Download Lecture 4 - Thyroid Disorders in Children: Objectives Define the

Lecture 4 - Thyroid Disorders in Children:
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Objectives
Define the clinical picture of hyperthyroidism and the typical onset in children.
Recognize autoimmune disorders associated with both Graves Disease and Hashimoto’s Thyroiditis.
Infer the treatment options for Grave’s Disease.
Recognize the symptoms and physical exam seen with congenital hypothyroidism.
Infer 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.
7. Identify the causes and treatments for the most common causes of congenital and acquired hypothyroidism.
8. Differentiate lab findings between primary and central hypothyroidism.
 What Thyroid Hormone Does
 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.
 How the Thyroid Works: (simple version)
 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”
 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”
 ONLY THE “FREE” T3 AND T4 IS ACTIVE
 T4 is also converted peripherally to T3 by thyroxine 5’ deiodinase
 Notes:
 Only 20% of circulating T3 is secreted by the thyroid; the remainder is produced by deiodination of T4 in the
liver, kidney, and other peripheral tissues by type I 5′-deiodinase
 Thyroid Regulation: (Hypothalamic-Pituitary- Thyroid Axis)
 TRH: secreted by hypothalamus
 TSH: glycoprotein secreted by anterior pituitary
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 Β subchain provides specificity
 TSH stimulates the thyroid gland to produce T3/T4
 Notes:
 The thyroid is regulated by TSH, a glycoprotein produced and secreted by the anterior pituitary. This
hormone activates adenylate cyclase in the thyroid gland and is important in all steps of thyroid hormone
biosynthesis, from trapping of iodine to release of thyroid hormones. TSH is composed of 2 noncovalently
bound subunits (chains): α and β
 TSH synthesis and release are stimulated by TSH-releasing hormone (TRH), which is synthesized in the
hypothalamus and secreted into the pituitary.
Case 1
 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.
 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.
 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
 Physical exam
 General: no acute distress, but does appear anxious, well hydrated, alert and oriented
 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?
A. 1
B. 2
C. 3
D. 4
E. 5
 Tanner Stages
 Know breast buds occur in tanner 4 staging
 Tanner 2 for boys enlargement of the scrotum
 Differential Dx of heart palpitations
 Cardiac
 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
 Italics = more life threatening etiologies
 Back to Case 1
 Workup and Evaluation
 Chest x-ray
 EKG
 CBC (complete blood count)
 Thyroid studies
 BMP (basic metabolic panel)
 Noncardiac
 Fever
 Anemia
 Exercise
 Emotional arousal
 Anxiety
 Panic attack
 Hyperventilation syndrome
 Drug-induced (caffeine, herbal medications,
dietary supplements, albuterol, isotretinoin)
 Hypoglycemia
 Toxic exposure
 Pheochromocytoma
 Hyperthyroidism
 Hyperthyroidism
 Symptoms
 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
 Sinus tachycardia, atrial fibrillation (rare in
children), supraventricular tachycardia
 Fine tremor, hyperkinesis, hyperreflexia
 Warm, moist skin
 Palmar erythema, onycholysis
 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****
 Hyperthyroidism results from excessive secretion of thyroid hormone and, during childhood, with few
exceptions, is due to Graves disease
 The clinical manifestations of hyperthyroidism in children and adolescents are similar to those seen in adults. In
addition, the disorder has unique effects on growth and development.
 Delay in puberty causes a secondary ammnorrhea
 loosening of the nails from the nail bed
Graves Disease
 Most common form of hyperthyroidism in children (90% of cases)
 Etiology: Excessive thyroid hormone production, caused by thyrotropin receptor-stimulating antibodies (TRSAb)
 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
 Notes:
 thyrotropin receptor-stimulating antibody (TRSAb). TRSAb binds to the receptor for TSH and stimulates
cyclic adenosine monophosphate, analogous to TSH itself.
 Graves disease is also associated with other HLA-D3-related disorders such as Addison disease, insulindependent 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 ophthalmopathy occurring in Graves disease appears to be caused by antibodies against antigens shared by
the thyroid and eye muscle. TSH receptors have been identified in retro-orbital adipocytes and may represent a
target for antibodies
 Ophthalmopathy is characterized by inflammation of the extraocular muscles and orbital fat and connective
tissue, which results in proptosis (exophthalmos), impairment of eye muscle function, and periorbital edema.
 symptoms tend to be milder than those seen in adults
 Lid lag is evaluated by having the patient follow the examiner's finger as it is moved up and down. The patient
has lid lag if sclera can be seen above the iris as the patient looks downward.
 in forward displacement and entrapment of the eye from behind by the eyelids
 Diagnosis and Treatment
 Diagnosis
 Elevated T3/T4
 Decreased TSH
 + TRS-Ab (Thyrotropin-receptor stimulating antibodies)
 +/- 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
 Notes:
 MMI- Inhibits the synthesis of thyroid hormones by blocking the oxidation of iodine in the thyroid gland,
blocking iodine's ability to combine with tyrosine to form thyroxine (T4) and triiodothyronine (T3)
 PTU - Inhibits the synthesis of thyroid hormones by blocking the oxidation of iodine in the thyroid gland;
blocks synthesis of thyroxine and triiodothyronine
 Clicker Question
 What is most one the earliest symptoms of hyperthyroid disease presenting in children/adolescents?
A. Decline in school performance
B. Thyroid enlargement
C. Exophthalmos
D. Extreme weight loss
E. Hair loss
 Notes:
 Symptoms develop gradually; the usual interval between onset and diagnosis is 6–12 mo and may be longer
in prepubertal children compared with adolescents. The earliest signs in children may be emotional
disturbances accompanied by motor hyperactivity. The children become irritable, excitable, and cry easily
because of emotional lability. They are restless sleepers and tend to kick their covers off. Their schoolwork
suffers as a result of a short attention span and poor sleep
Case 2:
 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.
 Birth history:
 Born 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
 Family history:
 Non contributory
 Social history:
 Lives at home with mother and father. No pets. No smokers.
 Physical exam
 General: quite newborn but arousable.
 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.
Congenital Hypothyroidism
 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)
 Girls > Boys
 Notes:
 1/3 cannot be found radionuclide scans 2/3 are in another location (ligual thyroid) or normal position
(hypoplasia)
 10% or inborn irro of thyroxine synthesis
 5% are result of transplacental maternal thyrotropin receptor blocking antibody (TRBAb)
 Signs and Symptoms
 Asymptomatic at birth
 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
 Notes:
 Asymptomatic at birth secondary to transplacental passage of maternal T4 which provides levels of 33% of
normal
 Prolonged jaundice secondary to delayed maturation of glucoronide conjugation
 Physical Exam
 Enlarged anterior and posterior fontanels
 Only 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)
 Labs/Diagnosis
 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
 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
 Notes:
 One must keep in mind that serum T4 concentrations are higher in the first few weeks of life in normal
infants than in adults because of the surge in TSH secretion that occurs soon after birth
 Clinical course
 Symptoms are progressive
 Clinical picture fully developed by 3-6 months
 Child’s growth stunted
 Shortened extremities
 Dentition delayed
 Myxedema of the eyelids, back of hands and genitals
 Carotemia (yellow discoloration of skin)
 Hair coarse, brittle and scanty
 Newborn Screen
 Programs common in North America and developed countries
 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
 Helpful in detecting affected infants before clinical symptoms and findings occur
 Ideal blood collection done between 2-4 days of life
 Routinely done prior to discharge
 IMPORTANT: Treatment is most effective if started before 2 weeks of age, so early screening is essential
 Notes:
 May result in increase false positives secondary to elevated TSH that is transient at delivery
 Treatment and Prognosis
 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
 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
 Figure 566-1 Congenital hypothyroidism in an infant 6 mo of age. The infant ate poorly in the neonatal period
and was constipated. She had a persistent nasal discharge and a large tongue; she was very lethargic and had
no social smile and no head control. A, Notice the puffy face, dull expression, and hirsute forehead. Tests
revealed a negligible uptake of radioiodine. Osseous development was that of a newborn. B, Four months
after treatment, note the decreased puffiness of the face, the decreased hirsutism of the forehead, and the
alert appearance.
Goiters
 Clicker Question
 Which of the following could be true of a person with a goiter?
A. They may have normal function of the thyroid gland.
B. They may have thyroid hormone deficiency.
C. They may have an overproduction of thyroid hormones.
D. The goiter may be congenital.
E. The goiter may be acquired.
 Goiter is an enlargement of the thyroid gland.
 Notes:
 Initial step in evaulating a child with a goiter is to determing if they are euthyroid, hypothyroid or
hyperthyroid.

