Patologia functionala a tiroidei

Hiper- si hipotiroidism

Corin Badiu, 2015

Hipertiroidismul

Definitie
Clasificare
Tablou clinic
Explorari paraclinice
Etiopatogenie
Anatomie patologica
Fiziopatologie
Evolutie, complicatii
Tratament

Particularitati
Boala Basedow Graves
Gusa hipertiroidizata
Sindromul Plummer
Tiroida in sarcina
Tiroidite subacute
Struma ovarii

Corin Badiu, 2015

Hipertiroidismul
Definitie: totalitatea manifestarilor clinice si biochimice
determinate de excesul hormonilor tiroidieni liberi la
nivelul receptorilor tisulari responsivi
Clasificare: cu functie tiroidiana crescuta
cu tiroida nefunctionala, blocata

Corin Badiu, 2015

Clasificare (RIC)
Cu productie tiroidiana
crescuta

Fara productie de hormoni

- Boala Graves

- Tiroidita subacuta

- Gusa multinodulara hipertiroidizata

- Tiroidita postpartum

- Nodulul tiroidian toxic (sd. Plummer)

- Iatrogen

- Paraneoplazic- coriocarcinom, mola

hidatiforma (hCG TSH-like)

- Tireotoxicoza factitia sau alimentara

hamburger

- tireotropinomul

- Carcinom tiroidian folicular metastazat

- sd. de rezistenta la hh. Tir

- Struma ovarii

Corin Badiu, 2015

Tablou clinic
scadere ponderala cu apetit crescut

palpitatii
dispnee
astenie, fatigabilitate
intoleranta la caldura, hipersudoratie
hiperactivitate, iritabilitate
tulburari de dispozitie, insomnie
tranzit accelerat

tegumente calde, fine, umede

tahicardie, fibrilatie atriala, IC cu debit
crescut
tremor fin, hiperkinezie, hiperreflexie
retractie palpebrala
caderea parului, onicoliza
miopatie, hipotrofie musculara

Corin Badiu, 2015

Particularitati
Exoftalmie (in boala Basedow Graves)

Mixedem pretibial

Corin Badiu, 2015

Particularitati
Exoftalmie (in boala Basedow Graves)

Corin Badiu, 2015

GO- QOL Chestionar n limba romn

(Calitatea vieii n oftalmopatia din boala Graves-Basedow)

GO-QOL (Graves ophthalmopathy- quality of life) evalueaz calitatea vieii pacienilor cu oftalmopatie
din boala Graves-Basedow.
GO-QOL apreciaz dou aspecte: (1) funcia vizual, prin efectele diplopiei i a scderii acuitii vizuale
(ntrebrile 1-8) i (2) funcia psihosocial, consecina efectelor estetice induse de oftalmopatie (ntrebrile
9-16).
Chestionarul va fi completat de ctre pacient, sau cu ajutorul personalului medical, fr a influena
rspunsurile.
Scorul GO-QOL:
Rspunsurile vor fi evaluate cu puncte de la 1 la 3 (rspunsul nu este cotat cu 3 puncte, puin limitat
cu 2 puncte, iar foarte limitat cu 1 punct). Rspunsurile vor fi sumate sub forma celor dou scoruri totale
(funcia vizual: ntrebrile 1-8 i funcia psiho-social: ntrebrile 9-16), dup urmtoarea formul:
(puncte totalizate 8) 1 100.
Cu ct scorurile sunt mai mari, cu att starea de sntate perceput de pacient este mai bun.
Dac pacientul nu poate rspunde la ntrebrile 1 (nu deine carnet de conducere) i sau 2 (nu poate
merge pe biciclet), rspunsurile respective nu se noteaz. n acest caz, scorul total va fi: (puncte totalizate
#)/(2 #) 100, unde # reprezint numrul de rspunsuri la ntrebri.

