Diagnosis and Management of Pituitary Disorders (eBook)

Preface 6
Contents 8
Contributors 10
Color Plate 13
Molecular Pathogenesis of Pituitary Adenomas 16
CONTENTS 16
1. INTRODUCTION 16
2. ACTIVATION OF PROTOONCOGENES IN PITUITARY TUMORS 17
2.1. Genetic Abnormalities of Protooncogenes 18
2.2. Overexpression of Protooncogenes and Proliferative Signals 20
3. LOSS OF ANTIPROLIFERATIVE SIGNALS 22
3.1. Inactivating Mutations of Antiproliferative Signals 22
3.2. Downregulation of Antiproliferative Signals 24
4. CONCLUSIONS 26
REFERENCES 26
Pathology of Pituitary Adenomas 31
CONTENTS 31
1. INTRODUCTION 31
2. TYPES OF PITUITARY ADENOMAS 33
2.1. Prolactin- Producing Adenomas 33
2.2. GH-Producing Adenomas 35
2.3. TSH-Producing Adenomas 36
2.4. ACTH-Producing Adenomas 37
2.5. Gonadotropin-Producing Adenomas 38
2.6. Null Cell Adenomas 38
2.7. Plurihormonal Adenomas 39
2.8. Pituitary Carcinomas 39
2.9. Morphologic Prognostic Factors in Pituitary Adenomas 40
2.10. Morphological and Diagnostically Useful Characteristics of Pituitary Adenomas 40
3. PATHOLOGY OF OTHER SELLAR LESIONS 40
3.1. Tumors 40
3.2. Cystic Lesions with Sellar Location 48
3.3. Vascular Lesions 49
3.4. Inflammatory Conditions 49
REFERENCES 50
Endocrinologic Approach to the Evaluation of Sellar Masses 53
CONTENTS 53
1. INTRODUCTION 53
2. IDENTIFICATION OF A SELLAR MASS AS A PITUITARY ADENOMA BY ITS HORMONAL HYPERSECRETION 54
2.1. Types of Pituitary Adenomas 54
2.2. Clinical Evaluation of Hormonal Hypersecretion by Pituitary Adenomas 54
3. LABORATORY EVALUATION OF HORMONAL HYPERSECRETION BY PITUITARY ADENOMAS 55
4. CLINICAL VALUE OF IDENTIFYING PITUITARY ADENOMAS 56
5. EVALUATION OF HORMONAL DEFICIENCIES ASSOCIATED WITH A SELLAR MASS 57
6. SUMMARY 57
REFERENCES 57
Imaging of the Pituitary Gland, Sella, and Parasellar Region 59
CONTENTS 59
1. INTRODUCTION 59
2. ANATOMY 60
2.1. Sella Turcica 60
2.2. Pituitary Gland and Infundibulum 60
2.3. Cavernous Sinuses 62
3. IMAGING MODALITIES AND TECHNIQUES 63
3.1. Magnetic Resonance Imaging 63
3.2. Computed Tomography 63
4. NORMAL VARIATION IN IMAGING APPEARANCE OF THE PITUITARY GLAND 64
5. NEOPLASTIC LESIONS 64
5.1. Pituitary Adenoma 64
5.2. Craniopharyngioma 68
5.3. Germ Cell Tumors 71
5.4. Optic Pathway Glioma 75
5.5. Meningioma 76
5.6. Metastatic Disease 78
5.7. Schwannoma 83
5.8. Osseous Tumors 83
6. CONGENITAL AND BENIGN CYSTIC LESIONS 87
6.1. Tuber Cinereum Hamartoma 87
6.2. Rathke’s Cleft Cyst 87
6.3. Arachnoid Cyst 90
6.4. Dermoid Inclusion Cyst 90
6.5. Epidermoid Inclusion Cyst 90
6.6. Empty Sella 91
7. INFLAMMATORY AND INFECTIOUS LESIONS 91
7.1. Lymphocytic Hypophysitis 91
7.2. Granulomatous Hypophysitis 91
