[05.15] PED - Pediatric Thyroid Gland Disorders V2.pdf

Anterior lower part of the neck, just below the larynx, beside and in front of the trachea

Where is the thyroid gland anatomically located?

Attached to the larynx

Why does the thyroid gland move with swallowing during physical examination?

Two lobes connected by an isthmus

What basic anatomical structure forms the butterfly-shaped thyroid gland?

Rich blood supply

What physical property of the thyroid gland reflects its high metabolic activity?

Growth, metabolism, and brain development

What three critical physiological roles does the thyroid gland play in children?

Follicular lumen of the thyroid gland

Where in the thyroid tissue does thyroid hormone synthesis take place?

Absorption of dietary iodine from the gastrointestinal tract into plasma as iodide

What initial step begins the production of thyroid hormone in the human body?

Sodium-Iodide Symporter (NIS)

Through which basolateral membrane transporter do follicular epithelial cells actively trap iodide from blood?

High iodine load or certain drugs

What two factors can inhibit basolateral iodide trapping via the NIS symporter?

Rough Endoplasmic Reticulum

In which cellular organelle of follicular cells is thyroglobulin continuously synthesized?

Tyrosine

Which specific amino acid residue on thyroglobulin binds to active iodine?

Thyroid Peroxidase (TPO)

Which enzyme catalyzes the oxidation of iodide ions into active iodine in the follicular lumen?

Organification (or iodination) of tyrosine

What process describes active iodine binding to tyrosine residues on thyroglobulin?

Monoiodotyrosine (MIT or T1) and Diiodotyrosine (DIT or T2)

What two iodinated tyrosine intermediates are formed during organification?

Coupling of MIT (T1) and DIT (T2) catalyzed by TPO

How is Triiodothyronine (T3) synthesized within thyroglobulin?

Coupling of two DIT (T2) units catalyzed by TPO

How is Tetraiodothyronine / Thyroxine (T4) synthesized within thyroglobulin?

Stored as colloid in the follicular lumen

How are synthesized T3 and T4 stored in the thyroid gland prior to secretion?

Endocytosis / Pinocytosis of thyroglobulin colloid followed by lysosomal digestion

How are T3 and T4 released from thyroglobulin when stimulated by TSH?

Thyroxine-Binding Globulin (TBG)

Which plasma protein is the main carrier responsible for transporting T3 and T4 in circulation?

Neurons in the median region of the parabrachial nucleus

Which central nervous system neurons control the Hypothalamic-Pituitary-Thyroid (HPT) axis?

Thyrotropin-Releasing Hormone (TRH)

Which hypothalamic hormone stimulates the anterior pituitary gland to release TSH?

Thyroid-Stimulating Hormone (TSH)

Which anterior pituitary hormone directly drives thyroid hormone synthesis and release?

Negative feedback on both the hypothalamus and pituitary gland

How do elevated circulating levels of T3 and T4 regulate TRH and TSH secretion?

TSH (Thyroid-Stimulating Hormone)

Which specific hormone is measured in newborn screening to detect primary congenital hypothyroidism?

Tertiary Hypothyroidism

What type of hypothyroidism results from hypothalamic TRH deficiency?

Low T3 and T4, Low TSH, and Low TRH

What pattern of circulating hormones characterizes Tertiary Hypothyroidism?

Secondary Hypothyroidism

What type of hypothyroidism results from pituitary failure to secrete TSH despite adequate TRH?

Low T3 and T4, Low TSH, and High TRH

What pattern of circulating hormones characterizes Secondary Hypothyroidism?

Primary Hypothyroidism

What type of hypothyroidism results from intrinsic thyroid gland dysfunction?

Low T3 and T4, High TSH, and High TRH

What pattern of circulating hormones characterizes Primary Hypothyroidism?

Cold intolerance

What clinical symptom develops in hypothyroidism due to failure to increase basal metabolic rate?

Long bone growth

Which aspect of skeletal development is promoted by thyroid hormones acting synergistically with Growth Hormone?

Calorigenesis

What process describes increased basal metabolic rate and body heat production driven by thyroid hormones?

Glycogenolysis, gluconeogenesis, and intestinal glucose absorption

Which three carbohydrate metabolic pathways are stimulated by thyroid hormones to increase available glucose?

Neuronal maturation and fetal brain development

Which major central nervous system function makes thyroid hormone essential during fetal and early infant life?

Increased sensitivity to catecholamines (increased heart rate and force of contraction)

By what mechanism do thyroid hormones affect cardiac function and pulse rate?

Bradycardia

What cardiac physical sign results from thyroid hormone deficiency due to blunted catecholamine sensitivity?

