Eric Sherman Pediatric Endo Fellow Captain, USAF, MC Hypothyroidism Eric Sherman Pediatric Endo Fellow Captain, USAF, MC

Who has ordered thyroid function tests (TFT)? Who has made decisions based on the results? Who has been confused by the results? Who has referred someone to peds endo for abnormal TFTs? Who follows patients with hypothyroidism without endocrine assistance?

Causes of hypothyroidism Congenital – 1 in 4000 live births Acquired Most common cause world wide?? Iodine was added to salt in the United States starting in 1929. The first two states to make this mandatory? Ohio and Michigan

Causes of congenital hypothyroidism (CH) Thyroid dysgenesis 1:4000 Thyroid dyshormonogenesis 1:40,000 Central hypothyroidism 1:100,000 Transient hypothyroidism 1:40,000 Sperling

Signs/symptoms of CH

Signs/symptoms of CH

Newborn Screen Mandatory in all 50 states If performed before 24 hours, must be repeated at least one more time Screening TSH: DC Screening FT4: VA, MD, overseas samples Advantages of screening T4: catches central hypothyroidism and children that have delayed rise in TSH, few false negatives Disadvantages: lots of false positives, may miss compensated hypothyroidism (T4 just high enough to escape detection) Advantages TSH: Ensures adequate iodine intake in a region (if TSH on high side), few false positives Disadvantages: miss central hypothyroidism and those with delayed rise in TSH

Positive newborn screen Confirmatory serum TSH and FT4 ASAP Call pediatric endocrinology Start Synthroid at 10-15 micrograms/kg/day (50 micrograms once daily in term infants) All of this depends on the age of the baby and how high the TSH is on the newborn screen. We suggest getting enough blood to run the sample twice in case it clots, the result seems strange

Example of MD newborn screen T4 10.8 (>7.0) T4 result is less than the 10th percentile for this run. A TSH has been performed on this specimen to complete the thyroid testing. TSH result is 74.9 uIU/mL (<28.5 uIU/mL). Consultation with a pediatric endocrinologist  and further serum thyroid studies are recommended.

How do you give Synthroid? Pill crushed Give with water or formula on a spoon, not in bottle or syringe Avoid soy formula (absorption issues) May double dose if previous day’s dose is missed

Just to show you that being a thyroidologist is not as easy as it seems

Follow up TSH and FT4 ever 1-2 months during year 1 Every 3-6 months from ages 1-3 Every 6-12 months from 3 until patient stops growing Goal: bring FT4 into high normal range as rapidly as possible (TSH may remain elevated in 10% of patients) There is some controversy about this goal

Why treat CH? Average IQ 76 in pre newborn screen era Untreated patients lose an average of 1-2 IQ points per month until age 2 40% of untreated patients require special education in school Data suggests that treatment should be initiated within 2 weeks (PREP says 3 months) Barbara Linder followed 14 patients with borderline TFTs on newborn screen until age 3 (TSH between 20 and 40). 13 remained hypothyroid.

Long term consequences w/ treatment Sensorineural hearing loss Decline in verbal IQ Head circumference 1 SD above the mean Normal height and weight

                           

Goitrogens Cabbage, kale and other cruciferous veggies Soybeans Animal fodder Lithium Amiodarone

Hashimoto’s (chronic lymphocytic) thyroiditis Most common cause of goiter in children over 6 F>M, family history in 30-40% More common in Down’s and Turner’s syndrome

Often has a very insidious presentation Often has a very insidious presentation. Classically they have delayed puberty, although occasionally severe hypothyroidism can present with precocious puberty

Often has a very insidious presentation Often has a very insidious presentation. Classically they have delayed puberty, although occasionally severe hypothyroidism can present with precocious puberty

Other S/S Cold intolerance Fatigue Relative bradycardia Unexpected weight gain (usually this is not the thyroid’s fault) Goiter in 2/3 of cases 5-10% of the time patients will present with thyrotoxicosis (hyperthyroid at type of symptoms)

