Malattie autoimmuni della tiroide

Relative frequencies of different
autoimmune diseases
The management of the patient with unexpected
autoantibody positivity.
Sezioni Regionali del Veneto, Friuli Venezia Giulia e Trentino Alto Adige
Programma di Formazione Permanente
Corso Residenziale
M.Bagnasco, L.Grassia, G.Pesce Autoimmunity Reviews, 2007
La Diagnostica di Laboratorio
delle Malattie Autoimmuni Organo-Specifiche
SLE
Bassano del Grappa (VI)
7-9 ottobre 2009
T1D
APS
CD
AITD
Corrado Betterle, Fabio Presotto, Renato Zanchetta
QuickTime™ e un
decompressore
sono necessari per visualizzare quest'immagine.
Malattie autoimmuni della tiroide
TA = Tiroidite Autoimmune
MB = Morbo di Basedow
OB = Oftalmopatia di Basedow
TA
autoimmunità
Giampaola Pesce, Irene Bossert, Marcello Bagnasco
Marcello Bagnasco
Di.M.I. Università degli Studi di Genova
Dipartimento di Patologie Immunoendocrinologiche,
A.O.U. San Martino Genova
autoinfiammazione
OTHERS
RA
AUTOANTICORPI ANTI-TIROIDE
Rare monogenic Autoinflammatory Diseases:
FMF, TRAPS, HIDS, PAPA
Blau’s Syndrome (Uveitis)
Polygenic Autoinflammatory Diseases:
Crohn’s Disease, Ulcerative Colitis
Self-limiting inflammatory arthritis including diseases clinically presenting as RA
Storage diseases/Congenital diseases with associated tissue inflammation
Non-antibody associated vasculitis including Giant Cell and Takayasu’s arteritis
Idiopathic Uveitis
Acne and Acneform associated diseases
Some neurological diseases eg. Acute disseminated encephalomyelitis
Erythema Nodosum associated disease, including Sarcoidosis
Mixed Pattern Diseases with evidence of acquired component (MHCI associations) and
autoinflammatory components:
Ankylosing Spondylitis
Reactive Arthritis
Psoriasis
Behcet’s Syndrome
Uveitis (HLA-B27 associated)
Classic Polygenic Autoimmune Diseases (Organ Specific and Non Specific):
Rheumatoid Arthritis
Autoimmune Uveitis (Sympathetic Ophthalmia)
Coeliac disease
Primary biliary Cirrhosis
Autoimmune gastrittis/pernicious anaemia
Autoimmune Thyroid Disease, Addison’s Disease,
Pemphigus, Pemphigoid, Vitiligo
Myasthenia Gravis, Dermatomyositis/polymyositis/scleroderma
Goodpasture’s Syndrome
ANCA associated Vasculitis
Type 1 diabetes
Cogan’s Syndrome
Sjogren’s Syndrome
Systemic Lupus Erythematosus
Rare Monogenic Autoimmune Disease: ALPs,Ipex, APECED
SS
MB
OB
Ipertiroidismo
Ipotiroidismo
da McGonagle e McDermott
1
TIROIDITE AUTOIMMUNE
DIAGNOSI DI TIREOPATIE AUTOIMMUNI:
PROBLEMI CLINICI ?
PROGRESSIONE
VERSO
L’IPOTIROIDISMO
VARIANTE
“classica” (hashimoto)
lenta, talora assente o
transitoria
atrofica
permanente
post-partum, “silente”
di solito transitoria (precede
fase iper)
focale
assente
IPERTIROIDISMO
OFTALMOPATIA
(MPC,ACROPACHIA)
IPOTIROIDISMO
SUBCLINICO
IPOTIROIDISMO
CONCLAMATO
SINDROMI POLIAUTOIMMUNI
NEOPLASIA ?
IN MOLTI CASI
PROBLEMI
TRASCURABILI !
