Reviewing the most current literature, this text is a guide to medical decision-making regarding the diagnosis and treatment of patients with acromegaly. The scope of the book is comprehensive, covering all relevant facets of acromegaly, beginning with a history of the disorder and a review of the somatotrophic axis. Etiology is then discussed, including growth hormone secreting pituitary adenomas and other neuroendocrine tumors. Subsequent chapters present imaging modalities and diagnosis via radiology and clinical findings, as well as comorbid symptoms such as sleep apnea, musculoskeletal considerations, cardiovascular disorders, cancer and diabetes. Both medical and surgical management chapters describe each in detail, including radiotherapy, transsphenoidal surgery, somatostatin analogues and dopamine agonists. Concluding chapters present long-term follow-up as well as an extended selected patient story detailing life with the disease.
Bringing together the latest in endocrinologic and neurosurgical evidence and practice, Acromegaly will be the go-to resource for this challenging condition for years to come.
Author(s): Lewis S. Blevins Jr., Manish K. Aghi
Series: Contemporary Endocrinology
Publisher: Springer
Year: 2022
Language: English
Pages: 299
City: Cham
Preface
Preface
Contents
Chapter 1: The Molecular Biology and Pathology of Acromegaly
Introduction
Physiological Features of GH and IGF1
GH Physiology
IGF1 Physiology
Pathogenesis of Somatotroph Adenomas
Altered cAMP Signaling in Somatotroph Adenomas
Epigenetic Gene Silencing in Somatotroph Adenomas
Gene Overexpression in Somatotroph Adenomas
The Impact of Histopathological Features in Somatotroph Adenoma Management
Classification of Pituitary Adenomas
Somatotroph Adenoma Behavior Based on Pathological Features
Somatostatin Receptor Subtypes in Somatotroph Adenomas
Densely Granulated Vs Sparsely Granulated Somatotroph Adenomas
Dual-Staining Somatotroph Adenomas
Conclusions
References
Chapter 2: Growth Hormone-Releasing Hormone-Secreting Neuroendocrine Tumors
Introduction
Causes of Ectopic GHRH Production
Clinical Presentation of Ectopic GHRH Production
Diagnostic Workup of Ectopic GHRH Syndrome
Differential Diagnosis for NETs According to Site
Treatment Options for NETs
Prognosis
References
Chapter 3: Diagnosis of Acromegaly
Introduction
Physiology and Pathophysiology
Clinical Evaluation
Laboratory Testing
Imaging Studies
Approach to the Patient
Summary and Future Directions
References
Chapter 4: Imaging in Acromegaly
Anatomy
Imaging of the Pituitary Gland
Imaging of Tumors in the Gland
Microadenoma (Fig. 4.2)
Macroadenoma (Fig. 4.3)
Mimics (Fig. 4.5)
Systemic Findings of Acromegaly
Advances in Imaging of the Pituitary Gland
References
Chapter 5: The Clinical Presentation of Acromegaly
Background and Historical Perspective
Signs and Symptoms Prompting Diagnosis
Why Is There a Prolonged Delay in Diagnosis of Acromegaly, Given the Classic and Recognizable Clinical Features of this Disease?
What Are the Signs, Symptoms, and/or Reasons That Ultimately Lead to the Diagnosis?
What Signs and Symptoms Are Present at the Time of Diagnosis of Acromegaly?
