Handbook of Clinical Pediatric Endocrinology, Second Edition

365 Pages·3.575 MB·English

by  Charles G. D. Brook, Mehul T. Dattani(auth.)

Handbook of Clinical Pediatric Endocrinology
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Handbook of
Clinical Pediatric
Endocrinology
Charles G. D. Brook
MA, MD, FRCP, FRCPCH
Emeritus Professor of Paediatric Endocrinology
University College London
London, UK
Mehul T. Dattani
MD, FRCP, FRCPCH, DCH
Professor of Paediatric and Adolescent Endocrinology
Academic and Clinical Lead in Paediatric Endocrinology
Developmental Endocrinology Research Group
Clinical and Molecular Genetics Unit
UCL Institute of Child Health, Great Ormond Street Hospital for Children
London and University College London Hospitals, UK
SECOND EDITION
A John Wiley & Sons, Ltd., Publication
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This edition first published 2012, © 2008, 2012 by John Wiley & Sons, Ltd.
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Library of Congress Cataloging-in-Publication Data
Handbook of clinical pediatric endocrinology / [edited by] Charles G.D. Brook, Mehul T. Dattani. – 2nd ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-470-65788-1 (pbk. : alk. paper)
I. Brook, C. G. D. (Charles Groves Darville) II. Dattani, Mehul T.
[DNLM: 1. Endocrine System Diseases–Handbooks. 2. Adolescent. 3. Child. 4. Infant. WK 39]
618.92′4–dc23
2011035465
A catalogue record for this book is available from the British Library.
Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be
available in electronic books.
Set in 9/12 pt Minion by SPi Publisher Services, Pondicherry, India
1 2012
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Contents
Preface , vii 11 Hypoglycemia , 230
List of Abbreviations , ix 12 Obesity and Type 2 Diabetes Mellitus , 248
1 The Relevance of Molecular Biology to Clinical 13 Type 1 Diabetes Mellitus , 267
Practice , 1
14 Endocrine Neoplasia , 296
2 Hormones: their Nature, Action
15 Tests and Normal Values in Pediatric
and Measurement , 15
Endocrinology , 309
3 The Hypothalamo-Pituitary Axis , 31
Appendix 1: Syndrome-Specifi c Growth Charts , 325
4 Endocrine Problems of Infancy , 48
Appendix 2: Normal Values , 337
5 The Management of Growth Disorders , 70
Index , 343
6 The Management of Puberty Disorders , 99
7 The Thyroid Gland , 129
8 The Adrenal Gland , 151
9 Disorders of Calcium and Bone Metabolism , 175
10 Water Balance , 210
v
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Preface
The first edition of this Handbook appeared four years and it is my hope that you will profit as much from his
ago and seems to have been useful, so this update, based extraordinary grasp of the science and practice of clinical
on the 6t h edition of Brook’s Clinical Pediatric Endo- pediatric endocrinology as I have. As always, we should
crinology , follows a very similar format but with some be very glad to have errors drawn to our attention.
notable additions. The team at Wiley-Blackwell, Oliver Walters, Jenny
Molecular biology has advanced rapidly in those years Seward, Rob Blundell and Helen Harvey, provides as
and is beginning to have a real clinical impact so consider- smooth an operation as an author could wish for; we are
able attention has been paid to this advance. You will also very grateful for their help in producing this book. We
find clinical pitfalls highlighted and self-assessment chal- hope that you will enjoy it.
