© Borgis - Postępy Nauk Medycznych 11/2012, s. 860-865
*Magdalena Kochman, Helena Jastrzębska, Ewa Szczepańska, Joanna Zgliczyńska-Widłak, Jadwiga Janik
Ocena skuteczności kortykoterapii dożylnej w prewencji zaostrzenia orbitopatii tarczycowej u osób z chorobą Gravesa i Basedowa leczonych radiojodem z powodu nadczynności tarczycy
Evaluation of the efficacy of intravenous corticotherapy in preventing exacerbation of thyroid orbitopathy in patients with Graves’ disease treated with radioactive iodine due to hyperthyroidism
Department of Endocrinology, Medical Centre of Postgraduate Education, Warsaw
Head of Department: prof. Wojciech Zgliczyński, MD, PhD
Streszczenie
Wstęp. Leczenie radiojodem nadczynności tarczycy u chorych z chorobą Gravesa i Basedowa może prowadzić do zaostrzenia orbitopatii tarczycowej. Standardowo w zapobieganiu nasileniu zmian ocznych stosuje się steroidy doustnie. Celem pracy była ocena skuteczności i bezpieczeństwa stosowania steroidoterapii dożylnej jako prewencji zaostrzenia orbitopatii po leczeniu 131I.
Materiał i metody. Badaniem objęto 32 osoby z chorobą Gravesa i Basedowa i orbitopatią tarczycową leczonych radiojodem w latach 2010-2011 w Klinice Endokrynologii CMKP z powodu nadczynności tarczycy. W ramach prewencji nasilenia zmian ocznych u 16 chorych (grupa 1) stosowano dożylnie metyloprednizolon (4 cotygodniowe wlewy po 250 mg), zaś pozostałych 16 osób (grupa 2) otrzymywało prednizon (0,3-0,5 mg na kg masy ciała przez 4-5 tygodni z redukcją dawki w ciągu 8 tygodni). Grupy porównywano przed oraz po upływie 1 miesiąca i 1 roku od leczenia 131I pod względem ciężkości orbitopatii (wg klasyfikacji NOSPECS) i jej aktywności (z użyciem wskaźnika CAS), stężenia przeciwciał przeciwko receptorowi TSH (TRAb), konieczności stosowania dodatkowej steroidoterapii systemowej z powodu zaostrzenia zmian ocznych oraz występowania działań niepożądanych.
Wyniki. Grupy 1 i 2 nie różniły się istotnie między sobą pod względem klasy NOSPECS, wskaźnika CAS, ani stężeń przeciwciał TRAb zarówno wyjściowo, po 1 miesiącu, jak i po 1 roku leczenia. W grupie 1 nie obserwowano działań niepożądanych kortykoterapii, natomiast w grupie 2 u 2 osób odstawiono prednizon – u 1 z powodu depresji, zaś u 2 – dolegliwości ze strony przewodu pokarmowego.
Wnioski. W porównaniu z powszechnie stosowanym leczeniem doustnym prednizonem, dożylne podawanie metyloprednizolonu w ramach prewencji zaostrzenia orbitopatii po leczeniu radiojodem wydaje się równie skuteczne i obarczone mniejszą ilością działań niepożądanych.
Summary
Introduction. Radioiodine treatment of thyrotoxicosis in Graves’ disease patients may lead to orbitopathy progression. Oral glucocorticoid therapy is a standard method in prevention of eye changes exacerbation. The aim of this study was to evaluate the efficacy and safety of intravenous steroid therapy in prevention of orbitopathy exacerbation after 131I treatment.
Material and methods. The study included 32 patients with Graves’ disease and ophthalmopathy, treated with radioiodine due to thyrotoxicosis in 2010-2011 in the Department of Endocrinology CMKP. To prevent ophthalmopathy exacerbation, 16 patients (group 1) received intravenous methylprednisolone (4 weekly infusions of 250 mg), while the remaining 16 patients (group 2) were treated with prednisone (0.3-0.5 mg per kg of body weight for 4-5 weeks with dose reduction during 8 weeks). The groups were compared before and 1 month and 1 year after 131I therapy in terms of severity of orbitopathy (NOSPECS classification) and its activity (using Clinical Activity Score – CAS), serum TSH receptor antibody (TRAb), the need for additional systemic steroid therapy due to exacerbation of eye changes and the occurrence of adverse events.
Results. Groups 1 and 2 did not differ significantly according to NOSPECS class, CAS, nor TRAb concentrations at baseline, after 1 month and after 1 year of treatment. In group 1, there were no side effects of corticosteroid therapy, while in group 2 two patients discontinued prednisone therapy – 1 because of depression, and 1 because of gastrointestinal disorders.
