Cretinism & hypothyroidism in children

1. Cretinism & Hypothyroidism in Children Dr.K.V.Giridhar Associate Prof. of Pediatrics GMC. Ananthapuramu , A.P., India. 9 May 2014 1

2. cretinism:   ’ congenital   disease’  due to  absence  or deficiency of normal thyroid secretion, characterized by  physicaldeformity , dwarfism, and mental retardation, and often by  goiter . Hypothyroidism: ‘acquired disease’ due to primary and other various causes of Thyraoid and hypothalamo , pitutory,thyraoid axis abnormaloties .

3. Etioliogy of Cretinism CONGENITAL Hypoplasia & mal-descent of thyraoid Familial enzyme defects Iodine deficiency in pregnacy (endemic cretinism ) Intake of ‘goitrogens’ during pregnancy Pituitary defects Idiopathic

4. Etiology of Hypothyroidism ACQUIRED Iodine deficiency Auto-immune thyroiditis Thyroidectomy or RAI therapy TSH or TRH deficiency Medications (iodide & Cobalt) Idiopathic

5. GOITROGENS DRUGS Anti-thyroid Cough medicines Sulfonamides Lithium Phenylbutazone PAS Oral hypoglycemic agents

6. GOITROGENS FOOD Soybeans Millets Cassava Cabbage

7. THYROID HORMONES Iodine & tyrosine, together form both, T3 & T4 under TSH stimulation, in thyroid gland. When released into circulation T4 binds to: Globulin(TBG)-75 % Prealbumin (TBPA)-20 % Albumin(TBA)- 5%

8. THYROID HORMONES ( c’d ) Less than 1% of T4 & T3 is free in plasma. T4 is deiodinated in the tissues to either T3 (active ) At birth T4 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 for ‘hypothyroidism’.

9. Thyroid stimulating Hormone (TSH) Is a Glyco -protein. Secreted by the anterior pituitary under influence of TRH(TSRH) It has trophic effect on thyroid gland It also stimulates, iodine trapping, oxidation, organification, coupling and proteolysis of T4 & T3 .

10. TSH ( c’d ) T4 & T3 are feed-back regulators of TSH TSH is stimulated by a-adrenergic agonists TSH secretion is inhibited by: Dopamine Bromocreptine Somatostatin Corticosteroids

11. Hypothalamo , pituitary, thyraoid Axis Pituitary gland Thyroid gland Hypothalamus T3 T4 TRH TSH

12. THYROID HORMONES ( c’d ) Acute & chronic illnesses b-adrenergic receptor blockers Starvation & severe PEM Corticosteroids Propylthiouracil High iodine intake (Wolff- Chaikoff effect) Conversion of T4 to T3 is decreased by:

13. THYROXINE ( c’d ) Premature infants Hypo pituitarism Nephrotic syndrome Liver cirrhosis PEM Protein losing enteropathy Total T4 level is decreased in:

14. THYROXINE ( c’d ) Steroids Phenytoin Salicylates Sulfonamides Testosterone Maternal TBIgs . D rugs, which decrease Total T4:

15. THYROXINE ( c’d ) Acute thyroiditis Acute hepatitis Estrogen therapy Clofibrate iodides Pregnancy Maternal TSH Total T4 is increased with:

16. FUNCTIONS OF THYROXINE Thyroid hormones are essential for: Linear growth & pubertal development Normal brain development & function Energy production Calcium mobilization from bone Increasing sensitivity of b-adrenergic receptors to catecholeamines

17. CLINICAL FEATURES Birth weight > 4 kg Open posterior fontanel Nasal stuffiness & discharge Macroglossia Constipation & abdominal distension Feeding problems & vomiting

18. CLINICAL FEATURES ( c’d ) Non pitting edema of limbs Coarse features Umbilical hernia Hoarseness of voice Anemia Decreased physical activity Prolonged (>3 weeks) neonatal jaundice

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

20. CLINICAL FEATURES ( c’d ) Skeletal abnormalities: Infantile proportions Hip & knee flexion Exaggerated lumbar lordosis Delayed teeth eruption Under developed mandible Delayed closure of anterior fontanel

21. OCCASIONAL FEATURES Overt obesity Myopathy & rheumatic pains Speech disorder Impaired night vision Sleep apnea (central & obstructive) Anasarca Achlorhydria & low intrinsic fac tor

22. OCCASIONAL FEATURES ( c’d ) 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

23. CLINICAL FEATURES ( c’d ) Neurological manifestations Hypotonia & later spasticity Lethargy Ataxia Deafness + Mutism Mental retardation Slow relaxation of deep tendon jerks

24. ASSOCIATIONS Autoimmune diseases Diabetes Mellitus Cardiomyopathy & CHD Galactorrhoea Muscular dystrophy + pseudo hypertrophy ( Kocher- Debre - Semelaigne Syndrome)

25. 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

26. LABROTARY TESTS Low ( T4& T3) High TSH High serum cholesterol & carotene levels Anaemia ( normo , micro or macrocytic ) High urinary creatinine / hydroxyproline ratio CXR: cardiomegaly ECG: low voltage & bradycardia

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

28. THYROID FUNCTION TESTS ( c’d ) Specific Tests: Thyroglobulin level Thyroid Stimulating Immunoglobulin Thyroid antibodies Thyroid radio-isotope scan Thyroid ultrasound CT & MRI Thyroid biopsy

29. TREATMENT L-Thyroxin is the drug of choice. Start with small dose. 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

30. TREATMENT( c’d) Life-long replacement therapy 5 types of preparations are available: L-thyroxin (T4) Triiodothyronine (T3) Synthetic mixture T4/T3 in 4:1 ratio Desiccated thyroid (38mg T4 & 9mg T3/grain) Thyroglobulin (36mg T4 & 12mg T3/grain)

31. PROGNOSIS Depends on: Early diagnosis Proper counselling Strict diet control Careful monitoring Compliance

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

33. THANKYOU 9 May 2014 35