Case 9: 2w old - Congenital hypothyroidism

Question 1

At what degree of weight loss in a newborn should you be concerned?

Answer 1

failure to regain birth weight by 2w –> concern & further evaluation

failure to regain birth weight by 3w / continuous weight loss after 10d –>”failure to thrive”

<6 wet diapers per day

Question 2

differences in weight between breast & formula fed infants

Answer 2

BREASTFED

• <7% birth weight in 3-4d of life
• small, frequent, 8-12 feedings every 24h

Question 3

signs of hunger

Answer 3

• increased alertness
• increased physical activity
• mouthing
• rooting

Question 4

assessing adequacy of feeds

Answer 4

• infant is gaining weight
• adequate UOP (3-5 voids by 3-5d old)
• adequate stool output (3-4 stools by 3-5d old)
• adequate frequency of feeding (q2-3h, for 10-15min per breast)

Question 5

define: lethargy

Answer 5

lethargy

• level of consciousness with poor / absent eye movement
• failure of child to recognize parents / interact with persons / objects in environment

Question 6

when to be concerned about dehydration in infant

Answer 6

• more at risk (v. larger children, adults)

- hx of vomiting and/or diarrhea

Question 7

diffdx: large fontanelle size

Answer 7

• skeletal d/o (rickets, osteogenesis imperfecta)
• chromosomal abnormalities (Down’s syndrome)
• hypothyroidism
• malnutrition
• increased intracranial pressures (+ splitting of sutures)
• shaken baby syndrome

Question 8

diffdx: small fontanelle size

Answer 8

"nml" - variant
==> premature closure / small fontanelle for age
- microcephay
- craniosynostosis
- hyperthyroidims

Question 9

diffdx: sunken fontanelle size

Answer 9

• dehydration

Question 10

diffdx: bulging fontanelle size

Answer 10

“nml” - if crying ==>increased intracranial pressure

• meningitis
• hydrocephalus
• subdural hematoma
• lead poisoning
• roseola

Question 11

most common cause of congenital hypothyroidism

Answer 11

==> thyroid dysgenesis

• aplasia
• hypoplasia
• ectopic gland (67%)

Question 12

causes of congenital hypothyroidism

Answer 12

• thyroid dysgenesis
• iodine deficiency

ANTITHYROID HYPOTHYROIDISM

• mothers with autoimmune thyroiditis –> transplacental passage of thyrotropin-receptor-blocking antibody
• mothers with Grave’s disease tx with antithyroid drugs

Question 13

hypothyroidism

• epidemiology:
• types of hypothyroidism
• presentation of congenital hypothyroidism
• screening
• treatment
• dx
• follow up
• prognosis

Answer 13

-epidemiology: 1:4000

TYPES

• congenital (more in Hispanic, Native American)
• primary (thyroid problem) = low T4, high TSH
• secondary (HPA problem) = low T4, low TSH

PRESENTATION

• BIRTH: normal (b/c of maternal T4)
• 3 MONTHS LATER - classic facies, feeding problems, decreased activity, constipation, dehydration, prolonged jaundice, skin mottling, umbilical hernia
• LATER - large tongue, hoarse cry, puffy myxedematous facies

SCREENING:
- newborn T4, TSH

TREATMENT:

• “prophylactic” levothyroxine until confirmatory results
• TSH = 1; T4 in upper 1/2 of normal range
• normalization of TSH by 1-2mo

Dx : all newborns with low T4, high TSh ==> have congenital hypothyroidism until proven otherwise
- confirmatory serum T4, TSH

FOLLOW UP (TSH, free T4)

• 2-4w after initiating therapy
• q1-2mo –> until 1yo
• q2-3mo –> until 3 yo
• q3-12mo –> until growth completed

PROGNOSIS:
- early detection & treatment ==> completely reverses the effects of fetal hypothyroidism
= more vigorous, cries more, sleeps less

Question 14

what is the most common type of hypothryoidism

Answer 14

primary

Question 15

what is one of the most common preventable causes of intellectual disability?

Answer 15

congenital hypothyroidism

the longer treatment is delayed, the greater the risk for morbidity for permanent mental disability

Question 16

phenylketonuria

• epidemiology:
• presentation of congenital PKU
• screening
• treatment
• dx
• prognosis

Answer 16

EPIDEMIOLOGY:

PRESENTATION (congenital PKU) :
==> BIRTH: normal
==> LATER: microcephaly, fail early develomental milestones, progressive cognitive impairment (+ seizures)
- albinism, musty odor of sweat & urine (pheylacetate)

PRESENTATION (exposure PKU) –> to mother with PKU, baby is a carrier & exposed to high intrauterine levels of phenylalanine :

• growth retardation
• micrcephaly
• intellectual disability
• congenital heart disease

Question 17

why do pregnant women with PKU have to maintain low pheylalanine levels?