Received 30-Jul-09; Returned for Revision 16-Aug-09; Finally Revised
12-Sep-09; Accepted 15-Sep-09
LETTER TO THE EDITOR
Levothyroxine in subclinical
hypothyroidism: a lifelong therapy?
Pedro Weslley Rosario
Subclinical hypothyroidism (SCH) is a frequent condition in
clinical practice. In patients with persistently TSH > 10
mIU/L, the risk of progression to overt hypothyroidism (OH)
is high, whereas spontaneous normalization of TSH only
occurs in exceptional cases.1,2 In contrast, during SCH with
TSH ≤ 10 mIU/L both progression to OH and spontaneous
TSH normalization are observed……. 2/3 of cases have
spontaneous TSH normalization within the first 2 years after
diagnosis….
Patients with autoimmune
thyroid diseases
184
Autoimmune
thyroiditis
81 (28%)
Other autoimmune
features
288
patients
104
Graves’ disease
69 (24%)
Other
autoantibodies
138 (48%)
Single autoimmune
disease
Type III APS
Betterle et al. 2001
SINDROMI POLIAUTOIMMUNI
Quando ricercarle?
M. di Addison autoimmune: SEMPRE
POF aut.: SEMPRE
Tireopatie autoimmuni:
in prenza di dati clinico- anamnestici
significativi anche minori.
2
Cancro tiroideo ed Autoimmunità
~ Bagnasco M et al. Phenotypic and functional analysis at the clonal
level of infiltrating T- lymphocytes in papillary carcinoma of the
thyroid. JCEM 1989; 69: 832-6
~ Singh B et al. Coexistent Hashimoto’s thyroiditis with papillary
thyroid carcinoma: impact on presentation, management, and
outcome. Surgery: 1999;126: 1070-7
~ Kollur SM et al. Follicular thyroid lesions coexisting with
Hashimoto's thyroiditis: incidence and possible sources of
diagnostic errors. Diagn Cytopathol. 2003;28(1):35-8.
Fiore E, Rago T, Scutari M, Ugolini C, Proietti A, Di Coscio G,
Provenzale MA, Berti P, Grasso L, Mariotti S, Pinchera A, Vitti P.
Papillary thyroid cancer, although strongly
associated with lymphocytic infiltration on
histology, is only weakly predicted by serum thyroid
auto-antibodies in patients with nodular thyroid
diseases. J Endocrinol Invest. 2009 Apr;32(4):344-51.
Fiore E, Rago T, Provenzale A, Scutari M, Ugolini C, Basolo F, Di
Coscio G, Berti P, Grasso L, Elisei R, Pinchera A, Vitti P.
Lower levels of TSH are associated to a lower risk
of papillary thyroid cancer in patients with thyroid
nodular disease: thyroid autoimmunity may play a
protective role.
Endocr Relat Cancer. 2009 Jun 15.
Journal of Autoimmunity 32 (2009) 231–239
The etiology of autoimmune thyroid
disease:
A story of genes and environment
Yaron Tomer, Amanda Huber
Thyroid Autoimmunity and Environment
M. L. Tanda1, E. Piantanida1, A. Lai1, V. Lombardi1, I. Dalle Mule1, L. Liparulo1,
N. Pariani1, L. Bartalena
… Autoimmune thyroid diseases arise due to complex interactions
between environmental and genetic factors. Significant progress
has been made in our understanding of the genetic and
environmental triggers contributing to AITD. However, the
interactions between genes and environment are yet to be defined.
Among the major AITD susceptibility genes that have been
identified and characterized is the HLA-DR gene locus, as well as
non-MHC genes including the CTLA-4, CD40, PTPN22,
thyroglobulin and TSH receptor genes. …
Horm Metab Res 2009; 41: 436-442
Autoimmune thyroiditis:
A story of chronic inflammation, cytokine/chemokines,
cell-mediated damage, autoantibodies…
Tiroidite autoimmune “classica”:
• abbondante infiltrato linfocitario (Th1 > Th2)
• morte dei tireociti per apoptosi
• importanza patogenetica di citochine Th1 – derivate, APC – derivate
• ruolo patogenetico di autoanticorpi?
