ETA: Nouvelles valeurs de reference pour la TSH ?

Beate
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Coucou,

je pense que le risque, en donnant du lévothyrox à quelqu'un qui n'en a pas besoin, est de rendre sa thyroide "faineante" ... elle produira moins d'hormones (puisque une partie sera apportée de l'extérieur), et risque de ne plus vouloir repartir si on l'arrête ... (mais comme apparemment, une grande partie des gens avec la TSH élevée finiront de toute façon par développer une hypo ... ce n'est peut-être pas si grave que ça, il leur faudra du Lévo un jour ou autre ...)

Avant de se jeter sur les hormones, on pourra peut-être (si on n'a pas d'anticorps et donc pas de maladie autoimmune - sinon, on s'en rendra assez vite compte par des symptômes d'intolérance) essayer de "booster" un peu la thyroïde en mangeant plus iodé que d'habitude: poisson, fruits de mer, algues etc au moins 2 fois par semaine ... dans certains cas, cela peut suffir pour la relancer, SANS la mettre au repos par le lévothyrox ...

Voilà, j'essayerai de grapiller d'autres informations à Buenos Aires !

Beate

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Merci, je file chez le poissonnier !
Cati

Beate
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Schilddrüsenpraxis - Newsletter de décembre 2005
www.schilddruesenpraxis.de (traduction CV/Beate)

Après "La guerre des étoiles" et "la guerre des mondes", maintenant la
"guerre des médecins", le combat pour de nouvelles références de TSH ?

Ca en a tout l’air :
Dans une newsletter américaine pour les patients thyroidiens (éditrice Mary Shomon), j'ai lu un article où l'on abordait un thème apparemment très controversé dans le monde médical américain. Shomon utilise dès le début de son article un vocabulaire martial. Dans le titre, il est question d’une «guerre autour des valeurs de référence de la TSH», dans l’introduction, elle dit qu’une «bataille fait rage au sein de la communauté des endocrinologues, concernant les valeurs de référence de la thyréostimuline (TSH)».

Qu'est-ce qui se cache là-dessous? Pour comprendre ce qui se passe, il faut revenir un peu en arrière.

Historique : en 2002, la National Academy of Clinical Biochemistry(NACB)
avait proposé de modifier les valeurs de référence de la TSH, c'est à dire de les passer à 0,4/2,5 (précédemment 0,4/4,0 mlUL) . A lire dans le guideline n° 27 : http://www.nacb.org/lmpg/thyroide/33thyroide.doc
Cette proposition se basait sur une vaste étude menée sur plusieurs années dans le cadre d’une NHANES (National Health and Nutrition Examination Survey). Ci-après, un résumé des résultats les plus importants en matière de paramètres thyroidiens (anticorps/TSH) et d'appartenance ethnique.

“For the disease-free population, mean serum TSH was 1.50 [(95% confidence interval, 1.46–1.54 mIU/liter)], was higher in females than males, and higher in white non-Hispanics (whites) [1.57 (1.52–1.62) mIU/liter] than black non-Hispanics (blacks) [1.18 (1.14–1.21) mIU/liter] (P < 0.001) or Mexican Americans [1.43 (1.40–1.46) mIU/liter] (P < 0.001).
TgAb were positive in 10.4 ± 0.5% and TPOAb, in 11.3 ± 0.4%; positive antibodies were more prevalent in women than men, increased with age, and TPOAb were less prevalent in blacks (4.5 ± 0.3%) than in whites (12.3 ± 0.5%) (P < 0.001). TPOAb were significantly associated with hypo or hyperthyroidism, but TgAb were not. Using the reference population, geometric mean TSH was 1.40 ± 0.02 mIU/liter and increased with age, and was significantly lower in blacks (1.18 ± 0.02 mIU/liter) than whites (1.45 ± 0.02 mIU/liter) (P < 0.001) and Mexican Americans (1.37 ± 0.02 mIU/liter) (P < 0.001”

Traduction:

Pour la population sans affection thyroidienne (thyroidite autoimmune), le taux moyen de TSH était de 1,50 (95% à 1,46/1,54 mIU/l); il se situait plus haut chez les femmes que chez les hommes et plus haut également chez les populations blanches, non hispaniques (1,57; 1,52-1,62) que chez les populations noires non hispaniques (1,18; 1,14-1,21), P<0,001 ou mexico-américaines( 1,43; 1,40-1,46) P<0,001. Les anticorps TG étaient positifs chez 10.4 +/- 0,5%, les anticorps TPO étaient positifs chez 11,3 +/- 0,40%. Les anticorps positifs se retrouvent plus chez les femmes que chez les hommes et augmentent avec l'âge.
Les anticorps TPO ont une présence moindre chez les Noirs (4,5+/-0,3%) que chez les Blancs (12,3+/0,5%) P<0,001. La présence d'anticorps TPO était fréquemment associée à une hypo ou hyperthyroidie, ce qui n'était pas le cas pour les anticorps TG.
Dans la population de référence, la moyenne géométrique de la TSH était de 1,40+/-0,02 mlUL. Elle augmentait avec l'âge et était nettement plus basse chez les Noirs (1,18 +/- 0,02mlUL) que chez les Blancs (1,45+/0,02mlUL)P<0,001 et les Américains d’origine mexicaine (1,37+/0,02 mlUL) P<0,001.

En matière de TSH, les normes de référence antérieures n'avaient pas pris en considération la présence ou non d'anticorps thyroidiens. Pour les nouvelles références, seules sont prises en compte les résultats de personnes sans anticorps.