Corin Badiu, 2015

GO- QOL Chestionar n limba romn

(Calitatea vieii n oftalmopatia din boala Graves-Basedow)

Corin Badiu, 2015

Hertel Exophtalmometer

Corin Badiu, 2015

Corin Badiu, 2015

CLASIFICAREA
WERNER (NOSPECS)
Fara simptomatologie oculara

1
O

numai simptome
(non-infiltrativ)

a)senzaie de corp strin, hiperlacrimare,

b)retracie palpebral

2
S

leziuni de esuturi moi

edem palpebral, chemosis (edem conjunctival)

0) absente
a) minime
b) moderate
c) marcate.

3
P

proptosis

Protruzia marcat a globilor oculari

(Exoftalmie 3 mm):
0) absenta
a) 3-4 mm
b) 5-7 mm
c) 8 mm.

4
E

afectarea muchilor
extraoculari

- diplopie, asinergism de convergen, oculofrontal i oculonazal

0) fara modificari
a) limitare la privirea laterala
b) restrictie evidenta a miscarii
c) glob ocular fix.

5
C

leziuni corneene

ulcer cornean
0) absenta
a) eroziune superficiala
b) ulcer corneal
c) necroza sau perforatie.

6
S

afectarea nervului optic

(scaderea AV)

pn la cecitate
0) absenta
a) 20/20-20/60
b) 20/70-20/200
c) 20/200.

Corin Badiu, 2015

Nodulul autonom tiroidian

(sdr. Plummer)

Corin Badiu, 2015

Teste diagnostice
Funcionale

Reglajul axei tiroidiene

Hormoni (totali/liberi)
Transport i efecte periferice
Metabolismul iodului
Autoimunitatea
Genetica

Morfologice

Ecografie
Scintigrafie
CT / IRM
Anatomie patologic

ALGORITMI
Corin Badiu, 2015

D2

Reglarea Axei Tiroidiene

TRH
TSH
T4 / T3
Deiodaze: D1, D2, D3

D2

Leptina
TR, TRH R, TSH R

D1

Corin Badiu, 2015

Teste TSH

Corin Badiu, 2015

TSH / T4 / fT4

The relationship between serum TSH and free T4 concentration is shown for normal subjects (N) and in the
typical abnormalities of thyroid function: A, primary hypothyroidism ; B, central or pituitary-dependent
hypothyroidism; C, thyrotoxicosis due to autonomy or abnormal stimulation of the gland; D, TSH-dependent
thyrotoxicosis or thyroid hormone resistance. Note that linear changes in the concentration of T4 correspond
to logarithmic changes in serum TSH.

Corin Badiu, 2015

TSH Mind the GAP!

Condition

TSH

fT4

fT3

Pituitary-hypothalamic abnormality

L-N

Extremely premature infants

L-N

Central TSH excess

N-H

T3 toxicosis

Subclinical

Early Treatment

H-N-L

H-N-L

L-N-H

Subclinical

Early Treatment

L-N

N-H

Dopamine

Glucocorticoids

L-N

Amiodarone (acute)

N-H

L-N

PrimaryabnormalityofTSHsecretion

Thyrotoxicosis

TSH assay artifact

Hypothyroidism

Thyroid hormone resistance

Medications

Pregnancy
N: normal; L: low; H: high; U: undetectable.

