Handbook of Diagnostic Endocrinology

Title-page_2021_Handbook-of-Diagnostic-Endocrinology......Page 1
Handbook of Diagnostic Endocrinology......Page 2
Copyright......Page 3
Dedications......Page 4
Contents......Page 5
List of Contributors......Page 12
Acknowledgments......Page 14
1 Maximizing the value of laboratory tests......Page 15
Interferences associated with mass spectrometry......Page 16
Hemolysis, lipemia, and icterus......Page 17
Matrix effects......Page 18
Tube wall......Page 19
Anticoagulants......Page 20
Separator gel......Page 21
Timing of sample collection......Page 22
Excess antigen interference (hook effect)......Page 23
Antibody specificity (cross-reactivity)......Page 24
Heterophile antibodies......Page 25
Human antianimal antibodies......Page 26
Human antimouse antibodies......Page 27
Rheumatoid factors......Page 28
Complement proteins......Page 29
Albumin......Page 30
Biotin......Page 31
Impact of biotin interference on diagnostic assays......Page 32
Detection of biotin interference......Page 34
Anti-ruthenium and anti-streptavidin antibody interference......Page 35
Physiological variation (intra-individual variation)......Page 36
Example 1—Is the statin working?......Page 37
Example 3—Sestamibi scan or surgical consult?......Page 38
Postanalytical errors......Page 39
Reference ranges, normal values, and desired results......Page 40
Sensitivity, specificity, and predictive value......Page 43
Receiver operating characteristic plot3......Page 47
Likelihood ratio......Page 48
Conclusion......Page 49
References......Page 50
Anterior pituitary......Page 60
Anterior pituitary hormone physiology and biochemistry......Page 61
Features of hypopituitarism......Page 63
Investigation of hypopituitarism......Page 64
Secretory pituitary tumors......Page 67
Prolactinomas......Page 68
Acromegaly......Page 70
Posterior pituitary......Page 71
Diabetes insipidus......Page 72
SIADH......Page 73
Conclusion......Page 74
References......Page 75
Suggested reading......Page 77
Physiology of the thyroid–pituitary–hypothalamic axis......Page 79
Metabolism......Page 82
Screening for thyroid dysfunction......Page 83
The serum TSH/FT4 relationship......Page 84
Effects of chronological age on thyroid test reference ranges......Page 85
Pregnancy......Page 86
Nonthyroidal illness......Page 87
Hepatic disorders......Page 89
Helpful clues to distinguish thyroid disease from nonthyroidal causes of abnormal hormone levels......Page 90
Hyperthyroidism......Page 91
Transient hyperthyroidism......Page 92
Primary hypothyroidism......Page 93
Neonatal hypothyroidism......Page 94
Screening for subclinical thyroid disease......Page 95
Thyroid-stimulating hormone (thyrotropin)......Page 96
Thyroid-stimulating hormone reference intervals......Page 97
Thyroid-stimulating hormone lower reference limits......Page 98
Elderly patients......Page 99
L-T4 replacement therapy......Page 100
Inappropriate thyroid-stimulating hormone secretion syndromes......Page 101
Thyrotropin-releasing hormone test......Page 102
Influence of methods of analysis on test results......Page 103
Normal range......Page 104
Normal range......Page 105
Free T3......Page 106
Analytical methods......Page 107
Analytical methods......Page 108
Interpretive hints when thyroid-stimulating hormone and FT4 results seem discrepant......Page 109
Further reading......Page 110
Adrenocortical insufficiency......Page 112
Clinical symptoms and signs of adrenocortical insufficiency......Page 115
Causes of adrenocortical insufficiency......Page 117
Patients presenting with Addisonian crisis......Page 120
Patients with suspected glucocorticoid deficiency who do not present acutely ill......Page 122
Adrenocorticotropic hormone stimulation tests......Page 123
The 1-h adrenocorticotropic hormone stimulation test......Page 124
Corticotropin-releasing hormone stimulation test......Page 125
Glucagon stimulation test......Page 126
Autoimmune Addison disease......Page 127
Congenital adrenal hyperplasia......Page 129
Adrenoleukodystrophy and adrenomyeloneuropathy......Page 134
Congenital adrenal hypoplasia......Page 135
Wolman disease......Page 136
Smith–Lemli–Opitz syndrome......Page 137
Clinical symptoms of glucocorticoid excess (Cushing syndrome)......Page 138
The differential diagnosis of glucocorticoid excess......Page 139
The biochemical diagnosis of glucocorticoid excess......Page 141
Plasma and salivary cortisol......Page 142
Overnight dexamethasone suppression test......Page 143
Low-dose dexamethasone-corticotropin-releasing hormone test......Page 144
Adrenocorticotropic hormone measurements......Page 145