En janvier 2003, l'association américaine des Endocrinologues Cliniques (AACE) s'était associée à la proposition du NACB et avait recommandé à ses membres du corps médical d'appliquer les nouvelles valeurs de référence. En octobre 2003, les données furent présentées pour la 1ère fois en Allemagne par le Prof. Carole Spencer et ce à l'occasion du congrès "Thyroïde 2003". Le texte a été publié dans un livre disponible en Allemagne (1). Les médecins internes allemands s'emparèrent du sujet en 2004. Article en allemand sur
http://www.infoline-schilddruese.de/ils/content/040/mmw2.pdf

Comment a évolué la situation aux Etats-Unis?
A l'époque de la publication des recommandations de l'AACE il y a trois ans, l'association estimait qu’en introduisant ces nouvelles valeurs de référence, le nombre de personnes atteints d’une hypothyroidie allait doubler, passant de 13 millions à 27 ; de nouvelles estimations vont même jusqu'à 42 millions. Cela fait 17,5%, dans la population blanche. Si l'on considère les 42 millions uniquement pour les femmes blanches (la thyroidite autoimmune est très rare chez les hommes), on obtient une valeur supérieure à 30%.

Or, de nombreux laboratoires aux Etats-Unis n'ont pas appliqué ces recommandations. Quelques médecins ont intégré les nouvelles valeurs de référence de la TSH dans leur concept de traitement, d'autres connaissaient la directive mais décidaient cependant de garder les anciennes normes. D’après la newsletter de Mary Shomon, il y a des médecins, et même des endocrinologues, qui ne connaissent même pas ces recommandations. Il arrive également que des patients parlant d'eux-mêmes au médecin des nouvelles recommandations se voient refuser le traitement, on demande même à certains de changer de médecin.

Ensuite apparurent en 2005 des études contradictoires dans un journal
américain spécialisé. Surks et al (3) ont écrit dans " Controversy in Endocrinology: the Thyrotropin Reference Range Should Remain Unchanged" que le traitement de routine des hypothyroidies subcliniques n’était pas recommandé, et encore moins chez les individus avec une TSH dans le haut de la fourchette (2,5 à 4,5). http://jcem.endojournals.org/cgi/content/abstract/90/9/5489

D'autres auteurs intitulent leur publication : « The evidence for a Narrower
Thyrotropin Reference Range is compelling” (4)
http://jcem.endojournals.org/cgi/content/abstact/90/9/5483

Ils présentent une série d'arguments:

- la population blanche a une valeur moyenne de TSH de 1,45
- les afro-américains ont une valeur moyenne de TSH de 1,18 (nettement plus basse)
- Double standard de nombreux médecins, qui certes recommandent une TSH de 1 à 1,5 chez les patients sous Levothyrox, mais considèrent une TSH jusqu'à 4,5 chez les patients non traités comme normale.

Où en est la situation en Allemagne?
Comme aux Etats-Unis: là aussi, quelques médecins et laboratoires utilisent les nouvelles normes, d'autres pas. Toutefois, jusqu'à présent il n'est pas apparu de controverse visible de l'extérieur au sein du corps médical. Pas encore?

Litérature :

(1) Spencer CA. Subclinical Hypothyroidism and TSH – New Insights on TSH Reference Values. Schilddrüse 2003; Hrsg.: de Gruyter (Berlin – New York); 2004: 338

(2) Hollowell JG, Staehling NW, Hannon WH, Flanders WD, Gunter EW, Spencer CA, Braverman LE. Serum thyrotropin, thyroxine, and thyroid antibodies in the United States population (1988 to 1994): NHANES III. J Clin Endocrinol Metab 87; 2002: 489

(3) Surks MI, Goswami G, Daniels H. Controversy in Endocrinology: The Thyrotropin Reference Range Should Remain Unchanged. J Clin Endocrinol Metabol 90; 2005: 5489

(4) Wartofsky L, Dickey RA. Controversy in Clinical Endocrinology:The Evidence for a Narrower Thyrotropin Reference Range Is Compelling. J Clin Endocrinol Metabol 90; 2005: 5483

Suite de cet article dans la newsletter de décembre 2006 (que je n'ai pas encore eu le temps de traduire ... avis aux volontaires :

http://www.schilddruesenpraxis.de/nl_200620.html

CHOUPI4  |  Votre adresse d'émail n'est pas correcte

Inscrit le: 25.09.05 |  Messages: 646  | Ablation totale de l...  | essonne  |   | 50+

coucou tt le monde et merci BEATE pr ces infos justement ,mon hypo qui dure depuis un moment m'as déclenché une pression au niveau de l'oeil..d'après l'ophtalmo ,c'est bien l'hypo qui a fatigué mes muscles occulaires!! et j'ai 12 séances d'orthoptie..

Inscrit le: 05.12.05 |  Messages: 1204  | 40+

Pour mon cas, ce serait presque risible de rester dans le monde de ceux qui veulent en rester avec un taux ok pour une TSH autour de 4...

C'est quand même la période ou mon syndrome dépressif était le plus fort avec des idées suicidaires de plus en plus violentes et nombreuses...
Là ou j'étais le plus mal, le moins sociable, le moins apte à avoir une vie "normale"

Mais non, décidement j'étais en pleine forme

Heureusement que je suis sorti de cette ornière...

@+

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Merci Beate et CV pour la traduction! Reste à convaincre les médecins; je comprends mieux mes problèmes d'yeux!

un grand merci

Mirane

Inscrit le: 05.05.05 |  Messages: 326  | 40+

j'ai commencé mais je remarque que çà ne sert à rien....

j'ai voulu sondé la quarantaine de laboratoire implanté dans le Haut Rhin, après 35 appels, j'arrête...

en effet, je me rends compte que les laboratoires sont comme les toubibs et qu'il y a un effet de pyramide où se trouve à la tête le fabricant qui vend les coffrets d'analyses (Roche par Ex.)

Tant que ces fabricants ne seront pas à la page en ce qui concerne les nouvelles normes de la TSH, les laboratoires appliqueront les anciennes normes, suivront les toubib.

