Download tyroiditis 2 - UMF IASI 2015

THYROIDITIS
Inflammatory diseases of the thyroid gland with different etiologic,
biologic, histologic and clinical aspects
CLASSIFICATION
• ACUTE: bacterial, viral
• SUBACUTE: de Quervain’s thryoiditis
• CHRONIC:
• chronic autoimmune thyroidits
• Tuberculous
• Mycotic
• Riedel’s thyroidits
ACUTE BACTERIAL THYROIDITIS
Signs and symptoms
• Fever
• Pain profound and severe
• Dysfagia - 90 % din cazuri
• Dyspnea – 50 %
• Spasmodic cough
Laboratory data
• increased ESR
• leukocytosis with neutrophilia
• Ultrasound: small or large hypoechoic areas
• FNB: isolation of germs
Treatment : antibiotics
ACUTE BACTERIAL
THYROIDITIS
Acute thyroiditis - histology
SUBACUTE ”DE QUERVAIN’S” THYROIDITIS
PREVALENTA
Sex ratio F/M: 3,6/1 – 10,6 /1
1 caz TS for 5 cases of Graves disease and for 20 cases of AIT
• 0,01 % of all hospitalized patients
• 1,89 % of all patiens hospitalized for thyroid diseases
• 9,9 % of subjects presenting with thyrotoxicosis
• 1,52 % of patients investigated by FNB
Szabolosz I. Subacute thyroidits Budapesta 2000
SUBACUTE THYROIDITIS
ETIOLOGY
• probably the disease is a response to a viral infection
GENETICS
• those with HLA-Bw35 have a risk to develop the disease of 8-56.6 %
• HLA-Bw35 allows the development of clincal symtoms
• it has no relatioship with the evolution of the disease
SUBACUTE THYROIDITIS
PATOGENICITY
• interleukine 6 produced by monocytes si macrophages determine
inflammation
• interleukine 2 +TNF  + interferon  determine destructive thyroiditis
in 10 % of cases
• VEGF, basic FGF, PDGF determine granulomatous reaction
• EGF determines by mitogenic effect the regeneration of the follicles
PATHOLOGY
• Follicular disruption with thyroglobulin liberation is responsible for the
initial phase of thyrotoxicosis
• granuloma:
• a center of giant cells surrounded by macrophages
• epithelial cells surrounded by a crown of macrophages involved
with antigen presentation
SUBACUTE THYROIDITIS
SUBACUTE THYROIDITIS
Clinical signs and symptoms
History of viral infection
Painful thyroid
Fever
Dysfagy
Painful thyroid enlargement
Pain irradiates to the ears
Simptoms of thyrotoxicosis
Malaise
Classical
form
Non
classical
form
1/3
90 %
90 %
18 %
90 %
50 %
76 %
42 %
SUBACUTE THYROIDITIS
Laboratory data
Imagery
Important increase of ESR
Leukocytosis
FT4 si FT3 increased
Suppressed TSH
Increased thyroglobulin
Transitory increased
antithyroid antibodies
HLA-Bw 35+
Hipoechogenicity
generalized or disseminated
points
Localized hipoechogenicity
Absent Tc 99 m uptake
Reduced iodine uptake
67 Gallium citrat: scintiscan
SUBACUTE THYROIDITIS
Differential diagnosis
Evolution and complications
Cyst with intracystic
hemorrhage
Tirotoxicosis induced by
iodine loading (amiodarone)
Interpheron induced
thyroiditis
Thyroid cancer: FNB
Transient hypothyroidism
second phase of evolution
Recurrent disease is
unpredictable
Heeling
Definitive hypothyroidism
<1/10
Painless forms
Subacute thyroiditis: generalized
hypoechogenicity
Subacute thyroiditis: patchy
hypoechogenicity
SUBACUTE THYROIDITIS
Color Doppler ultrasound examination
scintiscan
SUBACUTE THYROIDITIS – TREATMENT
FORME SEVERE:
GLUCOCORTICODS:
• Prednisone: 30-40 mg / day at the beginning of
the disease with further reduction of the dosage
• Dexametazone: 3-4 mg /zi
FORME USOARE:
Nonsteroidal anti inflammatory drugs: indometacin
AUTOIMMUNE THYROIDITIS
INCIDENCE
• 3,5 – 4,5 % of population present autoimmune thyroid diseases
• 4,6 % of women and 1,23 %of men have antithyroid antibodies
