Ziekte van Graves: welke factoren voorspellen terugval na behandeling met schildklierremmers?

Als je schildklier te veel hormoon maakt met aandacht voor klachten, symptomen en behandelingen als block/replace, titratie, radioactief jodium en operatie
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laura
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Lid geworden op: 11 sep 2013, 22:42
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Ziekte van Graves: welke factoren voorspellen terugval na behandeling met schildklierremmers?

Bericht door laura » 28 jan 2017, 10:31

Does meta-analysis prove which factors predict relapse after antithyroid drugs are discontinued?

To cite this article:
Spaulding Stephen W.. Clinical Thyroidology. January 2017, 29(1): 5-7. doi:10.1089/ct.2017;29.5-7.

Thyrotropin receptor antibody levels at diagnosis and after thionamide course predict Graves’ disease relapse.
NN Tun, G Beckett, N Zammitt, et al. | Thyroid 2016;26:1004-9. Epub July 6, 2016

SUMMARY

Background

Antithyroid drugs produce remissions in about half of Graves’ patients, but many of those patients will eventually have a relapse. Thus, patients often end up being exposed to the risks of antithyroid drugs first and then to the risks of radioiodine or surgery as well. Many retrospective and some prospective studies have suggested factors that might predict relapse. Some of these factors have not been confirmed in subsequent studies, and of the factors that have been confirmed, each contributes only a small amount of risk. The authors of the current study carefully selected some of these studies for meta-analysis in hopes of establishing which factors are important for predicting remission and/or relapse. It should not be assumed that factors associated with the risk for Graves’ disease or factors associated with the risk for side effects from antithyroid drugs will turn out to be the same as factors that affect the risk of relapse/remission.

Methods

Several databases were reviewed, and 1859 abstracts of papers published between 1977 and 2015 were examined for data on pretreatment factors associated with relapse. In the 350 full texts reviewed, trial characteristics, interventions, outcomes, pretreatment risk factors, and patient age and gender were carefully assessed. Studies on patients who were pregnant, were under 16 years of age, or had euthyroid Graves’ orbitopathy or whose treatment or follow-up period was less than 12 months were excluded. Fifty-four studies were finally chosen for analysis. Factors included in fewer than three studies were not analyzed (including urinary iodine, free T4 index, free T3, antithyroglobulin antibodies, scintigraphic studies, patient history, and family history). There were no data on the number of the patients who did not complete 12 months of drug treatment because of side effects or death, or who were exposed to prolonged periods of hyperthyroidism or hypothyroidism after therapy.

The authors performed formal meta-analysis on aggregate data from 31 studies on 4346 patients, of whom 2322 had had a relapse. If a study provided only the median and range for a given variable, the authors tried—without success—to obtain further data, but they had to impute the means and standard deviations assuming a Poisson distribution and using a multivariate truncated linear regression model. For dichotomous data, confidence intervals were calculated by a random-effects model. For continuous data, standardized mean differences (Hedge's g value) were calculated. HLA genotyping and single-nucleotide polymorphism (SNP) information from 13 studies on 2178 patients were assessed only qualitatively. The risk of bias in each study was also assessed.

Results

Of the 31 studies subjected to meta-analysis, the risk of bias was judged to be high in 5, moderate in 14, and low in 12. Random-effects meta-analysis indicated a small but statistically significant increase in the risk ratio for baseline smoking 1.13 (95% CI, 1.02–1.25) and for baseline orbitopathy 1.15 (95% CI, 1.08–1.25). The standardized mean difference g values indicated that ultrasound thyroid volume and TRAb and TBII levels were slightly greater risk factors than free T4, total T3 levels, TSAb, and goiter (based on WHO grades), whereas sex and total T4 level did not reach significance. However, when they used univariable meta-regression analysis, smoking, total T3, and TBII lost significance, and thyroid volume and free T4 were of only minor significance. On the other hand, the total T4 level had become a significant predictor of relapse. Based on weighted raw mean differences, there was a 1% increase in the risk of relapse for every 5.5 ml increase in thyroid volume, for every 4 pmol/L increase in free T4, for every 6 nmol/L increase in total T3, for every 8% rise in TBII, for every 127% rise in TSAb, and for every 17 U/L rise in TRAb. No receiver-operating-characteristic curves were available. The inverse analysis, looking for factors predictive of remission, produced the expected results, except that both remission and relapse were associated with increasing age. The risk of study bias in the 13 genotyping studies was judged to be high in 1, medium in 5, and low in 7. Certain HLA types seemed to be significant risk factors in individual studies. The effect size for individual SNPs tended to be small to moderate. Of note, for the one case in which there were replicate studies (SNP at +49 in exon 1 in cytotoxic T-lymphocyte–associated protein 4 [CTLA4]), an A/G heterozygote was at negative risk in one study, was at positive risk in a second study, and not at significant risk in a third study.