Answer 17

• protect developing fetus

==> mother with PKU, baby is a carrier & exposed to high intrauterine levels of phenylalanine :

• growth retardation
• micrcephaly
• intellectual disability
• congenital heart disease

Question 18

diffdx lethargy in a 2w

–> how to diagnose

Answer 18

INFECTION

• sepsis = poor feeding, decreased acitivity
• meningitis =
• botulism (3-4mo - when introduce other foods (raw honey)) = poor suck, weak cry, top-down weakness

INTRACRANIAL

• hemorrhage from trauma
• shaken baby syndrome = babies of young/single parents, significant stressors, lower education level; hx of seizures / irritability; large fontanelles, AMS, poor feeding, hypotonia
• hydrocephalus
• hydranencephaly
• hypoxemia-ischemic encephalopathy = AMS shortly after birth; low APGAR; multi-system dysfunction (poor cardiac contractility, perfusion, renal insufficiency, seizures)

METABOLIC

• congenital adrenal hyperplasia = decreased feeding, activity ==> low Na, high K, high 17-OH progesterone
• salt-losing CAH = lethargy, vomiting, dehydration –> shock
• inborn error of metabolism = BIRTH (nml for 1-2d); LATER (d/t protein load in breast milk / formula) = somnolence, poor feeding –> vomiting, lethargy –> progressive encephalopathy ==> high ammonia

ENDOCRINE

• congenital hypothyroidism = feeding problems, decreased activity, constipation, prolonged jaundice, skin mottling, umbilical hernia ==> nml ammonia; low T4, high TSH
• hypoglycemia = hypothermai, irritability, tremors, jitteriness

CHROMOSOMAL DEFICIT
- Down syndrome = hypotonia - poor feeding

HEME

• polycythemia (Hct <65%) - w/in first h-d of life = AMS, poor feeding, plethora (excess of blood in circulatory system / one organ area), acrocyanosis, hyperbilirubinemia
• hyperbiliruinemia = d/t underlying cause of jaundice (rather than to hyperbili itself)

Question 19

diagnostic workup for infant with hypotonia

Answer 19

• serum Na, K
  ==> CAH (low Na, high K)
• serum ammonia
  ==> high in many inborn errors of metabolism (urea cycle d/o, organicacdemias, fatty acid oxidation d/o)
  ==> high in ornithine transcarbamylase deficiency (OTC - hyperammonemia, elevated urine orotic acid)
  ==> nml in congenital hypothyroidism
• glucose
• T4, TSH
  ==> congenital hypothyroidism (low T4, high TSH)

Question 20

most common urea cycle d/o

Answer 20

ornithine transcarbamylase deficiency (OTC = x-linked.

Question 21

typical facies of Down syndrome

Answer 21

• prominent epicanthal folds (of medial corner of eye)

- upslanted palpebral fissures (of medial eye slits)

Question 22

differentiate palpebral fissures of Down syndrome v. fetal alcohol syndrome

Answer 22

Down syndrome - upslanted palpebral fissures (of medial eye slits)

Fetal alcohol syndrome

• short palpebral fissures
• thin upper lip + smooth philtrum
• growth retardation (microcephaly, height and weight <10%ile)
• cognitive deficits

Question 23

most common congenital adrenal hyperplasia

- labs

Answer 23

(21OH deficiency)==> decreased production of cortisol, aldosterone

• high 17OH progesterole ==> androgen formation
• virilized females
• virilized males (longer penis, darker scrotum)
• decreased Na, high K –> salt wasting = vomiting, dehydration, shock

Question 24

A two-month-old female presents to clinic for a well-baby checkup. Mom has been happy because the “baby rarely cries and sleeps all the time.” On exam, the baby has yellowing of the skin, decreased activity, appears to have decreased tone, and a large anterior fontanel. What is the most likely diagnosis?

A		Sepsis	
B		Congenital adrenal hyperplasia	
C		Congenital hypothyroidism	
D		Shaken baby syndrome	
E		Neonatal lupus

Answer 24

C

Congenital hypothyroidism may not be clinically evident until 6 weeks of age due to circulating maternal thyroid hormone transmitted from the placenta. Signs and symptoms of congenital hypothyroidism include feeding problems, large fontanels, hypotonia, large tongue, coarse cry, and frequently an umbilical hernia. Congenital hypothyroidism should be picked up on routine neonatal screening.

Question 25

Jade is a 2-week-old female who was born at home and received no newborn screenings for congenital disease. Her mother brought her to the pediatrician's office concerned that her daughter appeared to be jaundiced and was constipated, tired, and not feeding well most of the time. Physical exam was notable for enlarged fontanels, jaundice without bruising, hypotonia without tremor or clonus, and an umbilical hernia. There was no sign of virilization, no abnormal facies, and no history of vomiting. Review of systems was otherwise negative except as stated above. Which of the following is the most important next step in Jade's management? A Glucose and electrolyte supplementation B Glucocorticoid and mineralocorticoid supplementation C No treatment needed D Consult with pediatric endocrinologist and start treatment with 10 to 15 mcg/kg/day of crushed levothyroxine in liquid, and follow up every 12 months E Empiric antibiotics after collection of blood, urine, and CSF cultures.