Corin Badiu, 2015

Thyroid hormones evaluation

Hormone

Metric

SI Units

Variations unrelated to thyroid disease

Total T4

4-11 ug/dl

60-140 nM

Binding protein changes

competitors for T4 binding

Free T4 0.02%

0.7-2.1 ng/dl

10-25 pM

Methodologic factors
Albumin changes
Dilution effects

Total T3

75-175 ng/dl

1.1-2.7 nM*

Binding protein changes

competitors for T3 binding
Age-related changes
Nutrition, illness, drugs

Free T3
0.3%

0.2-0.5 ng/dl

3-8 pM*

Methodologic factors as for T4

and influences on total T3

Reverse T3

15-45 ng/dl

0.2-0.7 nM

Nutrition, illness, surgery, drugs

TSH

0.3-4.0 mU/l

1-15 pM#

Diurnal variation, pulsatile secretion

Medications

TSH -subunit

<0.2 ug/dl

<100 pM

Postmenopausal women
Primary Hypogonadism

Thyroglobulin

1-20 ug/l

1.5-30 pM+

Variation in assay standards and antibodies

Values in children may be higher

# Assumes biologic potency of 7-15 U/mg
+ Dependent on serum TSH and amount of thyroid tissue

Corin Badiu, 2015

Subclinical thyroid diseases

defined as abnormal TSH despite normal levels
of free thyroxine

subclinical

TSH

fT4

hyperthyroidism

hypothyroidism

Biochemical definition of thyroid dysfunction

Condition

TSH (mUI/l)

Thyroid hormones

Overt hyperthyroidism

<0.1

Elevated T4 or T3

Overt hypothyrpodism

>4.5

Low T4

Subclinical hyperthyroidism

< 0.1

Normal T4 and T3

Clearly low TSH

0.1 0.4

Normal T4 and T3

Low but detectable

4.5 10

Normal T4

Mildly elevated TSH

> 10

Normal T4

Markedly elevated

Subclinical hypothyroidism

Comments

Balshem et al, AHRQ, 2011

TSH fT4 correlation

Serum TSH - log-linear relationship with circulating thyroid
hormone levels
2 x fT4 100 x TSH
100
n = 3223
y = 0.0886x+1.1275
R2 = 0.236

TSH (mU/I)

10

0.1

0.01
0

12

16

20

24

28

32

fT4 (pmol/l)

Fatourechi V, Mayo Clin Proc, 2009; Hoerman et al, 2010, EJE

What is normal?
Diagnosis depends of the limits of TSH
normal, references, discrimination values

too simplistic, implying that everything not being normal must be corrected
absolute health does not exist!

discrimination values
cut-off values important for medical decisions
require knowledge of the disease
prevalence
the sensitivity and specificity of diagnostic tests
clinical consequences of a false positive / negative diagnosis

specifications concerning specimen collection

environmental and physiological conditions

techniques and timing
preparation and storage
analytical and the statistical methods
Brabant et al, EJE, 2006

TSH assays Mind the GAP!

Sensitivity
HAMA ( for immunometric assays) Mouse Ig
X-reactivity (specificity); SU
Age (immature feed-back)
Drugs (non-specific feed -back)
Transport high TBG

9,095 consecutive healthy subjects (5,214 M, 3,881 W)

TSH

Wang CY, Chang TC, Chen MF. Associations between subclinical thyroid disease and metabolic syndrome. Endocr J 2012.

TRH si masa tiroidiana

Relationship of TSH (after 400 m g TRH i.v.) and thyroid weight (g) in 22 women with clinically
euthyroid multinodular goiter (with permission from Smeulers J, Docter R, Visser TJ, Hennemann
G: Response to thyrotrophin-releasing hormone and triiodothyronine suppressibility in euthyroid
multinodular goitre. Clin Endocrinology 7:389,1977).
Corin Badiu, 2015

Gusa endemica

TSH = 3,5 mU/L

fT4 = 13,5 pmol/L

Corin Badiu, 2015

Gusa endemica

TSH = 0,15 mU/L

fT4 = 23,5 pmol/L
Corin Badiu, 2015

Transport

Corin Badiu, 2015

Coexistenta Anticorpilor

In this patient with Graves' Disease, the mixture of antibodies shifted during antithyroid
therapy from dominance by TSAb, to a dominant effect by TSBAb and TBII, leading to
spontaneous development of hypothyroidism. From Takasu et al, J. Endocrinol. Invest.
20:452-461, 1997.
Corin Badiu, 2015

