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medU | Instructors

Case 9
Author: Robert Wittler, M.D., University of Kansas.

Learning Objectives
1. Create a neonatal history using appropriate sources: hospital chart, mother,
nursing staff.
2. Develop a list of factors in the maternal and newborn history that may put a
newborn at risk for medical problems.
3. Describe possible complications of a home delivery and how they can be
4. Construct a diagnostic approach to a newborn with lethargy.
5. Compare and contrast the clinical manifestations of congenital
hypothyroidism relative to a normal newborn.
6. Describe core diseases screened for by neonatal blood screening.
7. Develop a strategy for educating families on the value of early
treatment/management of conditions that are included in the newborn

Summary of clinical scenario: Crimson is a jaundiced infant with decreased

feeding and activity. Physical exam narrows the differential, as Crimsons
hypotonia, large fontanels and jaundice are signs of congenital hypothyroidism,
and umbilical hernias are common in the disease. The lack of virilization argues
against congenital adrenal hyperplasia, and the normal facies effectively excludes
Down syndrome as the diagnosis. Low serum thyroxine (T4) and high thyroid
stimulating hormone (TSH) confirm the diagnosis of congenital hypothyroidism.

Decreased feeding and activity

No vomiting
Key Findings from History Constipation
Negative review of systems
Home delivery

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Large fontanels
Normal facies
Jaundice without bruising
Key Findings from Physical
Umbilical hernia
No virilization
Hypotonia without tremors or

Congenital adrenal hyperplasia

Congenital hypothyroidism
Down syndrome
Differential Diagnosis
Shaken-baby syndrome

Low free thyroxine (T4)

Key Findings from Testing High thyroid stimulating
hormone (TSH)

Final Diagnosis Congenital hypothyroidism

Case highlights: Students learn the definition of lethargy, information about

infant seizures, and the pros and cons of home births. They also learn how to
calculate fontanel size and what conclusions to draw from these measurements.
They select labs that will determine the diagnosis in this case and learn the
chemistry, symptoms, and consequences of congenital hypothyroidism.
Multimedia features include photos of an infant with scleral icterus and umbilical

Key Teaching Points

Newborn screening: Targets for newborn screening are serious diseases where
effective treatment is available and early diagnosis and treatment can prevent
morbidity and mortality. An example is congenital hypothyroidism: If detected on
a newborn screen (when signs and symptoms usually are not yet present), early
administration of thyroid hormone replacement prevents mental retardation.

The screening system consists of five parts:

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Newborn testing
Follow-up of abnormal screening results to facilitate timely diagnostic
testing and management
Diagnostic testing
Coordinating disease management with the medical home and genetic
Continuous evaluation and improvement of the newborn screening system

Benefits of screening

Detection of a serious, treatable disorder before symptoms are present

Institution of treatment that can prevent serious problems
Detection of carriers of certain genetic disorders

Risks of screening

Failure to identify some children who have the condition (false-negative

Parental anxiety in cases of false-positive results
Genetic tests revelation of misattributed paternity
Detection of disorders for which treatment is not effective

Congenital hypothyroidism (CH):


Primary hypothyroidismthe most common type of CH in the U.S.results

from some form of thyroid dysgenesis: Aplasia, hypoplasia, or an ectopic
Abnormalities at the level of the pituitary or hypothalamus (secondary or
tertiary hypothyroidism) result in a low TSH and a low T4 and represent <
4% of cases.
An infant of a mother with autoimmune thyroiditis may have transient
An infant born to a mother with Graves disease treated with antithyroid
drugs may also have transient hypothyroidism.
Worldwide, iodine deficiency is the most common cause of hypothyroidism
at birth.


In the U.S., incidence is approximately 1:4000 live births (range 1:3600

1:5000) based on newborn screening data.
CH is more prevalent in the Hispanic population (1 in 2,700) and Native
Americans (1 in 700).

Signs and symptoms

Usually not evident until after six weeks of age due to placental
transmission of maternal thyroid hormone.

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Early signs include feeding problems, decreased activity, constipation,

prolonged jaundice, skin mottling, large fontanels, hypotonia, hypothermia,
and umbilical hernia.
Later signs include large tongue, hoarse cry, and puffy myxedematous


Newborns with CH are now detected by the newborn screen.

Before newborn screening, approximately half of infants with CH were
missed before three months of age. Early detection and treatment can
completely reverse the effects of fetal hypothyroidism in all but the most
severe cases.
Low thyroxine (T4) and elevated thyroid stimulating hormone (TSH) on the
newborn screen must be confirmed with T4 and TSH measurements.
Because early treatment is critical for normal development, infants should
be started on levothyroxine (L-thyroxine) pending confirmatory lab results.
If an infant presents with symptoms and physical findings suggestive of CH,
the newborn screen should be sent, and specific tests for T4 and TSH should
be obtained.

Ballal SA and McIntosh P: Endocrinology. In: Custer JW and Rau RE: The Harriet
Lane Handbook, 18th Ed., Elsevier/Mosby, Philadelphia, 2009, p. 274-275.


