THYROID DISORDERS Dr mirzarahimi HYPOTHYROIDISMEPIDEMIOLOGY Neonatal screening reveals

THYROID DISORDERS Dr. mirzarahimi

HYPOTHYROIDISM-EPIDEMIOLOGY �Neonatal screening reveals incidence that varies between 1 -5/1000 live births �The most common cause of preventable mental retardation in children �Both acquired & congenital forms are linked to iodine deficiency �Diagnosis is easy & early treatment is beneficial

ETIOLOGY �CONGENITAL ØHypoplasia & mal-descent ØFamilial enzyme defects ØIodine deficiency (endemic cretinism) ØIntake of goitrogens during pregnancy ØPituitary defects ØIdiopathic

ETIOLOGY /2 �ACQUIRED üIodine deficiency üAuto-immune thyroiditis üThyroidectomy or RAI therapy üTSH or TRH deficiency üMedications (iodide & Cobalt) üIdiopathic

KILPATRIK GRADING OF GOITRE �Grade 0: Not visible neck extended & Not palpable �Grade 1: Not visible, but palpable �Grade 2: Visible only when neck is extended & on swallowing, �Grade 3: Visible in all positions �Grade 4: Large goiter

THYROID GLAND �Derived from pharyngeal endoderm at 4/40 �Migrate from base of the tongue to cover the 2&3 tracheal rings. �Blood supply from ext. carotid & subclavian and blood flow is twice renal blood flow/g tissue. �Starts producing thyroxin at 14/40.

OVERVIEW (2) �Maternal & fetal glands are independent with little transplacental transfer of T 4. �TSH doesn’t cross the placenta. �Fetal brain converts T 4 to T 3 efficiently. �Average intake of iodine is 500 mg/day. 70% of this is trapped by the gland against a concentration gradient up to 600: 1

THYROID HORMONES �Iodine & tyrosine form both T 3 & T 4 under TSH stimulation. However, 10% of T 4 production is autonomous and is present in patients with central hypothyroidism. �When released into circulation T 4 binds to: üGlobulin TBG üPrealbumin TBPA üAlbumin TBA 75% 20% 5%

THYROID HORMONES (2) �Less than 1% of T 4 & T 3 is free in plasma. �T 4 is deiodinated in the tissues to either T 3 (active) or reverse T 3 (inactive). �At birth T 4 level approximates maternal level but increases rapidly during the first week of life. �High TSH in the first 5 days of life can give false positive neonatal screening

TSH q Is a Glico-protein with Molecular Wt of 28000 q Secreted by the anterior pituitary under influence of TRH q It stimulates iodine trapping, oxidation, organification, coupling and proteolysis of T 4 & T 3 q It also has trophic effect on thyroid gland

TSH (2) q T 4 & T 3 are feed-back regulators of TSH q TSH is stimulated by a-adrenergic agonists q TSH secretion is inhibited by: üDopamine üBromocreptine üSomatostatin üCorticosteroids

THYROID HORMONES (3) q Conversion of T 4 to T 3 is decreased by: üAcute & chronic illnesses üb-adrenergic receptor blockers üStarvation & severe PEM üCorticosteroids üPropylthiouracil üHigh iodine intake (Wolff-Chaikoff effect)

THYROXINE (T 4) q Total T 4 level is decreased in: üPremature infants üHypopituitarism üNephrotic syndrome üLiver cirrhosis üPEM üProtein losing entropathy

THYROXINE (2) q Total T 4 is decreased when the following drugs are used: üSteroids üPhenytoin üSalicylates üSulfonamides üTestosterone üMaternal TBII

THYROXINE (3) q Total T 4 is increased with: ü Acute thyroiditis ü Acute hepatitis ü Estrogen therapy ü Clofibrate ü iodides ü Pregnancy ü Maternal TSI

FUNCTIONS OF THYROXINE q Thyroid hormones are essential for: üLinear growth & pubertal development üNormal brain development & function üEnergy production üCalcium mobilization from bone üIncreasing sensitivity of b-adrenergic receptors to catecholeamines

CLINICAL FEATURES Ø Gestational age > 42 weeks Ø Birth weight > 4 kg Ø Open posterior fontanel Ø Nasal stuffiness & discharge Ø Macroglossia Ø Constipation & abdominal distension Ø Feeding problems & vomiting

CLINICAL FEATURES (2) �Non pitting edema of lower limbs & feet �Coarse features �Umbilical hernia �Hoarseness of voice �Anemia �Decreased physical activity �Prolonged (>2/52) neonatal jaundice

CLINICAL FEATURES (3) �Dry, pale & mottled skin �Low hair line & dry, scanty hair �Hypothermia & peripheral cyanosis �Hypercarotenemia �Growth failure �Retarded bone age �Stumpy fingers & broad hands