Je remercie les secrétaires qui auront pris sur leur temps pour me répondre.

bonne journée

bizzzzzzzzzzzzzzzzz

Beate
Présidente

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Voir aussi les discussions :

Les normes pour la TSH? (décembre 2005) et
Besoin de documentation officielle ! (septembre 2006)

ooreen  |  Votre adresse d'émail n'est pas correcte

Inscrit le: 17.02.07 |  Messages: 28  | 

Merci pour toutes ces infos Beate.
J'aurais du commencer par lire le forum de manière complète mais je dois bien avouer que (comme beaucoup ici certainement) j'ai du mal à lire. J'ai moi aussi les yeux fatigués (je suis myope en plus), et j'arrive pas à me concentrer je louche sur les phrases, et des fois j'ai du mal à les comprendre.
Je pense que je vais essayer de prendre du fucus. Y'a pas de risque que ce soit nocif par exemple si on prend trop d'iode ? Comment connaitre la limite ?

Merci ^^

Bonjour tout le monde!

Tout ça n'est pas très claire pour moi.On parle de "set-point" personnel, c'est quoi ça?

Les ando.tatonnent pour trouver le dosage. Moi je suis à 0,04, je prends du lévo.à 100; j'assaye d'oublier mon état. Je ne sais pas si je vais bien ou pas.

Pour me donner la forme et oublier, je pratique depuis seulement 2 mois de la natation pendant 2 heures continue , une fois par semaine, soit tous les mercredis.

A dire vrais je perd confiance.

Détresse de RACHA

Beate
Présidente

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Bonjour,

le "set-point" personnel, c'est le taux auquel on se sent BIEN ! C'est un point quelque part à l'intérieur de la fourchette officielle - mais qui peut beaucoup varier d'une personne à l'autre !

Un patient se sentira mieux avec une TSH plutôt basse, vers 0,7 ou 0,8, un autre avec une TSH plutôt haute, à 2 ou 2,5 .... donc, le tout est de trouver SON taux idéal personnel, en ajustant à tout petits pas vers le haut ou vers le bas ! Si on a un taux déjà "dans la norme", mais qu'on ne sent pas encore très bien, on peut tout à fait continuer à chercher, en augmentant ou en diminuant un peu !

Toi, tu parles d'une TSH à 0,04 - c'est déjà EN-DEHORS de la fourchette, tu es surdosée ! As-tu eu un cancer ? Car après un cancer, les premiers mois, on garde ainsi la TSH très basse, "freinée", pour éviter les récidives - mais quand on n'a PAS eu de cancer, il ne faut pas maintenir la TSH si basse, mieux vaudra baisser un peu le dosage.

Courage, tu finiras par y arriver !

A bientôt,

Beate

FAQ : C'est quoi, le set-point personnel ?

Bonjour Beate

Le cancer, j'en ai pas, d'après l'anapathe. Le taux de 0.04, je l'ai eu quand j'étais à 1comprimé 1/4 il y'a 1 mois. Je suis maintanant à 1 comprimé. 2 mois après je dois refaire une TSH, c'est à dire dans un mois. Je verrais d'ici là ce que ça donnera.

Beate
Présidente

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Article intéressant : une interview "questions-réponses" sur la nouvelle limite haute de la TSH et ses implications, avec le Dr Carol Spencer, d'août 2006 (c'est en anglais, si quelqu'un a le temps de traduire ??) :

http://www.aacc.org/AACC/events/exp.....s/2006/TSHRange/qanda.htm

Citation:

Question and Answer Session August 15, 2006 Presentation: Clinical Implications of the New TSH Reference Welcome to AACC’s Expert Access Live Online program Clinical Implications of the New TSH Reference Range This month's expert is Carole Spencer, Ph.D., F.A.C.B.,from University of Southern California, Los Angeles, California. View the presentation and direct your questions to our online experts. AACC would like to thank Bayer HealthCare Diagnostics for making this program possible. -------------------------------------------------------------------------------- For the authoritative document describing use of thyroid function testing in the clinical laboratory, you can visit this web site ( http://www.aacc.org/AACC/members/nacb/LMPG/ OnlineGuide/PublishedGuidelines/ThyroidDisease/ ) to review the NACB Laboratory Medicine Practice Guideline titled "LABORATORY SUPPORT FOR THE DIAGNOSIS AND MONITORING OF THYROID DISEASE." This guideline was edited by today's moderator, Dr. Carole A. Spencer, and her NACB colleague Dr. Laurence Demers, and it is available in English, French and Spanish languages. Washington, DC AACC Moderator: In the spirit of full disclosure, this information has been provided by the Expert Access program moderator. -------------------------------------------------------------------------------- Why is the TSH measurement more clinically sensitive for assessing thyroid status than a free FT4 test? Paris, France Carole Spencer Ph.D., FACB.: Because the TSH/free T4 relationship is log/linear, when free T4 moves off the optimal setpoint for that individual this free T4 abnormality is magnified 50 times in terms of an inverse change in TSH. TSH measurement is the only test that can detect an abnormality in free T4 status because we do not typically know where the free T4 setpoint of an individual patient lies relative to the population reference range (~0.8-1.8 ng/ dL). -------------------------------------------------------------------------------- There seems to be an implication that an individual's "set point" TSH concentration is the optimal value for that individual. Is there any evidence to support that? (My weight "set point" is quite stable, but almost certainly not optimal.) Seattle, WA Carole Spencer Ph.D., FACB.: The set point is not in TSH but free T4. This has been established from free T4 studies in mono- and dizygotic twins. If free T4 is being maintained on it's setpoint and the pituitary is not sensing any free T4 deficiency or excess relative to this, the TSH remains within a fairly narrow range (~ 0.75 mIu/L) over long periods of time. -------------------------------------------------------------------------------- How about the correlation between TSH and Hyperthyroidism and the risk of Cardio-vascular disease? St.Louis, MO Carole Spencer Ph.D., FACB.: Thyroid status (as reflected by TSH) is only one of many factors that influence risk for cardiovascular disease (CVD). CVD and atrial fibrillation (AF) are exaccerbated with both thyroid hormone excess and deficiency (Sawin NEJM 331:1249,1994 and Hak Ann Intern Med 132:270). Thyroid-mediated CVD and AF risks increase with age and the degree and duration of thyroid dysfunction. The relationship is one of association rather than correlation. The strength of the relationship will vary depending on the selection criteria used for the patient cohort. For example, thyroid dysfunction would likely show a stronger association with CVD for groups already at risk (i.e. hyperlipidemia or diabetes or a previous history of CVD). This is why the risk of having a TSH outside the empirical range has to be weighed on a case-by-case basis. -------------------------------------------------------------------------------- When the TSH is between 2.5 and 4 mUI/L Why not to use the TRH test? Buenos Aires Carole Spencer Ph.D., FACB.: The TRH response is merely proportional to the basal TSH (Spencer JCEM 76:494–498, 1993) so that when basal TSH is detectable TRH stimulation provides no additional information. Currently TRH testing is only useful to test hypothalamic-pituitary function. Measurement of TPOAb would be far more predictive of underlying thyroid dysfunction than a TRH test. -------------------------------------------------------------------------------- Which reference interval for TSH do you reccomend for children and young adults? Porto Alegre, Brazil Carole Spencer Ph.D., FACB.: Clearly, TSH levels are highest at birth and decline throughout childhood until after the age of about 14 mIU/L (see Table 3 NACB guidelines on www.nacb.org). Again, a useful adjunctive test would be TPOAb. -------------------------------------------------------------------------------- Will there be any discussion on Hyperthyroidism? Albany, GA Carole Spencer Ph.D., FACB.: There is broad agreement that the lower TSH reference limit lies around 0.3 mIU/L. The risk of cardiovascular problems for patients having a low TSH depends on duration of the low TSH and patient-specific risk factors, especially age (Sawin NEJM 331:1249,1994 and Parle Lancet 258:861,2001). Osteoporotic fractures are also increased in post-menopausal women not taking estrogen replacement with a chronically low TSH in the 0.1 -0.5 mIU/L range (Bauer AIM 134:561,2001). Concerns of inducing iatrogenic subclinical hyperthyroidism is why it is critical to titrate an L-T4 dose to produce a TSH in the 0.5 to 2.0 mIU/L range, and not overtreat. It is difficult to diagnose hyperthyroidism in the first trimester of pregnancy because TSH can be as low as ~0.02 mIU/L (Slide 35) as a result of direct hCG stimulation of the thyroid - a physiological response to ensure adequate maternal thyroxine is available to the developing fetus. -------------------------------------------------------------------------------- Should we even attempt to establish reference ranges locally? Bangor, Maine Carole Spencer Ph.D., FACB.: I don't think it is useful to try to establish "local" reference ranges. There are differences in the reference ranges of different locations (d'Herbomez Clin Chem Lab Med 43:102,2005). There are also practical difficulties as a result of HIPPA, and the cohort the more likely a "ringer" with occult thyroid dysfunction or in the rebound phase of a NTI will be included who will skew the range for the entire cohort. Participants with outlying TSH values relative to the group median would need to be checked after several weeks according to the NACB guidelines (www.nacb.org) and in addition to TPOAb measurements ideally all participants should have ultrasound evaluations - which is impractical and expensive. It is much better not to be fixated on establishing "absolute" TSH limits but use the risk stratification approach described in Slides 42 and 43. For example, one would seriously consider L-T4 treatment for a 60 year old hypercholesterolemic woman with a TSH of 3.5 mIU/L but not a 28 year old active male with no TPOAb detected and an identical TSH. It is patients that are treated not a TSH result. -------------------------------------------------------------------------------- If you had discarted TSHoma or RTH and you suspect an inappropiate TSH syndrome, which diagnostic you consider if the patient shows no sintoms, normal proteinogram and high TSH and T4 L determined by two differents methods? POSGRADO DE ENDOCRINOLOGIA, HOSPITAL NACIONAL DE CLINICAS. CÓRDOBA ARGENTINA. Córdoba, Argentina Carole Spencer Ph.D., FACB.: If the TSH were high and a TSH-secreting pituitary tumor and thyroid hormone resistance (RTH) had been ruled out I would consider the following: 1. Obviously the first thing is to confirm the high TSH with a new blood specimen after 4-8 weeks.This was presumably done. 2. If TPOAb were positive this would suggest thyroid hormone deficiency. 