Pituitary Adenomas: The European Neuroendocrine Association’s Young Researcher Committee Overview

Description

Stemming from the ENEA Young Researcher Committee, this didactical book comprehensively discusses all aspects of pituitary adenomas, particularly the practical aspects arising in everyday clinical practice. Offering valuable tips, it serves as a guide for young trainee endocrinologists facing their first cases of pituitary adenomas. It also includes illustrative clinical cases of acromegaly, prolactinomas, Cushing’s disease, and TSHomas. In addition, a Questions & Answers section is available online. The mix of fresh enthusiasm and well-established expertise in the field provided by the editors and the committee they belong to make the book both solid and innovative, with an appropriate balance between the traditional knowledge and the most exciting innovations from recent or ongoing research. Written and edited by young researchers active in the field of neuroendocrinology, it is a valuable resource for anyone working or interested in the field. Preface Contents Contributors 1: Anatomy of the Pituitary Gland 1.1 Anatomy 1.2 Histology 1.2.1 Cell Types of the Adenohypophysis 1.3 Pathology 1.3.1 Pituitary Adenomas 1.3.1.1 Pit-1-Positive Tumors Somatotroph Adenomas Lactotroph Adenomas Thyrotroph Adenomas Monomorphous Plurihormonal Adenomas 1.3.1.2 Tpit-Positive Tumors Corticotroph Adenomas 1.3.1.3 SF-1-Positive Tumors Gonadotroph Adenomas 1.3.1.4 Polymorphous Plurihormonal Adenomas Plurihormonal Adenomas 1.3.1.5 Transcription Factor-Negative and Hormone-Negative Adenomas Null Cell Adenomas 1.3.2 Pituitary Carcinomas 1.3.3 Aggressive Pituitary Adenomas 1.4 Conclusion References 2: Physiology of the Pituitary Hormone Secretion 2.1 Introduction 2.2 Anterior Pituitary 2.2.1 Somatotrophs 2.2.1.1 Growth Hormone Releasing Hormone (GHRH) 2.2.1.2 Ghrelin (GHRL) 2.2.1.3 Somatostatin (SST) 2.2.1.4 Cortistatin (CST) 2.2.1.5 Neuronostatin (NST) 2.2.1.6 Kisspeptin (KISS1) 2.2.1.7 Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) 2.2.1.8 Melatonin (MT) 2.2.1.9 Thyrotropin-Releasing Hormone (TRH) 2.2.1.10 Neuropeptide Y (NPY) 2.2.1.11 Other Systemic/Potential Regulators 2.2.2 Lactotrophs 2.2.2.1 Dopamine (DA) 2.2.2.2 Thyrotropin Releasing Hormone (TRH) 2.2.2.3 Ghrelin (GHRL) 2.2.2.4 Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) 2.2.2.5 Melatonin (MT) 2.2.2.6 Somatostatin (SST) 2.2.2.7 Cortistatin (CST) 2.2.2.8 Other Systemic/Potential Regulators 2.2.3 Gonadotrophs 2.2.3.1 Gonadotropin-Releasing Hormone (GNRH) 2.2.3.2 Ghrelin (GHRL) 2.2.3.3 Somatostatin (SST) 2.2.3.4 Kisspeptins (KISS1) 2.2.3.5 Melatonin (MT) 2.2.3.6 Gonadotropin-Inhibitory Hormone (GnIH) 2.2.3.7 Neuropeptide-Y (NPY) 2.2.3.8 Other Systemic/Potential Regulators 2.2.4 Thyrotrophs 2.2.4.1 Thyrotropin-Releasing Hormone (TRH) 2.2.4.2 Somatostatin (SST) 2.2.4.3 Dopamine (DA) 2.2.4.4 Other Systemic/Potential Regulators 2.2.5 Corticotrophs 2.2.5.1 Corticotropin-Releasing Hormone (CRH) 2.2.5.2 Ghrelin (GHRL) 2.2.5.3 Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) 2.2.5.4 Vasopressin (AVP) 2.2.5.5 Somatostatin (SST) 2.2.5.6 Cortistatin (CST) 2.2.5.7 Other Systemic/Potential Regulators 2.3 Posterior Pituitary 2.3.1 