THYROID DISEASE/OFFICE EMERGENCIES
| THYROID DISEASE IN CHILDREN AND ADOLESCENTS —Daniel A. Doyle, MD, Assistant Professor of Pediatrics,
Jefferson Medical College at Thomas Jefferson University, Philadelphia, PA
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| Thyroid gland embryology: thyroid earliest endocrine structure; arises from endoderm; outpouching of pharyngeal
floor at 16 days gestation; develops from thickening between branchial arches 1 and 2 (medial thyroid from arches 4 and
5); remnants are foramen cecum and thyroglossal duct
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| Steps of thyroid hormone (TH) synthesis: trapping; oxidation; organification; coupling; storage; release; deiodination
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| Thyroid hormones: thyroxine (T4 ); triiodothyronine (T3 ; active form); reverse T3 (rT3 ; biologically inert form)
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| TH potency and binding: T3 3 to 4 times more potent metabolically than T4 ; T4 converted to T3 by 5'-deiodinase; T3
enters nucleus and binds to its receptor; T3 binding results in activation of response elements and production of encoded
messenger ribonucleic acid (mRNA); TH receptors part of steroid hormone superfamily of receptors
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| TH function: increases O2 consumption; stimulates protein synthesis; influences growth and differentiation; may affect
carbohydrate, lipid, and vitamin metabolism at increased rate
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| Congenital hypothyroidism: clinical manifestations—jaundice (patients present with indirect hyperbilirubinemia, as
opposed to patients with hypopituitarism, who present with direct hyperbilirubinemia); large, protuberant tongue; constipation;
hypothermia; edema; large persistent posterior fontanelle; delayed dentition; feeding difficulties; hypersomnolence;
umbilical hernia; mottled skin; sluggish appearance; initial evaluation—complete history and physical examination (PE);
repeat blood tests for T4 , T3 (total serum values), and thyroid-stimulating hormone (TSH; gold standard); thyroid ultrasonography
(US); differential diagnosis—thyroid aplasia; thyroid dysgenesis; dyshormonogenesis; maternal thyrotropin
receptor–blocking antibodies (extremely rare); treatment—L-thyroxine (levothyroxine [Synthroid]), 10 to 15 µg/kg per
day in neonate; given as crushed half-tablet dissolved in formula, usually between feedings so not lost with emesis; monitor
therapy at 1 mo of age, then every 3 mo until child 3 yr of age; TSH normalizes slowly
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| Case 1: 12-yr-old white girl with short stature and decelerating growth over last 2 yr; recent history of menarche with
spotty bleeding for 3 days, followed by second episode of bleeding that occurred 1 mo later and that also lasted 3 days;
PE—height considerably less than third percentile; weight 25% of normal for age; puffy-appearing face with sallow-
appearing skin and limp-appearing hair; 12-yr molars not present; thyroid slightly enlarged with no nodules; Tanner
stage II for breasts, with scant pubic hair; laboratory findings—TSH 2298 µU/mL; total T3 23 ng/dL; total T4 <0.5
µg/dL; luteinizing hormone (LH) <0.06 mIU/mL; follicle stimulating hormone (FSH) 4.8 mIU/mL; estradiol normal
for pubertal child; bone age 8 yr
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 | Treatment: TH replacement (with levothyroxine); about 3 to 6 mo into treatment, leuprolide (Lupron) added to slow rapid
progression of puberty and bone aging that occurs with TH replacement therapy
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| Clinical pearls: severe elevations of TSH may cause unusual form of precocious puberty; β-subunit of TSH cross-links
with FSH receptor; clinical findings may include paucity of pubic or axillary hair, breast development masked by
myxedema, and menarche with poor growth
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| Autoimmune hypothyroidism: clinical manifestations—goiter; constipation; decreased energy; dry skin; weight
gain; headaches; galactorrhea; growth retardation; cold intolerance; increased somnolence; sallow complexion; changes
in hair texture; precocious puberty; diagnosis—blood tests for T3 , T4 , TSH; thyroid peroxidase antibody (TPOAb) test