TSH, T4, antithyroid antibodies
 Autoimmune thyroiditis
 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 asymptomatic
 Notes
 thyroiditis encompasses a diverse group of disorders characterized by some form of thyroid inflammation
 Clicker Question
 When describing hypothyroidism, which organ’s failure is responsible for “tertiary” hypothyroidism?
A. Thyroid gland
B. Pituitary gland
C. Hypothalamus
D. Parathyroid gland
E. Thymus
 Notes:
 Results when the hypothalamus fails to produce sufficient thyrotropin-releasing hormone (TRH)
 Secondary : Occurs if the pituitary gland does not create enough thyroid-stimulating hormone (TSH
 Acquired Hypothyroidism
 Female predominance
 90% secondary to Autoimmune Thyroiditis (Hashimoto’s Thyroiditis)
 Other causes:
 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
 Presentation:
 Coarse, dry and thick skin
 Fatigue, lethargy
 Cold intolerance
 Pallor
 Somnolence
 Constipation
 Delayed linear growth
 Overweight for height
 Delayed reflexes
 Bradycardia
 Irregular menstrual cycles
 Delayed puberty (occasionally precocious puberty)
 Notes:
 Well behaved, do well in school. Obesity is rarely caused by hypothyroidism.
 Autoimmune Thyroiditis - Hashimoto Thyroiditis
 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:
 Trisomy 21
 Klinefelter’s syndrome
 Diabetes Type I



Addison’s Disease
Turner’s Syndrome
Celiac Disease
 Diagnosis
 Primary hypothyroidism
 Elevated TSH, Decreased T4
 Test for anti-thyroglobulin antibodies (Tg Ab) and anti-thyroid peroxidase antibodies (TPO Ab)
 85 to 90 percent of children with chronic autoimmune thyroiditis have high serum anti-TPO antibody
concentrations
 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
 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
D. Decreased TSH, normal T4
E. Decreased TSH, elevated T4
 Central Hypothyroidism
 Idiopathic
 Hypothalamic lesions
 Pituitary tumors, the most common of which is craniopharyngioma