Long-term Antithyroid Treatment Research Articles

Long-Term Antithyroid Treatment in Pediatric and Juvenile Graves’ Disease

Context: Thyroid hormones can affect the development and function of the central nervous system and various other organs. As such, the pathologic excess of these hormones, known as thyrotoxicosis, can be the source of significant damage during childhood and adolescence. The objective of this study was to review the management of Graves’ disease (GD) in the pediatric age group, especially concerning long-term antithyroid drug (ATD) treatment. Evidence Acquisition: A thorough search of literature published from 1980 to 2019 was performed in PubMed only for English language literature. The following key terms were used: “Graves’ disease, hyperthyroidism, thyrotoxicosis in children, thyrotoxicosis remission, thyrotoxicosis relapse, definite therapy, radioactive iodine, thyroidectomy, anti-thyroid drugs, propylthiouracil, methimazole, and carbimazole”. We also did a thorough search in review articles, observational studies, open-label/controlled randomized/non-randomized trials, and meta-analyses, as well as the articles cited by textbooks, chapters, and review articles, which led us to locate older sources of information on the topic. Results: More than 90% of thyrotoxicosis in the pediatric age group is attributable to GD. A host of strategies, including ATDs, radioiodine therapy, and surgery, are employed to treat this entity. However, there is still significant controversy regarding the most optimal strategy. Current evidence suggests that ATDs are the best initial treatment in pediatric patients with GD. Although ATDs are widely used, the duration of their administration is controversial and varies significantly between protocols. A major problem is the high relapse rate (up to 70%), but extending the duration of such treatment could potentially bring the remission rate up to 88%. Indications for using radioactive iodine treatment include the lack of remission following years of receiving ATDs, poor compliance, and the emergence of a major side effect. In pediatric patients aged five-years-old or younger who suffer from very large goiter, severe ophthalmopathy, and persistent hyperthyroidism, as well as those with the lack of response to or showing adverse effects of ATDs, it is advisable to consider total or near-total thyroidectomy. Conclusions: Antithyroid drugs are the mainstay of treatment of juvenile GD, and long-term methimazole therapy increases the remission rate in pediatric GD.

Long-term outcome of thyrotoxicosis in childhood and adolescence in the west of Scotland: the case for long-term antithyroid treatment and the importance of initial counselling

Management of thyrotoxicosis in children and adolescents remains challenging and treatment varies considerably among institutions. The patient’s age, clinical status and likelihood of remission should be considered when counseling patients and parents. Nevertheless, individual prognosis of antithyroid drug treated Graves’ disease in children is highly variable and studies with data on long-term outcome are scarce. Recommendation 58 of the 2016 American Thyroid Association guidelines state that children with Graves’ disease can be treated with either methimazole or thyroidectomy at any age. Alternatively, radioiodine ablation is a further option, but not before 5 years of age, and between 5-10 years only if radioiodine activity is <10mCi.

Long-term outcome of thyrotoxicosis in childhood and adolescence in the west of Scotland: the case for long-term antithyroid treatment and the importance of initial counselling

BackgroundThyrotoxicosis is both rarer and more severe in children than in adults, rendering management difficult and often unsatisfactory.ObjectiveTo ascertain outcome in a geographically defined area of Scotland between 1989 and...

Effects of long-term oral administration of methimazole on femur and tibia properties in male Wistar rats

