Genetic Steroid Disorders
- 2nd Edition - June 14, 2023
- Imprint: Academic Press
- Editors: Maria I. New, Bert O'Malley, Gary D. Hammer, Oksana Lekarev, Alan Parsa, Tony T. Yuen, Mone Zaidi, Ahmed Khattab, Anne MacDonald
- Language: English
- Paperback ISBN:9 7 8 - 0 - 1 2 - 8 2 1 4 2 4 - 4
- eBook ISBN:9 7 8 - 0 - 1 2 - 8 2 1 4 2 5 - 1
Genetic Steroid Disorders, Second Edition targets adult and pediatric endocrinologists, clinical geneticists, genetic counselors, reproductive endocrinologists, neonat… Read more
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Request a sales quoteGenetic Steroid Disorders, Second Edition targets adult and pediatric endocrinologists, clinical geneticists, genetic counselors, reproductive endocrinologists, neonatologists, urologists, and psychoendocrinologists. It is designed to assist these specialists in the diagnosis and treatment of steroid disorders. This revision includes a new chapter on "Gonadotropins, Obesity and Bone" and new research on non-invasive prenatal diagnosis with cell-free DNA. Chapters are thoroughly updated covering steroid disorders, the genetic bases for the disorder and case presentations, This definitive reference belongs in every medical library!
- Presents a comprehensive, translational look at all aspects of genetic steroid disorders in one reference work
- Provides a common language for endocrinologists, geneticists, molecular pathologists, and genetic counselors to discuss and diagnose genetic steroid disorders Saves clinicians and researchers time in quickly accessing the very latest details on genetic tests and diagnoses as opposed to searching through thousands of journal articles
- Highlights significant discoveries with clinical relevance, presenting insight into which medications to use based on the genetic makeup of a patient
- Teaches the best strategies and most effective use of genetic information in the patient counseling setting
Adult and pediatric endocrinologists, academic and clinical researchers in endocrinology and clinical genetics, geneticists, genetic counselors, and psychoendocrinologists; Psychoneuroendocrinologists will likely be uniquely interested in this as well as urologists and pediatric surgeons who deal with intersex patients, Clinical geneticists and genetic counselors
- Cover image
- Title page
- Table of Contents
- Copyright
- Dedication
- List of contributors
- Preface
- Chapter 1. Introduction
- References
- Chapter 2. Adrenal development
- Abstract
- Introduction
- Adrenal organogenesis
- Molecular mechanisms that regulate adrenal development
- Human adrenal development
- Adrenal disorders
- Secondary adrenal insufficiency
- Primary adrenal insufficiency
- Primary adrenal hypoplasia
- References
- Chapter 3A. Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency
- Abstract
- Introduction
- Endocrine function of the adrenal cortex
- The adrenal cortex as two glands
- Pathogenesis of 21-hydroxylase-deficiency
- Classical congenital adrenal hyperplasia
- Nonclassical congenital adrenal hyperplasia
- Postnatal diagnosis
- Molecular genetics of CYP21A2
- Molecular mechanisms creating CYP21A2 genetic defects
- Clinical features
- Treatment
- Prenatal diagnosis and treatment
- References
- Chapter 3B. Steroid 11β-hydroxylase deficiency and related disorders
- Abstract
- Biochemistry of adrenal steroid biosynthesis
- Genetics of steroid 11β-hydroxylase isozymes
- Steroid 11β-hydroxylase deficiency
- Aldosterone synthase (corticosterone methyloxidase) deficiency
- Glucocorticoid-suppressible hyperaldosteronism
- Acknowledgments
- References
- Chapter 3C. 3β-Hydroxysteroid dehydrogenase deficiency
- Abstract
- The 3β-HSD family: amino acid sequences and activities
