1. health and fitness
2. disease
3. thyroid disease

3/3/2014
Evaluation of Thyroid Disease in Children
SLCH Clinical Practice Update
Paul W Hruz M.D. Ph.D.
Director, Division of Pediatric Endocrinology and Diabetes
March 7, 2014
Overview
Goals & Objectives
• Recognize common signs of thyroid dysfunction in
children
• Know what thyroid tests to order and how to
correctly interpret results
• Develop greater confidence in determining
indication and timing of follow-up thyroid testing
and/or referral to an endocrinologist for abnormal
results
Thyroid Hormone Synthesis
• Review of Thyroid Physiology
• Laboratory Testing
• Congenital Hypothyroidism
• Acquired Hypothyroidism
• Hyperthyroidism
• Obesity
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•
Thyroid Hormone Action
Normal Thyroid Physiology
Thyroid Function Testing
Thyroid Imaging
Thyroid Stimulating Hormone
(TSH)
•
o Most sensitive indicator of thyroid function
o Not helpful in assessing secondary or
tertiary disease
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•
o Present in 10-20% of normal
people
o Cannot predict progression to
overt thyroid disease
Total T4
o Well established validated and reliable
assay
o Multiple influences on interpretation
Free T4
o Measures only ~0.1% of total circulating T4
o Reliability varies among laboratories
o Direct measurement (equilibrium dialysis)
with less interference
•
Total T3
•
T3U and T3RU
o Measures only 0.3% of total circulating T3
o Not routinely helpful
o Still present on some commercial lab
panels
o Allows indirect assessment of free
hormone levels
Thyroid peroxidase
antibody levels(TPO)
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•
Thyroid Stimulating
Antibodies (TSI)
Thyroid Binding Globulin
levels
o Can affect total T4 levels
•
Thyroglobulin
o Helpful in surveillance of
thyroid carcinoma
• Ultrasound
o Not generally helpful as initial test in evaluating simple
goiter
o Helpful in evaluating a palpable thyroid nodule or
distinguishing thyroid vs extrathyroid tissue (e.g.
thyroglossal duct cyst)
o Helpful in evaluating palpable nodule
• Scintigraphy
o Not generally a first line test in evaluating thyroid
disease
o Helpful in distinguishing Graves disease from
exogenous thyroid, hyperfunctioning nodule, and
subacute thyroiditis
o Often used to detect thyroid tissue in congenital
hypothyroidism
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Congenital Hypothyroidism
Case #1 (James) • A male infant is born at term following an
uncomplicated vaginal delivery. There is no maternal
history of thyroid disease. The infant appears normal
without goiter or any clinical evidence of
hypothyroidism. His newborn screen results drawn on
DOL #2 are reported as follows:
• Incidence- 1:4,000
• Etiology
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o
o
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Thyroid Dysgenesis (80-90%)
Transient Hypothyroidism
Maternal thionomide, iodine
Secondary hypothyroidism
Hormone synthetic defects
• Newborn Screening
• Audience Participation Questions
o Elevated TSH
o Low T4
o Confirmation with serum T4 & TSH
o What is Your Diagnosis?
o What is Your Management Plan?
Hypothyroidism:
Clinical Symptoms
Testing Considerations
• Method of Screening Varies by state
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Growth retardation
Diminished physical activity
Impaired tissue perfusion
Constipation
Thick tongue
Poor muscle tone
Hoarseness
Anemia
Intellectual retardation
o Primary T4
o Primary TSH (Both Illinois and Missouri)
• Maternal history can be helpful
o Maternal autoimmune thyroid disease
o Exposure to thionomides
• Testing prior to 48 hours of life
o Higher false positive NBS
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Neonatal Thyroid Physiology
Follow Up for Case #1 (James)
• Baby James is seen in your office on DOL#9. He is
bottle feeding well and has regained his
birthweight. There is no history of jaundice. His
thyroid studies are repeated.
Normal Ranges of TFTs by Age
Considerations for Treatment
• Hypothyroid symptoms can be mild, difficult to illicit
and may overlap with normal children
• Thyroxine is critically important for neurocognitive
development during the first 2 years of life
• Levothyroxine is inexpensive, easy to administer,
and generally safe
• Treatment of children with TSH between 6-10 for
congenital hypothyroidism can lead to parental
anxiety and additional cost of f/u testing
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3/3/2014
Key Take Home Points
Case #2 (Kiara)
• Mild-moderate elevation of TSH levels on newborn
screen performed within the first 48 hours of life with
an otherwise benign history and exam should be
repeated
• Kiara, a 12 year old obese girl is seen in your office
for her annual WCC. She has no goiter or family
history of thyroid disease. Her linear growth is
normal with a current stature and height at the 70th
percentile. The following laboratory studies are
obtained:
• Treatment of mildly elevated TSH (6-10 range) may
not require treatment.
