Graves’ disease is a common cause of hyperthyroidism. Treatment options for Graves’ disease include antithyroid medication, surgery or radioactive iodine (I-31) or RAI. This review will focus on the approach to RAI therapy; discussing dose selection, patient preparation, and consideration before and after administering RAI, examining aspects of pre-treatment with antithyroid medication as well as discussing possible adverse events including hypothyroidism and possible worsening of thyroid-associated opthalmopathy. Follow-up is lifelong with the aim of ensuring the patient remains euthyroid or on replacement therapy if there is evidence of hypothyroidism. While there are controversies in treatment of thyrotoxicosis with RAI, with appropriate patient selection and regular follow-up, radioiodine is a safe and effective modality in achieving high cure rates.
radioactive iodine; Graves’ disease; thyroid; treatment; medical sciences
Objective: Using radioactive iodine (RAI) as the first line therapy for Graves’ hyperthyroidism and as the treatment of choice for relapsed Graves’ disease is increasing in recent times. However, there has been little consensus on the most appropriate dose to use. So this study is to determine the response of hyperthyroidism to fixed doses of 370 MBq and 555 MBq RAI therapies and determine the incidence of hypothyroidism at 6 months post therapy.
Methods: Hyperthyroid patients’ case records treated with radioiodine was retrospectively reviewed to determine the response rate of hyperthyroidism to the two fixed dose regimens. Statistical analysis was done with SPSS version 15.0 and the level of statistical significance was taken as p<0.05. Forty subjects, 6 males (15%) and 34 females (85%) received RAI therapy for Graves’ hyperthyroidism, mean age was 49.4 years (range, 25-75years). The thyroid function status at 6 months post therapy was available for all subjects. 24 patients (60%) received 370 MBq while 16 patients (40%) received 555 MBq.
Results: The response for fixed doses of 370 MBq and 555 MBq were similar (100%). Also, the incidence of hypothyroidism in these subjects which was 66.6% with fixed dose of 370 MBq and 62.5% with fixed dose of 555 MBq within 6 months post RAI therapy were similar.
Conclusion: SRAI is highly effective for the treatment of hyperthyroidism, with a cure rate of 100%. However, it has proved impossible to determine a fixed dose regimen for individual patients accurately to guarantee an euthyroid state. This is because hypothyroidism is a natural predictable sequel of RAI therapy.
Conflict of interest:None declared.
Iodine radioisotopes; radioisotope therapy; Hyperthyroidism; treatment effectiveness; Nigeria
Radioiodine is the treatment of choice for relapsed hyperthyroidism although the optimum protocol is uncertain. Fixed dose radioiodine is increasingly popular but responses may vary.
To assess the outcome of 131I therapy in hyperthyroidism using a standard dose regimen in a regional referral centre and to explore factors influencing outcome.
We studied 449 patients (M:F 82:367; age range 13-89y, median 42y) with hyperthyroidism treated between 2003 and 2007 with a standard dose of 550MBq 131I. Patients were classified as either Graves’ disease, toxic multinodular goitre or indeterminate aetiology. Antithyroid drugs were routinely stopped at least 1 week before radioiodine.
One year after radioiodine 334 (74%) were hypothyroid, 85 (19%) were euthyroid and 30 (7%) had required a further dose of 131I. Patients with Graves’ disease were more likely to become hypothyroid than those with toxic multinodular goitre (78% v 37%, p<0.001) and less likely to become euthyroid (11% v 55%, p<0.001). Free T4 >80pmol/L (normal range 9.0 – 19.0 pmol/L) at presentation was associated with an increased failure rate (17% compared with 5% and 3% for 40-79pmol/L and <40pmol/L respectively; p=0.01). Patients with either a small or no goitre were more likely to be successfully treated by a single dose (96%) than those with a medium/large goitre (85%, p<0.001). Anti-thyroid medication was taken by 345 (77%) (carbimazole n=319) patients up to 1 week prior to 131I and was associated with an increased failure rate (8% v 2%, p=0.027) compared to those who had not had antithyroid medication. Logistic regression showed free T4 at presentation to be the only independent risk factor for failure of the first dose of radioiodine (OR 2.5; 95% CI, 1.2–5.1, p=0.012).
