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  1. Book: Pituitary disorders

    Ben-Shlomo, Anat

    (Endocrinology and metabolism clinics of North America ; 44,1)

    2015  

    Author's details ed. Anat Ben-Shlomo
    Series title Endocrinology and metabolism clinics of North America ; 44,1
    Collection
    Language English
    Size XXIII, 242 S. : Ill., graph. Darst.
    Publisher Elsevier
    Publishing place Philadelphia u.a.
    Publishing country United States
    Document type Book
    HBZ-ID HT018662492
    ISBN 978-0-323-35654-1 ; 0-323-35654-0
    Database Catalogue ZB MED Medicine, Health

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  2. Article: Opioid-induced adrenal insufficiency: diagnostic and management considerations.

    Patel, Erica / Ben-Shlomo, Anat

    Frontiers in endocrinology

    2024  Volume 14, Page(s) 1280603

    Abstract: The dramatic rise in opioid use over the last two decades has led to a surge in their harmful health effects. Lesser known among clinicians is the impact of opioids on the endocrine system, especially with regard to cortisol. Opioids can suppress the ... ...

    Abstract The dramatic rise in opioid use over the last two decades has led to a surge in their harmful health effects. Lesser known among clinicians is the impact of opioids on the endocrine system, especially with regard to cortisol. Opioids can suppress the hypothalamus-pituitary-adrenal (HPA) axis and may result in clinically significant adrenal insufficiency, especially in those treated at higher doses and for a longer time. A high clinical suspicion is necessary in this population for early diagnosis of opioid-induced adrenal insufficiency (OAI). Diagnosis of OAI is challenging, as the symptoms are often vague and overlap with those due to opioid use or the underlying pain disorder. Traditional assays to diagnose adrenal insufficiency have not been widely studied in this population, and more investigation is needed to determine how opioids might affect assay results. Once a diagnosis of adrenal insufficiency has been made, glucocorticoid replacement in the form of hydrocortisone is likely the mainstay of treatment, and effort should be made to taper down opioids where possible. Cortisol levels should be retested periodically, with the goal of stopping glucocorticoid replacement once the HPA axis has recovered. In this review, we provide context for diagnostic challenges in OAI, suggest diagnostic tools for this population based on available data, and offer recommendations for the management of this disorder. There is a paucity of literature in this field; given the widespread use of opioids in the general population, more investigation into the effects of opioids on the HPA axis is sorely needed.
    MeSH term(s) Humans ; Glucocorticoids/adverse effects ; Analgesics, Opioid ; Hydrocortisone/pharmacology ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Adrenal Insufficiency/drug therapy ; Opioid-Related Disorders/drug therapy
    Chemical Substances Glucocorticoids ; Analgesics, Opioid ; Hydrocortisone (WI4X0X7BPJ)
    Language English
    Publishing date 2024-02-27
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2023.1280603
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Exploring the role of the tumor microenvironment in refractory pituitary tumor pathogenesis.

    Ben-Shlomo, Anat

    Pituitary

    2023  Volume 26, Issue 3, Page(s) 263–265

    Abstract: Purpose: Treatment-refractory pituitary tumors demonstrate characteristics resembling those of highly aggressive tumors, in which the local tumor microenvironment (TME) plays a dominant role in promoting aggressiveness and refractoriness. However, role ... ...

