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Home , Hypopituitarism, Idiopathic short stature, Kallmann syndrome, Laron syndrome

Index

A description , 199 Abnormalities histology , 202 adiponectin , 187–188 ICU , 210–211 and loss, skeletal dynamics , 189–190 -induced , 209 growth , 188 mechanism, action , 200–201 hypothalamic-pituitary-ovarian axis , 188–189 test , 209–210 insulin , 187 neonates , 211 leptin , 187 pathologic process , 202 hormone , 188 primary (see Primary adrenal insuf fi ciency) prognosis, nineteenth century , 199–200 average intelligence , 61 quality of life (see Quality of life, adrenal insuf fi ciency) cartilage growth , 56 regulation, HPA axis , 201 clinical features , 61 secondary and tertiary (see Secondary and tertiary C-type natriuretic peptide(CNP) , 62 adrenal insuf fi ciency) management , 62 stimulation test mutation , 61–62 cosyntropin , 209 , 57 CRH , 209 Acid-labile subunit (ALS) , 30, 34–35 , 209 Acromesomelic dysplasia, type maroteaux (AMDM) , 69 therapy ACTH. See Adrenocorticotropic hormone (ACTH) central failure , 213 ACTH dependent , 253, 255, 256 chronic replacement , 211–212 ACTH independent , 249, 253 newer , 213–214 Addison’s disease standard , 213 screening , 575 stress replacement , 212–213 type 1 , 574 X-linked leukodystrophy , 214 Adolescents. See Contraception Adrenocortical hyperplasias , 250 Adrenal Adrenocorticotropic hormone (ACTH) carcinomas , 256 adrenal insuf fi ciency Cushing syndrome , 249 baseline level, cosyntropin stimulation test , 209 GIPR , 249 changes , 202 hypothalamic–pituitary , 248 CRH , 209 ultrasound , 255 elevation , 208 Adrenal dehydroepiandrosterone (DHEA), 187 glucocorticoid , 204 Adrenal axis management , 211 , 592 metyrapone inhibits , 210 diagnosis , 593 primary , 207, 212 disadvantages, hormonal constellation , 592–593 regulation, HPA axis , 201–202 potential mediators , 592–593 secondary , 208, 213 treatment , 593 CRH , 249 Adrenal insuf fi ciency Cushing syndrome , 249 ACTH , 201, 202 elevation , 405 animal systems , 199 hypothalamic–pituitary–adrenal axis , 248 baseline hormone measurements , 208 independent and dependent activation , 249 CRH , 201 pituitary tumors , 254, 256 CT and MRI , 210 stimulation , 406, 412

S. Radovick and M.H. MacGillivray (eds.), Pediatric : A Practical Clinical Guide, 605 Second Edition, Contemporary Endocrinology, DOI 10.1007/978-1-60761-395-4, © Springer Science+Business Media New York 2013 606 Index

Adrenoleukodystrophy , 215 Antithyroid medications , 282–283 Adult-onset de fi ciency (AOGHD) AOGHD. See Adult-onset growth hormone de fi ciency autoimmune , 145–146 (AOGHD) BMI , 144 APS-1. See Autoimmune polyglandular syndrome , 142 type 1 (APS-1) bone mineral density , 144 APS-2. See Autoimmune polyglandular syndrome clinical trail , 143–144 type 2 (APS-2) , 145 ARH. See Autosomal recessive hypercholesterolemia dose titration , 144–145 (ARH) glucagon stimulation test , 144 Arm span insulin hypoglycemia stimulation test , 144 AMDM , 69 mortality , 141 differences , 59–60 risk , 142 LWD , 63 therapy continuing , 141, 142 measurement , 58, 59 AIDS , 206 reference range , 60 Albumin , 292 Aromatase inhibitors , 79–80 ALS. See Acid-labile subunit (ALS) Atherosclerosis Ambiguous genitalia , 229, 234 adulthood , 545 AMDM. See Acromesomelic dysplasia, type maroteaux coronary, cerebral and peripheral arteries, (AMDM) adults , 552 and lesions, young adults , 557 DSD , 443 LDL in human , 549 hypothalamic , 445 Autoimmune endocrine disorders , 445 APS-2 , 574–576 OCP , 458 APS-1 and APECED , 572–574 PCOS ( see Polycystic syndrome (PCOS)) autoantibodies , 571, 572 steroidogenic blocks , 444 celiac disease , 571 patients , 444 hemoglobin A1c , 571 hypothesis , 570 adrenal, production , 397, 401, 406 IPEX , 576–577 effects , 401 multiple , 570–571 ratios , 398, 402 syndromes , 569–570 hyperandrogenism , 405, 406 type 1 diabetes , 570 premature adrenarche , 405–406 Autoimmune polyendocrinopathy candidiasis and therapy , 411 ectodermal dystrophy (APECED). Androgen excess See Autoimmune polyglandular syndrome children and adults , 229, 231, 232 type 1 (APS-1) and APECED signs, males and females , 225 Autoimmune polyglandular syndrome type 2 (APS-2) treatment , 230 Addison’s disease , 574 virilizing disorders , 236 APS-3 and APS-4 , 574 nervosa (AN) patients, type 1 diabetes , 574–575 clinical features , 186 screening , 575 description , 186 trearments , 575–576 DSM-IV criteria , 186 Autoimmune polyglandular syndrome type 1 (APS-1) endocrine dysfunction , 186 and APECED evaluation , 190–191 asplenia , 573 and peptide YY , 189 autoantibodies , 574 HPA axis ( see Hypothalamic-pituitary-adrenal (HPA)) autoimmune endocrine disorders , 572–573 management , 191–192 autoreactive T cells , 572 , 189 autosomal recessive disorder , 572 , 189 candidiasis association , 573–574 , 189 diagnosis , 574 Anovulation disease associations , 573 chronic disease , 445 patients , 572–573 description , 443–444 treatment , 574 FSH levels , 444 Autoimmune galactorrhea , 445 chronic (see Chronic autoimmune thyroiditis) de fi ciency , 444–445 Graves’ disease , 279–286 hypothalamic , 445 Autosomal recessive hypercholesterolemia PCOS , 445 (ARH) , 551 Index 607

B Beta-cell function, , 526–528 acute effects 3 b(Beta)-HSD/ D (delta)4,5-isomerase defi ciency , 228–229 ACTH , 168 11 b (Beta)-hydroxylase de fi ciency , 232 ADG , 168 Birth trauma , 206 brain and spinal cord tumors , 168 , 67 cerebral salt wasting (CSW) , 169 Blomstrand chondrodysplasia , 68–69 chemotherapy , 169–170 BMD. See Bone mineral density (BMD) DI (see (DI)) Body composition, PWS , 168 GHD , 101 SIADH , 168–169 lean body mass , 101–102 description , 167–168 obesity , 101 endocrine disorders , 168 REE , 101 late effects (see Late effects treatment, cancer) skinfold measurement, infants , 100, 101 skin , 17 strength and agility , 103–104 TN (see Thyroid neoplasia) Body mass index (BMI) , 144 Cardiac surgery, children , 297–298 Bone health CDC. See Center for Disease Control (CDC) age , 186 Center for Disease Control (CDC) bone mass , 186, 188, 192 combination hormonal contraception , 471 formation , 187 contraceptive use, MEC , 467, 469 loss , 189–190, 192 guidelines resorption , 187 DMPA , 482, 483 younger age , 186 hormonal contraception , 472 Bone mineral density (BMD) thromboembolism , 473 adults , 144 VTE , 473 issue , 483 women, well-controlled disease , 471 signi fi cant loss , 482 MEC indicate , 475 temporary loss , 482 Central DI. See Diabetes insipidus (DI) Bone strength , 177–178 Central thyroid function , 299 TSH , 290 C Central precocious (CPP) CAH. See Congenital adrenal hyperplasia (CAH) bone age , 407 CAIS. See Complete androgen insensitivity syndrome (CAIS) bone mineral density (BMD) , 408 Calciopenic and pubic hair development , 408 description , 363 children , 406 treatment CNS lesions , 406 anticonvulsant therapy , 369 differential diagnosis, gonadotropin dependent de fi ciency , 368 precocious puberty , 401, 406 CKD , 369 GnRH (see Gonadotropin-releasing hormone guidelines , 367–368 (GnRH)) heal , 367 hypothalamic–pituitary–gonadal axis , 407 knock-knee deformities , 367 identi fi cation , 406 monitoring and therapy complications , 370 “LH predominance” , 407 primary and secondary , 367 MRI , 407 severe hepatobiliary disease , 369 pelvic ultrasonography , 407 D ( see ) progestational agents , 408 Calciotropic , 340 Cerebral salt wasting (CSW) , 168–169 Calcitonin , 341–342 CETP. See Cholesteryl ester transfer protein (CETP) Calcium Challenges, DSD balance, children , 339–340 CAH , 433 calciotropic hormones , 340 differential diagnosis , 433, 434 calcitonin , 341–342 gender assignment , 435 distribution , 340 parents , 435 fetal and early neonatal period , 342 partial androgen insensitivity , 433 hypercalcemia (see Hypercalcemia) sexual hair , 436 hypocalcemia (see Hypocalcemia) surgical procedures , 435 parathyroid , 340–341 46,XX genetic males and female , 433 physiological functions , 339 46,XY infants with , 434–435 rickets (see Calciopenic rickets) young women complains , 435 608 Index

