Transcript Thyroid disorders in Children

THYROID DISORDERS IN CHILDREN
BLOCK 5
SEPTEMBER 13, 2012
Margot Butler M.D. F.A.A.P.
Objectives
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Know the clinical picture of hyperthyroidism and the typical onset in children.
Become familiar with the autoimmune disorders associated with both Grave’s
Disease and Hashimoto’s Thyroiditis
Know the treatment options for Grave’s Disease.
Recognize the symptoms and physical exam seen with congenital hypothyroidism.
Understand the importance of the neonatal state screen.
Recognize the importance of treatment and implications of inadequate treatment
of hypothyroidism in the neonate and young child.
Know the causes and treatments for the most common causes of congenital and
acquired hypothyroidism.
Differentiate the lab differences between primary and central hypothyroidism.
What Thyroid Hormone Does
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Increases O2 consumption
Stimulates protein synthesis
Influences growth and cell differentation
Affects carbohydrate, lipid and vitamin metabolism
T4 is critical to the myelinization of the central nervous system during
the first 3 year of life
The thyroid: How it works.
Thyroid gland develops the 7-10th week of gestation.
**Main function of thyroid gland is to synthesize T4 and T3.
T3= triiodothyronine
T4= thyroxine
**Physiological role of iodine is to synthesize T4/T3.
**Iodide reaches thyroid gland despite form ingested.
monoiodotyrosine
Monoiodotyrosine + diiodotyrosine = T3
Diiodotyrosine + diiodotyrosine = T4
Iodination of tyrosine
diiodotyrosine
***T3 is 3-4 times more potent metabolically than T4***
How the Thyroid Works:
simple version
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T4 binds tightly to Thyroxine Binding Globulin (TBG)
 Only
0.03% of T4 in serum is not bound
 70% is bound to TBG (also binds to prealbumin, albumin, transthyretin)
 Unbound T4 is “free T4”
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T3 also bind to TBG (but less strongly)
 0.3%
of T3 in serum is not bound
 50% is bound to TBG, 50% is bound to albumin
 Unbound T3 is “free T3”
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ONLY THE “FREE” T3 AND T4 IS ACTIVE
T4 is also converted peripherally to T3 by thyroxine 5’ deiodinase
 Deficiency
in this enzyme = hypothyroidism
Thyroid Regulation
Hypothalamic-Pituitary- Thyroid Axis
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TRH: secreted by hypothalamus
TSH: glycoprotein secreted by
anterior pituitary
subchain is similar to LH/FSH
 Β subchain provides specificity
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TSH stimulates the thyroid gland to
produce T3/T4
Case 1
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CC: Heart beating fast
HPI: 14 yo female presents to the ER with intermittent stabbing chest
pain and rapid heart rate for 2 weeks. Pain is not associated with
activity and does not radiate. Pain does not wake her at night. Patient
reports shortness of breath with activity. Denies any recent illnesses or
injuries. She has a history of anxiety, and her parents recently
announced their intentions to divorce about 1 month ago.
Case 1
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Review of Symptoms
General: decreased appetite x 1 month, no change in activity. No fever. Apprx 5
pound weight loss over the last 2 months
 HEENT: No changes in vision, hearing or smell, Denies neck pain, sore throat or LAD. +
nasal congestion (reports had a cold last week).
 Respiratory: Mild cough for 1 week. No difficulties breathing. +SOB as mentioned in
HPI. No wheezing.
 Cardiovascular: +palpitations. No hx of heart murmur.
 Gastrointestinal: No abdominal pain. Denies vomiting, diarrhea. Soft, nonbloody
stools daily.
 Genitourinary: Denies dysuria, polyuria or nocturia. Regular monthly menses since
age 12. Denies pregnancy.
 Musculoskeletal: Denies joint pain or swelling. No reported muscle weakness.
 Neurological: Daily headaches since onset of intermittent chest pain. +dizziness with
chest pain. No syncopal episodes.
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Case 1
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PMH: frequent ear infections, speech delay
PSH: myringotomy tubes at 1 year old
FH: Mother is hypothyroid. Congenital hearing loss in father.
SH: Lives at home with mother, 18yo and 7yo brothers. Denies use of
TOB, ETOH or other illicit drugs. Denies sexual activity. Is in the 8th
grade, making B’s and C’s (decreased from A’ s and B’s at the
beginning of the year)
Medications: none
Allergies: none
Case 1
Physical exam
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General: no acute distress, but does appear anxious, well hydrated, alert and oriented
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Height: 63” Weight: 52kg
VSS: HR 112, BP 131/70, RR 27
HEENT: mild R side proptosis, + lid lag. oropharanyx normal, neck supple with palpable thyroid gland, no
nodules
Chest: No reproducible pain to fingerpoint palpation of the costochondral or costosternal junctions, no
reproducible pain with trunk or shoulder movements. Breast tissue is nontender- Normal breast symmetry
with secondary nipple mound
Lungs: clear to ausciltation bilaterally
Cardiovascular: tachycardic, heart is regular rhythm, no murmur. Normal S1 and S2. No ejection click.
