thyroperoxidase and thyroid autoimmunity …les auto-anticorps anti-thyroperoxydase seriques dans la...
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Thyroperoxidase and Thyroid Autoimmunity
Thyroperoxydase et auto-immunite thyroidienne
Proceedings of the International Symposium on Thyroperoxidase and Thyroid Autoimmunity, held i n Marsei l le (France), June 28-30,1990
Sponsored by the Institut Nat ional de l a Sante et de l a Recherche Medicale ( INSERM)
Edited by
Pierre Carayon Jean Ruf
LES EDITIONS rr\
1MBRM öö
BH John Libbey E U R O T E X T
LONDON PARIS
Contents S o m m a i r e
V Preface V I Preface VI I Acknowledgments VI I I R e m e r c i e m e n t s
M O L E C U L A R B I O L O G Y A N D R E G U L A T I O N B I O L O G I E M O L E C U L A I R E E T R E G U L A T I O N
3 S. K imura Structure and regulation of the human thyroid peroxidase gene S t r u c t u r e et r e g u l a t i o n du g e n e de l a thyroperoxydase h u m a i n e
11 M . J . Abramowicz, D. Christophe and G. Vassart Regulation of the T P O gene transcription R e g u l a t i o n de l a t r a n s c r i p t i o n d u gene de l a T P O
17 K.D. Kaufman, S. Filetti, P. Seto and B. Rapoport Expression of recombinant, enzymatically-active, human thyroid peroxidase i n eukaryotic cells E x p r e s s i o n d ' u n e thyroperoxydase h u m a i n e r e c o m b i n a n t e a c t i v e dans les c e l l u l e s eucaryotes
25 H. Francis-Lang, M. Price, U. Martin and R. D i Lauro The thyroid specific nuclear factor, TTF-1, binds to the rat thyroperoxidase promoter L e f a c t e u r n u c U a i r e t h y r o i d i e n T T F - 1 se fixe sur le p r o m o t e u r de l a thyroperoxydase de r a t
33 B. Corvilain, C. Gerard, Raspe, A. Lefort, J . Mockel, J . Van Sande and J . E . Dumont Hormonal regulation of iodination R e g u l a t i o n h o r m o n a l e de V i o d a t i o n
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43 L. Chiovato, P. Vltti, C. Mammoli, F. Santini, M. Tonac-chera, P. Lapi , P. Cucchi, P. Carayon and A. Pinchera Regulation by T S H and thyroid st imulat ing antibodies of TPO expression R e g u l a t i o n de Vexpression de l a T P O p a r l a T S H et les a n t i c o r p s s t i m u l a n t de l a t h y r o i d e
53 R. Zarril l i , S. Formisano and B. D i Jeso Thyroglobulin, thyroid peroxidase and iodide carrier display diffe-rent sensitivities to hormonal induction and to neoplastic trans-formation L a t h y r o g l o b u l i n e , l a thyroperoxydase et le t r a n s p o r t e u r d ' i o d e m o n t r e n t des s e n s i b i l i t e s differentes ä V i n d u c t i o n h o r m o n a l e et ä l a t r a n s f o r m a t i o n m a l i g n e
55 P.S. Barnett, B. Bhatt, A. Pagliuca, G. Mufti, A.M. Mc Gregor and J.P. Banga The thyroid peroxidase gene : accurate localisation by non-isoto-pic in s i t u hybridisation to chromosome 2 p l 3 L e g e n e de l a thyroperoxydase : sa l o c a l i s a t i o n p r e c i s e s u r le c h r o m o s o m e 2 p l 3 p a r h y b r i d a t i o n i n s i tu non i s o t o p i q u e
S T R U C T U R E A N D F U N C T I O N S T R U C T U R E E T F U N C T I O N
59 B. Czarnocka, J . Ruf, M. Ferrand and P. Carayon Immunochemical properties of h T P O P r o p r i e t e s i m m u n o - c h i m i q u e s de l a T P O h u m a i n e
69 A.B. Rawitch, G. Pollock, S.X. Yang and A. Taurog The location and nature of the N- l inked Oligosaccharide units i n porcine thyroid peroxidase : studies on the tryptic glycopeptides N a t u r e et l o c a l i s a t i o n des unitös N - o l i g o s a c c h a r i d i q u e s dans l a thyroperoxydase p o r c i n e : etudes s u r les g l y c o p e p t i d e s trypsiques
77 M. Nakamura, I. Yamazaki and S. Ohtaki Thyroperoxidase selects either one-or two- electron oxidations of iodotyrosine and thyroglobulin, depending on their iodine contents L a t h y r o p e r o x i d a s e s e l e c t i o n n e des o x y d a t i o n s de t y r o s i n e iodee et de t h y r o g l o b u l i n e ä un ou deux älectrons s u i v a n t l e u r c o n t e n u en iode
85 A. Taurog Thyroid peroxidase as the target for the mechanism of action of the thioureylene antithyroid drugs
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L a t h y r o p e r o x y d a s e c o m m e c i b l e d u m e c a n i s m e d ' a c t i o n des d r o g u e s a n t i - t h y r o i d i e n n e s deriv&es d u t h i o u r a c i l e