Birth and neonatal history:

Maternal age and health, number of gestations, complications during

pregnancy, exposure to teratogens
Gestational age when born, how/where delivered, Apgar scores, birth
weight, vaccinations, neonatal screenings
Feeding regimen: Breast or bottle, frequency, duration, and/or amounts.
Stooling/voiding patterns

Breastfeeding assessment: Human milk is the preferred feeding for all infants,
including premature and sick newborns, with rare exceptions (human
immunodeficiency virus [HIV]infected mother):

A newborn should have 8 to 12 feedings at the breast every 24 hours

(approximately every 2 to 3 hours for 10 to 15 minutes per breast).
Mother should be encouraged to offer the breast whenever infant shows
early signs of hunger (such as increased alertness, physical activity,
mouthing, or rooting).
Weight gain:
Breastfed babies lose an average of 5.8% of their birth weight in the

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first few days of life

Failure to regain birth weight by three weeks of age or continuous
weight loss after 10 days of life has been defined as failure to thrive.
Urine output: 35 voids by 35 days of age; 46 voids by 57 days of age
Stool output: 34 stools per day by 35 days of age; 36 stools by 57
days of age

Physical exam:


Measurement: Fontanels are measured both by length (anterior-posterior

dimension) and width (transverse dimension). One can then take the
average of the length and width to determine a mean fontanel size and
compare it to normal values.
Large fontanels are associated with:
Skeletal disorders (e.g. rickets, osteogenesis imperfecta)
Chromosomal abnormalities (e.g., Down syndrome)
Other conditions (e.g., hypothyroidism, malnutrition, increased
intracranial pressure, shaken baby syndrome)
Premature closure or a small fontanel for age may be a feature of
microcephaly, craniosynostosis, hyperthyroidism, or a normal variant.
A sunken fontanel is a sign of dehydration.
A bulging fontanel is generally a sign of increased intracranial pressure
(e.g., meningitis, hydrocephalus, subdural hematoma, lead poisoning).


Defined as a level of consciousness characterized by poor or absent eye

movements, or failure of a child to recognize parents or to interact with
persons or objects in the environment.
The younger the child, the more difficult it is to assess lethargy. A
two-week-old child thought to be lethargic would have a differential
diagnosis that includes but is not limited to:
Infection(sepsis, meningitis)
Intracranial pathology (hemorrhage from trauma, hydrocephalus,
Metabolic disorder
Chromosomal anomaly

Differential diagnosis
More Likely Diagnses

1. Congenital hypothyroidism (CH): Due to maternal thyroid hormone,

newborns appear normal, and an infant born with CH usually has no
distinguishing features. If the condition is not detected by newborn
screening, CH presents in the first two months of life with characteristic

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facies, enlarged and protruding tongue, a hoarse cry, and delayed growth
and development. Constipation is common.
2. Down syndrome: Typically hypotonic at birth and in the first months of
life. May feed poorly. Review of systems otherwise normal.
3. Congenital adrenal hyperplasia (CAH): Decreased feeding and activity
are common in infants with CAH. Salt-losing CAH presents with irritability,
lethargy, vomiting, and dehydration that can progress to shock. Many, but
not all, states screen for CAH.
4. Hypoglycemia: Clinical manifestations of hypoglycemia are variable, and
infants are frequently asymptomatic. Typical signs in a newborn include
jitteriness, irritability, hypothermia, tremors, hypotonia, poor feeding, and

Less likely diagnoses

Sepsis: Presents as an acute illness. Absence of fever, negative review of

symptoms, and lack of any acute changes make sepsis unlikely.

Botulism: Infants with botulism present with a poor suck and weak cry. A rare
diagnosis (about 900 cases reported worldwide), and usually presents a little later
(median onset three to four months of age).

Shaken baby syndrome: Shaken baby syndrome with intracranial hemorrhage

could present with decreased activity and poor feeding, but would be an acute
presentation. A history of seizures or irritability would increase suspicion for this
diagnosis. Hypotonia or hypertonia with a large fontanel may be seen in shaken
baby syndrome. If bruising present, it would increase suspicion of non-accidental
trauma, but absence of bruising does not rule it out.

Hypoxic-ischemic encephalopathy: Secondary to prenatal or perinatal central

nervous system insult and usually presents shortly after birth. May present with
lethargy and poor feeding. Often find evidence of multi-system dysfunction.

Polycythemia: Occurs when the hematocrit is above the normal limit for
gestational age (usually defined as > 65% in a term newborn). Many infants are
asymptomatic, and hematocrits are not routinely checked. Associated symptoms
include altered mental status, poor feeding, plethora (an excess of blood in the
circulatory system or in one organ or area), acrocyanosis, and hyperbilirubinemia.
Typically, this condition occurs in the first few hours to days of life.

T4,TSH: T4 expected to be low and TSH elevated in congenital hypothyroidism.

Glucose: Critical to check in any infant with hypotonia.

Serum sodium and potassium: In a patient with CAH, low sodium and high
potassium would be expected. Even though congenital adrenal hyperplasia (CAH)
is very unlikely in the absence of virilization, serum sodium and potassium are

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reasonable to order to evaluate for this potentially life-threatening disorder.

Serum ammonia: Elevated in many inborn errors of metabolism, particularly

urea cycle disorders (such as ornithine transcarbamylase deficiency), organic
acidemias, and fatty acid oxidation disorders. Normal in congenital

Newborn metabolic screen: Every infant born in the U.S. should be screened
shortly after birth using heel-stick blood spots to detect a variety of congenital
conditions. Conditions included in newborn screening are congenital
hypothyroidism, congenital adrenal hyperplasia, hemoglobinopathies (sickle cell
disease), biotinidase deficiency, galactosemia, phenylketonuria, and cystic

1. Consultation with a pediatric endocrinologist

2. Thyroid hormone replacement:

The goal of treatment with levothyroxine is to maintain TSH at
approximately 1 mU/ml and T4 in the upper half of the normal range
for age.
Normalization of TSH by one to two months of age is associated with
improved neurologic outcome.
3. Frequent follow-up:
Recommended that TSH and free T4 be measured at two and four
weeks after initiating therapy, then every one to two months until one
year of age, every two to three months until three years of age, and
every three to twelve months until growth is completed.
Monitor development with appropriate screening tools.
4. Patient education

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