THE PEDIATRIC DIAGNOSTIC EXAMINATION - PART 6 pdf

Underweight infants who present with failure to gain weight or who lose weight may have nutrition, hyperthyroidism, or diabetes mellitus, whereas overweight infants usually are overfed b

demyelinating disease (multiple sclerosis, ADEM), progressive dementia, encephalopathy, and movement disorders If a finding on CT scan is suspi-

cious for a focal lesion, order an MRI for confirmation Also, if a CT scan

is not helpful to confirm a strong clinical suspicion, MRI is necessary

manage-may obviate the need for further consultation As a rule, only order nostic tests if they will influence patient management.Too often an unneces-sary imaging study done at the parent’s request identifies an unrelatednormal variant that leads to further anguish and expense A thoughtfulconsultant orders tests sequentially, and one who orders panels of tests

diag-at the onset has no idea whdiag-at is wrong and is fishing for an answer Theurgency for consultation should be a clinical decision based on rapidity

of onset and progression of symptoms In practice, parental concern andtolerance for delay often dictate urgency

Congenital CT scan detects most major malformations MRI is required

to observe many migrational defects and to further clarify the extent

of many congenital anomalies Inborn errors of metabolism may cause

structural abnormalities of the brain, and genetic consultation ishelpful even in the absence of dysmorphic features (see Chapter 6)

Genetic/metabolic Every pediatrician should be aware of the specific

dis-eases that comprise the newborn screen in the state of birth Mostinborn errors of metabolism have characteristic clinical features that

lead to specific evaluation Computer-based resources such as line Mendelian Inheritance in Man (OMIM) and Geneclinics provide

On-guidelines for evaluation and diagnosis See Chapter 5 for statescreening

After initial screening, separate organic acidemias from urea cycle defects and aminoacidopathies Acidosis owing to inborn errors of metab- olism and some aminoacidopathies will have an increased anion gap Some aminoacidopathies have normal pH and ammonia levels Aci- dosis is characteristic of organic acidemias, some aminoacidopathies, and carboxylase deficiencies Urea cycle disorders typically have elevated

ammonia levels with normal pH See TABLE 12–10 and consult aneurology text for more details about each of these metabolic dis-

orders, as well as mitochondrial, gray matter, white matter, myopathic,

Diagnosis Clinical Points

I Inborn errors of metabolism

a Aminoacidopathies

Phenylketonuria (PKU) Seizures, vomiting, DD, musty odor, fair skin, ↑ phenylketones

Tyrosinemia (type I) Boiled cabbage odor, hepatorenal disease, PN, ↑ fumaryloacetoacetateBranched-chain ketoaciduria Maple syrup urine (skin, cerumen); MR Sz, spasticity ↑Leu, Iso, Val

b Urea cycle defects ↑NH3, normal pH, AC, MR, ↑ornithine, citrulline, argininosuccinate

Isovaleric acidemia “Sweaty sock” odor, AC Sz, coma, occ ↑NH3, and hypoglycemia

Biotin deficiency Skin rash, Sz, hyp., MR, ↑ infection, biotin or biotinidase deficiencyMethylmalonic acidemia (MMA) Sz, lethargy vomiting, acidosis, ↑NH3 May have nl dev.; occurs in attacks

II Mitochondrial disorders

c Kearns-Sayre syndrome Retinal degen, ophthalmoplegia, at., heart block, ↑CSF protein

III Gray matter degeneration

d Ceroid lipofuscinosis Sz, DR, blindness, pigmented CNS and eyes; infantile and juvenile forms

a Alexander disease (dis) DR, Sz, ↑ head size, MRI criteria for dx, Rosenthal fibers on biopsy

b Pelizaeus-Merzbacher dis Head nod, at., MD, DR, optic atrophy, demyelination on MRI

c Canavan disease DR, hyp at first, then spastic, ↑ head, optic atrophy

d Adrenoleukodystrophy DR, at., behavioral change, blindness/deafness, adrenal insuff, ↑ long chain FA

V Storage diseases

a Gaucher type II, infantile Hyp → spasticity, head retraction, sucking prob., pursed lips, DR, ↑ spleen,

↓glucocerebroside activity

b Tay-Sachs GM2gangliosidosis ↑ Startle, DR (motor and mental), cherry red macula, ↑ in AJP, hex A defic

c Sandhoff GM2gangliosidosis Like Tay-Sachs + hepatosplenomegaly (HSM); hex A and hex B deficiency

d Niemann-Pick (sphingomyelin) DR, FTT, blindness, opisthotonus, emaciation, HSM, cherry red macula

e Metachromatic leukodyst At., DR quadriplegia; infantile and juvenile; arylsulfatase A deficiency

f Mucopolysaccharidoses Coarse facies, gibbus deform., corneal clouding, deafness, DR; see individual

types for degree of variation

VI Spinal musc atrophy

a Werdnig-Hoffman (SMA I) Infantile form, hyp (in ureters), facial weakness, swallowing problem, fasciculations

b Kugelberg-Welander (SMA III) Juvenile form, gait instability, proximal weakness, tremor, ↓ reflexes

VII Neuropathy

a Charcot-Marie-Tooth disease Childhood, slow onset, pes cavus, foot drop, distal weakness (peroneal →

gastrocnemius),↓ reflexes and position senseVIII Myopathy

A Musc dystrophy (limb-griddle)

a Duchenne (DMD) Onset < 5 y, ↓ motor dev., prox weakness, +Gower sign, toe-walking,

pseudohypertrophy, prog weakness, ↓ reflexes, contractures, cardiac, LD

b Becker (mild form of DMD) Onset >10 y, shoulder girdle → humerus → facial muscles, occ blind and deaf

c Facioscapulohumeral Emery-Dreifuss (onset age 5, slow progression, contractures, cardiomyopathy),

(Continued)

B Cong myopathy

a Nemaline myopathy Variable clinical forms, face, neck proximal weakness, rods on biopsy

b Central core disease Mild hypotonia at birth, slow prog., weakness prox > distal, upper ext >

lower, contractures, scoliosis, hip dislocation, malignant hypothermia, bx diagnosis

IX Neurocutaneous

a Incontinentia pigmenti Sz, MR, bullae → pigment whorls → depigmented whorls; spasticity, Sz, MR,

other ectodermal defects (hair, eyes)

b Linear nevus sebaceous Unilateral linear nevus, hemihypertrophy, ocular abn., Sz, MR, FW, ↑ head size

Ataxia, dev regression, ↓ reflexes, ↓ proprioception

c Hypomelanosis of Ito Sz, MR, eye abnorm., whorls of hypopigmentation, ↑ head size

X Progressive ataxias

Spinocerebellar degen

b Abetalipoproteinemia Retinitis pigmentosa, low cholesterol, acanthocytosis

c Refsum disease Retinitis pigmentosa, polyneuropathy, ataxia, ↑ phytanic acid

d Friedreich ataxia Children and adults, progressive, ataxia, pes cavus, ↓ position and vibration,

cardiac failure

Abbreviations: Sz = seizures; DD = developmental delay; PN = peripheral nerves; AC = altered consciousness; MR = mental retardataion; FTT = failue to thrive;

hyp = hypotonia; MD = movement disorder; at = ataxia; DR = developmental regression; AJP = Ashkenazi Jewish Population; at = ataxia; cong = congenital; degen = degeneration; def = deformity; dev = development; ext = extremity; HSM = hepatosplenomegaly; insuff = insufficiency; nl = normal; occ = occasional;

Cu = copper; leu = leucine; iso = isoleucine; val = valine; Hex A = hexosaminidase A; leukodyst = leukodystrophy; MELAS = mitochondrial encephalopathy lactic acidosis, strokelike episodes; MSUD = Maple Syrup Urine Disease; SMA: spinal muscular atrophy.

lysosomal storage, spinocerebellar degenerative diseases, and lar atrophies Note the recent advances in molecular genetics, and

spinomuscu-always include a geneticist in consultation with patients with theseconditions

Neurocutaneous syndromes such as neurofibromatosis I and II and tuberous sclerosis are usually clinical diagnoses with some help from

imaging However, molecular genetics studies are available for ous sclerosis and are employed to differentiate genotypes

tuber-Infectious/inflammatory Specific bacterial, viral, fungal, or rickettsial

cul-tures or other serologic or immunologic evidence of infection, e.g.,fluorescent antibodies, obtained by antibody titers is most helpful

to determine an etiology of an acute infectious or postinfectious

pro-cess, e.g., rubella, measles, EBV, or campylobacter in Guillain-Barré disease.