95 C. Dupuy, A. Virion, J . Kaniewski, D. Derne and J . Pommier Thyro id NADPH-dependent H 2 0 2 generating System : mechanism of H 2C>2 formation and regulation by C a 2 +
L e Systeme producteur d ' H 2 0 2 thyroidien N A D P H - d e p e n d a n t : mecanisme de la formation d'H2C>2 regule par Ca2*
103 Y. Long, J . L . Franc and A. Giraud Effect of deglycosylation on human and porcine thyroperoxidase activity Effet de l a d e g l y c o s y l a t i o n s u r V a c t i v i t e des t h y r o p e r o x y d a s e s h u m a i n e e t p o r c i n e
L O C A L I Z A T I O N A N D T R A F F I C L O C A L I S A T I O N E T T R A N S P O R T
107 L .E. Ericson, V. Johanson, J . Mölne, M. Nilsson and T. Ofverholm Intracel lular transport and cell surface expression of thyroperoxidase T r a n s p o r t i n t r a c e l l u l a i r e et expression s u r l a surface c e l l u l a i r e de l a t h y r o p e r o x y d a s e
117 B. Rousset, Z. Kostrouch, J . Pommier and Y. Munari-Silem Immunolocalization of functionnal thyroperoxidase and expression of thyroid cell differentiation I m m u n o l o c a l i s a t i o n de l a t h y r o p e r o x y d a s e f o n c t i o n n e l l e et express i o n de l a differenciation des c e l l u l e s t h y r o i d i e n n e s
127 P. Fragu, S. Halpern, J .C . Olivo and E . Kahn Microscopic imaging of human thyroid hormonosynthesis : digital correlation of ion and optical microscopic images I m a g e r i e m i c r o s c o p i q u e de l ' h o r m o n o s y n t h & s e t h y r o i d i e n n e h u m a i n e : c o r r e l a t i o n d i g i t a l e d ' i m a g e s o b t e n u e s p a r m i c r o s c o p i e op-t i q u e et i o n i q u e
133 C. de Micco, J . Ruf, M.A. Chrestian, N. Gros, J.F. Henry and P. Carayon TPO as marker of malignancy i n thyroid tumors : immunohisto-chemical study Etüde i m m u n o - h i s t o c h i m i q u e de l a T P O d a n s les t u m e u r s t h y r o i d i e n n e s : i n t e r e t c o m m e m a r q u e u r de m a l i g n i t e
137 D. Gruffat, S. Gonzalvez and O. Chabaud Long term iodination of thyroglobulin by porcine thyroid cells cul-tured i n porous bottom culture Chambers. Regulation by thyrotro-pin
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S u i v i de V i o d a t i o n de la t h y r o g l o b u l i n e p a r des c e l l u l e s t h y r o i -diennes p o r c i n e s c u l t i v e e s en c h a m b r e p o r e u s e . R e g u l a t i o n p a r l a t h y r o t r o p i n e
I N H E R I T E D D E F E C T S A N O M A L I E S C O N G E N I T A L E S
141 J . Leger, N. Hoog and P. Czernichow Iodine organification defect. Permanent and transient cases dia-gnosed early i n infancy Defaut de V o r g a n i f i c a t i o n de Viode. Cas p e r m a n e n t s et t r a n s i t o i r e s d i a g n o s t i q u e s p r e c o c e m e n t dans Venfance
149 J .J .M . De Vijlder, H . Bikker and T. Vulsma D N A polymorphisms i n the TPO gene and hereditary defects i n iodide organification P o l y m o r p h i s m e d u D N A dans le g e n e de l a T P O et defauts h e r e d i t a t e s dans V o r g a n i f i c a t i o n de Viode
157 G. Medeiros-Neto, A. Mangklabruks, N.J. Cox, D. Rosenthal, D.P. Carvalho-Guimaräes and L. J . DeGroot Defective expression of the thyroid peroxidase gene Expression defectueuse d u gene de la thyroperoxydase
165 M.T. den Hartog, B.E. Sjollema, A. Rijnberk, J . E . van Dijk and J . J .M . de Vijlder Loosely anchored peroxidase. A possible explanation for an iodide organification defect i n a hypothyroid cat A n c r a g e f a i b l e de la Peroxydase. Une e x p l i c a t i o n p o s s i b l e du defaut d ' o r g a n i f i c a t i o n de Viode chez un c h a t h y p o t h y r o i d i e n
C I R C U L A T I N G T P O L A T P O C I R C U L A N T E
169 T .J . Wilkin and J .L . Diaz Approaches to the measurement of T P O i n serum Tentatives de dosage de la T P O c i r c u l a n t e
173 U. Feldt-Rasmussen, M. Hoier-Madsen, J . Date and M. Bl i -chert-Toft Acute release of thyroid peroxidase dur ing subtotal thyroidectomy R e l a r g a g e a i g u de thyroperoxydase l o r s de l a t h y r o i d e c t o m i e subt o t a l e
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C H A R A C T E R I Z A T I O N O F T P O A U T O A N T I B O D I E S C A R A C T E R I S A T I O N D E S A U T O - A N T I C O R P S A N T I - T P O