(useful in detecting both autoimmune hypothyroidism and autoimmune hyperthyroidism); antithyroglobulin antibody test;
treatment—levothyroxine (3-5 µg/kg per day in older children); monitor therapy at 1 mo and every 3 to 6 mo thereafter
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| Euthyroid goiter: patient has positive thyroid antibodies and normal thyroid function; speaker gets many referrals for
this; in these cases, approach is to review all symptoms of hypothyroidism during patient history; if patient asymptomatic
and growing well, speaker simply monitors annually and advises patient’s parents to contact him if symptoms arise (approach
based on results of National Health and Nutrition Examination Survey [NHANES] study, which found that while
about 5% to 10% of population have positive thyroid antibodies, <1% actually hypothyroid)
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| Autoimmune hyperthyroidism (Graves’ disease): 8 times more common in girls than in boys; usually presents
during adolescence; clinical manifestations—hyperactivity; short attention span; tremor; goiter; diarrhea; diaphoresis;
anxiety; irritability; emotional lability; voracious appetite with weight loss; exophthalmos; tachycardia; headaches; increased
systolic blood pressure (BP); diagnosis—TSH suppressed; T3 and T4 elevated; TPOAb good marker of autoimmune
hyperthyroidism; thyroid-stimulating immunoglobulin (TSI) difficult test to get, and reliability poor; treatment—
speaker’s first-line treatment methimazole (Tapazole); easier to dose than propylthiouracil (PTU), as only need to give
10% of milligram amount required with PTU, and can be given bid, while PTU usually given tid
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| Neonatal thyrotoxicosis: clinical manifestations—small for gestational age; irritability; tachycardia; hyperthermia;
cranial synostosis; weight loss; jaundice; goiter; microcephaly; tachypnea; hypertension; voracious appetite; hepatosplenomegaly;
frequent stooling
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| Case 2 (patient with neonatal thyrotoxicosis): infant 4 wk of age; PE—weight less than third percentile; length
in fifth percentile; BP 84/60 mm Hg; heart rate 140/bpm; goiter with no nodules; tachycardia with no murmur; abdomen
scaphoid; thin-appearing limbs; bilateral ankle clonus; laboratory findings—TSH suppressed; total T4 29 µg/dL; total
T3 519 ng/dL (about twice normal); free T4 9 ng/dL; clinical pearls—state screens for elevations of TSH but not for
suppressed TSH, screens for low levels of T4 but not for elevated T4 ; maternal history can be deceiving (eg, mother on T4
after iodine-131 [131 I] ablation of thyroid, but still has TSI in her system affecting baby’s thyroid); maternal antithyroid
medication may cause euthyroid state in neonate; thus, thyroid function tests (TFTs) should be checked at 1 wk and at 1
mo of age
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| Postulated cause of Graves’ disease: primary defect in T suppressor cells; allows expression of T helper cells; T
helper cells become sensitized to TSH; sensitized T helper cells interact with B cells; B cells differentiate into plasma
cells; plasma cells produce thyroid receptor stimulating antibodies (TRSAbs); TRSAb binds to TSH receptor and activates
it
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| Onset of Graves’ disease: usually begins prenatally and present at birth; may be delayed several weeks after birth; if
mother on antithyroid medication, onset can be delayed 3 to 4 days, while neonate degrades maternally derived drug
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| Neonatal Graves’ disease: prevalence—occurs in 1% to 2% of infants born to mothers with history of Graves’ disease;
mothers whose disease cured by thyroidectomy may still produce TRSAb years later; neonatal form of disease affects boys
and girls equally; laboratory findings—T4 and T3 elevated; TSH suppressed; TPOAb often present; TSI elevated (level
usually >0.2 when disease present); thyroid receptor–blocking antibodies (TRBAb) may be elevated and their presence may
delay onset of clinical manifestations; treatment—if baby severely hyperthyroid, give saturated iodine solution (Lugol), 1
