Thyroid Disease in Children docx

• Thyroid Disease is the Most Common Endocrinopathy Observed in Children • While the Disease Processes Present are Similar to Those in Adults, the Incidences, Presentations, and Clinica

Thyroid Disease in Children

Paul Hruz MD PhD Department of Pediactrics

September 2005

• Thyroid Disease is the Most Common

Endocrinopathy Observed in Children

• While the Disease Processes Present are Similar to Those in Adults, the Incidences, Presentations, and Clinical Consequences Can Differ Markedly

• Failure to Diagnose and Treat Promply May Lead to Irreversible Neurologic Damage

Lecture Outline

• Disorders of Thyroid Development

• Thyroid Disease in the Newborn

• Hypothyroidism in Children

• Hyperthyroidism in Children

• Thryoid Nodules

Thyroid Physiology of the Fetus and Newborn

• Normal Thyroid Development

• Thyroid Status in Premature Infants

• Transplacental Passage of Thyroid Ab

• Newborn Screening

• Congenital Hypothyroidism

Thyroid Development

• Orignates from thyroid diverticulum

and ultimobranchial bodies

• Ontogeny influenced by several

transcription factors (TTF, PAX8,

HOX3)

• Largely complete by 10-12 weeks

• Gradual Maturation in Hypothalamic

-Pituitary-Thyroid Axis

Genetic Factors Impacting Thyroid Development

Fetal Thyroid Maturation

• TSH detectable by 12 wks

• Feedback mechanisms

established by 20 wks

• T3 levels remain low

• Reverse T3 levels high

Placental and Fetal Thyroid Metabolism

• Independent fetal axis

Thyroid Changes at Birth

Cord Blood Thryoid Levels

Thyroid Status in Premature Infants

• Relative immaturity of axis

Principles of Newborn Screening

• Relatively High Prevalence

• Deleterious Consequence of

Delayed Diagnosis

• Difficult Clinical Recognition

• Reliable Method of Screening

(sensitive & specific)

• Safe, Effective Treatment

Available

Thyroid Effects in the Fetus and Neonate

Congenital Hypothryoidism

• Incidence 1:4000

– Slightly higher in female infants

– Higher in Asian babies

– Lower in Black babies

• Primarily Sporadic Occurance

• Overt symptoms may not be present at birth

• Profound effects on brain development

• Reliable testing available (T4 and/or TSH)

• No sequelae if treatment initiated by 4 wks

– 10-15 mcg/kg/d

Etiology of Primary

Congenital Hypothryoidism

• Extensive testing for precise

etiology is generally not

necessary (will not change

immediate care plans)

• May allow assessment of risk

in future pregnancies

• May allow early

determination of transient vs

permanent disease

Transient Congenital

Hypothyroidism

• Defined as abnormal newborn screen with abnormal confirmatory labs

– 75-80% of abnormal screens due to false +

• Incidence estimated to be ~10% of cases

• Most common in premature infants

• Causes:

– Iodine deficiency or excess

– Maternal antithyroid medication

– Maternal TSH receptor blocking antibodies

Maternal TSH receptor

blocking antibodies

• Incidence estimated at 1:180,000

• Often history of treated Graves in mom

– Mothers may have unrecognized hypothryoidism

• Infant will not have goiter

– Difficult to distinguish from thyroid dysgenesis

• May have permanent neurocognitive deficit if present in utero

• Resolves in 2-3 months as antibody clears

Treatment Guidelines

• Confirm all abnormal newborn screens with

laboratory TSH and free T4

– Borderline results may require repeat testing in 2-4

wks

• If repeat labs abnormal, begin thryoxine (25-37.5 mcg/day)

– Goal is to start treatment within first month of life

• Recheck q 2-3 months and adjust dose if

necessary

• If no need to increase dose by 2 ½ -3 yrs, give 4

wk trial off of thyroxine

• Hypopituitarism

– Isolated – Multiple hormone deficiency

• Surgery

• Radiation

• Infiltrative

• Tumor

Common Symptoms and Signs

of Hypothyroidism in Children

Growth Failure in Childhood Hypothyroidism

Hypothyroidism: Treatment

Hashimotos Thyroiditis

• Most common cause of acquired hypothyroidism

• Female:Male (3:1)