Conclusions. In compare to the commonly used oral prednisone, intravenous administration of methylprednisolone seem to be equally effective in the prevention of exacerbation of orbitopathy after radioiodine therapy and carries fewer side effects.
INTRODUCTION
Therapy with radioactive iodine is currently the main method of radical treatment of hyperthyroidism in persons with Graves’ disease, and absent or present accompanying orbitopathy (1). However, as a result of destruction of the thyroid gland caused by radioactive iodine, stimulation of the autoimmune process occurs, which relates to release of thyroid antigens (2, 3). It has been established that in 15-33% of persons with hyperthyroidism and coexisting active thyroid orbitopathy, treatment with 131I may lead to exacerbation of eye lesions (4-6). Risk factors include: smoking (7), a high level of anti-TSH receptor antibodies (TRAb) (8), repeated treatment with 131I as well as uncontrolled hypothyroidism after treatment with 131I (9, 10). Normally, prophylaxis against intensification of the thyroid orbitopathy includes oral steroid therapy with prednisone (4, 6). In persons treated due to moderate or severe thyroid orbitopathy, intravenous administration of methylprednisolone in the form of repeated weekly infusions is more effective than oral treatment with prednisone. It also allows reducing the total dose of administered corticoids, which relates to less adverse reactions and better tolerance of treatment (11, 12).
The aim of this study is to evaluate the efficacy and safety of methylprednisolone use in the form of weekly intravenous infusions as prophylaxis against exacerbation of the thyroid orbitopathy after treatment with 131I due to hyperthyroidism in persons with Graves’ disease.
MATERIAL AND METHODS
The analysis included patients with Graves’ disease and coexisting thyroid orbitopathy, treated with 131I at the Clinic of Endocrinology of CMKP in 2010-2011 due to recurrent hyperthyroidism or hyperthyroidism resistant to conservative treatment. Subjects with moderate or severe orbitopathy, with a CAS (Clinical Activity Score) value of ≥ 3 (13) and patients treated in the past due to thyroid orbitopathy with intensive systemic steroid therapy or radiation treatment of the orbital cavities using the linear accelerator, were excluded from the study. Finally, 15 patients receiving systemic intravenous corticotherapy (group 1) underwent evaluation, and they were compared with a group of 15 patients selected according to gender, age and dose of 131I and receiving routine oral treatment with prednisone (group 2). All subjects were informed about the potential consequences, adverse reactions and complications of treatment with 131I and steroid prophylaxis, and they provided their written consents for the proposed treatment.
In group 1, methylprednisolone was used in a regimen of 4 weekly intravenous infusions in the dose of 250 mg of methylprednisolone (SoluMedrol) in 250 mL of 0.9% NaCl, and the first dose was administered on the same day when iodine isotope was administered. In group 2, according to the generally adopted regimen proposed by Barthalena et al. (4, 6), prednisone was used starting on the 1st day following administration of 131I in the dose of 0.3-0.5 mg per kg of body weight over 4-5 weeks, then the dose was gradually reduced during the next 8 weeks.
The studied groups were compared before treatment, after 1 month and 1 year following treatment with 131I in reference to severity and activity of orbitopathy, concentration of antibodies against the TSH receptor (TRAb), the necessity to use additional systemic steroid therapy due to exacerbation of eye lesions and the occurrence of side effects.
Severity of thyroid orbitopathy was evaluated with the NOSPECS classification (0 – No signs or symptoms; 1 – Only signs, no symptoms; 2 – Soft tissue involvement; 3 – Proptosis; 4 – Extraocular muscle involvement; 5 – Corneal involvement; 6 – Sight loss), and activity was evaluated with CAS (Clinical Activity Score) (1, 14, 15).
Before and during therapy, complete blood count, fasting glucose, concentration of sodium, potassium, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and total bilirubin were controlled.
The concentration of TSH, free thyroxine (fT4) and free triiodothyronine (fT3) were evaluated before treatment and then, every 4-8 weeks following treatment with 131I, with the chemiluminescence method using an automatic analyzer Immulite 2000. Reference values for the respective hormones amounted to: TSH 0.4-4.0 μIU/mL, fT4 10.4-24.4 pmol/l, fT3 1.8-4.2 pg/mL. Concentrations of TRAb were evaluated with the ELISA test using Euroimmun Analyzer 1 (negative result: below 1.8 IU/mL, doubtful result: 1.8-2.0 IU/mL, positive result: above 2.0).
Results were subject to statistical analysis using tests for non-parametric functions: the Shapiro-Wilk test for conformity, the Mann-Whitney test, Spearman’s rank correlation coefficient and the Wilcoxon test for paired samples. A value of p < 0.05 was assumed as a statistically significant result.
RESULTS
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Piśmiennictwo
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