- Epidemiology
- Clinical forms
- Biological diagnosis
- Molecular diagnosis
- Relationship between genotype and phenotype of patients
- Puberty and fertility
- Structure–function relationship
- Treatment
- References
- Chapter 3D. Genetic deficiencies of cytochrome P450c17 (CYP17A1) combined 17-hydroxylase/17,20-lyase deficiency and isolated 17,20-lyase deficiency
- Abstract
- Structure of the gene and mapping in human genome
- Genetic defects—mutation
- Hormonal abnormalities
- Diagnosis
- Epidemiology
- Ethnic diversity and clusters of the defect
- Psychoendocrine abnormalities resulting from the enzymatic defect
- Treatment: medical and surgical
- Long-range outcome medical psychological (gender, cognition)
- Life careers
- Prismatic cases
- Prenatal diagnosis and treatment
- References
- Chapter 4A. The history of prenatal diagnosis of congenital adrenal hyperplasia
- Abstract
- Introduction
- Hormonal measurements in amniotic fluid
- Molecular genetics
- Dexamethasone treatment and controversy
- Noninvasive prenatal diagnosis
- Fetal sex determination
- New directions
- Summary
- References
- Chapter 4B. Contemporary prenatal genetic diagnosis for congenital adrenal hyperplasia: preimplantation genetic testing and maternal cell-free DNA
- Abstract
- Historical overview
- Preconception ethnicity-based carrier screening to identify couples at risk for offspring with autosomal recessive disorders
- Panethnic expanded carrier screening
- Selection of embryos by preimplantation genetic testing
- Prenatal diagnosis of CAH by cell-free DNA in maternal blood
- References
- Chapter 5. The impact of genetic steroid disorders on human fertility
- Abstract
- Introduction
- Adrenal steroid enzyme deficiencies
- Steroidogenic acute regulatory protein
- 3-β dehydrogenase deficiency
- 11-β hydroxylase deficiency
- 17-α hydroxylase deficiency
- Gonadal steroid enzyme defects
- Conclusion
- References
- Chapter 6. Atypical genitalia in the newborn
- Abstract
- Introduction
- Typical sex determination and differentiation (Table 6.2)
- Differences of sex development
- Work-up of newborns with atypical genitalia
- Differential diagnosis
- Sex of rearing
- Parents and caregivers of children with atypical genitalia
- Surgery and fertility
- Summary
- References
- Chapter 7. Growth hormone treatment in children with congenital adrenal hyperplasia
- Abstract
- Introduction
- Adult height in congenital adrenal hyperplasia
- Factors affecting adult height in congenital adrenal hyperplasia
- Studies with growth hormone treatment to improve adult height in congenital adrenal hyperplasia
- Conclusion
- References
- Chapter 8. Bone mineral density and skeletal outcomes in congenital adrenal hyperplasia
- Abstract
- Introduction
- Bone physiology and biology
- Effects of glucocorticoids on bone cells
- Effects of adrenal androgens and sex steroids on bone
- Bone mineral density and other skeletal outcomes in individuals with congenital adrenal hyperplasia
- Fracture risk in congenital adrenal hyperplasia
- Bone turnover markers in congenital adrenal hyperplasia
- Relationship between bone mineral density and glucocorticoid treatment
- Summary
- References
- Chapter 9. Treatment and outcome of congenital adrenal hyperplasia: current reconstructive surgery
- Abstract
- Preoperative evaluation
- Endoscopy
- Surgical technique
- Clitoroplasty
- Labioplasty
- Vaginoplasty
- Outcomes
- References
- Chapter 10. Psychoendocrinology of congenital adrenal hyperplasia
- Abstract
- Introduction
- Gender
- General cognitive development
- Psychiatric outcome
- Sexuality
- Quality of life
- Implications for the organization of health services for CAH
- A final word
- References