• Persistent TSH >10 should be treated
Subclinical Hypothyroidism
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Hypothyroidism:
Treatment
Definition: Elevated TSH with normal T4 & T3
Prevalence in Pediatric Patients ~2%
Progression to overt disease is low (0-12.5%)
Treatment Recommendations:
o Indicated:
• TSH > 10
• Pregnant women
o Can be considered:
• Positive TPO antibodies
• “Symptomatic” Patients
• When present with other chronic disease
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Thyroid Function in Obesity
Follow Up for Case #2
• After counseling Kiara on lifestyle changes, she is
asked to have repeat thyroid testing in 2 months.
The results come back as follows:
• Typical Thyroid Function
Tests
o Mildly elevated TSH (<10)
o Normal Free T4
o High normal or mildly elevated
T3
• Believed to be an
adaptive response to
increase energy
expenditure
• Usually not the cause of
obesity
• Will resolve with weight
loss
• Does not require
treatment
Hyperthyroidism:
Clinical Features
Case #3 (Emily)
• Emily is a 14 year old girl who present with a 3 month
history of unintentional weight loss. She is otherwise
healthy. She is an “A” student. As part of your initial
workup you find the following results:
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Heat intolerance
Goiter
Widened pulse pressure
Tachycardia
Exophthalmos
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Nervousness
Irritability
Emotional lability
Tremor
Excessive appetite
Weight loss
Smooth, moist, warm skin
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Hyperthyroidism: Causes
• Autoimmune Thyroiditis
o Graves Disease
o Hashitoxicosis
• Autonomously Functioning Thyroid
o Toxic multinodular goiter
o Toxic adenoma
Graves Disease:
Diagnosis
• Suppressed TSH
• Elevated T4, Free T4, T3 levels
• Positive Thyroid Stimulating Antibodies
o Thyroid Peroxidase
o Thyroglobulin
o Thyroid Stimulating Immunoglobulin
• TSH mediated hyperthyroidism
o TSH secreting pituitary adenoma
• Subacute thyroiditis
• Exogenous thyroid adminisration
Graves Disease:
Treatment Options
Diagnostic Considerations for Low TSH and Normal FT4
• Normal lab variant
• Thionomides
o Methimazole
o PTU no longer prescribed due to toxicity
• Radioiodine Ablation
• Thyroidectomy
o My definition, 5% of labs will fall outside of “normal” range with 2.5% low
o Best assessed by repeating laboratory testing
• Subclinical hyperthyroidism
o TSH is generally the most sensitive marker of thyroid status and can be low
with normal T4 and/or T3 levels
o With overt hyperthyroidism, the T4 and/or T3 is elevated. A TSH of <0.1 is
also more suggestive of overt disease
• Drug Effects
o Several drugs are known to lower TSH levels (glucocorticoids, dopamine
agonists, octreotide, rexinoids, and possibly carbamazepine
• Subacute thyroiditis
o Can present with transient mild hyperthyroidism followed by transient mild
hypothyroidism without other symptoms
o Usually resolves spontaneously over several months
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Thyroiditis
• Acute Suppurative
o Tender swollen gland
o Fever, Toxic Appearance
o Requires Antibiotic Therapy
• Subacute
o Tender enlarged gland
o Negative antibodies
o Self-limited course (weeks-months)
Follow Up of Case #3
• Repeat TFTs 6 weeks after initial assessment
revealed a TSH of 0.25 µIU/ml with normal Free T4
• Emily was found to have positive TTG antibody
screening and subsequent duodenal biopsy
confirmed the diagnosis of celiac disease
• Chronic Lymphocytic (Hashimoto’s)
o Nontender goiter (cobblestone texture)
o Positive TPO, Thyroglobulin Antibodies
o Requires Thyroxine replacement
Case #4 (Richard)
• Richard is a 6 year old boy born in Chicago whose
family recently moved to St Louis. Thyroid studies
were obtained prior to you seeing him. He is
growing at the 50th percentile and has had normal
development.
