Polyendocrine Disorders and Endocrine Neoplastic Syndromes (Endocrinology)

Description

This comprehensive reference book is meant to support clinicians in the diagnosis and treatment of polyendocrine diseases and endocrine neoplastic syndromes.  Although a large majority of endocrine diseases present as sporadic cases, an increasing proportion can be identified as part of a polyendocrine or systemic syndrome. These include autoimmune endocrine  diseases, which may be part of autoimmune polyendocrine disorders (APS) or rare complex disorders such as POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) or IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndromes.  On the other hand, endocrine tumors may develop in a variety of clinical conditions, including multiple endocrine neoplasia (MEN) syndromes, syndromic diseases such as McCune Albright or Carney’s complex, or peculiar familial associations  such as pheochromocytoma/paraganglioma syndromes.  The book discusses the significant advances that have been made in the clinical and genetic characterization of such entities, with major implications in terms of diagnosis and clinical management  -  with special attention to emerging syndromes,  familial screening , multidisciplinarity and multimodal treatment.  This volume is intended for clinicians, residents, specialists and physicians involved in the diagnosis and treatment of affected patients, including specialists in endocrinology, internal medicine, oncology , genetics and imaging. https://doi.org/10.1007/978-3-319-89497-3 DOI: 10.1007/978-3-319-89497-3 Series Preface Volume Preface Contents About the Editors Contributors Part I: Polyendocrine Disorders in Autoimmune and Systemic Diseases 1 Autoimmune Polyendocrine Syndromes (APS) or Multiple Autoimmune Syndromes (MAS) Introduction Criteria for the Diagnosis of Autoimmune Diseases Classification of Autoimmune Diseases Natural History of Autoimmune Diseases Old Classification of APS New Classifications of APS/MAS Hypothesis on the Pathogenesis of APS/MAS APS/MAS-1 Historical Features Frequency and Epidemiology Animal Models of APS/MAS-1 Genetics of APS/MAS-1 Main Clinical Manifestations of APS/MAS-1 Chronic Mucocutaneous Candidiasis (CMC) Chronic Hypoparathyroidism (CH) Autoimmune Addison´s Disease (AAD) Minor Autoimmune Diseases Premature Ovarian Failure (POF) Autoimmune Gastritis (AG) Auto-Immune Thyroid Diseases (AITD) Type 1 Diabetes Mellitus (DM-1) Alopecia Areata (AA) Vitiligo Autoimmune Hepatitis (AH) Autoimmune Enteropathy (AE) Splenic Atrophy (SA) Pituitary Failure (PF) Renal Diseases Pulmonary Diseases (PD) Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) Vasculitis Ectodermal Dystrophy Cancer Other Rare Diseases Total Number of Diseases in the Italian Cohort of APS/MAS-1 Diseases of APS/MAS-1 and Related Autoantibodies New Diagnostic Criteria for APS/MAS-1 How to Manage Patients with ASP/MAS-1 When to Investigate for AIRE Gene Mutations Therapy APS/MAS-2 Historical Features Animal Models Genetics of APS/MAS-2 Frequency and Epidemiology of APS/MAS-2 Main Clinical Manifestations of APS/MAS-2 Autoimmune Addison´s Disease (AAD) Autoimmune Thyroid Diseases (AITD) Type 1 Diabetes Mellitus (DM-I) Combinations of the Three Major Diseases Incomplete or Subclinical Forms of APS/MAS-2 Minor Autoimmune Diseases Premature Ovarian Failure (POF) Autoimmune Gastritis (AG) Vitiligo Alopecia Celiac Disease Other Autoimmune Diseases Autoimmune Diseases and Autoantibodies in APS/MAS-2 Therapy APS/MAS-3 General Considerations Frequency of APS/MAS-3 A New Classification of APS/MAS-3 Genetics of APS/MAS-3 APS/MAS 3A: Association Between AITD and Other Autoimmune Endocrine Diseases AITD and DM-1 AITD and Hirata´s Disease (HD) AITD and Hypergonadotropic Hypogonadism (HH) AITD and Lymphocytic Adenohypophysitis (LAH) AITD and Lymphocytic