Chair of pediatrics with medical genetics

1. Chair of pediatrics with medical genetics THEME OF LECTION: “Diseases of thyroid gland”

2. Actuality Diseases of thyroid gland occupy 2nd place after saccharine diabetes. Thyroid gland (TG) – one of major organs of incretion. Alage of TG takes place on 4th week of gestation. Thyroid tissue appears on 2th month. On 16th week TGis differentiated. There are 2 periods of stormy growth of TG (5-7 and 12-15 years). Hormones of TGare: thyroxin (T4) and triiodo-thyronine (T3). T4 has 65 % iodine. Initial product of biosynthesis of thyroid hormones is AA – tyrosine and iodine.

3. Physiology of hormones of TG Main factor of regulation of function of TG is TTH. Regulation takes place on principle of feedbackbetween hypophysis and TG. Secretion of thyrotropin of adenohypophysis takes place under influence a hypothalamus (thyrotropin-releasing factor).

4. Physiological action of thyroid hormones: • influence on all types of metabolism; • important role in development of fetus, processes of growth and differentiation of tissues (especially brain); • assist normal physical and mental development of child; • strengthen lypolysis and metabolisn of carbonhydratess, decrease maintenance of glycogen in liver; • actively influence on a mineral and water metabolism; • in ordinary doses have an anabolic effect, in high – catastatic.

5. Hypothyroidism Hypothyroidism – endocrine-metabolitic disease in origin of which there is a decline or nonfunction of thyroid gland. Classification: I. By the time of origin: -congenital -acquired ІІ. By form: -primary -secondary -tertiary ІІІ. By degree of severity: -easy -intermedius -severe

6. Hypothyroidism • Primary– it is arisen up as a result of primary defeat of thyroid gland. • Secondary– at the defeat of hypophysis (as a result of hypopituitarism, isolated lack of TTH or secretion of nonactive TTH). More frequent meets at the tumours of hypophysis. • Tertiary– related to the defeat a hypothalamus and synthesis of thyroliberine.

7. Hypothyroidism I. Congenital hypothyroidism. Etiology: -90 % - defeat the precusor of thyroid gland on 4-9 week of gestation (dysgenesisandectopia); -thyrostatic medicinal therapy (mercasolil, iodine, bromide, salts of lithium, tranquilizers); -autoimmune thyroiditis at mother; -influence of different chemical substances,irradiationon fetus; -intrauterine infections. In 10 % of casesCongenital hypothyroidism arises up because of genetical deficit of synthesis of thyroid hormones. ІІ. Acquired. Etiology: -after ectomia of thyroid gland, as a result of autoimmune viral, bacterial or radioimmune thyroiditis.

8. Pathogenesis of congenital hypothyroidism In basis of pathogenesis is violation of metabolism of albumens, fats and carbonhydrates. Through the decline of synthesis of hormones of TG there is diminishing of amount of neurons, violation of differentiation of brain, suppression of function of CNS. Decline of metabolic processes causes delay of growth and forming of skeleton, processes of metabolism are violated (hyperketonemiaand lipidemia). For congenital hypothyroidism very important is early diagnostics of disease (pathological changes of CNS are reverse only to 4th week).

9. Clinical symtoms of congenital hypothyroidism: In new-born: • mass of body at birth more than 4 kg; • postmaturity; • bad increase of weight; • languor, somnolence, oppression, muscular hypotonia; • trophic disorders of skin (pallor, dryness, cold on touch); • late falling off of umbilical cord; • protracted icterus, mucinous edemas; • increase of stomach, constipation; • umbilical hernia; • large language; • low pitched voice; • stridor; • amimia; • bradycardia, deafness of cardiac tones, cardiomegalia

10. Clinical symptoms of congenital hypothyroidism At late diagnostic: -delay of psychomotoric development (cretinism); -considerable delay of growth (bone age); -violation of sexual development; -severe anaemia. Easy forms of innate thyroprivia Can be manifestated in 2-5 years or even during sexual development. Is characterized by the delay of growth and sexual development, decline of intellect, the symptoms of myocardial dystrophy, constipations, xerosis.

11. Diagnostic criterias of congenital hypothyroidism -decreased concentarion of T4 in blood (N=110-225 nmole/l) and Т3 (N=2-4 nmole/l); -increasedconcentration ofTTH (N=1,5-20 MCED/ml); -delay of bone age; -scannography of TG (agenesia, ectopia, enzymedisorders.)

12. Acquired hypothyroidism Is manifestated after 1 year of life. More frequent meets at girls. Clinical symptoms: -slow growth; -delay of sexual development; -intolerancetoovercooling; -bad appetite; -somnolence; -constipation; -at examination: edema of face, rough lines, flattened bridge of the nose, xerosis, dry and fragile hair.