A single standard dose of 550MBq 131I is highly effective in treating hyperthyroidism. The aetiology, severity of hyperthyroidism at diagnosis, goitre size and prior antithyroid medication all had a significant effect on outcome.
The outcome in 110 patients first treated with radioiodine (mean dose 6.56 mCi) for hyperthyroid Graves' disease in 1980 was reviewed. In 23% of the patients the disease had not been controlled by the initial dose after 3 months, and 17% were given one or two more doses. Within 2 years 65% of the patients required replacement thyroxine therapy. Although about half of the patients were biochemically hypothyroid 3 months after the last dose of iodine 131, this condition was transient in a third of them; five of these patients even became hyperthyroid again. Patients with transient, as opposed to permanent, hypothyroidism at 3 months tended to be clinically euthyroid but to have residual palpable thyroid tissue and only a modest reduction in the serum thyroxine level. It is therefore recommended that patients not overtly hypothyroid 3 months after treatment with 131I be observed still longer before thyroxine replacement therapy is instituted.
Radioiodine is used as the definitive treatment of choice in most patients with Graves' hyperthyroidism. Most patients with Graves' disease eventually develop hypothyroidism following I-131 therapy and require thyroid hormone replacement therapy. We present a patient with aortic stenotic cardiac disease and coronary artery disease who suffered from fatigue, weight loss and atrial fibrillation. The patient's radionuclide study, as well as the T4 and TSH, confirmed Graves' disease and he received I-131 therapy. Our patient's development of hypothyroidism following 5 mCi I-131 therapy after seven days later was considered as unusual; in addition, our patient, at autopsy, had documented histopathologic changes confirming atrophy and fibrosis of the thyroid gland.
Seventy five consecutive patients with Graves' disease complicated by atrial fibrillation were given a large single therapeutic dose of 600 MBq (16.2 mCi) iodine-131 in an effort to control their hyperthyroidism rapidly and thus restore sinus rhythm. Patients were initially followed up every three months after treatment and then at yearly intervals. The mean period of follow up was 3.1 years. A total of 44 of the patients became hypothyroid and 31 euthyroid, and 33 (75%) and 14 (45%) of these patients, respectively, reverted to sinus rhythm (p less than 0.01). Of the 33 who became hypothyroid and reverted to sinus rhythm, 30 had developed the hypothyroidism within six months after treatment. These results are a strong case for increasing the dose of radioiodine in patients with Graves' disease complicated by atrial fibrillation in an effort to speed the onset of thyroid failure and thus maximise the rate of reversion to sinus rhythm.
Compartmental analysis of the peripheral distribution of labeled thyroxine was applied to various groups of subjects with thyrotoxicosis and hypothyroidism. It was observed that the hepatic incorporation of thyroxine was augmented in subjects with Graves' disease when compared to non-Graves' disease control groups at all levels of thyroid function. Decreased values of hepatic incorporation occurred in primary hypothyroid subjects. These lowered values were not acutely corrected by elevation of the serum thyroxine level, but were observed to be rectified after several months' therapy with exogenous thyroid hormone. These alterations of the hepatic thyroxine-131I incorporation were independently verified by direct quantitative liver scintiscan determinations.
Employing a dual thyroxine tracer system, we were able to demonstrate that during the early phases of equilibration of a tracer dose of thyroxine, alterations in the rate of deiodination were observed to be present in the various thyroid disease states. Increased deiodination rates were found in subjects with Graves' disease and the reverse was noted in patients with primary hypothyroidism. Kinetic analysis of thyroxine compartmental distribution during this early phase of equilibration of a labeled thyroxine tracer indicated that the primary tissue uptake occurred in the liver. These findings supported the contention that the amount of labeled thyroxine incorporated in the liver may be directly related to the deiodination rate of thyroxine by that organ. The pathogenetic basis of these alterations is presently unknown.
