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Pediatric Thyroid Disease - Children's Hospital of Michigan resident lecture

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Kathleen Moltz

on 22 December 2014

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Transcript of Pediatric Thyroid Disease - Children's Hospital of Michigan resident lecture

Congenital Hypothyroidism
Treatment: start with 15 mCg/kg/day!
1-2 weeks
Then 10-12 mCg/kg/day
Tablet form, crushed, wiped into mouth just before feeding/nursing
NO SOY FORMULA
Monitor Free T4 and TSH
Every 2 months for first year
Every 3 months for second/third year
Every 4 months childhood
Every 6 months post-adolescent growth
Yearly in adults
Treat premature and ill neonates with care!
Thyroid hormone products
Desiccated porcine thyroid glands
Unithroid and Generic
Synthroid or Flint on pills!
Levoxyl
ALL BRANDS ARE NOT THE SAME! DIFFERENT ABSORPTION!
Not approved medications!
From left to right: God’s Herbs: thyroid, Slim Boost, Thyroid Strength, Thyrogen, Thyroid Health Formula, Thyromine
Deer thyroid gland activity (which mediates basal metabolic rate) decreases during cold weather.
Deer thyroid glands are used to monitor radioactive fallout.
Pediatric Thyroid disease
Pediatric Endocrinology Core Lecture Series

