Chair of pediatrics with medical geneticsChair of pediatrics with medical genetics

THEME OF LECTIONTHEME OF LECTION::

““Diseases of thyroid glandDiseases of thyroid gland””

Actuality

DDiseases of thyroidiseases of thyroid gland gland occupy 2 occupy 2ndnd place after place after saccharine diabetes.saccharine diabetes.

ThyroidThyroid gland gland ( (TGTG) – one of major organs of ) – one of major organs of incretion. incretion. AlageAlage of of TGTG takes place on 4 takes place on 4thth week of week of gestationgestation. Thyroid . Thyroid tissuetissue appears on 2 appears on 2thth month. On month. On 1616thth week week TGTG is is differentiated. There are 2 perioddifferentiated. There are 2 periodss of stormy growth of of stormy growth of TGTG (5-7 and 12-15 years). (5-7 and 12-15 years). HHormones ormones of TGof TG areare: : thyroxinthyroxin (T4) and triiodo- (T4) and triiodo-thyronine (T3). T4 thyronine (T3). T4 hashas 65 % iodine. 65 % iodine. IInitial product nitial product of biosynthesis of thyroid hormones is of biosynthesis of thyroid hormones is AAAA – – tyrosinetyrosine and iodine. and iodine.

Physiology of hormones of TG

MMain factor of ain factor of regulationregulation of function of of function of TGTG is TTis TTHH. . RegulationRegulation takes place on principle takes place on principle of feedbackof feedback between hypophysis andbetween hypophysis and TG TG. . SecretionSecretion of thyrotropin of thyrotropin of of adenohypophysis adenohypophysis takes placetakes place under under influence a hypothalamus (thyrotropin-influence a hypothalamus (thyrotropin-releasingreleasing factor). factor).

PhysiologPhysiologicalical action of thyroid hormones: action of thyroid hormones:influence on all types of influence on all types of metabolismmetabolism;;important role in development of important role in development of fetusfetus, processes of , processes of growth and differentiation of growth and differentiation of tissuestissues (especially (especially brainbrain););assist normal physical and mental development of assist normal physical and mental development of child;child;strengthen strengthen lypolysislypolysis and and metabolisnmetabolisn of of carbonhydratess, carbonhydratess, decreasedecrease maintenance of maintenance of glycogenglycogen in in liver;liver;actively influence on a mineral and water actively influence on a mineral and water metabolismmetabolism;;in ordinary doses have an anabolic effect, in high – in ordinary doses have an anabolic effect, in high – catastatic.catastatic.

HypothyroidismHypothyroidismHypothyroidism – endocrine- – endocrine-metaboliticmetabolitic disease in disease in originorigin of which there is a decline or nonfunction of of which there is a decline or nonfunction of thyroidthyroid gland gland..Classification:Classification:I. I. By the time of By the time of origin:origin:--congenitalcongenital--acquiredacquiredІІ. ІІ. ByBy form: form:-primary-primary-second-secondaryary-tertiary-tertiaryІІІ. ІІІ. ByBy degree of degree of severityseverity::-easy-easy--intermediusintermedius--severesevere

Hypothyroidism

PrimaryPrimary – it is arisen up as a result of primary – it is arisen up as a result of primary defeat of thyroid gland.defeat of thyroid gland.SecondarySecondary – at the defeat of hypophysis (as a – at the defeat of hypophysis (as a result of result of hypopituitarismhypopituitarism, isolated lack of TTH or , isolated lack of TTH or secretion of nonactive TTH). More frequent meets secretion of nonactive TTH). More frequent meets at the tumours of hypophysis.at the tumours of hypophysis.TertiaryTertiary – related to the defeat a hypothalamus – related to the defeat a hypothalamus and synthesis of thyroliberine.and synthesis of thyroliberine.