I I I L . J . DeGroot Heterogeneity of human autoantibodies to T P O H e t e r o g e n e i t e des a u t o - a n t i c o r p s a n t i - T P O h u m a i n s
183 J . Ruf, M . Ferrand and P. Carayon Cross-reactivity between antibodies to thyroglobulin and thyroperoxydase R e a c t i v i t e c r o i s e e e n t r e a n t i c o r p s a n t i - t h y r o g l o b u l i n e et a n t i - t h y r o -p e r o x y d a s e
195 N. Fukuma, D. Sarsero, J . Furmaniak, C.A.S. Pegg, S.M. McLachlan and B. Rees Smith B and T cell epitopes on thyroid peroxidase E p i t o p e s de c e l l u l e s B e t T sur l a thyroperoxydase
203 R. Elisei, S. Swillens, G. Vassart and M. Ludgate Molecular characterization of thyroid peroxidase epitopes C a r a c t e r i s a t i o n des epitopes de l a thyroperoxydase au n i v e a u m o -l e c u l a i r e
209 R. Finke, P. Seto, M. Derwahl and B. Rapoport Identification of nine amino acids as the epitope for two monoclonal anti-peroxidase antibodies I d e n t i f i c a t i o n de neuf a c i d e s a m i n e s c o r r e s p o n d a n t ä un epitope r e c o n n u p a r deux a n t i c o r p s m o n o c l o n a u x a n t i - t h y r o p e r o x y d a s e
211 D.L. Ewins, J.P. Banga, R.W.S. Tomlinson, P.S. Barnett and A.M. McGregor Determination of epitope specificities of monoclonal antibodies to thyroid peroxidase us ing recombinant antigen preparations D e t e r m i n a t i o n des specificites epitopiques d ' a n t i c o r p s m o n o c l o n a u x a n t i - t h y r o p e r o x y d a s e au moyen de p r e p a r a t i o n s d'antigäne r e c o m b i n a n t
E F F E C T S O F T P O A U T O A N T I B O D Y O N T H E T H Y R O I D C E L L E F F E T S D E S A U T O - A N T I C O R P S A N T I - T P O S U R L A C E L -L U L E T H Y R O I D I E N N E
215 Y. Kohno, N. Naito, F. Yamaguchi, K. Saito, H. Ni imi and T. Hosoya Autoantibodies inh ib i t ing thyroid peroxidase enzyme activity : specificities of anti-thyroid peroxidase antibodies i n healthy sub-jects and patients w i th systemic lupus erythematosus
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L e s a u t o - a n t i c o r p s i n h i b i t e u r s de Vactivitä e n z y m a t i q u e de l a thyroperoxydase : specificitäs des a n t i c o r p s a n t i - t h y r o p e r o x y d a s e chez les sujets n o r m a u x et les p a t i e n t s a t t e i n t s de lupus e r y t h e m a t e u x
225 R. Winand and P. Wadeleux Is T P O the only thyroid antigen involved i n the complement de-pendent cytotoxicity ? L a T P O e s t - e l l e le seul a n t i g e n e t h y r o i d i e n i m p l i q u e dans l a cyto-t o x i c i t e dependante d u c o m p l e m e n t
233 U. Bogner, H . Peters and H. Schleusener Thyroid cytotoxic antibodies are not identical w i th thyroid micro-somal/peroxidase antibodies L e s a n t i c o r p s t h y r o i d i e n s c y t o t o x i q u e s ne sont p a s les a n t i c o r p s a n t i - m i c r o s o m e t h y r o i d i e n I a n t i - p e r o x y d a s e
C E L L U L A R I M M U N O L O G Y A N D E X P E R I M E N T A L M O D E L S I M M U N O L O G I E C E L L U L A I R E E T M O D E L E S E X P E R I M E N -T A U X
243 F. Akasu, Y. Kasuga, S. Matsubayashi, P. Carayon and R. Volpe Induction of C D 4 + T cells from autoimmune thyroid disease by thyroperoxidase (TPO) in v i t r o I n d u c t i o n i n vitro, p a r l a thyroperoxydase ( T P O ) , de c e l l u l e s T C D 4 + dans les cas de m a l a d i e s t h y r o i d i e n n e s a u t o - i m m u n e s
251 H. Tang, E . Baudin and J . Charreire Localization i n tryptic fragments from thyroglobulin of epitope(s) related to Hashimoto 1 s thyroiditis or experimental autoimmune thyroiditis L o c a l i s a t i o n , dans des f r a g m e n t s trypsiques de t h y r o g l o b u l i n e , d'öpitope(s) impliquä(s) dans la t h y r o i d i t e d f H a s h i m o t o ou d a n s l a t h y r o i d i t e e x p e r i m e n t a l e a u t o - i m m u n e
257 N. Yokoyama, A. Taurog, S. Alex, R. Rajatanavin and L .E. Braverman Do TPO antibodies play a role i n lymphocytic thyroiditis i n the BB/Wor rat ? L e s a n t i c o r p s a n t i - T P O j o u e n t - i l s un röle dans l a t h y r o i d i t e l y m -p h o c y t a i r e d u r a t B B / W o r ?