lenges in each chapter. Where possible, we have included
links to established guidelines and consensus views. Charles Brook
The enrolment of Professor Mehul Dattani as co- editor Mehul Dattani
has been a great comfort to his (literally) senior colleague 2012
vii
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List of Abbreviations
1,25(OH)D 1,25-dihydroxyvitamin D BWS Beckwith–Wiedemann syndrome
2
11b-HSDII 11 β -hydroxysteroid dehydrogenase CAH congenital adrenal hyperplasia
type II CAIS complete androgen insensitivity syndrome
17PGN 17 α -hydroxypregnenolone cAMP cyclic adenosine monophosphate
AAA Achalasia, Addisonian, Alacrima CaSR calcium-sensing receptor
syndrome CBG corticosteroid-binding globulin
ACE angiotensin-converting enzyme CDG congenital disorders of glycosylation
ACT adrenocortical tumor CDGP constitutional delay of growth and
ACTH adrenocorticotropic hormone puberty
ADH antidiuretic hormone CDI central diabetes insipidus
ADHR autosomal-dominant CEA chorionic embryonic antigen
hypophosphatemic rickets CF cystic fi brosis
AES Androgen Excess Society CGH comparative genomic hybridization
AFP α -fetoprotein CGM continuous glucose monitoring
AHO Albright hereditary osteodystrophy CGMS continuous glucose monitoring sensor
AI aromatase inhibitor cGvHD chronic graft versus host disease
AJCC American Joint Committee on Cancer CH congenital hypothyroidism
ALS acid-labile subunit CHD chromodomain helicase DNA-binding
ALT alanine aminotransferase protein
AME apparent mineralocorticoid excess CHI congenital hyperinsulinism/congenital
AMH anti-müllerian hormone hyperinsulinism of infancy
ANCA antineutrophil cytoplasmic antibody CI cranial irradiation
ANP atrial natriuretic peptide CKK cholecystokinin
APECED autoimmune polyendocrinopathy- CLT chronic lymphocytic thyroiditis
candidiasis-ectodermal dysplasia CMO corticosterone methyl oxidase
APS autoimmune polyendocrine/glandular CNP C-type natriuretic peptide
syndrome CNS central nervous system
ARHR autosomal-recessive CNV copy number variation
hypophosphatemic rickets CPHD combined pituitary hormone defi ciency
ATD antithyroid drugs CPP central precocious puberty
ATP adenosine triphosphate CRF chronic renal failure
AVP arginine vasopressin CRH corticotropin-releasing hormone
AZF azoospermia factor CSI cranio-spinal irradiation
BG blood glucose CSII continuous subcutaneous insulin infusion
BMD bone mineral density CSW cerebral salt wasting
BMI Body Mass Index CT computed tomography/calcitonin
BMP bone morphometric protein CV analytical variance
a
BMT bone marrow transplant CV within-subject biological variation
i
BMU bone remodeling unit CYP cytochrome P450
BNP brain natriuretic peptide DAZ deleted in azoospermia
ix
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x List of Abbreviations
DBD DNA-binding domain GDPP gonadotropin-dependent precocious
DBP vitamin D-binding protein puberty
DDAVP desamino-D-arginine vasopressin GFR glomerular fi ltration rate
DECIPHER Database of Chromosomal Imbalance GH growth hormone
and Phenotype in Humans using GHBP growth hormone binding protein
Ensembl Resources GHD growth hormone defi ciency
DEXA dual energy X-ray absorptiometry GHI growth hormone insensitivity
DHEAS dehydroepiandrosterone sulfate GHIS growth hormone insensitivity syndrome
DHT dihydrotestosterone GHR growth hormone receptor
DI diabetes insipidus/dentinogenesis GHRH growth hormone-releasing hormone
imperfecta GI gastrointestinal/glycemic index
DIDMOAD diabetes insipidus, diabetes mellitus, GIP glucose-dependent insulinotropic peptide
optic atrophy and deafness GIPP gonadotropin-independent precocious
DIT di-iodotyrosine puberty
DKA diabetic ketoacidosis GLP glucagon-like peptide
DM diabetes mellitus GnRH gonadotropin-releasing hormone
DOC deoxycorticosterone GnRHa gonadotropin-releasing hormone analog
DQ developmental quotient GPCR guanine-protein-coupled receptor
DSD disorders of sex development GRA glucocorticoid-remediable
DWBS diagnostic whole-body scan aldosteronism
ECF extracellular fl uid Gsa G-protein α
ECG electrocardiogram GSD glycogen storage disease
ECLIA electrochemiluminescence GTP guanosine triphosphate
immunoassay GTT glucose tolerance test
EGF epidermal growth factor GWAS genome-wide association study
ELISA enzyme-linked immunosorbent assay hCG human chorionic gonadotropin
FA follicular adenoma HDL high-density lipoprotein
FBH familial benign hypercalcemia HH hypogonadotropic hypogonadism
FDA Food and Drug Administration HLA human leukocyte antigen