Brachial and femoral pulses are equal and strong.
Abdomen: Soft, nontender. +BS. No masses
GU: normal external genitalia- Pubic hair distribution is across the pubis but not extending to the inner thighs
Musculoskeletal: no joint swelling or redness
Neurologic: No focality. Cerebellar function intact. CN 2-12 intact. Strength 5/5 in all extremities.
Sensation and proprioreception normal. +2 DTRS in extremities
Clicker Question
What is the Tanner Stage of this patient?
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B.
C.
D.
E.
1
2
3
4
5
Tanner Stages
Tanner 1
Tanner 2
Tanner 3
Tanner 4
Tanner 5
Differential Dx of heart palpitations
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Cardiac
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Arrhythmia
Wolff Parkinson White syndrome
Prolonged QT syndrome
Hypertrophic cardiomyopathy (HCM)
Myocarditis
Sick sinus syndrome
Cardiac structural abnormalities (eg,
congenital heart disease, intracardiac
tumors
Premature atrial contractions
Premature ventricular contractions
Mitral valve prolapse
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Noncardiac
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Fever
Anemia
Exercise
Emotional arousal
Anxiety
Panic attack
Hyperventilation syndrome
Drug-induced (caffeine, herbal
medications, dietary supplements,
albuterol, isotretinoin)
Hypoglycemia
Toxic exposure
Pheochromocytoma
Hyperthyroidism
Case 1
Workup and Evaluation
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Chest x-ray
EKG
CBC (complete blood count)
Thyroid studies
BMP (basic metabolic panel)
Hyperthyroidism
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Symptoms
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Hyperactivity, irritability, altered mood,
insomnia, anxiety
Heat intolerance, increased sweating
Palpitations
Fatigue, weakness
Dyspnea
Weight loss with increased appetite
Pruritus
Thirst and polyuria
Oligomenorrhea or amenorrhea, loss of libido
Signs
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Sinus tachycardia, atrial fibrillation (rare in children),
supraventricular tachycardia
Fine tremor, hyperkinesis, hyperreflexia
Warm, moist skin
Palmar erythema, onycholysis (nails separate and fall
off)
Hair loss
Muscle weakness and wasting
High-output heart failure
Chorea
Diffuse Goiter
Ophthalmopathy, with proptosis and a gritty sensation
**** more commonly seen with Graves Disease****
KNOW that 90% of hypothyroidism is
caused by Graves disease in childhood
Graves Disease
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Most common form of hyperthyroidism in children (90% of cases)
Etiology: Excessive thyroid hormone production, caused by thyrotropin
receptor-stimulating antibodies (TRS-Ab)
 Ages
11-15yo most common
 Girls > boys
 Incidence 1:5000 children
 Family history of autoimmune disorder
 May be at increased risk for other autoimmune disorders
 Addison
disease, insulin-dependent diabetes mellitus, myasthenia gravis, and celiac
disease
 Systemic lupus erythematosus, rheumatoid arthritis, vitiligo, idiopathic
thrombocytopenic purpura, and pernicious anemia have been described in children
with Graves disease
Ophthalmopathy is a hallmark of Graves
disease
The major symptoms include one or more of the following: a sense of irritation in the eyes; excessive
tearing that is often made worse by exposure to cold air, wind, or bright lights; eye or retroorbital
discomfort or pain; blurring of vision; diplopia; and occasionally loss of vision.
Graves Disease
Diagnosis and Treatment
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Diagnosis
Elevated T3/T4
 Decreased TSH
 + TRS-Ab (Thyrotropin-receptor stimulating antibodies)
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+/- TPO-Ab (Thyroid peroxidase antibodies);
+ TBII (Thyrotropin binding inhibitor immunoglobulin)
High, diffuse RAI (radioactive iodine)
Treatment:
 Antithyroid
drugs
 Thionamides: methimazole (MMI), propylthiouracil (PTU)
 B-blockers
 Radioactive iodine
 Thyroidectomy
Clicker Question
What is most one the earliest symptoms of hyperthyroid
disease presenting in children/adolescents?
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Decline in school performance
Thyroid enlargement
Exophthalmos
Extreme weight loss
Hair loss
Case 2:
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CC: poor feeding
HPI: A 25 day old male infant is in your office with his mother
because of poor feeding and sleeping too much. She attempts to
breastfeed every 2 hours but reports the infant does not seem
interested and will not stay awake after latching on. Mother feels like
he has not gained enough weight since his birth. He voids normally.