ECOGRAFIA TIROIDIANA
Evidentiaza

Gusa si caracterul difuz sau nodular al acesteia

Nodulul < 1 cm / confirma nodulul > 1 cm
Chistii tiroidieni
Hipervascularizatie si calcificari

Masoara
Dimensiuni tiroida calcul volum [=*(d1+d2+d3)]
Dimensiuni nodul (in dinamica)

Diferentiaza
Nodulii tiroidieni de cei extratiroidieni
Nodulii de chisti

Teste morfologice
ECOGRAFIA TIROIDIANA

Corin Badiu, 2015

ECOGRAFIA TIROIDIANA

Corin Badiu, 2015

Radio Iodo Captarea

Valori crescute
Valori sczute
Sintez crescut de HTir Sintez scazut de HTir
Hipertiroidism

Hipotiroidism primar

(gusa polinodulara, Graves, Plummer)

(Hashimoto, ATS, tiroidectomie, 131I)

Depleie hormonal

Hipotiroidism secundar

(diaree cronic, sdr. nefrotic)

(leziuni hipotalamo-hipofizare)

Sintez normal de HTir

Caren iodat

Aport exogen de HTir

Fr scderea sintezei HTir

Aport iodat excesiv
(dieta, medicatie)

Corin Badiu, 2015

Scintigrama Tiroidiana

Scintiscans of thyroid. The scan on the left is normal. A typical scan of a "cold" thyroid nodule failing to
accumulate iodide isotope is shown on the right.

Corin Badiu, 2015

(A) Cross section of multinodular

goiter. (B) Gross radioautograph of
the thyroid in part a. Observe the
variation in 131I uptake in different
areas.

Corin Badiu, 2015

Autoradiografie / Morfologie

Heterogeneity of morphology and function in a human multinodular goiter. Autoradiographs of

two different areas of a typical multinodular euthyroid human goiter excised after administration
of radioiodine tracer to the patient. There are enormous differences of size, shape and function
among the individual follicles of the same goiter. Note also that there is no correlation between
the size or any other morphological hallmark of a single follicle and its iodine uptake. (with
permission from Peter HJ, Gerber H, Studer H, Smeds S: Pathogenesis of heterogeneity in
human multinodular goiter. J Clin Invest 76:1992,1985).
Corin Badiu, 2015

Anatomia Patologica
A) "Colloid nodules" display macrofollicles lined by flattened
thyroid epithelial cells. The nodules are circumscribed and do
not have a fibrous capsule.

B) Possible evolution of a "colloid nodule". An area of

nodular hyperplasia on left, and a "developing" colloid
nodule on right, with macrofollicles and some remaining
focal hyperplasia.

Corin Badiu, 2015

Fine needle aspiration cytology specimens.

(A) Benign epithelial cells, colloid, and

occasional macrophages, typical of a
"colloid nodule".

(B) Epithelial cells in a follicular

arrangement suggesting adenoma, but
which could be from a follicular carcinoma.

(C) Epithelial cells in a pappilary

formation from a papillary thyroid
carcinoma. Nuclear grooves are
also apparent. (Courtesy of Dr.
Richard DeMay, University of
Chicago/Chicago Lying-in Hospital)

Corin Badiu, 2015

Tratament
Obiective: Scderea nivelului de hormoni tiroidieni;
Prevenirea / tratarea complicaiilor
Metode:
A. Medicamentos
1. Antitiroidiene de sintez: n toate formele cu sintez hormonal crescut.