Experience using low-dose radioiodine given six-monthly instead of yearly in hyperthyroid patients with Graves' disease is reported. One hundred and thirty-five patients have been treated over a three-year period with 74 MBq (2 mCi) doses of 131I. Thirty-eight percent were controlled with a single dose. Those patients requiring more than one dose were treated with a further 74 MBq (2 mCi) 131I at six-monthly intervals until euthyroid. Using this approach, 46% were euthyroid one year after starting treatment, and 75% were euthyroid at two years. The incidence of hypothyroidism following treatment was 2.2% at one year, with a yearly incidence thereafter of 4-6%. Six-monthly scheduling of low-dose radioiodine in Graves' disease can reduce the time taken to become euthyroid, compared with conventional yearly low-dose treatments. Further follow up is required to confirm the present low incidence of hypothyroidism following treatment.
The goal of iodine-131 therapy for pediatric Graves' disease is to induce hypothyroidism. However, changes in post-treatment thyroid volume have not been investigated in pediatric and/or adolescent patients.
The aim of this retrospective study was to examine whether changes in thyroid volume predict post-treatment hypothyroidism in adolescent Graves' disease patients.
Patients and Methods
We used ultrasonography to examine changes in thyroid volume, and also assessed thyroid functions, at 0, 1, 3, 5, 8 and 12 months after iodine-131 treatment in 49 adolescents ranging in age from 12 to 19 years retrospectively. Based on thyroid function outcome at 12 months, patients were divided into two groups: 29 patients with overt hypothyroidism requiring levothyroxine replacement and 20 without overt hypothyroidism. We compared changes in post-radioiodine thyroid volume between the two groups.
About 90% of patients whose thyroid volume at 3 months after iodine-131 administration was less than 50% of the original volume were hypothyroid by one year after treatment (positive predictive value 88%, sensitivity 75.9%, specificity 85.0%).
We believe ultrasonographic measurement of thyroid volume at 3 months after iodine-131 to be clinically useful for predicting post-treatment hypothyroidism in adolescent Graves' disease patients.
The incidence of differentiated thyroid cancer is increasing in young adults and females in Korea. Some of them experience short-term hypothyroidism in preparation for radioiodine (RAI) therapy, which can have a deleterious effect on the cardiovascular system. However, it is not clear if short-term hypothyroidism induces endothelial dysfunction in patients with low cardiovascular risk. Therefore, the aim of this study was to investigate whether short-term hypothyroidism is associated with endothelial dysfunction in patients with low cardiovascular risk.
Materials and Methods
To evaluate the effect of short-term hypothyroidism on endothelial function in this group, we recruited fifteen female patients with low cardiovascular risk. We analyzed clinical, biochemical, and cardiovascular parameters at four time points: the last day on levothyroxine (LT4) at their usual thyroid-stimulating hormone (TSH)-suppressive doses (P1), 7 days (P2) & 4 weeks (P3) after withdrawal of LT4, and 8 weeks (P4) after replacement of the previous dose of LT4. A high resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia, and after sublingual nitroglycerin.
During short-term hypothyroidism (P3), serum concentrations of total cholesterol and low-density lipoprotein (LDL)-cholesterol were increased (p < 0.001 for each period). In spite of having worsened lipid states, serum high sensitivity C-reactive protein or flow-mediated vasodilatation, which is one of the surrogate markers of the endothelial function, did not change during short-term hypothyroidism.
Short-term hypothyroidism induced worsening of metabolic parameters, but not enough to induce the endothelial dysfunction in patients with low cardiovascular risk.