Has 1-2 hard stools every 3-4 days. He has been a good baby at
home and cries very little.
Case 2:
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Birth history:
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at 41 weeks to G1 mother. Natural water birth at home by a doula
with no complications. Mother denies any prenatal infections, medications or
health issues during her pregnancy. GBS unknown.
 Birthweight: 7#10 ounces Length: 19 inches Head circumference: 13
inches
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Family history:
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contributory
Social history:
 Lives
at home with mother and father. No pets. No smokers.
Case 2:
Physical exam
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General: quite newborn but arousable.
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Vitals: HR 130 RR 33 BP 89/65 Temp 99.1
Weight: 7lbs 11ounces Length: 20 inches
HC: 13.5 inches
Head: Normocephalic with large soft anterior fontanels, posterior fontanel is open
and soft, measures about 1.5 cm
EENT: PEERL. Palate intact. + macroglossia. Neck is soft without palpable masses
Chest: symmetric, normal breath sounds
Heart: RRR. No murmurs.
Abdomen: soft, no masses. +BS
GU: normal male. Testis descended bilaterally. Uncircumcised.
Extremities: no deformities
Neuro: + suck/moro/grasp reflexes. Decreased tone.
Clicker Question
Which of the following things done in the newborn nursery would
have been beneficial to this patient?
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D.
E.
Erthymocyin eye ointment
Vitamin K injection
Lactation consult
Newborn screen
Hepatitis B vaccination
Congenital Hypothyroidism
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Worldwide incidence 1/4000 worldwide
Most common preventable cause of mental retardation
Most cases are not hereditary
 85
% secondary to thyroid dysgenesis (aplasia, hypoplasia or ectopic
gland)
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Girls > Boys
Congenital Hypothyroidism
Signs and Symptoms
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Asymptomatic at birth
 secondary
to transplacental passage of maternal T4 which provides levels
of 33% of normal
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First month of life = nondescript symptoms
 Poor
feeding/poor weight gain
 Sluggishness/somnolence
 Choking spells
 Noisy respirations, nasal obstructions, respiratory difficulties
 Constipation
 Anemia (macrocytic)
 Prolonged neonatal jaundice
 secondary
to delayed maturation of glucoronide conjugation
Congenital Hypothyriodism
Physical Exam
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Enlarged anterior and posterior fontanels
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3% of normal infants have posterior fontanels > 0.5cm
Large thick tongue (macroglossia)
Hypotonia
Large abdomen with umbilical hernia
Cold mottled skin
Edema of genitals and extremities
Heart murmurs
Slow heart rate
Below normal temperature (<95 degrees F)
Congenital Hypothyroidism
Zitelli & Davis: Atlas of Pediatric Physical Diagnosis, 5th ed.
Congenital Hypothyroidism
Labs/Diagnosis
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Blood work
 Serum
levels of T4 or free T4 are low
 Serum levels of T3 are not helpful and may be normal
 TSH is elevated
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Radiographs
 Retardation
of osseous development on x-ray
 Cardiac enlargement on ultrasound
 Thyroid ultrasonography
 Radioiodine (123I) or sodium technetium 99m pertechnetate (99mTc) thyroid
uptake and/or scan to identify functional thyroid tissue
Congenital hypothyroidism
Clinical course
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Symptoms are progressive
 Clinical
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picture fully developed by 3-6 months
Child’s growth stunted
 Shortened
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Dentition delayed
Myxedema of the eyelids, back of hands and genitals
Carotemia (yellow discoloration of skin)
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extremities
younger it’s prolonged neonatal jaundice
Hair coarse, brittle and scanty
Congenital Hypothyroidism
Newborn Screen
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Programs common in North America and developed countries
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Pilot programs started in Pittsburg in 1974
Screening methods
Primary T4 With Backup TSH Measurements***
 Primary TSH With Backup T4 Measurements
 Combined Primary TSH Plus T4 Measurements
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Helpful in detecting affected infants before clinical symptoms and findings
occur
Ideal blood collection done between 2-4 days of life
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Routinely done prior to discharge
IMPORTANT: Treatment is most effective if started before 2 weeks of age,
so early screening is essential
Congenital Hypothyroidism
Newborn Screen
Congenital hypothyroidism
Treatment and Prognosis
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Levothyroxine daily with monthly monitoring of TSH and T4 for the first 6
months
Levothyroxine = T4
 Only tablets should be used- no FDA approved suspension approved
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Thyroid hormone is critical for normal cerebral development
Without treatment, affected infants are profoundly mentally deficient and
growth retarded
 IF treated by 2 weeks of age, linear growth and intelligence comparable to
unaffected siblings
 When replacement therapy is begun later but within the first 2 months of life,
infants with severe hypothyroidism at birth may still have a low-to-normal IQ, but
stature and linear growth is usually normal
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Congenital hypothyroidism
Kliegman: Nelson Textbook of Pediatrics, 18th ed.