- Chapter 11. Disorders in the initial steps in steroidogenesis
- Abstract
- Intracellular cholesterol trafficking
- Disorders of intracellular cholesterol trafficking
- Mitochondrial cholesterol import and the acute regulation of steroidogenesis
- References
- Chapter 12. P450 oxidoreductase deficiency
- Abstract
- Introduction
- The biological function of P450 oxidoreductase
- Clinical spectrum of P450 oxidoreductase deficiency
- The steroid metabolome of P450 oxidoreductase deficiency and diagnostic pitfalls
- P450 oxidoreductase structure to function correlations
- P450 oxidoreductase deficiency and skeletal malformations
- P450 oxidoreductase and drug metabolism
- Regulation of P450 oxidoreductase gene expression
- Conclusions and perspectives
- Acknowledgments
- References
- Chapter 13. Aromatase in human physiology and pathology: implications of human aromatase deficiency
- Abstract
- Introduction
- Significance of aromatase enzyme activity in human physiology
- Aromatase deficiency: clinical aspects
- Female phenotype
- Male phenotype
- Comments and conclusion
- References
- Chapter 14A. The genetics of ovotesticular differences of sex development
- Abstract
- Introduction
- Phenotypic features of OT-DSD
- Genotypes of OT-DSD
- Animal models
- Conclusion
- References
- Chapter 14B. 46,XY differences of sex development (DSD) due to 17β-hydroxysteroid dehydrogenase type 3 deficiency
- Abstract
- Introduction
- Epidemiology
- Clinical data in 46,XY individuals
- Biochemical diagnosis
- Molecular findings
- Clinical data in 46,XX individuals
- Histological aspects, gonadal tumor risk and infertility
- Medical management
- Gender role
- Conclusion
- Disclosure summary
- Funding information
- References
- Chapter 14C. Spectrum of activation and inactivation of gene for the luteinizing hormone chorionic gonadotrophin receptor
- Abstract
- Introduction
- Leydig cell hypoplasia (LCH) in 46,XY DSD
- Testotoxicosis or familial male-limited precocious puberty
- Case presentation
- Summary
- References
- Chapter 15. Steroid 5α-reductase 2 deficiency
- Abstract
- Introduction
- The enzymatic reaction
- Role of dihydrotestosterone in androgen physiology
- Why dihydrotestosterone?
- Role of dihydrotestosterone in male sexual development
- Steroid 5α-reductase 2 deficiency
- Clinical features in 46,XY subjects
- 5α-Reductase 2 deficiency and male gender role behavior
- Clinical features in 46,XX subjects
- Endocrine features in 46,XY subjects
- Diagnosis
- Molecular genetics
- Management
- Summary
- References
- Chapter 16. Androgen insensitivity syndrome
- Abstract
- Introduction
- Androgen action: structure and function of the androgen receptor
- Clinical features of androgen insensitivity syndrome
- Diagnosis of androgen insensitivity syndrome
- Phenotype–genotype correlations of androgen receptor mutations
- Sex of rearing
- Conclusion
- References
- Chapter 17. The Persistent Müllerian Duct Syndrome
- Abstract
- Introduction
- Anti-Müllerian hormone and the Müllerian duct: the basics
- The patient with Persistent Müllerian Duct Syndrome
- Differential diagnosis
- AMH gene mutations
- AMH receptor mutations
- Unexplained and noncharacterized persistent Müllerian duct syndrome
- References
- Chapter 18A. Clinical diagnosis and treatment of apparent mineralocorticoid excess
- Abstract
- Background
- Molecular genetics
- Clinical presentation
- Diagnosis
- Treatment
- Summary
- References
- Chapter 18B. The history, biology, and pathophysiology of apparent mineralocorticoid excess
- Abstract
- Sources of funding
- References
- Chapter 19. Primary aldosteronism: where are we now?
- Abstract
- Background
- A decade ago
- What is new? The decade to 2016
- What is really new?