Evaluation for adrenal tumors......Page 146
Adrenal tumors......Page 147
Biochemical evaluation of primary aldosteronism......Page 148
Clinical overview......Page 149
Von Hippel–Lindau disease......Page 150
Laboratory diagnosis of the pheochromocytoma/paraganglioma......Page 151
Urine catecholamines and metanephrines......Page 152
Plasma catecholamines and metanephrines......Page 153
Clonidine suppression test......Page 154
Neuroblastoma, ganglioneuroma, and ganglioneuroblastoma......Page 155
List of abbreviations......Page 156
References......Page 157
Prepubertal disorders......Page 166
Hirsutism......Page 168
Irregular menses......Page 169
Polycystic ovarian syndrome......Page 172
Infertility......Page 173
Ovarian reserve......Page 175
Treatments......Page 176
Male reproductive disorders......Page 177
Prepubertal disorders......Page 178
Hypergonadotropic hypogonadism......Page 179
Defects in androgen action......Page 180
Erectile dysfunction......Page 181
Gynecomastia......Page 182
Semen analysis......Page 183
Endocrine parameters......Page 185
References......Page 186
Biochemistry and physiology of the more common gastrointestinal hormones......Page 190
Somatostatin......Page 191
Pancreatic neuroendocrine tumors......Page 192
Glucagonoma......Page 193
Somatostatinoma......Page 195
VIPoma......Page 196
Gastrointestinal neuroendocrine tumors......Page 199
Carcinoid tumor......Page 201
Nonfunctioning neuroendocrine tumor (pancreatic neuroendocrine tumors)......Page 204
Conclusion......Page 205
References......Page 207
Clinical symptoms of hypoglycemia......Page 210
Diagnosis of hypoglycemia......Page 211
Causes of hypoglycemia......Page 212
Evaluation of acute hypoglycemia......Page 213
Prolonged fasts in the evaluation of hypoglycemia......Page 216
Testing strategy for evaluation of hypoglycemia......Page 217
Hypoglycemia syndromes with hyperinsulinism......Page 218
Neonatal hyperinsulinism......Page 221
Hyperinsulinism in children and adults......Page 222
Hyperinsulinism with suppressed C-peptide......Page 224
Hyperinsulinism: biochemical findings compatible with hyperinsulinism in the absence of measured hyperinsulinism......Page 225
Nonhyperinsulinemic hypoglycemia......Page 226
Endocrinopathies as causes of hypoglycemia......Page 227
Galactosemia and hereditary fructose intolerance......Page 228
The glycogen storage diseases......Page 229
Defects in gluconeogenic enzymes......Page 232
Aminoacidopathies with associated hypoglycemia......Page 233
Limited substrate/increased utilization as causes of hypoglycemia......Page 234
Summary of the evaluation of hypoglycemia......Page 235
References......Page 236
Hyperglycemia: acute versus chronic......Page 243
Clinical symptoms of diabetes......Page 244
Classification of diabetes......Page 246
Type 2 diabetes......Page 247
Metabolic syndrome......Page 248
Metabolic syndrome consequences that result from hyperinsulinism......Page 250
Other specific types of diabetes......Page 251
Neonatal diabetes......Page 252
Mitochondrial diabetes......Page 260
Other specific types of diabetes: considerations......Page 262
Genetic defects in insulin action......Page 263
Diseases of the exocrine pancreas......Page 264
Drug-induced diabetes......Page 266
Gestational diabetes mellitus......Page 267
Nonpregnant adults and children......Page 268
Choice of the blood specimen for measuring glucose......Page 269
The oral glucose tolerance test......Page 270
Measuring insulin or C-peptide......Page 271
Testing for gestational diabetes mellitus......Page 272
Adults......Page 273
Self-monitoring of blood glucose and point-of-care testing......Page 274
Assessment of diabetic control......Page 275
Evaluation of lipid status......Page 277
Renal evaluation......Page 278
Other testing......Page 279
Conclusion......Page 280
References......Page 282
Background......Page 293
Hypercholesterolemia......Page 296
Hypertriglyceridemia......Page 302
Combined hyperlipidemia......Page 304
Hypoalphalipoproteinemia......Page 305
Laboratory assessment of dyslipidemia......Page 306
References......Page 311
Calcium distribution in the body......Page 315
Calcium measurements......Page 316
Clinical indications to measure calcium, phosphate, and related analytes......Page 318
Parathyroid glands and parathyroid hormone......Page 320
Calcium and the renal tubules......Page 324
Phosphate and the renal tubules......Page 327
Parathyroid hormone and bone......Page 329
Calcitonin and bone......Page 330
Procalcitonin—a marker of bacterial infection......Page 331
Vitamin D physiology......Page 332