Chemotherapy, cancer side effects, combined hormonal contraception , bone strength , 177 478–479 childhood cancer , 168 Complete androgen insensitivity syndrome (CAIS) cytotoxic effects , 173, 175 babies , 432 diabetes mellitus , 170 individuals , 436 gastrointestinal side effects , 169 46,XY females , 436 GHD , 170 Congenital adrenal hyperplasia (CAH) , 169–170 autosomal recessive disorders , 223 heterogeneous tumor type , 169 clinical and hormonal data , 225–227 high-dose steroid therapy , 170 cortisol synthesis , 223, 224 parenteral nutrition , 169 de fi ciency side effects , 169 3 b (Beta)-HSD/D (delta)4,5-isomerase , Childhood obesity. See Type II diabetes mellitus 228–229 and obesity 11 b (Beta)-Hydroxylase , 232 Childhood-onset growth hormone de fi ciency (COGHD) 21-Hydroxylase , 230–232 AACE guidelines , 141 17-Hydroxylase/17,20-lyase , 229–230 adults ( see Adult-onset growth hormone de fi ciency P450-Oxidoreductase , 232–233 (AOGHD)) description , 223, 225 approved diagnosis, GHD , 139 diagnosis , 433 /GHRH test , 140–141 enzymes and genes , 225 causes, transition patients , 138 lipoid , 225, 228 consensus statements , 139 monitoring , 236 contraindications , 143 newborn screening , 239–240 description , 137–138 outcomes , 236–237 differences, AOGHD , 138 prenatal etiologies , 138–139 diagnosis , 237 laboratory test , 139–140 maternal complications , 238–239 metabolic consequences , 140 recommendations , 239 MRI , 141 treatment , 237–238 pituitary tumors , 139 primary , 204 therapy , 140 symptoms , 225 transition patients , 138 therapy (TBI) , 139 adrenalectomy , 236 Child, thyroid neoplasia. See Thyroid neoplasia anti-androgen and aromatase inhibitor , 236 Cholesteryl ester transfer protein (CETP) , 555 genitalia surgery , 235 Chronic autoimmune thyroiditis glucocorticoids , 234 childhood prevalence , 275 LHRH , 235 clinical presentation , 276–278 mineralocorticoids , 234–235 diagnosis , 277–279 newer , 213–214 pathophysiology , 276 objective , 234 terminology and de fi nitions , 276 prediction, adult height , 236 therapy , 279 sex steroids , 235 Chronic kidney disease (CKD), rickets , 369 standard , 213 Chylomicron retention disease (CRD) , 554 46,XY males , 433 Clinical approach, DSD Congenital hypothyroidism (CH) abdominal structures , 431 cardiac malformations , 264 designated team members meeting with family , 431 causes , 261, 262 gender assignment , 429 cognitive defects , 269 institution , 431 Down’s syndrome , 264 multidisciplinary team , 429–431 fetal and early child development , 270 outline, protocol , 429, 430 hypothyroidism , 263–264 physician , 429 iodine de fi ciency , 261, 262 team meeting , 431 neonatal Graves’ disease , 269 COGHD. See Childhood-onset growth hormone newborn screening de fi ciency (COGHD) con fi rmatory testing , 267–268 Combined hormonal contraception (CHC) GBIA , 265 contraception (see Contraception) hypothyroid infants , 265 ef fi cacy, combined hormonal contraception , 477 low T4 and non-elevated TSH , 266–267 and Implanon® , 474 PKU , 265 Index 609

thyroid , 265–266 Cortisol , 292 TSH elevations , 266 CPP. See Central precocious puberty (CPP) work-up, screen-positive cases , 266 Craniopharyngioma , 145 screening , 265 CRD. See Chylomicron retention disease (CRD) septo-optic dysplasia , 264 CRH. See Corticotropin-releasing hormone (CRH) , 262–264 Critical illness, endocrine response. See Endocrine thyroid functional outcome , 269–270 response treatment , 268–269 CSW. See Cerebral salt wasting (CSW) Contraception C-type natriuretic peptide , 62, 69 adolescents, United States , 466 Cushing syndrome advantages and limitations, hormonal and clinical presentation , 250–252 nonhormonal , 466, 468 description , 247 available, hormonal and nonhormonal , 466, 467 diagnostic cancer and benign medical conditions , 486 ACTH , 252–253, 255 CDC , 467 CT , 254, 255 combined hormonal dexamethasone , 252 DMPA injectable , 481–483 hypercortisolemia , 251, 253 ef fi cacy, CHC , 477 IPSS , 255–256 etonorgestrel implantable , 483 Liddle’s test , 253–254 hormone formulations and dosing regimens , MRI , 254, 255 477–478 oCRH , 254 methods , 477 therapeutic interventions , 250 progestin-only , 479–480 UFC , 251–252 progestin-only pills , 480–481 epidemiology and etiology , 248–250 side effects, CHC , 478–479 glucocorticoid replacement , 257 disease processes , 485–486 hypothalamic–pituitary–adrenal axis , 248 effectiveness, hormonal and nonhormonal , 466–468 molecular genetics hormonal methods adrenocortical hyperplasias , 250 adolescents , 470 pituitary corticotropinomas , 250 agents , 470 pituitary basophil adenomas , 247 cardiovascular effects , 471 psychosocial implications , 257 CHC , 470–471 treatment , 256–257 drug interactions , 475 Cytokines , 291, 292 effects, , 471–472 OCPs , 470 reproductive cancer , 475–477 D screening and follow-up , 474–475 DCCT. See Diabetes Control and Complications systemic effects , 471 Trial (DCCT) VTE , 472–473 Dehydroepiandrosterone (DHEA) , 447, 451, 456, 457 , 473–474 Deiodinase type 1 (D1) , 291–293, 295 intrauterine devices , 484 Deiodinase type 2 (D2) , 291, 292, 299 long-acting methods , 485 Deiodinase type 3 (D3) , 291–293 non-contraceptive bene fi ts , 484–485 nonhormonal methods de fi nition , 381 barrier methods , 469–470 development behavior , 469 chronic systemic disease , 382–383 condoms , 467–469 constitutional , 382 spermicides , 469 endocrinopathies , 383 STIs , 467 evaluation unplanned and teen , 466 estrogen therapy , 391–392 Contraceptive use family history , 388 FDA approval , 476 GnRH and gonadotropin therapy , 392 hormonal contraceptive methods , 467 initial evaluation , 389–390 vs. , 474 physical examination , 388–389 teens , 484 plotting growth data , 388 women, medical conditions , 467 therapy , 390–391 Corticotropin-releasing hormone (CRH) Depo-Provera® ACTH , 248 adolescents , 481–482 dexamethasone , 252 BMD , 482–483 610 Index