Associated illnesses 25-30% of Type I diabetics have + antibodies and 10% have elevated TSH Occasionally seen with celiac disease, JRA and IBD Can be part of autoimmune syndromes like APS type 1 APS type I = systemic candida, hypoparathyroidism, adrenal insufficiency

Diagnosis Elevated TSH and low or normal FT4 Anti-TPO and/or anti-TG antibodies in 90-95% of patients TPO more sensitive and specific Ultrasound not a part of routine screening TSH the most sensitive indicator of primary hypothyroidism

Treatment Synthroid 100 micrograms/m2/day Profoundly hypothyroid patients undergoing treatment can present with ??? Follow TSH to ensure adequate treatment Pseudotumor cerebri

Untreated Final adult height decreased Progressive thyroid enlargement Occasional significant pituitary enlargement Increased risk of thyroid cancer (even in treated patients)

On a routine annual evaluation, a 13 year old girl from the Midwest is found to have a diffusely enlarged thyroid gland that is approximately 3 times the normal size according the World Health Organization criteria. She is active, healthy, clinically euthyroid, and has no other abnormalities on physical examination. The family history discloses that two maternal aunts and two cousins each were told that they had a "goiter." Among the following, the most likely cause of this patient's thyroid enlargement is: A. Adolescent goiter B. Autoimmune thyroiditis C. Familial thyroid dyshormonogenesis D. Nutritional deficiency goiter E. Thyroid neoplasia

On a routine annual evaluation, a 13 year old girl from the Midwest is found to have a diffusely enlarged thyroid gland that is approximately 3 times the normal size according the World Health Organization criteria. She is active, healthy, clinically euthyroid, and has no other abnormalities on physical examination. The family history discloses that two maternal aunts and two cousins each were told that they had a "goiter." Among the following, the most likely cause of this patient's thyroid enlargement is: A. Adolescent goiter B. Autoimmune thyroiditis C. Familial thyroid dyshormonogenesis D. Nutritional deficiency goiter E. Thyroid neoplasia

Among the following, the most sensitive laboratory test to diagnose primary hypothyroidism is measurement of serum: A. Free T4 B. Thyroglobulin C. Thyroid antibodies D. Total T3 E. TSH 

Among the following, the most sensitive laboratory test to diagnose primary hypothyroidism is measurement of serum: A. Free T4 B. Thyroglobulin C. Thyroid antibodies D. Total T3 E. TSH 

An 8-year-old girl has a 2 year decline in growth velocity, as determined by plotting her height on a standard growth curve. At age 6 years, her height was at the 60th %; at age 7 years, it was at the 40 %; at age 8 years, it was at the 10th %. Her parents are of average height. Her history is otherwise unremarkable, and physical exam reveals no abnormalities, although her thyroid gland cannot be palpated. The pair of laboratory tests that would best help explain the cause of this patient's recent growth retardation is: A. Free T4 and T3 B. Growth hormone and blood urea nitrogen C. Thyroid ultrasonography and technetium pertechnate scan D. T4 and free T4 E. TSH and free T4

An 8-year-old girl has a 2 year decline in growth velocity, as determined by plotting her height on a standard growth curve. At age 6 years, her height was at the 60th %; at age 7 years, it was at the 40 %; at age 8 years, it was at the 10th %. Her parents are of average height. Her history is otherwise unremarkable, and physical exam reveals no abnormalities, although her thyroid gland cannot be palpated. The pair of laboratory tests that would best help explain the cause of this patient's recent growth retardation is: A. Free T4 and T3 B. Growth hormone and blood urea nitrogen C. Thyroid ultrasonography and technetium pertechnate scan D. T4 and free T4 E. TSH and free T4

You receive notice that a male infant in your practice had an elevated TSH level on newborn screening. The most important laboratory test to obtain immediately is a measure of: A. Free T4 B. Thyroglobulin C. Thyroid antibody D. Total T3 E. Thyroid stimulating hormone