3. Even if TSH were high by two different methods you cannot entirely rule out heterophilc antibody (HAMA) interference - no IMA method is immune. I would check with a blocker tube. 4. I would look at where the total and free T4 fell relative to their respective population reference ranges. I would expect T4 status to be in the lower third of the range. 5. TRH testing was presumably done to exclude central hypothyroidism. 6. Ultrasound might show a hypoechoic pattern suggestive of lymphocytic infiltration. 7. If there appeared absolutely no reason for the high TSH I would consider the possibility that the patient had an inactivating TSH receptor polymorphism requiring a higher TSH to maintain euthyroidism (? test family members). 8. Cases of patients secreting a high MW bioinactive TSH have been described. (identified by gel chromatography). -------------------------------------------------------------------------------- Dr. Spencer, Your excellent documented presentation covers the most important and controversial aspects on the topic. In a recent European Journal of Endocrinology ( 2006) 154 633: 637, Dr. Brabant and colleagues say that there is only one study providing direct data to support an upper normal limit of 2.0-2.5 (Ship-1), which probably still included people with autonomous functioning areas in the thyroid as judged from the fall in median TSH values with age, that probably reflecting the previously moderately severe iodine deficiency in the population studied. Question: Based on this: Do you have any comment on this? Specifically, do you believe that reference range should be geographical area specific and not “universalâ€�, the same way as the threshold for treatment should be patient specific? Thanks Laboratory of Endocrinology. Hospital de Clínicas. Córdoba.Argentina Cordoba, Argentina, Laboratory of Endocrinology,Hospital de Clínicas Carole Spencer Ph.D., FACB.: A comparison of the NHANES (USA) and SHIP (Germany) TPOAb negative cohorts across decades of age clearly show that the TSH upper limit increases with NHANES and decreases with SHIP. In the high iodine environment of the USA the underlying pathology is an increasing prevalence of Hashimotos' thyroiditis and hypothyroidism with aging. In contrast, previous iodine deficiency in the German cohort has left an underlying pathology of nodular goiter and thyroid autonomy that increases with age. This is responsible for an apparent increasing TSH with age in NHANES and decreasing TSH with age in SHIP. It is clear that it is impossible to completely remove the effects of the underlying pathology of a population by TPOAb or even ultrasound exclusions. The underlying pathology always "contaminates" the mathematically calculated TSH reference limits. Thus, because it is impossible to establish a fixed TSH upper limit the risk stratification approach described in slides 42 and 43 is more appropriate. -------------------------------------------------------------------------------- I presume all the data presented here is based on an adult population. Are these recommendations applicable to pediatrics? Memphis, TN Carole Spencer Ph.D., FACB.: Yes, I was discussing only the TSH reference range for adults. TSH levels are highest at birth and decline throughout childhood until after the age of about 14 mIU/L (see Table 3 NACB guidelines on www.nacb.org). -------------------------------------------------------------------------------- do you recommend the TSH-TRH test in the patients with TSH basal levels in the upper limmits? iorcansky_sonia@yahoo.com.ar buenos Aires-Argentina Carole Spencer Ph.D., FACB.: This has been an active question. The TRH response is merely proportional to the basal TSH (Spencer JCEM 76:494–498, 1993) so that when basal TSH is detectable TRH stimulation provides no additional information. Currently TRH testing is only useful to test hypothalamic-pituitary function. There are also issues regarding how a reference range for the TRH test is established. It is necessary to standardize for time of day because the TRH response is much higher in the morning than the afternoon - again amplification of the physiologic TSH diurnal variation. Also, it is important to consider the CV of repetitive TRH testing (at the same time of day, allowing a week at least between tests to allow thyroid hormones to return to baseline) i.e the biologic variability of the TRH response. In my view, I do not think TRH testing adds any value to basal TSH. Furthermore, TRH stimulated values are assay dependent because different TSH IMAs have been shown to detect the more biologically active, newly released TSH to differing degrees (Clin Chem 39:2167,1993). -------------------------------------------------------------------------------- Should we discourage the use of Total T4 in favor of the Free T4 assay. I still have physicians that order it and would like discontinue the test. Very low volume. Thanks Waconia, MN Carole Spencer Ph.D., FACB.: It is critical to retain total T4 as an accessible lab test. Unfortunately, current free T4 immunoassays are merely ESTIMATE tests and do not measure free T4 directly. They are still all binding protein dependant and prone to give false values when binding proteins are very abnormal, especially in patients with nonthyroidal illness (NTI) (Sapin Clin Chem 46:418,2000). Also, it is apparent that the non-pregnant FT4 reference ranges cannot be used to manage pregnant patients. FT4 reference ranges are both trimester and method-specfic and there are currently no appropriate ranges established for pregnancy. Current guidelines (NACB) suggest the continued use of total T4 (TT4) and FT4 indexes to assess the thyroid status of hospitalized patients. In this setting the total T4 has to be interpreted relative to the severity of illness. For example, the low T4 state of NTI only occurs with severe illness (TSH is not elevated >10 mIU/ L). If TT4 is low and TSH not elevated and the patient is not severely sick, a diagnosis of central hypothyroidism should be excluded. New guidelines for pregnancy (Mandel Thyroid 15:44,2005) also recommend the use of the total T4 and free T4 index or total T4 if the reference limits are adjusts by multiplying by 1.5 to account for the increased TBG. -------------------------------------------------------------------------------- Does T3 or Ft3 has any diagnostic importance as on date?? India Carole Spencer Ph.D., FACB.: T3 is a tertiary test and only needed for investigating unusual presentations of hyperthyroidism or factitious hyperthyroidism which can be induced by certain over the counter (? weight loss) preparations containing T3 or Triac. Current automated T3 assays are set up to measure high T3 levels. Total T3 assays are far more robust and preferred over current free T3 immunoassays which offer little benefit. By the time a T3 status is needed for the diagnosis binding protein abnormalities are not usually an issue. NACB guideline #14 lists the uses for T3 measurements. -------------------------------------------------------------------------------- I have been approached about refining local strategies to evaluate thyroid status in pregnancy (a topic a considerable controversy in past decades). (1) Please comment on the utility of TSH in first trimester...New guidelines suggest maintaining TSH <2>20:1 indicating active stimulation caused by TSH receptor antibodies. The other way to distinguish is a radioiodine uptake which will be suppressed in thyroiditis and high in Graves'. If the FT3 was highly elevated I would guess that your patient has Graves' hyperthyroidism. -------------------------------------------------------------------------------- why is 3rd gen TSH more important than second gen Durham, NC Carole Spencer Ph.D., FACB.: Reliable TSH measurement in the 0.01-0.1 mIu/L range can only be guaranteed using 3rd. generation assays. It is critical to be able to detect the difference between a fully suppressed TSH <0.01 mIU/L and a partially suppressed TSH in many situations: 1. In hospitalized patients with nonthyroidal illness (NTI) a TSH < 0.01mIU/L suggests hyperthyroidism whereas a TSH of ~0.04 mIU/L would suggest a transient effect of NTI. Treatment or non-treatment strategy would differ. 