Desmopressin Diabetes mellitus acetate , 161 autoimmune conditions , 517 dDAVP , 160–161 children and teenagers , 508–509 formulation , 161 classi fi cation , 507 , 162 diagnosis , 508 injections , 163 hyperglycemia , 507 maintain water balance , 162 , 177 nasal administration , 161, 162 obesity , 177 nephrogenic DI , 158 pancreatic b -cells , 507–508 oral intake , 161 patients , 508 primary , 158 psychosocial considerations , 516–517 risk , 162 screening, complications therapy , 159, 160, 162, 163 children, T1D , 518 treatment , 152 hypertension , 517–518 Development microalbuminuria , 518 RTH retinopathy , 518 CNS , 307 treatment, T2D (see Type 2 diabetes (T2D)) delay , 307 sick day management , 515–516 neonatal , 309 systemic sensitivity, insulin , 508 therapy , 310 treatment, T1D (see Type 1 diabetes (T1D)) TSH receptor mutations , 312 treatment, type 2 , 170, 177 DHEA. See Dehydroepiandrosterone (DHEA) Diabetic ketoacidosis Diabetes acute complication , 517 diagnosis , 508 children, T1D , 508 GH therapy , 17 ketonuria , 517 Diabetes Control and Complications Trial Diagnosing growth hormone de fi ciency and pituitary (DCCT) , 509, 513, 514 tumors , 139 Diabetes insipidus (DI) Disorder of sexual differentiation (DSD) , 443, causes , 154–156, 168 452, 458 clinical presentation , 152–154 Disorders of sex development (DSD) description , 152 bipotential external genitalia diagnosis androgen , 428 basal testing , 157 female , 429 CT and MRI , 159–160 genital tubercle , 428 family history , 160 labios crotal folds/genital swellings , 428 nephrogenic , 160 male , 428–429 pituitary surgery/head trauma , 157 urethral folds , 428 (see Polyuria) care of infants saline infusion , 157, 158 abdominal structures , 431 urination , 156–157 designated team members meeting vasopressin administration , 157–158 with family , 431 water deprivation , 157 gender assignment , 429 management , 169 institution , 431 physiology, water balance , 152 multidisciplinary team , 429–431 symptoms , 168 outline, protocol , 429, 430 treatment physician , 429 amiloride , 163 team meeting , 431 anti-in fl ammatory agents , 163 classi fi cation , 424 hydrochlorothiazide , 163 description , 424 hyperparathyroidism , 163 diagnosis and treatment infants , 162–163 CAH , 433 intake water , 160 differential diagnosis , 433, 434 medical alert bracelet , 164 gender assignment , 435 nasal administration , 161 parents , 435 nephrogenic , 163 partial androgen insensitivity , 433 perioperative and postoperative management , 162 sexual hair , 436 sleep disruption , 164 surgical procedures , 435 thiazide diuretics , 163–164 46,XX genetic males and female , 433 thirst mechanism , 161–162 46,XY infants with micropenis , 434–435 vasopressin/ therapy , 160–161 young women complains , 435 tumors , 168 gender change and dysphoria , 436 Index 611

medical management lipoprotein lipase de fi ciency , 545–546 antenatal data , 432 reduced LDL-C levels , 552–554 differential diagnosis and tests , 431–432 reverse transport (see Reverse physical examination , 432–433 cholesterol transport) medical management, infant born , 423 Type III hyperlipoproteinemia , 551–552 paired internal ducts VLDL overproduction , 547–548 Müllerian ducts , 428 lipid, lipoprotein and apolipoprotein levels , Wolf fi an ducts , 428 544–545 patient-centered care , 437 plasma lipid and lipoprotein metabolism research , 437 apolipoproteins , 539, 541 sexual differentiation (see Sexual exogenous and endogenous pathways , differentiation, DSD) 537–538 Dominant mutations reverse cholesterol transport pathway and ABCC8 and KCNJ11 , 500 interaction , 538–539 glucokinase (GK) , 500 structure , 539, 540 glutamate dehydrogenase (GLUDI) , 500 primary vs. secondary dyslipidemia , 545 hepatocyte nuclear factor 4 (HNF4A) , 501 Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X E chromosome, 1 (DAX1) Endocrine IGF-I replacement , 46–47 activation , 427 Endocrine response duplication , 426 acute and chronic responses , 591–592 Down’s syndrome , 264 adrenal axis , 592–593 Drugs, hypoglycemic disorders gonadal axis , 597–598 dextrose , 503 growth hormone (GH) axis , 596–597 diazoxide , 503 therapeutic hormonal interventions, protein glucagon , 503 catabolism octreotide , 503 anabolic sex steroid therapy , 599 DSD. See Disorder of sexual differentiation (DSD) GH , 598 Dwar fi sm , 63, 65, 68, 69 hyperglycemia , 599–600 Dyslipidemia , 600 dietary therapy , 558 IGF-I therapy , 598–599 human plasma TC levels , 557 infants and children , 598 measurement , 556–557 insulin therapy , 599 nephrotic syndrome , 562 thyroid axis , 593–596 NHANES survey , 557 Endogenous lipoprotein metabolism , 542–543 obesity and metabolic syndrome , 557–558 Estrogen pediatric endocrinology , 556 androgen , 398 pharmacological therapy antiandrogenic activities , 402 drug treatment, LDL-C goals , 559 antiestrogens/aromatase inhibitors , 413–414 HMG-CoA reductase inhibitors , 559–560 effects , 410 instituting drug therapy , 559 “estrogenization” , 400 start drug therapy , 559 exogenous agents , 402 statins, children and adolescents , 560 nonsteroidal estrogen–antiestrogen tamoxifen , 410 young females, issues , 560–562 vaginal mucosa , 407 polycystic ovarian syndrome , 562 Ethanol intoxication , 498 Type I diabetes , 562 Dyslipoproteinemias disorders , 537 F dyslipidemia (see Dyslipidemia) Familial (FCHL) endogenous lipoprotein metabolism , 542–543 genetic defects , 548 exogenous lipoprotein metabolism , 541–542 metabolic derangement , 547–548 high-density lipoproteins and reverse cholesterol treatment and prognosis , 548 transport , 543–544 Familial hypercholesterolemia (FH) hyperlipoproteinemias clinical presentation , 549 ApoC-II de fi ciency , 546 familial ligand-defective ApoB , 550 children and adolescents , 552 heterozygous FH3 , 550–551 endogenous lipoprotein metabolism , 547 homozygotes , 550 exogenous lipoprotein metabolism , 545–546 metabolic derangement and genetics , 549 hepatic lipase de fi ciency , 552 monogenic diseases , 549 LDL removal (see LDL removal disorders) treatment , 550 612 Index

Familial hypocalciuric hypercalcemia (FHH) , 350–351 hepatic , 497 Familial male precocious puberty (FMPP) monitor plasma , 503 boys , 411 6-phosphatase de fi ciency , 497, 498 fertility , 411 production declines , 497 ketoconazole , 411 stimulation , 501 leydig cells , 410, 411 GnRH. See Gonadotropin-releasing hormone (GnRH) mutations , 410–411 GnRHa. See GnRH agonist (GnRHa) Familial medullary thyroid carcinoma (FMTC) , 329 GnRH agonist (GnRHa) Familial short stature (FSS) , 74 application , 407 Fanconi syndrome , 366 BMD , 408 FCHL. See Familial combined hyperlipidemia (FCHL) growth velocity , 408 FGF23 , 364–365, 374 MAS , 410 FHH. See Familial hypocalciuric hypercalcemia (FHH) Gonadal axis Fibroblast -3 (FGFR3) , 61–62 diagnosis , 598 FMPP. See Familial male precocious puberty (FMPP) hypogonadotropic , 597 FMTC. See Familial medullary thyroid carcinoma treatment , 598 (FMTC) Gonadal dysgenesis , 127–129 Follicle-stimulating hormone (FSH) Gonadotropin-releasing hormone (GnRH) and LH secretion agonist therapy , 408 gonadal , 413 gene , 384 hypothalamic–pituitary–gonadal axis , 396 glucocorticoid , 445 sex-steroid production , 408, 411 gonadotropin therapy , 392 response to GnRH , 454 hypothalamic anovulation , 445 Follicular thyroid carcinoma (FTC) , 325 Kallmann’s syndrome , 444 Free T3 (FT3) , 290, 291, 293, 297 LH levels, PCOS , 446–447, 454 Free T4 (FT4) , 290–291, 293, 299 neuron and olfactory nerve migration , 384 FSH. See Follicle-stimulating hormone (FSH) neurosecretory neurons , 396, 397, 406, 407 FSS. See Familial short stature (FSS) production/regulation , 384 FTC. See Follicular thyroid carcinoma (FTC) pulsatile manner , 386 Fungal disease, adrenal insuf fi ciency , 206 secretion , 396 stimulation , 407 Granulosa cell tumors , 411–412 G Graves’ disease Gastric inhibitory polypeptide receptor (GIPR) , 249 antithyroid medications , 282–283 GBIA. See Guthrie bacterial inhibition assay (GBIA) clinical presentation , 280–281 Gender change , 436 clinical syndrome , 279 Gender dysphoria , 436 de fi nitive therapy , 283–285 GH-binding protein (BP) , 40–41 diagnosis , 281–282 GHD. See Growth hormone de fi ciency (GHD) , 279 GH-GHR signal transduction and transcription neonatal , 285–286 PTPN11 , 34 pathophysiology , 280 STAT5b , 33–34 transition to adult care , 285 GHR gene mutations Growth disorders, ISS , 74 acid-labile subunit gene , 34–35 Growth failure, TS clinical features, severe IGF-I de fi ciency , 32–33 gastrointestinal , 116 de fi ciency , 39–40 health-care checklist, childhood , 121 GH-binding protein , 32, 33 linear , 122–123 heterozygous defects , 32 recommendations , 125 IGF-I gene , 34 short stature and skeletal , 113–114 IGF-1 receptor , 35 Growth hormone (GH) , 32 action representation , 32 adenosine triphosphate (ATP)-binding , 7 STAT5b , 40 circulation, GH-binding protein (GHBP) , 5–6 GIPR. See Gastric inhibitory polypeptide receptor GH-R binding and signaling , 6 (GIPR) IGF-1R , 6–7 Glucocorticoid replacement , 257 IGFs circulation , 6–7 Glucose metabolic and mitogenic , 6 activation, counter-regulatory systems , 496 axis blood , 502 diagnosis , 597 GK Km , 500 glucocorticoid , 597 Index 613