• Most children present with asymptomatic goiter

• Clinical Symptoms may be nonspecific

• More frequent in Down and Turner Syndrome

Goiter: Differential Diagnosis

• PTU, methimazole – TSH receptor Activating

Mutation – McCune Albright Syndrome

– Thyroid Tumor

• Acquired

– Inflammation– Colloid

– Iodine Deficiency– Goiterogen

– Infiltrative disease– Toxic goiter

– Thyroglossal duct cyst

– Adenoma– Carcinoma

Endemic Goiter

• Usually euthryoid

• Diffuse gland enlargement

• Rare in US (iodized salt provides adequate iodine source)

• Rule out autoimmune thyroiditis

• Treament Doses in Children (6-12 months)

– Infants 100 mcg/d

– Children 200 mcg/day

– Adolescents 200-300 mcg/d

• Graves Disease (>95% of Cases)

– Relatively rare in children

– Incidence increases with puberty

– Female:Male (3-5:1)

• Neonatal Graves

– Transplacental Antibodies

• Hashitoxicosis

• TSH receptor mutations (gain of function)

– McCune Albright syndrome

• Subacute Thyroiditis

• Exogenous thyroxine Exposure

Neonatal Hyperthyroidism

• Almost always transient

• Usually associated with maternal Graves

– Transplacental passage of TSI

– Blocking and stimulating Abs may coexist

• Incidence ~1:50,000 infants

– 1-2% of moms with Graves disease

• Often presents in first week of life

– Emerges with clearance of maternal thionamide

• Treatment

– PTU or Methimazole

– SSKI (If severe symptoms)

– Propranolol (If significant sympathetic symptoms (HR>160)

• Other classic signs

– Weight Loss, Polyphagia, Tachycardia, Increased Pulse

Pressure, Heat Intolerance, Diarrhea, Tremor

Graves Disease: Diagnosis

• Suppressed TSH

• Elevated T4, Free T4, T3 levels

• Positive Thyroid Stimulating Antibodies:

(May be helpful if exophthalmos absent)

– Thyroid Peroxidase

– Thyroglobulin

– Thyroid Stimulating Immunoglobulin

Treatment of Graves’ Disease

• Radioactive Iodine

– Preferred treatment in older children and adolescents– Theoretical risk of radiation not established

– Possible increased risk of thryoid cancer (<5yrs)

• Thionamides (methimazole, PTU)

– Agranulocytosis, hepatitis, rash

– Poor long term remission rates

– Difficult to titrate dose, frequent monitoring

– Poor compliance in adolescents

• Surgical Thyroidectomy

– Rarely indicated

Colloid (Nontoxic) Goiter

• Diffuse enlargement of thryoid gland evident

usually during pubertal years

• Normal thyroid function tests

• Often family history

• May represent mild autoimmune thryoiditis

– TPO Ab titer may be helpful to distinguish

• May be associated with nodular goiter as adults

• Therapy usually not necessary

– May respond to thryoid suppression (controversial)

Thryoid Nodules

• Low Prevalence in Children (0.2% <16 yrs)

• Higher Incidence of Malignancy (18-22%)

• Evaluation

– Ultrasound can assist in detection but not helpful to distinguish

benign from malignant nodules

– Uptake scan generally not helpful (Hot nodules can be malignant) – Fine needle aspiration (90% accuracy)

– Excisional biopsy

• Majority are due to colloid cysts or follicular adenomas

Thyroid Cancer in MEN

Case #1

• Term 3.25 kg male newborn infant with newborn screen (obtained on DOL #3)

reported on DOL#10 with T4 of 20

mcg/dL and TSH 12.5 Infant doing well

No family history of thryoid disease

Mom healthy 3 healthy sibs

– What would you do next?

Case #1 (Continued)

• Repeat TSH: 8.5 mcIU/ml, free T4: 1.2 ng/dL

– What would you do now?

• Follow-up labs in 2 weeks:

– TSH 8, T4 8.5 mcg/dL

• Started 25 mcg Synthroid q day, repeat labs 4 weeks later with TSH 2.5, T4 10.5

• At 2 ½ years of age, pt is still on 25 mcg

Synthroid with normal TFTs

Case #2

• 3 wk old former 25 wk EGA female infant followed in NICU On ventillator, PDA,

TPN dependent, Wt 700 gm TSH 2.3, free T4 0.6 ng/dL.

– To treat or not to treat?

Case #3

• 13 year old girl with declining growth

velocity for “several years” No pubertal changes Height currently at -3 S.D., Wt

at 25%ile Quiet personality Presented with hip pain No goiter

• Initial labs showed TSH >300, T4 1.6

mcg/dL