Kathleen Moltz M.D.
Objectives
Thyroid Anatomy, Histology & Embryology
Thyroid hormone synthesis and regulation
Hypothyroidism: general information
Hashimoto's thyroiditis
Congenital hypothyroidism
Acquired hypothyroidism
Hyperthyroidism
Nodules, Cysts and Cancer
Extras
Mosby 2006
Hormone
Regulator
The Thyroid
Thyroid Anatomy, Histology & Embryology
Mosby 2006
Thyroid production
Calcitonin production
Thyroid Anatomy, Histology & Embryology
Thyroid embryology
3 weeks: second branchial arch
5 weeks: in position
8 weeks: thyroglossal duct gone.
10 weeks: iodide concentration
12 weeks: T4, T3 and TSH
18-20 weeks: increasing T4, T3
25 weeks: TSH responsive to TRH
24-27 weeks: TSH regulated by T4
If the gland doesn’t migrate it remains ectopic!
Thyroid hormone synthesis
Thyroid regulation
Thyroid regulation
Symptoms and Signs
Weakness
Fatigue
Muscle soreness
Cold intolerance
Weight gain
Menstrual irregularity
Poor growth
Hypoactivity
Hyporeflexia
Bradycardia
Small pulse pressure
+/- Goiter
Edema
Many of these signs and symptoms are also seen in depression, overwork, chronic illness……
The Faces of Hypothyroidism
Congenital Hypothyroidism
Congenital Hypothyroidism
Congenital Hypothyroidism
Prolonged jaundice 33%
Cutis marmorata 33%
Constipation 32%
Umbilical hernia 31%
Lethargy 30%
Postmaturity (>42 weeks) 30%
Macroglossia 27%
Large fontanelles 25%
Feeding problems 22%
Hypotonia, distended abdomen, hoarse cry 20%
Congenital Hypothyroidism
Newborn screening as part of the “PKU”
TSH level checked
Normal or low birth weight
Age (in hours) since birth
Birth weight
Gestational age
Pediatrician/birth hospital notified
A Pediatric Endocrine “emergency” to start medication ASAP!
Congenital Hypothyroidism
Remember the normal pattern of thyroid hormone changes with birth!
Acquired Hypothyroidism
Any age; 2:1 female preponderance
Prevalence ? 0.14%
Increased in certain populations
Down syndrome
Turner syndrome
Type 1 diabetes mellitus
Autoimmune polyendocrinopathies
Acquired Hypothyroidism
Primary
Hashimoto’s thyroiditis
Irradiation of thyroid
Thyroidectomy
Drug-induced: interferon-a, lithium, iodine containing drugs
Consumptive (liver/skin hemangiomas)
Iodine deficiency
Secondary to pituitary/hypothalamic disease
Acquired Hypothyroidism
Diagnosis
Free T4, TSH
Thyroid antibodies
Ultrasound or thyroid scan if goiter or nodules
Treatment
T4 replacement ~100 mcg/m2 BSA
5 mcg/kg ages 1-5
4 mcg/kg ages 6-12
3 mcg/kg ages 13-18
1-2 mcg/kg adults
Monitor levels 4-6 weeks after any dose change, and intermittently similar to CH
Watch Soy, Calcium supplements, Citrus juice, Aluminum-antacids, anticonvulsants and cardiac meds
Acquired hypothyroidism
Age at diagnosis
? Thyroid failure?
Special circumstances
Down’s syndrome!
Psych meds!
ICU patients!
Premature infants!
Secondary hypothyroidism: just monitor free T4! (TSH useless!)
Hypothyroidism complications
Myxedema coma
Hyperlipidemia
Menstrual irregularity / infertility
Precocious or delayed puberty
Growth delay with overweight
December 1, 2014 kmoltz@med.wayne.edu
Thyroid
Somatostatin
Hypothyroidism
T4 & T3
TSH
Euthyroid
TSH
T4 & T3
...except secondary hypothyroidism with low TSH
Kathleen Moltz MD kmoltz@med.wayne.edu
We talk about him…
www.thyroidmanager.org/Chapter8/8-frame.htm
Dr. Hakaru Hashimoto
Kathleen Moltz MD kmoltz@med.wayne.edu
Thyroid disorders –
Hashimoto’s thyroiditis
The most common cause of goiter in adolescents
May be associated with other autoimmune disorders
Adrenal hypofunction & Diabetes = type 2 Autoimmune polyglandular syndrome
Adrenal hypofunction, hypoparathyroidism, mucocutaneous candidiasis = type 1 APS
Others: atrophic gastritis, pernicious anemia, systemic sclerosis, celiac, vitiligo
Kathleen Moltz MD kmoltz@med.wayne.edu
Thyroid disorders –
Hashimoto’s thyroiditis
Natural history: gradual development of symptoms / enlargement of gland, F>M
Signs: ±Goiter, generally non-tender
Symptoms: May be euthyroid, hypothyroid or hyperthyroid
Lab studies: TFTs plus
Antithyroid peroxidase (microsomal) ab
Antithyroglobulin ab (less sensitive)
10% can be histologically dx with negative ab
Kathleen Moltz MD kmoltz@med.wayne.edu
Thyroid disorders –
Hashimoto’s thyroiditis
www.unomaha.edu/hpa/endocrinehistology.html
peir2.path.uab.edu/scripts/acdis.dll?cmd=see&fp=/dbih/peir2/00025285.tif&fmt=jpg&q=50&h=450
Kathleen Moltz MD kmoltz@med.wayne.edu
Thyroid prenatal
Placenta has
limited permeability
to T4
Maternal hormone still critically important
Post-delivery t1/2= 3-4 d
Placenta is permeable to
Methimazole
PTU
Iodine
TRH
Antibodies
Placenta impermeable to TSH, Tg
Thyroidmanager.org
Kathleen Moltz MD kmoltz@med.wayne.edu
Normal perinatal period pattern of changes in thyroid hormone
Thyroidmanager.org
Hashimoto's thyroiditis can cause hypothyroidism, hyperthyroidism, euthyroid goiter, nodules, and slight increased risk for thyroid cancer
Congenital Hypothyroidism causes
Causes
Thyroid dysgenesis – sporadic: 80-85%
Agenesis
Hypoplasia
Ectopic
Thyroid hormone synthesis defect – AR: 10% (goiter at birth is common)
TSH/TRH synthesis defect (secondary or tertiary hypothyroidism) – AR/AD: 5%
Thyroid hormone action abnormality – AR/AD/x-linked
Transient: Iodine, meds, abs, sick euthyr, preemie
Endemic Iodine deficiency…
Kathleen Moltz MD kmoltz@med.wayne.edu
Congenital Hypothyroidism
Key concepts
1:2500-3500 live births
Most common treatable cause of MR
1st pilot screening Quebec 1972
TSH screening on NBS in all USA states
Only 10% can be clinically diagnosed in the 1st month of life
Failure to tx FTT and permanent MR
Acquired Hypothyroidism
Hashimoto's thyroiditis
Kathleen Moltz MD kmoltz@med.wayne.edu
HOT --Thyroid scan--COLD
Endocrineweb.com
Kathleen Moltz MD kmoltz@med.wayne.edu
Hyperthyroidism - presentation
Thyroid enlargement
Tremors
Inability to fall asleep and fatigue
Weight loss despite an increased appetite
Proximal muscle weakness
Heat intolerance
Tachycardia
Shortened attention span
Emotional lability
Polyuria and of nocturia
the result of an increased glomerular filtration rate
Acceleration in linear growth, Advancement in bone age
Puberty delayed
Secondary amenorrhea or menstrual irregularity if post-menarche
Change in school performance?
Change in sports performance?
Kathleen Moltz MD kmoltz@med.wayne.edu
Hyperthyroidism - neonatal
Transient: 2-3 months
Rarely permanent TSH constitutive activation
Results from the transplacental passage of maternal TSH receptor stimulating ab
1-2% of mothers w/ Graves’ disease
1 in 50,000 newborns
Most often onset is 1st week of life: often severely
clearance of maternally-administered Antithyroid drug from the infant’s circulation
increased conversion of T4  T3 after birth
Kathleen Moltz MD kmoltz@med.wayne.edu
Hyperthyroidism - treatments
Medical
Methimazole
NOT PTU in kids any more – liver failure!
Symptomatic blockade: beta-blocker
Surgical
Radioablation
Iodine - 131
Kathleen Moltz MD kmoltz@med.wayne.edu
Thyroid CA in kids
In papillary thyroid ca
Lymph node & pulmonary metastases common at diagnosis
Medullary thyroid ca
MEN2
Calcitonin
Preventative thyroidectomy (generally < 6 yo)
Highly malignant and poor prognosis
Kathleen Moltz MD kmoltz@med.wayne.edu
Thyroglossal duct cyst?
Neck mass that develops from cells and tissues remaining after the formation of the thyroid gland during embryonic development.
Most commonly diagnosed in preschool-aged children or during mid-adolescence
Often appears after an upper respiratory infection when it enlarges and becomes painful.
Features:
a small, soft, round mass in the center front of the neck
tenderness, redness, and swelling of the mass, if infected
a small opening in the skin near the mass, with drainage of mucus
difficulty swallowing or breathing
Treatment:
antibiotic medication (to treat the infection)
surgical removal of cyst & thyroglossal duct (Sistrunk procedure)
Kathleen Moltz MD kmoltz@med.wayne.edu
Hyperthyroidism
95% Graves disease
Hashitoxicosis
Thyroid Adenoma
McCune Albright
Ingestion
Hydatidiform mole
TSH pituitary adenoma
Non-hyperthyroid abnl labs
Oral contraceptive use
Pregnancy
Congenital TBG excess
Dysalbuminemic hyperthyroxinemia
Thyroid hormone resistance
Kathleen Moltz MD kmoltz@med.wayne.edu
Hyperthyroidism - neonatal
Fetal hyperthyroidism: fetal tachycardia (pulse >160/min) + failure to thrive.
Newborn: tachycardia, irritability, poor weight gain, prominent eyes, goiter
Rarely presentation with thrombocytopenia, jaundice, hepatosplenomegaly & hypoprothrombinemia
May be confused with congenital infections such as toxoplasmosis, rubella, or cytomegalovirus
Arrhythmia, cardiac failure if untreated
Increased craniosynostosis, FTT, DD
Scoring criteria for thyroid storm:
≥45 highly suggestive
25–44 suggestive of impending storm
≤ 25 is unlikely to be thyroid storm.
Nayak B, Endocrinology and Metabolism Clinic of North America. 2006
Kathleen Moltz MD kmoltz@med.wayne.edu
Nodule: Cyst or Tumor
Nodules are rare in the 1st two decades
Colloid cyst
Thyroglossal duct cyst
Follicular adenoma
Papillary thyroid carcinoma
A Solitary nodule can be cancerous
High risk groups:
Prior radiation exposure
Hodgkin & Leukemia
Chernobyl
Clinical monitoring controversial: labs / ultrasound
Kathleen Moltz MD kmoltz@med.wayne.edu
Nodules: risks
In favor a Benign Thyroid Nodule:
FH of Hashimoto's thyroiditis
FH of benign thyroid nodule or goiter
Symptoms of hyperthyroidism or hypothyroidism
Pain / tenderness with a nodule
A soft, smooth, mobile nodule
Multi-nodular goiter without a predominant nodule (lots of nodules, not one main nodule)
"Warm" nodule on thyroid scan (produces normal amount of hormone)
Simple cyst on an ultrasound
↑ Suspicion of a Malignant Nodule:
Age < 20 years! (Age > 70)
Rapid growth
Male gender
New swallowing difficulties
New hoarseness
History of external neck irradiation during childhood
Firm, irregular, and fixed nodule
Presence of cervical LN
Previous history of thyroid cancer
Nodule that is "cold" on scan
Solid or complex on an ultrasound
Kathleen Moltz MD kmoltz@med.wayne.edu
Nodule: Cyst or Tumor
Initial evaluation
Free T4, TSH + Thyroid antibodies
Ultrasound
If solid  Radionucleotide scan (worry about cold nodules!)
If mixed solid/cystic, or scan cold  FNA ultrasound-guided
Referral to who?:
If + antibodies  Endo
If – antibodies  FNA (interventional radiology)
If FNA + or ? surgery for partial-total thyroidectomy
At CHM general surgery; some locations ENT
MEN2
Multiple neuromas
mucosal neuromas of the eyelids, lips, and tongue, marfanoid habitus, and hyperflexible joints
do not have the marfanoid lens or aortic abnormalities
may also have abnormal gastrointestinal motility
even at a young age: diarrhea, constipation, colonic dilatation, megacolon, diverticulosis, diverticulitis, abscess and other complications
Kathleen Moltz MD kmoltz@med.wayne.edu
Thyroglossal duct cyst?
www.primehealthchannel.com/wp-content/uploads/2011/03/Thyroglossal-Duct-Cyst.jpg
Hyperthyroidism
Thyroid Storm: Scoring
Practice questions!
Pediatric Endocrinology Core Lecture Series
Kathleen C. Moltz MD FAAP
kmoltz@med.wayne.edu

