Gigantism and Acromegaly

1st Edition - June 1, 2021
Editor: Constantine A. Stratakis
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 1 4 5 3 7 - 1
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 1 4 5 3 8 - 8

Gigantism and Acromegaly brings together pituitary experts, taking readers from bench research, to genetic analysis, clinical analysis, and new therapeutic approaches. This book… Read more

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Gigantism and Acromegaly brings together pituitary experts, taking readers from bench research, to genetic analysis, clinical analysis, and new therapeutic approaches. This book serves as a reference for growth hormone over-secretion and its diagnosis and treatment for endocrinologists, pediatricians, internists, and neurosurgeons, and for geneticists. Pharmaceutical companies may use it as a reference for drug development and research. Students, residents and fellows in medicine and endocrinology and genetics will also find it valuable as it provides a single up-to-date review of the molecular biology of gigantism and acromegaly as well as recommended approaches to evaluation and management.

Acromegaly is a rare pituitary disorder that slowly changes its adult victim’s appearance over time: larger hands and feet, bigger jaw, forehead, nose, and lips. Generally, a benign pituitary tumor is the cause and symptoms of acromegaly can vary from patient to patient, making a diagnosis difficult and prolonging suffering for years. Early detection is key in the management of acromegaly as the pathologic effects of increased growth hormone (GH) production are progressive and can be life-threatening as the result of associated cardiovascular, cerebrovascular, and respiratory disorders and malignancies.

Cover image
Title page
Table of Contents
Copyright
List of contributors
About the editor
An introduction to “Gigantism and Acromegaly: Genetics, Diagnosis, and Treatment”
Acknowledgments
Chapter 1. History of the identification of gigantism and acromegaly
Abstract
1.1 Historic times
1.2 First medical reports
1.3 The discovery of the role of growth hormone
1.4 The discovery of hypothalamic regulation
1.5 Syndromic forms of acromegaly
1.6 The contributions of genetics
1.7 Going toward a new face of acromegaly
1.8 Conclusion
References
Chapter 2. Pathology of pituitary growth hormone excess
Abstract
2.1 Introduction
2.2 Classification of pituitary pathology in growth hormone excess
2.3 Pituitary hyperplasias associated with growth hormone excess
2.4 Pituitary neuroendocrine tumors causing growth hormone excess
2.5 Clinical implications of pathologic classification
References
Chapter 3. Gigantism: clinical diagnosis and description
Abstract
3.1 Clinical diagnosis—general aspects
3.2 Clinical diagnosis—specific aspects
3.3 Conclusion
References
Chapter 4. Acromegaly: clinical description and diagnosis
Abstract
4.1 Introduction
4.2 General clinical manifestations
4.3 Mass effects of the tumor
4.4 Systemic effects of excess GHRH/GH/IGF-I
4.5 Differences in clinical manifestations based on clinicopathological findings
4.6 Pseudoacromegaly
4.7 Clinical description and diagnosis
4.8 Summary of the two cases
4.9 Conclusion
References
Chapter 5. GPR101, an orphan G-protein coupled receptor, with roles in growth, puberty, and possibly appetite regulation
Abstract
5.1 Introduction
5.2 Identification of GPR101 in X-LAG: is it the causative gene?
5.3 The GPR101 gene and protein: structure and expression
5.4 GPR101 possible ligands: GnRH-(1–5) and Rvd5n-3 DPA
5.5 Is GPR101 involved in other diseases?
Funding
References
Chapter 6. The role of the aryl hydrocarbon receptor interacting protein in pituitary tumorigenesis
Abstract
6.1 Introduction
6.2 AIP variants in FIPA
6.3 AIP variants in sporadic PitNETs
6.4 AIP variants associated with PitNETs
6.5 Physiological roles of the AIP protein
6.6 Pathophysiology of AIP LOF-associated pituitary tumorigenesis
6.7 Animal models of AIP loss-of-function
6.8 Clinical features
6.9 Histopathological and immunohistochemical features
6.10 Genetic testing and AIP variant characterization
6.11 Clinical screening and genetic counseling of AIP mutation carriers
6.12 Conclusions
References
Chapter 7. The 3PAs syndrome and succinate dehydrogenase deficiency in pituitary tumors
Abstract
7.1 Introduction
7.2 The role of SDH in physiology and disease
7.3 SDHx mutations in pituitary adenomas and a new syndromic association (3PAs)
7.4 Clinical and pathology characteristics of SDHx-deficient pituitary adenomas
7.5 Possible pathogenetic mechanism for pituitary adenomas development due to SDHx deficiency
7.6 Recommendation for diagnosis, follow-up, and screening in 3PAs with genetic alterations
7.7 Future therapeutic implications and final remarks
References
Chapter 8. CDKN1B (p27) defects leading to pituitary tumors
Abstract
8.1 Introduction
8.2 Structure, regulation, and function of p27
8.3 p27 and cancer
8.4 CDKN1B mutations and pituitary tumors
8.5 Conclusions
References
Chapter 9. Multiple endocrine neoplasia syndromes and somatotroph adenomas
Abstract
9.1 Introduction
9.2 Multiple endocrine neoplasia type 1
9.3 Tumorigenesis of pituitary adenomas in MEN1
9.4 Epidemiology and clinical characteristics of somatotroph adenomas in MEN1
9.5 Apparently sporadic somatotroph adenomas: when to think of MEN1
9.6 Screening and surveillance of pituitary tumors in MEN1
9.7 Treatment of somatotroph adenomas in MEN1
9.8 Somatotroph adenomas in multiple endocrine neoplasia type 2
9.9 Concluding remarks
References
Chapter 10. GNAS, McCune–Albright syndrome, and GH-producing tumors
Abstract
10.1 GNAS
10.2 Somatic activating mutations in GNAS: the McCune–Albright syndrome
10.3 GH-producing tumors and acromegaly
References
Chapter 11. Surgical management of growth hormone-secreting adenomas
Abstract
11.1 Introduction
11.2 History of surgical treatment of pituitary pathology
11.3 Approach to the sella
11.4 Pituitary adenoma dissection
11.5 Complications
11.6 Endocrine outcomes
11.7 Adjunct treatments
11.8 New technologies
11.9 Conclusions
References
Chapter 12. Medical management of pituitary gigantism and acromegaly
Abstract
12.1 Introduction
12.2 Summary
References
Chapter 13. GHRH-producing tumors and other neuroendocrine neoplasms associated with acromegaly and/or gigantism
Abstract
13.1 Introduction
13.2 Epidemiology and background
13.3 Clinical, radiological, and biochemical findings
13.4 Pathological diagnosis
13.5 Treatment
13.6 Prognosis
References
Chapter 14. Increased growth hormone secretion from lesions outside the anterior pituitary
Abstract
14.1 Introduction
14.2 Physiology of growth hormone secretion
14.3 Causes of abnormal pituitary function without pituitary tumors
14.4 Causes of increased growth hormone secretion without abnormal pituitary function
14.5 Conclusions
References
Index