HypothyroidismI. I. Congenital hypothyroidismCongenital hypothyroidism..Etiology:Etiology:-90 % - defeat the -90 % - defeat the precusorprecusor of thyroid of thyroid gland gland on 4-9 week of on 4-9 week of gestationgestation ( (dysgenesisdysgenesis andand ectopiaectopia););--thyrostaticthyrostatic medicinal therapy ( medicinal therapy (mercasolilmercasolil, iodine, bromide, salts , iodine, bromide, salts of lithium, tranquilizers);of lithium, tranquilizers);--autoimmune thyroiditis at autoimmune thyroiditis at mother;mother;-influence of different chemical -influence of different chemical substances,substances, irirradiationradiation on on fetusfetus;;--intrauterineintrauterine infections. infections.In 10 % In 10 % of casesof cases Congenital hypothyroidismCongenital hypothyroidism arises up arises up because ofbecause of genegeneticaltical deficit of synthesis of thyroid hormones. deficit of synthesis of thyroid hormones.ІІ. ІІ. AcquiredAcquired..Etiology:Etiology:-after -after ectomiaectomia of thyroid of thyroid gland, gland, as a result of as a result of autoimmuneautoimmune viral, viral, bacterial or radioimmune bacterial or radioimmune thyroiditisthyroiditis..

Pathogenesis of congenital hypothyroidism

In basis ofIn basis of p pathogenathogenesis isesis is violation of violation of metabolism of albumens, fats and carbonhydrates. metabolism of albumens, fats and carbonhydrates. Through the decline of synthesis of hormones of Through the decline of synthesis of hormones of TGTG there is diminishing of amount of neurons, violation there is diminishing of amount of neurons, violation of differentiation of brain, suppression of function of differentiation of brain, suppression of function of of CNSCNS. . DDecline of metabolic processes ecline of metabolic processes causescauses delay of growth and forming delay of growth and forming ofof skeleton, processes skeleton, processes of metabolism are violated (hyperketonemiaof metabolism are violated (hyperketonemia and and lipidemia). lipidemia).

For For congenital hypothyroidismcongenital hypothyroidism very important very important is early diagnostics of disease (pathological changes is early diagnostics of disease (pathological changes of of CNSCNS are reverse only to 4 are reverse only to 4thth week). week).

Clinical symtoms of congenital hypothyroidism:In new-born:In new-born: mass of body at birth more than 4 kg;mass of body at birth more than 4 kg; postmaturity;postmaturity; bad increase of bad increase of weightweight;; languor, somnolence, oppression, muscular languor, somnolence, oppression, muscular hypotoniahypotonia;; trophic disorders of skin (pallor, dryness, cold trophic disorders of skin (pallor, dryness, cold onon touch); touch); late falling off of umbilical cord;late falling off of umbilical cord; protracted icterus, protracted icterus, mucinousmucinous edema edemass;; increase of stomach, increase of stomach, constipationconstipation;; umbilical hernia;umbilical hernia; large language;large language; low pitched low pitched voice;voice; stridorstridor;; amimiaamimia;; bradycardiabradycardia, deafness of cardiac tones, , deafness of cardiac tones, cardiomegaliacardiomegalia

Clinical symptoms of congenital hypothyroidism

At lateAt late diagnostic: diagnostic:-delay of -delay of psychomotoricpsychomotoric development development (cretinism);(cretinism);-considerable delay of growth (bone age);-considerable delay of growth (bone age);-violation of sexual development;-violation of sexual development;--severesevere anaemia. anaemia.

Easy forms of innate thyropriviaEasy forms of innate thyropriviaCan Can be manifestatedbe manifestated in 2-5 in 2-5 yearsyears or even or even

during sexual development. during sexual development. Is cIs characterizedharacterized by by the delay of growth and sexual development, the delay of growth and sexual development, decline of intellect, the symptoms of myocardial decline of intellect, the symptoms of myocardial dystrophy, dystrophy, constipationsconstipations, , xerosisxerosis..