Kathleen Moltz MD kmoltz@med.wayne.edu
Question
1. In the NICU a 7-day-old boy has abnormal thyroid function from the state NBS. -born at 30 weeks of gestation -respiratory distress syndrome and prematurity. -nasal CPAP machine -full enteral feeds.
Repeat TFTs: low total T4 value 4.7 μg/dL, and the TSH 3.6 mIU/L. Additional test: free T4 1.1 ng/dL; (normal 0.4-2.8 ng/dL)
The mother has no history of hypo- or hyperthyroidism. The newborn’s 2-year-old brother is receiving thyroxine-replacement therapy. The most likely diagnosis of the infant’s condition is:
A. central hypothyroidism
B. familial hypothyroidism
C. low T4 secondary to prematurity
D. sick euthyroid syndrome
E. thyroxine-binding globulin deficiency
Kathleen Moltz MD kmoltz@med.wayne.edu
Question
6-year-old girl with a goiter. + family history of autoimmune thyroid disease -no symptoms of hyper- or hypothyroidism. -Her height and weight have tracked along the 75th percentile. –PE: two times enlarged, smooth thyroid without any nodules palpated.
TFTs: TSH level is 2.20 mIU/L, free T4 is 1.1 ng/dL. Total T3 is 125 ng/dl and TSI is 75% (normal <130%). Antithyroglobulin antibodies +1:128, Antithyroid peroxidase antibodies +1:32. Of the following, the next step in the evaluation should be:
CT scan of the neck
fine-needle aspiration
nuclear imaging study
repeat thyroid function tests in 6 to 12 months
thyroid ultrasound
Hyperthyroidism
T4 & T3
TSH
Euthyroid
TSH
T4 & T3
...except secondary hyperthyroidism with high TSH
5' deiodinase de-activates!
Higher brain function excitory and inhibitory effects
newborns.stanford.edu
adam.com
Call to the hospital/physician listed on the card; speak with a nurse or doctor.
Request Thyroid Stimulating Hormone (TSH) & Free Thyroxine (FT4) be drawn today.
Fax a copy of the screen result and our cover sheet to the listed physician.
Call back the following day
Confirm that the newborn screen result was received
Confirm that the serum TSH & FT4 were drawn.
Request fax of the serum results, along with results of thyroid ultrasound / technetium scan.
If the serum results are normal (TSH ≤ 9 uIU/mL, FT4 0.9 – 2.6 ng/dL), close case.
If the serum results are abnormal (TSH > 9 uIU/mL, FT4 < 0.9 ng/dL), call the physician, and request that a pediatric endocrinologist be consulted for further follow-up; recommend phone consultation.
Continue to follow the infant until a normal serum result is obtained, or the infant is placed on treatment.

