Practical

Algorithms in
Pediatric
Endocrinology
2nd, revised edition

Editor
Zeev Hochberg, Haifa

53 graphs, 7 figures and 3 tables, 2007

 Contents
Contributors Puberty Intersex

1 Introduction 14 Precocious breast development 36 Micropenis at age 1 year to puberty

Z. Hochberg in a girl M. Ritzn; R.L. Hintz
J.-P. Bourguignon; R.L. Rosenfield
38 Micropenis in a newborn
16 Precocious genital development M. Ritzn; R.L. Hintz
Growth in a boy 40 Hypospadias/virilization
J.-P. Bourguignon; R.L. Rosenfield M. Ritzn; R.L. Hintz
2 Failure to thrive
18 Precocious pubarche 42 Cryptorchidism
R.L. Hintz; Z. Hochberg
J.-P. Bourguignon; R.L. Rosenfield A.D. Rogol; Z. Hochberg
4 Short stature
20 Gynecomastia 44 Turner syndrome
R.L. Hintz; M. Ritzn
N. Zuckerman-Levin; Z. Hochberg; R.L. Hintz; Z. Hochberg
6 Growth hormone treatment R.L. Rosenfield
R.L. Hintz; J.-P. Bourguignon
22 Delayed or absent testicular
8 Tall stature development Adrenal
N. Zuckerman-Levin; Z. Hochberg; M. Ritzn J.-P. Bourguignon; R.L. Rosenfield

10 Overweight and obesity/ 24 Delayed or absent breast 46 Hypertension

Infantile obesity development F. Riepe; W.G. Sippell; Z. Hochberg
Z. Hochberg; A.D. Rogol J.-P. Bourguignon; R.L. Rosenfield
48 Cushing syndrome
12 Brain irradiation 26 Primary amenorrhea and A.D. Rogol; Z. Hochberg
A.D. Rogol; D.B. Dunger abnormal genital anatomy 50 Congenital adrenal hyperplasia
R.L. Rosenfield
(CAH) in the newborn period
28 Secondary amenorrhea or M. Ritzn; R.L. Hintz
oligomenorrhea 52 Congenital adrenal hyperplasia
R.L. Rosenfield
(CAH) presenting after the newborn
30 Anovulatory disorders period
R.L. Rosenfield; J.-P. Bourguignon M. Ritzn; R.L. Hintz

32 Hirsutism
R.L. Rosenfield; F. Riepe; W.G. Sippell

34 Hyperandrogenemia
R.L. Rosenfield; F. Riepe; W.G. Sippell
Water and electrolytes Thyroid Carbohydrates

54 Polyuria 76 Congenital hypothyroidism 94 Hypoglycemia

N. Zuckerman-Levin; Z. Hochberg; A.D. Rogol T.P. Foley, Jr.; F. Pter M.A. Sperling; O. Escobar; R.K. Menon;
D.B. Dunger
56 Hyperhydration 78 Juvenile hypothyroidism
W.G. Sippell; Z. Hochberg F. Pter; T.P. Foley, Jr. 96 Hyperglycemia
D.B. Dunger; O. Escobar; R.K. Menon;
58 Dehydration 80 Hyperthyroidism M.A. Sperling
W.G. Sippell; Z. Hochberg F. Pter; T.P. Foley, Jr.
98 Prediabetes and prediction of
60 Hypernatremia 82 Neonatal hyperthyroidism diabetes
W.G. Sippell; Z. Hochberg T.P. Foley, Jr.; F. Pter
D.B. Dunger; O. Escobar; R.K. Menon;
62 Hyponatremia 84 Goiter M.A. Sperling
W.G. Sippell; Z. Hochberg T.P. Foley, Jr.; F. Pter 100 T2DM
64 Hyperkalemia 86 Thyroid nodules in children and D.B. Dunger; O. Escobar; R.K. Menon;
M.A. Sperling
F. Riepe; W.G. Sippell; Z. Hochberg adolescents
T.P. Foley, Jr.; F. Pter 102 Type 1 diabetes mellitus
66 Hypokalemia
D.B. Dunger; O. Escobar; R.K. Menon;
F. Riepe; W.G. Sippell; Z. Hochberg 88 Thyroid carcinoma
M.A. Sperling
T.P. Foley, Jr.; F. Pter
104 Maturity-onset diabetes of youth
90 Hypothyroxinemia
Calcium metabolism (MODY)
T.P. Foley, Jr.; F. Pter
M.A. Sperling; O. Escobar; R.K. Menon;
92 Hyperthyroxinemia D.B. Dunger
68 Hypercalcemia F. Pter; T.P. Foley, Jr.
D. Tiosano; Z. Hochberg 106 Diabetic ketoacidosis
D.B. Dunger; O. Escobar; R.K. Menon;
70 Hypocalcemia M.A. Sperling
D. Tiosano; Z. Hochberg

72 Rickets
D. Tiosano; Z. Hochberg
108 Index of Signs and Symptoms
74 Hypomagnesemia 112 Abbreviations
A.D. Rogol; Z. Hochberg
 Contributors
Jean-Pierre Bourguignon, MD, PhD Zeev Hochberg, MD, PhD Robert L. Rosenfield, MD
CHU Sart Tilman Rambam Medical Center The University of Chicago
Lige, Belgium Technion Israel Institute of Technology Childrens Hospital
Haifa, Israel Chicago, Illinois, USA

David B. Dunger, MD
Department of Paediatrics Ram K. Menon, MD Wolfgang G. Sippell, MD
University of Cambridge, Addenbrookes Hospital Childrens Hospital Universitts-Kinderklinik
Cambridge, UK Pittsburgh, Pennsylvania, USA Kiel, Germany

Oscar Escobar, MD Ferenc Pter, MD, PhD, DSc Mark A. Sperling, MD

Childrens Hospital Buda Childrens Hospital and Policlinic Childrens Hospital
Pittsburgh, Pennsylvania, USA Budapest, Hungary Pittsburgh, Pennsylvania, USA

Thomas P. Foley, Jr., MD Felix Riepe, MD Dov Tiosano, MD

University of Pittsburgh Universitts-Kinderklinik Meyer Childrens Hospital
Pittsburgh, Pennsylvania, USA Kiel, Germany Haifa, Israel

Raymond L. Hintz, MD Martin Ritzn, MD, PhD Nehama Zuckerman-Levin, MD

Stanford University Medical Center Karolinska Hospital Rambam Medical Center
Stanford, California, USA Stockholm, Sweden Haifa, Israel