• Treg? Th17?
Graves’ Disease:
A story of TSH-receptor stimulating autoantibodies…
M. di Basedow / oftalmopatia basedowiana:
• infiltrato linfocitario presente, di entità variabile (Th1 / Th2?)
• scarsa apoptosi dei tireociti, marcata apoptosi dei linfociti T
infiltranti
• ruolo patogenetico preminente degli autoanticorpi anti –
recettore TSH
Tiroidite atrofica (alcune forme):
• ruolo patogenetico di autoanticorpi anti – recettore TSH “bloccanti”
bloccanti”
Thyroid. 2001 Giordano C, Richiusa P,
Bagnasco M, et all
Science. 1997 Giordano C, Stassi G, De
Maria R, Todaro M, Richiusa P, Papoff
G, Ruberti G, Bagnasco M, Testi R,
Galluzzo A.
Thyroid. 2001 Giordano C, Richiusa P,
Bagnasco M, et all
3
Tireopatie Autoimmuni:
Sistemi AutoAntigene-Anticorpo
J Clin Endocrinol Metab,
February 2009, 94(2):442–448
Pendrin Is a Novel Autoantigen Recognized by
Patients with Autoimmune Thyroid Diseases
Akio Yoshida, Ichiro Hisatome, Shinichi Taniguchi, Yasuaki Shirayoshi,Yasutaka
Yamamoto, Junichiro Miake, Tsuyoshi Ohkura, Takeshi Akama, Osamu Igawa,Chiaki
Shigemasa, Keiichi Kamijo, Shoichiro Ikuyama, Patrizio Caturegli, and Koichi Suzuki
•Tireoperossidasi
•Tireoglobulina
•Recettore TSH
•NIS
•Pendrina
…Pendrin antibodies correlated
significantly with thyroglobulin,
thyroperoxidase, and sodium iodide
symporter antibodies but not with TSH
receptor antibodies. Pendrin antibodies
were equally effective as thyroglobulin and
thyroperoxidase antibodies in diagnosis of
autoimmune thyroid diseases, especially
Hashimoto’s thyroiditis…
METODI DI DOSAGGIO
DEGLI AUTOANTICORPI ANTI-M/TPO
Estienne, et al. J Biol Chem 1999; 274: 35313-7
Hobby et al. Endocrinology 2000; 141: 2018-26
Prima generazione (Anti/M)
Fissazione del complemento (FC)
Trotter et al, 1957
Agglutinazione passiva di eritrociti (PHA) o lattice (LAP)
Immunofluorescenza indiretta (IIF)
Immunoenzimatico (ELISA)
Fujita et al, 1970
Doniach, 1967
Radiobinding e Radioimmunologico (RIA)
Immunoradiometrico (IRMA)
Caratteristiche molecolari
del dominio extramembrana di TPO
Mori et al, 1971
Mariotti et al, 1983
Dominio N-terminale (AA 1-141)
Dominio MPO-simile (AA 142738) Identità: 46%, Analogia: 71% con
mieloperossidasi
N-terminale
MPOsimile
Goodburn et al, 1981
Seconda generazione (Anti-TPO)
Immunometrico (IRMA) (TPO marcata in fase solida)
Mariotti et al, 1987
Immunologico (RIA, LIA) competitivo (TPO marcata libera)
Ruf et al, 1987
Immunometrico (IRMA, IEMA) (proteina A libera marcata)
Furmaniak et al, 1987
Immunologico competitivo (RIA, EIA) (prot. A fase solida) Beever et al, 1989
fattore H del complemento: modulo CCP
Kendler et al, 1990
Immunometrici (IEMA, ILMA) automatizzati (TPO adesa)Bohuslavizki et al, 2000
Anticorpi anti-tireoperossidasi
(Anti-TPO, TPOAbs)
Sottoclassi: IgG1-IgG4
Ruolo patogenetico ?