- Prevalence and public health
- Stop press
- References
- Chapter 20. Nuclear receptors and coactivators
- Abstract
- Introduction
- Common attributes of coactivators
- Coactivators function as dynamic, multisubunit protein complexes
- Coactivators coordinately regulate broad gene expression programs in furtherance of distinct physiological goals
- Coactivators as drug targets
- Conclusions
- Acknowlegments
- References
- Chapter 21. Genetics of adrenal tumors
- Abstract
- Introduction
- Molecular genetics of syndromes with adrenal manifestations
- Molecular genetics of sporadic adrenocortical tumors
- References
- Chapter 22. Genetic factors in Cushing disease pathogenesis
- Abstract
- Introduction
- Pituitary corticotroph tumors
- Animal models
- References
- Chapter 23. Debates and controversies in genetic steroid disorders
- Abstract
- Controversy no. 1: prenatal treatment of virilizing congenital adrenal hyperplasia
- Controversy no. 2: genital surgery
- Controversy no. 3: growth enhancement
- References
- Chapter 24. Geographical endocrinology of genetic steroid disorders
- Abstract
- Introduction
- Epidemiology—screening data
- Genetic studies in various ethnic groups
- Lessons learned from “Consanguineous Populations”
- Carrier frequency of CAH in the general population
- Heterozygote advantage in CAH caused by 21OHD
- Summary
- References
- Chapter 25A. Animal models of adrenal genetic disorders
- Abstract
- Introduction
- Mouse models for congenital adrenal hypoplasia
- Mouse models for familial glucocorticoid deficiency (ACTH resistance syndromes)
- Mouse models for congenital adrenal hyperplasia
- Mouse models of congenital lipoid adrenal hyperplasia
- Genetically modified mouse models displaying an adrenal tumor phenotype
- Mouse models with targeted deletions inducing adrenal tumors
- References
- Chapter 25B. Steroidogenesis across species: aldo keto reductases in marsupials, fish and humans
- Abstract
- Role of androgens in fetal male differentiation
- Sexual determination and sexual differentiation
- The “classic” pathway of androgen biosynthesis
- The alternative “backdoor” pathway of androgen synthesis
- Aldo keto reductases and steroidogenesis
- Significance for sexual development
- AKR1C2 mutations show that the backdoor pathway is essential in humans
- Activities of the human AKR1C2 and AKR1C4 variants
- An unrelated individual confirms the key role of AKR1C2
- Modeling studies
- Sites of dihydrotestosterone synthesis
- Conclusions
- Acknowledgments
- References
- Index
- Edition: 2
- Published: June 14, 2023
- Imprint: Academic Press
- No. of pages: 468
- Language: English
- Paperback ISBN: 9780128214244
- eBook ISBN: 9780128214251
MN
Maria I. New
Dr. New received her Bachelors degree from Cornell University and her Doctor of Medicine degree from the University of Pennsylvania, where she was awarded the Distinguished Graduate Award.
She was Chairman of Pediatrics at Weill Medical College of Cornell University from 1980 to 2002 and Founding Director of its Children’s Clinical Research Center, where she also served as Chief of Pediatric Endocrinology from 1964 to 2002.
Dr. Maria New is Professor of Pediatrics, Professor of Genetics and Genomic Sciences, and Director of the Adrenal Steroid Disorders Program at Mount Sinai School of Medicine in New York City. She is also serving as Associate Dean for Clinical Research at the Florida International University Herbert Wertheim College of Medicine.
Former president of the Endocrine Society, Dr. New has edited or co-edited 12 medical textbooks, published more than 600 peer-reviewed papers and served as editor-in-chief of the Journal of Clinical Endocrinology and Metabolism. She has trained more than 100 young physician-scientists who have become chiefs of pediatric endocrinology and leaders in their field.
Her research, clinical work and teaching have taken her around the world. In 2005 and 2006, she led genetics research expeditions to Siberia in collaboration with the School of Medicine, St. Petersburg University, Russia.
Dr. New’s contributions have been recognized by her being selected as one of the few pediatricians in the National Academy of Sciences. She has received numerous honors including: the Robert H. Williams Distinguished Leadership Award; the Rhone-Poulenc Rorer Clinical Investigator Award from the American Endocrine Society; the 1996 Dale Medal, the highest award given by the British Endocrine Society; and the 2003 Fred Conrad Koch Award, the highest award given by the American Endocrine Society. In 2010, she received the Van Wyk Prize, the highest award given in pediatric endocrinology.