Alan D. Rogol, MD, PhD

University of Virginia
Health Science Center
Charlottesville, Virginia, USA

Library of Congress Cataloging-in-Publication Data Disclaimer. The statements, options and data contained in this publi- All rights reserved. No part of this publication may be translated into
Practical algorithms in pediatric endocrinology / cation are solely those of the individual authors and contributors and other languages, reproduced or utilized in any form or by any means,
editor, Zeev Hochberg. 2nd, rev. ed. not of the publisher and the editor(s). The appearance of advertise- electronic or mechanical, including photocopying, recording, micro-
p. ; cm. ments in the book is not a warranty, endorsement, or approval of the copying, or by any information storage and retrieval system, without
Includes bibliographical references and index. products or services advertised or of their effectiveness, quality or permission in writing from the publisher.
ISBN-13: 978-3-8055-8220-9 (softcover : alk. paper) safety. The publisher and the editor(s) disclaim responsibility for any
1. Pediatric endocrinology Diagnosis Decision making. 2. Decision injury to persons or property resulting from any ideas, methods, in- 1st edition: Practical Algorithms in Pediatric Endocrinology
trees. structions or products referred to in the content or advertisements. Editor: Z. Hochberg, Haifa
I. Hochberg, Z. [DNLM: 1. Endocrine System Diseases. 2. Adolescent. IV + 110 p., 52 graphs, 4 fig., 1 tab., spiral bound, 1999
3. Child. 4. Decision Trees. 5. Endocrine System Diseases diagnosis. Drug Dosage. The authors and the publisher have exerted every effort ISBN 380556693X
6. Infant. WS 330 P8949 2007] to ensure that drug selection and dosage set forth in this text are in
RJ418.P69 2007 accord with current recommendations and practice at the time of pub- Copyright 2007 by S. Karger AG, P.O. Box, CH4009 Basel
618.924 dc22 lication. However, in view of ongoing research, changes in government (Switzerland)
2007012334 regulations, and the constant flow of information relating to drug ther- Printed in Switzerland on acid-free paper by Reinhardt Druck, Basel
ISBN 9783805582209 (spiral bound: alk. paper) apy and drug reactions, the reader is urged to check the package insert ISBN 9783805582209
for each drug for any change in indications and dosage and for added
warnings and precautions. This is particularly important when the rec-
ommended agent is a new and/or infrequently employed drug.
 Introduction

The first edition of Practical Algorithms in Pediatric Several chapters include suggestions made by our experienced with a given problem, a prepared algo-
Endocrinology was compiled in 1998 and published in readers and, as before, I invite comments to correct rithm would provide a logical, concise, cost-effective
1999. In the 8 years between its publication and this any mistakes which may have occurred or to make any approach prepared by a specialist who is experienced
second edition, molecular endocrinology has changed improvements to the diagnostic algorithms we offer. with the given problem. It would also train a young
our clinical practices to a level unimaginable only a practitioner in medical reasoning. This book is, there-
I hope you will find this book helpful in managing the
decade ago. The colossal pace of discovery in both fore, aimed at an audience of general practitioners
children under your care.
basic and clinical endocrinology has changed not only or pediatricians who are not exposed on a daily basis
our understanding, but also our daily engagement with to pediatric endocrine problems. It would also aid
Zeev Hochberg, MD, PhD
patients and parents. trainees in pediatric endocrinology as they presume
April 2007, Haifa
familiarity with clinical problem-solving to make
The first edition has sold over 3,000 copies. It is a
rational choices in approaching a clinical dilemma.
tribute to the 12 contributors to the first edition in that it
has become a leading bedside source for general prac- Certainly, there is more than one way to approach a
titioners, pediatricians and pediatric endocrine fellows. Introduction to 1st edition clinical problem, and this book presents one such way
The same contributors responded willingly to revise for each problem, prepared by skilled, experienced
each of the 50 algorithms. Naturally, we have additional Textbooks of medicine are oriented by body systems, specialists in pediatric endocrinology. The algorithms
younger contributors who have grown to be among the by disease or by diagnoses. Yet, the practicing physi- were prepared through discussion and deliberation
new leadership in pediatric endocrinology worldwide. cian is encountered by a patients complaint, by a symp- among the authors of this book. By no means should
tom, by a physical sign or by a laboratory abnormality, they be viewed dogmatically as the one and only ap-
The basic outline remains unchanged. Algorithms are
from which he is expected to proceed to diagnosis and proach. We paid special attention to simple passages,
practical tools to help us address diagnostic and
to plan management. The traditional medical approach rejecting groups of diagnoses first by history and
therapeutic problems in a logical, efficient and cost-
is through differential diagnosis by exclusion. Algo- physical examination, then by simple laboratory tests
effective fashion. The enormous success and sell-out
rithms provide a direct approach to breaking down long common to any clinical setting, and only finally, in
of the first edition confirmed that this approach was
list tables of differential diagnosis into smaller, more some cases, to more sophisticated laboratory means,
useful for clinicians caring for children with endocrine
manageable lists, as often a whole group of diagnoses which may require specialized proficiencies.
disorders.
can be excluded by a single or a group of signs, blood
The term algorithm is derived from the name of the
As with any approach that attempts to simplify com- tests or imaging.
ninth century Arabic mathematician Algawrismi, who
plex problems, there will always be exceptions. Each
Practical Algorithms in Pediatric Endocrinology is also gave his name to algebra. His algorismus indi-
algorithm must be used in the context of the individual
meant as a pragmatic text to be used at the patients cated a step-by-step logical approach to mathematical
findings of each patient under examination and in
bedside. It classifies common clinical symptoms, signs problem-solving. It is presented hereby to the medical
conjunction with the published literature. The clinician
and laboratory abnormalities as they present to us in practitioner in that same spirit.
1 must always be aware that any individual patients
daily practice. The experienced practitioner applies
presentation may be atypical enough, or confounded
step-by-step logical problem-solving for each patient Zeev Hochberg, MD, PhD
by concomitant disorders or complications, to render
individually. Decision trees prepared in advance April 1999, Haifa
our approaches invalid. In addition, advances in diag-
have the disadvantage of unacquaintedness with the
nosis and management can render current approaches
individual patient. Yet, for the physician who is less
obsolete.
 Growth R.L. Hintz Z. Hochberg Failure to thrive

>ii /

2
`i>`i}}>0

]>i>`V>i>>1

>i}}>

>

}}iivVV>Li2 ]* ii>}3 * }}iiv iVi>V`i7

}iiV`i6

"Li>v>i>V`i>V iVi
ii`}L>iiiVi`i i>>
i
>iv>L i>LVi}
-i`i>>i -iVvV`i
/{/- }Li8>

i`i>>L`i
-i>V`i4

i

-ii->i]{

`Vi715

> >i>`i> -iVvV`>}

iVV>i *V}V>ii i>iiVvVi>i
 Growth R.L. Hintz J.-P. Bourguignon Growth hormone treatment

ii>i
/

6 ,i>Vii ->Li

`
` /i`i ,i>v>i 1, "i
,i`Vi`}>iq-- viiiV`` ->iq-- *} Vi>
->iq-- *>``i0
{i>1
{i>2 `V>