Conclusions

Orbitopathy, smoking, larger thyroid volumes, and higher TRAb and TBII levels all probably predict relapse, but each individually is not very useful clinically. A large carefully planned prospective study is needed to see whether these (and other) factors could be combined to provide a clinically useful way to predict the risk of relapse.

ANALYSIS AND COMMENTARY

Patients and clinicians probably would lean toward radioiodine ablation or surgery as the primary treatment if they knew that the risk of relapse was high. Despite the labor expended in this study (detailed in over 40 pages of supplementary figures and tables), the meta-analysis results are a bit disappointing. This might have been foreseen in view of the excessive heterogeneity of studies and the five decades over which the data were collected. During this period, major improvements were made in laboratory testing. There were also major changes in environmental factors, such as dietary iodine and therapy for concomitant disorders, like amiodarone, glucocorticoids, as well as anti-TNF-alfa, anti-HIV, and anti–hepatitis C agents.

Beyond these problems, the authors found bias in many studies, did not have data from individual patients, had to perform imputation to deal with missing data in most of the studies, and only assessed risk factors separately. Still, some factors remained significant under several analyses. No factor had a major impact on risk, however, and no new factors were identified.

Perhaps it would have helped if the minimum follow-up period had been longer than 12 months. In at least four of the studies, the duration of follow-up was not a minimum of 12 months, but actually was a maximum of 12 months. Furthermore, the ranges given for follow-up times in other studies show that some patients were also followed for less than 12 months after discontinuing the antithyroid drug. A good demonstration of the need for longer follow-up times is provided in a recent paper from the Royal Infirmary of Edinburgh (1). Between 2006 and 2011, a total of 266 new Graves’ patients had completed an 18-month course of carbimazole and were then followed for up to 4 years. By 4 years, 42 of 48 patients (84%) with pretreatment TSH receptor antibody levels (second-generation assays) above 12 IU/L had had a relapse, whereas only 28 of 49 (57%) of those with a pretreatment TRAb level under 5 IU/L had had a relapse (P<0.002). Patients with low initial TRAb levels had about half the risk of relapse at 1 year, about 45% of the risk at 2 years, 25% of the risk at 3 years, and 30% of the risk at 4 years, when compared to the patients with high initial TRAb levels (1). Thus, although 55% (37 of 67) of patients with high initial TRAb levels had not relapsed at 1 year, by 4 years only 16% (8 of 49) remained in remission.

So where does this leave the physician and patient? This meta-analysis indicates that no single factor is a major predictor of relapse, but the risk of relapse did increase with higher pretreatment TRAb levels and also with greater pretreatment goiter size. Individual HLA types and SNPs may be important in some populations but are not yet routinely available. At any rate, it might be good clinical judgment to recommend definitive treatment if a new Graves’ patient smokes or has orbitopathy and has a high pretreatment TRAb level and a large goiter.
laura

Kijk voor meer informatie ook eens op Schildkliertje.

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Het Schildklierforum kan niet worden beschouwd als vervanging van een consult of een behandeling.

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laura
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Lid geworden op: 11 sep 2013, 22:42
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GREAT score bij Graves

Bericht door laura » 28 jun 2017, 16:35

Heb jij ervaring met de GREAT score bij de ziekte van Graves?