Answer 25

D congenital hypothyroidism American Academy of Pediatrics recommends this treatment regimen for infants age 0 to 6 months old. Dosing is based upon age and weight. It would also be important to consult with a pediatric endocrinologist to evaluate the short and long-term treatment plan. In addition, the specialist could also recommend screening for other autoimmune disorders.

Question 26

A 6-week-old infant girl whose family recently immigrated from Mexico is brought to clinic for “excessive sleepiness.” The mother states the infant is not easily aroused for feedings and is not as active as she was previously. She is also concerned about her daughter's large “outtie" belly button. On exam, the patient is afebrile and jaundiced, with a puffy myxedematous face. The fontanels are large but flat. There is a large umbilical hernia. When asked about the results of a newborn screening exam, mom states that the screening was never performed. What would be an expected abnormal lab value(s) associated with her condition? A Low sodium, high potassium B Glucose < 40 mg/dL C High WBC with bandemia D High TSH, low T4

Answer 26

D congenital hypothyroidism ``` umbilical hernia sleepy less active jaundiced myxedematous face ``` Congenital hypothyroidism may present with poor feeding, constipation, jaundice (longer and more persistent than physiologic jaundice of newborn), mottled skin, large fontanels, hypotonia, hypothermia and an umbilical hernia. Later findings include a hoarse cry, macroglossia, and myxedematous facies. Patients usually remain asymptomatic until after 6 weeks of age, as maternal thyroid hormones may still be in younger infants. Patients with primary hypothyroidism will have high TSH and low T4 levels. The most common cause of primary hypothyroidism will be aplasia or hypoplasia of the thyroid gland, and—much less commonly—inborn errors of metabolism. Secondary or tertiary hypothyroidism (HPA dysfunction) will have both low TSH and low T4, and are relatively rare causes of hypothyroidism in infants.

Question 27

A 45-day-old infant is brought in by his mother due to lethargy, constipation, and yellow skin color noted since birth. The mother and the baby moved to the U.S. from a foreign country that does not screen its newborns. The baby has been fed only formula since birth. Physical exam of the neonate reveals additional findings of large fontanelles, umbilical hernia, a large tongue, and abdominal distension. What is the next best step in diagnosis? ``` A Phototherapy B Exchange transfusion C TSH D Head ultrasound E Obtain a family history of jaundice to rule in or out a defect in bilirubin metabolism ```

Answer 27

C only formula fed ==> no likely breast milk / breastfeeding jaundice the constellation of baby’s problems is best accounted for by untreated congenital hypothyroidism. Unfortunately, severe mental retardation is unavoidable at this point because this condition should have been treated since birth. In the U.S., it would have been detected on the newborn screen.

Question 28

``` The parents of 5-month-old Tiffany are concerned about Tiffany’s decreasing oral intake over the past 4 days. They report that she has been sleeping more but seems to tire out when feeding; in fact, mom’s breasts have become quite engorged and she needs to pump to relieve the pressure. In addition to the sleepiness and poor feeding they report that she has not had a bowel movement in 3 days. She has no fever or respiratory symptoms. You note a weak cry on your exam, and a floppy baby when you try to sit her up. What additional finding are you likely to find on your exam? A Vesicular rash on her scalp B Large tongue and umbilical hernia C III/VI systolic murmur D Absent deep tendon reflexes E Cataracts and hepatosplenomegaly ```

Answer 28

D ``` sleepy poor feeding constipation weak cry floppy baby ==> more likely to be botulism v. congenital hypothyroidism (too old = more likely at 3mo) ``` this baby is at an age when likely introduced to different foods (raw honey) infant botulism which usually presents in the first year of life with hypotonia, lethargy, constipation, weak cry and can eventually lead to respiratory failure. These infants will have absent DTRs.

Question 29

You are called down to the nursery to evaluate a newborn girl who is ready to be discharged. The mom is concerned because this 3-day-old has become lethargic and doesn’t want to feed. She has vomited twice and is showing no interest in feeding. On physical exam you note a lethargic infant with an enlarged liver and worry about an inborn error of metabolism. Which test would be diagnostic for an ornithine transcarbamylase (OTC) deficiency? ``` A Hypoglycemia B Hyperammonemia and elevated urine orotic acid C Elevated 17-OH progesterone D Elevated TSH E Hyponatremia ```

Answer 29

B Both hyperammonemia and elevated urine orotic acid are diagnostic of OTC deficiency, an x-linked condition, the most common urea cycle disorder. ALSO - hypoglycemia