You receive notice that a male infant in your practice had an elevated TSH level on newborn screening. The most important laboratory test to obtain immediately is a measure of: A. Free T4 B. Thyroglobulin C. Thyroid antibody D. Total T3 E. Thyroid stimulating hormone

Although the prognosis for normal intellectual and neurologic function and linear growth can be excellent for children who have congenital hypothyroidism, delaying treatment beyond which of the following ages is likely to be associated with impairments: A. 24 hours B. 2 weeks C. 3 months D. 6 months E. 1 year

Although the prognosis for normal intellectual and neurologic function and linear growth can be excellent for children who have congenital hypothyroidism, delaying treatment beyond which of the following ages is likely to be associated with impairments: A. 24 hours B. 2 weeks C. 3 months D. 6 months E. 1 year

A 15-year old female presents with an asymptomatic goiter A 15-year old female presents with an asymptomatic goiter. She has type I diabetes that was diagnosed at age 7 years. Of the following, the study that is most likely to be used to establish the diagnosis is: A. Measurement of antiperoxidase antibodies B. Needle biopsy of the thyroid C. Technetium thyroid scan D. Thyroid binding globulin level E. Ultrasonography of the thyroid

A 15-year old female presents with an asymptomatic goiter A 15-year old female presents with an asymptomatic goiter. She has type I diabetes that was diagnosed at age 7 years. Of the following, the study that is most likely to be used to establish the diagnosis is: A. Measurement of antiperoxidase antibodies B. Needle biopsy of the thyroid C. Technetium thyroid scan D. Thyroid binding globulin level E. Ultrasonography of the thyroid

A. Hashimotos thyroiditis B. Hyperthyroidism You are evaluating a 15-year-old girl who is concerned about being overweight. Physical examination reveals a weight of 90.9 kg (>95%) and height of 170 cm (90%). Findings on the remainder of the examination, including the thyroid gland, are normal. The total T4 concentration is 3.1 mcg/dL (normal is 5.6-11.7) and the TSH level is 4.5 microIU/mL (normal 0.6-6.3). Repeat studies confirm these results, and a 3,5,3-triiodothyronine (T3) resin uptake is 52% (normal 25-35%). Of the following the most likely diagnosis is: A. Hashimotos thyroiditis B. Hyperthyroidism C. Primary (thyroid) hypothyroidism D. Secondary (central) hypothyroidism E. Thyroid binding globulin deficiency Thyroid binding globulin deficiency (seen in severe illness and androgen excess) leads to decreased total T4 and normal free T4. It is also associated with increased T3 resin uptake. TBG excess (occurs in pregnancy and excess estrogen/OCP administration) gives you elevated total T4, normal free T4 and decreased T3 resin uptake.

A. Hashimotos thyroiditis B. Hyperthyroidism You are evaluating a 15-year-old girl who is concerned about being overweight. Physical examination reveals a weight of 90.9 kg (>95%) and height of 170 cm (90%). Findings on the remainder of the examination, including the thyroid gland, are normal. The total T4 concentration is 3.1 mcg/dL (normal is 5.6-11.7) and the TSH level is 4.5 microIU/mL (normal 0.6-6.3). Repeat studies confirm these results, and a 3,5,3-triiodothyronine (T3) resin uptake is 52% (normal 25-35%). Of the following the most likely diagnosis is: A. Hashimotos thyroiditis B. Hyperthyroidism C. Primary (thyroid) hypothyroidism D. Secondary (central) hypothyroidism E. Thyroid binding globulin deficiency Thyroid binding globulin deficiency (seen in severe illness and androgen excess) leads to decreased total T4 and normal free T4. It is also associated with increased T3 resin uptake. TBG excess (occurs in pregnancy and excess estrogen/OCP administration) gives you elevated total T4, normal free T4 and decreased T3 resin uptake.

?Questions?