Short-term hypothyroidism; endothelial dysfunction; thyroid cancer; radioactive iodine; flow-mediated vasodilatation
Over a 7-year period transient hyperthyroidism was diagnosed in 35 patients seen in a consulting practice in a community hospital. The patients were followed up for an average of 15 months. Initially all of them had biochemical evidence of hyperthyroidism but a very low 24-hour uptake of radioiodine. The hyperthyroid phase was short, and there were no relapses. Seventeen patients subsequently became hypothyroid; this phase, too, was almost always transient. The clinical course of the disease in the 11 women who became hyperthyroid within 6 months after giving birth was similar to that experienced by the other patients, but of the 11 who had increased titres of antimicrosomal antibodies a significantly greater proportion (73%) showed at least transient evidence of hypothyroidism; 1 patient remained frankly hypothyroid for a year. Transient hyperthyroidism can be distinguished from Graves' disease only if the uptake of radioiodine is measured. It is important to make this distinction, as transient hyperthyroidism can be managed safely and symptomatically with beta-blockers alone. The propensity of this disease for the postpartum period and the high proportion of patients with antithyroid antibodies suggest an autoimmune cause.
Ablative approaches using radioiodine are increasingly proposed for the treatment of Graves′ disease (GD) but their ophthalmologic and biological autoimmune responses remain controversial and data concerning clinical and biochemical outcomes are limited. The aim of this study was to evaluate thyroid function, TSH-receptor antibodies (TRAb) and Graves′ ophthalmopathy (GO) occurrence after radioiodine thyroid ablation in GD. We reviewed 162 patients treated for GD by iodine-131 (131I) with doses ranging from 370 to 740 MBq, adjusted to thyroid uptake and sex, over a 6-year period in a tertiary referral center. Collected data were compared for outcomes, including effectiveness of radioiodine therapy (RIT) as primary endpoint, evolution of TRAb, and occurrence of GO as secondary endpoints. The success rate was 88.3% within the first 6 months after the treatment. The RIT failure was increased in the presence of goiter (adjusted odds ratio = 4.1, 95% confidence interval 1.4–12.0, P = 0.010). The TRAb values regressed with time (r = −0.147; P = 0.042) and patients with a favorable outcome had a lower TRAb value (6.5 ± 16.4 U/L) than those with treatment failure (23.7 ± 24.2 U/L, P < 0.001). At the final status, 48.1% of patients achieved normalization of serum TRAb. GO occurred for the first time in 5 patients (3.7%) who were successfully cured for hyperthyroidism but developed early and prolonged period of hypothyroidism in the context of antithyroid drugs (ATD) intolerance (P = 0.003) and high TRAb level (P = 0.012). On the basis the results of this study we conclude that ablative RIT is effective in eradicating Graves’ hyperthyroidism but may be accompanied by GO occurrence, particularly in patients with early hypothyroidism and high pretreatment TRAb and/or ATD intolerance. In these patients, we recommend an early introduction of LT4 to reduce the duration and the degree of the radioiodine-induced hypothyroidism.
Autoimmunity; Graves’ disease; ophthalmopathy; radioiodine therapy
There are 3 treatment options for thyrotoxicosis: Antithyroid drugs, Surgery and radioiodine. The choice of treatment varies geographically. Radioiodine therapy is preferred in the United States. The aim of radioiodine is to destroy sufficient thyroid tissue to cure the hyperthyroidism. There is a lack of consensus towards what dose of radioiodine should be used. Several methods are used to determine the dose. In our practice we administer 400 MBq to patients with Graves and in patients with large multinodular goiter, we would administer 800 MBq.