IGF-I , 596–597 gene mutations (see GHR gene mutations) secretion , 597 GH-GHR signal transduction and transcription treatment , 597 PTPN11, 34 de fi ciency (see Growth hormone de fi ciency STAT5b , 33–34 (GHD)) growth pituitary gland , 3–4 de fi ciency , 38 PWS, children (see , PWS) length declines , 36, 37 secretion , 4–5 pubertal and adolescent spurt , 37–38 and SGA velocities , 36, 37 complications, height , 93 IGFALS mutation , 40 criteria , 91–92 IGF-I receptor , 40 dosing and monitoring , 92 insulin-like growth factor I , 29–31 effects, somatic growth , 88–89 intellectual and social development (see GHR gene heterogeneous nature , 92–93 mutations) long-term adverse effects , 93 musculoskeletal and body composition , 38–39 safety , 89–91 mutations (see GHR gene mutations) short children born , 88 reproduction , 39 US Food and Drug Administration , 88 signal transduction and transcription effects therapy (see GH-GHR signal transduction and antibodies , 16 transcription) IGF-I and IGFBP-3 levels monitoring , 17 treatment (see Treatment, GHI) prediction, adult height , 16–17 unresponsiveness, endogenous/exogenous rhGH dosage , 16 hormone , 31 side effects (see Side effects, GH therapy) Growth hormone (GH) receptor , 35, 40 TS ( see Short stature and skeletal abnormalities, TS) Growth hormone therapy, PWS Growth hormone de fi ciency (GHD) energy expenditure , 102–103 adult height , 15 growth and body composition , 102 adults ( see Adult-onset growth hormone de fi ciency safety , 106 (AOGHD)) strength and agility assessment, GH secretion , 14–15 body composition , 103–104 bone age evaluation , 15 carbohydrate and lipid metabolism , childhood ( see Childhood-onset growth hormone 104–105 de fi ciency (COGHD)) children , 103, 104 clinical trials , 13 development, children activity , 103 diagnosis , 13 measures, physical function , 103 features , 13 motor function , 105–106 ( see Hypopituitarism) new gross motor skills , 103 infancy and childhood , 7 Growth hormone treatment MRI , 15–16 anastrozol , 80 stimulation tests aromatase inhibitors , 79–80 GH secretion , 14 Bakker curve , 78 pharmacological , 13 cost-bene fi t analysis , 79 radioimmuno and immunometric assays , 13 dosage , 78–79 sex steroid , 14 GH therapy , 77–78 Growth hormone insensitivity (GHI) GnRH anonists , 79 biochemical features oxandrolone , 80 GHBP , 40–41 recombinant human IGF-I therapy , 80–81 GHR de fi ciency , 40 side effects , 79 IGFBP-3 , 41–42 Guthrie bacterial inhibition assay (GBIA) , 265 IGF-I , 41 craniofacial characteristics , 38 de fi nition , 31 H diagnosis hCG. See Human chorionic gonadotropin (hCG) GHR affecting factors , 42 HDDST. See High-dose dexamethasone suppression and disease , 42 test (HDDST) partial GH resistance , 42–44 Hereditary hypophosphatemic rickets , 365–366 epidemiology HI. See Hyperinsulinism (HI) gender , 36 High-density lipoproteins (HDL) morbidity and mortality , 36 High-dose dexamethasone suppression test race/nationality , 35–36 (HDDST) , 253, 254 614 Index

HIV , 206 Hypocalcemia Hormones acute , 347–348 cortisol de fi ciencies , 499 causes , 342, 345 counter-regulatory , 495 chronic , 348–349 fuels , 503 de fi ciency/resistance, vitamin D , 344–345 insulinotropic , 502 diagnosis and evaluation , 346–347 regulation, fasting metabolic systems , 496 differential diagnosis , 342, 343 HPA. See Hypothalamic-pituitary-adrenal (HPA) hypoparathyroidism , 342–344 Human chorionic gonadotropin (hCG) neonatal , 412 early , 345 Leydig cell production , 412 late , 345 precocious puberty , 412 management , 349 tumor markers , 412 , 62–63 21-Hydroxylase de fi ciency , 230–232 Hypoglycemia 17-Hydroxylase/17,20-lyase de fi ciency , 229–230 de fi nition , 496 Hyperandrogenism. See Menstrual disorders and diagnostic approach hyperandrogenism acidemia due to ketones , 499 Hypercalcemia acidemia owing to lactate , 498 causes , 351 categories , 497–498 development , 349 Didja Tubes , 497 diagnosis and evaluation , 352–353 drugs , 503 differential diagnosis , 349 fasting systems , 496–497 FHH , 350–351 no acidemia with ketones and fatty acids , hyperparathyroidism , 350 499–502 management , 353–354 tests , 503–504 vitamin D , 351 therapeutic goals , 502 XLH , 373–374 “Didja Tubes” , 495–496 Hypergonadotropic hypogonadism “Fasting Systems” approach , 495 androgen insensitivity , 388 Hypogonadism , 174, 175, 177 5 a -reductase de fi ciency , 387–388 Hypogonadotropic hypogonadism congenital leydig cell aplasia , 386–387 acquired causes , 385–386 gonadal dysgenesis , 387 idiopathic , 384 gonadal failure bilater , 388 , 384 Klinefelter’s syndrome , 386 mutations , 384–385 noonan syndrome , 387 normosmic idiopathic , 384 patients , 386 syndromes , 385 testosterone biosynthesis , 387 Hypolipoproteinemia , 545 turner syndrome , 386 Hypopituitarism vanishing testes syndrome , 386 acquired forms Hyperinsulinism (HI) etiologies , 12 cause , 500 GHD , 12–13 congenital , 497, 499 head trauma , 12 focal , 501 metabolic disorders , 12 hyperammonemia , 500 causes , 139 transient neonatal , 501–502 congenital malformation Hyperlipoproteinemias bioactive GH , 11 ApoC-II de fi ciency , 546 GHRH receptor mutations , 7 children and adolescents , 552 GH-R mutations , 11 endogenous lipoprotein metabolism , 547 HESX1 , 8–9 exogenous lipoprotein metabolism , 545–546 IGF-! and IGF-1R mutations , 11–12 hepatic lipase de fi ciency , 552 IGHD Type IA and IB , 10 LDL removal (see LDL removal disorders) IGHD Type I1 and III , 10 lipoprotein lipase de fi ciency , 545–546 Lhx3 and Pitx2 , 9 reduced LDL-C levels , 552–554 pituitary development and function , 7, 8 reverse cholesterol transport (see Reverse cholesterol pitutiary , 8 transport) Pou1f1 , 10 Type III hyperlipoproteinemia , 551–552 Prop1 , 9–10 VLDL overproduction , 547–548 elements , 139 Hyperparathyroidism , 373 Hypothalamic amenorrhea , 188 Hyperthyroidism , 572, 574, 575 Hypothalamic-pituitary-adrenal (HPA) axis Index 615