Diagnostic criterias of congenital hypothyroidism

-decreased concentarion of T4 in blood (N=110-225 nmole/l) and Т3 (N=2-4 nmole/l);

-increased concentration of TTH (N=1,5-20 MCED/ml);

-delay of bone age;

-scannography of TG (agenesia, ectopia, enzyme disorders.)

Acquired hypothyroidism

Is manifestated after 1 year of life. More frequent meets at girls.

Clinical symptoms:

-slow growth;

-delay of sexual development;

-intolerance to overcooling;

-bad appetite;

-somnolence;

-constipation;

-at examination: edema of face, rough lines, flattened bridge of the nose, xerosis, dry and fragile hair.

Laboratory diagnostics of acquired hypothyroidism

--decreasing of concentration of T3 and T4decreasing of concentration of T3 and T4;;

--increasing of TTHincreasing of TTH;;

--expressed delay of bone ageexpressed delay of bone age;;

--determining of antithyroid antibodiesdetermining of antithyroid antibodies;;

--scanography ofscanography of TGTG..

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

Euthyroid goiterEutEuthyrosishyrosis (diffuse (diffuse non-non-toxic goitre) is toxic goitre) is euthyroideuthyroid hyperplasyhyperplasy of of TGTG, which , which is manifestated as itsis manifestated as its enlargementenlargement without parafunction. without parafunction. EnlargementEnlargement of of TGTG is scray reaction which is directed on providing of is scray reaction which is directed on providing of synthesis of enough synthesis of enough quantityquantity of thyroid hormones in of thyroid hormones in the conditions of iodic deficit. the conditions of iodic deficit.

Theories of origin:Theories of origin:

inherited defects of delight and organization of inherited defects of delight and organization of iodine;iodine;

disbalance of oligoelementss (surplus of Cu and Co);disbalance of oligoelementss (surplus of Cu and Co);

influence of small doses of influence of small doses of radionuclidesradionuclides;;

hasty growth of organism.hasty growth of organism.

Classification of euthyrosis

I. Endemic goitre – it is arisen up as a result of I. Endemic goitre – it is arisen up as a result of deficit of endogen iodides and other deficit of endogen iodides and other oligoelementss in soil.oligoelementss in soil.ІІ. Sporadic goitre – arises up in eІІ. Sporadic goitre – arises up in enndemic demic districts,districts, is is provoked provoked by by the protracted use of the protracted use of goitriferous preparations and influence of goitriferous preparations and influence of ecological situation.ecological situation.ІІІ. ІІІ. JuvenileJuvenile hyperplasyhyperplasy of of TGTG – provoked – provoked by by increasedincreased requirement in iodine and thyroid requirement in iodine and thyroid hormones during sexual development.hormones during sexual development.

Diagnostic criterias of severity of euthyrosis by WHO

І. І. On spreading of goiterOn spreading of goiter ( (results of palpationresults of palpation).).

ІІ. ІІ. On sizes of TGOn sizes of TG ( (results of USresults of US).).

ІІІ. ІІІ. On concentration of TTHOn concentration of TTH..

ІІVV. . On concentration of thyreoglobulinOn concentration of thyreoglobulin..

VV. . On mediana of iodineuriaOn mediana of iodineuria..

Epidemiological criterias of estimation of severity of Epidemiological criterias of estimation of severity of euthyrosis on frequency of determining in populationeuthyrosis on frequency of determining in population

Degree ofDegree of severityseverity Frequency of determiningFrequency of determining