2. In patients receiving high doses of L-T4 to suppress TSH for thyroid cancer it is essential to be able to accurately titrate the degree of TSH suppression. Studies have shown that thyroglobulin levels respond to changes in TSH in the range below 0.1 mIU/L. 3. Most thyroid testing is performed in outpatients being monitored for L-T4 replacement therapy. It is critical to titrate L-T4 dose to give a TSH in the range 0.5-2.0 mIU/L. There is always concern for overtreating and causing iatrogenic hyperthyroidism with the attendant risk of atrial fibrillation (slide 19). The assay needs to be really solid in the range below 0.1 mIu/L to reliably detect this. 4. Assays always exhibit 'noise" around their sensitivity level. This noise is always positive - i.e. falsely high TSH values. There is no rationale for using a second generation method and "reflex" low values to a 3rd. generation because low values cannot be reliably detected (NACB guideline 21). -------------------------------------------------------------------------------- What resource do you recommend for pediatric ranges? How does lowering the TSH range affect pediatric ranges Springfield, MO. Carole Spencer Ph.D., FACB.: My presentation relates to the adult TSH range. Clearly, TSH levels are highest at birth and decline throughout childhood until after the age of about 14 mIU/L (see Table 3 NACB guidelines on www.nacb.org). Carole Spencer Ph.D., FACB.: My presentation relates to the adult TSH range. Clearly, TSH levels are highest at birth and decline throughout childhood until after the age of about 14 mIU/L (see Table 3 NACB guidelines on www.nacb.org ). -------------------------------------------------------------------------------- If the patient's TSH is 3.0 mIU/L or greater, should a aTPO test follow? New York, NY Carole Spencer Ph.D., FACB.: Yes, that would be a good strategy. A positive TPOAb result elevates the risk category for current or risk for developing hypothyroidism in the future (Whickham study, slide 32). It the patient is a young woman desiring pregnancy there would be concern that thyroid stress in the first trimester might result in thyroxine insufficiency for the developing fetus. Guidelines suggest prepregnancy TSH should be below 2.5 mIU/L. A positive TPOAb in the first trimester conveys a 30% risk for post- partum thyroiditis, if TPOAb is positive in the 3rd. trimester the risk is 50%. A TPOAb-positive patient with a TSH of 3.0 mIU/L would also be at risk for developing thyroid dysfunction if started on medications such as interferon, interleukin, lithium or amiodarone (NACB guideline #34). -------------------------------------------------------------------------------- At the bottom of page 33 it says, "New guidelines now..." and doesn't complete the sentence or thought. Would you please finish the sentence? Thank you! Terre Haute, IN Carole Spencer Ph.D., FACB.: My apologies. New guidelines now recommend that optimally, TSH should be maintained below 2.5 mIU/L during pregnancy. -------------------------------------------------------------------------------- Any comment on the low free T4 levels during pregnancy despite increases in L-T4 dose that consistently decrease TSH? Argentina Carole Spencer Ph.D., FACB.: I do not think we know why FT4 (even when measured by equilibrium dialysis) progressively decreases with gestation. It is probably related to binding protein changes (? albumin status) maybe T4 clearance. The general consensus (CDC conference) that TSH is the better marker for thyroid status, however, TSH does not respond instantaneously to changes in thyroxine or thyroxine dosing so perhaps pregnancy is one situation to order both TSH and a free T4 index or total T4 (not a free T4 immunoassay for the reasons previously covered). -------------------------------------------------------------------------------- Do you see a shift in normal ranges in TSH in the same way you see a shift in FT4 in pregnancy? Birmingham, Alabama Carole Spencer Ph.D., FACB.: Usually the TSH is lower in the first trimester because of the high hCG stimulation and then gradually increases to pre-pregnancy levels by mid- gestation. The FT4 shifts (progressive lowering as pregnancy progresses) is not seen with TSH. Also if iodine intake is normal TSH does not increase as gestation progresses. There is in essence a disconnect between the TSH and FT4 patterns seen during gestation and TSH is considered the more reliable indicator of thyroid status. -------------------------------------------------------------------------------- Do you believe the disparity betwwen TSH assays is a major problem and is there any resolution to it? Germany Carole Spencer Ph.D., FACB.: The disparity between TSH assays is only a problem if you are trying to establish a rigid TSH reference range that covers all groups. The disparity between assays is likely to reflect TSH heterogeneity recognized by the monoclonal antibodies - it's not fixable. 2.5-3.0 mIU/L measured by one assay will always likely to be 3.0-3.5 mIU/L in another. It is better for us to abandon this concept of a fixed TSH range. It cannot be rationalized on either a methodology, biologic or practical basis. -------------------------------------------------------------------------------- I agree that the upper TSH limit should be at 3.0 mIU/L. It seems to me though that most primary physicians treat TSH like any other chemistry test. When the results come back from the reference lab,and your TSH is within the noted "normal" range, they do absolutely nothing. They do not track the individual' normal range or worry that a 3.0 may be subclinical hypothyroidism. What would do you recommend as the best approach ( by KOLs,labs or assay manufacturers ) to having physicians understand the idiosyncracies of TSH and the individual patient? NY, NY Carole Spencer Ph.D., FACB.: Physicians need education. it is to easy for them to "treat the number" and not the patient. I do think that labs should post a separate range for pregnancy (~0.02-2.5 mIU/L). Many physicians are chasing a diagnosis of hyperthyroidism when they see a low TSH in the first trimester. -------------------------------------------------------------------------------- in light of these new recommendations how should TSH measurements be used in monitoring patients on thyroxin replacement therapy for hypothyroidism New Haven, CT Carole Spencer Ph.D., FACB.: The guidelines (NACB, AACE and Endo Soc) all recommend that a TSH between 0.5 and 2.5-3.0 mIU/L is the recommended target for L-T4 replacement dose adjustment. Thyroxine has a long half-life and if the same dose is taken daily (without food etc) the TSH on long term replacement therapy remains remarkably constant (within the expected 0.75 mIU/L - NACB guideline 8). -------------------------------------------------------------------------------- TRH stimulated TSH can serve as a peripheral marker of thyroid hormone action at the pituitary? Argentina