FGD familial glucocorticoid defi ciency HMGCoA hydroxymethylglutaryl coenzyme A
FGF fi broblast growth factor HOCM hypertrophic obstructive
FGFR fi broblast growth factor receptor cardiomyopathy
FH fi nal height HPA hypothalamo-pituitary axis
FIGO International Federation of Gynecology HPG hypothalamo-pituitary-gonadal
and Obstetrics HPLC high-performance liquid
FIPH familial isolated primary chromatography
hyperparathyroidism HRE hormone response element
FISH fl uorescence i n situ hybridization HSD hydroxysteroid dehydrogenase
FNA fi ne needle aspiration HVDRR hereditary 1α ,25(OH) D-resistant rickets
2
FSH follicle-stimulating hormone IA immunoassay
FT free thyroxine ICF intracellular fl uid compartment
FT-UMP follicular tumor of uncertain ICSI intracytoplasmic sperm injection
malignant potential IFA immunofunctional assay
GABA γ -aminobutyric acid IFG impaired fasting glucose
G-CSF granulocyte-colony stimulating IGF insulin-like growth factor
factor IGFBP insulin-like growth factor binding
GDP guanosine diphosphate protein
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List of Abbreviations xi
IGHD idiopathic isolated GH defi ciency MRI magnetic resonance imaging
IGT impaired glucose tolerance mRNA messenger RNA
IHH isolated/idiopathic hypogonadotropic MRS magnetic resonance spectroscopy
hypogonadism MSH melanocyte-stimulating hormone
IJO idiopathic juvenile osteoporosis MTC medullary thyroid carcinoma
IL interleukin mtDNA mitochondrial DNA
IM intramuscular MUAC mid-upper arm circumference
IMA immunometric assay NDI nephrogenic diabetes insipidus
IP inositol 1,4,5-triphosphate NF neurofi bromatosis
3
IPEX immune dysregulation, NGS next-generation sequencing
polyendocrinopathy, enteropathy, X-linked NSPHT neonatal severe primary
syndrome hyperparathyroidism
IQ intellectual quotient OCP oral contraceptive pill
IRS insulin receptor substrate OGTT oral glucose tolerance test
ISS idiopathic short stature OHD hydroxylase defi ciency/hydroxyvitamin D
ITT insulin tolerance test OHP hydroxyprogesterone
IUGR intrauterine growth restriction OI osteogenesis imperfecta
IV intravenous OMIM Online Mendelian Inheritance in Man
KL Klotho OPG osteoporosis-pseudoglioma syndrome
KS Kallman syndrome PAI plasminogen activator inhibitor
LBD ligand binding domain PAIS partial androgen insensitivity syndrome
LCAD long-chain acyl CoA dehydrogenase PCOS polycystic ovarian syndrome
LCH Langerhans cell histiocytosis PCR polymerase chain reaction
LDL low-density lipoprotein PDGF platelet-derived growth factor
LH luteinizing hormone PET positron emission tomography
LHR luteinizing hormone receptor PFD polyostotic fi brous dysplasia
LHRH luteinizing hormone-releasing hormone PG plasma glucose
lod logarithm of odds PHA pseudohypoaldosteronism
MAPK mitogen-activated protein kinase PHHI persistent hyperinsulinemic hypoglycemia
MAS McCune–Albright syndrome of infancy
MC4R melanocortin 4 receptor PHP pseudohypoparathyroidism
MCAD medium-chain acyl CoA dehydrogenase PLC phospholipase C
defi ciency PNDM permanent neonatal-onset diabetes
MCP monocyte chemoattractant protein mellitus
M-CSF macrophage-colony stimulating factor POMC pro-opiomelanocortin
MCT monocarboxylate transporter POR P450 oxidoreductase
MEN multiple endocrine neoplasia PP pancreatic polypeptide
MHC major histocompatibility complex PPHP pseudo-pseudohypoparathyroidism
MIBG meta-iodobenzylguanidine PPP pseudo precocious puberty
miRNA micro RNA PRA plasma renin activity
MIT mono-iodotyrosine PRL prolactin
MMI methimazole PROK prokineticin
MODY maturity-onset of diabetes in the young PROKR prokineticin receptor
MOPD microcephalic osteodysplastic primordial PTH parathyroid hormone
dwarfi sm PTHrP parathyroid hormone-related peptide
MPHD multiple pituitary hormone defi ciency PTU propylthiouracil
MR magnetic resonance PWS Prader–Willi syndrome
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xii List of Abbreviations
QC quality control SS somatostatin
RAI radioactive iodine StAR steroidogenic acute regulatory protein
RANKL RANK-ligand STK serine-threonine kinase
RBP retinol binding protein STR short tandem repeat
RCV reference change value T testosterone
rhIGF recombinant human insulin-like growth TACE tumor necrosis factor α converting
factor enzyme
rhTSH recombinant human thyroid-stimulating TBG thyroxine-binding globulin
hormone TBI total body irradiation
RRA radioreceptor assay/radioiodine remnant TDF testis-determining factor
ablation Tg thyroglobulin
rRNA ribosomal RNA TG triglyceride
RSV respiratory syncytial virus TGCT testicular germ cell tumor