7.3. Tolosa–Hunt Syndrome 95
7.4. Pituitary Abscess 95
8. HEMORRHAGIC AND VASCULAR LESIONS 95
8.1. Pituitary Apoplexy and Infarction 95
8.2. Aneurysms 98
8.3. Cavernous Sinus Thrombosis 98
REFERENCES 101
Neuro-ophthalmology of Sellar Disease 106
CONTENTS 106
1. INTRODUCTION 107
2. ANATOMY OF THE OPTIC CHIASM AND THE PARASELLAR REGION 108
3. SIGNS AND SYMPTOMS OF SELLA AND PARASELLAR LESIONS 114
4. AFFERENT DYSFUNCTION 114
4.1. Central Acuity 115
4.2. Color Vision 116
4.3. Pupil 116
4.4. Funduscopy 119
4.5. Visual Field Testing 121
5. DIAGNOSTICALLY USEFUL CHARACTERISTICS OF VISUAL FIELD DEFECTS ASSOCIATED WITH CHIASMAL LESIONS 124
6. CORRELATION OF NEUROIMAGING TO VISUAL FIELD DEFECT 129
7. PROGNOSIS OF VISUAL FIELD DEFECTS PRODUCED BY CHIASMAL MASS LESIONS 130
7.1. Pseudo-Bitemporal Visual Field Defect 130
7.2. Ocular Motor Dysfunction in Patients with Chiasmal Lesions 131
7.3. See-saw Nystagmus 132
7.4. Visual Symptoms Experienced by Patients Who Develop Chiasmal Lesions 133
7.5. Pituitary Apoplexy 134
7.6. Role of the Neuro-ophthalmologist in Diagnosing and Managing Sellar Lesions 135
REFERENCES 136
Prolactinomas: Diagnosis and Management 138
CONTENTS 138
1. INTRODUCTION 139
2. CLINICAL PRESENTATION 139
3. OTHER CAUSES OF HYPERPROLACTINEMIA 141
3.1. Medications 142
3.2. Pituitary/Hypothalamic Disorders 143
3.3. Other Disorders 143
3.4. Macroprolactin 143
4. DIAGNOSTIC EVALUATION 144
5. DOPAMINE AGONIST THERAPY 144
6. TREATMENT WHEN FERTILITY IS THE GOAL 146
7. TREATMENT WHEN FERTILITY IS NOT AN ISSUE 148
8. IS MEDICAL THERAPY THE ONLY OPTION? 149
9. CAN DOPAMINE AGONIST THERAPY BE DISCONTINUED? 149
REFERENCES 150
Acromegaly: Pathogenesis, Natural History, and Diagnosis 154
CONTENTS 154
1. INTRODUCTION 155
2. CAUSES OF GH HYPERSCRETION 155
3. NATURAL HISTORY 156
4. CLINICAL CHARACTERISTICS 156
5. LABORATORY CONFIRMATION USING GH AND IGF-I MEASUREMENTS 158
6. ROLE OF OTHER DIAGNOSTIC TESTS 160
7. OTHER LABORATORY ABNORMALITIES AT DIAGNOSIS 161
8. FURTHER DIAGNOSTIC EVALUATION 161
9. SUMMARY 161
REFERENCES 162
Acromegaly: Medical Management 164
CONTENTS 164
1. INTRODUCTION 165
2. DOPAMINE AGONISTS 166
3. SOMATOSTATIN ANALOGS 167
3.1. Efficacy: GH and IGF-I Levels 168
3.2. Clinical and Metabolic Effects 169
3.3. Effects on Pituitary Tumor Size 170
3.4. Side Effects 171
3.5. Somatostatin Analogs in Clinical Development 172
4. GH RECEPTOR ANTAGONIST: PEGVISOMANT 172
4.1. Efficacy: Normalization of IGF-I Levels 172
4.2. Clinical, Metabolic, and Other Endocrine Effects 172
4.3. Safety and Tolerability 173
4.4. Effects on Tumor Size 174
5. CONCLUSION 174
REFERENCES 176
Acromegaly: Surgical Management 183