drop q8h; other treatment options include PTU (5-10 mg/kg per day divided q8h); methimazole (0.5-1.0 mg/kg per day, divided
q12h); propranolol may be needed if patient has many clinical symptoms (atenolol preferred for older children)
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| Mechanism of action of thionamides: inhibit TH synthesis (inhibit organification of trapped inorganic iodide; suppress
levels of TRSAb; do not activate previously stored or circulating T3 or T4 ); clinical response may take 2 to 3 wk;
PTU usually preferred drug in pregnancy; side effects—agranulocytosis; leukopenia; avasculitic rash
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| Treatment with 131I: appears to be much safer in children than previously thought; in past, feared that use of 131 I could
affect fertility and cancer development; however, recent study found use produced no fertility issues and no higher incidence
of malignancies than in general population; thus, speaker now first treats teenager with Graves’ disease with
methimazole for 6 mo to 1 yr; if remission not apparent at that time (to point where medication can be discontinued), patient
referred for treatment with 131 I
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| Remission of Graves’ disease: all patients with neonatal Graves’ disease remit (by 3-4 mo of age); remission rate of
childhood Graves’ disease 25% per year; thionamide dose must be tapered once euthyroid state reached; Graves’ disease
from TSH-activating mutations persists past neonatal period
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| OFFICE EMERGENCY: A CASE-BASED APPROACH —Jane Knapp, MD, Professor of Pediatrics, University of Missouri,
Kansas City School of Medicine; Vice Chair of Pediatrics, Children’s Mercy Hospital, Kansas City, MO
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| Office emergency essentials: have in place trained physician, capable staff, and right equipment (including supplies
and medications); essential equipment—O2 and delivery system (because most pediatric emergencies respiratory); face
masks and bags (because bag-mask ventilation is “your single most important” airway skill); intraosseous (IO) needle for
emergency access (because IO access much easier and usually much faster to accomplish than intravenous [IV] access in
emergency situation); isotonic fluid for resuscitation (to restore and support circulation in patient with shock; suction (to
clear airway)
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| Emergency training for pediatricians: position of Committee on Pediatric Emergency Medicine for American
Academy of Pediatrics (AAP) is that all pediatricians should have training in basic life support (BLS) and some training
in pediatric advanced life support (PALS); recommendations controversial (pediatricians complained PALS training expensive,
time-consuming, and not relevant to practice); thus, American Heart Association (AHA) and other organizations
working on easier, more user-friendly training courses (description of video course developed by AHA called “BLS Your
Way”); manual for Advanced Pediatric Life Support (APLS) course developed by AHA, AAP, and American College of
Emergency Physicians (ACEP) has chapter on office emergencies
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| Other sources of information: Duke University Office Preparedness for Pediatric Emergencies Manual available at
http://dukehealth1.org/deps/provider_manual.pdf; Office Preparedness for Emergency Response to Children (PERC)
available for $5 at www.ems-c.org
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| Recognition of office emergency: every person in office should be trained to recognize potential emergency; signs
and symptoms—difficulty breathing; cyanosis or pallor; altered level of consciousness; seizures; history of ingestion or
overdose
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| Office emergency response and preparation plan: all offices should have plan for calling for help; level of office
preparation determined by—distance from emergency department (ED)/hospital; quality of emergency response/prehospital
care in area; size of practice
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| Essential medications for office emergency: epinephrine; dextrose; inhaled bronchodilator; analgesic; activated