She has conducted pioneering research in the area of Congenital Adrenal Hyperplasia, a term used to describe a family of monogenic autosomal recessive disorders of steroidogenesis in which enzymatic defects result in impaired synthesis of cortisol by the adrenal cortex. In addition, Dr. New discovered a new form of hypertension, Apparent Mineralocorticoid Excess, which opened a new field of receptor biology. She was also the first to describe Dexamethasone-Suppressible Hyperaldosteronism, another form of low-renin hypertension. In 1999, she reported what may be the first example of a transcription factor defect in human beings.
Affiliations and expertise
Professor of Pediatrics, Professor of Genetics and Genomic Sciences, and Director, Adrenal Steroid Disorders Program, Mount Sinai School of Medicine, NY, USABO
Bert O'Malley
Dr. Bert O’Malley was first to discover that nuclear receptors are transcription factors that regulate specific mRNA production in target cells in response to intracellular hormones. He uncovered mechanisms for activating steroid receptors, and discovered the existence of ‘coactivators’, the ‘master genes of transcription that regulate normal and disease functions in reproduction, growth and metabolism. He developed the concept that small molecule drugs can regulate coactivators to produce therapeutic outcomes for diseases such as cancer and heart disease. Dr. O’Malley is the founding father of the field of Molecular Endocrinology and a member of the National Academy of Sciences, National Academy of Medicine, and National Academy of Inventors.
Affiliations and expertise
Thompson Distinguished Leadership Professor of MCB, Chancellor, Baylor College of Medicine, Houston, TX, USAGH
Gary D. Hammer
Gary Hammer, MD, PhD serves as Director of the Endocrine Oncology Program in the Rogel Cancer Center at the University of Michigan where he holds the Millie Schembechler Professorship in Adrenal Cancer. The Program is recognized as a worldwide leader in endocrine cancers - exemplified by its recent leadership role in the 3 recent endocrine cancer platforms of the NCI TCGA (papillary thyroid cancer, adrenocortical carcinoma and pheochromocytoma). A worldwide leader in the adrenal community, Dr. Hammer is best recognized for his research in adrenal homeostasis and neoplasia and for the treatment of adrenal cancer. Most recently, Dr. Hammer cofounded Millendo Inc., a biotechnology company focusing on therapies for adrenal cancer and other related endocrine diseases of steroid excess. Dr. Hammer has been the PI or Co-Investigator on several NIH and institutional funded grants.
Affiliations and expertise
Director of the Endocrine Oncology Program, Rogel Cancer Center, University of Michigan, MI, USAOL
Oksana Lekarev
Oksana Lekarev, DO is the Associate Medical Director of the Comprehensive Care Center for Congenital Adrenal Hyperplasia (CAH) at Weill Cornell Medicine, the first multi-disciplinary center of excellence in the United States dedicated to patients with CAH. She is also an Assistant Professor of Clinical Pediatrics at Weill Cornell Medicine and Assistant Attending Pediatrician at NewYork-Presbyterian/Weill Cornell Medical Center. Dr. Lekarev is board certified in Pediatric Endocrinology and Pediatrics. In addition to her expertise in CAH and adrenal steroid disorders, Dr. Lekarev’s areas of interest include disorders of growth, disorders of pubertal and sexual development, and thyroid disease. She has published a number of original and review articles in peer-reviewed journals and has presented her work at national and international meetings.
Affiliations and expertise
Associate Medical Director, Comprehensive Care Center for Congenital Adrenal Hyperplasia (CAH), Weill Cornell Medicine, NY, USAAP
Alan Parsa
Alan Parsa trained in adrenal steroid disorders under the mentorship of Dr. Maria New at Mount Sinai School of Medicine in Manhattan, New York. He then completed a fellowship training in endocrinology, diabetes, and metabolism at Cedars Sinai Medical Center in Los Angeles under the mentorship of Dr. Shlomo Melmed. He has authored over 20 peer-reviewed articles and book chapters on multiple topics including adrenal, pituitary, and thyroid conditions. He has a clinical practice in Honolulu and teaches at the John A. Burns medical school. In addition, he currently conducts several ongoing clinical trials.