25-OHD and 1,25-OH2D metabolism......Page 335
Calcium and phosphate absorption from the gut......Page 336
Parathyroid hormone assays......Page 338
Clinical manifestations of disordered calcium or phosphate metabolism......Page 340
Decreased parathyroid hormone action......Page 341
Parathyroid hormone deficiency—acquired hypoparathyroidism......Page 342
Parathyroid hormone deficiency—genetic causes of hypoparathyroidism......Page 343
Parathyroid hormone receptor defects: parathyroid hormone receptor-1 mutations......Page 347
Postparathyroid hormone receptor-1 signaling......Page 350
Guanine nucleotide-binding protein (G protein), alpha guanine nucleotide-binding protein, α stimulating defects......Page 351
Defects distal to guanine nucleotide-binding protein, α stimulating......Page 354
Vitamin D-deficient rickets/osteomalacia......Page 355
Vitamin D–dependent rickets/osteomalacia......Page 356
Renal tubular disorders: primary and secondary conditions......Page 357
Hereditary forms of hypophosphatemic rickets/osteomalacia......Page 358
Autosomal-dominant hypophosphatemic rickets......Page 359
Autosomal-recessive hypophosphatemic rickets......Page 360
Dietary calcium deficiency......Page 361
Laboratory approach to hypocalcemia......Page 362
Hyperparathyroidism......Page 364
Intraoperative parathyroid hormone measurements......Page 370
Nonparathyroid hormone-dependent causes of hypercalcemia......Page 371
Laboratory approach to hypercalcemia......Page 373
Laboratory monitoring of bone turnover......Page 374
Other bone diseases with possible laboratory implications......Page 375
References......Page 376
Introduction......Page 395
Definition of hypertension......Page 397
Causes of hypertension......Page 398
Laboratory evaluation of hypertension in adults......Page 399
Endocrine hypertension and mechanisms......Page 404
Physiology......Page 405
Laboratory notes......Page 412
Hyperaldosteronism (mechanism 1a1)......Page 413
Oral salt loading or IV saline infusion......Page 414
Renin-dependent hyperaldosteronism (also known as hyperreninemic hyperaldosteronism) (mechanism 1a1)......Page 415
Renovascular hypertension (mechanism 1a1)......Page 416
Renin-independent hyperaldosteronism, sporadic causes (mechanism 1a1)......Page 417
Aldosterone-producing adenoma......Page 418
Bilateral adrenal hyperplasia......Page 419
Renin-independent hyperaldosteronism, inherited causes (mechanism 1a1)......Page 420
Glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type I) (mechanism 1a1)......Page 421
Familial aldosterone-producing adrenal adenomas or hyperplasia (familial hyperaldosteronism type II) (mechanism 1a1)......Page 422
Excess desoxycorticosterone (mechanism 1a1)......Page 423
11β-Hydroxylase deficiency (mechanism 1a1)......Page 424
CYP17 deficiency (mechanism 1a1)......Page 425
Excess cortisol (mechanism 1a1)......Page 427
Laboratory notes......Page 428
Laboratory notes......Page 429
Apparent mineralocorticoid excess (mechanism 1a2)......Page 430
Laboratory notes......Page 431
Laboratory notes......Page 432
Laboratory notes......Page 433
Insulin resistance (mechanism 1b): obesity, type 2 diabetes, the metabolic syndrome, and acromegaly: multiple mechanisms of.........Page 434
Hyperthyroidism (mechanism 2a) and hypothyroidism......Page 435
Laboratory testing......Page 436
Laboratory testing......Page 437
Approach to the patient......Page 438
References......Page 442
Introduction......Page 452
Risk and inheritance factors......Page 453
Characterization......Page 454
Diagnostic and screening laboratory tests......Page 456
Characterization......Page 457
Diagnostic and screening laboratory tests......Page 458
MEN4 [5–8]......Page 459
Clinical features and laboratory tests......Page 460
Clinical features and laboratory tests......Page 461
Risk and hereditary factors......Page 462
Epidemiology......Page 463
Clinical features......Page 464
Risk and inheritance factors......Page 465
Tumor imaging......Page 466
Pathology......Page 467
Risk and hereditary factors......Page 468
Clinical features......Page 469
Epidemiology......Page 470
Pathology......Page 471
Laboratory tests......Page 472
Other tests......Page 474
References......Page 475
Lipid, glucose, and fat metabolism......Page 479
Thyroid disorders......Page 482
Infections and neoplasms......Page 483
Thyroid function test profile......Page 484
Glucocorticoids......Page 485
Gonadal function......Page 487
Hyponatremia......Page 489
Bone and mineral metabolism......Page 490
Endocrine and metabolic emergencies......Page 491
Conclusions......Page 492
References......Page 493