267 C M . Dayan, M. Londei, A .E. Corcoran, B. Rapoport and M. Feldmann Specific recognition of thyroid peroxidase by thyroid inf i l t rat ing T cell clones i n human autoimmune thyroiditis
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R e c o n n a i s s a n c e specifique de l a Peroxydase t h y r o i d i e n n e p a r des c l o n e s de c e l l u l e s T i n f i l t r a n t l a t h y r o i d e dans l a t h y r o i d i t e a u t o i m m u n e h u m a i n e
T P O A U T O A N T I B O D I E S I N H U M A N A U T O - A N T I C O R P S A N T I - T P O C H E Z L ' H O M M E
271 D.I.W. Phillips, L. Prentice, D. Sarsero, S.M. McLachlan, M. Upadhyaya, P.W. Lunt and B. Rees Smith Autoantibodies to thyroid peroxidase and thyroglobulin are inhe-r i ted as an autosomal dominant characteristic i n families not se-lected for autoimmune thyroid disease L e s a u t o - a n t i c o r p s a n t i - t h y r o p e r o x y d a s e et a n t i - t h y r o g l o b u l i n e s o n t t r a n s m i s c o m m e u n t r a i t c a r a c t e r i s t i q u e a u t o s o m i q u e d o m i n a n t d a n s des f a m i l i e s n o n selectionnees p o u r une m a l a d i e a u t o i m m u n e t h y r o i d i e n n e
275 S. Mariotti, P. Caturegli, G. Barbesino and A. Pinchera Serum anti-thyroid peroxidase autoantibody i n autoimmune thyroid disease L e s a u t o - a n t i c o r p s a n t i - t h y r o p e r o x y d a s e seriques dans l a m a l a d i e t h y r o i d i e n n e a u t o - i m m u n e
285 F. Doullay, J . Ruf, P. Carayon and J .L . Codaccioni Autoantibodies to thyroperoxidase i n various thyroid and autoimmune diseases L e s a u t o - a n t i c o r p s a n t i - t h y r o p e r o x y d a s e dans diverses m a l a d i e s t h y r o i d i e n n e s et a u t o - i m m u n e s
297 U. Feldt-Rasmussen, M. Hoier-Madsen, K. Bech, L. He-gedüs, H . Perri ld, H . Bliddal, B. Danneskiod-Samso, B. Ras-musson, N.J. Kriegbaum, K. Müller, A. Schouboe and E . Hippe Ant i -TPO antibodies i n non-thyroid autoimmune diseases L e s a n t i c o r p s a n t i - T P O dans les m a l a d i e s a u t o - i m m u n e s non thyr o i d i e n n e s
303 D. Glinoer, P. de Nayer, B. Lejeune, J . Kinthaert, J . Ruf, G. Servais and P. Carayon Ant i thyro id peroxidase antibodies i n normal pregnancy L e s a n t i c o r p s a n t i - t h y r o p e r o x y d a s e l o r s de grossesse n o r m a l e
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I N V E S T I G A T I O N O F T H Y R O I D A U T O I M M U N I T Y E X P L O R A T I O N D E L A U T O - I M M U N I T E T H Y R O I D I E N N E
315 H. Bornet, A.M. Madec, P. Rodien, R. Latter, P. Haond, H. Allannic and J . Orgiazzi Evaluat ion of ant i -TPO antibody determination i n various cl inical situations E v a l u a t i o n d u dosage des a n t i c o r p s a n t i - T P O dans differents cas c l i n i q u e s
321 R. Gutekunst, W. Hafermann, U. Lohrs and P.C. Scriba The value of ultrasonography i n the detection of lymphocytic thyroiditis Valeur de VEchographie dans le döpistage des t h y r o i d i t e s l y m p h o -c y t a i r e s
329 K. Weber and H. Schatz Autoantibodies to thyroid peroxidase and microsomal antigen i n autoimmune thyroid diseases L e s a u t o - a n t i c o r p s a n t i - t h y r o p e r o x y d a s e et a n t i - a n t i g e n e m i c r o s o m a l dans les m a l a d i e s t h y r o i d i e n n e s a u t o - i m m u n e s
331 L. Baldet, J . Faure and C. Jaffiol Auto-anticorps anti-thyroperoxydase (anti-TPO) en pathologie thyroidienne A n t i - t h y r o p e r o x i d a s e a u t o a n t i b o d i e s ( a n t i - T P O ) in t h y r o i d d i seases