a) attività citotossica destruente (attivazione di complemento e
mediazione di ADCC). Rodien P , JCEM 1996, Guo J, JCEM 1997
CCP-simile
2 ponti S-S: dominio sushi
Dominio EGF-simile (AA: 796841)Identità 36%; analogia 62% con
Terza generazione (Anti-TPO)
Immunometrici (IRMA, IEMA, ILMA) manuali (TPO adesa)
Dominio CCP-simile (AA 739795) Identità 21%; analogia 48% con
EGF-simile
fibrillina: modulo EGF
3 ponti S-S
A role for autoantibodies in enhancement of
pro-inflammatory cytokine responses to a
self-antigen, thyroid peroxidase
Claus H. Nielsen, Thomas H. Brix, R.
Graham Q. Lesliec, Laszlo Hegedüsb
Clin. Immunol. 2009
b) coinvolgimento nella presentazione autoantigenica. Guo J, Clin
Exp Immunol 2000
c) Aumento del rilascio di citochine proinfiammatorie indotto da TPO
Nielsen C, Clin Immunol 2009
Policolonalità, eterogeneità molecolare: profili o 'fingerprints' epitopici
(Nishikawa T, JCEM 1994), trasmessi geneticamente (Jaume JC, JCEM
1995)
Anticorpi anti-epitopo 742-848 specifici per Hashimoto, non per Greaves
(Estienne V, JBC 1999)
4
Prevalence of positive antianti-TPO by passive
agglutination (PA) and RIA in autoimmune and
nonautoimmune thyroid disease and normal
controls
UK Guidelines for the Use of Thyroid Function Tests, 2006
Association for Clinical Biochemistry, British Thyroid
Association, British Thyroid Foundation
Laboratory Tests Used to Determine the Cause of Thyroid Dysfunction
THYROID PEROXIDASE ANTIBODIES (TPOAb)
These are present in the serum of patients with a wide range of
immunologically mediated thyroid disorders …
They may also be found in a small proportion of apparently healthy
individuals but the appearance of TPOAb usually precedes the
development of thyroid disorders.
The measurement of TPOAb is of clinical use: (III, B)
- In diagnosis of autoimmune thyroid disorders.
- As a risk factor for autoimmune thyroid disorders.
- As a risk factor for hypothyroidism during treatment with interferon
alpha,interleukin-2 or lithium.
- As a risk factor for thyroid dysfunction during lithium amiodarone
therapy.”
100
80
%
60
PA
RIA
40
20
0
Graves’
Graves’
disease
Autoimmune Non autoimmune Normal
thyroiditis thyroid disease controls
From Mariotti et al 1990, 1994
UK Guidelines for the Use of Thyroid Function Tests, 2006
Association for Clinical Biochemistry, British Thyroid Association,
British Thyroid Foundation
TPO Ab in normal subjects
Thyroglobulin Antibodies (TgAb)
Activation of
autoimmune
process
Antibodies to thyroglobulin (TgAb) are found in many patients
with autoimmune thyroid disorders; however, in most
circumstances TgAb measurements have no additional value
over the measurement of TPOAb and need not be done if T
POAb is present (IV). TgAb should be measured in patients
with differentiated thyroid cancer (IV).
TPO elevation
=
TSH elevation
mild”subclinical”
hypothyroidism
Genetic
predisposition
FT4decrease
= clinical
hypothyroidism
Environmental Factor(s)
• In iodine sufficient areas it is of no value to measure both TgAb and
TPOAb in non-neoplastic conditions. (III,B)
• The only reasons to measure Tg antibodies are i) in differentiated
thyroid cancer to determine possible interference from these
antibodies in immunoassays for thyroglobulin. ii) Serial
measurements may prove to beuseful as a prognostic indicator.