It still may be necessary for the neurologist to order nerve tion velocities or electromyography to differentiate neuropathy frommyopathy Imaging studies may be helpful, examples of which are

conduc-localization in the temporal lobe of herpes encephalitis and nating lesions in ADEM.

demyeli-Traumatic Most acute trauma is diagnosed immediately during the acute

event History, physical examination, and imaging studies are ally sufficient to elucidate the diagnosis

usu-Neoplastic The primary care physician may identify tumors, but the

neu-rologist and/or neurosurgeon is necessary to delineate the specifichistologic type If neuroimaging studies are normal and there is stillclinical suspicion of a space-occupying lesion, a neurologist is help-ful to review findings and to consider additional studies

Vascular The primary care physician always should be mindful of

clot-ting disorders, vasculitides, and congenital malformations that maycause thrombotic or hemorrhagic strokes If CT scan and MRI are nor-mal and the clinician still suspects vascular disease, arteriographymay be necessary

The Endocrine System

13

The goals of this chapter are

1 To summarize developmental, anatomic, and functional aspects ofthe endocrine system(s)

2 To review symptoms that suggest an endocrine disorder as sented by infants, children, and adolescents and to suggest differentendocrine diagnoses that may explain these symptoms

pre-3 To present details of physical findings that are due to endocrine orders and discuss how they support consideration of endocrinediagnoses

dis-4 To provide a systematic approach to laboratory evaluation based onthe history and physical examination

5 To assist with the decision about when a consultation with anendocrinologist is helpful

Anatomy and Developmental

Physiology

There is truly a plethora of substances that can act as hormones mones are produced in one cell, transmitted to another cell by means otherthan direct cell-to-cell contact (as in neuronal transmission of signals), in-teract with specific receptors of the target cell, and have an effect on a spe-

Hor-cific function or functions of that cell There is often a negative-feedback loop

operating between the hormone-secreting cell and the hormone target cell

to maintain homeostasis and avoid oscillation of the effects of the mone One typically thinks of the hypothalamic-pituitary-endocrine glandaxes as being of major importance; however, the gastrointestinal tract can

hor-be considered to interact in a pseudoendocrine manner with the pancreas

by providing changing concentrations of nutrients as a signal derived peptides not only signal satiety but influence release of insulinand growth hormone The central nervous system (CNS) is also involved

Gut-in meal-related activation of the pancreas The immune system and docrine system have numerous interactions as well For purposes ofdiagnosis, we will limit this chapter to the more classically defined en-docrine subsystems, their development and function, and disorders thatmanifest when they malfunction FIGURE 13–1 shows the anatomiclocation of the endocrine glands

en-Martin B Draznin and Manmohan Kamboj

Copyright © 2008 by The McGraw-Hill Companies, Inc Click here for terms of use

The role of hormones begins in utero One critical function is sexualdifferentiation This process requires chromosomal components to causethe gonad to differentiate either to ovary or testis The gonad then mi-grates caudally to a location appropriate for the sex of the embryounder the influence of human chorionic gonadotropin (hCG) and, later,pituitary luteinizing hormone (LH) The testes release testosterone tovirilize the external genitalia and mullerian inhibiting hormone to sup-press the persistence of the uterus and fallopian tubes to complete maledifferentiation Female structures seem to develop without requiring anyfurther stimulus at this stage There is evidence that male and femalebrains contain subtle structural differences owing in part to androgenexposure during the gestation, but there also may be genetic differences.The thyroid gland coalesces from branchial clefts and migrates to thefront of the lower neck by 40 days of gestational age Its secretion of thy-roid hormone gradually increases throughout gestation, more duringthe third trimester, and then with the postdelivery surge of thyroid-stimulating hormone (TSH), it increases dramatically The peripheraldeiodination of T during gestation is preferentially to the inactive reverse

Pineal glandHypothalamus

T3form On delivery, the newborn preferentially produces T3; thus thegland works in concert with the peripheral tissues, as well as the hy-pothalamus and pituitary, to control thyroid economy Deficiency ofboth fetal and maternal thyroid hormone leads to profound hypothy-roidism at birth with attendant high risk of severe developmental delay

if not rapidly treated Calcitonin from the thyroid C cells is involved incalcium accretion by bones in utero

Parathyroid hormone is relatively inactive, but a parathyroid hormone–like peptide is of vital importance in tissue differentiation and develop-ment in many organ systems The vitamin D receptor is very important

in embryogenesis

Adrenal hormones generated in the fetal zone of the adrenal passthrough the placenta They are vital in maintaining the pregnancy toterm The fetal pancreas is capable of secreting insulin to allow nutrientsentry to cells Insulin acts as a growth peptide in utero

Following delivery, the endocrine systems mediate growth anddevelopment, energy metabolism, balance of fluids and electrolytes,control of circulating calcium within a narrow range of concentration,and sexual maturation and function Symptoms owing to endocrinedysfunction may be very subtle or quite dramatic Signs also maynot be readily apparent early in the course of an endocrine disorder.Numerous other conditions may suggest an endocrine problem whennone is present

History

Infants

Infants have a limited repertoire of symptoms, exhibit a few more signsthan symptoms, and do not speak for themselves Thus the ability to in-terpret parents’ understanding of their problems is the key to progress

in making a diagnosis

There are few symptoms that by themselves declare an endocrinediagnosis As with any subspecialty area, a thorough general history isthe foundation on which to base endocrine-specific questions Present-ing problems that are due to endocrine dysfunction include changes ingeneral well-being, disordered growth, disordered energy metabolism,disordered sexual development or function, alterations of skin and its ap-pendages, and altered gastrointestinal motility, thirst, and urine output.The review of systems from the general history touches on endocrinefunction at many levels

We address growth disorders by focusing on the complaint—toolittle or too much growth—in a comprehensive manner; i.e., when wasthe problem first noted, how has the growth changed, does it cause dif-ficulties for the patient, and did other family members have problems

or concerns with their growth? Other helpful questions include whetherthe parent replaces clothes and shoes because they are worn out or be-cause they are outgrown, whether the patient can keep up with age peers

in all activities, what psychosocial stressors may have occurred,changes in appetite, use of stimulant medications for attention-deficit/hyperactivity disorder (ADHD), pregnancy, delivery, and neonatalgrowth characteristics It is important to understand what and howmuch the patient actually eats and to elicit symptoms of chronic renal,gastrointestinal, cardiac, pulmonary, or inflammatory disorders becausepoor growth statistically is more likely to be due to undernutrition orchronic nonendocrine disorders than to deficiency of hormones thatpromote growth.