charcoal; benzodiazepine (eg, midazolam)
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| Case presentation (baby with seizure): at 4 AM , ambulance called to home of 3-mo-old baby with seizure; temperature
103°F; emergency medical service (EMS) used O2 to “perk the baby up”; felt that baby had febrile seizure and decided
to wait and see primary care physician (PCP) in morning; at 9 AM , baby brought to PCP’s office; PCP called urgent
care clinic for referral; clinic recommended transport to ED; ambulance left physician’s office at 10:45 AM and arrived at
children’s hospital at 11:35 AM .; EMS reported not being able to obtain O2 saturation en route; baby became apneic and
asystolic in ED; resuscitation unsuccessful; looking at this case from EMS standpoint, can see that baby’s death resulted
from failure of system at several levels
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| Transport rules: person arranging transport is person responsible for safety of patient; call ahead and talk to physician
(to give idea of what he or she should be prepared for); have plan for arranging transport (how you are going to do it and
where you are going to send child); this means knowing that ED adequately prepared for dealing with pediatric emergencies
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| Management of shock in children: early recognition, resuscitation, and reversal of septic shock in children improves
outcome; therapy should be initiated from time of diagnosis, not time of transport; fluid therapy tends to be “way too conservative”
(physicians start with 20 mL/kg fluid bolus and think this is adequate; in many cases of septic shock, not unusual
to need ≥60 mL/kg; fear of causing fluid overload in child, cerebral edema, herniation, and death, but this is not
what happens; need to “fill up the tank” and reverse child’s shock before worrying about cerebral edema); bottom line is
that physician can make a difference
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| Guidelines for resuscitation of shock: first, make diagnosis (helpful clues patient’s temperature, tachycardia, decreased
perfusion); rapidly push 20 mL/kg normal saline boluses (“don’t be afraid to use more”); remember to check for
hypoglycemia (correcting hypoglycemia helps to restore circulation)
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| Rollerblading injury: do not forget that pain also emergency; in treating fractures, if you do not have stronger opioid in
place at office, can start with ibuprofen; splinting helpful for cutting down on motion; ice also helps; remember to check
distal circulation; if prescribing oral analgesic, speaker recommends acetaminophen with oxycodone over acetaminophen
with codeine (oxycodone stronger opioid than codeine and does not have metabolism problems that can occur with codeine)
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Educational Objectives
| The goal of this activity is to provide a better understanding of the diagnosis and management of pediatric thyroid disease
and to review office preparation for pediatric emergencies. After hearing and assimilating this program, the clinician will be
better able to:
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| 1. Recognize the clinical manifestations of congenital hypothryroidism, autoimmune hypothyroidism, neonatal thyrotoxicosis,
and autoimmune hyperthyroidism (Graves’ disease).
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| 2. Evaluate and treat the pediatric patient with suspected congenital hypothyroidism, autoimmune hypothyroidism, or
Graves’ disease.
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| 3. Discuss the recent evidence for, and consider the potential role of, radioactive iodine 131 (131 I) in the treatment of
pediatric thyroid disease.
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| 4. List the essential equipment needed to prepare for office pediatric emergencies.
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| 5. Develop an effective recognition and response plan for managing pediatric emergencies.
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Discussed on This Program
Acetaminophen (N -acetyl-P -aminophenol; APAP) [several trade names and preparations]
Acetaminophen with codeine [several trade names]
Atenolol [Tenormin]
