L., Vogel, H., Katznelson, L., Fraenkel, M., Harsh, G., Dulai, M., Perry, A., Tihan, T. 2017; 28 (4): 287–92

    Abstract

    Pit-1 immunostaining is not routinely used in the characterization of pituitary adenomas, and its utility in distinguishing adenomas dedicated towards the lactotroph, somatotroph, and thyrotroph lineage from null cell adenomas warrants further evaluation. Pituitary adenomas that were negative for expression of a basic panel of hormonal markers (ACTH, prolactin, and growth hormone) were further evaluated for TSH, SF-1, and Pit-1 expression using a tissue microarray. Among the 147 identified pituitary adenomas that were negative for ACTH, prolactin, growth hormone, and TSH, expression of SF-1 was present in 68 cases (46%). Of the remaining 72 cases with sufficient tissue for further analysis, four were Pit-1 positive (6% of the adenomas negative for ACTH, prolactin, growth hormone, TSH, and SF-1); the remaining 68 were potentially null cell adenomas. Two of the Pit-1-positive adenomas displayed a paranuclear CAM 5.2 staining pattern suggestive of a sparsely granulated somatotroph adenoma; however, only one case contained fibrous bodies within a majority of the adenoma cells. Our data suggests that Pit-1 can be utilized as a second tier immunostain in cases of clinically non-functioning adenomas that are immunonegative for ACTH, prolactin, growth hormone, TSH, and SF-1 in order to further segregate rare cases of Pit-1-positive adenomas from null cell adenomas. Pit-1 immunostaining can recognize rare cases of sparsely granulated somatotroph adenomas that appear immunonegative for growth hormone, as well as rare cases of other Pit-1-positive adenomas that are negative for Pit-1 lineage hormones. Overall, pituitary adenomas of the Pit-1 lineage that do not produce prolactin, growth hormone, or TSH are rare, with only four cases identified in the current study.

    View details for PubMedID 28994039

  • Follow-up intervals in patients with Cushing's disease: recommendations from a panel of experienced pituitary clinicians. Pituitary Geer, E. B., Ayala, A., Bonert, V., Carmichael, J. D., Gordon, M. B., Katznelson, L., Manuylova, E., Shafiq, I., Surampudi, V., Swerdloff, R. S., Broder, M. S., Cherepanov, D., Eagan, M., Lee, J., Said, Q., Neary, M. P., Biller, B. M. 2017

    Abstract

    Follow-up guidelines are needed to assess quality of care and to ensure best long-term outcomes for patients with Cushing's disease (CD). The purpose of this study was to assess agreement by experts on recommended follow-up intervals for CD patients at different phases in their treatment course.The RAND/UCLA modified Delphi process was used to assess expert consensus. Eleven clinicians who regularly manage CD patients rated 79 hypothetical patient scenarios before and after ("second round") an in-person panel discussion to clarify definitions. Scenarios described CD patients at various time points after treatment. For each scenario, panelists recommended follow-up intervals in weeks. Panel consensus was assigned as follows: "agreement" if no more than two responses were outside a 2 week window around the median response; "disagreement" if more than two responses were outside a 2 week window around the median response. Recommendations were developed based on second round results.Panel agreement was 65.9% before and 88.6% after the in-person discussion. The panel recommended follow-up within 8 weeks for patients in remission on glucocorticoid replacement and within 1 year of surgery; within 4 weeks for patients with uncontrolled persistent or recurrent disease; within 8-24 weeks in post-radiotherapy patients controlled on medical therapy; and within 24 weeks in asymptomatic patients with stable plasma ACTH concentrations after bilateral adrenalectomy.With a high level of consensus using the Delphi process, panelists recommended regular follow-up in most patient scenarios for this chronic condition. These recommendations may be useful for assessment of CD care both in research and clinical practice.

    View details for DOI 10.1007/s11102-017-0801-2

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