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  • A Acanthosis nigricans, with Cushing's

    disease, 281 Acne, with Cushing's disease, 281 ACTH deficiency, isolated, 9-10 ACTH precursors, pathological conditions,

    85-\08 biological significance of, 10 I-I 02 Cushing's syndrome, pituitary dependent,

    96 ectopic ACTH syndrome, ACTH

    precursors in, 93-95 measurement, ACTH related peptides,

    87-88 mechanisms for secretion, 101 Nelson's syndrome, ACTH precursors in,

    97-99 normal tissues, ACTH precursors in,

    89-92 cerebrospinal fluid, POMC, derived

    peptides in, 91 hypothalamus, POMC, derived

    peptides in, 90-91 pituitary, POMC peptides, release into

    circulation, 89-90 pregnancy, POMC peptides in, 92 skin, POMC, derived peptides in, 92

    pituitary tumors, large, invasive, ACTH precursors in, 96-97

    POMC, processing to ACTH related peptides, 85-86

    regulation of secretion, 100 ACTH receptor, mutations, 171-190

    adrenal tumors, ACTH receptor in, 185 clinical features, 181-182 differential diagnosis, 181-182 in disease, 180·185 expression, cloned MC2R, 179-180 ligand binding, 171-173 MC2R promotor, 178-179 melanocortin receptors, human

    chromosomal location, ligand selectivity of, 176

    molecular pathogenesis, 182-183

    Index

    normal ACTH receptors, FGD with, 184 receptor purification, cloning, 175-177 regulation of MC2R, 178 signal transduction, 173-175 targets of ACTH-stimulated protein

    kinase A regulation, 174 tissue distribution, 177-178 triple A syndrome, 184-185

    ACTH secretion bronchial carcinoid tumors, V3 gene

    expression, POMC gene, 40-41 ectopic, non-pituitary tumors responsible

    for, POMC gene, 36-42 entities for, 41--42 POMC gene transcription, 37--42 POMC processing, 36-37

    Addison's disease, 181 Adrenal cytokine level,

    hypothalamo-pituitary-adrenal axis modulation, liS

    Adrenal hormone receptors, aberrant, Cushing's syndrome due to, 207-228

    angiotensin-responsive Cushing's syndrome, 215

    catecholamine-dependent Cushing's syndrome, 212

    clinical screening, 218 ectopic adrenal hormone receptors, 208 food-dependent Cushing's syndrome,

    209-210 functional aberrant adrenal receptors,

    clinical demonstration, 209-216 GIP-dependent Cushing's syndrome,

    209-210 investigation strategy, 216-218 LH-dependent adrenal androgen-secreting

    tumors, 214 LH/hcG-dependent Cushing's syndrome,

    212-214 molecular mechanisms, 219-221 pharmacological therapies, 221-222 serotonin-responsive Cushing's

    syndrome, 214

  • 330

    vasopressin-responsive Cushing's syndrome, 210-211

    Adrenal hyperplasia, 181 Adrenal hypoplasia, 181 Adrenal imaging

    in diagnosis of Cushing's syndrome, 247, 293-294

    Adrenalectomy, bilateral, in treatment of Cushing's syndrome, 300

    Adrenoleukodystrophy, 181 Alcoholism, with pseudo-Cushing's

    syndrome,287-288 Alkalosis, with Cushing's disease, 281 Allgrove's syndrome, 181, 184-185 Alzheimer's disease, 74 Amenorrhea, with Cushing's disease, 281 Aminoglutethimide, 300 Angiotensin-responsive Cushing's

    syndrome, 215 Anxiety, with pseudo-Cushing's syndrome,

    288 Appetite, melanocortin pathway and,

    153-170 agouti-related protein, 158 anorexia, role in, 162-164 arcuate nucleus, 159-160

    efferent signals, integration of, 160· 162 cachexia, role in, 162-164 human obesity and MC4-R, 157 leptin, energy homeostasis and, 154-155 melanocortin-3 receptor, 158-159 murine obesity syndromes,

    melanocortin-4 receptors, 155-157 Arthritis, 125, 320

    5 Letter = B Baseline hormone determinations, in

    diagnosis of Cushing's syndrome, 289 bHLH factor NeuroDI,

    corticotroph-specific, 7-8 ACTH-secreting pituitary tumors, 8

    Bilateral adrenalectomy, in treatment of Cushing's syndrome, 300

    Bilateral inferior petrosal sinus sampling, 239,244,294

    Biochemical confirmation, Cushing's syndrome, 232-236

    circadian rhythm assessment, 233-234 low-dose dexamethasone suppression test,

    235-236 urinary free cortisol, 234-235

    Index

    Blood-brain barrier, cytokines, hypothalamo-pituitary-adrenal axis modulation, 116--118

    Bronchial carcinoid tumors ACTH-secreting, V3 gene expression,

    POMC gene, 40-41 POMC gene expression, corticotroph

    phenotype, 40-41 Bruising, with Cushing's disease, 281

    5 Letter = C Catecholamine-dependent Cushing's

    syndrome, 212 Catheterization studies, in diagnosis of

    Cushing's syndrome, 294-296 Cerebrospinal fluid, POMC, derived

    peptides in, 91 Chemical transformations,

    proopiomelanocortin gene expression, processing, 35

    Circadian rhythm assessment, Cushing's syndrome, 233--234

    Complications, from Cushing's syndrome, follow-up after, post-op evaluation for, 301302