• 15 % of women over 60 years
• lymphocytic infiltrations: 6,8 5 of women and 2,7 % of men
• 50 % of those with antithyroid antibodies have TSH > 6 U.I./ml
• 60 % of those with TSH > 6 U.I./ml have antithyroid antibodies
• 80 % of those with TSH > 10 6 U.I./ml have antithyroid antibodies
• 5 % of those with TSH > 6 U.I./ml develop overt hypothyroidism each
year
AUTOIMMUNE THYROIDITIS
PATOGENY
• genetic predisposition
•Viral aggression
• excessive iodine supply
GENETIC PREDISPOSITION
• relatives with autoimmune thyroid diseases
• patients with genetic abnormalities :Turner, Klinefelter, Down syndrome
• association with other autoimmune diseases:
• multiple autoimune endocrine diseases type I and II (ICSR, ovarian
failure with precocious menopause ) autoimmune hypophysitis Biermer
disease , sd, Sjogren, lupus, rheumatoid arthritis , miastenia gravis,
interstitial lung disease
• HLA-DR3 si HLA-DR4
AUTOIMMUNE THYROIDITIS
ANTIBODIES
THIROIDITIS
ANTI-TPO (PEROXIDASE)
HH, PTP
ANTI – Tg Ab
HH
TSH -receptor stimulating antibodies
hashitoxicosis
TGI – thyroid growth immunoglobulins
HT with goiter
Thyroid stimulating blocking Ab
Atrophic thyroiditis
Spontaneous mixoedema
TGBI – thyroid growth blocking
immunoglobulins
Atrophic thyroiditis
Spontaneous mixoedema
Anti T3 –Ab , anti T4 - Ab
May interfere with hormone
assessment
Anti pancreatic islet
Anti salivary ducts
Anti other nedocrine glands
Multiple autoimmune
endocrine diseases
AUTOIMMUNE THYROIDITIS
LABORATORY DATA
HASHIMOTO’S thyroiditis
• T4, T3 frequently normal
• goiter
• TSH normal or slightly elevated
• metabolic state
• increased response of TSH to TRH
• eutiroidism – 80 %
• hipothyroidism – 15 %
• hiperthyroidism – 5 %
TREATMENT
THYROID HORMONES
• anti TPO – ab – 100 %
• anti TG-ab – 90 %
• TBII – 15-20 %
ULTRASOUND EXAMINATION
THYROID VOLUME: Increased,
normal or decreased
Intense hypoechogenicity
Scintiscan : patchy hypoechogenicity
FNB: lymphocytes and Hurthle cells
AUTOIMMUNE THYROIDITIS
CLINICAL FORMS
• HASHOTOXICOSIS
• IN CHILDREN AND ADOLESCENTS: diffuse euthyroid goiter 10-15 %
of goiters at these ages
• ATROPHIC
• SILENT or PAINLESS
• POSTPARTUM THYROIDITIS : TPO-Ab are detectable in predisposed
cases in the 6th month of pregnancy: hiperthyroid state + depression it
occurs postpartum weeks 11-12 and is followed by transient or definitive
hypothyroidism
• AUTOIMMUNE THYROIDITIS SI MALIGN LYMPHOMA
• AUTOIMMUNE THYROIDITIS and THYROID CANCER
• IATROGENIC: interpheron, increased iodine intake, external radiotherapy
AUTOIMMUNE THYROIDITIS-HISTOLOGY
AUTOIMMUNE THYROIDITIS CLINICAL
ASPECT
AUTOIMMUNE THYROIDITIS CLINICAL
ASPECT
AUTOIMMUNE THYROIDITIS CLINICAL
ASPECT
POSTPARTUM - AUTOIMMUNE THYROIDITIS
AUTOIMMUNE THYROIDITIS - ULTRASOUND
AUTOIMMUNE
THYROIDITIS
ATROPHIC
VARIANT
THYROID NODULES
THYROID NODULES
•
CLINICAL : 4-7 % (5-20%)
• NECROPSIES:40-50 % (30-60%)
• ULTRASOUND EXAMINATION 16-67 %
CLINICA OF ENDOCRINOLOGY IASI:
- MEN : 27,37 %
- WOMEN: 30,3 %
CHILDREN: 1-2%
•THE PREVALENCE INCREASES WITH AGE BY : 0,08 % / year
THYROID CANCER: < 10 % OF PALPABLE NODULES, <5 % OF NODULES DETECTED BY US
NODULS 4 % OF POPULATION X 4% RISK= POSSIBLE INCIDENCE: 1,6/103
TRUE PREVALENCE : 0.025-0,050/103
1/30 MICROCANCERS BECOME CLINICALY DETECTABLE (MEYER 2000)
THYROID NODULES
•CYST
• HETEROGENOUS ENDEMIC GOITER
• ADENOMA
• THYROIDIS
• CANCER
• LYMPHOMA
• EXTRATHYROIDAL LESION
THYROID NODULES
AUTHOR (YEAR)
INVESTIGATED AREA
INCIDENCE OF NODULS
Reshetnikov 1990