    Abstract Purpose: Treatment-refractory pituitary tumors demonstrate characteristics resembling those of highly aggressive tumors, in which the local tumor microenvironment (TME) plays a dominant role in promoting aggressiveness and refractoriness. However, role of the TME in pituitary tumors is not well studied.
    Methods: Literature on the TME and development of refractory pituitary tumors was reviewed RESULTS: TME harbors tumorigenic immune cells, cancer-associated fibroblasts (CAF), extracellular matrix, and other factors that have been shown to affect behavior of tumor tissue. For example, tumor-associated macrophages and tumor-infiltrating lymphocytes correlate with aggressive and invasive tumor behavior in nonfunctioning and growth hormone-secreting (GH) pituitary tumors, while CAF release of TGFβ, FGF2, cytokines, chemokines, and growth factors may promote treatment resistance, tumor fibrosis, and inflammation in prolactinomas and GH-secreting tumors. In turn, Wnt pathway activation can further promote cell growth in dopamine-resistant prolactinomas. Finally, proteins secreted by extracellular matrix are associated with increased angiogenesis in invasive tumors.
    Conclusion: It is likely that multiple mechanisms, including TME, contribute to the development of aggressive refractory pituitary tumors. Given the increased morbidity and mortality associated with pituitary tumor refractoriness, more research on the role of TME is warranted.
    MeSH term(s) Humans ; Pituitary Neoplasms/pathology ; Prolactinoma ; Tumor Microenvironment/physiology ; Pituitary Gland/pathology ; Growth Hormone ; Human Growth Hormone
    Chemical Substances Growth Hormone (9002-72-6) ; Human Growth Hormone (12629-01-5)
    Language English
    Publishing date 2023-03-04
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1385151-2
    ISSN 1573-7403 ; 1386-341X
    ISSN (online) 1573-7403
    ISSN 1386-341X
    DOI 10.1007/s11102-023-01301-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Adrenal Cushing's Syndrome Treated With Preoperative Osilodrostat and Adrenalectomy.

    Malik, Risha B / Ben-Shlomo, Anat

    AACE clinical case reports

    2022  Volume 8, Issue 6, Page(s) 267–270

    Abstract: Background/objective: Reducing severity of Cushing's syndrome caused by an adrenal adenoma (adrenal Cushing's syndrome [ACS]) might decrease morbidity and mortality risk in adrenalectomy. We used off-label osilodrostat, approved in the United States for ...

    Abstract Background/objective: Reducing severity of Cushing's syndrome caused by an adrenal adenoma (adrenal Cushing's syndrome [ACS]) might decrease morbidity and mortality risk in adrenalectomy. We used off-label osilodrostat, approved in the United States for pituitary Cushing's disease, to reduce cortisol levels and disease severity before adrenalectomy 3 weeks later.
    Case report: A 48-year-old woman with a 6-year history of obesity, depression, and anxiety and 3-year history of diabetes and hypertension was admitted with vomiting and lumbar back pain. Facial plethora and hirsutism, posterior cervicothoracic fat pad, and truncal obesity coupled with morning serum cortisol >13 μg/dL after 1 mg oral dexamethasone suppression, urinary free cortisol 1324 μg/24hr (4.0-50.0 μg/24 h), and adrenocorticotropin <5 pg/mL (6-50 pg/mL) confirmed ACS. Computed tomography with contrast revealed a 3.4-cm right adrenal mass. Osilodrostat 2 mg twice daily initiated at discharge was increased to 4 mg twice daily on day 6. Three days later, she reported nausea, vomiting, and fatigue. Despite 7.2 μg/dL morning cortisol, adrenal insufficiency was suspected; osilodrostat was reduced to 2 mg twice daily and maintenance oral hydrocortisone 20 mg daily was added with symptom resolution. Prior to adrenalectomy, morning cortisol was 5.1 μg/dL, fasting glucose was 122 mg/dL, and she self-discontinued diabetes medications. Hypertension remained unchanged (149/100 vs 151/94 mmHg). Adrenalectomy revealed a 3.4-cm focally pigmented adrenocortical adenoma.
    Discussion: Three-week treatment of overt ACS with off-label osilodrostat reduced cortisol and glucose levels before curative adrenalectomy. Abrupt cortisol reduction led to suspected adrenal insufficiency managed with maintenance hydrocortisone.
    Conclusion: Osilodrostat might help reduce ACS severity before adrenalectomy. Adrenal insufficiency is a risk but can be safely managed with hydrocortisone.
    Language English
    Publishing date 2022-10-10
    Publishing country United States
    Document type Case Reports
    ISSN 2376-0605
    ISSN (online) 2376-0605
    DOI 10.1016/j.aace.2022.10.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Generation of isogenic and homozygous MEN1 mutant cell lines from patient-derived iPSCs using CRISPR/Cas9.

    Even-Zohar, Naomi / Metin-Armagan, Derya / Ben-Shlomo, Anat / Sareen, Dhruv / Melmed, Shlomo

    Stem cell research

    2023  Volume 69, Page(s) 103124

    Abstract: MEN1, an autosomal dominant disorder caused by mutations in the tumor suppressor gene MEN1, manifests with co-occurrence of multiple endocrine/neuroendocrine neoplasms. An iPSC line derived from an index patient carrying the mutation c.1273C>T (p.Arg465*) ...