ACTH , 186 hyperinsulinism (see Hyperinsulinism) cortisol metabolism , 187 immaturity , 498 CRH production , 186, 187 pancreatic beta-cell insulin secretion pathways , 501 DHEA and sulfate , 187 Insulin-like growth factor I Hypothalamic–pituitary–gonadal axis autocrine and paracrine production , 31 fetal development , 396 GH synthesis and secretion , 29 GABA inhibition , 396 hypothalamic-pituitary-GH/GF-1 axis image , 29, 30 GnRH (see Gonadotropin-releasing hormone (GnRH)) IGFBPs , 30–31 “intrinsic CNS inhibitory mechanism” , 396 IUGR , 84–96 LH and FSH secretion , 396 molecule binds , 30 nerve termini , 396 production , 30 Hypothalamic–pituitary–thyroid (HPT) axis receptors , 31 cardiac surgery , 297 Insulin pump therapy NTIS , 290 calculator , 512 preterm infants , 294–295 children and families , 512 Hypothyroidism correction bolus , 512 APS-1 , 573 CSII , 511 autoimmune endocrine disorders , 572 de fi nition , 511 celiac disease, risk , 575 deliverance insulin , 511–512 central , 173 glycemic control , 512 development , 173 meal/snack bolus , 512 primary , 172 patients , 515 secondary , 173 postprandial blood glucose levels , 512 Insulin resistance , 525–526 Intensive care units (ICU) I GH secretion , 597 ICU. See Intensive care units (ICU) HPT axis , 595 Idiopathic short stature (ISS) intensive glycemic control , 599 biochemical , 74 multiple trauma , 593 de fi nition , 73 Intrauterine devices, contraception , 484 diagnosis Intrauterine growth retardation (IUGR) algorithm , 74, 75 changes, IGF axis , 86 , 77 complication , 83 history and physical exam , 74 de fi nition , 84 screening tests, 74–75 description , 83 skeletal survey , 75 genetic anomalies causes , 84, 85 stimulation test , 76 GH insensitivity , 85 epidemiology , 73 IGF-1 and IGF-2 , 84–85 exclusion, disorders , 74 insulin secretion de fi ciency , 84 FSS and non-FSS, 74 long-term sequelae , 83 management , 77 newborns , 84 pubertal onset , 74 postnatal growth , 83 treatment (see Growth hormone treatment) Iodine de fi ciency IGFALS mutation , 40 congenital hypothyroidism , 261, 262 IGFBP , 40–41 dyshormonogenesis , 267 IGT. See Impaired glucose tolerance (IGT) screening , 262 Immunodysregulation polyendocrinopathy enteropathy thyroid disorders , 261, 262 x-linked syndrome (IPEX) , 576–577 IPEX. See Immunodysregulation polyendocrinopathy Impaired glucose tolerance (IGT) enteropathy x-linked syndrome (IPEX) adults, progression rate , 525 IPSS. See Inferior petrosal sinus sampling (IPSS) glucose, insulin and C-peptide , 528 ISS. See Idiopathic short stature (ISS) glucose sensitivity , 527 IFG , 526 insulin resistance , 525 J Inducible nitric oxide synthetase (iNOS) , 592 Jansen-type metaphyseal chondrodysplasia , 68–69 Inferior petrosal sinus sampling (IPSS) , 255–256 iNOS. See Inducible nitric oxide synthetase (iNOS) Insulin K dysregulation , 502 , 499 exogenous administration , 497 Klinefelter’s syndrome , 386 616 Index

L Low-density lipoproteins (LDL) Laron syndrome , 32, 39 binding and internalization , 543 Late effects treatment, cancer cholesterol derived , 543 adrenal axis , 175–176 degradation , 543 bone strength , 177–178 scavenger receptors , 543 chronic DI and SIADH , 176 (LH) and FSH production gonadal axis b -subunit mutations , 385 delayed puberty , 174–175 LHX3 and HESX1 mutations , 385 fertility options , 175 pulsatility , 389–390 precocious puberty , 173–174 serum/ gonadotropin levels , 389 growth failure/GHD , 170–172 Luteinizing hormone-releasing hormone (LHRH) , 235 obesity and metabolic syndrome , 176–177 LWPES. See Lawson Wilkins Pediatric Endocrine thyroid , 172–173 Society (LWPES) Lawson Wilkins Pediatric Endocrine Society (LWPES) , 423 LCAT. See Lecithin cholesterol acyltransferase (LCAT) M LDL removal disorders Madelung deformity , 64, 65 autosomal recessive hypercholesterolemia , 551 Malnutrition, anorexia nervosa , 192 cholesterol 7a-hydroxylase de fi ciency , 551 MAS. See McCune–Albright syndrome (MAS) FH ( see Familial hypercholesterolemia (FH)) Massive macronodular adrenal hyperplasia sitosterolemia , 551 (MMAD) , 249, 250, 255 Lecithin cholesterol acyltransferase (LCAT) , 555 McCune–Albright syndrome (MAS) Leptin , 292 adult patients , 410 Léri-Weill osteodyschondrosteosis cAMP , 409 characteristics , 63 children , 410

heterozygous deletion , 65 Gs a gene, mutations , 410 idiopathic short stature , 65 laboratory evaluation , 410 madelung deformity , 63–65 side effects , 410 SHOX , 65 skeletal lesions , 410 turner syndrome , 65 therapeutic interventions , 410 X-chromosome , 65 Medullary thyroid carcinoma (MTC) Leukemia , 17 evaluation , 328–329 Leydig cell monogenic disorder , 327 FMPP , 410–411 mutations, RET receptor , 327, 328 testicular tumors , 412 neuroendocrine C cells , 327 LH. See Luteinizing hormone (LH) pediatrics , 327 Lipoid adrenal hyperplasia treatment guidelines , 327 bronzing, newborn , 225 MEN. See Multiple endocrine neoplasia (MEN) cholesterol desmolase activity , 225 Menin , 583 enzymatic activity , 225 Menstrual disorders and hyperandrogenism evaluation , 228 ACTH testing , 452 female , 225, 228 adolescent menstrual disorders , 442–443 gonadectomy , 228 advise further diagnostic evaluation , 452, 456 males , 228 androgen , 445 mutations , 228 anovulatory disorders (see Anovulation) nonclassic form , 228 DHEAS , 451 Lipoproteins FAH , 446, 448–449 endogenous metabolism FOH , 446, 448 LDL , 543–544 genital tract disorders , 443 VLDL , 542–543 GnRH testing , 451 exogenous metabolism , 541–542 hyperandrogenism and hirsutism , 452, 457 high-density lipoproteins and reverse cholesterol idiopathic cases , 449 transport , 543–544 initial laboratory tests , 449 lipid and apolipoprotein levels , 544–545 management and plasma lipid metabolism amenorrhea , 452 apolipoproteins , 539, 541 chronic diseases , 452, 455 exogenous and endogenous pathways , 537–538 cosmetic treatments, OCPs , 459 reverse cholesterol transport pathway and estrogen , 458 interaction , 538–539 hormone replacement , 455 structure , 539, 540 hypovolemic , 458 Index 617