Opioids 2.3.2 Glucocorticoids 2.3.3 Angiotensin II (AII) 2.3.4 Norepinephrine (NE) 2.3.5 Other Systemic/Potential Regulators 2.4 Pars Intermedia 2.4.1 DA, NPY, and γ-Aminobutyric Acid 2.4.2 Other Systemic/Potential Regulators 2.5 Conclusion References 3: Pathogenesis of Pituitary Adenomas 3.1 Introduction 3.2 Hypothalamic and Peripheral Feedback Regulatory Circuits 3.2.1 Hypothalamic Regulation 3.2.2 Negative Feedback Regulation 3.3 Signaling and Cellular Processes 3.3.1 EGF & EGFR 3.3.2 TGF-β 3.3.3 Cytokines 3.3.4 Hedgehog Pathway 3.3.5 Wnt Pathway 3.3.6 Hippo Pathway 3.3.7 Cadherins 3.3.8 Cell Cycle 3.3.9 PTTG 3.3.10 Senescence 3.4 Genetics of Sporadic Pituitary Tumors 3.4.1 Chromosome Instability 3.4.2 Mutations 3.4.3 GNAS 3.4.4 USP8 3.4.5 USP48 3.4.6 SF3B1 3.4.7 RAS-BRAF 3.4.8 TP53 3.4.9 Other 3.4.10 Noncoding RNAs 3.5 Conclusion References 4: Genetics of Pituitary Adenomas 4.1 Introduction 4.2 Epidemiology 4.3 Pathogenesis 4.3.1 Somatic Mutation 4.3.2 Germline Mutations 4.3.3 Mosaic Mutations 4.3.4 Epigenetic Mechanisms 4.4 Clinical Presentation 4.4.1 Local Symptoms 4.4.2 Hormonal Excess Symptoms 4.4.2.1 GH Excess 4.4.2.2 ACTH Excess 4.4.2.3 Hyperprolactinaemia 4.4.2.4 TSH Excess 4.4.2.5 LH/FSH Excess 4.4.3 Clinical Features Suggesting Genetic Background 4.4.4 Pituitary Adenomas Associated with Hereditary Diseases 4.4.4.1 Familial Isolated Pituitary Adenomas (FIPA) AIP GPR101 Duplication Other 4.4.4.2 Multiple Endocrine Neoplasia Type 1 (MEN1) 4.4.4.3 Multiple Endocrine Neoplasia Type 4 (MEN 4) 4.4.4.4 Multiple Endocrine Neoplasia Type 2 (MEN2) 4.4.4.5 Carney Complex 4.4.4.6 McCune-Albright Syndrome 4.4.4.7 The Three P Association (3 Pa) SDHx MYC-Associated Factor (MAX) 4.4.4.8 Neurofibromatosis 1 (NF1) 4.4.4.9 DICER1 Syndrome 4.5 Patients with Pituitary Adenomas 4.5.1 Somatotroph Adenoma 4.5.2 Corticotroph Adenoma 4.5.3 Lactotroph Adenoma 4.5.4 Thyrotrope Adenoma 4.5.5 Non-functioning Pituitary Adenoma/(Gonadotroph Adenoma and Null Cell Pituitary Adenoma) 4.6 Follow-Up and Prognosis 4.7 Further Considerations on Genetic Testing 4.8 Highlighted Definitions References 5: Acromegaly 5.1 Introduction 5.2 Epidemiology 5.3 Pathogenesis 5.3.1 Somatotroph Pituitary Adenoma 5.3.2 Mixed Somatotroph Adenoma 5.3.3 Genetic Syndromes Associated with Acromegaly 5.3.4 GH-Secreting Carcinomas 5.3.5 Extrapituitary Acromegaly 5.4 Clinical Presentation 5.4.1 The Dysmorphic Syndrome 5.4.2 Symptoms 5.4.2.1 Skin Changes 5.4.2.2 Bone Changes 5.4.2.3 Rheumatologic Comorbidity Peripheral Osteoarthritis Spinal Involvement 5.4.2.4 Neuropathies 5.4.2.5 Psychologic Consequences 5.4.2.6 Cardiovascular Manifestations Arterial Hypertension Cardiomyopathy Cardiac Valve Disease 5.4.2.7 Metabolic Complications 5.4.2.8 Respiratory Complications 5.4.2.9 Pituitary and Sellar Mass Effects 5.4.2.10 Neoplasia and Acromegaly 5.5 Diagnosis of Acromegaly 5.5.1 GH and IGF-I 5.5.2 Neuroimaging 5.5.3 Pituitary Assessment 5.5.4 Total Body Imaging 5.6 Management and Follow-Up 5.6.1 Neurosurgery 5.6.2 Radiating Techniques 5.6.3 Medical Treatment 5.6.3.1 Dopamine Agonists (DA) 5.6.3.2 Somatostatin Receptor Ligands (SRLs) 5.6.3.3 GH-Receptor Antagonists 5.6.4 Treatment Strategy 5.7 Prognosis 5.8 Conclusion 5.9 Learning Points