333 P. Caron, T. Babin and M. Hoff Etüde comparative des methodes de dosage des auto-anticorps anti-thyroidiens en pathologie thyroidienne A n t i - t h y r o i d a u t o a n t i b o d i e s : c o m p a r a t i v e study in t h y r o i d d i seases
335 C. Massart, I. Guilhem, J . Gibassier, M. Nicol and H. Allannic Anticorps anti-thyroperoxydase et maladie de Basedow : interet dans l a surveillance du traitement par anti-thyroidiens de Synthese A n t i - t h y r o p e r o x i d a s e a n t i b o d i e s a n d G r a v e s ' disease : i n t e r e s t i n the f o l l o w - u p o f p a t i e n t s treated with a n t i - t h y r o i d d r u g s
337 C. Poustis-Delpont, S. Altare, S. Hieronimus, A.M. Guedj, M. Harter and P. Sudaka Evaluat ion d'une technique de dosage des anticorps ant i -thyroperoxydase par radiocompetition
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E v a l u a t i o n of a r a d i o c o m p e t i t i o n assay for a n t i - t h y r o p e r o x i d a s e a n t i b o d i e s
339 C. Schvartz, H . Larbre, B. Maes, M.J. Delisle and G. Del-tour Dosage des anticorps ant i -TPO et anti-microsomes dans diffe-rentes pathologies thyroi'diennes A n t i - T P O a n d a n t i - m i c r o s o m a l a n t i b o d y assays i n several t h y r o i d diseases
341 M. Izembart and G. Vallee Interet clinique de l a determination des anticorps anti-thyroperoxydase : resultats prel iminaires C l i n i c a l i n t e r e s t of a n t i - t h y r o p e r o x i d a s e a n t i b o d y : p r e l i m i n a r y re-s u l t s
343 Y. Ful la, L. Nonnenmacher and B. Weill Comparaison entre le dosage des anticorps anti-TPO en radioim-munologie et le dosage des anticorps anti-microsomes en immuno-fluorescence C o m p a r i s o n between r a d i o i m m u n o a s s a y o r a n t i - T P O a u t o - a n t i b o -dies a n d i n d i r e c t i m m u n o f l u o r e s c e n c e assay for a n t i - m i c r o s o m a l a n t i b o d i e s
345 S. Dimackie, P. Courriere, A. Boneu and G. Soula Interet du dosage des anticorps anti-recepteurs de l a T S H (TBII) dans l a maladie de Basedow Usefulness of a n t i - T S H receptor a n t i b o d y assay ( T B I I ) in G r a v e s ' disease
347 V.J.M. Pop, H.A.M. de Rooy, H.L. Vader and D.Van der Heide Prevalence of Postpartum thyroid dysfunction i n The Netherlands P r e v a l e n c e du d y s f o n c t i o n n e m e n t t h y r o i d i e n au c o u r s p o s t - p a r t u m aux P a y s - B a s
M I S C E L L A N E O U S D I V E R S
351 J.P. Banga, D.L. Ewins, P.S. Barnett, R.W.S. Tomlinson, D. Mahadevan, G.J. Barton, B.J. Sutton, J.W. Saldanha, E . Odell and A.M. McGregor Thyroid peroxidase autoantigen : localization of autoantigenic epitopes on recombinant protein and prediction of secondary structure U a u t o - a n t i g e n e thyroperoxydase : l o c a l i s a t i o n des Epitopes a u t o -antigäniques s u r l a p r o t e i n e r e c o m b i n a n t e et p r e d i c t i o n de l a s t r u c t u r e s e c o n d a i r e
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Thyroperoxidase and T h y r o i d Autoimmunity. Ed. P. Carayon, J . Ruf. Colloque INSERM/John Libbey Eurotext Ltd. © 1990. Vol. 207, pp. 321-327
The value of ultrasonography in the detection of lymphocytie thyroiditis
R. Gutekunst, W. Hafermann, U. Lohrs and P.C. Scriba
D e p a r t m e n t s of I n t e r n a l M e d i c i n e a n d P a t h o l o g y , M e d i c a l U n i v e r s i t y Lübeck, F R G
INTRODUCTION Lymphocytie t h y r o i d i t i s (LT) i s believed to be a rare disease i n Germany that i s not w e l l appreciated (13). The aim of t h i s study was to ^valuate d i f f e r e n t diagnostic procedures for the study of LT (10).