- derivai de tiouree: Propiltiouracil (PTU, 50mg/tb), Metiltiouracil (MTU, 50mg/tb);

- derivai de imidazol: Carbimazol (5mg/tb), Metimazol (Thyamazol, 5mg/tb, de electie)
Mecanism de aciune: inhib organificarea iodului (formarea MIT i DIT) prin blocarea peroxidazei. PTU inhib i
cuplarea MIT+DIT i conversia periferic a T4 n T3, dar are eficacitate mai mica dect tiamazolul; este de
electie la gravide, deoarece trece mai greu bariera fetoplacentara.
Reacii adverse: erupii alergice; rareori (0.1%): agranulocitoz
Efecte secundare: hipotiroidie, creterea de volum a guii (prin scderea hormonilor tiroidieni i dezinhibarea TSH)
indeosebi n supradozare
Posologie: se ncepe tratamentul cu 9-12 tb/zi i se scade progresiv, n 2 luni, pn la doza de ntreinere = 2-3
cp/zi.
2. Blocante beta-adrenergice: Propranolol 120mg/zi (inhib i conversia T4 - T3), sau alte blocante.
3. Sedative i hipnotice

B. Radioiod (I 131) in doze de 5-20 mCi

C. Chirurgie
Corin Badiu, 2015

Terapia chirurgicala

Corin Badiu, 2015

Sarcina i funcia tiroidei

Corin Badiu, 2015

Sarcina i funcia tiroidei

Sarcina modifica echilibrul tiroidian:
aport de iod crescut (200 ug/zi)
volum circulant / de distributie
cresterea RFG cu turnoverului iodului
imunosupresie
interferente hCG TSH
nivel crescut de TBG
activitatea deiodazei tip III pacentara
Necesar de H tiroidieni pentru dezvoltarea fetala
Tiroida fetala functioneaza dupa 12 saptamani
fT4 si fT3 in primul trimestru
Corin Badiu, 2015

Sarcina i funcia tiroidei

Patel et al., Delivery of maternal thyroid hormones to the fetus, TEM 2011, 22,
5, 164-170
Corin Badiu, 2015

Hipertiroidia neonatala

Corin Badiu, 2015

Tiroiditele

Corin Badiu, 2015

Corin Badiu, 2015

Corin Badiu, 2015

Hipotiroidismul

Definitie
Clasificare
Tablou clinic
Etiopatogenie
Evolutie, complicatii
Tratament

Particularitati
Mixedemul congenital

Corin Badiu, 2015

Etiologia hipotiroidismului
Primar
iatrogen sau autoimun

Secundar
Sdr. Sheehan, tumori
hipofizare, deficit
congenital de TSH

Corin Badiu, 2015

Disgenezii tiroidiene

Corin Badiu, 2015

Disgenezii tiroidiene
Semne de mixedem congenital:
la nou nscut : fontanela posterioar mai mare de 1 cm, icter
prelungit, macroglosie, abdomen destins, hipotonie
muscular, hernie ombilical, gu
la copil / adult:
semne neurologice
deficit intelectual
dificulti n dez-voltarea psihomotorie
cretere lent i nanism dizarmonic (cu membre scurte)
pubertate ntrziat / hipogonadism
eventual gu
eventual semne de hipotiroidism actual (cretinism - forma
mixedematoas)

Corin Badiu, 2015

Hipotiroidismul neonatal
Definiie
Clasificare:
Congenital (1:3000-4000)
Permanent
Tranzitor

Dobandit

Impact asupra dezvoltarii (neuropsihice, staturale, pubertare)

Teste: screening pentru hipotiroidie neonatala
Profilaxie si Tratament: aportul de iod la mama, hormoni tiroidieni la copil

Corin Badiu, 2015

Fatul depinde de T3, T4

Dezvoltarea fetusului depinde de H tiroidieni, in special in ceea ce

priveste Sistemul Nervos

Fatul depinde deT4-T3 produsi de mama pana in sapt 8-11

Fatul foloseste T4-T3 materne pentru dezvoltarea hipotalamusului,

hipofizei si glandei tiroide.

Sistemul Nervos Central depinde de hormonii tiroidieni.