Diagnostic Considerations
• Central Hypothyroidism
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o
o
o
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Can present with a normal TSH and Low T4/Free T4
Prevalence is 1:20,000- 1:80,000
TSH based newborn screening will miss central hypothyroidism
Usually occurs with other pituitary deficiency
Very unlikely if development and clinical history are normal
• Thyroid-binding globulin (TBG) deficiency
o Prevalence is 1:5,000- 1:12,000
o Hereditary form is X-linked (Males more severely affected)
o Acquired forms include Cushings disease, acromegaly, nephrotic syndrome
• Drug induced lowering of T4 with normal TSH and TBG
o Salicylates, lasix, NSAIDS, heparin, phenytoin, carbamazepin
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Additonal Testing
Case #4 Follow Up
• T3 resin uptake (T3RU)
o Patient serum incubated with labeled T3 which binds to TBG, followed by
pulldown of unlabeled T3 by an insoluble resin
o Inverse association: i.e High uptake = low TBG
• Free T4
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Preferred method of testing
Level will be low in central hypothyroidism but normal in TBG deficiency
If concern about interference, can be done via equilibrium dialysis
Pay attention to lab normal ranges, results differ by lab
• TBG level
o Can be measured directly by commercial assay
Case #5 (Emily) • Emily is a 17 year old girl is evaluated for symptoms
of fatigue. Mother has a history of Grave’s disease.
Emily has no goiter and is otherwise doing well.
• Studies demonstrate normal Free T4 and elevated
T3RU confirming TBG deficiency
• No further f/u is needed
Diagnostic Considerations for elevated T4 and normal TSH
• TGB excess
o Decreased clearance (occurs in pregnancy and with contraceptive use)
o Increased synthesis (X-linked disorder with incidence of ~1:40,000)
• Familial dysalbuminemic hyperthyroxinemia
o Autosomal dominant disorder due to mutation in albumin
o Results in albumin with 60 fold increased affinity for T4
• Generalized thyroid hormone resistance
• Diagnostic considerations?
o Most often caused by autosomal dominant mutation in thyroid receptor
gene (THRβ)
• Drug induced effects
o Amiodorone, propranolol, iodinated contrast agents, amphetamines
• Other causes
o Acute psychosis, high altitude
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Case #5 Follow Up • Further history revealed that Emily was taking oral
contraceptive pills for the past 4 months due to
irregular menses
• No further testing was performed
(If additional testing had been done, her Free T4 level
would have been normal. T3RU would have been
normal)
Goiter:
Differential Diagnosis
• Congenital
o Dyshormonogenesis
o Maternal Antibodies
• Blocking
• Stimulating
o Maternal Antithyroid drug
• PTU, methimazole
• Iodine
o TSH receptor Activating
Mutation
o McCune Albright
Syndrome
o Thyroid Tumor
• Acquired
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Inflammation
Colloid
Iodine Deficiency
Goiterogen
Infiltrative disease
Toxic goiter
Thyroglossal duct cyst
Andenoma
Carcinoma
Case #6
• Abby is a 13 year old girl who is noted to have
swelling of the anterior neck on routine examination
during a WCC. She has no complaints. There is no
tenderness to palpation. No nodules are felt.
Texture is smooth. The tissue moves with swallowing
• You obtain some laboratory studies
o TSH 3.2 µIU/ml (0.5-5.5), Free T4 1.3 ng/dL (0.8-1.8)
Follow Up Case #6
• Meliquia is seen again in 6 months and there has
been no change in the size of the goiter. She
continues to deny symptoms. She underwent
menarche 2 months ago.
• Thyroid studies remain normal and TPO antibodies
are negative
• She is reassured that this is a benign process.
Symptoms of hyper and hypothyroidism are
reviewed.
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3/3/2014
Case #7 (Meliquia)
• Abby is a 13 year old girl who had thyroid studies
obtained because of modest weight gain over the
past 2 years. Her BMI is currently at the 75th
percentile. There is a history of Hashimoto’s
thyroiditis in Abby’s mother. Abby denies any other
symptoms. She does not have a goiter.
Follow Up Case #7
Significance of TPO Autoantibodies
• More sensitive for Hashimoto’s thyroiditis
(prevalence up to 95%)
• Can be present in over 70% of patients with Grave’s
disease
• Are present in 15-20% of normal individuals
• Higher titers are more often found in patients with
disease but do not directly correlate with thyroid
function
Treatment
• Meliquia had repeat thyroid studies obtained 6
months later and was found to have a TSH of 15
µIU/ml with a Free T4 of 0.8 ng/dL. She continued to
gain weight. She also complained of mild cold
intolerance.
• She was started on 50 mcg of levothyroxine daily.
• 6 weeks later her TSH was 4 µIU/ml. She continued
to experience gradual weight gain.
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Summary
Questions??
• Newborn screen results are influenced by the timing
of testing and should be interpreted according to
age-specific normal ranges
• Obesity is frequently associated with mildly elevated
TSH which does not warrant treatment
• Treatment of subclinical hypothyroidism (TSH <10) is
not necessarily required and the likelihood of
progression to overt disease should be considered
• Recognition of the factors that can influence
thyroid test results (e.g. Abnl TGB, medications) can
aid in interpretation and ordering of f/u tests
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