-i>`i>0
iiV

,ii>iviVi3

>  x}}`> x}}`> x}}`>

i`Li>

>`>
*>>>V`i>i x}}`>V`
/iviVi3

> 

>i

9i4



i`Li> , /i>i }

ii
`\xqx}}`>qx1}`> 
>i
`\xq}`>{xq1`> -`iivviV5
 *
>i``>i "i

q>i`6 ,i>iL//>viLi
 Evaluation The key to the initial evaluation for 2 A child with significant short stature and/or 7 During GH therapy, occurrence of side ef-
GH treatment is a careful history and decreased growth rate (Ht <2.5 SDS for age, Ht veloc- fects has been reported in <1% of the patients, includ-
physical examination. ity <1 SDS) and/or a history of CNS lesions or irradia- ing benign acute intracranial hypertension and Legg-
tion treatment, or an adult with a history of childhood- Calv-Perths disease. Assessment is required in pa-
History Birth history and past growth onset GH deficiency or an acquired pituitary/hypotha- tients complaining about headaches or leg pain and
Family history of height and lamic disorder should be tested for the ability to se- limp. The dose of GH can be adjusted to obtain a
development crete GH by one or several standardized methods. Se- growth response with IGF-1 levels or free IGF-1 index
CNS lesion or history of CNS rum IGF-1 and/or IGFBP-3 are helpful screening tests (IGF-1/IGF-BP3 ratio) in the upper normal range for
irradiation or surgery of GH secretion. If GH secretion is below normal (see age.
Evidence for systemic disease footnote 5) then the diagnosis of GH deficiency is
Nutrition made, imaging of the brain and evaluation of other 8 After completion of growth on GH treatment
Use of medications influencing pituitary hormones should be completed, and GH in a GH-deficient patient, the question has to be ad-
growth, such as glucocorticoids treatment instituted. dressed whether or not GH replacement should be fur-
Genetic forms ther provided in adulthood. In patients with isolated
3 Patients with diagnosed Turner syndrome and idiopathic forms of GH deficiency, retesting (ITT)
Physical Any evidence of systemic disease or (see p. 44), short stature, and open epiphyses can be after several weeks of treatment withdrawal is impor-
examination malnutrition treated with GH without the necessity of testing GH tant since 1/2 to 2/3 patients will exhibit normalized GH
Anomalies suggestive of secretion. response to ITT.
chromosomal disease
U/L ratio (or sitting height) and span 4 Children with slow growth due to chronic
renal failure or IUGR can also be treated with GH with- Selected reading
Laboratory T4, TSH, BUN or creatinine, ESR, CO2, out the necessity of testing of GH secretion.
CBC and others as indicated Molitch ME, Clemmons DR, Malozowski S, Merriam
BA 5 It is important that any hypothyroidism be GR, Shalet SM, Vance ML: Endocrine Societys
Chromosomes in female, or in male diagnosed and adequately treated before testing for Clinical Guidelines Subcommittee: Stephens PA:
with anomalies GH deficiency is carried out. IGF-1 and IGFBP-3 levels Evaluation and treatment of adult growth hormone
IGF-1, IGFBP-3, GHBP and basal GH are valuable screening tests for inadequate GH secre- deficiency: an Endocrine Society Clinical Practice
GH provocative testing (or GH tion in childhood. Values of IGF-1 above 1 SDS for age Guideline. J Clin Endocrinol Metab 2006;91:
endogenous secretion) in children essentially rule out GH deficiency, and val- 16211634.
Gene mutations (Pit-1, ) ues of IGF-1 and IGFBP-3 below 2 SDS strongly sug- Thomas M, Massa G, Craen M, de Zegher F,
gest an abnormality of GH secretion or action. How- Bourguignon JP, Heinrichs C, De Schepper J,
ever, there are many causes of low IGF-1 levels in addi- Du Caju M, Thiry-Counson G, Maes M: Prevalence
tion to GH deficiency, such as malnutrition and chronic and demographic features of childhood growth
disease. IGF-1 and IGFBP-3 levels are less helpful in the hormone deficiency in Belgium during the period
diagnosis of adult GHD. Provocative GH testing in chil- 19862001. Eur J Endocrinol 2004;151:6772.
dren uses many standardized protocols. A peak value
of GH in two provocative tests below 10 g/l in a poly- Thomas M, Massa G, Maes M, Beckers D, Craen M,
clonal GH RIA (or equivalent lower value in two-site Franois I, Heinrichs C, Bourguignon JP, in collabo-
GH assays) is consistent with GH deficiency in a child. ration with the BSGPE: Growth hormone secretion
Sex hormone priming may be needed in cases of con- in patients with childhood-onset GH deficiency:
stitutional delay of growth and puberty to distinguish retesting after one year of therapy and at final
this normal variant from GH deficiency. The recom- height. Horm Res 2003;59:715.
1 The commonly approved indications for GH mended GH provocative test in adults is insulin hypo-
treatment are for children with significant short stature glycemia and the diagnostic level is below 3 g/l.
due to inadequate GH secretion; adults with GH defi-
ciency and changes in body composition, energy level, 6 A child with GH secretion not consistent
7 strength and metabolism; children with Turner syn- with the diagnosis of classic GH deficiency, but with
drome and poor growth, and chronic renal failure with significant short stature and persistently low growth
slow growth rate and intrauterine growth retardation rate for age may still be considered for a trial of GH
(IUGR). The commonly recommended daily dose of treatment, especially if there is a history of hypotha-
GH vary depending on the conditions. lamic-pituitary disease or cranial irradiation.

Growth R.L. Hintz J.-P. Bourguignon Growth hormone treatment

 Puberty J.-P. Bourguignon R.L. Rosenfield Precocious breast development in a girl