5%
per years
(III,B)
Age
Autoantibody profiling of patients with
autoimmune thyroid disease using a new
multiplexed immunoassay method
Sensibilita’ diagnostica di TGA e TPO
Tozzoli R., Villalta D., Kodermaz G., Bagnasco M., Tonutti
E., and Bizzaro N.
Clin Chem Lab Med 2006;44(7):837-842
95,6
100
sensibilità %
90,1
80
63,5
60
40
20
6,6
0
TPOAb+
TgAb+
TgAb+/TPOAb-
4,4
TgAb/TPOAb+
TgAb-/TPOAb-
classi di pz
5
AACE/AME/ETA Thyroid nodules
guidelines (2009 edition-in preparation)
LABORATORY EVALUATION OF PATIENTS WITH THYROID
NODULES
Always measure TSH
… if TSH is elevated measure free T4 and TPOAb (grade C:1)
TgAb determination show be restricted to patients with US and
clinical findings suggestive of chronic lymphocytic thyroiditis
when TPOAb level is normal (grade C:1)
TPO Ab e Tg Ab:
standardizzazione dei risultati
• Standards primari da rinnovare
• Standards secondari poco paragonabili
• Cut off points non paragonabili tra
metodiche
• U.I.= U.A.??
• Determinazione della sensibilità?
(N.B. per TgAb)
Tireopatie Autoimmuni:
Sistemi AutoAntigene-Anticorpo
•Tireoperossidasi
•Tireoglobulina
•Recettore TSH
•NIS
•Pendrina
TSH receptor autoantibodies
Michalek K, Morshed SA, Latif R, Davies TF. Autoimmun Rev 2009
Anticorpi anti-TSHR: ad attività stimolante (TSAb), ad attività bloccante
(TBAb), ad attività neutra
Distinct but overlapping TSH and TRAb binding sites
Rapoport B, McLachlan SM. Thyroid 2007
II
generazione
I TRAb sono IgG a bassa concentrazione, oligoclonali, prevalentemente
IgG2, dirette verso diversi epitopi
Epitopi immunodominanti conformazionali, come piccoli (5-12 aa),
discontinui e multipli punti di contatto sulla superficie del recettore
per TSAb: regione aminoterminale (22-80), ma anche carbossiterminale
(360-418): domini A-E
per TBAb: regione carbossiterminale (AA 262-360): domini C-D
per TSH: regione centrale (AA 170-360): domini C-D-E
III
generazione
6
METODI CONVENZIONALI DI DOSAGGIO
DEGLI AUTOANTICORPI ANTI-TSHR (TRAb)
Autoanticorpi inibenti il legame del
TSH (TBIAb)
Autoanticorpi stimolanti la
funzione (TSAb)
Metodi recettoriali di I generazione
(RRA, ERA)
TSHR porcini solubilizzati
Metodi biologici
cellule FRTL-5, CHO transfettate
Produzione di AMP ciclico
Metodi recettoriali di II generazione
(RRA, LRA)
TSHR umani ricombinanti
Anticorpi monoclonali adesi
Autoanticorpi bloccanti l’azione del
TSH (TBAb)
Metodi recettoriali di III generazione
(ELISA)
TSHR umani purificati
Anticorpi monoclonali M22
biotinilati
Metodi biologici
cellule FRTL-5, CHO transfettate
Produzione di AMP ciclico
TRAb: metodi di dosaggio
commerciali di III generazione
Produttore
Formato
Tempo
Coniugato
Metodo
Metodi ad automazione parziale
Euroimmun
Micropiastra
120’
M22-biotina-streptavidinaperossidasi
ELISA
Radim
Micropiastra
210’
M22-biotina-streptavidinaperossidasi
ELISA
Pantec
Micropiastra
210’
M22-biotina-streptavidinaperossidasi
ELISA
Medipan
Micropiastra
210’
M22-biotina-streptavidinaperossidasi
ELISA
Roche (ElecsysModular)
Microparticell
e
27’
M22-rutenio
CLIA
RAD 120
Microparticell
e magnetiche
210’
M22-fosfatasi alcalina
(4-MUP)
FIA
Metodi ad automazione totale
7
Casistica studio policentrico:
Latisana, Pordenone, Genova
(n. 520)
Risultati dello studio:
la distribuzione dei valori
10
9
8
7
6
5
4
3
2
1
0
Correlazione tra metodi (IIIG vs IIG)
(n. 114)
GD
Hyper-P
Hyper-L
Eu
TGD
UK Guidelines for the Use of Thyroid Function Tests, 2006
Association for Clinical Biochemistry, British Thyroid Association,
British Thyroid Foundation
TSH Receptor Antibodies (TSH-RAb)
In most patients the measurement of TSH-RAb is not an
essential investigation for diagnostic purposes.