Charcoal, activated [Actidose-Aqua, Actidose with Sorbitol, CharcoAid, CharcoAid 2000, Liqui-Char]
Dextrose-electrolyte solutions [several trade names]
Epinephrine [Adrenalin Chloride, Adrenalin Chloride Solution, Epifrin, EpiPen, EpiPen Jr., Glaucon, microNefrin,
Nephron, Primatene Mist, S2]
Ibuprofen [several trade names and preparations]
Iodine compounds [Iodine Topical, Strong Iodine (Lugol’s Solution), Strong Iodine Tincture]
Leuprolide acetate [Eligard, Lupron, Lupron Depot, Lupron Depot—3 month, Lupron Depot—4 month, Lupron Injection,
Lupron Depot-Ped, Lupron for Pediatric Use, Viadur]
Levothyroxine sodium (T4 ; L -thyroxine) [Levothroid, Levoxyl, Synthroid, Thyro-Tabs, Unithroid]
Methimazole [Tapazole]
Midazolam HCl [Versed]
Propranolol HCl [Inderal, Inderal LA, InnoPran XL]
Propylthiouracil (PTU)
Suggested Reading
Beck-Peccoz P et al: Safety of medications and hormones used in the treatment of pediatric thyroid disorders. Pediatr
Endocrinol Rev 2 Suppl 1:124, 2004; Bettendorf M: Thyroid disorders in children from birth to adolescence. Eur J
Nucl Med Mol Imaging 29 Suppl 2:S439, 2002; Buyukgebiz A: Congenital hypothyroidism clinical aspects and late
consequences. Pediatr Endocrinol Rev 1 Suppl 2:185, 2003; Cearnal L: Only six percent of hospitals prepared for pediatric
emergencies? The controversy and facts about the fearsome statistic. Ann Emerg Med 48:403, 2006; Hung W,
Sarlis NJ: Autoimmune and non-autoimmune hyperthyroidism in pediatric patients: a review and personal commentary
on management. Pediatr Endocrinol Rev 2:21, 2004; Jaruratanasirikul S et al: Thyrotoxicosis in children: treatment
and outcome. J Med Assoc Thai 89:967, 2006; Kempers MJ et al: Neonatal screening for congenital hypothyroidism
based on thyroxine, thyrotropin, and thyroxine-binding globulin measurement: potentials and pitfalls. J Clin Endocrinol
Metab 91:3370, 2006; Knapp JF: Practical issues in the care of pediatric trauma patients. Curr Probl Pediatr 28:309,
1998; Knapp JF: Updates in wound management for the pediatrician. Pediatr Clin North Am 46:1201, 1999; Knapp
JF, Schremmer RD: Pediatric advanced life support your way. Arch Pediatr Adolesc Med 160:658, 2006; Koch
CA, Sarlis NJ: The spectrum of thyroid diseases in childhood and its evolution during transition to adulthood: natural
history, diagnosis, differential diagnosis and management. J Endocrinol Invest 24:659, 2001; Losek JD: Office preparedness
for pediatric emergencies. J S C Med Assoc 100:337, 2004; Mengreli C et al: Transient Congenital Hypothyroidism
due to maternal autoimmune thyroid disease. Hormones (Athens) 2:113, 2003; Murdock TC et al: Bridging
the emergency medical services for children information gap. Arch Pediatr Adolesc Med 153:281, 1999; Niedziela M:
Pathogenesis, diagnosis and management of thyroid nodules in children. Endocr Relat Cancer 13:427, 2006; Rivkees
SA: The management of hyperthyroidism in children with emphasis on the use of radioactive iodine. Pediatr Endocrinol
Rev 1 Suppl 2:212, 2003; Seidel JS, Knapp JF: Pediatric emergencies in the office, hospital, and community: organizing
systems of care. Pediatrics 106:337, 2000; Svensson J et al: Levothyroxine treatment reduces thyroid size in children
and adolescents with chronic autoimmune thyroiditis. J Clin Endocrinol Metab 91:1729, 2006; Walsh-Kelly CM
et al: Office preparedness for pediatric emergencies: baseline preparedness and the impact of guideline distribution. Pediatr
Emerg Care 20:289, 2004; Yang RL et al: Treatment and follow-up of children with transient congenital hypothyroidism.
J Zhejiang Univ Sci B 6:1206, 2005; Yordam N, Ozon A: Neonatal thyroid screening: methods-efficiency-
failures. Pediatr Endocrinol Rev 1 Suppl 2:177, 2003.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue, the
faculty reported nothing to disclose.
Dr. Doyle was recorded at Cape Cod Conference on Pediatrics 2006, held August 4-6, 2006, at Hyannis, MA, and
sponsored by the Nemours Children’s Clinic. Dr. Knapp spoke at the 39th Annual Advances and Controversies in
Clinical Pediatrics, held June 1-3, 2006, in San Francisco, CA, and sponsored by the University of California, San
Francisco, School of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation
in the production of this program.
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