. Common Thyroid Disorders in Children

FUNCTIONS OF THYROXINE  Thyroid hormones are essential for: Linear growth & pubertal development Normal brain development & function Calcium mobilization from bone

Effects of thyroid hormones Fetal brain & skeletal maturation Increase in basal metabolic rate Inotropic & chronotropic effects on heart Stimulates gut motility Increase bone turnover Increase in serum glucose, decrease in serum cholesterol Play role in thermal regulation

Thyroid Function: blood tests TSH Free T4 Free T3

Dysfunction Thyroid Gland 1. Too little thyroxin – hypothyroidism a. short stature (acquired), developmental delay (congenital) 2. Too much thyroxin – hyperthyroidism a. Agitation, irritability, & weight loss

Hypothyroidism Decreased thyroid hormone levels Low T4 Possibly Low T3 too. Raised TSH (unless pituitary problem!)

Introduction Thyroid hormone is essential for the growth and maturation of many target tissues, including the brain and skeleton. As a result, abnormalities of thyroid gland function in infancy and childhood result not only in the metabolic consequences of thyroid dysfunction seen in adult patients, but in unique effects on the growth and /or maturation of these thyroid hormone-dependent tissues as well i.e. brain and bones.

Introduction Newborns with Hypothyroidism, if not diagnosed and treated early, are going to have severe mental retardation besides effects on growth and other systems. In contrast, hypothyroidism that develops after the age of three years (when most thyroid hormone-dependent brain development is complete) is characterized predominantly by a deceleration in linear growth and skeletal maturation but there is no permanent effect on cognitive development.

8-Jun Ethnic Variation Prevalence White Infants 1:4000 Hispanic Infants 1:2000 Saudi Arabia 1:3800 Etiology

ETIOLOGY CONGENITAL  Hypoplasia(agenesis/dysgenesis)  Familial enzyme defects (dyshormonogenesis)  Iodine deficiency (endemic cretinism)  Intake of goitrogens during pregnancy  Pituitary defects  Idiopathic

Newborn Screening Clinical Features of Congenital Hypothyroidism Finding % Lethargy96% Constipation92% Feeding problems83% Respiratory problems76% Dry skin76% Thick tongue67% Hoarse cry67% Umbilical hernia67% Prolonged jaundice12% Goiter8%

8-Jun Newborns With Congenital Hypothyroidism May have few or no clinical manifestations of Thyroid Deficiency

8-Jun Congenital Hypothyroidism The Longer The Condition Goes Undetected, The Lower The IQ

Newborn Screening Success Stories in Pediatric Medicine Immunization programs Newborn Screening program Oral Rehydration Therapy Pencillin

Newborn Screening

suspect Clinical Confirm Rx & FU Biochemical (screening) Lab ( TSH & FT4 ) T scan B age Optional Thyroxin Congenital Hypothyroidism X Growth & D TSH & FT4

ETIOLOGY /2 ACQUIRED Iodine deficiency Auto-immune thyroiditis Thyroidectomy or RAI therapy TSH or TRH deficiency Medications (iodide & Cobalt) Idiopathic

Autoimmune hypothyroidism

Hashimoto’s Disease Most common cause of hypothyroidism Autoimmune lymphocytic thyroiditis Antithyroid antibodies: Thyroglobulin Ab Microsomal Ab TSH-R Ab (block) Females > Males Runs in Families!

Clinical features of Acquired hypothyroidism Weight gain Goitre Short sature Fatigue Constipation Dry skin Cold Intolerance Hoarseness Sinus Bradycardia.

Hypothyroidism with short stature

Diagnosis High TSH, low T4 Thyroid antibodies.

Treatment of Hypothyroidism Replacement thyroid hormone medication: Thyroxin

Newborn Screening High TSH & Low T4 Management Hypothyroidism Thyroxine ug/kg/day ug/kg/day 37.5 – 50 ug/day Higher dose in Severe cases T4< 5ug/dl Tablets ug Crush it, add to 5-10 cc water Or milk Normal T4 In 2 wks (upper ½ of N) Normal TSH In one month (lower ½ of N ) Dose FormGoals

8-Jun Treatment Follow-Up - After 2 weeks (Clinical and Hormonal Evaluation) - After one month - Every 2 months for the first year - Every 4 months for the second year - Every 6 months thereafter

Newborn Screening

8-Jun Congenital Hypothyroidism One year after treatment L-Thyroxin 8-12 microgram /Kg/ Day

8-Jun Congenital Hypothyroidism At 4-Years of Age Normal Milestones Maintenance Therapy: L-Thyroxine75 microgram/day

8-Jun Congenital Hypothyroidism 4 Years After Treatment Normal Milestones For His Age His sister was screened AFTER 24 hr of delivery, with TSH above 80 mU/L, Eltroxin was initiated after diagnosis. She has normal milestones

8-Jun Conclusion “ There are few instances in the practice of medicine where the health and welfare of generations can be positively affected; early treatment of congenital hypothyroidism through newborn screening is one of those instances ”

Hyperthyroidism Increased thyroid hormone levels High T4 +/- High T3 Low (suppressed) TSH

Proptosis Lid lag Thyroid Ophthalmopathy

Grave’s ophthalmopathy

Hyperthyroidism is a relatively rare condition in children Graves disease accounts for more than 95% of childhood cases of hyperthyroidism

Causes of hyperthyroidism Graves Disease Overtreatment with thyroxin Thyroid adenoma (rare) Transient neonatal thyrotoxicosis.

Hyperthyroidism S&S Heat intolerance Hyperactivity, irritability Weight loss (normal to increased appetite) diarrhea Tremor, Palpitations Diaphoresis (sweating) Lid retraction & Lid Lag (thyroid stare) proptosis menstrual irregularity Goitre Tachcardia

Tremor of the hand A Color Atlas of Endocrinology p49

Neonatal hyperthyroidism born to mother with Graves’ disease A Color Atlas of Endocrinology p51

investigations TSH, free T3&T4 Thyroid antibodies (TSH receptors antibodies) Radionucleotide thyroid scan (increase uptake).

Isotope scan is very important

Graves Disease I 123 or TC 99m Normal v/s Graves

Treatment Three modalities for more than last 50 years Radioactive iodine, anti-thyroid drugs & surgery None is optimal None interrupts the autoimmune process Each has a drawbacks No other research options so far

TreatmentAdvantageDisadvantageFor who? I 131 Definitive, Safe Lifelong T4 RxMost patients Antithyroid Drugs May need life long medication Side effects, frequent visits, lower rate of remission, compliance Pre RAI Rx, mild disease small goiter SurgeryDefinitive, rapid Side effects, life long T4 Rx Toxic nodule, allergy to drugs, large goiter, ? CA

Hyperthyroidism Drug Treatment –Beta-blockers –Carbimazole –PTU (propylthiouracil)

Key Points Hyperthyroidism is a relatively rare condition in children Graves disease accounts for more than 95% of childhood cases of hyperthyroidism Neonatal Graves disease is rare even among mothers with known hyperthyroidism Only 1 in 70 infants of thyrotoxic mothers has clinical symptoms Treatment options depending on age of the patient, goiter size, urgency of treatment, RAIU by the thyroid, physician preference & patient choice Radio-active Iodine therapy is safe in children with thyrotoxicosis

Goiter A swollen thyroid gland

Causes of goitre Congenital (maternal antithyroid drugs, maternal hyperthyroidism, dyshormonogenesis) Physiological (puberty) Iodine deficiency Graves disease Hashimoto thyroiditis Tumor.

Newborn Screening Thank You!