Erythropoiesis / Biosynthesis of hemoglobin

Which hematologic process requires thyroid hormones, leading to anemia when deficient?

1 in 4,000 live births globally

What is the global prevalence of Congenital Hypothyroidism in newborn infants?

Primary Congenital Hypothyroidism

Which category of CH involves intrinsic anatomical or functional defects of the thyroid gland itself?

Central (Secondary/Tertiary) Congenital Hypothyroidism

Which category of CH involves TSH or TRH deficiency associated with pituitary or hypothalamic disorders?

Thyroid Dysgenesis

What is the most common overall cause of primary permanent Congenital Hypothyroidism (85% of cases)?

Aplasia / Athyrosis

Which form of thyroid dysgenesis describes total failure of the thyroid gland to develop during organogenesis?

Hypoplasia

Which form of thyroid dysgenesis describes an abnormally small thyroid gland?

Ectopic Thyroid (e.g., Lingual Thyroid)

Which form of thyroid dysgenesis describes a thyroid gland located outside its normal anatomical anterior neck position?

Base of the tongue at the center

Where is a lingual ectopic thyroid gland typically visualized on physical exam?

Thyroid Dyshormonogenesis

Which cause of primary permanent CH accounts for 10% of cases and involves enzymatic defects in hormone synthesis?

Thyroid Dyshormonogenesis

What is the ONLY form of Congenital Hypothyroidism that presents with a goiter at birth?

Thyroid Dyshormonogenesis

What is the ONLY form of Congenital Hypothyroidism that can be inherited as an autosomal recessive trait?

TSH receptor abnormalities (unresponsiveness), iodide uptake defects, TPO/organification defects, thyroglobulin defects, and deiodinase defects

What are five biochemical steps where defects cause thyroid dyshormonogenesis?

Pendred Syndrome

Which inherited familial organification defect presents with congenital sensorineural deafness and goiter?

5% of cases

What proportion of Congenital Hypothyroidism cases are transient rather than permanent?

Maternal TSH receptor blocking antibodies (TRAb)

Which maternal autoimmune immunoglobulins cross the placenta to cause transient neonatal hypothyroidism?

3 to 6 months

After what duration does transient congenital hypothyroidism caused by maternal TRAb typically undergo spontaneous remission?

Thionamides (Carbimazole, Methimazole, Propylthiouracil), Lithium, and Amiodarone

Which three maternal drug exposures during pregnancy can induce transient congenital hypothyroidism in the neonate?

Wolff-Chaikoff effect

What acute phenomenon causes inhibition of thyroid organification following fetal exposure to excessive iodides?

Perinatal iodine antiseptics (e.g., applied to the umbilical cord)

Which common nursery procedure should be avoided to prevent acute Wolff-Chaikoff hypothyroid induction in newborns?

Midline facial/brain defects (e.g., septo-optic dysplasia, midline cleft lip/palate, midface hypoplasia)

What anatomical clues should raise immediate clinical suspicion for central (secondary/tertiary) hypothyroidism in a neonate?

Hypoglycemia (ACTH deficiency), persistent jaundice (glucuronyl transferase immaturity), and micropenis (GnRH deficiency)

What three systemic clinical features indicate multiple anterior pituitary hormone deficiencies in a neonate with central CH?

At least 2 cm

What minimum stretched penile length defines normal penile size versus micropenis in a newborn male?

Low Free T4 with an inappropriately normal or low TSH

What laboratory pattern on thyroid function tests identifies central (secondary/tertiary) hypothyroidism?

Most look completely normal at birth due to maternal transplacental thyroid hormones

Why do the vast majority of newborns with Congenital Hypothyroidism fail to demonstrate overt physical symptoms at birth?

Feeding problems, failure to thrive, constipation, hoarse cry, laryngeal edema, macroglossia, and goiter

What seven early infant symptoms develop as maternal thyroid hormone protection wanes in CH?

Constipation and abdominal distention

Which gastrointestinal signs in CH result from decreased alimentary tract peristalsis?

Prolonged neonatal jaundice

Which hepatic manifestation in CH results from delayed maturation of glucuronide conjugation?

Bradycardia

Which cardiovascular sign in CH results from loss of thyroid hormone inotropic and chronotropic cardiac effects?

Growth failure, wide anterior fontanelles, and delayed dentition/bone age

Which three skeletal and growth abnormalities in CH result from impaired protein synthesis and decreased IGF-1?

Increased total cholesterol and LDL levels

Which lipid panel abnormalities develop in CH due to decreased lipid degradation?