Thyrotoxicosis; radiodine therapy; Dose
Graves' disease is a thyroid-specific autoimmune disorder in which the body makes antibodies to the thyroid-stimulating hormone receptor leading to hyperthyroidism. Therapeutic options for the treatment of Graves' disease include medication, radioactive iodine ablation, and surgery. Radioactive iodine is absolutely contraindicated in pregnancy as exposure to I-131 to the fetal thyroid can result in fetal hypothyroidism and cretinism. Here we describe a case of a female patient with recurrent Graves' disease, who inadvertently received I-131 therapy when she was estimated to be eight days pregnant. This was despite the obtaining of a negative history of pregnancy and a negative urine pregnancy test less than 24 hours prior to ablation. At birth, the infant was found to have neonatal Graves' disease. The neonatal Graves' disease resolved spontaneously. It was suspected that the fetal thyroid did not trap any I-131 as it does not concentrate iodine until 10 weeks of gestation.
Hypocalcemia is a rarely recognized complication of 131I therapy that has been previously reported in only one child with Graves' disease treated with radioiodine (RAI). Here we report a second child with this occurrence.
A 12-year-old African American girl with hyperthyroidism due to Graves' disease and moderate persistent asthma, requiring oral prednisone, was treated with 11.1 mCi of RAI. While normocalcemic initially, the patient developed symptomatic hypocalcemia (6.6 mg/dL), within 3 months postablation. Concomitant findings included hyperphosphatemia, an inappropriately normal parathyroid hormone (PTH) level, vitamin D deficiency, and normal axial bone mineral density. After 2 weeks of treatment with calcium and calcitriol the symptoms of hypocalcemia resolved, and the calcium level returned to normal. PTH levels remained within the reference range throughout.
In this child with Graves' disease, who was normocalcemic on presentation, RAI treatment was followed by compromised function of the parathyroid glands which was sufficient to produce symptomatic hypocalcemia. It is noteworthy and likely pertinent that the patient had a background of vitamin D deficiency and was receiving prednisone for asthma.
Patients scheduled to receive 131I should be evaluated for risk factors for hypocalcemia in order to minimize the likelihood of this potentially serious complication.
There is no consensus on the optimal treatment of multinodular goiter (MNG), but in the past few years, the use of radioiodine has increased. This study’s objective was to evaluate adjuvant methimazole (MMI) therapy to increase and standardize radioiodine uptake (RAIU) with a fixed therapeutic 131I dose of 1110 MBq (30 mCi).
Our study included 5 women with MNG treated with MMI, 10 - 15 mg/day for 2 to 4 months, prior to the administration of 1110 MBq 131I (30 mCi); none of the patients developed hypothyroidism during MMI therapy and had average basal TSH levels of 0.32 ± 0.39 mIU/L that increased to 2.6 ± 0.9 mIU/L (P = 0.07).
RAIU increased from 25.6 ± 8.7% to 49.2 ± 8.3% (P = 0.003). All patients were followed for 12 months: median thyroid volume (TV) decreased from 77.2 mL (32.9 - 124.2) to 48.8 ml (12.4 - 68.9) with an average decrease of 46.4 ± 14.8% (P = 0.01). All patients developed hypothyroidism during the first 6 months after radioiodine therapy.
This new therapeutic protocol using MMI as adjuvant therapy is effective in increasing RAIU as well as the deleterious effects of 131I, without increasing the required dose, but leading to thyroid volume decreases similar to those reported with the use of recombinant human thyrotropin (rhTSH) or higher radioiodine doses.
Methimazole; Radioiodine; Multinodular goiter; Thyroid; Uptake; 131I; Treatment; Hyperthyroidism
The cloning and sequencing of thyroid-stimulating hormone (TSH) receptor (TSHR), combined with advances in molecular techniques, have facilitated the understanding of the interaction of the TSHR antibodies (TSHRAbs) with the TSHR at the molecular level and have allowed the delineation of their clinical role. TSHRAbs in vivo are functionally heterogeneous; the stimulating TSHRAbs cause hyperthyroidism and diffuse goiter in patients with Graves' disease, whereas, the blocking TSHRAbs cause hypothyroidism in some patients with autoimmune hypothyroidism and are the cause of transient neonatal hypothyroidism. Measuring TSHRAbs has potential clinical implications in differential diagnosis of Graves' disease, predicting the outcome of Graves' disease after antithyroid drug treatment, and predicting the fetal/neonatal hyperthyroidism or neonatal hypothyroidism. The existence of epitope heterogeneity in a patient, i.e., of stimulating TSHRAbs with epitopes other than on the N-terminal region of the extracellular domain, is significantly associated with favorable long-term clinical response to antithyroid drug treatment. Measuring these subtypes for thyroid-stimulating antibody (TSAb) has potential clinical implications, for example, in predicting responsiveness to treatment in untreated patients with Graves' disease.