CIS
18,8 %
Filatov 1991
CIS
3,45 %
Brander 1991
27,3 %Solitar – 57 %
Finlanda
Hintze 1992
Germany
> 60 YEARS
Multinodular 43 %
24,78 %
ENDEMIC AREA
Grun 1992
Mettler1992
Mogos 1994
Germany
27,6 %
Goiter prevalence: 37,7 %,
women 36 %, men: 18,8 %
Ukrain,
Cernobil area
Iasi, Romania
children: 0,5 %
Adults 14,9 %
women: 30,3 %
meni: 27,7 %
61,84 < 1 cm, 21 % 1-2 cm.9,2 %>
3 cm
THYROID CANCERS
INCIDENCE
MORBIDITY:
B/106
• USA:
F/106
2,4-2,8
5,6-6,2
• Australia: 0,7
• Japan:
2,1
1.1
• Hawai:
2,7
= 1 % Cancer Data Base
Honolulu: 15,16%
Hiroshima 25,3
USA: 1,09-1,84
12 / 106/ year
femei: 52 /106/year
barbati: 21/ 106/year
4
•USA: ’85-’95: 13.856 cases
Necropsies:
• SOKAL 1954:
• CUTTLER 1975:
2
3,1
• Germany:
NEW CASES /106/ year
• INGBAR 1981:
36 / 106/year
• IMPIERI 1984:
10-30 / 106/year
• MAZAFFERRY 1988 : 37 / 106/year
THYROID CANCERS
THYROID CANCERS
THYROID CANCERS
THYROID CANCERS
THYROID CANCERS
THYROID CANCERS
THYROID CANCERS
THYROID CANCER papillary form
FOLLICULAR
THYROID CANCER
MEDULLARY
THYROID CANCER
THYROID LYMPHOMA
Steady increase of thyroid cancer
all over the world
Between 1973-2002
2.4 times increase in
thyroid cancer incidence
All

thyroid cancer
3.6/105 
8.7/105/year
Papillary

cancer
2.7/105 
7.7/105/year
Small
papillary
cancer

87 % of the cancer
increase
Mortality decreased from
0.57 to 0.47/105/year
 external
irradiation stopped
after 1961
 precocious diagnosis by
ultrasound and FNB
 increased incidence but
stable mortality
 Papillary cancer has a long
evolution and excellent
survival
Trends in thyroid cancer
There was noticed steady increase of thyroid
cancer all over the world
External irradiation is the only well documented
cause in papillary thyroid cancer leading to
RET/PTC re-arrangements
Iodine deficiency may play a role in the
development of follicular cancer and may favor the
development of anaplastic carcinoma
Iodine repletion is associated with increased
incidence of papillary carcinoma with excellent
prognosis
The ratio of papillary to
follicular thyroid cancer
(M.Goldust, S.Samankan etc
al,2012)
(J. D. Cramer, 2010)
Interval
Number of
cases
Age
Females
Males
1975 1979
19
45.7 ±
10.9
18
1
1980 1984
18
52.9 ±
14.9
15
3
1985 1989
17
49.5 ±
15.6
13
4
1990 1994
37
48.6 ±
16.8
32
5
1995 1999
52
51.5 ±
15.8
43
9
2000 -2004
71
53.1 ±
15
53
18
2005-2009
131
51.8 ±
14.2
109
22
1975 2009
345
51.3 ±
14.8
283
62
Table 1. Demographic data of 345 patients with thyroid cancer operated between 1975-2009 in
the Ist. Surgery Clinic
Figure 4. Percentage of thyroid
cancer operated for each period
of 5 years from the entire
examined cohort
Etiology and patogeny of thyroid cancers
external irradiation:
“ ..until now the only carcinogenetic factor for the thyroid in man is external irradiation
Duffy si Fitzgerald 1936: firs obsercation of radiatioon induced thyroid cancer in children irradiated for
benign lesions of head and neck
New cases of thyroid cancer in in Belarus 1990-1995 –Cernobil effect
( Pacini: J.Clin.Endorinol.Metab.1997)
1990 – 31, 1991 – 66, 1992 – 72, 1993 – 94, 1994 – 96, 1995 – 90
78.8 % sub 14 ani
Prezumed thyroid cancer: 10- 40
Excess of thryodi cancer due to external
irradiation after Cernobil: 200 - 800
Increased susceptibility:
Irradiation of head and neck in all children
- external irradiation for othe rcancers
-Vage less than 20 years
-Female sex
-Genetic predisposition
CONTAMINAREA RADIOACTIVA DUPA
CERNOBIL 1986
THYROID CANCER – CERNOBIL ACCIDENT
Irradiation induced thyroid cancer
(E.Cardis,2005).