Puffy appearance, macroglossia, and thickening of laryngeal/pharyngeal mucous membranes

What three clinical physical features result from accumulation of hyaluronic acid-mucinous edema (myxedema) in CH?

Hoarse cry

Which vocal sign in CH results from mucous membrane thickening in the larynx and pharynx?

Dry and coarse skin

Which cutaneous sign in CH results from decreased sweat and sebaceous gland secretions?

Hearing loss

Which sensory loss can occur in CH due to myxedema of the eighth cranial nerve?

Rough dry skin, wide fontanelles, coarse features, flat nasal bridge, macroglossia, abdominal distention, umbilical hernia, constipation, and hypotonia

What physical signs characterize a toddler with untreated chronic Congenital Hypothyroidism?

Intellectual disability (mental retardation), growth retardation, delayed skeletal/dental maturation, and delayed puberty

What four late clinical manifestations persist into adulthood in unscreened, untreated Congenital Hypothyroidism?

29 diseases (including 2 endocrine disorders: CH and CAH)

How many total diseases are screened in the current Philippine Expanded Newborn Screening panel?

Heel prick dried blood spot card

What collection method is used to obtain capillary blood for newborn screening?

Raised TSH level > 15 IU/L (µIU/mL)

What TSH threshold on a newborn screening heel prick sample indicates a positive screen for Congenital Hypothyroidism?

Immediate confirmatory venous blood test (decreased total/free T4 and elevated TSH)

What immediate step must be taken following a positive newborn screen for CH before initiating lifelong label?

Decreased Free T4 and elevated serum TSH

What laboratory pattern on confirmatory serum testing establishes primary Congenital Hypothyroidism?

Radionuclide thyroid scanning (using Technetium Tc-99m or Iodine-131)

Which imaging modality documents the anatomical etiology of CH by identifying aplasia, hypoplasia, or ectopic glands?

Never delay levothyroxine treatment while waiting for a thyroid scan, as delay compromises brain development

What critical rule governs the timing of levothyroxine initiation relative to diagnostic thyroid scanning?

Thyroid Ultrasonography

Which non-invasive imaging modality easily evaluates thyroid anatomy without radiation, though crying due to cold gel can occur?

Lateral radiograph of the knee looking for distal femoral epiphysis ossification

Which radiological test evaluates skeletal bone age in a newborn with suspected florid hypothyroidism?

Perchlorate Discharge Test

Which specialized diagnostic test evaluates thyroid peroxidase defects or Pendred Syndrome (unavailable in the Philippines)?

Oral Levothyroxine (L-thyroxine)

What is the drug of choice for treating Congenital Hypothyroidism?

Normalize serum T4 within 2 weeks and normalize TSH within 1 month

What are the two target biochemical timeline goals when initiating levothyroxine in CH?

Upper half of the normal reference range

In what portion of the normal reference range should Free T4 levels be maintained during CH therapy?

Within the first 2 weeks of age

Initiating levothyroxine replacement within what age window is critical to achieve normal cognitive development?

Treat continuously until 3 years of age, then temporarily withdraw therapy to re-evaluate permanence

How should an infant with an uncertain diagnosis of CH be managed to protect brain development?

Brain development is largely complete by age 3, making temporary medication withdrawal safe

Why is 3 years of age chosen as the landmark to test for permanence of Congenital Hypothyroidism?

Initial high loading dose of 10 to 15 µg/kg/day

What initial daily levothyroxine dosage is recommended by the AAP for newborns with CH?

Monthly during the first 6 months of life

How frequently should thyroid function tests (FT4, TSH) be monitored during the first 6 months of levothyroxine therapy?

2 to 3 times monthly between 6 months and 2 years of age

How frequently should TFTs be monitored between 6 months and 2 years of age in treated CH?

4 to 6 times monthly (every 2-3 months) after 2 years of age

How frequently should TFTs be monitored in children with CH after 2 years of age?

Crush tablet and suspend in a few mL of water, milk formula, or breastmilk

How should levothyroxine tablets be prepared for infant administration?

Never place in a feeding bottle, as powder sticks to bottle walls/nipple and infant may not finish

Why must crushed levothyroxine NEVER be added directly into a baby's full feeding bottle?

Soy, iron, fiber, and calcium

Which four dietary substances or supplements interfere with intestinal levothyroxine absorption?

Administer on an empty stomach 30 minutes to 1 hour before feeding

What timing rule must be followed when administering levothyroxine relative to milk or food intake?

Give double the missed dose the following day

What advice is provided if an infant occasionally misses a daily levothyroxine dose?

Neuron number and synaptic contacts are permanently reduced (irreversible brain damage)

Which organ damage from untreated CH is completely irreversible despite late levothyroxine treatment?