CLINICAL FEATURES (5) �Skeletal abnormalities: üInfantile proportions üHip & knee flexion üExaggerated lumbar lordosis üDelayed teeth eruption üUnder developed mandible üDelayed closure of anterior fontanel

OCCASIONAL FEATURES �Overt obesity �Myopathy & rheumatic pains �Speech disorder �Impaired night vision �Sleep apnea (central & obstructive) �Anasarca �Achlorhydria & low intrinsic factor

OCCASIONAL FEATURES (2) �Decreased bone turnover �Decreased VIII, IX & platelets adhesion �Decreased GFR & hyponatremia �Hypertension �Increased levels of CK, LDH & AST �Abnormal EEG & high CSF protein �Psychiatric manifestations

ASSOCIATIONS �Autoimmune diseases (Diabetes Mellitus) �Cardiomyopathy & CHD �Galactorrhoea �Muscular dystrophy + pseudohypertrophy (Kocher. Debre-Semelaigne)

GOITROGENS �DRUGS ØAnti-thyroid ØCough medicines ØSulfonamides ØLithium ØPhenylbutazone ØPAS ØOral hypoglycemic agents

GOITROGENS q FOOD üSoybeans üMillet üCassava üCabbage

CLINICAL FEATURES (4) q Neurological manifestations üHypotonia & later spasticity üLethargy üAtaxia üDeafness + Mutism üMental retardation üSlow relaxation of deep tendon jerks

CONGENITAL HYPOTHYRODISM �Primary thyroid defect: usually associated with goiter. �Secondary to hypothalamic or pituitary lesions: not associated with goiter. � 2 distinct types of presentation: ü Neurological with MR-deafness & ataxia ü Myxodematous with dwarfism & dysmorphism

DIAGNOSIS �Early detection by neonatal screening �High index of suspicion in all infants with increased risk �Overt clinical presentation �Confirm diagnosis by appropriate lab and radiological tests

LABROTARY FINDINGS �Low (T 4, RI uptake & T 3 resin uptake) �High TSH in primary hypothyroidism �High serum cholesterol & carotene levels �Anaemia (normo, micro or macrocytic) �High urinary creatinine/hydroxyproline ratio �CXR: cardiomegaly �ECG: low voltage & bradycardia

IMAGING TESTS q X-ray films can show: ü Delayed bone age or epiphyseal dysgenesis ü Anterior peaking of vertebrae ü Coxavara & coxa plana q Thyroid radio-isotope scan q Thyroid ultrasound q CT or MRI

TREATMENT (2) �L-Thyroxin is the drug of choice. Start with small dose to avoid cardiac strain. �Dose is 10 mg/kg/day in infancy. In older children start with 25 mg/day and increase by 25 mg every 2 weeks till required dose. �Monitor clinical progress & hormones level

TREATMENT q Life-long replacement therapy q 5 types of preparations are available: ü L-thyroxin (T 4) ü Triiodothyronine (T 3) ü Synthetic mixture T 4/T 3 in 4: 1 ratio ü Desiccated thyroid (38 mg T 4 & 9 mg T 3/grain) ü Thyroglobulin (36 mg T 4 & 12 mg T 3/grain)

THYROID FUNCTION TESTS 1. Peripheral effects: ü BMR ü Deep Tendon Reflex ü Cardiovascular indices (pulse, BP, LV function tests) ü Serum parameters (high cholesterol, CK, AST, LDH & carcino-embryonic antigen)

THYROID FUNCTION TESTS (2) 2. Thyroid gland economy: Ø Radio iodine uptake Ø Perchlorate discharge test (+ve in Pendred syndrome & autoimmune thyroiditis) Ø TSH level Ø TRH stimulation tests Ø Thyroid scan

THYROID FUNCTION TESTS (3) 3. Tests for thyroid hormone: Ø Total & free T 4 & T 3 Ø Reverse T 3 level Ø T 3 Resin Uptake Ø T 3 RU x total T 4= Thyroid Hormone Binding Index (formerly Free Thyroxin Index)

THYROID FUNCTION TESTS (4) q Special Tests: Ø Thyroglobulin level Ø Thyroid Stimulating Immunoglobulin Ø Thyroid antibodies Ø Thyroid radio-isotope scan Ø Thyroid ultrasound Ø CT & MRI Ø Thyroid biopsy

PROGNOSIS q. Depends on: ØEarly diagnosis ØProper diabetes education ØStrict diabetic control ØCareful monitoring ØCompliance

MYXOEDMATOUS COMA q Impaired sensorium, hypoventilation bradycardia, hypotension & hypothermia q Precipitated by: üInfections üTrauma (including surgery) üExposure to cold üCardio-vascular problems üDrugs

PROGNOSIS q Is good for linear growth & physical features even if treatment is delayed, but for mental and intellectual development early treatment is crucial. q Sometimes early treatment may fail to prevent mental subnormality due to severe intra-uterine deficiency of thyroid hormones