Neurohypophysitis (LNH) AITD and Chronic Hypoparathyroidism (CH) AITD and Lymphocytic Mastopathy Incomplete APS/MAS 3A APS/MAS-3B: Association Between AITD and Other Autoimmune Diseases of the Digestive System AITD and Autoimmune Gastritis (AG) AITD and Pernicious Anemia (PA) AITD and Celiac Disease (CD) AITD and Autoimmune Hepatitis (AH) AITD and Primary Biliary Cholangitis (PBC) AITD and Primary Sclerosing Cholangitis (PSC) AITD and Autoimmune Pancreatitis (APa) AITD and Inflammatory Bowel Diseases (IBD) Incomplete APS/MAS-3B APS/MAS-3C: Association Between AITD and Autoimmune Diseases of the Skin, Nervous System, and Hemopoietic System AITD and Vitiligo AITD and Alopecia Areata (AA) AITD and Autoimmune Bullous Diseases AITD and Chronic Idiopathic Urticaria (CIU) AITD and Myasthenia Gravis AITD and Lambert-Eaton Syndrome (LES) AITD and Multiple Sclerosis AITD and Neuromyelitis Optica (NMO) AITD and Guillain-Barré Syndrome (GBS) AITD and Stiff-Man Syndrome (SMS) AITD and Autoimmune Cytopenias Incomplete APS/MAS-3C APS/MAS-3D: Association Between AITD and Autoimmune Rheumatic and Cardiac Diseases or Vasculitis AITD and Systemic Lupus Erythematosus (SLE) AITD and Rheumatoid Arthritis (RA) AITD and Systemic Scleroderma (SS) AITD and Mixed Connective Tissue Disease (MCTD) AITD and Sjögren´s Syndrome (SSj) AITD and Dermatomyositis/Polymyositis AITD and Anti-Phospholipid Syndrome AITD and Vasculitis AITD and Rheumatic Fever AITD and Autoimmune Myocardial Diseases Incomplete APS/MAS-3D Concluding Comments on APS/MAS-3 APS/MAS-4 Presentation of APS/MAS-4 IPEX Syndrome (Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked) Clinical Manifestations and Autoantibodies Pathology Therapy Poems Syndrome (Polyradiculoneuropathy, Organomegaly, Endocrinopathy, Monoclonal Plasma Cell Disorder, and Skin Changes) Diagnosis Therapy Conclusions References 2 The Natural History of APS1 Introduction Clinical Definition and Diagnostic Criteria The Major Components of APS-1 Chronic Mucocutaneous Candidiasis Hypoparathyroidism Primary Adrenal Insufficiency Other Endocrine Components Gastrointestinal Components Ectodermal Manifestations Other Components Nonclassical APS-1 Diagnostic Tools in APS-1 Cytokine Autoantibodies in APS-1 Natural Course Pathogenesis of APS-1 Concluding Remarks References 3 Genetics of Autoimmune Regulator (AIRE) and Clinical Implications in Childhood Introduction Genetics of Aire Aire Partners and Mechanism of Action Clinical Implications in Childhood Conclusion References 4 Autoantibodies in Autoimmune Polyendocrine Syndrome Introduction Autoimmune Polyglandular Syndrome Type 1 APS-1 Organ-Specific Autoantibodies Parathyroid Autoimmunity Adrenal Autoimmunity Chronic Mucocutaneous Candidiasis Ovarian Autoimmunity Other APS-1 Features Systemic Autoantibodies X-Linked Immunodysregulation Polyendocrinopathy Enteropathy Autoimmune Polyglandular Syndrome Type 2 Adrenal Autoimmunity Thyroid Autoimmunity Pancreatic Autoimmunity Conclusion Cross-References References 5 Genetic Heterogeneity in Adrenal Insufficiency Introduction Genetic Forms of Primary Adrenal Insufficiency Congenital Adrenal Hyperplasia 21OH-D CAH 11βOH-D CAH 17αOH-D CAH 3βHSD2-D CAH POR-D CAH StAR Deficiency or LCAH SCC-D CAH Adrenoleukodystrophy Adrenal Hypoplasia Congenita Familial Glucocorticoid Deficiency Allgrove Syndrome Aldosterone Synthase Deficiency Primary Generalized Glucocorticoid Resistance Type 1 Pseudohypoaldosteronism Genetic Forms of Secondary Adrenal Insufficiency Isolated ACTH Deficiency ACTH Deficiency in Combined Pituitary Hormonal Deficiency PROP1 HESX1 LHX3 LHX4 SOX3 GLI2 OTX2 RBM28 Conclusions References 6 Hypophysitis and Granulomatous Pituitary Lesions in Systemic Diseases Introduction Part I: Autoimmune Lymphocytic Hypophysitis (LYH) in Systemic Diseases LYH in Autoimmune Polyendocrine Syndromes (APS) Miscellaneous Part II: Hypophysitis in Systemic Diseases Granulomatous Hypophysitis Langerhans Cell Histiocytosis (LCH) and Other Histiocytic Diseases IgG4-Related Hypophysitis Part III: The Pituitary Gland in Cancer Patients and Immunotherapy-Related Hypophysitis Part IV: Infections and the Pituitary Bacterial Infections and Abscesses Specific Bacterial Infections Viral Infections Fungal and Parasitic Infections Conclusion Cross-References References 7 Rare Forms of Endocrine and Systemic Autoimmune Disorders Introduction IPEX (Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked) Syndrome Epidemiology and Demographics Etiopathogenesis and Antigen Targets Clinical Manifestations Pathological Features and Immunological Profile Diagnosis Management IPEX-Related Diseases: CD25 Deficiency and IPEX-Like Disease Due to STAT1 Mutations POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, Skin Changes) Syndrome Epidemiology and Demographics Pathogenesis Clinical Manifestations Treatment and Outcome Anti-Pit-1 Antibody Syndrome Epidemiology and Demographics Etiopathogenesis and Antigen Targets Clinical Manifestations Treatment IgG4-Related Disease Epidemiology and Demographics Etiopathogenesis and Antigen Targets Clinical and Histopathological Features IgG4-Related Thyroid Diseases Riedel´s Thyroiditis (RT) IgG4-Related Hashimoto Thyroiditis (HT) Graves´ Disease Related to Elevated Levels of IgG4 (IgG4-GD) IgG4-Related Hypophysitis IgG4-Related Endocrine Pancreas Disorders Treatment and Outcome ROHHADNET (Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, Neuroendocrine Tumor) Syndrome Epidemiology and Demographics Etiopathogenesis Clinical Manifestations Treatment and Outcome Conclusions Cross-References References Part II: Endocrine Tumors in Complex and Genetic Syndromes 8 Multiple Endocrine Neoplasia Type 1 Introduction The Story of MEN1 Genetic Diagnosis The MEN1 Molecular Diagnosis Limitations and Pitfalls of MEN1 Genetic Testing Phenocopies Pitfalls of MEN1 Sequencing Mosaicism of MEN1 Mutations The Contribution of Technological Improvements Identification of Sequence Variants and Classification Impact of MEN1 Variant Identification on Clinical Care Impact of the Classification on Clinical Care Positive Result: Identification of a PV or LPV in the MEN1 Gene Negative Result: No Variant Identification or Identification of a BV or LBV in the MEN1 Gene Current Classification Difficulties Understanding VUSs Reclassifying VUSs Impact of Genetics on Clinical Practice Impact of Genetics on Care of Index Cases Genetics Helps Identify MEN1 Patients Genetics Can Change the Surgical Strategy Primary Hyperparathyroidism Duodeno-Pancreatic Neuroendocrine Tumors Impact of Genetics on Care of Relatives Risk Stratification MEN1 and MEN Diseases Genotype-Phenotype Studies Intra-Familial Lesion Occurrences Impact of Genetics on Patient Outcomes Conclusion Cross-References References 9 Multiple Endocrine Neoplasia-Type 2 Introduction Classification of MEN2 Variants MEN2A MEN2B Features of the Familial Type of Medullary Thyroid Cancer Tumor Histology and Hormonal Secretion Calcitonin (Ct) The RET Proto-oncogene Clinical and Genetic Features of MEN2 MEN2A MTC Pheochromocytoma Hyperparathyroidism Cutaneous Lichen Amyloidosis (Notalgia) (CLA) Hirschsprung´s Disease MEN2B Isolated Familial MTC (FMTC) Role of RET Testing and Calcitonin Level Measurement for the Surgical Treatment of MTC in MEN2 MTC Surgery in the Index Case Preoperative Imaging Extent of Thyroid Surgery Surgery and Cure Rates Indications for Thyroid Surgery in Family Members Bearing RET Gene Mutations Impact of the RET Gene Mutation on MTC Prognosis and Postsurgical Follow-Up Remission and Recurrence Follow-Up of Patients with Residual or Recurrent MTC Treatment of MTC Recurrences Treatment of Pheochromocytoma in MEN2 Treatment