Physiological concentrations of thyroid hormones are crucial for skeletal growth and development, physiological bone turnover and bone homeostasis maintenance. Methimazole (1-methyl-2-mercaptoimidazole) is an antithyroid drug used for the treatment of the hyperthyroidism in humans and animals. The aim of the study was to determine effects of long-term oral methimazole treatment in male Wistar rats on biochemical bone metabolism markers, as well as morphological, geometric, densitometric and mechanical properties of femur and tibia. Experimental rats were subjected to 90-day-long oral treatment with 0.05% water solution of methimazole and were kept under identical environmental conditions and received the same diet ad libitum as the control group. Serum concentration of osteocalcin (OC) and C-terminal telopeptides of type I collagen (CTX-I) was determined. Femur and tibia were evaluated using quantitative computed tomography (QCT), peripheral QCT (pQCT) and three-point bending test. Final body weight of the experimental group was significantly decreased by 30% (P=0.01). Methimazole treatment significantly decreased serum OC concentration by 21% (P=0.02) and increased CTX-I concentration by 17% (P=0.06). Methimazole decreased morphological, geometric and densitometric parameters of femur and tibia in rats. Mechanical evaluation of bones has shown significantly decreased maximum elastic strength and ultimate strength of femur in rats treated with methimazole by 36% and 40% when compared to the control group (P<0.05). In conclusion, this study has shown that long-term treatment with methimazole inhibits bone formation and accelerates bone resorption processes. The observed negative effects of methimazole treatment on body weight gain and skeletal properties may be considered as additional possible side effects in living organisms to those reported in the previous studies. It may be suggested that long-term antithyroid treatment should be combined with prevention of the negative effects of methimazole on bone tissue and whole body metabolism.

Simultaneous assay for three types of thyrotropin receptor antibody activities using FRTL-5 cells in patients with autoimmune thyroid diseases.

The relationships between the different circulating thyrotropin receptor antibodies (TSH-R-abs) in autoimmune thyroid disease (AITD) are complex. In order to investigate them, we have developed an assay for the simultaneous measurement of three types of TSH-R-abs: TSH-binding inhibiting immunoglobulin (TBII): thyroid-stimulating antibody (TS-ab) and TSH-stimulation blocking antibody (TSB-ab). A large number of patients with Graves' disease (GD)--untreated and treated--Hashimoto's thyroiditis (HT), primary myxedema (PM) and non-immune goiter (NIG) were investigated. In untreated Graves' patients the frequency of positive TS-ab and TBII sera was found to be 90 and 69%, respectively, the presence of TS-ab and/or TBII being detected in 98%. After long-term antithyroid treatment administered to GD patients, the frequency of positivity of both TBII and TS-ab was decreased, whether hyperthyroidism was cured or not. The TSB-ab was detected in the serum of 8% of patients with GD, and the frequency of TSB-ab did not increase following treatment and alteration in thyroid function. No significant correlation was found between TSB-ab and thyroid function in Graves' patients. Besides, we found that all the GD patients presenting positive TSB-ab were also TBII positive. A follow-up study of the three TSH-R-abs was performed in 35 patients with GD during a mean of 14.3 +/- 8.5 months (4-34 months) of antithyroid drug treatment. Ten out of 24 patients (42%) with positive TBII and 16 out of 32 (50%) with positive TS-ab turned from positive to negative during the time of follow-up. Regarding relapse in hyperthyroid GD, we found that TS-ab was positive in 80% and TBII was positive in 40% of the patients with Graves' relapse, indicating that the presence of TS-ab is a better index for relapse prediction in Graves' hyperthyroidism than TBII. The TSB-ab was found with higher frequency in HT and PM than in GD, i.e. 21%, 18% and 8%, respectively., The TSB-ab positivity was correlated significantly with TBII in our patients with AITD when TSB-ab was positive. This new simultaneous assay of the three TSH-R-abs should be very helpful for further investigation of the autoimmune aspects of AITD and it should help us to progress in a better understanding of the pathogeny of the different AITDs.

The prognostic value of parallel measurements of thyrotropin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cyclase stimulating antibodies (TSAb) in Graves' disease after longterm antithyroid treatment.

Thyroid stimulating immunoglobulins were measured in 43 patients with Graves' disease both before and at the end of longterm antithyroid treatment. Parallel determinations were performed of thyrotropin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cyclase stimulating antibodies (TSAb). Before treatment 33 patients were TBII positive and 32 TSAb positive, and at the end of treatment 19 remained TBII positive and 14 TSAb positive. The frequency of relapse was about 70% in the positive patients and about 40% in the patients, who became negative in either test for thyroid stimulating immunoglobulins. By combination of the two assays 23 patients were positive in both before treatment. In these patients 5 relapsed of the 6 who remained positive for both, while none relapsed of the 5 patients, who became negative during treatment. In the remaining 12 patients either TBII or TSAb became negative during treatment and 7 of these relapsed. It is concluded, that the combined measurement of TBII and TSAb in this study seemed superior to the separate determinations of either activity in predicting relapse after medical treatment of Graves' disease, though this evaluation was only possible in part of the patients.