    Abstract MEN1, an autosomal dominant disorder caused by mutations in the tumor suppressor gene MEN1, manifests with co-occurrence of multiple endocrine/neuroendocrine neoplasms. An iPSC line derived from an index patient carrying the mutation c.1273C>T (p.Arg465*) was edited using a single multiplex CRISPR/Cas approach to create an isogenic control non-mutated line and a homozygous double mutant line. These cell lines will be useful for elucidating subcellular MEN1 pathophysiology and for screening to identify potential MEN1 therapeutic targets.
    MeSH term(s) Humans ; CRISPR-Cas Systems/genetics ; Induced Pluripotent Stem Cells/metabolism ; Mutation/genetics ; Cell Line ; Homozygote
    Language English
    Publishing date 2023-05-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2393143-7
    ISSN 1876-7753 ; 1873-5061
    ISSN (online) 1876-7753
    ISSN 1873-5061
    DOI 10.1016/j.scr.2023.103124
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Generation of isogenic and homozygous MEN1 mutant cell lines from patient-derived iPSCs using CRISPR/Cas9

    Naomi Even-Zohar / Derya Metin-Armagan / Anat Ben-Shlomo / Dhruv Sareen / Shlomo Melmed

    Stem Cell Research, Vol 69, Iss , Pp 103124- (2023)

    2023  

    Abstract: MEN1, an autosomal dominant disorder caused by mutations in the tumor suppressor gene MEN1, manifests with co-occurrence of multiple endocrine/neuroendocrine neoplasms. An iPSC line derived from an index patient carrying the mutation c.1273C>T (p.Arg465*) ...

    Abstract MEN1, an autosomal dominant disorder caused by mutations in the tumor suppressor gene MEN1, manifests with co-occurrence of multiple endocrine/neuroendocrine neoplasms. An iPSC line derived from an index patient carrying the mutation c.1273C>T (p.Arg465*) was edited using a single multiplex CRISPR/Cas approach to create an isogenic control non-mutated line and a homozygous double mutant line. These cell lines will be useful for elucidating subcellular MEN1 pathophysiology and for screening to identify potential MEN1 therapeutic targets.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Silent corticotroph adenomas.

    Ben-Shlomo, Anat / Cooper, Odelia

    Pituitary

    2018  Volume 21, Issue 2, Page(s) 183–193

    Abstract: Purpose: Silent corticotroph adenomas (SCAs) present clinically as non-functioning adenomas (NFAs) but are immunopositive for adrenocorticotrophic hormone (ACTH) without biochemical and clinical manifestation of hypercortisolism. Pathologic examination ... ...

    Abstract Purpose: Silent corticotroph adenomas (SCAs) present clinically as non-functioning adenomas (NFAs) but are immunopositive for adrenocorticotrophic hormone (ACTH) without biochemical and clinical manifestation of hypercortisolism. Pathologic examination of resected NFAs that demonstrate positive ACTH and/or TPIT expression confirms its corticotroph lineage. SCAs comprise up to 20% of NFAs and exhibit a higher rate of recurrence. Studies of molecular mechanisms have generated multiple hypotheses on SCA tumorigenesis, pathophysiology, and growth that as yet remain to be proven. An improved understanding of their pathologic and clinical characteristics is needed.
    Methods: A literature review was performed using PubMed to identify research reports and clinical case series on SCAs.
    Results: Up to date findings regarding epidemiology, mechanisms of pathogenesis, differentiation, progression, and growth, as well as clinical presentation, postoperative course, and treatment options for patients with SCAs are presented. Pooled results demonstrate that 25-40% of cases show cavernous sinus invasion, preoperative hypopituitarism, new-onset hypopituitarism, and recurrence.
    Conclusion: This article reviews the incidence, molecular pathology, and clinical behavior of these unique non-functioning pituitary corticotroph adenomas, and highlights the need for rigorous monitoring for recurrences and hypopituitarism in patients with SCAs.
    MeSH term(s) ACTH-Secreting Pituitary Adenoma/epidemiology ; ACTH-Secreting Pituitary Adenoma/pathology ; Adenoma/epidemiology ; Adenoma/pathology ; Female ; Humans ; Incidence ; Male ; Pituitary Neoplasms/epidemiology ; Pituitary Neoplasms/pathology
    Language English
    Publishing date 2018-01-17
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1385151-2
    ISSN 1573-7403 ; 1386-341X
    ISSN (online) 1573-7403
    ISSN 1386-341X
    DOI 10.1007/s11102-018-0864-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6139: Show issues Location:
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  8. Article ; Online: Foreword.