metformin , 460 Neoplasia syndromes. See Multiple endocrine optimal estrogen replacement therapy , 455 neoplasia (MEN) PCOS , 458 Nephrocalcinosis , 373 progestin and hirsutism , 459 Nephrogenic DI sexually mature adolescents , 458 causes , 156 teenagers , 460 chronic , 155 treatment, hypogonadism , 452 lithium therapy , 163 lengths , 441–442 treatment , 152, 163 PCOS ( see Polycystic ovary syndrome) vasopressin , 155, 157–160 physical examination , 449 Neuroendocrine tumors, MEN 1 primary amenorrhea , 449, 450 clinical presentation , 581 primary and secondary amenorrhea , 442 diagnosis , 581–582 secondary amenorrhea , 449, 453 PNTs , 581 SHBG , 451 therapy , 582 testosterone assays , 451 Newborn screening, CAH , 237, 239–240 Metabolic syndrome , 176–177 NHANES. See National Health and Nutrition MMAD. See Massive macronodular adrenal hyperplasia Examination Survey (NHANES) (MMAD) Nodule, thyroid , 320 3-month depot intramuscular injection of Nonclassical congenital adrenal hyperplasia (NCAH) medroxyprogesterone acetate (DMPA) ACTH administration , 231 breast cancer , 476 3 b (Beta)-HSD de fi ciency , 226, 229 CHC and Implanonr , 474 excess androgens , 406 Depo-Provera® , 481–482 glucocorticoid doses , 234 glucose/insulin levels , 472 21-Hydroxylase de fi ciency , 226, 231–232 injection ( see Depo-Provera® ) 17-Hydroxyprogesterone , 231 mild hypertension outweigh , 471 incidence , 405 and patch users , 477 mutation, StAR , 228 MTC. See Medullary thyroid carcinoma (MTC) newborn screening , 239 Multiple endocrine neoplasia 1 (MEN1) screening , 405 children and adolescents, risk , 583–584 Non-thyroidal illness (NTI) genetics , 583 hypothyroidism , 597 Multiple endocrine neoplasia (MEN) hypothyroxinemia , 595 2A , 327, 329 PRCTs , 595 , tumors , 582–583 TBG , 595 2B , 329 thyroid function tests , 593 medullary thyroid carcinoma , 584–585 thyroid hormone , 595 MEN1 ( see Multiple endocrine neoplasia 1 (MEN1)) T3 measurement , 595 MEN2 TSH , 593 genetics , 585–586 Non-thyroidal illness syndrome management , 587 clinical syndrome , 300 screening , 586–587 description , 290 pancreatic neuroendocrine tumors , 581–582 NTIS–thyroid changes pheochromocytoma , 585 hypothalamic–pituitary–thyroid axis , 291–292 primary hyperparathyroidism , 580–581, 585 pathogenesis , 293, 294 syndromes , 579, 580 peripheral thyroid hormone metabolism , 292 Multiple epiphyseal dysplasia (MED) , 63 thyroid hormone-binding protein kinetics , 292–293 transport and action, tissue level , 293 pediatric clinical NTI syndromes N acutely ill children , 296–297 National Health and Nutrition Examination Survey cardiac surgery, children , 297–298 (NHANES) , 525 neonatal intensive care units , 294 Natriuretic peptide receptor B , 69 preterm infants , 294–296 NCAH. See Nonclassical congenital adrenal hyperplasia psychiatric disorders , 299–300 (NCAH) renal insuf fi ciency , 298–299 Neonate Non-thyroidal illness syndrome (cont.) application , 496 thyroid dysfunction , 293–294 children and adults , 496 thyroid hormone , 290–291 normal , 498, 502 Noonan syndrome , 34 octreotide , 503 Normal neonates , 498, 502 618 Index

NTI. See Non-thyroidal illness (NTI) 402, 409 Nutritional rickets , 362–363 exogenous sex-steroid exposure , 409 FMPP , 410–411 gynecomastia , 413 O hCG , 412 Obesity MAS , 409–410 acceleration, linear growth , 174 ovarian cysts , 409 cranial radiation exposure , 177 ovarian tumors , 411–412 description , 176–177 severe hypothyroidism , 412–413 and metabolic syndrome , 176–177 testicular tumors , 412 precocious puberty , 174 Pharmacological therapy, dyslipidemia risk , 177 drug treatment, LDL-C goals , 559 routine annual follow-up care , 177 HMG-CoA reductase inhibitors , 559–560 treatments , 177 instituting drug therapy , 559 oCRH. See Ovine CRH (oCRH) start drug therapy , 559 Osteochondrodysplasia , 56 statins, children and adolescents , 560 Osteogenesis imperfecta (OI) , 65, 67–68 young females, issues , 560–562 , 357–358 Phenylethanolamine-N-methyl-transferase Ovarian failure (PNMT) , 592–593 prediction , 117 Phenylketonuria (PKU) , 265 premature , 112, 117 Phosphate primary , 128 calcium reguation , 340 Ovine CRH (oCRH) , 252–254 hypercalcemia , 352 hypocalcemia , 345 ion homeostasis , 346 P neonatal hypocalcemia , 349 Pamidronate , 67 rhabdomyolysis , 343 Papillary thyroid carcinoma (PTC) rich foods , 347 CT/MRI , 322 rickets (see Phosphopenic rickets) histology, children , 322, 323 transport , 340 hypocalcemia , 324 tubularreabsorption , 347 laryngeal nerve risk , 323 tumor lysis syndrome , 343 lobectomy and isthmusectomy , 323 and vitamin D , 340 lymph node dissection , 324 Phosphopenic rickets meticulous hemostasis , 323 fanconic sydrome , 366 micro-PTC , 325 hereditary hypophosphatemic , 365–366 positron emission tomography , 322 recessive hypercalciuric nephrolithiasis , 366 PTH , 324 treatment pulmonary/distant metastases and treatment , FGF23-mediated causes , 374 325–327 monitoring and complications , 372–374 RAI , 324–325 non-FGF23 , 374 residual/recurrent , 326 nutritional phosphate deprivation , 370 rhTSH , 325 XLH and FGF23 , 364–365 TNM staging system , 322–323 Pituitary voice changes , 323 ACTH , 249, 254, 255 Parathyroidectomy , 373 adrenal axis , 257 Parathyroid hormone (PTH) , 324, 340–341 corticotropinomas , 250 Parathyroid (PTHIR) , 68 Cushing disease , 248, 254 Parathyroid hormone-related protein hypothalamus , 248 (PTHrP) , 68 irradiation , 256 Pathophysiology, type 2 diabetes Pituitary adenomas adults , 525 anterior , 582 beta-cell function , 526–528 clinical presentation , 582 insulin resistance , 525–526 Pitutiary. See Hypopituitarism prediabetic conditions , 524–525 PKU. See Phenylketonuria (PKU) PCOS. See Polycystic ovary syndrome (PCOS) PNMT. See Phenylethanolamine-N-methyl-transferase Peripheral precocious puberty (PNMT) adrenal tumors , 412 Polycystic ovary syndrome (PCOS) CAH , 411 adolescence , 562 differential diagnosis, gonadotropin-independent , androgen excess , 445 Index 619

endometrial hyperplasia , 453 hypothalamic–pituitary–gonadal axis , 396–397 FOH and FAH , 447 molecular biological techniques , 395–396 girls, CPP , 408 normal pubertal development , 397–400 hirsutism , 445–446 pediatric , 167–168 hyperandrogenemic anovulation , 456 peripheral (see Peripheral precocious puberty) insulin-lowering agents , 459–460 premature pubarche , 403–406 LH levels , 446–447 premature thelarche , 402–403 manifestations , 446 primary pediatrician , 395 menstrual irregularities , 459 risk factors , 173 menstrual pattern , 458 treatment , 174 metabolic syndrome and type 2 diabetes treatmentaromatase inhibitors , 174 mellitus , 458 Pregnancy prevention pathophysiology , 446 ef fi cacy , 469 premature adrenarche , 403, 406 STI protection , 469 prenatal androgen excess , 448 Primary adrenal insuf fi ciency prognostic indicators , 403 AIDS and HIV , 206 testosterone , 451 Allgrove’s syndrome , 205 trophic hormone action , 447 birth trauma , 206 Polyglandular autoimmune syndromes , 214 CAH , 204 Polyuria causes , 202–203 causes , 153 clinical presentation , 207 characterization , 153 cortisol biosynthetic , 204, 205 chronic lithium therapy , 164 fungal disease , 206 decreases , 163 glucocorticoid , 204–205 de fi nition , 152–153 polyglandular autoimmune type I and desmopressin therapy , 162 type II , 203–204 evaluation , 153 Smith–Lemli–Opitz syndrome , 204 head trauma , 153 steroidogenic factor-1 (SF-1) , 204 and , 157–158 therapy low-salt and protein diet , 163 chronic replacement , 211–212 management , 164 stress replacement , 212–213 severity , 162 tuberculosis , 206 vasopressin de fi ciency , 152 Wolman’s disease , 205–206 P450-Oxidoreductase de fi ciency , 232–233 X-ALD , 204 PPNAD. See Primary pigmented adrenocortical nodular Primary pigmented adrenocortical nodular diseases diseases (PPNAD) (PPNAD) , 249, 255, 256 Prader-Willi syndrome (PWS) Psychiatric disorders , 299–300 abnormalities , 100 PTC. See Papillary thyroid carcinoma (PTC) body composition , 101–102 PTH. See Parathyroid hormone (PTH) description , 99–100 PTHIR. See Parathyroid hormone receptor (PTHIR) features , 100 PWS. See Prader-Willi syndrome (PWS) GH therapy (see Growth hormone therapy, PWS) growth and hormone, children , 100–101 region , 100 Q Prathyroid hormone Quality of life, adrenal insuf fi ciency hyperparathyroidism , 350 , 215 hypoparathyroidism , 342–343 CAH , 214–215 serum calcium , 340–341 children , 214 Precocious puberty oral intake medications , 214 benign premature development , 401–402 polyglandular autoimmune syndromes , 214 bone age assessment , 174 secondary and tertiary , 214 chemotherapy and radiation , 173–174 CPP (see Central precocious puberty (CPP)) cranial irradiation , 173 R de fi nition , 173, 400–401 Recessive hypercalciuric nephrolithiasis , 366 diagnostic approach Recessive mutations in boys , 414, 416 HADH , 501 in girls , 415, 416 KATP-channel genes , 499 GnRH agonist stimulation tests , 174 Recombinant human growth hormone (rhGH) , 62, 65 GnRHa therapy , 416 Recombinant IGF-I , 48–49 620 Index