The influence of demographic and clinical factors on the outcome of 131I therapy in hyperthyroid patients has been examined, based on a retrospective evaluation of results obtained in patients submitted to 131I treatment at the Department of Nuclear Medicine and Oncological Endocrinology, Medical University of Lodz (Province Hospital, Zgierz). The goal of the study was to analyse such factors as the age and sex of patients, disease duration, as well as the hormonal status before 131I application, which could have an influence on the effects of therapy with radioiodine 131I.
Material and methods
The study involved 500 randomly selected patients with hyperthyroidism, treated with 131I radioiodine. The following 3 groups were defined: group 1 – patients with multinodular goitre (MNG), n = 200; group 2 – patients with a single autonomous nodule of the thyroid (AFTN), n = 100; group 3 – patients with Graves’ disease (GD), n = 200. The local ethics committee (in the Polish Mother's Memorial Hospital – Research Institute, Lodz) approved the study.
The obtained results indicate that the efficacy of therapy with 131I applied in patients with MNG, AFTN and GD does not depend on either patient sex or patient age. The length of antithyroid treatment before 131I therapy onset does not appear to have any effect on the therapy outcome, and the baseline thyrotropin concentration seems to be significant only in the case of GD.
The analysed demographic factors do not affect the outcome of 131I therapy in hyperthyroidism.
thyroid; hyperthyroidism; 131I radioiodine therapy
One hundred and sixty-four patients with Graves' disease were treated with low-dose radioiodine (2 mCi), with a mean follow up of 4 1/2 years. At this time 74 (45%) were euthyroid having had a single dose, with a total of 131 (80%) being controlled with one or more doses. Three (2%) were still toxic but their mean follow up was only 3 years. Thirty (18%) were rendered hypothyroid, two-thirds of these after a single dose of 2 mCi 131I. The one-year incidence of hypothyroidism was 6%, with an incidence at 6 years of 20%. Previous surgery, medical treatment and thyroid antibody status appeared to have no influence on the outcome.
Radioiodine (131I) therapy is widely accepted as an essential part of therapeutic regimens in many cases of differentiated thyroid cancer. Radiation-induced oxidative damage to macromolecules is a well known phenomenon. Frequently examined process to evaluate oxidative damage to macromolecules is lipid peroxidation (LPO), resulting from oxidative damage to membrane lipids. The aim of the study was to examine serum LPO level in hypothyroid (after total thyroidectomy) cancer patients subjected to ablative activities of 131I.
Materials and methods
The study was carried out in 21 patients (18 females and 3 males, average age 52.4 ± 16.5 years) after total thyroidectomy for papillary (17 patients) or follicular (4 patients) thyroid carcinoma. Hypothyroidism was confirmed by increased TSH blood concentration (BRAHMS, Germany), measured before 131I therapy. Activity of 2.8 - 6.9 GBq of 131I was administered to the patients orally as sodium iodide (OBRI, Poland). Concentrations of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA), as an index of LPO (LPO-586 kit, Calbiochem, USA), were measured in blood serum just before 131I administration (day "0") and on the days 1-4 after 131I therapy. Sera from 23 euthyroid patients served as controls. Correlations between LPO and TSH or 131I activity were calculated.