References 6: Prolactinoma 6.1 Introduction 6.2 Epidemiology 6.3 Pathophysiology 6.4 Clinical Presentation 6.5 Diagnosis 6.6 Management 6.7 Peculiar Aspects 6.7.1 Prolactinoma in Pregnancy 6.7.2 Giant Prolactinoma 6.7.3 Malignant Prolactinomas 6.7.4 Inherited Prolactinomas 6.8 Prognosis References 7: Cushing’s Disease 7.1 Introduction 7.2 Epidemiology 7.3 Pathogenesis 7.4 Clinical Presentation 7.5 Diagnosis 7.5.1 Establishing the Diagnosis of Cushing’s Syndrome 7.5.2 Establishing the Etiology of CS 7.5.3 Localization of the ACTH Source 7.6 Management 7.6.1 Surgical Treatment 7.6.2 Radiotherapy 7.6.3 Bilateral Adrenalectomy 7.6.4 Medical Therapy 7.6.4.1 Steroidogenesis Inhibitors 7.6.4.2 Another Modality for Treating CS 7.6.4.3 Tumor-Directed Therapeutic Agents 7.6.5 Perioperative Management 7.7 Follow-Up 7.8 Prognosis 7.8.1 Mortality 7.8.2 Cardiovascular Risk and Metabolic Syndrome 7.8.3 Psychopathology and Cognition 7.8.4 Bone Metabolism 7.8.5 Quality of Life 7.8.6 Other Cortisol-Related Comorbidities 7.9 Summary and Conclusions References 8: TSH-oma 8.1 Introduction 8.2 Epidemiology 8.3 Pathogenesis 8.4 Clinical Presentation 8.5 Diagnosis 8.5.1 Dynamic Tests 8.5.2 Differential Diagnosis 8.5.3 Imaging Studies and Localization of the Tumor 8.6 Management 8.7 Follow-Up 8.8 Prognosis References 9: Nonfunctioning Pituitary Adenoma 9.1 Introduction 9.2 Epidemiology 9.3 Histopathological Classification 9.3.1 Subtypes of Nonfunctioning Pituitary Adenomas 9.3.1.1 Nonfunctioning Silent Gonadotroph Adenomas 9.3.1.2 Nonfunctioning/Silent Corticotroph Adenomas 9.3.1.3 Nonfunctioning/Silent Somatotroph Adenomas 9.3.1.4 Nonfunctioning/Silent Thyrotroph Adenomas 9.3.1.5 Nonfunctioning/Silent Lactotroph Adenomas 9.3.1.6 Null Cell Adenomas 9.3.1.7 Plurihormonal Pit-1-Positive 9.3.2 Nonfunctioning Pituitary Carcinomas 9.4 Pathophysiology 9.4.1 Genetics 9.4.2 Epigenetics 9.4.3 Intracellular Molecular Signaling Pathways 9.4.3.1 The Role of Notch Intracellular Signaling Pathway in the Pathophysiology of NFPAs 9.4.3.2 The Role of Wnt Intracellular Signaling Pathway in the Pathophysiology of NFPAs 9.5 Clinical Presentation 9.6 Diagnostic Evaluation 9.7 Differential Diagnosis 9.8 Treatment 9.8.1 Active Surveillance 9.8.2 Surgery 9.8.3 Radiotherapy (RT) 9.8.4 Medical Therapy 9.9 Quality of Life (QoL) and Mortality 9.10 Conclusion References 10: Clinical Case 1 10.1 Case Report 10.2 Differential Diagnosis 10.3 Diagnostic Aspects 10.4 Treatment 10.5 Follow-Up 10.6 Learning Points Questions and Answers References 11: Clinical Case 2 11.1 Case Report 11.2 Differential Diagnosis 11.3 Diagnostic Aspects 11.4 Treatment 11.5 Follow-Up 11.6 Learning Points Questions and Answers References 12: Clinical Case 3 12.1 Case Report 12.2 Differential Diagnosis 12.3 Diagnostic Aspects 12.4 Treatment 12.5 Follow-up 12.6 Learning Points Questions and Answers References 13: Clinical Case 4 13.1 Case Report 13.2 Differential Diagnosis 13.3 Diagnostic Aspects 13.3.1 Clinical Presentation 13.3.2 Hormonal Evaluation 13.3.3 Radiological Diagnosis 13.4 Treatment 13.4.1 Surgery 13.4.2 Radiotherapy 13.4.3 Medical Therapy 13.5 Follow-up 13.6 Learning Points Questions and Answers References 14: Questions and Answers 14.1 Questions 14.2 Answers