*iVVLi>`iii>} /

0
14

Li
V>i`}vLi1 *ii

> i}iV2 Vi>i`

1iiVi`
>
3
`>Vi`

*Li>iV
**/{`ivViV

}V>
}V> >`5
i/{iVi
>}ii> >}ii>

*iLi>iV -ii,6 ->`ii,6

>`5

*ii>iVV
- i}>i
->}}8 *i
->}}8 Li<
ii,6
">>>`i>>}}

i`V>>ViV
}i

>vj>>

v>i *i>i 6>>9 `>VVi> "}>VVi> V

i
L}`i= ">>V
>>>4 i>Vi7 iVVLi: iVVLi: }ii`

iVi}
`

-iV`>
**

}>` ,>}i>; }V>i>
>>i ,>} i`V>>`

`iii L }V>>>}ii

i}i
 1 Precocious breast development is the occurrence of breast 7 Pelvic ultrasound is a noninvasive method to evaluate 13 GnRH agonist therapy, particularly the long-acting forms
tissue before the chronological age of 8 years in a girl. A different morphology and size of the ovaries and the uterus. The ovaries of the given as i.m. injections every 4 weeks or every 3 months, is the treat-
age limit may have to be used in particular environmental and ethnic prepubertal child may normally have a few follicles or microcysts ment of choice of CPP. The promoting effects on adult height are lim-
groups (e.g. Black Americans are about 1 year ahead of White Ameri- up to 4 mm in diameter. The volume of the prepubertal uterus should ited when PP started after 6 years but psychosocial aspects may still
cans); the reader should refer to the local standards and experience. be 2 ml (length 4 cm). Additional information comes from the provide an indication. Cyproterone or medroxyprogesterone show
In developed countries, the secular reduction in average timing of Doppler study of uterine vessel resistance. Early pubertal stages are less-specific and more-undesirable (glucocorticoid-like) effects.
puberty has apparently come to an end but the early age limits may associated with a reduced pulsatility index. Pelvic ultrasound is pref- They can be considered when adult stature is not an objective while
still further decrease. The epidemic of obesity has been incriminated. erable to the vaginal smear which provides an alternative but inva- arrest of puberty and menses is wanted, e.g. in the severely mentally
Alternative factors are the endocrine disrupters. The tempo of devel- sive method to assess estrogenization of the female genital tract. retarded.
opment is important information that can be obtained through a 3- to Plasma estradiol measurements are not reliable unless an assay sen-
6-month follow-up. This tempo is usually low and comparable to sitive to <10 pg/ml is used, and cyclic fluctuations must be taken into 14 PPP involves estrogens of ovarian, adrenal or exogenous
normal puberty in the early variants of physiological development. In consideration in interpreting the value. In some patients seen very origin. True sexual precocity may rarely be caused by intracranial
contrast, fast progression throughout pubertal stages may be seen early during puberty, pelvic ultrasound may not yet show evidence human CG-producing germ cell tumors. A rare form of PPP can be
in patients with precocious puberty of abnormal organic or idiopath- of an estrogenic effect while measurement of the gonadotropins will associated with severe juvenile hypothyroidism and is reversible un-
ic origin. provide evidence of CPP. der thyroxine substitution. The advanced hypothalamic maturation
resulting from PPP may secondarily cause CPP. Ovarian imaging can
2 History is critical regarding disorders or symptoms orient- 8 Gonadotropin secretion (FSH and LH) can be assessed in be initially obtained through pelvic echography, while reliable adre-
ing towards an organic CNS cause. In several countries, migration different ways. A classical manner is the measurement of plasma nal imaging usually requires a CT or MRI scan.
for international adoption has emerged as a new cause of precocious gonadotropins before,
puberty. 20 min, and 60 min after a bolus injection of GnRH at a dose of 1 g/ 15 McCune-Albright syndrome results from tissue-specific
kg (max. 100 g). Typically, the secretory response of FSH predomi- auto-activating mutation in the signaling G-protein system (constitu-
3 Associated signs may involve pubic and axillary hair, nates while the LH response is low in premature thelarche. In con- tive mutation only observable in cells from affected tissues). It asso-
swelling of vulvar mucosa, vaginal discharge or bleeding. Sexual trast, LH response shows a characteristic pubertal increase in CPP ciates caf-au-lait spots and dysplastic lesions of the long bones. Ca-
hair is often absent early. and the response of both FSH and LH is low in peripheral sexual pre- f-au-lait spots are also observed in neurofibromatosis which can be
cocity. Some authors have suggested the use of urinary gonadotro- associated with CPP and adrenal tumors as well.
4 Height velocity shows early and rapid acceleration under pin measurement as a convenient and reliable index. The critical is-
estrogen action. It should be calculated retrospectively (when data sue is the availability of normative values to interpret the data ob-
from school or medical records are available) or prospectively. In- tained from the laboratory. Selected reading
creased height velocity should be > the 90th centile (78 cm/year be-
tween 5 and 9 years of age). When height velocity is unexpectedly 9 Premature thelarche is usually a self-limited condition but Feuillan P, Merke D, Leschek EW, Cutler GB Jr: Use of aromatase
low while the other findings indicate increased estrogen activity, GH may be the initial manifestation of CPP and requires clinical follow- inhibitors in precocious puberty. Endocrine-Related Cancer
deficiency could be associated with central precocious puberty, par- up of growth and pubertal development. 1999;6:303306.
ticularly if there is any organic cause. Then, a prepubertal level of Himes JH: Examining the evidence for recent secular changes in
serum IGF-1 is suggestive and GH stimulation test should be consid- 10 CNS imaging is required when gonadotropin secretion the timing of puberty in US children in light of increases in the
ered (see p. 6). Likewise, hypothyroidism should be ruled out since it shows a pubertal secretory pattern indicating hypothalamopituitary prevalence of obesity. Mol Cell Endocrinol 2006;254255:1321.
can account for sexual precocity and slow height velocity. maturation. Though optimal imaging of this region is provided by
MRI, a CT scan is informative as well. Lebrethon MC, Bourguignon JP: Central and peripheral isosexual
5 BA (X-ray film of left hand and wrist read according to precocious puberty. Curr Opin Endocr Diab 2001;8:1722.
standards such as Greulich and Pyle) advancement means at least 2 11 Idiopathic CPP (or complete, true precocious puberty) is Parent AS, Teilmann G, Juul A, Skakkebaek N, Toppari J,
SDs ahead of chronological age (12 years depending on age). When diagnosed when the history, physical examination and imaging of Bourguignon JP: The timing of normal puberty and the age limits
increased estrogen secretion has occurred very recently, BA ad- the CNS do not indicate any possible etiology or mechanism. In girls, of sexual precocity: variations around the world, secular trends
vancement may not be significant initially. idiopathic CPP is about 45 times more common than organic CPP and changes after migration. Endocr Rev 2003;24:668693.
which involves causes such as CNS tumors.
6 Infantile mammoplasia is a self-limited early form of pre-
mature thelarche which may develop during the neonatal period or 12 It is now recognized that there is a continuum of conditions
infancy. Follow-up involves assessment of breast development and between premature thelarche and idiopathic CPP, with partial evi-
15 growth rate every 36 months as well as bone maturation at 1- to dence of premature estrogenization besides breast development.
2-year intervals. If a persisting estrogenic effect is suspected, pelvic Such conditions involve the slowly progressive variants of CPP and
ultrasound will be requested. If ultrasound is prepubertal, no endo- advanced PP starting at borderline age, for which no treatment is
crine assessment is mandatory but follow-up is necessary. Indeed, usually required, although follow-up is necessary.
this condition may rarely be the initial manifestation of true sexual
precocity.

Puberty J.-P. Bourguignon R.L. Rosenfield Precocious breast development in a girl

 Intersex M. Ritzn R.L. Hintz Micropenis at age 1 year to puberty

Vi>>}ii>Li /

36

-}0 >}

iV\ ,i4
i


/{]/-
/
,i
,v
-

>
L>v>}i v>}i
L> > 

V] /
]->`/

- -
i}{ /v>}i /v>}i

   /ii>>Li /ii

>>Li

i

/Vi>i /
>vi
 ii

*>>1 2  /iV> /iV> /iV> >` Vii

i3 `}ii5 `}ii >7 `ivViV >`}i
VV`6 i:

>
>>`i8
-Li] i>i 
V>`i i>i

/iiii>i9
 Adrenal F. Riepe W.G. Sippell Z. Hochberg Hypertension

ii /

46 7i} *>>i>V0

i>i
VV>`}>

i }i

`ii1
`ii1

>iV>i

`ii2
`ii6
`ii

i>i>i
>`>7

*>>V *i}ii] iV- iLi -iLi

i }iii >`"
>` >`i >`i


/ >`"
>` >/-
1>// > > >`/"

i}>`

,i>`i>i ``i`i

`i *>> ,i>V> *iVV>;

>V> A`>i`iviV4 i>`i iVV>

`i8 -iV`>
i>`i:

 3 Vi>Li

`i VVV`iLirii`>Li
B`>i`ivViV5 i>`i9
 Water and electrolytes N. Zuckerman-Levin Z. Hochberg A.D. Rogol Polyuria