The measurement of TSH-RAb is particularly useful in
pregnancy and may also be helpful l in the following
situations:
• To investigate hyperthyroidism of uncertain aetiology
(IV,C)
• To investigate patients with suspected euthyroid Graves’
opthalmopathy (IV,C)
• For pregnant women with a past or present history of
Graves Disease (IV,C)
• To identify neonates with transient hypothyroidism due to
TSH blocking antibodies (IV,C)
Subclinical hypothyroidism (serum TSH concentration above the upper limit
of the reference range with a normal free T4) has been shown to be
associated with an adverse outcome for both the mother and offspring. T4
treatment has been shown to improve obstetrical outcome but has not been
proved to modify long-term neurological development in the offspring.
However, given that the potential benefits outweigh he potential risks, the
panel recommends T4 replacement in women with subclinical
hypothyroidism. For obstetrical outcome, USPSTF recommendation level is
B; evidence is fair. For neurological outcome, USPSTF recommendation
level is I; evidence is poor.
J Clin Endocrinol Metab 92: S1-S47, 2007
Women with thyroid autoimmunity who are euthyroid in the
early stages of pregnancy are at risk of developing
hypothyroidism and should be monitored for elevation of TSH
above the normal range. USPSTF recommendation level is A;
evidence is good (GRADE 1)
J Clin Endocrinol Metab 92: S1-S47, 2007
8
Subclinical hypothyroidism (serum TSH concentration above the upper
limit of the reference range with a normal free T4) has been shown to
be associated with an adverse outcome for both the mother and
offspring. T4 treatment has been shown to improve obstetrical
outcome but has not been proved to modify long-term neurological
development in the offspring. However, given that the potential
benefits outweigh he potential risks, the panel recommends T4
replacement in women with subclinical hypothyroidism. For obstetrical
outcome, USPSTF recommendation level is B; evidence is fair. For
neurological outcome, USPSTF recommendation level is I; evidence is
poor.
TRAb (either TSH receptor-stimulating or -binding antibodies) freely cross
the placenta and can stimulate the fetal thyroid. These antibodies should be
measured before pregnancy or by the end of the second trimester in mothers
with current Graves’ disease, with a history of Graves’ disease and treatment
with 131I or thyroidectomy, or with a previous neonate with Graves’ disease.
Women who have a negative TRAb and do not require ATD have a very low
risk of fetal or neonatal thyroid dysfunction. USPSTF recommendation level
is B; evidence is fair (GRADE 1 ).
J Clin Endocrinol Metab 92: S1-S47, 2007
J Clin Endocrinol Metab 92: S1-S47, 2007
Although a positive association exists between the presence of thyroid
antibodies and pregnancy loss, universal screening for antithyroid
antibodies and possible treatment cannot be recommended at this
time.
As of this date, only one adequately designed intervention trial has
demonstrated a decrease in the miscarriage rate in thyroid antibodypositive euthyroid women. USPSTF recommendation level is C;
evidence is fair (GRADE 2).