- Proliferare neuronala
- Maturare neuronala
- Mielinizare neuronala
- Formarea sinapselor

Corin Badiu, 2015

Dezvoltarea sistemului nervos

1. Diviziune

2. Migrare

3. Agregare si
4.

Diferentiere

5. Sinaptogeneza 6.Moarte cel. 7. Rearanjare

8. Mielinizare

Corin Badiu, 2015

Reeaua de conexiuni neurale

este mai puin dens
Creierul cu aport suficient
de iod

Creierul cu deficit de iod

Corin Badiu, 2015

Hipotiroidism congenital
Clinica deceleaza 1:5000-1:10000
(10% 1 luna, 35% primele 3 luni,
70% primul an, 100% la 3-4 ani)
Incidenta: 1 la 3.000
Una din cele mai obisnuite cauze
tratabile de retard mental

Corin Badiu, 2015

Cretinism
Statura scunda,
disarmonica,
retardare mentala

14 ani, hipotiroidism
sever congenital
2 luni, hipotiroidism congenital:
fata infiltrata, limba marita

Corin Badiu, 2015

Criterii pentru monitorizarea programelor de

control al carentei iodate
Indicator

Scop

Iodarea srii
Proporia de consum casnic a srii iodate

>90%

Ioduria proporia sub 100 g/L

proporia sub 50 g/L

<50%
<20%

Volum tiroidian - copii 6-12 ani

proporia cu gusa (clinic sau eco)

<5%

TSH neonatal
proporia cu nivel peste 5 mU/L

<3%

Corin Badiu, 2015

Indicatori de prevalenta ai deficitului de iod

criterii pentru o problema importanta de sntate publica
Normal

DI usor

DI moderat

DI sever

Prevalenta guii
(copii 7-14 ani)

<5%

5-19.9%

20-29.9%

>30%

Iodurie (mg/l)

100-200

50-99

20-49

<20

TSH neonatal
>5 U/ml (%)

<3%

3-19.9

20-39.9

>40

Corin Badiu, 2015

Screening pentru hipotiroidie neonatala

Corin Badiu, 2015

Valori de referinta

Corin Badiu, 2015

Mixedem la adult

Corin Badiu, 2015

Profil sanguin

fT4 , T4 , T3
TSH - hipotiroidism primar, N sau - hipotiroidism central
Dislipidemie mixta II b (colesterol + TG )
CK , ALT, AST
Anemie macrocitara
ATPO - marker etiologic de autoimunitate
Na - aparent SIADH, mai ales in hipotiroidismul central
PRL - in hipotiroidismul primar

Corin Badiu, 2015

Tratament
Administrare orala de hormoni tiroidieni
Tratament prompt, imediat dupa diagnostic
Doze progresiv crescatoare la 4-8 sapt.
Mentinerea terapiei permanente este CRUCIALA!
Complianta!
Corin Badiu, 2015

Tratament
Tiroxina (LT4)
Varsta

Doza zilnica
g

recomandata
g/Kgc

0-6 luni

25-50

8-10

6-12 luni

50-75

6-8

1-5 ani

75-100

5-6

6-12 ani

100-150

4-5

>12 ani

100-200

2-3

Corin Badiu, 2015

Recomandarile OMS pentru aportul zilnic minim de iod

(WHO, UNICEF, ICCIDD-1996)
Grup

Vrsta

nainte de 1992
g iod/zi

Din 1992
g iod/zi

nedefinit

30 ug /kg

0-12 luni

35-50

50

1-6 ani

70-90

90

7-12 ani

120

120

Aduli

150

150

Sarcina

175

200

Lactaie

200

200

Prematuri
Copii

Corin Badiu, 2015

Verificarea tratamentului
Consecinele pe termen lung ale tratamentul HC sunt strns legate de
calitatea urmririi evoluiei pacienilor sub tratament.
Examinarea clinic include evaluarea creterii i dezvoltrii neuro-motorii
si trebuie efectuata la fiecare cteva luni n timpul primilor 3 ani de via.

Corin Badiu, 2015

CONCLUZII

Corin Badiu, 2015