Carole Spencer Ph.D., FACB.: I do not believe that TRH conveys any additional information over TSH as indicated in previous questions. -------------------------------------------------------------------------------- By lowering TSH lower reference range to 0.3, do you not increase risk of including some with subclinical hyperthyroid? Lexington.KY Carole Spencer Ph.D., FACB.: Young people with iatrogenic hyperthyroidism (thyroid cancer patients receiving high L-T4 for suppression do not have problems with marginally low TSH. A TSH of 0.3 mIu/L is not an absolute. TSH has an episodic and diurnal variability such that a 0.3 in the afternoon could well be 0.6 mIu/L at an early morning appointment. So setting the lower limit to 0.3 or 0.4 mIu/L does not impact the diagnosis of subclinical hyperthyroidism. For example, if you had an elderly patient receiving L-T4 replacement you would try to titre the dose to give a TSH in the 1.0-1.5 mIu/L range rather than down around the lower limit. -------------------------------------------------------------------------------- In regards to TRH challange related to hypothyroid my understanding is: Primary is due to the thyroid and a TRH challenge leads to TSH increasing 2-3x normal. Secondary is due to the pituitary and a TRH challenge leads to low/normal TSH (ie no response). Tertiary is due to the hypothalamus and a TRH challenge leads to increased TSH (after a delay). Is this correct? Another question, what is the actual new TSH value, is it 2 or 2.5 and how many labs are using it? Thanks Fort McMurray, Alberta Carole Spencer Ph.D., FACB.: You are correct in your comments regarding the type of TRH responses. The relationship between basal and fold TRH response tends to be biphasic (Spencer JCEM 76:494,1993). I do not know how many labs are lowering their upper limit. We use an upper limit of 3.0 mIU/L in accord with the AACE guidelines. However, the increasing concerns regarding pregnancy suggest that perhaps we should lower it to 2.5 mIU/L. We are using the Roche Elecsys. Note in slide 23 this has a trend for higher values than the Access 2. If we changed methods we might consider reducing from 3.0 - 2.5 mIU/L for technical reasons. -------------------------------------------------------------------------------- Are TPOAb and TSH a valuable test in considering reasons behind a patient's multiple reoccurring spontaneous abortions? Birmingham, AL Carole Spencer Ph.D., FACB.: Most definitely. This is well established (NACB guideline #34). -------------------------------------------------------------------------------- Would you recommend using Anti-TPO or free T4 as the next test for an abnormal (high) TSH result. Peterborough, ON Carole Spencer Ph.D., FACB.: Because of the log/linear TSH/free T4 relationship you do not expect an abnormal FT4 unless TSH were <0>10 mIU/L (slide 8). TPOAb is by far the more important test to use to investigate whether a mild TSH abnormality might have an autoimmune basis. -------------------------------------------------------------------------------- WHAT IS YOUR RECOMMENDATION REGARDING THE UPPER REFERENCE RANGE FOR THE NEWNATES? TABUK,,SAUDI ARABIA Carole Spencer Ph.D., FACB.: Table 3 of the NACB guidelines gives some data regarding neonatal age and TSH. However this data was only obtained with one method (? Nichols). -------------------------------------------------------------------------------- Since there is currently no standardization of TSH assays, how can one reference interval be defined for all assays? Memphis, TN Carole Spencer Ph.D., FACB.: I believe an empiric reference range of 0.3-3.0 mIu/L is the best generalization we can make to cover all assays FOR NON-PREGNANT PATIENTS. The pregnancy reference range needs to be lower as discussed earlier. -------------------------------------------------------------------------------- A question of Tg assay. In patients with anti-Tg antibody, is the Tg level useful? What is the difference between immunoassay Tg and RIA Tg? Can the Tg level by RIA be used as a marker to monitor the recurrence of the cancer? Chantilly, Virginia Carole Spencer Ph.D., FACB.: I recommend the Tg/TgAb method comparison paper Spencer JCEM 90:5566,2005. Clearly all Tg IMAs are prone to produce falsely low or undetectable values in the presence of TgAb and not all TgAb methods detect all cases of interfering TgAb. The absolute TgAb concentrations reported by different methods vary widely and the same method needs to be used for serial monitoring. Serial TgAb can be used as a surrogate tumor marker test. Tg recovery tests are useless and the NACB guidelines state these should be discouraged and abandoned (NACB guideline 46). Tg RIA methods are clearly less prone to TgAb (or HAMA) interferences than IMAs. The best approach is to first assess the TgAb status of the specimen (by sensitive immunoassay) and if positive measure the Tg by RIA. TgAb positive patients can be monitored by serial TgAb and Tg RIA measurements. If RIA is not available monitor serial TgAb as a surrogate tumor marker (using the same method). -------------------------------------------------------------------------------- For subclinical hypothyroidism (TSH 3-10), how important are symptoms like tiredness, weight gain etc in deciding on replacement therapy? Saskatoon, Canada Carole Spencer Ph.D., FACB.: Clinical symptoms are weak indicators but because it is patients that are treated and not a number one cannot ignore them. Furthermore it is not unrealistic to assume that some patients will be more susceptible to slight degrees of thyroid hormone insufficiency (? different efficiency of the intracellular deiodinases for example could be postulated). If the patient has symptoms, a clinical trial of L-T4 treatment may be helpful. -------------------------------------------------------------------------------- When would you test for Anti-TG? Would it only be in patients receiving high doses of L-T4 to suppress TSH post-thyroidectomy for thyroid cancer? When would you test for anti-TSH receptor antibodies? Los Angels, California Carole Spencer Ph.D., FACB.: Ordering TgAb in addition to TPOAb is not useful to make the diagnosis of thyroid autoimmunity (NHANES study). The main use of TgAb is as an adjunctive test to Tg in patients with differentiated thyroid cancers in whom TgAb prevalence is twice the general population (~20%). It is rare to need TSH receptor antibody (TRAb). Most Graves' hyperthyroidism is self evident. Also, TRAb is not helpful stratifying patients for antithyroid drug treatment (until remission) versus radioiodine ablation. The primary use of TRAb is in pregnant patients with Graves' disease or a past history of RAI ablation for Graves' in whom there is risk of neonatal thyroid dysfunction caused by transplacental passage of the TRAb (blocking or stimulating). -------------------------------------------------------------------------------- You stated that 3rd gen TSH assays are important for hospitalized patients since they can detect levels <0.01 mIU/L. When looking at 3rd gen TSH assays, what is the lowest detectable concentration that is useful clinically? Is 0.0020 mIU/L any more useful than 0.004 ? New York, NY Carole Spencer Ph.D., FACB.: Current assays cannot reliably measure below 0.01 mIU/L. If a 4th. generation assay were available, the degree of suppression below 0.01 mIU/L might correlate with the chronicity of the thyroid hormone excess. For example, a patient entering the hospital with chronic undiagnosed hyperthyroidism might have a lower TSH <0.001 mIU/L than a patient with a mere transitory suppression perhaps due to high endogenous glucocorticoids of NTI.