Severity of the Disease
Diseases or Conditions with Clinical Overlap That May Mimic Acromegaly
Conclusions
References
Chapter 6: Sleep-Disordered Breathing in Acromegaly
Introduction
Obstructive Sleep Apnea
Definition and Diagnosis
Epidemiology
Symptoms and Risk Factors
Complications of Untreated Obstructive Sleep Apnea
Treatment of Obstructive Sleep Apnea
Central Sleep Apnea
Conclusion
References
Chapter 7: Cardiovascular Pathology in Acromegaly
Background
Pathogenesis
Acromegalic Cardiomyopathy
Hypertension
Coronary Arterial Disease
Arrythmias
Valvular Heart Disease
Diagnostic Evaluation
HTN
Cardiomyopathy
Arrythmias
Atherosclerotic Arterial Disease
Treatment of Cardiovascular Complications in Acromegaly
Transsphenoidal Surgery
Somatostatin Analogs
GHR Antagonists
Summary
References
Chapter 8: Diabetes Mellitus in Acromegaly
Epidemiology
Pathogenesis of Diabetes in Acromegaly
Excess Growth Hormone Leads to Increased Lipolysis
Increased Free Fatty Acids Interfere with Insulin Signaling Pathway
Increased Free Fatty Acids Promote Gluconeogenesis and Inhibit Glycolysis
Increased Expression of Pro-inflammatory Adipokines and Cytokines
β-Cell Dysfunction
Treatment
Choice of Therapy for Acromegaly
Treatment of Diabetes in Patients with Acromegaly
References
Chapter 9: Musculoskeletal Disorders of Acromegaly
References
Chapter 10: Acromegaly and Cancer
Acromegaly and Cancer Mortality
Disease Control and Cancer Mortality
Evidence for Involvement of the GH/IGF Axis in Cancer Development
Height and Cancer
GH/IGF-1 and Cancer in General Populations
GH/IGF Receptor Signaling in Cancer
Cancer Incidence in Acromegaly
Specific Cancer Incidence
Colon Cancer and Acromegaly
Thyroid Cancer and Acromegaly
Breast Cancer and Acromegaly
Prostate Cancer and Acromegaly
Other Cancers and Acromegaly
Summary of Cancer Incidence
Diabetes and Cancer Incidence in Acromegaly
Conclusion
References
Chapter 11: Mortality in Acromegaly
Introduction
GH and IGF-1 Levels as Predictors of Mortality
Hypopituitarism and Mortality
Radiotherapy and Mortality
Cancer Incidence, Mortality, and Acromegaly
Other Causes of Mortality
Cardiovascular Disease
Sleep Apnea
Diabetes
Conclusions
References
Chapter 12: An Overview of the Approach to the Management of Acromegaly
References
Chapter 13: Transsphenoidal Surgery for Acromegaly
Introduction
Diagnosis and Referral
Preoperative Management
Preoperative Imaging
Premedication
Operative Details: Transsphenoidal Surgery
Technique
Anesthetic Considerations
Positioning
Typical Surgical Steps
Morbidity of Transsphenoidal Surgery for Acromegaly
Vascular Complications
CSF Leak
Adenohypophysis Hormonal Deficits
Diabetes Insipidus and SIADH
Biochemical Outcomes and Management of Residual Tumor
References
Chapter 14: Stereotactic Radiosurgery and Radiation Therapy for Acromegaly
Introduction
Historical Perspective
Stereotactic Radiosurgery for Acromegaly
Patient Selection and Pre-SRS Evaluation
SRS Procedure
Endocrine Control
Complications from SRS
Repeated GKRS
Brief Cessation of Antisecretory Medication around the Time of SRS
Fractionated Radiation Therapy for Acromegaly
Endocrine Control
Complications Following FRT
Proton Beam Irradiation
Conclusions
References
Untitled
Chapter 15: Challenging Questions in the Management of Acromegaly in the Young
Introduction
Case Presentation
Challenging Clinical Management Questions
Conclusions
References
Chapter 16: Somatostatin Analogues in the Management of Patients with Acromegaly
References
Chapter 17: Use of Dopamine Agonists for Acromegaly
History of Acromegaly Treatment and Use of Dopamine Agonists
Mechanism of Action of Dopamine Agonists in Acromegaly
Acromegaly Treatment Algorithm
Dopamine Agonist Dosing in Acromegaly
Dopamine Agonists as Monotherapy
Dopamine Agonists as Combination Therapy
Dopamine Agonists and Somatostatin Analogues
Dopamine Agonists and Growth Hormone Receptor Antagonists
Side Effects of Dopamine Agonists
Summary
References
Chapter 18: Pegvisomant: Lessons Learned After 20 Years and Practical Recommendations of Its Use for the Treatment of Acromegaly
Introduction
Data from Clinical Studies of Pegvisomant
When to Consider Pegvisomant Therapy in Patients with Acromegaly
Initiation, Titration, and Maintenance of Pegvisomant Therapy
Precautions When Using Pegvisomant
Cost Considerations When Using Pegvisomant
Conclusion
References
Chapter 19: Perspectives on Combination Medical Therapy in the Treatment of Acromegaly
Introduction
Somatostatin Receptor Ligand and Dopamine Agonist Combination Treatment
Adverse Effects
Somatostatin Receptor Ligand and Growth Hormone Receptor Antagonist Combined Treatment
Long-Acting First-Generation Somatostatin Receptor Ligands and Pegvisomant (SRL-PEG)
Primary Efficacy Endpoints
Secondary Efficacy Endpoints
Adverse Effects
Pasireotide Long-Acting Release and Pegvisomant (PAS-PEG)
Primary Efficacy Endpoints
Secondary Efficacy Endpoints
Adverse Effects
Cabergoline and Pegvisomant Combination Treatment
Conclusion
References
Chapter 20: Long-Term Follow-up of Patients with Acromegaly
References
Chapter 21: Acromegaly from the Perspective of a Patient
A Perspective
The Diagnosis Story
The Surgery and Treatment
Pituitary World News
The Work and the Learning Continues
About Insights
On Family and Genetics
How Awareness Works: One Story
References
Index