SUBJECTS and METHODS The Charts of 106 h o s p i t a l i z e d and arabulatory patients with LT treated between January 1984 and December 1987 were reviewed. The diagnosis of LT was based on p h y s i c a l examination and confirmatory findings i n at l e a s t two of the fo l l o w i n g four procedures: measurement of antimicrosomal antibodies [TPO(mic)]; TSH; u l t r a sonography (US) and f i n e needle a s p i r a t i o n cytology (FNA) of the thyr o i d . Only patients (n=92, 88 women, 4 men, age 11-81, mean age 47 yr) where a l l four diagnostic procedures were a v a i l a b l e , were included i n the study. C l i n i c a l manifestations were recorded; TPO(mic) was determined by immunofluorescence (20), TSH run i n duplicate by a supersensitive luminescence immunoassay (24), T4 and T3 were measured using com-mercial k i t s (Henning B e r l i n , FRG). Thyroid s i z e and raorphology were investigated by ultrasound using SRT, l i n e a r Mhz 5, General E l e c t r i c , Rancho Cordova, CA (9). Sonograms from population stud-ies were used as cont r o l s (8). In add i t i o n both t h y r o i d lobes were biopsied under Sonographie c o n t r o l with a f i n e needle (od, 0.6-0.7mm). The smears were a i r d r i e d and stained by the May-Grünwald-Giemsa technique f o r morphological evaluation.
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RESULTS
C l i n i c a l manifestations PERCENT n=92
NO SYMPTOMS 29.3 27 INCREASE IN WEIGHT 44.6 41 GOITRE 37.0 34 MENTAL COMPLAINTS 34.8 32 MYXEDEMA 23.9 22 PARAESTHESIA 19.6 18 FATIGUE 18.5 17 ARTHRALGIA 18.5 17 GLOBUS HYSTERICUS 17.4 16 EPIGASTRIC DISCOMFORT 15.2 14 ANAEMIA 11.9 11 DYSPHAGIA 8.7 8 HYPERCHOLESTEROLEMIA 6.5 6 THYROTOXICOSIS 6.5 6 TPO(mic) In 12 (13%) p a t i e n t s TPO(mic) were undetectable. TPO(mic) t i t e r s of 1:32 were found i n 5 (5.4%), 1:100 i n 11 (12%), 1:320 i n 19 (20.7%), 1:1000 i n 31 (33.7%) and >1:1000 i n 14 (15.2%) p a t i e n t s r e s p e c t i v e l y . The frequency d i s t r i b u t i o n i s s h i f t e d towards higher t i t e r s . TSH In 4 pati e n t s (4.3%) TSH serum l e v e l s were <0.3 uU/ml (normal ränge 0.3-3.9). Three of those p a t i e n t s had elevated T3, but only one of those three had an elevated serum T4 l e v e l . Forty-one (44.6%) p a t i e n t s had TSH l e v e l s 0.3-3.9, 26 (28.3%) 4-20, 14 (15.2%) >20 - 50, and 7 (7.6%) >50 uU/ml. Ultrasonography Thyroid volume: 43 (48.9%) women had normal t h y r o i d volume (<18ml, ränge 3-17.8, mean 12), and 45 (51.1.%) had enlarged glands (ränge 18.2- >140, mean 35.3). The four men had thyr o i d volume (normal >25ml) of 8, 23, 27 and 64 ml. Echopatterns: a l l except 5 (5.4%) p a t i e n t s had scattered sonolu-cent echopatterns. In 13 (14%) pa t i e n t s s o l i d nodules were de-tected. ( F i g . 1 A and B).
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Figure 1. Transverse sonograms of the th y r o i d (T): A. normal echopattern compared to the sonolucent muscles (M) from a healthy person.
B. sonolucent echopattern from a patient with LT.
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r
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Cytology T h i r t y (32.6%) patients had h y p e r c e l l u l a r sraears; 54 (58.7%) smears presented a scanty to moderate o v e r a l l c e l l u l a r i t y ; and 8 (8.7%) smears showed sparse lymphocytes and were not diagnostic for LT alone. Correlations There were no c o r r e l a t i o n s between the c e l l u l a r i t y of the smear f thyroid function and/or the TPO(mic) t i t e r .