*>
/

54
Vi  *12
i>i
>

*"}C
{ *
1
-ii`i`>iC
x

*"}
* *1>
13 1n"}
/iV>Vi *>`>

>Liii0 >i>1 >Lii`3 *VV`>

iiL> > ,i>`i>i iV>Vi>C

7v>`i }iV`>Lii`C
>>}C
n

>`i i``i ->V`C

`i

1V>}i` 6>ii4 1

i}iV`>Lii`
i>`>Lii`

> >
qi i
>}};
qi i

qi i

iV >
vi<

1V>}i` -i"/= 1n"}

}5 8i`6
i>`>Lii i> *>>`>Lii
-B]V8C] >>Vi>

>iVii7 ` i>i>> `? >>C
]ViiL>>v>] `>Lii`C

i}]ii`>`><

 >`i ii`i@
/>`i`iV8 ,A
-
9
iiVVi}:
 Calcium metabolism D. Tiosano Z. Hochberg Hypercalcemia

iV>Vi> /
iV>ViVV0

i>>iV>Vi>I -i>L

68

Lx}
Lx}

i`
>

]V>i>>]}V>]
Vi>i]L`}>i]/-]n>V
>/
>

1>V>V7

 } *i`iV>Vi>

-i>`>*9

-
1I: -

*/]*/; -i>

*/ */ */  

7>`iI >> i>>`I< >i >}>V; V>I? >>`i>i@

L>1 V>VV  = i>i>
i`2 iV>Vi>I8 `>>>
>}iVI3

>4

`i>vvViV5
,i>v>i6

>}} >ii>
 Thyroid T.P. Foley, Jr. F. Pter Congenital hypothyroidism

}i>`
iLViii/
>i>]V>i>>0
76 -iVv>i
/->`vii/{1
,"`iii0

/- /- i>>Li/-

/{ /{

/-v>}i /-v>}i /- /- 1`iiV>Li/-

ii/{v>}i vii/{v>}i v`i vii/{ /-14 ii/{>`/vii/
ii ii/{
}i>` L`iV
V> `>
/`>}iiVi`i`2 /`>}iiVi`i`2 1i`i
>`V> >`V> / >i>`
>iiVi`i`
>>iviV`>
/-
i>`
->ii>vV>
>`i>
>L>>`/-x1]
/  /  i`ivViVi
i/-v/-x1
>``iVi>}]>`vii/{i>> vii/{
,v>>
>`>

`i
i }ii VV` V` `iiVi / `ivViV /{L`}i -iV`>i>

`ivViV >L> `

->/{ iiV vi ,ii>>i>>}ii> i> i> /{i>ViiVi

i>Livi Vi} `i>` v`}ii `vV V>i>
ivi i>vvi >ii>>> i>i`
V>> ` >>iv*>`
i3 /-}ii`iviV

`i/,i>vi
,iv/-`} ->/{ v/-i>ii>i` >}ii>
i>ii >`Vi
>i` >`i>
>i>v -i
` }L3
>`>i >vii
``i>i >i
i>i/,
L] >}i
/*"
L]/
L0
 1 Newborn screening tests: The dried blood 4 A thyroid image by ultrasound or scan with
Selected reading
specimen is collected by heel prick of the infant usu- technetium pertechnetate will confirm within 2 h, the
ally prior to discharge, preferably after 24 h of age to suspected diagnosis of these disorders: (a) ectopic American Academy of Pediatrics; Rose SR; Section
avoid a higher frequency of false-positive values. The thyroid dysgenesis and the life-long need for thyroxine on Endocrinology and Committee on Genetics,
three most common screening methods for congenital therapy; (b) athyreosis (in the absence of TSH-receptor American Thyroid Association; Brown RS; Public
hypothyroidism using dried blood specimens are: antibodies); (c) familial dyshormonogenesis with goi- Health Committee, Lawson Wilkins Pediatric
(a) primary TSH screen; (b) primary T4 screen with con- ter in the absence of iodine deficiency. The procedure Endocrine Society; Foley T, Kaplowitz PB, Kaye CI,
firmatory TSH on the lowest 520% of T4 values, and has no known risk and can be easily and accurately Sundararajan S, Varma SK: Update of newborn
(c) primary TSH and primary T4 screen. The measure- performed and interpreted by experienced pediatric screening and therapy for congenital hypothyroid-
ment of TSH and total T4 on every neonate provides nuclear medicine specialists. A scan to suggest the ism. Pediatrics 2006;117:22902303.
comprehensive screening for CH of primary and cen- presence of familial disease is important for genetic
Fisher D: Next generation newborn screening for
tral (hypothalamic-pituitary) etiology with the lowest counseling of the parents.
congenital hypothyroidism? J Clin Endocrinol
false-negative results. The addition of TBG screening
Metab 2005;90:37973799.
on specimens with low T4 screening results reduces 5 Undetectable serum thyroglobulin values
the number of false-positive rates on with low T4 confirm the absence of thyroid tissue or the diagnosis Fu J, Jiang Y, Liang L, Zhu H: Risk factors of primary
screening values. The use of tandem mass spectrom- of thyroglobulin synthetic defects in neonates or chil- thyroid dysfunction in early infants born to mothers
etry to measure along with many other analytes keeps dren with a eutopic thyroid, thyromegaly, or a normal- with autoimmune thyroid disease. Acta Paediatr
the cost of screening for CH as low or lower than the sized thyroid, and primary hypothyroidism. 2005;94:10431048.
other two programs. To date no valid and reproducible
Kempers MJ, Lanting CI, van Heijst AF, van
free T4 screening method is available, though very de- 6 Neonates with low serum total and free T4
Trotsenburg AS, Wiedijk BM, de Vijlder JJ, Vulsma T:
sirable. and low, normal or mildly elevated serum TSH must
Neonatal screening for congenital hypothyroidism
be evaluated for hypothalamic-pituitary hypothyroid-
based on thyroxine, thyrotropin, and thyroxine-
2 Maternal history and physical examination ism. Clinical features often seen in infants with con-
binding globulin measurement: potentials and
of the infant may disclose the etiology for abnormal genital hypopituitarism include: (a) unexplained hypo-
pitfalls. J Clin Endocrinol Metab 2006;91:33703376.
screening tests for hypothyroidism: (a) maternal auto- insulinemic hypoglycemia; (b) combined direct and
immune thyroid disease may be associated with trans- indirect hyperbilirubinemia; (c) midline facial and/or Knobel M, Medeiros-Neto G: An outline of inherited
placentally acquired TSH-receptor-blocking antibodies CNS birth defects, and (d) hypogonadism in male in- disorders of the thyroid hormone generating
that may induce transient primary congenital hypothy- fants (micropenis and testicular volume 1 ml). A serum system. Thyroid 2003;13:771801.
roidism in the neonate; (b) maternal autoimmune thy- cortisol test is required before T4 therapy is started in
La Gamma EF, van Wassenaer AG, Golombek SG,
roid disease may be associated with transplacentally order to determine or exclude the presence of CRF-
Morreale de Escobar G, Kok JH, Quero J, Ares S,
acquired TSH-receptor-stimulating antibodies from ACTH-Adrenal Insufficiency. Infants with low cortisol
Paneth N, Fisher D: Neonatal thyroxine supplemen-
mothers with active Graves disease who are receiving values must be treated with hydrocortisone before T4
tation for transient hypothyroxinemia of prematu-
treatment with antithyroid drugs that cross the pla- therapy is initiated in order to prevent the induction of
rity: beneficial or detrimental? Treat Endocrinol
centa and may cause neonatal goiter with/without acute adrenal insufficiency.
2006;5:335346.
transient primary hypothyroidism; (c) maternal iodine
deficiency or exposure of mother and/or neonate to Nelson JC, Wilcox RB: Analytical performance of
supraphysiologic amounts of iodide may cause tran- free and total thyroxine assays. Clin Chem
sient neonatal goiter and hypothyroidism. 1996;42:146154.
Peter F: Thyroid dysfunction in the offspring of
3 Serum free T4 should be measured by direct
mothers with autoimmune thyroid diseases.
dialysis or methods whose validity has been docu-
Acta Paediatr 2005;94:10081010.
mented in cord or neonatal serum specimens by cor-
relation with values obtained by direct dialysis. van Tijn DA, de Vijlder JJM, Verbeeten B Jr, Verkerk
PH, Vulsma T: Neonatal detection of congenital
hypothyroidism of central origin. J Clin Endocrinol
Metab 2005;90:33503359.
77
Van Vliet G, Polak M: Thyroid disorders in infancy;
in Lifshitz F (ed): Pediatric Endocrinology, ed 5.
New York, Informa Healthcare, 2007, vol 2, Section
III: Thyroid Disorders, chap 16, pp 391404.