Disorders of sexual differentiation usually manifest early in life.Questions that are useful in a family history are whether there are anyother affected family members, whether there were any early infantdeaths, whether there were any exposures of the mother to androgenicagents during the pregnancy or if she experienced virilization, or forundervirilized males, if there was any exposure to putative endocrinedisruptors or estrogenic compounds Sexual maturation may occurprecociously or very late, and a family history again is of primary im-portance, especially because a history of delayed onset of puberty inhealthy parents suggests that the child has a different pattern of growthand development from the norm rather than a disorder Exposure toexogenous sex steroids should be investigated; these may be present incosmetics in the case of estrogen and also in substances used by bodybuilders such as skin bronzing treatments that also contained testos-terone, to name two sources

Disorders of energy metabolism suggesting thyroid problems presentwith changes in activity, in tolerance to heat or cold, in duration of sleep,and in an increase in fidgeting or a decrease in the ability to pay atten-tion; even emotional lability may be due to hyperthyroidism Hypothy-roid patients may have increased gut transit time or frank constipation;hyperthyroid patients may have hyperdefecation or diarrhea Precociouspuberty with a “muscular” appearance owing to pseudohypertrophy ofcalf muscles may occur in school-age hypothyroid children Adolescentfemales may experience menometrorrhagia to the point of becominganemic with hypothyroidism; conversely, hyperthyroid adolescents mayhave scanty to absent menses

Adrenal insufficiency may lead to fatigue, mental status changes,chronic diarrhea, and collapse It may be insidious, so the diagnosis may

be delayed until obvious signs are found

Skin changes in endocrine disorders include pallor, plethora, striae,early acne, subcutaneous deposits of glycoproteins (myxedema),thickening and darkening of intertriginous areas (pseudoacanthosis ni-gricans), tanning (the color in Addison disease is unusual), and “bronz-ing” of the skin, including areas that receive little or no sun exposure.Some of these will be part of the complaint, whereas the examiner mayhave to elicit others

Increased thirst and urine output can mark diabetes mellitus or betes insipidus The preferred fluid may be a clue because cold waterseems to be most satisfying to persons with diabetes insipidus Ques-tions should focus on onset, timing, whether the increase in drinkingpreceded or followed the increased urine output, whether sleep is affected

dia-or there is enuresis, and how much liquid intake is needed to satisfythirst.

Disorders of calcium metabolism affect rapidly growing bone as well

as the function of nerves and muscles because calcium flux across cellmembranes is a critical signaling mechanism for many vital cellularprocesses Excess calcium adversely affects renal function, whereas cal-cium deficiency may lead to elevated parathyroid hormone, which mayinduce phosphaturia and even a Fanconi syndrome-like effect withglycosuria and aminoaciduria

Constitutional Infants may show little energy, poor feeding,weak cry, poor muscle tone, and other nonspecific variations of activ-ity The older they are, the more specific the parents can make their char-acterizations The endocrine and endocrine-related conditions that may

present with these complaints include hypoglycemia, dehydration, roidism, and electrolyte imbalance Jitteriness, tremors, agitation, excessive crying, and inconsolability may be signs of hyperthyroidism, hypoglycemia,

hypothy-or hypocalcemia Relation of these symptoms to timing of feedings and

relief with food may suggest hypoglycemia Heat or cold intolerance isnot likely to be a complaint related to infants, but mottling of the skinmay indicate hypothyroidism Altered consciousness or frank seizuresmay be hard to discern at times in infants but become more typical withincreased age, and their investigation should include tests for hypoglycemiaand hypocalcemia

Growth Issues Small stature is a common complaint in older

children but may occur even in newborns Intrauterine growth retardation (IUGR), placental disorders, Turner syndrome, Russell-Silver syndrome, and growth hormone resistancecan yield a small neonate or may appear later

in infancy Overgrowth, usually defined as a birth weight above 90th

percentile, is associated with maternal diabetes and genetic syndromes, cluding Beckwith-Wiedemann syndrome in early infancy Later, excessive

in-size may be secondary to exogenous obesity Underweight infants who

present with failure to gain weight or who lose weight may have nutrition, hyperthyroidism, or diabetes mellitus, whereas overweight infants usually are overfed but may occasionally have an overgrowth syndrome or hyperinsulinemia (see anthropometric measurements under “Physical

under-Examination” below)

Abnormalities of Skin and Cutaneous dages Infants may have hairiness, which may be hypertrichosis

Appen-owing to hyperinsulinemia or some medications (e.g., diazoxide), or it may

be a familial pattern Their hair may be coarse, dry, and brittle in

pothyroidism The skin may appear pale, thickened, and waxy if pothyroidism has persisted for weeks or months without treatment There

hy-may be a history of unusual pigmentation that might include café-au-lait

spots with an irregular border, tending to be unilateral in McCune-Albright

KEY PROBLEM

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syndrome Fingernails and toenails may be unusual, such as the convex nails in Turner syndrome.

hyper-Abnormalities of the Head A “ping pong ball skull”

suggests neonatal rickets Persistence of an open posterior fontanel or a very large anterior fontanel suggests hypothyroidism.

Abnormalities of the Eyes Parents may observe tagmus, especially if it is associated with signs of poor visual fixation,

nys-suggesting septo-optic dysplasia, often associated with

hypothalamic-pituitary deficiency A defect of the iris also may accompany amic malformation

hypothal-Abnormalities of the Ears Deafness may be part of

hereditary syndromes such as Pendred syndrome, which also includes hypothyroidism, but deafness is also a consequence of untreated hypothy-

med-a thyroglossmed-al duct cyst An orifice in the midline thmed-at drmed-ains clemed-ar fluid

may be a thyroglossal duct sinus

Respiratory Symptoms Irregular breathing may

indi-cate CNS effects of hypoglycemia or hypocalcemia Hyperventilation or hyperpnea often occurs in new onset of diabetes mellitus in infants.

Cardiovascular Symptoms High heart rate is often

apparent in hyperthyroidism, whereas low heart rate accompanies roidism but is less likely to be discovered by parents

hypothy-Gastrointestinal Symptoms Abdominal pain may

indicate diabetic ketoacidosis, adrenal failure, or hypercalcemia.

CNS Symptoms Parents usually will not comment on

re-flexes but may comment on stiffness (consider hypocalcemia as an crine cause) or floppiness (consider hypercalcemia) Abnormality of gait may be due to rickets The bending of the limbs is due to walking on

them when there is an enlarged and abnormal zone of osteoid that not calcify These bones are also painful on weight bearing.

can-Breast Changes Early breast development may representretained neonatal breast buds that enlarge slightly or may be due to a

functioning ovarian follicle, exogenous estrogen exposure, or precocious berty Infants may have physiologic galactorrhea.

pu-Male Genitalia Abnormalities Undescended testes

may be physiologic when due to prematurity, or they may be due to dromes A virilized female infant with congenital adrenal hyperplasia may

syn-appear to be a male with undescended testes Enlarged, firm testes may

be physiologic or due to tumor, torsion, hydrocele, etc Microphallus can accompany hypopituitarism, androgen insensitivity, or premature testicular failure and loss Hypospadias can accompany disorders of sexual dif-

ferentiation and some syndromes

Premature Appearance of Pubic Hair When just

on the scrotum or labia majora in infants, this may be a benign findingand will not progress However, when there is progression or spread

over the pubes, congenital adrenal hyperplasia and androgen-producing tumors are more likely.

Menstrual Disturbances Postdelivery estrogen drawal may eventuate in vaginal bleeding in normal female neonates

with-Polyuria and Polydipsia Diabetes insipidus may lead to

very frequent feeding in infants or increased thirst in toddlers and

increased urine output Diabetes mellitus may present in a similar

manner

Children

Constitutional Children may complain of fatigue or have

reduced exercise tolerance, increased sleep, lethargy, etc from roidism, hypoglycemia, dehydration, electrolyte and/or calcium abnormalities, adrenal insufficiency, or diabetes mellitus They may have irritability,

hypothy-agitation, difficulty concentrating in school, and emotional lability

from hyperthyroidism, hypocalcemia, or hypoglycemia Heat intolerance

may accompany hyperthyroidism, whereas cold intolerance is a frequent

complaint with hypothyroidism Fainting may be due to hypoglycemia, adrenal insufficiency, or hypocalcemia Seizures may be due to hypoglycemia or

Heat or Cold Intolerance Children and adolescents aremore able to articulate these symptoms, and they will be uncomfort-

able in a warm or cool office setting Think hypothyroidism for cold tolerance and hyperthyroidism for heat intolerance

in-Growth Children notice that they are shorter than their peers,

as do their parents A change in the rate of growth also may be the plaint, well before the child is actually short Causes include the phys-iologic, such as familial short stature and constitutional delay of growth

com-and maturation Others include malnutrition, chronic illness, tory bowel disease, congenital syndromes such as Turner syndrome and oth- ers, hypothyroidism, growth hormone deficiency, and Cushing syndrome Excessively tall stature may be secondary to exogenous obesity, precocious puberty, genetic overgrowth syndromes, and growth hormone excess owing

inflamma-to tumor.