Clicker Question
Which of the following could be true of a person with a
goiter?
A.
B.
C.
D.
E.
F.
They may have normal function of the thyroid gland.
They may have thyroid hormone deficiency.
They may have an overproduction of thyroid hormones.
The goiter may be congenital.
The goiter may be acquired.
All the above (except she forgot this answer choice…good. Awesome.
Great)
Goiters
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Goiter is an enlargement of the thyroid gland.
Goiters
Autoimmune thyroiditis
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Most common cause of acquired goiter in the US in children > 6yo
Peak incidence = adolescents
Girls >> boys
Genetic predisposition
Characterized histologically by lymphocytic infiltration of the thyroid
Thyroid feels enlarged, firm, irregular and nontender
Can present as a euthyroid, hypothyroid or transient hyperthyroidism
 Most
affected children are clinically aysmptomatic
 most
are hypothyroid
Clicker Question
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a)
b)
c)
d)
e)
When describing hypothyroidism, which organ’s failure is responsible
for “tertiary” hypothyroidism?
Thyroid gland
Pituitary gland
Hypothalamus
Parathyroid gland
Thymus
Acquired Hypothyroidism
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Female predominance
90% secondary to Autoimmune Thyroiditis (Hashimoto’s Thyroiditis)
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Other causes:
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Mild inborn errors of thyroxine metabolism
Side effects of medical therapy
s/p treatment/surgery fro hyperthyroidism or thyroid cancer
Iodine Defiency
Strong familial pattern
GROWTH FAILURE is most common presenting manifestation
Acquired Hypothyroidism
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Coarse, dry and thick skin
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Fatigue, lethargy
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Cold intolerance
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Pallor
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Somnolence
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Constipation
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Delayed linear growth
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Overweight for height
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Delayed reflexes
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Bradycardia
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Irregular menstrual cycles
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Delayed puberty (occasionally precocious puberty)
Autoimmune Thyroiditis
Hashimoto Thyroiditis
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Most common cause of acquired hypothyroidism in children
Hashimoto Thyroiditis = autoimmune destruction of the thyroid secondary to chronic
lymphocytic thyroiditis
Activation of the CD4 helper T lymphocytes specific for thyroid antigens
Thyroid atrophy or goiter
More common in girls
Associated with other autoimmune disorders:
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Trisomy 21
Klinefelter’s syndrome
Diabetes Type I
Addison’s Disease
Turner’s Syndrome
Celiac Disease
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Note those in red = same as with Graves
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Autoimmune Thyroiditis
Hashimoto Thyroiditis - Diagnosis
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Primary hypothyroidism
 Elevated
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TSH, Decreased T4
Test for anti-thyroglobulin antibodies (Tg Ab) and anti-thyroid
peroxidase antibodies (TPO Ab)
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85 to 90 percent of children with chronic autoimmune thyroiditis have high serum anti-TPO
antibody concentrations
Autoimmune Thyroiditis
Hashimoto Thyroiditis - Treatment
 T4
replacement (Levothyroxine)
 Treat thru pubertal development and bone maturation before doing trial
off medication
 Some patients will eventually become euthyroid and can be taken off
medication
 Once patient becomes euthyroid, many of the symptoms disappear
Autoimmune Thyroiditis
Hashimoto Thyroiditis
Zitelli & Davis: Atlas of Pediatric Physical Diagnosis, 5th ed
Autoimmune Thyroiditis
Hashimoto Thyroiditis
Kliegman: Nelson Textbook of Pediatrics, 18th ed
Clicker Question
Which of the following results is most consistent with
central hypothyroidism?
A. Elevated TSH, normal T4
B. Elevated TSH, low T4
C. Decreased TSH, low T4
(she researched this and said TSH normal….so doubt she will ask this)
D. Decreased TSH, normal T4
E. Decreased TSH, elevated T4
Central Hypothyroidism
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Idiopathic
Hypothalamic lesions
Pituitary tumors, the most common of which is craniopharyngioma
Can also be caused by
 Subarachnoid
hemorrhages
 Radiation for cancer
References
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Counts, D. Varma, SK. Hypothyroidism in Children. Pediatr. Rev. 2009;
30; 251-258.
Kliegman: Nelson Textbook of Pediatrics, 18th ed
Kokotos, F. Adam, HM. Hyperthyroidism. Pediatr. Rev. 2006; 27; 155157.
Newborn Screening for Congenital Hypothyroidism: Recommended
Guidelines. AAP Section on Endocrinology and Committee on Genetics.
Pediatrics. Vol. 91 No. 6 June 1993; 1204-1209.
Zitelli & Davis: Atlas of Pediatric Physical Diagnosis, 5th ed.
www.uptodate.com