Renal insuf fi ciency , 298–299 physical examination , 359–360 Resistance to thyroid hormone (RTH) Schmidtype metaphyseal dysplasia , 367 abnormal I , 307 TNALP , 366 characteristics , 306, 307 treatment children and adults calciopenic (see calciopenic rickets) binding proteins , 307 phosphopenic (see Phosphopenic rickets) causes euthyroid hyperthyroxinemia , 307–308 psychosocial , 374–375 routine tests , 307 vitamin D and calcium de fi ciency , 358–359 thyrotroph adenoma (see Thyrotroph adenoma) RTH. See Resistance to thyroid hormone (RTH) CNS functions , 307 de fi nition , 303 description , 303–304 S effects , 306 Safety, PWS , 106 elements , 304 SCFE. See Slipped capital femoral epiphysis (SCFE) GRTH and PRTH , 305–306 Secondary and tertiary adrenal insuf fi ciency hypothalamic–pituitary–thyroid axis , 304 CAH therapy insensitivity syndromes , 310–311 newer , 213–214 neonatal , 309 standard , 213 receptor (see Thyroid hormone receptor) clinical presentation , 208 syndromes , 304 corticotroph function , 206 TFTs , 303 Cushing syndrome , 206 therapy , 310 hypothalamus and pituitary abnormalities , 206–207 TSH resistance, neonatal , 312 inherited abnormalities , 207 RET gene MRI , 208 germline mutations , 586 pituitary hormones , 208 mutation , 586, 587 PWS , 207 proto-oncogene , 586 quality of life , 214 screening , 586 septo-optic dysplasia , 207 Reverse cholesterol transport Self-monitoring of blood glucose (SMBG) , 512–513 apolipoprotein A-I mutations , 554–555 Serum transducers and activator of transcription 5b cholesteryl ester transfer protein de fi ciency , 555 (STAT5b) endothelial lipase , 556 clinical and biochemical characteristics , 31 familial hypoalphalipoproteinemia , 554 craniofacial characteristics , 38 lecithin cholesterol acyltransferase de fi ciency , 555 gene mutation , 40 lipoprotein , 556 genetic disorders , 33–34 scavenger receptor Class B Type I receptor mechanism , 30 de fi ciency , 556 mutation , 33 tangier disease , 555 Sex chromosome abnormalities. See X-chromosome Reverse T3 (rT3) , 290, 291, 297 Sex-determining region Y (SRY) gene rhGH. See Recombinant human growth hormone (rhGH) gonadal sex , 425 Rickets mutations , 425 abnormalities Sexual differentiation, DSD biochemical , 360–362 bipotential gonad , 424–425 radiographic , 360 ovarian , 426–428 calciopenic and phosphopenic , 358 testicular , 425–426 classi fi cation scheme , 359 Sexually transmitted (STIs) differential diagnosis latex condoms , 467–469 nutritional , 362–363 potential prevention , 467 phosphopenic (see Phosphopenic rickets) Short stature (SS) vitamin D type I , 363 idiopathic (see Idiopathic short stature (ISS)) vitamin D type II , 364 SGA (see Small for gestational age (SGA)) exposure, toxic agents , 359 Short stature and skeletal abnormalities, TS fat malaborption , 359 diagnosis , 120 hypophosphatasia , 366–367 growth charts, girls , 120, 122 inborn errors , 359 growth hormone meaning , 357 body proportions , 123 nutritional de fi ciency , 358 bone mineral density (BMD) , 123 and osteomalacia , 357–358 , 123 , 358 childhood , 122 , 358 Craniofacial development , 123 Index 621

linear growth failure , 122–123 children , 103, 104 psychosocial function , 124 development, children activity , 103 safety , 124 measures, physical function , 103 side effects, anabolic steroids , 124–125 motor function , 105–106 timing and administration, therapies , 122 new gross motor skills , 103 Short-stature homeobox-containing gene (SHOX) , 65 Stress response , 598 SHOX . See Short-stature homeobox-containing gene Syndrome of inappropriate antidiuretic hormone (SIADH) (SHOX) chronic , 176 SIADH. See Syndrome of inappropriate antidiuretic CSW , 169 hormone (SIADH) hypothalamic-pituitary surgery , 168 Side effects, GH therapy permanent DI , 169 benign intracranial hypertension , 17–18 secretion , 168–169 diabetes and insulin resistance , 17 synthesizes , 168 leukemia , 17 recurrence, CNS tumors , 17 SCFE , 18 T skin cancers , 17 Tangier disease , 555 Skeletal dysplasias Tanner stages anatomy and nonmenclature, long bones , 56, 57 female genital and pubic hair , 399 arm span/height difference , 59 male genital and pubic hair , 397–398 common syndromes sequence, pubertal development , 399–400 achondroplasia , 61–62 Tanycyte , 292 hypochondroplasia , 62–63 TBG. See Thyroxine-binding globulin (TBG) LWD , 63–65 T1D. See Type 1 diabetes (T1D) multiple epiphyseal , 63 Teens osteogenesis imperfecta (OI) , 65, 67–68 BMD , 483 de fi nitive diagnosis , 56 contraceptive use , 484 detection , 57 OCP , 477 genetic disorders , 56 unplanned pregnancies , 466 initial diagnostic evaluation , 60–61 Therapy physical examination , 60 TS short stature , 57 cardiovascular disorders , 120 single-gene abnormalities , 59 dermatological , 126 uncommon syndromes eye , 126 acromesomelic , 69 gastrointestinal disorders , 126 Jansen-type and blomstrand chondrodysplasia , glucose homeostasis , 127 68–69 gonadal failure , 127–129 upper-to-lower segment ratio , 57, 58 health-care checklists , 120 vocabulary , 56–57 hearing loss , 125–126 Skin cancers, side effects, GH therapy , 17 hypothyroidism autoimmune disorders , Slipped capital femoral epiphysis (SCFE) , 18 126–127 Small for gestational age (SGA) learning disabilities , 129 clinical presentation , 86 lipids , 127 diagnostic evaluation lymphedema , 120 biochemical criteria , 88 obesity , 127 catch-up growth , 87 orthodontic complexities , 125 GH secretion and release , 87–88 plastic surgery , 120 growth failure , 86 primary care , 120 pre-and postnatal growth , 86 recommendations , 125 tests, IUGR-associated short stature , 86–87 renal , 126 GH therapy (see Growth hormone) short stature and skeletal (see Short stature IUGR ( see Intrauterine growth retardation (IUGR)) and skeletal abnormalities, TS) SMBG. See Self-monitoring of blood glucose (SMBG) strabismus , 126 Smith–Lemli–Opitz syndrome , 204 tumors , 127–129 STAT5b. See Serum transducers and activator of type II diabetes mellitus and obesity transcription 5b (STAT5b) non-pharmacological and pharmacological STIs. See Sexually transmitted infections (STIs) approaches , 531–532 Strength and agility, growth hormone therapy prevention strategies , 529–531 body composition , 103–104 treatments , 528–529 carbohydrate and lipid metabolism , 104–105 THR. See Thyroid hormone receptor (THR) 622 Index