Affiliations and expertise
Professor, University of Hawaii, John A Burns School of Medicine, Honolulu, Hawaii, USATY
Tony T. Yuen
Assistant Professor of Medicine, Endocrinology, Diabetes and Bone Disease, Department of Pediatrics, Mount Sinai Medical Center, New York, NY, USA
Affiliations and expertise
Assistant Professor, Department of Pediatrics, Mount Sinai Medical Center, New York, NY, USAMZ
Mone Zaidi
Professor Mone Zaidi, MBBS, PhD, MD, FRCP, FRCPI, FRCPath, MACP, MD (h.c.), DSc (h.c.)
Mone Zaidi graduated in medicine from King George’s Medical College, India, and trained clinically at the Hammersmith Hospital, London, under the tutelage of Professor Iain MacIntyre, FRS, who discovered calcitonin. After obtaining a PhD and MD from the University of London, Dr. Zaidi held appointments as Lecturer at the Royal Postgraduate Medical School and Senior Lecturer and Consultant at St. George’s Hospital Medical School for over 8 years. In 1999, he was recruited to Mount Sinai School of Medicine in New York as Professor of Medicine and Founding Director of The Mount Sinai Bone Program. Zaidi has made groundbreaking discoveries on the mechanisms of skeletal homeostasis in health and its dysregulation in common and rare diseases. These studies, spanning over 30 years, included the first description of calcium sensing in the osteoclast and the discovery that locally released nitric oxide acts to suppress bone cells. In 2003, Zaidi’s group published the first evidence for a pituitary–bone axis of medical significance, a breakthrough in physiology in which pituitary hormones could affect the skeleton directly. In a recent groundbreaking paper in Nature, he found that inhibiting FSH not only increased bone mass, but also reduced body fat–in essence, laying a firm foundation for a single anti-FSH agent to treat both osteoporosis and obesity. This corpus of work was selected by Nature Medicine as one of eight “Notable Advances” in biomedicine for 2017, and was editorialized widely in the scientific and lay press, including New York Times. Constituting a total of over 409 publications in quality journals, including Cell, Nature and PNAS, Zaidi’s research has been funded continuously by the U.S. National Institutes of Health. He has been bestowed upon by many honors, such as his election to the Association of American Physicians, the Interurban Clinical Club (established by Sir William Osler in 1905) of which he is President, the Practitioners’ Society (the oldest medical society in the U.S.) and the Association of Professors of Medicine. Zaidi was made Master of the American College of Physicians, received the Harrington Scholar–Innovator Award, was elected as Fellow of the American Association of Advancement of Science, and is recipient of three honorary doctorates.
Affiliations and expertise
Professor, Icahn School of Medicine at Mount Sinai, NY, USAAK
Ahmed Khattab
Ahmed Khattab, MD, received his medical degree for the University of Cairo and did a Fellowship in Pediatric Endocrinology at Mount Sinai Hospital in New York. His clinical interests include autoimmune hypothyroidism, congenital adrenal hyperplasia, congenital hypothyroidism, delayed puberty, disorders of the adrenal, ovary and testis, growth failure, hypogonadotropic hypogonadism, obesity, and precocious puberty. Dr. Khattab's research involves evolving techniques for earlier prenatal diagnosis of steroidogenic disorders and innovative protocols for treating the growth disorders associated with genetic disorders of adrenal and gonadal steroidogenesis.
Affiliations and expertise
Doctor, Department of Pediatrics, Robert Wood Johnson University Hospital, New Brunswick, New Jersey, USAAM
Anne MacDonald
Affiliations and expertise
Anne McDonald, Academic Research Manager, Center for Translational Research and Pharmacology, Department of Pharmacology, Icahn School of Medicine, Mount Sinai, New York, USA.Read Genetic Steroid Disorders on ScienceDirect