CONTENTS 183
1. INTRODUCTION 183
2. INDICATIONS FOR SURGERY 184
3. PREOPERATIVE EVALUATION 184
4. SURGICAL TECHNIQUES 185
5. SURGICAL OUTCOME 186
6. COMPLICATIONS 191
7. RECURRENCES 192
REFERENCES 195
Cushing’s Disease: Diagnostic Evaluation 199
CONTENTS 199
1. INTRODUCTION 199
2. SCREENING FOR CUSHING’S SYNDROME 200
2.1. Specific Signs and Symptoms 200
2.2. Clinical Diagnoses Associated with Hypercortisolism 201
3. DIAGNOSTIC TESTS 202
3.1. Urine Free Cortisol 202
3.2. Low-Dose Dexamethasone Suppression Test 203
3.3. Nocturnal Salivary Cortisol 204
4. DIFFERENTIAL DIAGNOSIS 205
4.1. Pathologic Hypercortisolism versus Physiologic Hypercortisolism 205
4.2. ACTH-Dependent versus ACTH-Independent Cushing’s Syndrome 207
4.3. Differentiation of the Pituitary and Ectopic ACTH-Dependent Cushing’s Syndrome 209
4.4. Search for the Occult Ectopic ACTH-Secreting Tumor 210
REFERENCES 211
Cushing’s Disease: Surgical Management 215
CONTENTS 215
1. INTRODUCTION 215
1.1. Incidence and Rationale for Treatment 215
1.2. Diagnosis of Cushing’s Disease and Pituitary Imaging 216
1.3. Imaging 217
1.4. Preoperative Medical Evaluation 217
2. SUCCESS RATE OF TRANSSPHENOIDAL SURGERY FOR CUSHING’S DISEASE 218
2.1. Introduction 218
2.2. Long-term Outcome in Contemporary Transsphenoidal Microsurgical Series for Cushing’s Disease 218
2.3. Selective Adenomectomy versus Hypophysectomy 222
2.4. New Pituitary Failure and Other Complications 222
2.5. Early Reoperations for Persistent Cushing’s Disease 222
3. ENDONASAL TRANSSPHENOIDAL SURGICAL TECHNIQUE 223
3.1. Introduction 223
3.2. Endonasal Approach, Sphenoidotomy and Sellar Bone Removal 223
3.3. Dural Opening and Tumor Removal 224
3.4. CSF Leak Repair and Closure 224
3.5. General Postoperative Care and Discharge 224
3.6. Postoperative Endocrine Management and Follow-up 225
4. PREDICTING LONG-TERM REMISSION AFTER TRANSSPHENOIDAL SURGERY 225
5. MANAGEMENT OF CUSHING’S DISEASE AFTER FAILED TRANSSPHENOIDAL SURGERY 226
6. NELSON’S SYNDROME—TREATMENT 228
7. SUMMARY 228
REFERENCES 228
Cushing’s Disease: Medical Management 234
CONTENTS 234
1. INTRODUCTION 234
2. ESTABLISHED TREATMENTS AND CHRONOLOGY 235
3. INHIBITORS OF STEROIDOGENESIS 238
3.1. Mitotane 238
3.2. Metyrapone 238
3.3. Trilostane 239
3.4. Ketoconazole 239
3.5. Etomidate 240
4. NEUROMODULATORY AGENTS 240
4.1. Dopamine Agonists 240
4.2. Somatostatin Analogs 241
4.3. Glucocorticoid Receptor Antagonists 241
5. PPAR LIGANDS 242
6. OTHER NEUROMODULATORY AGENTS 242
7. SUMMARY AND CONCLUSION 243
ACKNOWLEDGMENT 243
REFERENCES 243
Thyrotropin-secreting Pituitary Adenomas 248
CONTENTS 248
1. EPIDEMIOLOGY 249
2. MOLECULAR PATHOPHYSIOLOGY 249