(E.Cardis,2005).
(E.Cardis,2005).
THYROID CANCER
THYROID CANCER
FCMT
MEN-2A
MEN-2B
CMT
sporadic
germinal
germinal
germinal
somatic
Exon
10,11,13,14,15
10,11
16,(15), 918
10,11,13,16
CMT
100%
100%
100%
100%
AGE
<20,>50
<20
<20
<40
Multicentricity
100%
100%
100%
rara
Bilateral lesions
100%
100%
100%
rara
Hiperplasia of C cells
100%
100%
100%
rar
Feocromocytoma
0%
10-60%
50%
0%
Hiperparathiroidism
0%
10-25 %
0%
0%
Notalgia –cutaneous
lichen amyloidosis
Hirschprung disease
0%
< 10 %
Codon:
618,620
0%
0%
Ganglioneuromatosis
0%
0%
100 %
0%
Dismorphism
0%
0%
100 %
0%
RET MUTATION
MEN TYPE IIB - GORLIN’S SYNDROME
MEN TYPE IIB - GORLIN’S SYNDROME
THYROID CANCER- ultrasound exam
THYROID CANCER- ultrasound exam
THYROID CANCER
THYROID CANCER - FNB
Risk factors for malignancy in thryoid nodules
element
benign
malignant
history
Endemic area, female sex, aged
patients
History of cranial irradiation, other
medullary thyroid carcinomas in the
family, solitary thyroid nodule rapidly
growing, compressive symptoms, male
sex, child, young adult
Clinical data
Multinodular goiter,soft nodule, lack of
palpable lymph nodes,
Solitary ferm nodule, lymph node
enlargement, distant metastases
Biologgical data
AAT+, deceased TSH ,increased T3,T4
Increased calcitonine
ultrasoud
Pure cyst, peripheral hallo, hyper, iso
or hypoechoic, without calcification.
Doppler exam:peripheral ring of
vassels
Irregular margins, absence of hallo,
increased intranodular vascularity
scintigraphy
“worm nodule” a cold nodule is not
surely a malignant one
“cold nodule”
ABC (FNB)
“benign”
Suspicious or malignant
Response to thyroid
hormone treatment
Reduction of volume
Increased volume under treatment
FINE NEEDLE BIOPSY
Algorithm for investigation and treatment of thyroid
nodules
TYOROID NODULE
CYST
ULTRASOUND
SOLID or partially cyst
FNB
BENIGN
FNB
SCINTIGRAPHY
SUSPECT SAU
NEOPL.FOLIC
MALIGN
ASPIRATION
SCLEROSING
Heeled
T4
WARM
COLD
LOW RISK
REFACERE
HIGH
RISK
THYROIDECTOMY
Follow up
E.Zbranca si col.Simp.Nat.Endocrinol.1995,
Endocrinologie Clinica 1997
Clinical staging of differentiated thyroid cancer
Papillary and follicular
Patients under 45 years old
Patients over 45 years old
STAGE I - any T, any N, M0
STAGE I - T1, N0, M0
STAGE II - any T, any N, M1
STAGE II - T2 / T3, N0, M0
STAGE III - T4, N0,M0, any T,N1,M0
STAGE IV – any T, any N, M1
Clinical staging of medullary thyroid carcinoma
STAGE I - T1, N0, M0
STAGE II - T2 / T3 / T4 , N0, M0
STAGE III – any T, N1, M0
STAGE IV – any T, any N, M1
Treatment of diffentiated thyroid cancers
Surgery
• total thyroidectomy +control of lymph nodes
• loboistmectomy: only in microcarcinomas with low risk (young
age, female sex, well differentiated papillary
Complication:
• recurrent nerve palsy: 2-8 %
• hipoparathyroidism: 1-4 %
• intra or postoperative hemorrhage
Treatment of diffentiated thyroid cancers
Radioactive iodine -
131I
Indication (Schlumberger 2000)
- incomplete surgery
- compete surgery with risk of reccurence: less than 16 years or > 45 ani