No deficit No deficit <<5 %5 %

EasyEasy deficit deficit 5-19,9 % 5-19,9 %

Intermedius severityIntermedius severity 20-29,9 % 20-29,9 %

Severe deficit Severe deficit >>30 %30 %

Clinical symptomsI. PalpatorI. Palpatoryy increase of increase of TGTG..ІІ. Visual increase of ІІ. Visual increase of TGTG..ІІІ. PalpatorІІІ. Palpatoryy and visual increase of and visual increase of TGTG, but it is in, but it is insside m. ide m. sternocleidomastoideus.sternocleidomastoideus.IV. It is outside m. sternocleidomastoideus.IV. It is outside m. sternocleidomastoideus.V. Giant goitre.V. Giant goitre.Sizes of goitre after Sizes of goitre after WHOWHO0 degree – a goitre is 0 degree – a goitre is absentabsent, size of , size of each lobe each lobe is not is not biggerbigger thanthan size of distal phalanx of pollex of hand size of distal phalanx of pollex of hand of examinated of examinated patientpatient..II degree –gland degree –gland is palpatedis palpated, but it is absent visual increase., but it is absent visual increase.ІІ degree ІІ degree -- visual increase of visual increase of TGTG at normal position of neck. at normal position of neck.

Estimation of degree of severity of euthyrosis by concentration of J in urine

Mediana of concentrationMediana of concentration Наявність дефіциту Наявність дефіциту JJ

of J of J ііn urinen urine, , mcg/lmcg/l

100-200 100-200 no deficitno deficit

50-99 50-99 easy deficiteasy deficit

20-49 20-49 intermedius deficitintermedius deficit

<<20 20 severe deficitsevere deficit

Plan of research at presence of goiterPlan of research at presence of goiter Palpation of TGPalpation of TG.. USUS.. Determining of level of thyroid hormones in bloodDetermining of level of thyroid hormones in blood.. Determining of antibodies to tissue of thyroid glandDetermining of antibodies to tissue of thyroid gland.. Determining of level of day iodineuriaDetermining of level of day iodineuria.. By prescriptionsBy prescriptions - - punctional biopsypunctional biopsy. .

Prophylaxis of iodine-deficit

1.1. Mass – Mass – substances withsubstances with iodine iodine are are artificially artificially plugpluggedged in feed (salt, bread, dairy products). in feed (salt, bread, dairy products).

2.2. Group Group -- preparations which contain preparations which contain physiologphysiologicalical dose of iodine dose of iodine are usedare used the origin the origin in the groups of in the groups of iodine deficitiodine deficit risk (to put, risk (to put, teenagers, pregnant).teenagers, pregnant).

3.3. Individual Individual -- use of products with use of products with increasedincreased maintenance of iodine (maintenance of iodine (seafoodseafood, oarweed) and , oarweed) and use of medications (use of medications (antistruminantistrumin, potassium , potassium iodide 200).iodide 200).

Requirement in J in different age (WHO)

Adults – 150 mcg/day

Pregant – 200 mcg/day

Mature newborns – 15 mcg/kg/day

Premature newborns – 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

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.

Hyperthyroidism

Diffuse toxic goitre (thyrotoxicosis, Diffuse toxic goitre (thyrotoxicosis, Basedow’s Basedow’s diseasedisease, Gr, Graves diseaseaves disease) – endocrine-exchange disease in ) – endocrine-exchange disease in basis of which there are hyperproductbasis of which there are hyperproductionion of hormones of of hormones of TGTG. On the modern stage a toxic goitre is . On the modern stage a toxic goitre is determined determined as as autoimmuneautoimmune disease disease at at which LATS- which LATS-factorfactor is increasedis increased ((longitude actionlongitude action stimulatorstimulator of synthesis of thyroid of synthesis of thyroid hormones). hormones).

Etiology: Etiology: infections;infections;stresses;stresses;psychical and physical traumas;psychical and physical traumas;overheat in the sunshineoverheat in the sunshine

Clinical manifestations of hyperthyroidismenlargement 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, systolic murmur, 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.

Laboratory changes at hyperthyroidism

--increasing of concentrationincreasing of concentration Т3, Т4; Т3, Т4;

--decreasing of concentration ofdecreasing of concentration of ТТ ТТHH;;

--bone age prevails factical onbone age prevails factical on 2-5 2-5 yearsyears;;

--decreasing of cholesterol in blood serumdecreasing of cholesterol in blood serum;;

--CBACBA: : leucopenialeucopenia, , lymphocytosislymphocytosis, , increasing of ESRincreasing of ESR..