Thyroid T.P. Foley, Jr. F. Pter Congenital hypothyroidism

 Carbohydrates M.A. Sperling O. Escobar R.K. Menon D.B. Dunger Hypoglycemia

}Vi>
,>`}Vi`ii>0 -}}iiii/ -ii
94 -i>}
/>VV>`>
}Vi>qi>>iviV>i2 /ii
}Vi>ii1 ii`>i}Vi{q}`

,ii>}Vi3

xqL`>L>3 i}Vix}} }Vi>Vvi`

>`V>i>>4

]]V]
]B"L]>V>i>ii5

ii>i>>Li ii>i>ii

1>}Vii`V}L>Vi6
>`
>V> >V>] *i>]
V> }` >V}>] >i> -
]
>` i>Li `>Lii >i>
*ii
Li
i>i}> x} vi `>Lii
iiiVi
vVvi`
iiii>i` ii >V>] >`Vi]
9i }Vi>
ii>i` >i> >}]
Q>V>iR `>Lii Vi
iixq1 1

"L>
i`iii 9i
>}}V>}
i7
} 

V i

>

i ;
> i

i
i <

= >
>

>

} 9

> >

>V

i `
i

V >
>

i V

>

>
vv > >
>

i v
n v i

i i

`i
Vi v

>L

i >

> V

V
i
>} i

q > V
V >

` >

`
}
v

}

> i >

}i }

>

v
V

i


}> `

i

i
V> ` V

iv

i



>

ii

V i

vi

iV


>
i



/
v> }

iiVVi}8 -}i  Viviivii`

>>>>v}iiV>


n /`i >`ixq}`>
VVV`

i`>`i v`>`iv>\* /V>n>v>>>Li
`}vV>v`vviLivi}i
 Index of Signs and Symptoms
A Abdominal pain 106 Athyreosis 76 Conn syndrome 56, 66
108 Acanthosis nigricans 32, 98, 100 Autonomous nervous system, activation 95 Convulsions 63
Acne 11, 32, 53 Autosomal-dominant inheritance 104 Corneal drying 81
Adipomastia 21 Coronary heart diseases 11
Adrenal hyperandrogenism,
primary functional 32, 34
B Bardet-Biedel syndrome 54
Bartter syndrome 66, 74
Cortical suppression normal 34
Cortisol resistance and metabolic defects 34
Adrenal hyperplasia, congenital Beckwith-Wiedemann syndrome 8, 10, 94 Craniopharyngioma 10
after newborn period 52 Bicarbonaturia 62 Cryptorchidism 22, 38, 42
in newborn period 50 Blue diaper syndrome 69 Cushing
nonclassical 18, 34 Body disease 48
Adrenal insufficiency 58, 62 fat, redistribution 48 syndrome 10, 22, 32, 34, 48, 56
Adrenal rests 34 mass index 10
Adrenal tumor 16
Adrenarche 18, 52
odors, changed 19
Bone age 6, 14, 18, 52
D Dehydration 50, 58, 106
fever 58
Adrenocorticotropic hormone, insensitivity 8 advanced 16 hypertonic 60
African-American 100 Brain Diabetes
Albright osteodystrophy 11 damage 39 drug-induced 98
Albumin 68 irradiation 12 insipidus 58, 60
Aldosteronism 46, 66 Breast(s) central 54
Alopecia 32 bloody discharge 21 dipsogenic, partial, pituitary 54
Alstrm syndrome 10, 54 development maternal 94
Amenorrhea delayed or absent 24 maturity-onset of the young 96, 98, 100, 104
athletic, hypothalamic 30 precocious 14 mellitus 54, 100, 104
primary, secondary 28, 44 hard 21 immune-mediated 96, 98, 100, 104
Androgen(s) irregular consistency 21 non-immune-mediated 96, 98, 100
excess, signs 53 Burns 60 Type 1 100, 102
exogenous 16 Type 2 98, 100
insensitivity, incomplete 36, 38 C Calcium levels Diabetic ketoacidosis 106
insensitivity syndrome 8 serum 72 Diabetic mother 10
resistance 26 urine 72 Diarrhea 58
suppression 34 Calcium receptor defects 70 chronic 74
normal 34 Caloric intake 10 profuse 66
subnormal 34 Cardiac arrest 64 Diencephalic syndrome 2
Anorexia 24, 58, 60 Cardiac insufficiency, mild 56 Diuresis, insufficient 56
nervosa 25, 29 Carpenter syndrome 10 Diuretic (ab)use 63
Anosmia 22, 24, 31 Central nervous system lesion 6 Diuretic excess 62
Anovulation 29, 32 Chemotherapy 74 Dyshormonogenesis of thyroid 76, 78, 84, 85
Anovulatory disorders 30 Chorionic gonadotropin-secreting
Anthropometry 2
Aortic stenosis, supravalvular 69
syndrome, human 14
tumors 16
E Ear lobe fissures 94
Eating disorder 30
Apocrine sweat odor 53 Clitoral hypertrophy 19 Edema, female newborn 44
Appetite, uncontrollable 11 Clitoromegaly 52 Electrolytes, urea 106
Aromatase isolated, vaginal fusion 26 Elfin faces 69
deficiency 9, 40 Coarctation 46 Enterostomy losses 66
inhibitors 16 Cohen syndrome 10 Estradiol 30
Aromatization excess, familial 20 Coma 106 Estrogen
Athlete 24 Confusion 106 deficiency, insensitivity 8
Athletic amenorrhea 26, 30 Conscious level, reduced 106 receptor defects 9
 Ethnic background 100 isolated 22 Hypercalcemia 54, 68
high risk for diabetes 100 organic 30 neonatal 68
Ethnic groups 19 secretion 17 Hypercalcemic crisis 68
Eunuchoid habitus 9, 22 Graves disease 80 Hypercortisolism 11
Euthyroid 82 maternal, neonatal 82 Hyperglycemia 96, 100, 102
hyperthyroxinemia 92 Growth mild/moderate 100
Exophthalmos 80 abnormal 12 severe 100
acceleration 9, 19, 52 Hyperhidrosis 32
F Failure to thrive 2 hormone Hyperhydration 56
Fanconi syndrome(s) 66, 70, 72 deficiency 6, 10, 12, 38 Hyperinsulinemia 11, 94
Fat childhood 6 Hyperkalemia 64
distribution 10 classic 4 Hyperlipidemia 11
subcutaneous 69 insensitivity 36, 38 Hypernatremia 60
Feminizing disorders 21 excess 8 essential 54
Fever 80, 84 insensitivity 38 Hyperosmolar nonketotic state 100
Fibrous dysplasia 72 syndrome 4 Hyperphosphatemic rickets
First-degree relative treatment 6 autosomal-dominant 72
type 1 diabetes mellitus 98 normal 36 autosomal-recessive 72
type 2 diabetes mellitus 98 rate 8 calciuria 73
Fluid poor 44 Hyperpigmentation 52
depletion 58 rate, reduced 6 Hyperplasia, congenital adrenal 16, 64
overload 56 poor 6 Hyperprolactinemia 32
requirements 107 retardation 11 Hypertension 11, 46, 52
resuscitation 107 slow 36 renovascular 46
Fragile X syndrome 17 velocity, declining 48 Hyperthermia, malignant 64
Fructose intolerance 94 Gynecomastia Hyperthyroidism 8, 15, 68, 80, 84
false 20 neonatal 82
G Galactorrhea 31 idiopathic prepubertal 20 Hyperthyroxinemia 90, 92
Gastrointestinal injury 75 autoantibody-associated 92
Genetic counseling 19 H Hair, axillary, pubic 19 familial dysalbuminemic 92
Genital anatomy, abnormal 26 Hashitoxicosis 80 Hypertrichosis 32
Genital development, precocious, boy 16 Heart Hyperventilation 60
Genitalia disease, congenital 45 Hypocalcemia
ambiguous 50 failure, congestive 62 neonatal 70
internal, abnormal 32 Hearing 44 late 74
Germinal failure, primary 22 Height velocity 4 severe 74
Gigantism, cerebral 8, 9 decreased 22, 23, 24 Hypodipsia 60
Glucocorticoid deficiency 62 increased 8, 14, 15, 16, 18 Hypoglycemia 9, 10
isolated 9 normal 8, 14, 18, 22, 24 infants and children 94
Glucocorticoids 7 Hemodialysis 60 Hypogonadism 8
Glucose 38 Hepatocellular insult, acute 92 congenital 28
determination, rapid 94 Hermaphrodite, true 40 primary, other 20
intolerance 11 Hirsutism 11, 30, 32, 98, 100 Hypokalemia 54, 66
Glucose blood idiopathic 31 Hypomagnesemia 70, 74
fasting 96 Histiocytosis X 55 Hyponatremia
random 96 Homocystinuria 8 hypervolemic 62
109 Glucosuria 60 21-Hydroxylase deficiency hypovolemic 62
Glycosuria 102 mild 52 normovolemic 62
Goiter 29, 76, 80, 82, 84 moderate 52 Hypoparathyroidism, maternal 70
Goitrogens 84 secondary 46, 60 Hypopituitarism 39
Gonadotropin Hyperandrogenemia 32, 34 Hypophosphatemic rickets 72
deficiency 24, 26 Hyperandrogenism, idiopathic 32, 34 Hypospadias 37, 38, 40
idiopathic 30