RTA renal tubular acidosis TNF tumor necrosis factor
RT-PCR reverse transcription polymerase chain TPO thyroid peroxidase
reaction TPP thyrotoxic periodic paralysis
SC subcutaneous TRH thyrotropin-releasing hormone
SCAD short-chain acyl CoA dehydrogenase tRNA transfer RNA
defi ciency TRP tubular reabsorption of phosphate
scc side chain cleavage TSH thyroid-stimulating hormone
SCID severe combined immunodefi ciency UFC urine free cortisol
SCST sex cord stromal cell tumors UV ultraviolet
SD standard deviation VDDR vitamin D-dependent rickets
SDH succinate dehydrogenase VDR vitamin D receptor
SDS standard deviation (Z) score VDRR vitamin D-resistant rickets
SG specifi c gravity VHL Von Hippel–Lindau
SGA small for gestational age VIP vasoactive intestinal peptide
SHBG sex hormone-binding globulin VLCAD very long-chain acyl CoA dehydrogenase
SHH Sonic Hedgehog VNTR variable number of tandem repeats
SIADH syndrome of inappropriate antidiuretic WAGR Wilms tumor, aniridia, genital anomalies
hormone and mental retardation
siRNA small interfering RNA WDR WD-repeat containing protein
SLE systemic lupus erythematosus WDT-UMP well-differentiated tumor of uncertain
SMBG self-monitoring of blood glucose malignant potential
SNP single nucleotide polymorphism XLH X-linked dominant hypophosphatemic
SOD septo-optic dysplasia (vitamin D-resistant) rickets
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1 CHAPTER 1
The Relevance of Molecular Biology
to Clinical Practice
Key learning points
1.The inheritance of genetic disorders in humans may be mendelian or more complex.
2.The human genome contains around 30,000–40,000 genes, and its complexity is further increased by the use
of alternative promoters, epigenetic phenomena and alternative splicing.
3.Further complexity is imparted by disorders of imprinting, mitochondrial disorders, mosaicism, digenic/
oligogenic inheritance, sex-influenced phenotypes and variability of penetrance and expressivity.
4.Novel genetic techniques such as array-CGH and next-generation sequencing will revolutionize molecular
diagnostics over the next few years.
5.Molecular diagnosis is increasingly important for optimal medical management of a number of human
disorders.
An understanding of and a facility with the molecular Genetics (Fig. 1.1 ) is the science of heredity and variation
basis of many endocrine and non-endocrine disorders is and has heretofore focused on chromosomal abnormal-
essential to the practice of pediatric endocrinology in the ities and inborn errors of metabolism. Analysis of the
21st century and knowledge is accumulating rapidly transmission of human traits and disease within families
(see Online Mendelian Inheritance in Man [OMIM], a has led to understanding many monogenic disorders.
comprehensive catalog of human genes and genetic Diabetes mellitus type 2, obesity, hypertension, heart
d isorders in order to keep pace with this field: w ww.ncbi. disease, asthma and mental illnesses are complex and the
nlm.nih.gov/sites/entrez?db=omim ) (see also Web links genetic susceptibilities to these disorders are influenced by
box). With the exception of simple trauma, every disease exogenous factors interacting with genetic susceptibilities.
has a genetic component. Phenotype can also be influenced by genetic and
In monogenic disorders, for example, congenital a drenal environmental modifiers in monogenic disorders. For
hyperplasia (CAH), the genetic component is the major example, the expression of the phenotype in monogenic
etiological factor. Multiple genes operating in conjunction forms of diabetes mellitus due to mutations in the
with environmental and lifestyle factors contribute to the maturity onset of diabetes in the young (MODY) genes is
pathogenesis of polygenic or multifactorial disorders. influenced by factors such as diet and physical activity.
Genetic factors also influence the manifestation of disease The term genome , introduced before the recognition
directly through the genetic defect or indirectly by defining that DNA is the genetic material, designates the totality
the host ’ s susceptibility and resistance to an environmental of all genes on all chromosomes in the nucleus of a cell.
disease such as i nfection. Genomics refers to the discipline of mapping, sequencing
Handbook of Clinical Pediatric Endocrinology, Second Edition. Charles G. D. Brook and Mehul T. Dattani.
© 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.
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