Weight Underweight children have too little intake or too

much expenditure of nutrients Hyperthyroidism and diabetes mellitus cause wasting of energy and nutrients, and diabetes insipidus substi-

tutes drinking of water for eating and also may suppress appetite ifthere is electrolyte imbalance Overweight in children is occasionally

due to hormone deficiency, as in hypothyroidism, or hormone excess, as

in Cushing syndrome These usually are readily distinguishable from

exogenous obesity because hormone-induced obesity almost alwaysaccompanies diminished linear growth Overgrowth syndromes may be

associated with overweight Prader-Willi syndrome is usually associated

with short stature and delayed puberty, even with growth hormonedeficiency

Skin and Cutaneous Appendages Stretch marks

accompany weight gain and may occur in exogenous obesity or Cushing syndrome Dark skin in creases and around the neck may be a complaint.

Generalized hairiness or just increased hair in androgen-sensitive areas

may be a concern Hair that breaks suggests hypothyroidism, whereas hair that falls out in a diffuse manner suggests telogen effluvium, with syn-

chronization of follicles after an endocrine change, and leads to more

profuse loss More circumscribed hair loss suggests alopecia areata, an autoimmune condition that may accompany autoimmune endocrinopathy Thick, waxy skin is characteristic of hypothyroidism, whereas thin skin accompanies Cushing syndrome Pigmented patches are seen in infants and may signify McCune-Albright syndrome, whereas generalized bronzing,

with absent tan lines (i.e., areas not exposed to sun are also

hyperpig-mented), suggests Addison disease Candidiasis of nails suggests dular autoimmune endocrinopathy, hyperconvex nails occur in Turner syndrome, and onycholysis occurs in Graves disease.

polyglan-KEY PROBLEM

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Head Abnormalities Children complain of headache, which

may be due to increased intracranial pressure associated with tumors in the region of the pituitary, as well as pseudotumor cerebri associated with start-

ing/cessation of endocrine hormone therapy, including starting growth

hormone Hypoglycemia may trigger migraine headaches.

Eye Abnormalities Children have less frequent and less

severe exophthalmos with Graves disease than do adults but may

com-plain of dry, red, or burning eyes Diplopia on upward or lateral gazemay indicate extraocular muscle involvement Visual field defects maymanifest as tripping over or running into objects that are low and to

one side and indicate a search for a pituitary mass lesion Nystagmus

is associated with septo-optic dysplasia Blurring of vision may be due to hyperglycemia with swelling of the crystalline lens and loss of accom-

modation

Ear Abnormalities Deafness associated with hypothyroidism

is the same as in infants

Neck Abnormalities Thyroid enlargement with or without

pressure symptoms can be a complaint in hypothyroidism or roidism or thyroiditis, as in infants Pain is a usual accompaniment of acute

hyperthy-or subacute thyroiditis; it is not often part of chronic thyroiditis hyperthy-or Graves disease Swallowing may be difficult in the presence of a large goiter.

Cardiovascular Symptoms Palpitations, or a high andregular heart rate, indicate increased adrenergic effect that may be due

to hyperthyroidism, whereas most children will not complain of a slow

heart rate

Gastrointestinal Symptoms Pain in diabetic

ketoaci-dosis or Addison disease may be quite severe and suggests other conditions such as appendicitis or gastroenteritis Constipation may be due to hypothy- roidism, whereas hyperthyroid children may have increased numbers of

bowel movements in a day or even diarrhea

Neurologic Symptoms These are the same as with infants

Breast Changes Early development of breasts, younger

than 8 years of age, may be isolated premature thelarche without true

pre-cocious puberty or may signal a more serious condition Questions toask include possible exposure to estrogen-containing medications or

cosmetics Androgen symptoms such as sexual hair, acne, or body odorsuggest puberty rather than an isolated growth of breast tissue Dis-comfort in the breast bud and asymmetry in size are not usually symp-toms suggesting pathology, although chest wall tumors and indolentinfections may give rise to masses in the area of the breast Galactorrheamay be due to medication or increased pituitary release of prolactin.

Gynecomastia, breast growth in males, may be prepubertal, in which case

there may be no identified pathology, or there may have been exposure

to exogenous estrogen

Male Genitalia Abnormalities Undescended testes

may be idiopathic, part of a syndrome, or due to a disorder of sexual velopment Enlarged testes may be due to onset of puberty, genetic causes such as fragile-X syndrome or autonomous testicular function in the ab- sence of pituitary activation, or tumors, including adrenal rest tissue in poorly controlled congenital adrenal hyperplasia Painful testes may be due

de-to de-torsion or tumor.

Polyuria and Polydipsia These may be due to diabetes insipidus or diabetes mellitus A form of diabetes insipidus can be due to hypercalcemia.

Adolescents

Constitutional Since adolescents have a different wake/sleep cycle than adults and children yet are expected to be awake andalert in the early morning for school, it is often difficult to differentiate

pathologic fatigue from a mismatch of physiology with schedule pothyroidism, adrenal insufficiency, diabetes mellitus, hypoglycemia, and hypocalcemia are all possible causes of nonspecific fatigue As for shaki- ness and agitation, they can be associated with hyperthyroidism, hypo-

Hy-glycemia, or hypocalcemia Emotional lability from hyperthyroidismalso may be harder to differentiate from the typical adolescent experi-ence of strong and shifting emotions Heat and cold intolerance are stillhelpful clues to hyper- or hypothyroidism Poor athletic performance

even though training hard may be a sign of reversible hypopituitarism;

in females it would accompany menstrual irregularity Fainting spellsand seizures may begin with adolescence; hypoglycemia and hypocal-

cemia are still the most profitable areas to pursue Adrenal insufficiency

may manifest with orthostatic hypotension and fainting

Heat or Cold Intolerance This is similar to children andadolescents

KEY PROBLEM

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Growth Short stature in adolescents is often due to delay of set of puberty and not to a disorder of growth Delayed puberty may or

on-may not be a physiologic variant; hypogonadal hypogonadism or primary gonadal failuremay be the cause All causes of short stature in childrenapply to adolescents as well Tall stature is similar in this regard and

with delayed puberty may indicate Klinefelter syndrome Complaint of

underweight, isolated or associated with undergrowth, can be part of

diabetes mellitus, hyperthyroidism, or undernutrition Overweight

adoles-cents almost all have exogenous obesity, but rare overgrowth syndromes

may include obesity Adolescents with Cushing syndrome, hypothyroidism, and Prader-Willi syndrome are usually not tall.

Skin and Cutaneous Appendages There may becomplaints of stretch marks in children; acne may be extreme in hyper-

androgenic states such as undertreated congenital adrenal hyperplasia or the metabolic syndrome–polycystic ovarian syndrome continuum Hirsutism

in females suggests androgen excess; generalized hairiness may just behypertrichosis Hair changes such as increased falling hair from a sud-den change in endocrine balance and dryness and breaking in hy-pothyroidism are important symptoms Patchy hair loss again is more

from autoimmune causes The dry, waxy skin of hypothyroidism may be

a complaint A very unusual tan involving areas that are not sun-exposed

may indicate Addison disease Nail abnormalities are similar to those in

children

Head Abnormalities Symptoms are much as in children

Eye Abnormalities Adolescents are more likely than dren but less likely than adults to have exophthalmos Other eye complaints

chil-in Graves disease are the same as experienced by children Adolescents

are more likely to articulate visual field defects as blind spots, althoughthey too may just trip over or bump into objects that are in the blindspot Blurring of vision and loss of accommodation can accompany

diabetes mellitus until the blood sugar levels are controlled.