Features of DTG at children

--girls are more frequently illgirls are more frequently ill (95 %); (95 %);

--family anamnesisfamily anamnesis;;

--manifestation of disease in pubertal periodmanifestation of disease in pubertal period;;

--course on background of chronic disease of course on background of chronic disease of nasopharynxnasopharynx;;

--in anamnesis in anamnesis – – psychical traumapsychical trauma..

Treatment of hyperthyroidism

MercaMercasosolil - 30-40 lil - 30-40 mgmg//dayday during 10-15 days, during 10-15 days, with the gradual (5 with the gradual (5 mgmg//weekweek) ) decreasingdecreasing to the to the minimminimalal maintainingmaintaining dose (5 dose (5 mgmg//dayday).).PropiltiouraPropiltiouraccil il -- initial dose – 150-300 мг/м initial dose – 150-300 мг/м22, , with a gradual decline to with a gradual decline to maintainingmaintaining– 100 мг/м– 100 мг/м22

Duration of treatment in maintaining doses is Duration of treatment in maintaining doses is from 2 to 6 years.from 2 to 6 years.

Thyroiditis

Chronic Chronic lymphocyticlymphocytic, , autoimmuneautoimmune thyroiditisthyroiditis ((Hashimoto’s diseaseHashimoto’s disease). ). OrganospecificOrganospecific autoimmuneautoimmune disease, disease, which is which is accompaniedaccompanied by by formation of autoantibodies formation of autoantibodies to to tissuetissue of of TGTG. More frequent meets . More frequent meets atat childchildrenren and juvenile age. Girls are ill twice and juvenile age. Girls are ill twice more frequent boys. more frequent boys. Is characterised byIs characterised by lymphocyticlymphocytic infiltration infiltration of of TGTG, there can be only , there can be only hyperplasiahyperplasia of of TGTG on the early stages. on the early stages. DDisease isease isis inheritedinherited with with the system HLA.the system HLA.

Clinical manifestations of Hashimoto’s disease

disease begins during 3 firstdisease begins during 3 first years years of life, after 6 of life, after 6 frequency is increased (max – in teens);frequency is increased (max – in teens);goitre develops gradually and goitre develops gradually and without symptomswithout symptoms (diffuse (diffuse enlargement ofenlargement of TGTG, a surface is uneven by touch, , a surface is uneven by touch, in course of time becomes in course of time becomes solidsolid with with nodesnodes););children are children are irritable, easily excitative, irritable, easily excitative, hiperhydrosishiperhydrosis, , hyperactive (it is possible to suspect hyperthyroidism, hyperactive (it is possible to suspect hyperthyroidism, but not confirmed laboratory);but not confirmed laboratory);clinical clinical course iscourse is various (spontaneous diminishing and various (spontaneous diminishing and disappearance or remain without changes during many disappearance or remain without changes during many years);years);stages of disease: hyperthyroidism (stages of disease: hyperthyroidism (transitorytransitory stage) – stage) – euthyrosiseuthyrosis – –hypothyroidismhypothyroidism..

Diagnostics of Hashimoto’s diseasehigh titehigh titerr of autoantibodies in blood of autoantibodies in blood serum serum (more frequent (more frequent ABAB to to thyroglobulinethyroglobuline 1:100 and 1:100 and AG AG of microsomesof microsomes >1:32); >1:32);level of T4 and TTlevel of T4 and TTHH in blood in blood isis norm normalal, or , or increasedincreased concentrationconcentration of TT of TTHH at normal level at normal level of T4 (“compensated” of T4 (“compensated” hypothyroidismhypothyroidism), or ), or decline of level of T4 at decline of level of T4 at increasedincreased concentrationconcentration of TTof TTHH ( (hypothyroidismhypothyroidism););unclear and unclear and roughrough contours of contours of TGTG at at USUS;;scanscanningning of of TGTG is is prescribedprescribed at suspicion on at suspicion on forming of nodesforming of nodes;;biopsy – biopsy – lymphoidlymphoid infiltration is expressed (for infiltration is expressed (for childrenchildren is is conducted very rarely). conducted very rarely).