Expectedly, serum LPO level, when measured before 131I therapy, was several times higher (p < 0.00001) in cancer patients than in healthy subjects, which is probably due to hypothyroidism caused by total thyroidectomy. However, we did not observe any differences between LPO levels after and before 131I therapy. LPO did not correlate with TSH concentration. In turn, negative correlation was found between 131I activity and LPO level on the day "2" after radioiodine treatment.
Radioiodine remnant ablation of differentiated thyroid cancer does not further increase oxidative damage to membrane lipids, at least early, after therapy.
Using plasma glutathione S-transferase measurements hepatocellular integrity was assessed in groups of hyperthyroid and hypothyroid patients before and after treatment. Ten of 14 hyperthyroid patients had clearly raised plasma glutathione S-transferase values at presentation and in each patient treatment with either iodine-131 or carbimazole resulted in a significant fall in glutathione S-transferase. The eight hypothyroid patients had normal glutathione S-transferase values at presentation and all showed a significant increase in these after thyroxine replacement therapy. In three of these patients in whom standard doses of replacement therapy were associated with a raised free thyroxine (T4) concentration but normal total and free triiodothyronine (T3) values glutathione S-transferase was increased. Similar though less consistent changes were seen in the results of standard chemical tests of liver function. It is concluded that hyperthyroidism may produce subclinical liver damage in a high proportion of patients and that this resolves with effective treatment. More important, the data suggest that hypothyroid patients receiving thyroxine replacement therapy may have similar subclinical liver damage. Patients receiving thyroxine should be monitored by the measurement of free, not total hormone concentrations, and in those in whom free T4 is raised the dose of thyroxine should be reduced. It would also be expedient to include periodic biochemical assessment of liver function in patients receiving thyroxine.
Management of Graves′ ophthalmopathy (GO) is based on three pillars: to stop smoking, to restore and maintain euthyroidism, and to treat the eye changes according to severity and activity of GO. Difficulties are frequently encountered in each of these three management issues. The advice to discontinue smoking is straightforward, but just a small minority of smokers is able to quit smoking. Detailed information on how smoking adversely affects the outcome of Graves′ disease may convince patients they have to stop smoking right away. Controversy exists on the most appropriate treatment of Graves′ hyperthyroidism in the presence of GO. 131I therapy is associated with a risk of about 15% for worsening of GO; a preventive course of steroids is indicated in the presence of risk factors (smoking, biochemically severe hyperthyroidism, high level of TSH receptor antibodies, active GO). Alternatives are thyroidectomy or long-term treatment with antithyroid drugs, which apparently are rather neutral with respect to the course of GO. Mild GO is not always perceived as being mild by the patients themselves. Selenium improves mild GO. Moderate-to-severe GO is preferably treated with intravenous methylprednisolone pulses, but serious side effects and relapsing GO do occur. After steroid failure combination therapy with low-dose oral prednisone with either cyclosporine or retrobulbar irradiation can be effective. Dysthyroid optic neuropathy is best treated with IV pulses, followed by orbital decompression if visual functions do not improve. In resistant cases, rituximab might be considered, although failures of this drug are also described.
Decompression; Graves′ Orbitopathy; hyperthyroidism; immunosuppression; management; smoking; unilateral eye disease
Background & objectives:
Radioiodine (131I) or radioactive iodine in low doses is used worldwide as the first line of management in the treatment of hyperthyroidism. Information is available on the extent and severity of cell damage after a high dose radioiodine (131I) therapy for thyroid cancer, but information is scanty on its cellular effects, its extent and severity of cell damage after a low dose 131I therapy. The present investigation was aimed to study the cytotoxic effects of a low dose 131I therapy in varying doses as is normally being used in routine clinical practice in the treatment of various forms of hyperthyroidism.