Neck Symptoms Adolescents are more likely to notice a

pressure sensation and/or mass in the neck from a goiter; there may be painful symptoms from subacute or acute thyroiditis The causes are similar

to those in children

Cardiovascular Symptoms Adolescents may notice and

be concerned about heart rhythm disturbances or rapid rate more thanchildren They are more prone to orthostatic hypotension of a physiologicnature

Abdominal Symptoms These are much the same as in

children owing to diabetes with ketoacidosis or Addisonian crisis Diarrhea associated with Graves disease and constipation owing to hypothyroidism

are still useful symptoms to pursue

Neurologic Symptoms Adolescents are more aware of

loss of function or tightness of muscles as with hypocalcemia and ness from hypoglycemia or hyperthyroidism and may complain of these

shaki-symptoms or answer in the affirmative on the review of shaki-symptoms

Breast Changes Galactorrhea in males or females is more

common and can be due to hyperprolactinemia from a pituitary adenoma

or to medication or chronic nipple stimulation Mild gynecomastia with

small breast buds that regress spontaneously is physiologic in malepuberty Persistent gynecomastia is still usually not due to an endo-

crine disorder, but it also may indicate disorders of androgen synthesis, felter syndrome, feminizing adrenal tumors, aromatase hyperactivation, drugs and medicines (including spironolactone, cimetidine, phenothiazines, cannabis, and others), and testicular failure.

Kline-External Male Genitalia Abnormalities scended testes are the same as in infants and children Testicular masses

Unde-may be tumors; if painful and enlarged, they Unde-may be due to torsion or hydrocele.

Female External Genitalia Abnormalities ilization occurs when the androgen levels are high enough to produceclitoral hypertrophy This may be associated with male-pattern hair loss.Virilization occurring postnatally does not induce labial fusion and am-biguity, except for the increased size of the clitoris

Vir-Menstrual Disturbances Primary amenorrhea occurs

in physiologic delay of puberty, in Turner syndrome, in disorders of

sex-ual differentiation, and in gynecologic abnormalities Oligomenorrhea

occurs in hyperthyroidism, the female athlete triad, and the first year or

so after menarche in some adolescents until they start having mostly

ovulatory cycles Secondary amenorrhea occurs in pregnancy, polycystic ovarian syndrome, hyperthyroidism, and the female athlete triad Menorrhagia/ metrorrhagia occurs in hypothyroidism.

Polyuria and Polydipsia These occur in diabetes insipidus and diabetes mellitus.

Menstrual Disturbances Premature menses in hood require evaluation for precocious puberty or pseudopubertyand for exposure to exogenous estrogen Primary amenorrhea sug-

child-gests ovarian dysgenesis as in Turner syndrome, other disorders of ual differentiation, hematocolpos, a thick hymen, or absence of a uterus.

sex-Secondary amenorrhea may be due to pregnancy, polycystic ovarian

syndrome, androgen excess from uncontrolled congenital adrenal perplasia, or tumors Oligoamenorrhea may be part of the female ath-

hy-lete triad; it may be due to hyperthyroidism or significant weight loss

from other causes Menorrhagia and metrorrhagia may be due to pothyroidism.

hy-Physical Examination

Endocrinology is quantitative, and how much of what, when, and whereare central themes Measurements of stature and body proportion areonly useful if done consistently and correctly throughout the growthand development of the patient Proper plotting of values, at the pre-cise age and on the correct chart, will maximize ability to interpret thesevalues Measure length in infants supine on a flat, firm surface with afixed surface at right angles to the horizontal backboard at one end,against which an assistant gently holds the vertex of the skull The ex-aminer gently but fully stretches the legs and places the bottom of theheels on another right-angle surface that slides to adjust to the length

of the infant Measuring in any other fashion introduces significanterrors Measure heights with feet flat on a stationary surface instead ofthe movable doctor’s office scale The back of the heels, the sacrum, thethoracic spine, and the occiput should all touch this plane with the kneesfully locked Pull the head gently upward with pressure on the mastoidprocesses while the Frankfort plane (outer canthus of the eye to the top

of the auditory canal) is parallel to the floor Measurement at the vertex

of the skull is then possible While a wall-mounted stadiometer-likedevice is preferable, a metal tape and right-angle triangle used for me-chanical drawing can work as well The most recent growth norms arelisted in Chapter 2

Growth velocity is critical to assess, especially around the time ofadolescence (TABLE 13–1) This should be part of a generalist’s evalu-ation of growth

Measure the anterior fontanel from each opposite apex of its mond shape; record both sagittal and coronal distances

dia-Proceeding caudally, palpate the thyroid gland Move the skin lying the gland without allowing the examiner’s fingertips to slide onthe skin; the sensation will be like wearing a glove If the fingertipsslide on the skin, that tactile impression may interfere with feeling thegland Depending on the age of the child and the skill of the examiner,palpation from behind, from the side, or from directly in front of theKEY PROBLEM

over-patient may be more appropriate Younger over-patients do not trust or

tol-erate examiners coming at them from behind A helpful technique tobring the thyroid into relief from behind the strap muscles is to allowthe patient’s head to hang over the end of the examination table in thesupine position Again, do this in such a way as to avoid frighteningthe patient Measure the length of each lobe, measure the distancebetween the upper poles of the thyroid across the neck, measure thediameter of the neck at the level of the isthmus, and measure thecephalad-to-caudal distance across the isthmus Feel for, and measure,

if possible, a “Delphian” lymph node just above the isthmus or for apyramidal thyroid lobe arising from the cephalad edge of the isthmus.These measurements make it much easier to compare thyroid size atsubsequent visits than guesses of thyroid weight or estimates such as

“twice normal size.”

Quantify breast buds and early to middle-development breast tissue

by measuring the diameter at the base of the tissue in a plane parallel

to the floor when standing for ready comparison with later tions It may be difficult to differentiate breast gland tissue from adiposetissue unless the patient is of normal body habitus

examina-Perform genital measurements as follows: Express testicular volume

in milliliters, comparing the patient with the Prader orchidometer dards Stretch the penis and measure the length from the base of the shaft

stan-at the pubic symphysis to the tip of the glans This may require pressingthe end of the ruler down into a significant fat pad for an accurate mea-surement Likewise, measure clitoral length from the suspensory liga-ment to the tip of the glans Do not include the preputial skin Also mea-sure the diameter of just the erectile tissue Measurements of anon-endocrine-specific nature such as limb lengths are helpful to assist

in endocrine evaluations Tanner staging has been the “gold standard”for objective evaluation of pubertal status and appears in FIGURES 13–2through 13–4

Infants

Constitutional Poor tone, poor suck, poor feeding, lethargy,and fussiness are all nonspecific but indicate a need to evaluate forKEY FINDING

TABLE 13–1 Average Growth Velocity per Year

hypoglycemia, hypocalcemia, and hypothyroidism Agitation, jitteriness,

tremors, or increased tone may suggest hyperthyroidism, hypocalcemia,and hypoglycemia Increased mottling of skin in older infants suggestshypothyroidism

General Observation of the Infant Lymphedema of hands and feet is frequent in Turner syndrome, as is neck webbing and

low posterior hairline A shield-shaped chest with widely spaced

nip-ples and narrow shoulders is also a clue to Turner syndrome A rachitic

rosary, broadening of the costochondral junctions (in the anterior lary line not the midclavicular line in newborns), and flared wrists sug-gest rickets Bowing of the legs occurs on walking; prewalking infantshave flared distal ends of the femora, which are harder to see and feelthan the changes in the wrists

axil-Measurements Small-for-dates infants may have IUGR,

other syndrome diagnoses, chromosomal disorders such as Turner drome, or hypopituitarism Large infants may be infants of diabetic moth- ers, have overgrowth syndromes, or have Beckwith-Wiedemann syndrome.

syn-Underweight but normal-length infants usually are malnourished The

FIGURE 13–2 Sexual Maturity Rating: Breasts (From Greydanus DE, Patel DR, Pratt HD: Essential Adolescent Medicine New York: McGraw-Hill, 2006.)