3. CLINICAL PRESENTATION 252
4. CLINICAL EVALUATION 4.1. Differential Diagnosis 253
5. LABORATORY EVALUATION 255
5.1. Thyrotropin 255
5.2. Thyroid Hormone Action: Clinical Endpoints 257
5.3. Dynamic Testing of Thyroid Axis 257
5.4. Summary of Diagnostic Tests 258
6. RADIOGRAPHIC FEATURES 259
6.1. Somatostatin Analog Scintigraphy 265
6.2. Petrosal Sinus Sampling 265
7. TREATMENT 265
8. CRITERIA FOR CURE 271
9. CLINICAL OUTCOMES 271
10. CONCLUSION 272
ACKNOWLEDGMENTS 272
REFERENCES 272
Non-functioning Adenomas: Diagnosis and Treatment 282
CONTENTS 282
1. INTRODUCTION 282
2. CLINICAL PRESENTATION 284
3. DIAGNOSIS 286
4. TREATMENT OPTIONS 288
5. PATHOLOGY 295
6. FOLLOW-UP 296
7. CONCLUSION 296
REFERENCES 297
Pituitary Surgery: Techniques 300
CONTENTS 300
1. INTRODUCTION 300
2. TRANSSPHENOIDAL APPROACHES 301
2.1. Transnasal Approach 301
2.2. Sublabial Approach 305
2.3. Extended Transsphenoidal Approach 305
3. TRANSCRANIAL APPROACHES 306
3.1. Unilateral Subfrontal Approach 306
3.2. Pterional Approach 307
4. INDICATIONS FOR SURGERY 307
4.1. Nonfunctional Macroadenomas 308
4.2. Cushing’s Disease 308
4.3. Acromegaly 308
4.4. Prolactinoma 309
4.5. Pituitary Apoplexy 309
4.6. Cysts 309
4.7. Stalk and Hypothalmic Lesions 309
5. CHOICE OF APPROACH 310
6. REOPERATION 311
REFERENCES 311
Pituitary Surgery: Peri-operative Management 313
CONTENTS 313
1. INTRODUCTION 313
2. PRE-OPERATIVE AND POST-OPERATIVE ASSESSMENT AND MANAGEMENT 314
2.1. Question 1: What Is the Likely Nature of the Mass? 314
2.2. Question 2: Is There Any Mass Effect? 317
2.3. Question 3: Is There Any Evidence of Hormone Hypersecretion? 319
2.4. Question 4: Is There Evidence Of Pituitary Hypofunction? 321
3. DISORDERS OF WATER AND SALT METABOLISM IN THE POSTOPERATIVE PERIOD 325
REFERENCES 329
Radiation Therapy for Pituitary Adenomas 331
CONTENTS 331
1. INTRODUCTION 331
2. MODALITIES OF RADIATION THERAPY 332
2.1. GK Radiation Therapy 332
2.2. Linear Accelerator-Based SRS 333
2.3. Stereotactic Radiotherapy 333
2.4. Three-Dimensional Conformal Radiation Therapy 334
2.5. Proton Radiation Therapy 334
3. NONFUNCTIONING TUMORS 335
4. HORMONE-SECRETING TUMORS 337
4.1. Acromegaly 338
4.2. Cushing’s Disease 339
4.3. Prolactinoma 340
4.4. Other Functional Adenomas 341
5. RADIATION-RELATED ADVERSE EFFECTS 341
5.1. Hypopituitarism 341
5.2. Visual Pathway Injury 342
5.3. Other Cranial Nerve Deficits 343
5.4. Brain Necrosis 343
5.5. Second Tumors 344
5.6. Internal Carotid Artery Stenosis 344
6. CONCLUSION 345
REFERENCES 345
Lymphocytic Hypophysitis and Inflammatory Disease of the Pituitary 349
CONTENTS 349
1. DIFFERENTIAL DIAGNOSIS OF INFLAMMATORY DISEASE OF THE PITUITARY 1.1. Lymphocytic Hypophysitis 349