Index of Signs and Symptoms

 Index of Signs and Symptoms

Hypothyroidism 7, 1012, 14, 16, 62, 84 M McCune-Albright syndrome 14 polycystic 34

acquired, other types 78 Macroglossia 94 Overweight 10
congenital 76, 90 Macro-orchidism, without virilization 16
hypothalamic pituitary 90 Macrosomia, no maternal diabetes 94 P Panhypopituitarism 3638
juvenile 78, 90 Malabsorption 70, 72 Parents, tall, non-tall 8
primary 30 Malnutrition 2 Penile length, mean, stretched 17
110 secondary, tertiary 76, 78 short gut syndrome 74 Penis
Hypothyroxinemia 90 Mammoplasia, infantile 14 large 19, 52
Marfan syndrome 8 size, increase 23
I Iatrogenic reasons 20, 56, 60, 62, 66, 68, 70 Maternal deprivation 2 Peutz-Jeghers syndrome 21
Ileus 66 Menstrual disorder 11 Pheochromocytoma 46
Immobilization 68 Mental retardation 69 renal 46
Incubator temperature 60 Micropenis 36, 38, 42, 94 Phosphate deficiency 72
Infant Mineralocorticoid excess 46, 66 Pima Indian 100
diabetic mother 74 5-Monodeiodinase, generalized deficiency 92 Pituitary
feed, mistake in preparing 60 Mumps orchitis 21 disorder 6
Infertility 44 Muscular twitching 75 multiple, hormonal deficiency 92
Inflammatory bowel disease 27 tumor 30
Insulin N Nasogastric reflux/aspirate 66 Pituitary/hypothalamic disease 6
exogenous (factitious hypoglycemia) 94 Neonatal goiter 84 Polycystic ovaries syndrome 10, 19, 32, 98, 100
requirements 102 Neonatal rickets 72 atypical 34
Insulinoma 94 Neonatal thyrotoxicosis 82 classical 34
Intersex 26, 34, 40 Nephrotic syndrome 56, 62, 70 nonclassical 34
Intestinal absorption defect 74 Neurofibromatosis 8 Polydipsia 102, 106
Intrauterine adhesions 28 Neuroglycemia 95 primary 62
Iodine Newborn screening tests 76 Polyuria 54, 102, 106
deficiency 76, 84 Nonpathogenetic stigmata 28 Poor length gain 2
exposure 76 Nystagmus 94 Prader-Willi syndrome 10
Prealbumin (transthyretin) hyperthyroxinemia 92
J Jansens metaphyseal dysplasia 68 O Obesity 10, 30, 32, 48, 58, 100 Precocious pubarche 18
Jaundice 94 infantile 10 Prediabetes, prediction of diabetes 98
mild truncal 11 Pregnancy 28
K Kallmann syndrome 29, 36 simple 10 test positive 26
Ketoacidosis 100, 102, 106 Oily skin 53 Prematurity 94
Ketonemia 94 Oligomenorrhea 28, 29 Prolactin 30
Ketones, smell of 106 Omphalocele 9 Prolactinoma 22
Ketonuria 62, 94 Optic glioma 9 Pseudogynecomastia 21
acidemia 106 Orchidopexy 22 Pseudohypoaldosteronism 64
Ketotic hypoglycemia 94 Orchitis 20 Pseudohypocalcemia 70
Kidney malformation 45 torsion 22 Pseudohypoparathyroidism 10, 70
Klinefelter syndrome 9, 20 Organomegaly 9 Psychological problems 102
Osmolality 62 Psychological stress 2, 29
L Laurence-Moon-Biedl syndrome 10 Osteomalacia Puberty 8, 102
Laxative abuse 66 tumor-induced 72 abnormal 12
Leptin 10 Osmotic diuresis 62 delayed 42
Lethargy 106 Otitis media 45 idiopathic central precocious 14
Liddle syndrome 46 Ovaria 28, 30 infantile central precocious 14
Lipodystrophy, total 8 Ovarian/adrenal tumor 34 organic central precocious 14
Liquorice abuse 66 Ovarian cyst/tumor 14 peripheral (pseudo)precocious,
Liver Ovarian failure, primary 24, 28 central (true) precocious 16
cirrhosis 56, 62 Ovarian hyperandrogenism, functional 32 precocious, delayed 12
disease 20, 70 Ovaries true, precocious 8
chronic 21 not polycystic 34 Pubic hair 53
Lymphedema 45 absent, present 20
development 17
 R Rachitic bone changes 73 T T4-binding protein abnormality 76 Thyrotoxicosis
Radiation Tachycardia 80, 82, 94 biochemical 92
exposure 88 Tall stature clinical 86, 92
no exposure 88 familial 8 factitia 80
Renal disease 54 unexplained 9 non-immune-mediated 83
Renal failure 56, 62, 70 Testes Tingling 75
acute 74 small 10, 38 Toxicosis, hyperpyretic 58
Renal insufficiency, chronic 60 retractile, vanishing 42 Tremor 75
Renal tubular injury 75 two prepubertal 16 Tremulousness 94
Respiration deep-sighing, Kussmaul 106 Testicular atrophy 36, 38 Turner syndrome 24, 44
Rheumatic disease 25 Testicular development, delayed or absent 22 Type 1 diabetes mellitus 100, 102
Rickets 70 Testicular dysgenesis 38 Type 2 diabetes mellitus 98, 100
calcitriol-resistant, vitamin D-dependent, Testicular failure, primary 22
hypophosphatemic, hepatic 72
hypoparathyroidism 72
Testicular volume 17
bilateral increase, unilateral increase 16
U Undernutrition 30
Undervirilized boy 40
neonatal 72 Testosterone-binding globulin Underweight 26
X-Iinked hypophosphatemic, autosomal-recessive deficiency 76 Urinary tract infection 50
hypophosphatemic with calciuria 72 increased concentration 92 severe 96
Rokitansky syndrome 26 Testotoxicosis 16 Uterine bleeding, dysfunctional 29
Thelarche, premature 14
S Salt-losing nephropathies 62
Salt loss, renal 58
Thyroglossal duct, abscess 85
Thyroid
V Vagina
blind, isolated 26
wasting, cerebral 54 adenoma 88 congenital absence 27
Sarcoidosis 54 toxic 86 Vaginal aplasia 26
Scrotal size, texture, pigmentation 17, 19, 23 carcinoma 86, 88 Ventricular fibrillation 64
Sea water intoxication 60 cyst, isolated 86 Vitamin D 25-hydroxylase deficiency 72
Seborrhea 32 disease 82 Virilization 18, 40
Seizure 94 ectopic 76 absent, partial or adult, but small testes 22
Sex eutopic 76 girl 40, 50
characteristics, secondary 9 hormone(s) maternal 41
chromosome disorders 8 generalized resistance to 92 rapid 29
differentiation 39 partial peripheral resistance 78 Vomiting 50, 58, 106
Sexual precocity, central, peripheral 18 pituitary resistance 80 prolonged 66
Shock 63, 106 medullary carcinoma 86
volume depletion, acute 58 nodule(s) 84 W Water depletion 60
Short stature 4, 6, 23 autonomous 80 Weakness 106
female 44 children, adolescents 86 Weight 46
idiopathic 4 clinically euthyroid 86 gain
Sleep apnea 11 multiple 87 poor 2
Small for gestational age 74, 94 storm 80 rapid 48
Sodium overload 60 tender/painful swelling 84 loss 102, 106
Steroidogenic block(s), 28 tenderness 80 Williams syndrome 68
Steroids, exogenous 14 Thyroid-stimulating hormone receptor Wolfram syndrome 54
Sweatiest 62 activating mutation 80
Sweating 94 Thyroid-stimulating hormone-secreting pituitary
adenoma 80
X X chromosome defects 28
111 Thyroiditis
autoimmune, with hypothyroidism 88
(juvenile) chronic lymphocytic 78, 80, 84, 87
increased incidence 45
subacute 80, 84
suppurative 84