KEY FINDING

KEY FINDING

FIGURE 13–3 Sexual Maturity Rating: Pubic Hair (From Greydanus DE, Patel DR and Pratt HD: Essential Adolescent Medicine New York: McGraw- Hill, 2006.)

growth curve will assist in the short and underweight infant becausenutritional causes usually manifest first with underweight, then thelength “falls off the chart,” and finally, the head circumference suf-

fers if there is no correction of prolonged undernutrition Diabetes litus or hyperthyroidism may lead to underweight in infancy Overweight infants are almost all over-nourished; rarely, Cushing syndrome in in-

mel-fancy leads to overweight with diminishing linear growth Infants withpersistent hyperinsulinemia may be overgrown owing to constanthunger and feeding as protection from hypoglycemia

Skin and Cutaneous Appendages Infants may have

hypertrichosis owing to drugs or hyperinsulinemia Prolonged jaundice can be a sign of hypothyroidism Nails may be small and hyperconvex and appear to curve up at the tips of the fingers in Turner syndrome Dry

skin and myxedematous changes may be a sign of acquired as well as

long-standing congenital hypothyroidism in infants Hair that is dry and

breaks suggests hypothyroidism but also nonendocrine syndromes (seeChapter 16)

Head Abnormalities The “ping pong ball skull” in tal rickets has very thin bones that feel flexible The anterior fontanel be-

neona-comes large in hypothyroidism with growth of the brain and lack of

FIGURE 13–4 Sexual Maturity Rating: Male Genitalia (From Greydanus

DE, Patel DR, Pratt HD: Essential Adolescent Medicine New York: McGraw-Hill, 2006.)

KEY FINDING

KEY FINDING

bony growth, so its absence in the newborn is unreliable An open

pos-terior fontanel after a month or two of age is associated with congenital hypothyroidism.

Eye Abnormalities Pendular nystagmus may be hard todetect early on, but poor fixation may be a clue to optic nerve involve-

ment such as septo-optic dysplasia or other midline defects in the CNS associated with the hypothalamus Colobomata of the iris and retina sug-

gest midline CNS defects as well Persistent myelination of the corneal

nerves occurs in multiple endocrine neoplasia (MEN) type 2b.

Ear Abnormalities The helix of the ear is often unusual as

in DiGeorge syndrome Deafness is associated with Pendred syndrome and can result from late treatment of congenital hypothyroidism.

Neck Abnormalities The newborn thyroid is hard to feel;

thus a goiter would suggest a disorder of thyroid hormone synthesis.

This may be hereditary or may be due to iodine deficiency in utero or

in later infancy, maternal Graves disease with transplacental transfer of

thyroid-stimulating immunoglobulins, or transplacental transfer of tithyroid drugs such as propylthiouracil A fluctuant mass in the anterior midline of the neck is consistent with at thyroglossal duct cyst A thy- roglossal duct sinus is rare.

an-Cardiovascular Tachycardia may be due to Graves disease, bradycardia to hypothyroidism Hypotension is associated with adrenal insufficiency, as in salt-wasting congenital adrenal hyperplasia, adrenal hemorrhage, etc There is an association of congenital heart disease with DiGeorge syndrome (conotruncal defects) Diminished and delayed femoral pulses in Turner syndrome are due to coarctation of the aorta.

Neurologic Hyperreflexia may occur in hyperthyroidism, and

increased tone and reflexes may be seen in hypocalcemia, especially the

Chvostek sign and the Trousseau sign Hypothyroidism causes

hypore-flexia with “hung up” deep tendon reflexes Test anosmia in adolescents

with delayed onset of puberty in whom Kallmann syndrome is under

con-sideration Coffee grounds and orange peels are good substances to use

Breast Abnormalities While the breast tissue noted inthe full-term neonate is usually up to 1 cm in diameter, it may be more

If it enlarges during the first year of life or emerges for the first timelater in infancy, an evaluation for etiology is in order Consider a spon-

taneously active ovarian follicle, precocious puberty (either central or ripheral), and exposure to exogenous estrogen Galactorrhea is physiologic

soon after birth Expression of more than colostrum, persistence out ofthe neonatal period, or new onset after the neonatal period should trig-ger a search for an endogenous or exogenous source of stimulus for pro-lactin release.

External Female Genitalia Neonatal genital nation should have revealed any ambiguities Rarely, an infant withvirilization will go undetected The newborn endocrine screen for con-genital adrenal hyperplasia is useful to find affected males because theytypically do not appear abnormal at birth, but it also has been instru-mental in identifying the rare virilized undiagnosed female The cli-toral index is normally less than 16 This is the product of length andthe diameter, in millimeters, of the erectile tissue only, ignoringpreputial size The distance from the anus to the posterior edge of thevaginal opening or fourchette should be less than 50 percent of the dis-tance from the anus to the pubis (anogenital ratio normally less than

exami-50 percent) There should not be fusion or rugation of the labia majora

in a female newborn

External Male Genitalia Testes should be in the scrotum

by 32 weeks of gestational age and usually have a volume of 1 to 3 ml

Nondescent may indicate hypopituitarism, especially when associated with micropenis Androgen insensitivity syndromes are associated with maldescent of the testes as well The median penis stretched length at

birth is 3.5 cm, with a diameter of about 1 cm Microphallus (<2.5 cm

in length at full term) can occur with hypopituitarism, vanishingtestes, and androgen insensitivity syndromes Testicular torsion can

occur in infancy Isolated mild hypospadias is not usually due to

endo-crine disorders, but the more severe forms may be due to androgen ceptor mutations or disorders of sexual differentiation, as well as othergenetic syndromes Enlargement of the penis with no enlargement of thetestes suggests an adrenal source of excess androgen or an exogenousandrogen exposure

re-Premature Pubarche Premature adrenarche can be pathic or due to precocious puberty, congenital adrenal hyperplasia that did

idio-not significantly virilize female external genitalia (in males there is no

external sign), exposure to exogenous androgens, or the rare producing tumors of adrenals or gonads

androgen-Other Key Findings

Diabetes insipidus and diabetes mellitus in infants may present with a

well-appearing infant or one that is profoundly dehydrated and acidotic pending on circumstances No particular physical findings are of specifichelp in making this diagnosis

de-KEY FINDING

KEY FINDING

KEY FINDING

Children and Adolescents

Approach to physical findings in adolescents and children is similar tothat in infants Please refer to the preceding section

Constitutional Fatigue and lethargy are nonspecific

Endo-crine causes such as hypoglycemia, hypothyroidism, and adrenal insufficiency

may present with a very tired-appearing child

General Puffiness of hands and feet, webbed neck, low posterior

hairline, and other findings suggestive of Turner syndrome may be obvious

to the examiner, also noting the widely spaced nipples and shield-shapedchest Bowed legs and flaring of the wrists are easy to see, whereas therachitic rosary again is part of the chest examination Bony abnormalities

such as the Madelung deformity or short fourth metacarpals are also readily

apparent

Agitation, Tremors The hyperthyroid school child or lescent may seem to have ADHD Hypoglycemia leads to epinephrine release with tremors, clammy skin, and a feeling of dread Hypocalcemia

ado-can cause muscle irritability as well These signs ado-can progress to franksyncopal episodes or seizures

Measurements Refer to the “History” section for the tions associated with short stature, tall stature, underweight, or over-weight Repeated accurate measurements spaced 6 or more months apartyield rate-of-growth information that helps to distinguish between a pat-tern of growth that is a variant and a disorder of growth Variant pat-terns of growth ultimately yield normal adult size A key feature is thatthey usually have appropriate growth velocity, whereas growth disor-ders are most often characterized by abnormal rates and poor outcome

condi-Skin and Cutaneous Appendages The stretch marks

of obesity are usually thinner and pink or pale, whereas those from ing syndrome are wider and purpler; there is a sensation of fullness in