Beate
Présidente

Inscrit le: 10.10.00 |  Messages: 50414  | Carcinome papillaire...  |  Léguevin  |   | 60+

Bonjour,

je vais vous faire un petit résumé de ce que j'ai appris au dernier congrès internationale de la thyroide (ETA2007), à Leipzig, début septembre 2007 ! Et tenez-vous bien : la "baisse de la limite supérieure de la TSH à 2,5", dont on parle pourtant depuis déjà 3 ans (voir mon récit d'Istanbul, en 2004 : Sujet ) n'est toujours pas "officielle" ... et ne le deviendra vraisemblablement jamais !

Apparemment, il y a différents courants, chez les médecins, et dans les grandes organisations (ETA, ATA, AACE ...), voir notamment l'article un peu plus haut sur "la guerre de la TSH" - il y en a qui voudraient bien abaisser la limite à 2,5 (c'est le courant autour de Carol Spencer, notamment), il y a aussi une certaine pression de la part des patients (voir p.ex. le site web de Mary Shomon, thyroidabout.com), et bien sûr, les labos sont A FOND derrière ca, car cela leur apporterait des millions de clients supplémentaires (imaginez un peu, si tout d'un coup on décide que tous ceux qui sont au-dessus de 2,5 sont "en hypo" et doivent recevoir un traitement ... quelle aubaine !)

Mais c'est plus difficile que ca ... car traiter trop vite, ou donner un dosage trop important, peut également comporter des risques, dont les patients n'ont pas toujours conscience !

J'en ai déjà souvent discuté avec des médecins, et certains m'ont dit avoir vu des cas de patients, surdosés pendant de longues années (par exemple en prenant trop de Lévo, ou, surtout, trop de T3), qui étaient "pliés en deux par l'ostéoporose", avaient des fractures graves ou de sérieux problèmes cardiaques ... il faut donc comprendre que quand un médecin a vu ce genre de chose, qui bien sûr ne se produit pas tout de suite, mais après un surdosage au long terme, ils sont hésitants à lancer le patient trop rapidement sur le chemin du traitement substitutif (et en particulier de la T3) ...

Pendant l'un des exposés auxquels j'ai assisté à Leipzig, on nous avait donné des boitiers électroniques pour "voter" ... et pendant le discours, très intéressant, on nous présentait différents exemples et on nous demandait comment on réagirait (en tant que médecin ... nous n'étions qu'une poignée de patients égarés dans l'assistance, mais je me suis régalée de pouvoir "voter" moi aussi ...)

Conclusion : il y a encore BEAUCOUP de médecins qui ne traitent pas quand la TSH est à 3 ou à 4 (ce qu'on peut comprendre, s'ils sont convaincus que la limite de 4,5 est justifiée ...) - et il y en a même pas mal qui ont voté "je ne traiterais PAS" lorsque la question concernait une TSH de 7,5 ... (bien entendu, on parle ici de l'hypo subclinique, où il n'y a QUE la TSH qui est hors norme ... si la TSH est haute ET la T4 et T3 trop basse, donc hypo franche, là les médecins n'hésitent pas à traiter !)

Mais bon, "ca dépend" ... le consensus était quand-même de dire "on ne traite pas une TSH, mais des SYMPTOMES", et donc, on ne traiterait pas quelqu'un qui, malgré une TSH un peu haute, va BIEN, mais il n'y a pas de raison de ne pas traiter si le patient, en plus de sa TSH élevée, présente des symptômes prononcés d'hypo.

Et à plus forte raison lorsqu'il y a, en même temps, des ANTICORPS : car quand on SAIT qu'il y a la maladie d'Hashimoto, on sait aussi que ca va forcément progresser, et qu'il faudra traiter un jour ou autre, et donc, autant commencer dès que le patient présente des symptômes.

Voilà ... désolée de ne pas pouvoir vous apporter des nouvelles plus réjouissantes, je peux d'ailleurs vous dire que j'étais toute confuse de me trouver là, dans cette salle, et de voir que RIEN n'a changé et que ce n'est toujours pas clair, alors que j'étais convaincue depuis 2004 que ce n'était qu'une question de temps ....

... mais en même temps, je comprends certains raisonnements et craintes (et je pense qu'il ne faut pas non plus "se laisser forcer la main par l'industrie pharmaceutique", qui ont bien sûr un intérêt énorme à ce qu'on traite le plus de gens possible ... et qui sont très puissants ... (d'ailleurs, dans les belles brochures qu'ils donnaient sur les différents stands des labos, la limite était tout naturellement indiquée avec 2,5 ...)

L'important est sans doûte d'avoir un médecin à l'écoute, qui nous connait et qui sait distinguer ce qui est "normal" et ce qui ne va pas, qui ne regarde pas seulement les analyses, mais le patient dans son ensemble, qui sait que chaque personne est différente et qu'il n'est pas tout d'être "dans la norme", mais qu'il faut encore atteindre son "set-point" personnel ...

... et pour quelqu'un chez qui la maladie d'Hashimoto est avérée, je pense qu'il n'y a aucune raison de ne PAS traiter, dès que les symptomes deviennent évidents !

Bon courage à tous !

Beate

Bonsoir Beate,
merci pour le compte rendu!
Bisous
florence