Vaak wordt de ziekte van Graves eerst behandeld met schildklierremmende medicijnen, zoals strumazol en PTU. De kans op terugval na deze behandeling is groot (50-75%) waardoor een definitieve behandeling met radioactief jodium of een operatie nodig is. Een middel waarmee de kans op terugval voorspeld kan worden, zou handig zijn. De Graves’ Recurrent Events After Therapy (GREAT) score zou zo’n middel kunnen zijn.

Met de berekening van de GREAT-score krijgen leeftijd, struma, vrij T4 en antistoffen punten (in totaal zes punten):
- leeftijd - jonger dan 40 = 1; ouder dan 40 = 0
- struma - niet zichtbaar = 0; een beetje zichtbaar = 1; duidelijk zichtbaar = 2
- vrij T4 - lager dan 3.1 ng/dl (40 pmol/l) = 0; hoger dan 3.1 ng/dl (40 pmol/l) = 1
- TBII antistoffen - lager dan 6 IU/L = 0; 6–19,9 IU/L = 1; hoger dan 19,9 IU/L = 2

Tel je de punten op dan krijg je drie GREAT-score klassen:
- I (0–1 punten)
- II (2–3 punten)
- III (4–6 points)

Conclusie
Volgens de onderzoekers ondersteunt deze studie het gebruik van de GREAT-score. De score kan gemakkelijk worden berekend op het moment van diagnose, om het succes van behandeling met schildklierremmers te voorspellen. De personen die vallen in GREAT-score klasse II en III hebben een grotere kans op terugval na een behandeling van 12-18 maanden met schildklierremmers. Zij kunnen daarom vanaf het begin besluiten om te kiezen voor een andere behandeling.

Meer informatie
Predicting the risk of recurrence before the start of antithyroid drug therapy (ADT) in patients with Graves’ hyperthyroidism
Xander G. Vos, Erik Endert, A. H. Zwinderman, Jan G. P. Tijssen, Wilmar M. Wiersinga

External validation of the GREAT score to predict relapse risk in Graves’ disease: results from a multicenter, retrospective study with 741 patients
T Struja et al

The ‘GREAT’ score, a clinical tool that predicts the success of antithyroid drug therapy for Graves’ disease
Clinical thyroidology for the public
laura

Kijk voor meer informatie ook eens op Schildkliertje.

Raadpleeg altijd een arts als je twijfelt over je gezondheid.
Het Schildklierforum kan niet worden beschouwd als vervanging van een consult of een behandeling.

Liekie
Berichten: 52
Lid geworden op: 16 okt 2016, 19:10

Re: GREAT score bij Graves

Bericht door Liekie » 23 sep 2017, 21:52

Had ik dit maar eerder geweten.....ik kwam direct al uit op lll

Dan was ik misschien wel anders gaan denken.

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laura
Berichten: 2996
Lid geworden op: 11 sep 2013, 22:42
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Re: Ziekte van Graves: welke factoren voorspellen terugval na behandeling met schildklierremmers?

Bericht door laura » 17 sep 2018, 12:11

Op een huisartsenbijscholing werd de volgende slide getoond: https://twitter.com/RietjeMeijer/status ... 2355846144
Helaas met enkele punten die afwijken van conclusies in recente onderzoeken en geldende aanbevelingen in richtlijnen.

Genoemd wordt dat '60 tot 70% geneest na 1 jaar medicatie, of strumazol alleen, of in combinatie met thyrax'.
Helaas gelden die percentages voor het aantal mensen die na een behandeling met medicatie weer geconfronteerd worden met hyperthyreoïdie.

In bovengenoemde onderzoeken kom je die terugval-percentages tegen.
Ook zie je die cijfers in Thyroid Manager.

Het is heel spijtig als patiënten op basis van onvolledige informatie geen goede keus kunnen maken.
laura

Kijk voor meer informatie ook eens op Schildkliertje.

Raadpleeg altijd een arts als je twijfelt over je gezondheid.
Het Schildklierforum kan niet worden beschouwd als vervanging van een consult of een behandeling.

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