Cush-stretched skin from obesity, whereas the striae of Cushing syndrome are

associated with cutaneous atrophy Acanthosis nigricans is dark and

“velvety” and found in intertriginous areas Attempts to scrub it offmay have traumatized the skin There is thickening of the skin withdeep creases in this lesion Very fair-skinned individuals may have alighter-colored lesion, with less melanin, but the other characteristicsare the same In children and adolescents this is usually a consequence

of insulin resistance Hirsutism is the growth of hair in a sexually propriate manner Facial and body hair in females growing in a malepattern may be due to androgen excess or can be idiopathic with normal

hormone levels Hypertrichosis, increased hairiness of the rest of the

body, may accompany hyperinsulinemia or exposure to medications such

as minoxidil or be familial Dry or breaking hair or hair that falls outmore than usual can be due to hypothyroidism Skin that is dry and

waxy or sallow in appearance and nonpitting edema (myxedema) owing

to accumulation of glycoprotein in the subcutaneous layer are features

of hypothyroidism Pretibial myxedema also may be present in Graves disease Café-au-lait spots with irregular border suggest McCune-Albright syndrome A generalized bronzing of the skin with no tan line is more

typical of Addison disease or out-of-control congenital adrenal plasia A more subtle manifestation is hyperpigmentation just of skin

hyper-creases and the knuckles Nail changes appear in Graves disease with onycholysis, in Turner syndrome with hyperconvexity, and in Candida infection associated with autoimmune polyendocrinopathy.

Eyes Exophthalmos is common in Graves disease but also occurs occasionally with Hashimoto thyroiditis The distance from the outer can-

thus of the orbit to the anterior surface of the cornea is usually less than

15 mm This is measured with an inexpensive Luedde mometer or with one of the more costly exophthalmometers employingprisms Chemosis of the sclera is often apparent even when the patientcan fully close the eyes during sleep There may be stare and lid lag,with or without exophthalmos Extraocular muscle involvement maylead to partial paralysis of gaze in one or more directions Visual fielddefects may be due to optic nerve pressure from lesions in or near the

exophthal-pituitary Nystagmus occurs in septo-optic dysplasia, often associated with hypothalamic-pituitary deficiency Occasionally, iris coloboma and/or coloboma

of the retina is associated with hypothalamic-pituitary deficiency

Per-sistent myelination of the corneal nerves occurs in MEN 2b Cataracts

may be present in diabetes mellitus, sometimes paradoxically during

improvement of glycemic control Retinal changes of diabetes include udates, microaneurysms, occasional hemorrhage, and uncommonly in this age group, neovascularization.

ex-Ears External ear malformations suggest genetic disorders (see

Chapter 6) Deafness is associated with the Pendred syndrome and with

inadequately treated congenital hypothyroidism for some period afterbirth

Neck Goiters from iodine deficiency, hereditary deficiency of enzyme(s) needed in thyroid hormone synthesis, chronic lymphocytic thy- roiditis, and Graves disease are usually painless, whereas those from acute and subacute thyroiditis are painful A bruit over the thyroid gland de- notes hypermetabolism with increased blood flow in Graves disease A Delphian lymph node may be present in autoimmune thyroid disease; it is

located just above the isthmus It differs from a pyramidal lobe, a

nor-mal variant of thyroid formation Thyroglossal duct cysts may present in

KEY FINDING

KEY FINDING

KEY FINDING

childhood and adolescence as a cystic or fluctuant mass in the anteriorneck, and there may be recurrent episodes of infection, pain, andswelling before the diagnosis becomes apparent.

Cardiovascular Tachycardia with or without widened pulsepressure (systolic pressure minus diastolic pressure is often more than

50 percent of systolic pressure) and “water-hammer pulses” suggest

increased adrenergic sensitivity owing to Graves disease Bradycardia is common in hypothyroidism A systolic flow murmur may be present in

Graves disease, whereas diminished heart sounds owing to pericardialeffusion suggest hypothyroidism

Abdominal Pain and tenderness of diabetic ketoacidosis can mimic appendicitis or ureteral obstruction The abdominal pain of Addisonian crisis

also may suggest a “surgical abdomen.”

Neurologic Increased deep tendon reflexes can occur in thyroidism or hypocalcemia The Chvostek sign and the Trousseau sign are detectable in hypocalcemia Fine-intention tremor and fasciculation of the tongue on protrusion are frequent in Graves disease To amplify the

hyper-hand tremor, place a small, light piece of paper on the dorsum of theoutstretched hand It is possible to demonstrate an intention tremor byasking the patient to firmly grasp and shake both the examiner’s hands(the examiner crosses hands to make it easy for the patient) Decreased

deep tendon reflexes may occur in hypothyroidism or hypercalcemia, the

“hung up” or late and prolonged reflex is a sign of hypothyroidism

Breasts Onset of thelarche in girls is normal after age 8 ate an investigation for precocious puberty or exogenous estrogen ex-posure for girls manifesting thelarche earlier than 8 The tissue may betender or painful in early stages because the capsule is under tension.Asymmetry of breast development is sometimes distressing to child orparent; however, it is usually not permanent or pronounced by late ado-lescence or adulthood and is most often physiologic There are somenon-endocrine-related malformations of breast tissue to consider De-layed onset of development of breast tissue, i.e., no development by age

Initi-13, indicates a need to evaluate the child for causes of delayed puberty,

e.g., ovarian failure, chronic illness, malnutrition, hypogonadism of pituitary origin, etc Galactorrhea may be due to medication, prolactinoma, chronic

irritation of the nipple, and in adolescents, during a pregnancy and

post-partum; lactation is physiologic Gynecomastia, development of breast

tis-sue in males, is of unclear etiology in preadolescents Certain drugs may

induce it, and rarely, estrogen-producing tumors are causes Adolescent gynecomastia is a physiologic process; estradiol is derived from testos-

terone by adipocytes in the skin of the chest when testosterone levelsare at early pubertal levels, and there is spontaneous resolution of breast

KEY FINDING

KEY FINDING

KEY FINDING

KEY FINDING

hypertrophy in most males Persistence or continued growth of the tissue

may not be consistent with endocrine disorder, but Klinefelter syndrome, anorchia, other acquired testicular failure, defects of testosterone synthesis, an- drogen receptor defects, feminizing adrenal tumors, drugs, aromatase overac- tivity, and possibly hyperprolactinemia may be causes.

Male External Genitalia Testicular enlargement is one

of the first signs of puberty; it is normal after 9 years of age, associatedwith a thinned and pendulous scrotum Hard and/or irregular en-

largement of testes may be a sign of tumor Hydrocele and torsion may

be painful Hydroceles will transilluminate; torsion and tumors will not.

Delayed onset of puberty, no changes by age 14, merits an evaluation

It may be due to extreme constitutional delay of growth and tion, it may be familial, or it may be due to defects anywhere in thehypothalamic-pituitary-testicular axis or to chronic illness Precocious

matura-puberty with early enlargement of testes may be central from activation

of hypothalamic and pituitary hormone release, it may be peripheral as

in familial gonadotrophin-independent precocious puberty, and it may

be due to McCune-Albright syndrome If the phallus grows and pubic hair appears but the testes remain small, consider adrenal androgen excess,

as in simple virilizing congenital adrenal hyperplasia or tumor Exogenous exposure to testosterone also may produce this picture Microphallus may

be due to androgen insensitivity or hypopituitarism Hypospadias has

similar etiologies as in infants Premature onset of pubic hair may bephysiologic if there is no enlargement of the testes or phallus and boneage is not advanced Otherwise, it may be the earliest manifestation ofprecocious puberty or androgen excess of endogenous or exogenousorigin

Exhaustion, lethargy, Infants Hypoglycemia

Electrolyte abnormalities.HypothyroidismChildren and All the aboveadolescents Diabetes mellitus

Adrenal insufficiency

(Continued)

IB General physical

Puffiness of hands Infants Turner syndromeand feet

Neck webbing and I, C, A Turner syndromeLow hair line

Widely spaced nipples, I, C, A Turner syndromeand Widened chest

of wrist and forearm)