Thyroid family history , 308 neoplasia (see Thyroid neoplasia) MRI , 308–309 WHO , 320 mutations , 309 Thyroid axis stimulation testing , 309 fatal arrhythmia , 596 symptoms, hyperthyroidism , 308 hypothyroxinemia , 595 T3 and measure , 309 in fl uence thyroid function , 595, 596 thyroid ultrasonography , 309 , 596 Thyrotropin (TSH) receptor mutations measurement of TSH , 595 biological properties and activities , 311 non-thyroidal illness , 595 causes , 312 NTI , 595 characteristics , 312 physiologic effects, de fi ciency , 594 euthyroid hyperthyrotropinemia , 312 postoperative cardiac patients , 595–596 follicular cells , 311 TBG , 594–595 G-coupled receptor , 311, 312 TSH and TRH , 593–594 homozygotes/ heterozygotes , 311 type I and II deiodinases , 594 infant born , 311 Thyroid dysgenesis , 262–263 location , 311 Thyroid function tests , 307 loss-of-function , 311 Thyroid hormone secretion , 311 binding protein kinetics , 292–293 Thyrotropin-releasing hormone (TRH) metabolism , 292 acute illness , 293 non-thyroidal illness , 290 diminished TSH secretion , 291 NTIS , 290–291 NTIS , 292 preterm infants , 295 Thyroxine (T4) transport and action, tissue level , 293 hypothyroxinemia , 296 treatment , 294 placebo-controlled trial , 296 Thyroid hormone receptor (THR) randomized trial , 297 acute illness , 293 TSH , 295 NTIS , 293 Thyroxine-binding globulin (TBG) , 292 RTH Thyroxine-stimulating hormone (TSH) abnormal , 304–305 elevation , 266 elements , 304 iodine de fi ciency , 262 modulate gene transcription , 304 non-elevation , 266–267 mutations, TR a and TR b , 305 thyroid newborn screening , 265 nTREs and pTREs , 304 Tissue nonspeci fi c alkaline phosphatase (TNALP) , 366 Thyroid neoplasia T O D A Y. See Type 2 Diabetes in Adolescents DTC , 320–321 and Youth (TODAY) evaluation and treatment, FNA , 320, 321 Transient neonatal hyperinsulinism FMTC , 329 infant of diabetic mother (IDM) , 501 FTC , 325 malformations , 502 hormone suppression and follow-up , 325–326 perinatal stress-induced , 501–502 management, papillary cancer , 320, 322 Transition patients , 138 MEN (TSS) , 256 2A , 327, 329 Transthyretin , 292 2B , 329 Traumatic brain injury (TBI) , 139 MTC ( see Medullary thyroid carcinoma (MTC)) Treatment, GHI newter techniques , 327 GHR de fi ciency , 44–46 PTC ( see Papillary thyroid carcinoma (PTC)) limitations, endocrine IGF-I replacement , 46–47 residual/recurrent cervical disease , 326 purported partial , 47–48 risk factors , 320 rhIGF-I , 44, 45 surgeries , 320 safety, recombinant IGF-I , 48–49 ultrasound (US) , 320 therapy , 49–50 Thyroid screening , 265, 267, 270 TRH. See Thyrotropin-releasing hormone (TRH) Thyroid-stimulating hormone (TSH) (T3) measurement , 595 binding proteins , 299 non-thyroidal illness , 290 enzyme , 292 thyroxine (T4) and triiodothyronine (T3) , 593 GRTH , 299 TRH , 594 measurements , 291 Thyrotroph adenoma vs. RTH NTIS , 290 alpha subunit measurement , 308 placebo treatment , 297 Index 623

preterm infants , 295 Y-chromosome material , 119 TSH , 293 dysmorphic features , 112–113 Triple-phase response , 154 ear and hearing disorders , 115 TSH. See Thyroid-stimulating hormone (TSH); eye disorders , 115 Thyroxine-stimulating hormone (TSH) gastrointestinal disorders , 115–116 TSS. See Transsphenoidal surgery (TSS) glucose , 117 Tumor gonadal failure , 117–118 ACTH , 255, 256 hypothyroidism , 116 adrenal , 254 learning disabilities , 118 adrenocortical , 249 lipids , 117 neuroendocrine , 249 lymphedema , 112 pituitary , 250 obesity , 117 Turner, Kallmann and Noonan syndromes orthodontic , 114–115 associated syndromes , 385 pathogenesis , 110–112 categories , 382 premature ovarian failure , 112 chronic systemic disease , 382–383 renal malformation , 115 clinical and laboratory assessment , 382 strabismus , 115 constitutional delayed puberty , 382 therapy (see Therapy) delayed puberty , 381–382 Type 1 diabetes (T1D) endocrinopathies , 383 basal-bolus regimen with multiple daily injections , 510 hypergonadotropic hypogonadism DCCT , 509 acquired causes, gonadal failure , 388 exercise , 515 androgen insensitivity , 388 hypoglycemia , 513–514 5 a -reductase de fi ciency , 387–388 insulin doses , 512–513 congenital leydig cell aplasia , 386–387 insulin management , 509 GnRH , 386 insulin pumps , 511–512 gonadal dysgenesis , 387 medical nutrition therapy , 514–515 karyotype , 386 regimens , 509–511 Klinefelter’s syndrome , 386 Type 2 diabetes (T2D) testosterone biosynthesis , 387 pediatric population , 507 vanishing testes syndrome , 386 systemic sensitivity, insulin , 508 hypogonadotropic hypogonadism treatment ( see Hypogonadotropic hypogonadism) behavior modi fi cations , 519 normal puberty , 382 gastrointestinal side effects , 519 pathologic abnormalities , 382 high-risk populations , 518 pubertal delay insulin resistance (IR) , 518 family history , 388 medications , 519 GnRH and gonadotropin therapy , 392 numerous oral agents , 519 initial evaluation , 389–390 patients evaluation , 519 physical examination , 388–389 principles , 519 plotting growth data , 388 screening , 518 treatment , 390–392 Type 2 Diabetes in Adolescents and Youth Turner syndrome (TS) (TODAY) , 532 abnormalities Type II diabetes mellitus and obesity cardiovascular , 113 glucose metabolism , 532 short stature and skeletal , 113–114 lipid deposition , 532 autoimmune disease , 116 “obesity epidemic” , 523 cancers , 118 pathophysiology (see Pathophysiology, type 2 diabetes) dermatological abnormalities , 116 therapy (see Therapy) description , 110 “toxic environment” , 523–524 diagnostic guidelines worldwide epidemiology , 524 ACMG , 119 children , 119 clinical features , 118–119 U delayed , 119–120 UFC. See Urinary free cortisol (UFC) FISH , 119 Upper-to-lower segment ratio , 57, 58 girls , 119 Urinary free cortisol (UFC) , 251, 252, 254 obstacles , 119 U.S. Medical Eligibility Criteria (MEC) PCR , 119 contraceptive use , 467, 469 prenatal , 119 indication , 475 624 Index

V X Van Wyk–Grumbach syndrome , 412–413 X-chromosome Vasopressin. See Diabetes insipidus (DI) disomy function , 112 Venous thromboembolism (VTE) , 472–473 haploinsuf fi ciency, gene expression , 110–111 Very low-density lipoproteins (VLDL) imprinting , 111–112 biosynthesis , 542 location , 110 secretion and metabolism , 542–543 loss , 110 Vitamin D maternal/paternal , 110 hypercalcemia , 351 structural abnormalities , 110 hypocalcemia , 344–345 X-linked recessive disorders , 112 rickets X-linked hypophosphatemic rickets de fi ciency , 368 diagnosis , 364–365 diagnosis, 1a -Hydroxylase de fi ciency treatment (type I) , 363 administration phosphate salts , 370–371 herediatry Vitamin D resistance (type II) alfacalcidol , 371–372 diagnosis , 364 calcimimetics , 372 serum calcium , 341 diarrhea , 371 treatment FGF23 , 374 absorption , 369 growth hormone , 372 1 a -hydroxylase de fi ciency , 369 hyperparathyroidism , 373 hereditary vitamin D resistance , 369 D , 373 XLH , 373 monitoring , 372–273 VLDL. See Very low-density lipoproteins (VLDL) nephrocalcinosis , 373 VTE. See Venous thromboembolism (VTE) nocturnal dosing , 371 parathyroidectomy , 373 screening , 370 W therapy , 371 Wolman’s disease , 205–206 X-Linked leukodystrophy , 214