2. MANAGEMENT OF LH 355
REFERENCES 358
Pituitary Apoplexy 362
CONTENTS 362
1. INTRODUCTION 363
2. EPIDEMIOLOGY OF PITUITARY APOPLEXY 364
3. THE CLINICAL SYNDROME OF PITUITARY APOPLEXY 366
4. PATHOPHYSIOLOGY OF PITUITARY APOPLEXY AND REPORTED PREDISPOSING FACTORS 368
5. DIAGNOSIS OF PITUITARY APOPLEXY 371
6. STABILIZATION AND MEDICAL EVALUATION OF PATIENTS WITH PITUITARY APOPLEXY 373
7. ACUTE MANAGEMENT OF PITUITARY APOPLEXY 374
8. INTERMEDIATE AND LONG-TERM MANAGEMENT AFTER PITUITARY APOPLEXY 377
9. CONCLUSIONS 379
REFERENCES 379
Pituitary Tumors and Pregnancy 385
CONTENTS 385
1. ANTERIOR PITUITARY GLAND AND PREGNANCY 385
2. PROLACTINOMA 387
2.1. Effects of Pregnancy on Prolactinoma Growth 388
2.2. Effects of Hyperprolactinemia and Its Treatment on Pregnancy 389
2.3. Management of Prolactinoma in Pregnancy 391
3. ACROMEGALY 392
3.1. Diagnosis of Acromegaly During Pregnancy 392
3.2. Effects of Pregnancy on Tumor Size and Acromegaly 393
3.3. Effects of Acromegaly on the Pregnancy 393
3.4. Management of Acromegaly and Pregnancy 393
4. CUSHING’S SYNDROME 394
4.1. Diagnosis of Cushing’s Syndrome During Pregnancy 394
4.2. Effects of Cushing’s Syndrome on the Pregnancy 395
4.3. Management of Cushing’s Syndrome During Pregnancy 396
5. TSH-SECRETING TUMORS 396
6. CLINICALLY NONFUNCTIONING ADENOMAS 397
7. HYPOPITUITARISM 397
7.1. Lymphocytic Hypophysitis 398
7.2. Sheehan’s Syndrome 399
7.3. Synopsis 400
REFERENCES 400
Management of Pituitary Incidentalomas 407
CONTENTS 407
1. INTRODUCTION 408
2. PREVALENCE AND INCIDENCE 408
3. SPECIFIC PATHOLOGIC DISEASES 409
4. NATURAL HISTORY 412
5. SCREENING FOR ENDOCRINE DYSFUNCTION 413
6. APPROACH TO EVALUATION AND MANAGEMENT OF INCIDENTALOMAS 415
REFERENCES 416
Sellar and Pituitary Tumors in Children 418
CONTENTS 418
1. INTRODUCTION 419
2. CRANIOPHARYNGIOMAS 419
2.1. Epidemiology 420
2.2. Presentation 420
2.3. Diagnosis 421
2.4. Treatment and Outcome 422
2.5. Posttreatment Outcome 423
3. PITUITARY ADENOMAS 426
3.1. Prolactinomas 428
3.2. ACTH-Secreting Pituitary Adenomas 433
3.3. Other Pituitary Adenomas 437
4. SELLAR CYSTS 439
4.1. Rathke’s Cleft Cysts 439
4.2. Arachnoid Cysts 440
5. PARASELLAR TUMORS 441
5.1. Germ Cell Tumors 441
5.2. Hypothalamic Hamartomas 445
6. INFILTRATIVE PROCESSES 445
7. CONCLUSION 446
REFERENCES 446
Cystic Lesions of the Sella 452
CONTENTS 452
1. INTRODUCTION 452
2. CRANIOPHARYNGIOMA 453
3. RATHKE’S CLEFT CYST 459
4. CYSTIC PITUITARY ADENOMA 464
5. MENINGIOMA 466
6. ARACHNOID CYSTS 466
7. SPHENOID SINUS MUCOCELE 468
8. EPIDERMOID AND DERMOID 469
9. OTHER LESIONS 469
10. CONCLUSION 469
REFERENCES 470
Subject Index 474