- papillary variant less differentiated: columnar, diffuse sclerozing
- faollicular variant: invasive, less differentiated, Hurthle cell
- large tumors with capsular invasion
- Tiroglobulin over 3 ng/ml after 3 month of treatment
Ablative iodine therapy: 30 mCi or more if a certain volume of cancer tissue was
left in place
Iodine therapy after previous ablation: 100-150 mCi for local recurrences or
distant metastases
for children: 1 mCi/Kg bw
Treatment and follow up of differentiated thyroid cancers
Suppressive thyroxine treatment :
Follow Up:
• L-Thyroxine >/= 200 g/day
Tiroglobuline (IRMA)
• 2,1-2,8 g/Kg.bw/day
• for TSH < 0.1 UI/ml
Suppression is switched to
replacement dosage if there are not risk
factors, serum Tg levels are less than 1
ng/mL
after total thyrodectomy
• not detectable in 98 % of those with remission
• detectable in 5 % of those with reccurences
• in those with reccurences or metastases
increaeses after T4 withdrawal (56 %) of after rhTSH
(52%)
• errors: AAT tg.
• RT-PCR mARN for Tg
WBS: every 6-12 luni:
Protocol for hr TSH adminstration prior
diagnostic or therapeutic 131 Iodine
administration
0.9 mg hrTSH day 1 and 2
131 Iodine id given day 3
TG measurements in days 1-3-5
WBS in day 5
Tg < 10 ng/ml : 100 mCi2-5 mCi
Tg . 10 ng/ml: 100 mCi
For Tg + si WBS negativ: 18 F-FDG-PET
Treatment of diffentiated thyroid cancer
Total thyroidectomy
131 I ablation + WBS
3 month fT4:
FT3-TSH-Tg
Tg> 5 ng/ml
6-12 luni- stop T4
TSH/Tg
131 I WBS (2-5 mCi
Not
detectable
Yearly Tg
control on T4
Tg < 10 ng/ml
131I
Tg +
WBS ( 2-5 mCi)
Negative: repeat every 2-5
years
Tg > 10ng/ml
or WBS +
131I100
mCi
+WBS
DIFFERENTIATED THYROID CANCER
TREATMENT
1. THYROIDECTOMY AND LYMPH NODE DISSECTION
2. RADIOIODINE TREATMENT
3. HIGH DOSES OF THYROID HORMONE – LT4 TO SUPPRESS
TSH
4. INTERRUPTION OF THYROID HORMONE FOR 4 WEEKS TO
ALLOW TSH TO INCREASE AND TO STIMULATE IODINE
UPTAKE IN NEOPLASTIC CELLS
5. THYROGLOBULIN ASSESSMENT: IF > 10 ng/dL
6. THYROID AND WHOLE BODY SCANNING + RADIOIODINE
TREATMENT IF METASTASES OR LOCAL RECURENCE ARE
DETECTED
7.
THYROID HORMONE AT SUPPRESSIVE DOSES
Treatment and follow up of medullary thyroid cancers
Total
thyroidecotmy
Every 6 month
N
CEA,CT,Test
PG
Repeat
yearly
N
Repeat at 2
years
Stable.follow
CT<50
Repat yearly
Pg-CT<500
increased
No meta
CT>50
PG-CT>500
US,CT,RMIN
negatives
Immunoscintigraphy
Micrometa
Distant meta
PG – CT =N
Medical treat.
Repat
anually
Incomplete
surgery
Modigliani 2000
No tumor
Lymph
nodes meta
Repeat annually
MEN 2A or 2B
Patient with MTC (index case)
Germ line mutation of RET analysis
RET pozitive/hereditary
disease
RET negative
RET mutation analysis in
first degree relatives
PG-CT test
•RET positive
Negative
No other
investigation
needed
Surgery as soon
as possible if
some aggressive
mutation are
detected
Positive- surgery
Surgery postponed
No calcitonine
increase
Test PG-CT
Negative repeat
PG- CT every year
THYROID CANCER- SURVIVAL RATE
120
100
80
PAPILAR
FOLICULAR
60
MEDULAR
NEDIF
40
20
0
0
5ANI
10 ANI
15 ANI