DISCUSSION As i n previous studies (2, 12, 17, 18) we also found great c l i n i -c a l V a r i a t i o n . A quarter of the patients had no complaints or ph y s i c a l f i n d i n g s . Many Symptoms were nonspecific and subject to the i n d i v i d u a l bias of the physician. Determination of serum TPO(mic) i s not always conclusive f o r the diagnosis of LT. In t h i s study TPO(mic) were absent i n 13% and low i n 17.4% (<1:320), generally considered as negative (1). More than t h i r t e e n percent of a l l cases would have been missed without ultrasound and/or FNA. On the other hand, i n 2 - 20% of the healthy population TPO(mic) can be found without apparent t h y r o i d disease (1, 3 - 5, 7, 11, 21, 22); i n our area 3% (20). Our data c l e a r l y support the assumption, that serum findin g s only incom-p l e t e l y r e f l e c t t h y r o i d Status. Thyroid function i s poorly r e l a t e d to LT (2, 3, 12, 17, 18). The prevalence of hypothyroidism underestimates the prevalence of LT. Since TSH and TPO(mic) t i t e r s are poorly c o r r e l a t e d , the s e n s i t i v -i t y of the combination of elevated TSH and detectable TPO(mic) f o r detection of LT i n population studies must be even lower. Scintiscanning i s i m p r a c t i c a l and rather u n r e l i a b l e as a diagnostic t o o l f or LT, since the uptake of radionuclides depends on thyro i d function as w e l l as the iodine content of the gland (13). Although ultrasound does not d i f f e r e n t i a t e between LT and Graves' disease (6, 15, 19, 23), i t surely i s a use f u l t o o l f o r Screening i n unselected groups. I f a selected population of pa t i e n t s with t h y r o i d diseases i s considered, the s p e c i f i c i t y of ultrasound alone f o r detecting LT must be low, since t h i s group w i l l contain many patients with Graves 1 disease. However the combination of u l trasound and c l i n i c a l evaluation w i l l r e s u l t i n a high s p e c i f i c i t y even i n a selected group. FNA has a high diagnostic accuracy. I n t e r p r e t a t i o n of the varying amounts of lymphocytes i s however d i f f i c u l t (14). These f i n d i n g s could e i t h e r i n d i c a t e d i f f e r e n t LT diseases or merely r e f l e c t various inflammatory stages. I f only one lobe i s aspirated LT may be confused with f o c a l lymphocytic reactions, which are common i n endemic go i t r e s (16). Only i n rare instances can lymphocytes be found i n f o c a l sonolucent or s o l i d a l t e r a t i o n s . To confirm the d i agnosis of LT, FNA from one s i t e probably s u f f i c e s , i f the scan i s homogeneously sonolucent. Otherwise both lobes have to be a s p i rated. In conclusion, t h i s study confirms that sonography combined with c l i n i c a l evaluation i s rather s p e c i f i c f o r LT. Ultrasound addi-t i o n a l l y provides Information about the s i z e , topography and the nodularity of the th y r o i d . In cases where ultrasound i s performed p r i m a r i l y , one can proceed to further examinations. Otherwise, i t can support the laboratory and/or c l i n i c a l f i n d i n g s that suggest
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LT. When c l i n i c a l features are inconclusive LT can only be con-firmed by appropriate combination of s e r o l o g i c a l and morphological t e s t s . These conclusions have to be confirmed i n a prospective study.
SUMMARY The value of ultrasound (US) compared to established diagnostic procedures was in v e s t i g a t e d by r e t r o s p e c t i v e l y reviewing medical records of 92 patients (88 women and 4 men, age 11-81 y r , mean age 47 yr) with lymphocytic t h y r o i d i t i s (LT). C l i n i c a l manifestations of the disease, serum antimicrosomal antibodies and TSH were de-termined i n a l l p a t i e n t s . The t h y r o i d was examined by US. Both lobes were aspirated by a f i n e needle under Sonographie c o n t r o l and smears examined c y t o l o g i c a l l y . A t o t a l of 27 (29.3%) patients had no c l i n i c a l Symptoms. TPO(mic) were undetectable i n 12 (13%) patients, 16 (17.4%) had low t i t e r s 1:32-1:100, and 64 (69.6%) >1:320. TSH (normal ränge 0.3-3.9 uU/ml) was <0.3 i n 4 (4,3%), 0.3-3.9 i n 41 (44.6%), 4-20 i n 26 (28.3%), and >20 i n 21 (22.8%) cases. US revealed a scattered sonolucent echo i n 87 (94.6%) pat i e n t s , and i n 45 (48.9%) a normal th y r o i d volume (women <18, men <25 ml). Cytology was diagnostic i n 84 (91.3%) p a t i e n t s . In conclusion, US can suggest LT. I f TPO(mic) are undetectable or TPO(mic) t i t e r s are not s i g n i f i c a n t and/or c l i n i c a l Symptoms are uncertain, f i n e needle a s p i r a t i o n (FNA) can confirm the Sonographie f i n d i n g . LT can only be confirmed by appropriate combinat i o n of s e r o l o g i c a l and morphological t e s t s . F i n a l l y , LT s i obvi-ously be more common i n iodine d e f i c i e n t areas than generally as-sumed.