Index of Signs and Symptoms

 Abbreviations
4 = Androstenedione FPG = Fasting plasma glucose PCR = Polymerase chain reaction
112 ACTH = Adrenocorticotropic hormone FPIR = First-phase insulin response PE = Physical examination
ADH = Alcohol dehydrogenase FSH = Follicle-stimulating hormone PG = Prostaglandin
AIS = Androgen-insensitivity syndrome PPP = Peripheral precocious puberty
AME = Apparent mineralocorticoid excess GAD = Glutamic acid decarboxylase PRA = Plasma renin activity
APA = Aldosterone-producing adenoma GH = Growth hormone PRL = Prolactin
ATPO = Antithyroid peroxidase GHBP = Growth hormone-binding protein PTH = Parathyroidhormone
GHD = Growth hormone deficiency PTHrp = PTH-related protein
BA = Bone age GHRH = Growth hormone-releasing hormone PTU = Propylthiouracil
BMI = Body Mass Index GI = Gastrointestinal
BUN = Blood urea nitrogen GnRH = Gonadotropin-releasing hormone RDS = Respiratory distress syndrome
RU = Resin uptake
CAH = Congenital adrenal hyperplasia hCG = Human chorionic gonadotropin
CBC = Complete blood count HNF = Hepatocyte nuclear factor S = Serum
CDGP = Constitutional delay of growth and 11-HSD = 11-Hydroxysteroid dehydrogenase SDS = Standard deviation score
puberty Ht = Height SGA = Small for gestational age
CF = Cystic fibrosis SHBG = Sex-hormone-binding globulin
CG = Chorionic gonadotropin IAA = Insulin autoantibodies SIADH = Syndrome of inappropriate ADH secretion
CHO = Carbohydrate ICA = Islet cell antibodies
CIS = Carcinoma in situ IGF-1 = Insulin-like growth factor T = Testosterone
CMO = Corticosterone methyl oxidase IGFBP = IGF-binding protein TBG = Thyroxin-binding globulin
CPP = Central precocious puberty IGT = Impaired glucose tolerance TBPA = Thyroxin-binding prealbumin
CRH = Corticotropin-releasing hormone IHA = Idiopathic hyperaldosteronism T1DM = Type 1 diabetes mellitus
CT = Calcitonin T2DM = Type 2 diabetes mellitus
CVP = Central venous pressure JDF = Juvenile Diabetes Foundation TGAb = Thyroglobulin antibody
THE = Tetrahydrocortisone
DCCT = Diabetes complications and LH = Luteinizing hormone THF = Tetrahydrocortisol
control trial THS = Tetrahydro-11-deoxycortisol
DDAVP = 1-Deamino-d-arginine vasopressin MCT = Medullary carcinoma of thyroid TPOAb = Thyroid peroxidase antibody
DHEAS = Dehydroepiandrosterone sulfate MCV = Mean corpuscular volume TRAb = Thyrotropin receptor antibodies
DHT = Dihydrotestosterone MEN = Multiple endocrine neoplasia TRH = Thyrotropin-releasing hormone
DI = Diabetes insipidus MODY = Maturity-onset diabetes of the young TRP = Tubular resorption of phosphones
DKA = Diabetic ketoacidosis MRI = Magnetic resonance imaging TSAb = Thyroid-stimulating antibodies
DOC = Deoxycorticosterone TSH = Thyroid-stimulating hormone
DSH = Dexamethasone-suppressible nl = Normal TSHR = Thyroid-stimulating hormone receptor
hyperaldosteronism NOCAH = Nonclassical adrenal hyperplasia TSI = Thyroid-stimulating immunoglobulin
NSD1 = Nuclear receptor set domain containing
E1 = Estrone protein 1 gene U = Urinary
E2 = Estradiol NSAID = Nonsteroidal anti-inflammatory drugs U/L = Upper/lower
ECF = Extracellular fluid UFC = Urinary free cortisol
ERG = Electroretinography OGTT = Oral glucose tolerance test URTI = Upper respiratory tract infection
ESR = Erythrocyte sedimentation rate OHD = Hydroxylase deficiency UTI = Urinary tract infection
OHP = Hydroxyprogesterone
F = Follicular OT = Osmotic threshold W/U = Work-up
FAH = Functional adrenal hyperandrogenism WBC = White blood cell count
FNA = Fine-needle biopsy P = Plasma
FOH = Functional ovarian hyperandrogenism PCO = Polycystic ovary
-FP = -Fetoprotein PCOS = Polycystic ovary syndrome