Peripheral blood lymphocytes were analyzed in 32 hyperthyroid patients. All of them received
131I in the form of sodium iodide solution orally. Blood lymphocytes were studied for the presence of chromosomal aberrations (CA) and micro nucleus (MN) using micronucleus assay. Blood samples of these patients were drawn prior to the treatment, on 7
thdays after the treatment.
The results indicated a positive relationship between 131I dose, CA and MN frequency. A statistically significant increase in CA and MN frequency in day 7 post- therapy and a decrease in mean levels of CA and MN on day 30 post-therapy were observed when compared to pre-therapy.
Interpretation & conclusions:
This study showed that the cytogenetic damage induced by
131I in low doses i.e., less than 555MBq was minimal and reversible. Patients can be motivated to undertake this safe and easy procedure as a first line of therapy in the treatment of hyperthyroidism.
chromosomal aberrations; hyperthyroidism; low dose 131I therapy; micronucleus assay
The effect of hypothyroidism on non-specific bronchial reactivity was studied in 11 patients without pulmonary disease (mean age 40 (SD 13) years) who had had a total thyroidectomy and radioiodine treatment for thyroid cancer 41 (36) months before the study. All patients when mildly hyperthyroid while having long term thyroxine replacement treatment and once when hypothyroid two weeks after stopping triiodothyronine for the purpose of screening for metastases. Bronchial reactivity was assessed by measuring specific airways conductance (sGaw) after increasing doses of inhaled carbachol (45-1260 micrograms). The dose producing a 35% decrease in sGaw (PD35) was determined from the cumulative log dose-response curve by linear regression analysis. Mean baseline sGaw values were similar when the patients were hypothyroid and when they were hyperthyroid (1.35 (0.36) and 1.41 (0.56) s-1 kPa-1). The interstudy coefficients of variation of baseline sGaw were higher in the thyroid patients than in a euthyroid control group (14% versus 8%). Geometric mean PD35 was lower when the patients were hypothyroid (97 micrograms) than when they were mildly hyperthyroid (192 micrograms). It is concluded that acute hypothyroidism increases non-specific bronchial reactivity in nonasthmatic subjects.
Two TRAbs: TSBAb and TSAb. TSBAb causes hypothyroidism. TSAb causes Graves' hyperthyroidism. TSBAb and TSAb block TSH-binding to cells as TRAb, measured as TSH-binding inhibitory immunoglobulin (TBII). We reevaluate TSBAb and TSAb. We studied TSBAb, TSAb, and TBII over 10 years in 34 TSBAb-positives with hypothyroidism and in 98 TSAb-positives with hyperthyroidism. Half of the 34 TSBAb-positives with hypothyroidism continued to have persistently positive TSBAb, continued to have hypothyroidism, and did not recover from hypothyroidism. Ten of the 98 TSAb-positives with hyperthyroidism continued to have positive TSAb and continued to have hyperthyroidism. TSBAb had disappeared in 15 of the 34 TSBAb-positives with hypothyroidism. With the disappearance of TSBAb, recovery from hypothyroidism was noted in 13 (87%) of the 15 patients. TSAb had disappeared in 73 of the 98 TSAb-positives with hyperthyroidism. With the disappearance of TSAb, remissions of hyperthyroidism were noted in 60 (82%) of the 73. Two of the 34 TSBAb-positives with hypothyroidism developed TSAb-positive Graves' hyperthyroidism. Two of the 98 TSAb-positive Graves' patients with hyperthyroidism developed TSBAb-positive hypothyroidism. TSBAb and TSAb are TRAbs. TSBAb-hypothyroidism and TSAb-hyperthyroidism may be two aspects of one disease (TRAb disease). Two forms of autoimmune thyroiditis: atrophic and goitrous. We followed 34 TSBAb-positive patients with hypothyroidism (24 atrophic and 10 goitrous) over 10 years. All of the 10 TSBAb-positive goitrous patients recovered from hypothyroidism and 19 (79%) of the 24 TSBAb-positive atrophic patients continued to have hypothyroidism.