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14. Löwhagen, T. & Linsk, J . A. (1983) A s p i r a t i o n biopsy cytology of the thyr o i d gland. In C l i n i c a l a s p i r a t i o n cytology (eds J. A. Linsk & S. Franzen) pp 61-83. J . B. L i p p i n c o t t Company, London.
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21. Tanner, A. R. , Scott-Morgan, L., Mardell, R. & Lloyd, R. S. (1982) The incidence of occult t h y r o i d disease associated with t h y r o i d antibodies i d e n t i f i e d on routine autoantibidy Screening. Acta Endocrinologica 100, 31-35.
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24. Wood, W. G., Waller, D. & Hantke, U. (1985) An evaluation of s i x solid-phase t h y r o t r o p i n (TSH) k i t s . Journal of C l i n i c a l Chemestry and C l i n i c a l Biochemistry 23, 461-471.
Resume Line e t u d e r e t r o s p e c t i ve des d o s s i e r s med i c a u x de 92 p a t i e n t s (88 fernmes et 4 hommes, ages de 11 ä 81 a n s , moyenne d ' ä g e : 4 7 a n s ) , p r e s e n l a n t u n e t h y r o i d i t e 1 y m p h o c y t a i r e (LT) a p e r rn i s u n e c o m p a r a i s o n e n t r e le d i a g n o s t i c e t ab I i pa r u l t r a s o n s (US) e t un d i a g n o s t i c e t a b l i p a r des rnethodes h a b i t u e l l e s . Le s m a n i f e s t a t i o n s c l i r i i q u e s de l a m a l a d i e , l e s a n t i c o r p s a n t i - m i c r o s o m i a u x s e r i q u e s e t 1 a TSH o n t e t e eva l u e e s che/: t o u s l e s p a t i e n t s . Oes p r e l e v e m e n t s p a r a i g u i l l e f i n e s ou s c o n t r ö l e e c h o g r a p h i q u e on t e t e e f f e c t u e s s u r l e s l o b e s , e t un exarnen c y t o l o g i q u e a e t e e f f e c t u e s u r l e s p r e l e v e m e n t s . LI n t o t a l de 2 7 p a t i e n t s ( 2 9 . 3 % ) n e p r e s e n t a i e n t aucun a u c u n Symptome c 1 i n i q u e. La TPO n 1 e t a i t p a s d e c e l a b ' l e c h e z 12 p a t i e n t s ( 1 3 % ) , 16, ( 1 7 . 4 % ) p r e s e n t a i e n t une c o n c e n t r a t i o n b a s s e de TPO 1:32 - 1 :100 , e t 64 ( 6 9 . 6 % ) un t aux > 1 /320 . La TSH ( z o n e n o r m a l e 0 .3 - 3.9 u l l /m l ) e t a i t < 0 .3 dans 4 c a s ( 4 , 3 % ) , 0 .3 - 3.9 dans 41 ca s ( 4 4 . 6 % ) , 4 - 20 dans 26 c a s ( 2 8 . 3 % ) , e t > 20 dan s 21 c a s ( 2 2 . 8 % . Les US on t r e v e l e une r e p o n s e p o s i t i v e d i f f u s e c h e z 88 p a t i e n t s ( 9 4 . 6 % ) e t un vo l ume t h y r o i d i e n n o r m a l chez 413 s u j e t s ( 4 8 . 9 % ) (fernmes <18, hommes <25ml ) . Chez 84 p a t i e n t s ( 9 1 . 3 % ) , l e d i a g n o s t i c a pu e t r e c o n f i r m e pa r un exarnen c y t o l o g i q u e . En c o n c l u s i o n , l e s US l a i s s e n t s u p p o s e r une t h y r o i d i t e 1 y m p h o c y t a i r e . S i l e s a n t i c o r p s a n t i - T P O s o n t i n d e t e c t a b l e s ou p r e s e n t e n t des t i t r e s non s i g n i f i c a t i f s e t / o u s i l e s symptürnes c l i n i q u e s s o n t i n c e r t a i n s , une a s p i r a t i o n pa r a i g u i l l e f i n e p e u t c o n f i r m e r l e s r e su 1 t a t s e c h o g r a p h i q u e s . Les t h y r o i d i t e s 1 y m p h o c y t a i r e s p e u v e n t s e u l e m e n t e t r e con f i r m e e s pa r une c o m b i n a l s o n a p p r o p r i e e de t e s t s s e r o l o g i q u e s e t morpho l o g l q u e s . En c o n c l u s i o n , l e s t h y r o i d i t e s 1 yrnp hoc y t a i r e s s o n t p l u s r e p a n d u e s dans l e s z o n e s d e f i c i e n t e s en i o d e q u ' o n ne T a g e n e r a lernent s u p p o s e .
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