J Clin Endocrinol Metab 92: S1-S47, 2007
1.
2.
3.
4.
5.
Stagnaro-Green,1990
Glinoer, 1991
Lejeune, 1993
Iijima, 1997
Bagis, 2001
% di aborti ricorrenti
precoci e positività degli
autoanticorpi anti-tiroide
1.
2.
3.
4.
5.
6.
7.
Pratt, 1993
Bussen, 1995
Roberts, 1996
Bussen, 1997
Esplin, 1998
Kutteh, 1999
Dendrinos, 2000
50
45
40
35
30
25
20
15
10
5
0
40
35
% aborti
% di aborti spontanei e
positività degli
autoanticorpi anti-tiroide
% aborti
Autoimmunità tiroidea e aborto
30
25
20
15
*
Autoanticorpi
anti-tiroide +
Autoanticorpi
anti-tiroide -
*
*
*
*
*
*
*
*
*
Autoanticorpi antitiroide +
Autoanticorpi antitiroide -
10
5
0
Subclinical hypothyroidism and thyroid autoimmunity
in women with infertility.
Marcos Abalovich; Laura Mitelberg; Carlos Allami; Silvia Gutierrez ;
Graciela Alcaraz; Patricia Otero; Oscar Levalle
CONCLUSIONS: We observed a higher prevalence of SH, but not of TAI, in
patients with infertility. Our results support thyroid screening in women with
reproductive failure.
J Clin Endocrinol Metab 91: 2587-91, 2006
Gynecol Endocrinol 2007; 23: 279-83
9
POSTPARTUM THYROIDITIS
There are insufficient data to recommend screening of all
women for PPT.
USPSTF recommendation level is I; evidence is poor.
J Clin Endocrinol Metab 92: S1-S47, 2007
1. Women with a history of hyperthyroid or hypothyroid disease, PPT,
or thyroid lobectomy.
2. Women with a family history of thyroid disease.
3. Women with a goiter.
4. Women with thyroid antibodies (when known).
5. Women with symptoms or clinical signs suggestive of thyroid
underfunction or overfunction, including anemia, elevated
cholesterol, and hyponatremia.
J Clin Endocrinol Metab 92: S1-S47, 2007
Take-home messages
• Il dosaggio degli autoanticorpi anti tiroide
rappresenta quantitativamente una quota importante
del lavoro del laboratorio di autoimmunità
Although the benefits of universal screening for thyroid dysfunction
(primarily hypothyroidism) may not be justified by the current
evidence (presented above), we recommend case finding among
the following groups of women at high risk for thyroid disease by
measurement of TSH:
J Clin Endocrinol Metab 92: S1-S47, 2007
6. Women with type I diabetes.
7. Women with other autoimmune disorders.
8. Women with infertility who should have screening with TSH as
part of their infertility work-up.
9. Women with previous therapeutic head or neck irradiation.
10. Women with a history of miscarriage or preterm delivery.
USPSTF recommendation level is B;
evidence is fair (GRADE 1).
J Clin Endocrinol Metab 92: S1-S47, 2007
Take-home messages
• Il dosaggio dei TgAb ha valore sussidiario (ma non
inesistente) nella diagnostica autoimmunologica
• il problema del suo corretto posizionamento nel
percorso diagnostico del paziente con tireopatia è
rilevante sul piano clinico e organizzativo
• un valore diagnostico aggiuntivo dei “nuovi”
autoanticorpi non è tuttora provato
•Il dosaggio dei TPOAb è un indicatore sensibile ma
non strettamente specifico di tireopatia autoimmune
in atto e un buon marcatore predittivo
• il dosaggio dei TRAb ha raggiunto livelli di elevata
performance con più metodiche commercialmente
disponibili e costituisce un marcatore diagnostico e
probabilmente di follow-up del Morbo di Basedow
10