II Anthropometric measurements

Placental insufficiencyTurner syndrome (in females)

Russell-Silver syndromeChildren Genetic short stature

Turner syndromeGrowth hormonedeficiencyHypothyroidismMalnutritionCeliac diseaseCushing syndromePrader-Willi syndromeAdolescents Constitutional delay

Delayed pubertySame as above in children

TABLE 13–2 Synthesizing a Diagnosis from Endocrine Signs and Symptoms (Continued)

Signs and Symptoms Age Group Possible Disorders

syndromeGenetic overgrowth syndromesChildren Genetic overgrowth

syndromesGrowth hormone–producing tumorsAcromegalyObesityPrecocious pubertyAdolescents Same as above

Klinefelter syndrome

III Weight

Underweight, failure to I, C, A Undernutrition

thrive, failure to gain Hyperthyroidismweight, or weight loss Diabetes mellitus

Overgrowth genetic syndromesHyperinsulinemiaChildren and Over nutritionadolescents Metabolic syndrome

Overgrowth genetic syndromesPrader-Willi syndromeCushing syndrome

IV Skin and cutaneous appendages

Stretch marks (pale or Children and Obesity (pale)

(purplish)Acanthosis nigricans Children and Insulin resistance(dark, velvety adolescents

pigmentation on

the neck, flexors)

Hirsutism (abnormal I, C, A, Ethnic

syndromeVirilizing forms of CAH

(Continued)

TABLE 13–2 Synthesizing a Diagnosis from Endocrine Signs and Symptoms (Continued)

Signs and Symptoms Age Group Possible Disorders

Coarse, dry, brittle hair, Children and Hypothyroidism

generalized hair adolescents Hypothyroidism

adolescentsHyperconvex nails I, C, A Turner syndrome

VII Head

Ping pong ball skull Infants Neonatal rickets

Treatment with growthhormone

HypoglycemiaHyperglycemiaOpen posterior fontanel Infants Neonatal hypothyroidism

VIII Eyes

Exophthalmos, lid lag, Children and Graves disease

Partial gaze paralysis adolescents

Visual field defects Children and Pituitary tumors

adolescents

(Continued)

TABLE 13–2 Synthesizing a Diagnosis from Endocrine Signs and Symptoms (Continued)

Signs and Symptoms Age Group Possible Disorders

hypothalamopituitarydeficiency

Coloboma of iris I, C, A Hypothalamic-pituitary

defects

Persistent corneal I, C, A MEN 2b

nerve myelination

Retinopathy Children and Diabetes mellitus

adolescents

IX Ears

External ear I, C, A Genetic syndromes,

X Neck

Thyroid gland Infants Iodine deficiency

enlargement (goiter) Enzymatic defects of

thyroid hormonogenesisChildren and As in infants aboveadolescents Graves disease

Hashimoto thyroiditisIodine deficiencySubacute hypothyroidismPainful goiter Adolescents Subacute thyroiditisBruit over the thyroid Children and Graves disease

Delphian node Children and Autoimmune thyroiditis

adolescentsCystic neck mass in I, C, A Thyroglossal duct

midline anteriorly Ectopic thyroid gland

XI Cardiovascular findings

TABLE 13–2 Synthesizing a Diagnosis from Endocrine Signs and Symptoms (Continued)

Signs and Symptoms Age Group Possible Disorders

Salt-wasting CAH

Hypertension Children and Cushing syndrome

adolescents Metabolic syndrome

PheochromocytomaTurner syndromeWidened pulse I, C, A Graves disease

pressure

Diminished heart Children and Pericardial effusion due

Flow murmurs Children and Graves disease

adolescentsCongenital heart I, C, A In association with

Coarctation of aorta I, C, A Turner syndrome

XII Abdominal signs and symptoms

Abdominal pain and I, C, A Diabetes mellitus in

Addison disease

XIII Neurologic signs and symptoms

or bilateral)

Premature thelarche in Children Rule out causes of early childhood precocious puberty.(2–8 years), unilateral Benign follicular cyst

or bilateral in females Exogenous exposure to

estrogens or phytoestrogens

(Continued)

TABLE 13–2 Synthesizing a Diagnosis from Endocrine Signs and Symptoms (Continued)

Signs and Symptoms Age Group Possible Disorders

Painful and tender early Children Normal

pubertal breast buds

Asymmetric breast I, C, A Local exogenous

or phytoestrogensRule out local infections,inflammations—ifindicatedGalactorrhea Infants Physiologic in early

infancyChildren Medicinal/drug intake,

e.g., risperidone, prolactinomaLocal infection Adolescents As above in children

Pregnancy and postpartumGynecomastia—breast Infants Normal in early infancytissue development Children Prepubertal

physiologicEstrogen producing tumorsDrugs/medications(below)

Adolescents Physiologic

Klinefelter syndromeAnorchia

Acquired testicular failureBiosynthetic defects of testosterone synthesisAndrogen receptor defectsHyperprolactinemiaFeminizing adrenal tumorsAromatase overactivityDrugs: cimetidine, spironolactone, digitalis, phenothiazines,

marijuanaHormonal treatments: estrogens, hCG, testosterone

(Continued)

TABLE 13–2 Synthesizing a Diagnosis from Endocrine Signs and Symptoms (Continued)

Signs and Symptoms Age Group Possible Disorders

XV External male genitalia

Undescended testes Infants Prematurity

(cryptorchidism) Delayed testicular descent

Genetic—in multiple family membersGenetic syndromes—25% chance of Intersex problem in cryptorchidism and HypospadiasAndrogen insensitivitysyndrome

Children and Genetic—in multiple adolescents family members

Genetic syndromes—25%chance of intersex problem in cryptorchidism and hypospadias

Androgen insensitivity syndrome

Symmetric bilateral Children and Pubertal onset

(Continued)

TABLE 13–2 Synthesizing a Diagnosis from Endocrine Signs and Symptoms (Continued)

Signs and Symptoms Age Group Possible Disorders

XVI Premature pubarche

Premature appearance Infants and Idiopathic premature

Simple virilizing CAHNonclassic CAHAndrogen-producingtumors need to be ruled out

XVII Menstrual disturbances

Primary amenorrhea Adolescents Turner syndrome

Rokitansky-Kuster-Hausersyndrome

Disorders of sexual differentiationSecondary amenorrhea Adolescents Pregnancy

Polycystic ovarian syndromeAnovulatory cycles—fewyears postmenarcheOligomenorrhea Adolescents Hyperthyroidism

Menorrhagia/ Adolescents Hypothyroidism

metrorrhagia

XVIII Others

Abbreviations: I= infants; C = children; A = adolescents.

Laboratory, Imaging, and Referral

for Endocrine Disorders

The endocrine evaluation depends on the signs and symptoms of thepatient Nonendocrine causes are more common for growth disorders,

so nonendocrine tests are essential before ordering a complete endocrineevaluation A stepwise approach actually may save time as well asmoney compared with a shotgun approach to laboratory testing Hor-mones do mediate growth, but most patients with a growth complaint

do not have an endocrine cause TABLE 13–3 lists the suggested

labo-ratory tests for short stature The order in which to obtain these testsrelates to the particulars of the case It is easiest to start with knowledge

of the rate of growth and current bone age If the rate is appropriate andbone age is similar to height age (age at which height is 50th percentile),

Endocrine Disorder Laboratory Imaging Further Testing

IGF-1, IGFBP3 Growth hormone stimulation test

3 Obesity—nutritional Workup depends on BMI

2-hour OGTTLipid profile Insulin level

Serum calcitonin levels

Puberty workup

abdomen

Karyotype

ACTH level Low-dose ACTH stimulation test Metyrapone test

3 Congenital adrenal 17OHP, DHEAS, androstenedione,

Plasma renin activity

Disorders of calcium

metabolism

Parathyroid gland Vitamin D levels

1, 25-hydroxyvitamin D)Urine calcium: urine creatinine ratio

(Continued)