    Corticotrope axis, leptin and, 193-195 "Corticotroph" adenomas, silent, pars

    intermedia, pituitary, role in histogenesis of, 259-276

    historical overview, 259-260 subtype 1,265-269 subtype 2, 269-271

    Corticotroph axis, multifactorial regulation, 47-64

    11 beta dehydrogenase 1, 61 corticotrophin releasing hormone, 4851

    receptor lIcorticotrophin releasing hormone receptor 2,55-57

    receptors, 51-55 leukemia inhibiting factor, 58-59 proinflammatory cytokines, 59-60

    interleukin-6, 59-{i0 steroidogenic factor I, 60-{i I tumor necrosis factor alpha, 59

    vasopressin, 57 Corticotroph differentiation, 6--9

    Pitx factors as general pituitary regulators, 6--7

    Corticotroph ontogenesis, l-{i Corticotroph phenotype, bronchial carcinoid

    tumors, POMC gene expression, 40-41 Corticotrophin releasing hormone

  • Index

    altered expression, animal models with, 72-73

    binding protein, 73-74 corticotroph axis regulation, 48-51

    receptor 1,52-54 receptor 2,54-55

    Cushing's syndrome, 240--242 in diagnosis of Cushing's syndrome,

    292-293 historical review, 65 ligands, 74-75

    non-peptidic, 76-77 peptidic,75

    receptor, ligands, 65-84 receptor I, 52-54, 71

    tissue distribution of, 71 receptor 2,54-55,71

    tissue distribution of, 71 receptors, 68-70 related peptides

    affinities, activities of, 72 amino acid sequences, 66 isolation, characterization of, 65-66

    tissue distribution, 70--72 urocortin, corticotrophin releasing

    hormone physiological, pathophysiological roles,

    66-67 tissue distribution, 67-68

    Corticotrophin releasing hormone test. See Corticotrophin releasing hormone

    Corticotrophin releasing hormone-BP, corticotroph axis regulation, 57

    Corticotroph-specific bHLH factor NeuroDI,7-8

    ACTH-secreting pituitary tumors, 8 Corticotroph-specific transcription, POMC

    gene, 10--14 NeuroDI heterodimers, cell specificity

    and, 13-14 Pitx I, protein interactions, 12--13 POMC promoter, 10--12 Tpit, as Ptix I obligate partner, 14

    Cushing's disease, 97, 99, 321 algorithm, diagnostic, 296-298 baseline hormone determinations, 289 catheterization studies, 294-296 chronic disease, 286 clinical presentation, 280284 corticotrophin releasing hormone,

    292-293 diagnosis, 284--285, 290, 291 differential diagnosis, 287-298

    331

    mild Cushing's syndrome, vs. pseudo-Cushing states, 287-289

    endocrine dynamic testing ofHPA axis, 289-291

    endogenous, classification of, 279 etiology of, 278-280 follow-up after treatment, 301-302

    complications, post-op evaluation for, 301-302

    patient cure, determination of, 30 I postoperative glucocorticoid

    replacement, 301 hypercortisolemic states, with unusual

    laboratory behavior, 285-287 hypercortisolism, classification of, 288 hypothalamic-pituitary-adrenal axis,

    physiology of, 278 imaging evaluation, 293

    adrenals, 293-294 pituitary, 293

    Liddle dexamethasone suppression test, 290,292

    metyrapone stimulation test, 290, 292 periodic Cushing's syndrome, 285 POMC gene expression, 35-36 in pregnancy, 286 primary cortisol resistance, 286 symptoms/signs, frequency of

    in adults, 280 in pediatric patients, 281

    therapeutic strategies, 277-306 treatment, 299-300

    bilateral adrenalectomy, 300 drug therapy, 287, 300. See also under

    specific drug gamma knife, 299 linear accelerator-mediated

    radiosurgery, 299 pituitary X-irradiation, mitotane,

    combined, 299 transphenoidal adenomectomy, 299

    Cushing's syndrome, 93, 96, 99, 198, 232, 242,308

    angiotensin-responsive Cushing's syndrome, 215

    biochemical confirmation of, 232--236 circadian rhythm assessment, 233-234 low-dose dexamethasone suppression

    test, 235---236 urinary free cortisol, 234-235

    catecholamine-dependent Cushing's syndrome, 212

    clinical features, 232

  • 332

    clinical screening, 218 corticotrophin releasing hormone test,

    240--242 diagnosis, 229-258 differential diagnosis of, 236-237 due to aberrant adrenal hormone

    receptors, 207-228 investigation strategy, 216-218 molecular mechanisms, 219-221

    dynamic tests, 239-240 high dose dexamethasone suppression

    test, 239-240 ectopic ACTH syndrome, etiology, 231 ectopic adrenal hormone receptors, 208 etiology, 230--231 food-dependent Cushing's syndrome,

    209-2\0 functional aberrant adrenal receptors,

    clinical demonstration,