Definition of short stature......Page 499
Familial short stature......Page 502
Constitutional delay in growth and adolescence......Page 503
Short stature with low growth velocity......Page 507
Turner syndrome......Page 508
Psychosocial short stature......Page 510
Hypothyroidism......Page 511
Growth hormone deficiency......Page 512
Growth hormone testing......Page 516
Growth hormone treatment......Page 520
Insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-3......Page 523
Insulin-like growth factor-I as a therapeutic agent......Page 526
Type I insulin-like growth factor receptor mutations......Page 528
Evaluation of individuals diagnosed with growth hormone deficiency......Page 530
Other endocrine and genetic causes of short stature......Page 532
Conclusion......Page 534
References......Page 535
Feto-placental unit......Page 544
Conception and implantation......Page 545
Human chorionic gonadotropin......Page 546
Placental growth hormone......Page 547
Human placental lactogen......Page 548
Placental adrenocorticotropic hormone......Page 549
Pregnancy-associated plasma protein A......Page 550
Angiogenic factors......Page 551
Inhibin and activin......Page 552
Estrogens......Page 553
Hypothalamus and pituitary......Page 554
Fetal adrenal glands......Page 555
Hypothalamus and pituitary......Page 557
Normal thyroid function in pregnancy......Page 558
Maternal thyroid disease......Page 559
Laboratory assessment of thyroid function in pregnancy......Page 560
Preeclampsia......Page 561
Laboratory testing in preeclampsia......Page 564
Preterm delivery......Page 565
Premature rupture of membranes......Page 566
Phosphatidylglycerol......Page 567
Multiple of the median......Page 568
Neural tube defects......Page 569
Trisomy 13......Page 570
First trimester serum screen......Page 571
Quad screen......Page 572
Combined first and second trimester screening......Page 573
Cell-free DNA screening......Page 574
References......Page 576
Introduction......Page 581
Genitalia: structure and development......Page 583
A clinical and laboratory approach to disorders of sexual development......Page 585
Sex chromosome disorders of sexual development......Page 587
Turner syndrome......Page 588
Trisomy (triple) X......Page 589
Laboratory findings –......Page 590
Laboratory findings –......Page 591
Laboratory findings –......Page 592
Sex chromosome disorders of sexual development—ovotesticular disorders of sexual development......Page 593
Sex chromosome disorders of sexual development—summary......Page 594
Complete gonadal dysgenesis......Page 596
Gonadal regression......Page 597
Testosterone—a Leydig cell marker......Page 598
Inhibin B—a Sertoli cell marker......Page 601
46, XY disorders of sexual development—gonadotropin deficiency......Page 602
Laboratory findings –......Page 603
Laboratory findings –......Page 606
3 beta-hydroxysteroid dehydrogenase-delta4,5isomerase deficiency......Page 608
Cytochrome P450 oxidoreductase (POR) deficiency......Page 610
Laboratory findings......Page 612
Laboratory findings –......Page 613
Laboratory findings......Page 614
46, XX disorders of sexual development—fetal androgen excess......Page 615
21-hydroxylase deficiency......Page 618
11-beta hydroxylase deficiency......Page 620
Nonadrenal fetal androgen excess......Page 622
Maternal androgen exposure......Page 623
Approaching the laboratory diagnosis of disorders of sexual development......Page 624
46, XY disorders of sexual development......Page 627
46, XX disorders of sexual development......Page 629
References......Page 630
Introduction......Page 639
Diagnosing gender dysphoria in minors......Page 641
Monitoring for puberty onset......Page 642
Beginning pubertal suppression......Page 643
Initiating gender-affirming hormones......Page 645
Feminizing therapies......Page 646
Masculinizing......Page 653
Overarching concerns......Page 657
References......Page 658
Background......Page 662
Estradiol and progesterone......Page 663
Sex hormone binding globulin......Page 664
Pituitary human chorionic gonadotropin in females......Page 665
Testosterone deficiency in older males......Page 666
Declines in dehydroepiandrosterone its sulfate ester......Page 667
Growth hormone......Page 668
Hypothalamic-pituitary-adrenal axis......Page 669
Dexamethasone suppression......Page 670
Adrenocorticotropic hormone stimulation......Page 671
Mild abnormalities: normal aging or disease?......Page 672
Paradoxes and presumed benefits......Page 673
The effect of comorbidities......Page 674
Conclusion......Page 675
References......Page 676
Index......Page 685