Case 9

Question 1

What are key history findings in an infant with congenital hypothyroidism?

Answer 1

Decreased feeding and activity, constipation, home delivery.

Question 2

What are key physical findings in an infant with congenital hypothyroidism?

Answer 2

Large fontanelle, jaundice without bruising, umbilical hernia, no virilization, hypotonia without tremors or clonus

Question 3

What is the differential diagnosis for congenital hypothyroidism?

Answer 3

Congenital adrenal hyperplasia, Congenital hypothyroidism, Down syndrome, Hypoglycemia, Sepsis, Shaken-baby syndrome, Hypoxic-ischemic encephalopathy

Question 4

What are key lab findings in testing for congenital hypothyroidism?

Answer 4

Low free thyroxine (T4), High thyroid stimulating hormone (TSH)

Question 5

Why is it important to detect congenital hypothyroidism so early?

Answer 5

If detected early on a newborn screen (when signs and symptoms usually are not yet present), early administration of thyroid hormone replacement prevents mental retardation.

Question 6

The newborn screening system consists of five parts:

Answer 6

(1) Newborn testing
(2) Follow up of abnormal screening results to facilitate timely diagnostic testing and management
(3) Diagnostic testing
(4) Coordinating disease management with the medical home and genetic counseling
(5) Continuous evaluation and improvement of the newborn screening system

Question 7

What are benefits of the newborn screening?

Answer 7

• Detect of a serious, treatable disorder before sx are present
• Institution of tx that can prevent serious problems
• Detection of carriers of certain genetic disorders

Question 8

What are the risks of the newborn screening?

Answer 8

• Failure to identify some children who have the condition (false-negative result)
• Parental anxiety in cases of false-positive results
• Genetic test’s revelation of misattributed paternity
• Detection of disorders for which treatment is not effective

Question 9

What is the etiology of congenital hypothyroidism?

Answer 9

• Primary hypothyroidism - the most common type of CH In the US - results from some form of thyroid dysgenesis: Aplasia, hypoplasia, or an ectopic gland.
• Abnormalities at the level of the pituitary or hypothalamus (secondary or tertiary hypothyroidism) result in a low TSH and a low T4 and represent less than 4 percent of cases.
• An infant of a mother with autoimmune thyroiditis may have transient hypothyroidism
• An infant born to a mother with Grave’s disease treated with antithyroid drugs may also have transient hypothyroidism
• Worldwide, iodine deficiency is the most common cause of hypothyroidism at birth

Question 10

What is the epidemiology of congenital hypothyroidism?

Answer 10

• In the US, incidence is approx. 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)

Question 11

What signs and symptoms does congenital hypothyroidism present with?

Answer 11

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

Question 12

Diagnosis of congenital hypothyroidism:

Answer 12

• Newborns with CH are now detected by the newborn screen
• Before newborn screening, approx. half of infants with CH were missed before 3 mo 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 tx 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.

Question 13

Weight gain in the breast fed baby:

Answer 13

Breastfed babies lose an average of 5.8 percent of their birth weight in the 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.

Question 14

What should urine output be for a breastfed baby?

Answer 14

3-5 voids by 3-5 days of age. 4-6 voids by 5-7 days of age.

Question 15

What should stool output be for a breastfed baby?

Answer 15

3-4 stools per day by 3-5 days of age. 3-6 stools by 5-7 days of age.

Question 16

How are fontanels measured?

Answer 16

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.

Question 17

What are large fontanels associated with?

Answer 17

• Skeletal disorders (eg rickets, osteogenesis imperfecta)
• Chromosomal abnormalities (eg Down syndrome)
• Other conditions (eg hypothyroidism, malnutrition, increased ICP, shaken baby syndrome)

Question 18

What is premature closure or a small fontanel associated with?

Answer 18

Premature closure or a small fontanel for age may be a feature of microcephaly, craniosynostosis, hyperthyroidism, or a normal variant.

Question 19

What is a sunken fontanel a sign of?

Answer 19

Dehydration

Question 20

What is a bulging fontanel a sign of?

Answer 20

Generally a sign of increased intracranial pressure (eg, meningitis, hydrocephalus, subdural hematoma, lead poisoning)

Question 21

What is lethargy defined as?

Answer 21

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.

Question 22

The younger the child…

Answer 22

…the more difficult it is to assess lethargy.

Question 23

A two-week-old child thought to be lethargic would have a differential diagnosis that includes but is not limited to:

Answer 23

• Infection (sepsis, meningitis)
• Intracranial pathology (hemorrhage from trauma, hydrocephalus, hydraencephaly)
• Metabolic disorder
• Chromosomal anomaly

Question 24

What are the most likely differential diagnosis with congenital hypothyroidism?

Answer 24

CH, Down syndrome, congenital adrenal hyperplasia (CAH), Hypoglycemia.

Question 25

What are less likely differential diagnosis with CH?

Answer 25

Sepsis, botulism, shaken baby syndrome, hypoxic-ischemic encephalopathy, polycythemia.

Question 26

Congenital hypothyroidism (CH):

Answer 26

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 facies, enlarged and protruding tongue, a hoarse cry, and delayed growth and development. Constipation is common.

Question 27

Down syndrome:

Answer 27

Typically hypotonic at brith and in the first months of life. May feed poorly. ROS otherwise normal.

Question 28

Congenital adrenal hyperplasia (CAH):

Answer 28

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.

Question 29

Hypoglycemia:

Answer 29

Clinical manifestations are variable and infants are frequently asymptomatic. Typical signs in a newborn include jitteriness, irritability, hypothermia, tremors, hypotonia, poor feeding and seizures.

Question 30

Sepsis:

Answer 30

Presents as an acute illness with fever.

Question 31

Botulism:

Answer 31

Infants with botulism present with poor suck and weak cry. A rare diagnosis (about 900 cases reported worldwide) and usually presents a little later (median onset 3-4 mo of age).

Question 32

Shaken baby syndrome:

Answer 32

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.

Question 33

Hypoxic-ischemic encephalopathy:

Answer 33

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.

Question 34

Polycythemia:

Answer 34

Occurs when the hematocrit is above the normal limit for gestational age (usually defined as greater than 65 percent 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 occur in the first few hours to days of life.

Question 35

T4, TSH:

Answer 35

T4 expected to be low and TSH elevated in CH.

Question 36

Glucose:

Answer 36

Critical to check in any infant with hypotonia.

Question 37

Serum sodium and potassium:

Answer 37

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

Question 38

Serum ammonia:

Answer 38

Elevated in many inborn errors of metabolism, particularly urea cycle disorders (such as ornithine transcarbamylase deficiency), organic academias, and fatty acid oxidation disorders. Normal in congenital hypothyroidism.

Question 39

Newborn metabolic screen:

Answer 39

Every infant born in the US 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 fibrosis.

Question 40

How do you best manage congenital hypothyroidism?

Answer 40

1. Consultation with pediatric endocrinologist
2. Thyroid hormone replacement
3. Frequent follow up
4. Patient education

Question 41

What is the goal of thyroid hormone replacement?

Answer 41

• The goal of tx with levothyroxine is to maintain TSH at approx. 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 neurological outcome.

Question 42

What is the importance of frequent follow up?

Answer 42

• Recc. 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 12 months until growth is completed.
• Monitor development with appropriate screening tools.