13. Laboratory diagnostics of acquired hypothyroidism -decreasing of concentration of T3 and T4; -increasing of TTH; -expressed delay of bone age; -determining of antithyroid antibodies; -scanography ofTG.

14. Treatment of hypothyroidism L-tyroxine (thyreocomb). Initial dose – 3-5 mcg/kg, with a gradual increase each 3-5 days on 10-15 mcg to 10 mcg/kg. Treatment of congenital hypothroidism continues to 1-3 years. Criteria of adequacy of choice of endocrinotherapy dose: -pulse -AP -weight -activity of child -level of TTH, T3 and T4 -estimation of growth and bone age

15. Euthyroid goiter Euthyrosis (diffuse non-toxic goitre) is euthyroidhyperplasy of TG, which is manifestated as itsenlargement without parafunction. Enlargement of TG is scray reaction which is directed on providing of synthesis of enough quantity of thyroid hormones in the conditions of iodic deficit. Theories of origin: inherited defects of delight and organization of iodine; disbalance of oligoelementss (surplus of Cu and Co); influence of small doses of radionuclides; hasty growth of organism.

16. Classification of euthyrosis I. Endemic goitre – it is arisen up as a result of deficit of endogen iodides and other oligoelementss in soil. ІІ. Sporadic goitre – arises up in endemic districts, is provoked by the protracted use of goitriferous preparations and influence of ecological situation. ІІІ. Juvenilehyperplasy of TG – provoked byincreased requirement in iodine and thyroid hormones during sexual development.

17. Diagnostic criterias of severity of euthyrosis by WHO І. On spreading of goiter (results of palpation). ІІ. On sizes of TG (results of US). ІІІ. On concentration of TTH. ІV. On concentration of thyreoglobulin. V. On mediana of iodineuria. Epidemiological criterias of estimation of severity of euthyrosis on frequency of determining in population Degree ofseverityFrequency of determining No deficit <5 % Easydeficit 5-19,9 % Intermedius severity 20-29,9 % Severe deficit >30 %

18. Clinical symptoms I. Palpatory increase of TG. ІІ. Visual increase of TG. ІІІ. Palpatory and visual increase of TG, but it is inside m. sternocleidomastoideus. IV. It is outside m. sternocleidomastoideus. V. Giant goitre. Sizes of goitre after WHO 0 degree – a goitre is absent, size of each lobe is not biggerthan size of distal phalanx of pollex of hand of examinated patient. I degree –gland is palpated, but it is absent visual increase. ІІ degree - visual increase of TG at normal position of neck.

19. Estimation of degree of severity of euthyrosis by concentration of J in urine Mediana of concentration Наявність дефіциту J of J іn urine, mcg/l 100-200 no deficit 50-99 easy deficit 20-49 intermedius deficit <20 severe deficit Plan of research at presence of goiter • Palpation of TG. • US. • Determining of level of thyroid hormones in blood. • Determining of antibodies to tissue of thyroid gland. • Determining of level of day iodineuria. • By prescriptions - punctional biopsy.

20. Prophylaxis of iodine-deficit • Mass – substances with iodine are artificially plugged in feed (salt, bread, dairy products). • Group - preparations which contain physiological dose of iodine are used the origin in the groups of iodine deficit risk (to put, teenagers, pregnant). • Individual - use of products with increased maintenance of iodine (seafood, oarweed) and use of medications (antistrumin, potassium iodide 200).

21. Requirement in J in different age (WHO) Adults – 150 mcg/day Pregant – 200 mcg/day Mature newborns – 15 mcg/kg/day Prematurenewborns – 30 mcg/kg/day First year children – 50 mcg/day Children of 1-6 years – 90 mcg/day Children of 7-12 years – 120 mcg/day

22. Treatment of euthyrosis Always begins with prescribing of iodinated preparations: KJ - 100 mcg/day. If on background of treatment with preparations of iodine there is not normalization of sizes of TG during 6 month –L-тироксин (initial dose – 3 mcg/day, in future chosing of dose takes place under control of determination of TTH in blood of patient) is prescribed.

23. Hyperthyroidism • Diffuse toxic goitre (thyrotoxicosis, Basedow’s disease, Graves disease) – endocrine-exchange disease in basis of which there are hyperproduction of hormones of TG. On the modern stage a toxic goitre is determined as autoimmune disease at which LATS-factoris increased (longitude actionstimulator of synthesis of thyroid hormones). Etiology: • infections; • stresses; • psychical and physical traumas; • overheat in the sunshine

24. Clinical manifestations of hyperthyroidism • enlargement of TG; • violation of activity of CNS (crossness, fussiness, enhanceable motive activity, rapid fatigueability, emotional lability, sleep disturbance, headache, tremor of extremities); • violation of activity of CVS (tachycardia, arhythmia, systolicmurmur, increased voltage of indents on ECG); • cachexia; • eye symptoms (exophthalmus; Graves oculopathy -lymphoid infiltration of conjunctiva, its hyperemia and edema; Dalrimil’s symptom- wide opening eye crack; Ellinec’s- strengthening of pigmentation of eyelids; Zinger’s- an edema of eyelids; Rosenbach's symptom –tremor of eyelids; Kraus’ symptom- increased brilliance of eyes; Stellwag’s is the infrequent blinking and retraction of overhead eyelid; Möbius's symptom- violation of convergence; Graefe's sign- lag of overhead eyelid at a look downward.