Treatment of Hashimoto’s disease

Medicinal treatment depends on stage of diseaseMedicinal treatment depends on stage of disease

Prescriptions to surgical treatment of thyroiditisPrescriptions to surgical treatment of thyroiditis::

--symptoms of compressing and stenosis of symptoms of compressing and stenosis of trachea and esophagustrachea and esophagus;;

--progressive growth of goiterprogressive growth of goiter ( (in spite of in spite of medicinal therapymedicinal therapy););

--suspicion on malignant neoplasmsuspicion on malignant neoplasm..

Subacute thyroiditis

Disease of Disease of TGTG of inflammatory character of inflammatory character (for certain viral etiology), meets rarely.(for certain viral etiology), meets rarely.

Clinical Clinical signssigns::sore throatsore throat and and pain pain in the area of in the area of TGTG (it can (it can arise up also in the area of ear and jaw, arise up also in the area of ear and jaw, cancan become become acuteacute at motions of neck); at motions of neck);fever, weakness;fever, weakness;at at examinationexamination – – algeticalgetic and swollen and swollen TGTG..

Subacute thyroiditisDiagnostics:Diagnostics:on early stages – on early stages – concentrationconcentration of T4 in blood is of T4 in blood is moderatmoderatelyely increasedincreased, level of TT, level of TTHH is is decreaseddecreased;;decreased decreased absorption absorption byby TGTG of of radionuclidesradionuclides;;poorly expressed and not needing correction poorly expressed and not needing correction symptoms of symptoms of hypothyroidismhypothyroidism;;presence of symptoms of general intoxication presence of symptoms of general intoxication leucocytosisleucocytosis and increase of and increase of ESRESR;;on the late stages (2-6 months) on the late stages (2-6 months) -- symptomssymptoms of of hypothyroidismhypothyroidism..Treatment:Treatment:Symptomatic (anaesthetic preparations – at Symptomatic (anaesthetic preparations – at easy cases, easy cases, steroidsteroid hormones – at hormones – at severesevere cases) cases)

Acute thyroiditis

Develops at Develops at acuteacute ( (purulentpurulent and and non-purulentnon-purulent) ) infectionsinfections of of TG TG (more frequent staphylococcus (more frequent staphylococcus aureus,aureus, ββ-hemolytic-hemolytic streptococcus, streptococcus, pneumococcuspneumococcus).).

Clinical Clinical symptomssymptoms::acuteacute toxic fever; toxic fever;expressedexpressed pain pain in the area of in the area of TGTG, which , which increases at increases at tension oftension of neck; neck;expressed painexpressed pain of of TGTG at at palpationpalpation;;hyperemia and local increase of temperature in hyperemia and local increase of temperature in the area of the area of TGTG;;

Acute thyroiditisDiagnosticsDiagnostics::--clinical pictureclinical picture;;--leukocytosis with prevailing of young formsleukocytosis with prevailing of young forms;;--increasing of ESRincreasing of ESR;;--normal level ofnormal level of Т4 та ТТ Т4 та ТТHH;;--normalnormal absorption of radioactiveabsorption of radioactive JJ;;--US ofUS of TGTG ( (determining of abscessdetermining of abscess););--punctionpunction of TGof TG with aspiration of content with aspiration of content ((by by prescriptionsprescriptions).).TreatmentTreatment..Is begun immediatelyIs begun immediately. . Parenteral injection of big doses of Parenteral injection of big doses of broad spectrum antibioticsbroad spectrum antibiotics. . SurgicalSurgical drain drainage of abscess age of abscess of TGof TG..

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