Constantine A. Stratakis

Dr. Stratakis was named Scientific Director of the NICHD in 2011, after serving as Acting Scientific Director of the NICHD since 2009. He received his M.D. and Doctor of Medical Sciences degrees from the National and Capodistrian University of Athens. He did predoctoral work at the Unit of Endocrinology, Department of Experimental Pharmacology at the same University, and at Hospital Cochin, Paris, France, before joining the Developmental Endocrinology Branch of the then National Institute of Child Health & Human Development, first as a student, and then as a postdoctoral fellow in 1988. In 1990, he continued his post-graduate medical education at Georgetown University Medical School, Washington, D.C., where he finished a residency in pediatrics and two fellowships in pediatric endocrinology (as part of the NICHD/Georgetown training program) and in medical genetics and clinical dysmorphology. He is Board certified in pediatrics, pediatric endocrinology, and medical genetics. Dr. Stratakis identified the genes for Carney complex and Carney-Stratakis syndrome, and other genetic defects leading to adrenal and other tumors, and he and his laboratory have published extensively in the fields of pediatric inherited disorders and cancer genetics, and on other pediatric adrenal and pituitary disorders. He is the author of more than 300 publications and has served as a regular reviewer. He is the author or co-author of nearly 600 publications, and has served as a regular reviewer for more than 100 journals, including Science, Nature Genetics, and the New England Journal of Medicine; he is currently Deputy Editor of the Journal of Clinical Endocrinology & Metabolism, the leading journal in Endocrinology. He has been the recipient of the 1999 Pharmacia-Endocrine Society Award for Excellence in Published Clinical Research, and NIH Merit Awards, and named Visiting Professor in academic centers around the world. In 2009, he was awarded the Ernst Oppenheimer Award of the Endocrine Society.

Affiliations and expertise

Senior Investigator & Scientific Director (ret) Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA; Professor, Pediatrics, Athens, GR & Director, Human Genetics & Precision Medicine & DIGENIA, IMBB, FORTH, Heraklion & ASTREA Health, Athens, GR

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Gigantism and Acromegaly

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Constantine A. Stratakis