Congenital Hypothyroidism: Strong Positive TSH Result ≥ 100
On the first phone call, in addition to requesting thyroid serum that day, recommend that a phone consultation to a pediatric endocrinologist to be done that day without awaiting the results

Congenital hypothyroidism:
Strong Positive ≥ 50-99+

Report the abnormal result and request that a newborn screen be repeated as soon as possible.
Fax a copy of the abnormal screen result to the physician.
Send the parent a letter stating the abnormal result, requesting a repeat sample.
Wait one week and check for repeat test results.

Sometimes both a repeat NBS and serums are done; the serum results are more accurate – and therefore supersede the repeat NBS results.
If the repeat screen result is negative, close the case.
If the repeat screen result is positive (but TSH is <50), request serum tests and follow

Extended follow up (2+ months) including home nurse referral if screen or serum not repeated and reported.

Congenital hypothyroidism:
Borderline Positive ≥ 40-49

Fax a copy of the abnormal screen result to the physician or hospital listed on the newborn screen card.
Send the parent a letter stating the infant had an abnormal screen and that parent needs to have the infant re-tested.
Wait two weeks and check for repeat test results.
Congenital hypothyroidism:
Borderline Positive ≤ 39

If stress related, the screen may be repeated at 1500 grams
If infant has been transfused please wait to collect repeat specimen until >28 hours after last transfusion date
It is recommended families be directed to the birthing hospital for the repeat newborn screen; they have repeat cards and are set up with courier service for prompt delivery of specimens.
The MDCH recommends repeat newborn screen at 2-4 weeks of age for
Preterm infants (<34 weeks gestation)
Same sex twins
Infants with Down Syndrome

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