of Hyperparathyroidism Conclusion References 10 Multiple Endocrine Neoplasia-Type 4 (MEN4) and Other MEN1-Like Syndromes Introduction MENX, a MEN1-Like Multi-tumor Syndrome in the Rat Adrenal Glands Pituitary Gland Thyroid Gland The CDKN1B Gene and the p27 Protein: Structure and Function The Role of p27 in Tumorigenesis Lessons Learned from Engineered Mouse Models The Discovery of MEN4, a Novel MEN Syndrome in Human Patients Conclusion References 11 Molecular Alterations of the cAMP Signaling Leading to Endocrine Tumors Introduction Brief Overview of the Physiology of the cAMP Signaling Pathway Cascade (Fig. 1) Molecular Alterations of G Protein-Coupled Receptors (GPCR) in Endocrine Tumors Molecular Alterations of G Proteins in Endocrine Tumors: Sporadic Tumors and the McCune-Albright Syndrome Molecular Alterations of Phosphodiesterases in Endocrine Tumors Molecular Alterations of the Protein Kinase A in Endocrine Tumors and the Carney Complex Conclusion References 12 Genetics of Pituitary Gigantism: Syndromic and Nonsyndromic Causes Introduction Nonsyndromic Pituitary Gigantism Familial Isolated Pituitary Adenomas (FIPA) X-Linked Acrogigantism (X-LAG) Genetically Negative Nonsyndromic Pituitary Gigantism Syndromic Pituitary Gigantism Multiple Endocrine Neoplasia Type 1 (MEN1) and MEN1-Like Syndromes Carney Complex (CNC) 3P Association - Pituitary Adenomas, Paragangliomas, and Pheochromocytomas (3PAs) McCune-Albright Syndrome (MAS) Conclusion Cross-References References 13 Pheochromocytomas, Paragangliomas, and Pituitary Adenomas (3PAs) and Succinate Dehydrogenase Defects Introduction Succinate Dehydrogenase Complex Genetics of SDHx Tumors Pheochromocytoma/Paraganglioma Pituitary Adenomas and the 3PAs Association Other Tumors Conclusions Cross-References References 14 Pheochromocytomas in Complex Genetic Disorders Introduction Genetics of Pheochromocytoma and Paraganglioma Syndromic Pheochromocytoma Von Hippel-Lindau Disease Neurofibromatosis Type 1 Multiple Endocrine Neoplasia Type 2 The Paraganglioma Syndromes, Type 1 to Type 5 Type 1 Paraganglioma Syndrome Type 2 Paraganglioma Syndrome Type 3 Paraganglioma Syndrome Type 4 Paraganglioma Syndrome Type 5 Paraganglioma Syndrome The Paraganglioma/Pheochromocytoma/Pituitary Syndrome Familial Non-syndromic Pheochromocytoma Familial Pheochromocytoma Associated with TMEM127 Gene Mutations Familial Pheochromocytoma Associated with MAX Gene Mutations New Pheochromocytoma-Predisposing Genes Conclusions Cross-References References 15 Hyperparathyroidism in Complex Genetic Disorders Introduction Familial Isolated Hyperparathyroidism Familial Hypocalciuric Hypercalcaemia Neonatal Severe Primary Hyperparathyroidism Multiple Endocrine Neoplasia Type 1 Multiple Endocrine Neoplasia Type 4 Multiple Endocrine Neoplasia Type 2A Hyperparathyroidism Jaw Tumor Syndrome Conclusions Cross-References References 16 Neuroendocrine Neoplasms (NENs) in Complex Genetic Disorders Introduction MEN1 Syndrome von Hippel-Lindau Disease Neurofibromatosis Type 1 Tuberous Sclerosis Complex Cross-References References Part III: Clinical Cases 17 McCune-Albright Syndrome in Clinical Practice Clinical Cases Discussion Acromegaly Precocious Puberty In Girls In Adult Women In Men Thyroid Adrenal Gland References 18 Carney Complex in Clinical Practice Introduction Clinical Case Description Discussion Conclusion Cross-References References 19 Multiple Endocrine Neoplasia Type 1 in Clinical Practice Introduction Clinical Case Presentation Discussion Conclusion Cross-References References 20 Coexistence of Endocrine Side Effects of Immunotherapy in Clinical Practice Introduction Clinical Case Description Discussion Conclusion Cross-References References 21 MEN2 in Clinical Practice Introduction Clinical Cases Presentation Discussion Conclusions Cross-References References Index