25. Laboratory changes at hyperthyroidism -increasing of concentration Т3, Т4; -decreasing of concentration of ТТH; -bone age prevails factical on 2-5 years; -decreasing of cholesterol in blood serum; -CBA: leucopenia, lymphocytosis, increasing of ESR.

26. Features of DTG at children -girls are more frequently ill (95 %); -family anamnesis; -manifestation of disease in pubertal period; -course on background of chronic disease of nasopharynx; -in anamnesis – psychical trauma.

27. Treatment of hyperthyroidism • Mercasolil - 30-40 mg/day during 10-15 days, with the gradual (5 mg/week) decreasing to the minimalmaintaining dose (5 mg/day). • Propiltiouracil - initial dose – 150-300 мг/м2, with a gradual decline to maintaining– 100 мг/м2 • Duration of treatment in maintaining doses is from 2 to 6 years.

28. Thyroiditis Chronic lymphocytic, autoimmunethyroiditis (Hashimoto’s disease). Organospecificautoimmune disease, which is accompanied by formation of autoantibodies to tissue of TG. More frequent meets at children and juvenile age. Girls are ill twice more frequent boys. Is characterised bylymphocytic infiltration of TG, there can be only hyperplasia of TG on the early stages. Disease isinherited with the system HLA.

29. Clinical manifestations of Hashimoto’s disease • disease begins during 3 first years of life, after 6 frequency is increased (max – in teens); • goitre develops gradually and without symptoms (diffuse enlargement ofTG, a surface is uneven by touch, in course of time becomes solid with nodes); • children are irritable, easily excitative, hiperhydrosis, hyperactive (it is possible to suspect hyperthyroidism, but not confirmed laboratory); • clinical course is various (spontaneous diminishing and disappearance or remain without changes during many years); • stages of disease: hyperthyroidism (transitory stage) – euthyrosis –hypothyroidism.

30. Diagnostics of Hashimoto’s disease • high titer of autoantibodies in blood serum (more frequent AB to thyroglobuline 1:100 and AG of microsomes >1:32); • level of T4 and TTH in blood is normal, or increasedconcentration of TTH at normal level of T4 (“compensated” hypothyroidism), or decline of level of T4 at increasedconcentration of TTH (hypothyroidism); • unclear and rough contours of TG at US; • scanning of TG is prescribed at suspicion on forming of nodes; • biopsy – lymphoid infiltration is expressed (for children is conducted very rarely).

31. Treatment of Hashimoto’s disease Medicinal treatment depends on stage of disease Prescriptions to surgical treatment of thyroiditis: -symptoms of compressing and stenosis of trachea and esophagus; -progressive growth of goiter (in spite of medicinal therapy); -suspicion on malignant neoplasm.

32. Subacute thyroiditis Disease of TG of inflammatory character (for certain viral etiology), meets rarely. Clinical signs: • sore throat and pain in the area of TG (it can arise up also in the area of ear and jaw, can become acute at motions of neck); • fever, weakness; • at examination – algetic and swollen TG.

33. Subacute thyroiditis Diagnostics: • on early stages – concentration of T4 in blood is moderatelyincreased, level of TTH is decreased; • decreased absorption byTG of radionuclides; • poorly expressed and not needing correction symptoms of hypothyroidism; • presence of symptoms of general intoxication leucocytosis and increase of ESR; • on the late stages (2-6 months) -symptoms of hypothyroidism. Treatment: • Symptomatic (anaesthetic preparations – at easy cases, steroid hormones – at severe cases)

34. Acute thyroiditis Develops at acute (purulent and non-purulent) infections of TG (more frequent staphylococcus aureus,β-hemolytic streptococcus, pneumococcus). Clinical symptoms: • acute toxic fever; • expressed pain in the area of TG, which increases at tension of neck; • expressed pain of TG at palpation; • hyperemia and local increase of temperature in the area of TG;

35. Diagnostics: -clinical picture; -leukocytosis with prevailing of young forms; -increasing of ESR; -normal level of Т4 та ТТH; -normalabsorption of radioactiveJ; -US ofTG (determining of abscess); -punctionof TGwith aspiration of content (by prescriptions). Treatment. Is begun immediately. Parenteral injection of big doses of broad spectrum antibiotics. Surgical drainage of abscess of TG. Acute thyroiditis

36. Thank you for your attention!