    Ben-Shlomo, Anat / Fleseriu, Maria

    Endocrinology and metabolism clinics of North America

    2017  Volume 46, Issue 1, Page(s) xiii–xv

    MeSH term(s) Bone Diseases/etiology ; Bone Diseases/genetics ; Bone and Bones/physiology ; Endocrinology/methods ; Endocrinology/trends ; Humans ; Osteocytes/physiology ; Review Literature as Topic
    Language English
    Publishing date 2017-02-01
    Publishing country United States
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 92116-6
    ISSN 1558-4410 ; 0889-8529
    ISSN (online) 1558-4410
    ISSN 0889-8529
    DOI 10.1016/j.ecl.2016.12.002
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  9. Article ; Online: Opioids and pituitary function: expert opinion.

    Gadelha, Mônica R / Karavitaki, Niki / Fudin, Jeffrey / Bettinger, Jeffrey J / Raff, Hershel / Ben-Shlomo, Anat

    Pituitary

    2022  Volume 25, Issue 1, Page(s) 52–63

    Abstract: Purpose: Opioids are highly addictive potent analgesics and anti-allodynics whose use has dramatically increased in recent decades. The precipitous rise in opioid dependency and opioid use disorder is an important public health challenge given the risks ...

    Abstract Purpose: Opioids are highly addictive potent analgesics and anti-allodynics whose use has dramatically increased in recent decades. The precipitous rise in opioid dependency and opioid use disorder is an important public health challenge given the risks for severely adverse health outcomes. The long-term opioid impact on hypothalamic-pituitary axes is particularly underappreciated among both endocrinologists and primary care physicians. We review the effects of opioids on hypothalamic-pituitary-target gland function and their implications for clinical practice.
    Methods: Experts in hypothalamic-pituitary disorders and opioid pharmacology reviewed recently published literature and considered strategies for diagnosing and managing these opioid-induced endocrine effects.
    Results: Opioid suppression of hypothalamic-pituitary axes can lead to hypogonadotropic hypogonadism, central adrenal insufficiency, and hyperprolactinemia. These important clinical manifestations are often under-estimated, poorly evaluated, and typically either untreated or not optimally managed. Data on biochemical testing for diagnosis and on the effect of hormone replacement in these patients is limited and prospective randomized controlled studies for guiding clinical practice are lacking.
    Conclusions: Patients should be informed about risks for hypogonadism, adrenal insufficiency, and hyperprolactinemia, and encouraged to report associated symptoms. Based on currently available evidence, we recommend clinical and biochemical evaluation for potential central adrenal insufficiency, central hypogonadism, and/or hyperprolactinemia in patients chronically treated with opioids as well as the use of current expert guidelines for the diagnosis and treatment of these conditions.
    MeSH term(s) Analgesics, Opioid/adverse effects ; Expert Testimony ; Humans ; Hyperprolactinemia ; Hypogonadism/chemically induced ; Hypogonadism/diagnosis ; Hypogonadism/drug therapy ; Prospective Studies
    Chemical Substances Analgesics, Opioid
    Language English
    Publishing date 2022-01-23
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1385151-2
    ISSN 1573-7403 ; 1386-341X
    ISSN (online) 1573-7403
    ISSN 1386-341X
    DOI 10.1007/s11102-021-01202-y
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  10. Article ; Online: Diabetes Mellitus.

    Ben-Shlomo, Anat / Fleseriu, Maria

    Endocrinology and metabolism clinics of North America

    2016  Volume 45, Issue 4, Page(s) xiii–xiv

    Language English
    Publishing date 2016-12
    Publishing country United States
    Document type Editorial
    ZDB-ID 92116-6
    ISSN 1558-4410 ; 0889-8529
    ISSN (online) 1558-4410
    ISSN 0889-8529
    DOI 10.1016/j.ecl.2016.09.002
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