Evidence of a correlation between thyrotrophin receptor binding inhibition and thyroid adenylate cyclase activation by immunoglobulins in Graves' disease before and during long-term antithyroid treatment.

In the present study we have measured in parallel thyrotrophin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cylase stimulating immunoglobulins (TACSI) in patients with Graves' disease (GD) both before and during long-term antithyroid treatment. A statistical model based on the calculation of the differences (TACSI-TBII) is presented, comparing the changes in this parameter to the analytical variation. The correlation between TBII and TACSI in 52 patients with GD before treatment was: r = 0.58, P less than 0.0001. During long-term antithyroid treatment of GD the 2 activities changed in parallel in 39 of 45 patients followed. In a few patients discrepancies were observed, and 1 patient, initially TACSI positive, developed adenylate cyclase inhibiting IgG during treatment but without detectable TBII. In conclusion, 1) TBII and TACSI are significantly correlated in patients with GD both before and during long-term antithyroid treatment, 2) in some patients discrepancies between TBII and TACSI suggest, that these IgGs are heterogeneous with varying capacity for stimulation of the adenylate cyclase and receptor binding, and 3) adenylate cyclase inhibitory IgG without TBII activity was demonstrated in GD.

Prognostic value of thyrotrophin binding inhibiting immunoglobulins (TBII) in longterm antithyroid treatment, 131I therapy given in combination with carbimazole and in euthyroid ophthalmopathy.

Thyrotrophin binding inhibiting immunoglobulins (TBII) were measured in 27 patients with Graves' disease during and after longterm antithyroid treatment. The median observation period after treatment was 24 months. During the first 6 months of treatment the TBII index increased significantly in both the relapse and the remission group, but during the rest of the treatment and the observation no further change was observed. Patients with a TBII index below 0.35 at drug withdrawal (n = 8) all relapsed and patients with values above 1.00 (n = 5) all stayed in remission. There was a significant correlation between the TBII index at drug withdrawal and the time elapsed before a relapse. Graves' disease was treated with 131I in combination with carbimazole in 22 patients. The TBII index of these patients decreased after 131I and increased towards normal values during longterm observation of median 33 months. Of 4 patients with euthyroid ophthalmopathy one was TBII positive. This patient became overt hyperthyroid after an observation period of two years of prednisone treatment. It is concluded, that the TBII index is of some prognostic value after longterm antithyroid treatment, but is of no clinical importance following 131I treatment.

Long-term antithyroid treatment in hyperthyroidism

Long-term antithyroid treatment in hyperthyroidism

Long-term Antithyroid Treatment in Hyperthyroidism

The major drawback to treatment of hyperthyroidism with antithyroid compounds is the reported low rate of remission. Eighty patients have been given long-term (at least one year; average, 4.4 years; range, one to 14 years) continuous treatment with a remission rate of 76% and an average follow-up of 7.8 years (one to 21 years). The prognostic test of suppressed uptake by the thyroid of less than 20% was about 75% accurate in predicting continuing remission when treatment was stopped. Of those in remission, 14 (23%) were treated for one year, 35 (57%) for one to five years, and 12 (20%) for more than five years. Mild reactions occurred in five (6%), hypothyroidism in two (3%). An antithyroid drug is safe and effective therapy for hyperthyroidism.

Recovery of initially suppressed thyroidal radioiodine uptake during long-term antithyroid treatment of euthyroid volunteers and hyperthyroid patients.

ABSTRACT Carbimazole in daily doses of either 15 or 45 mg acutely depressed the thyroidal 131I-uptake (measured at 2, 8 and 24 hours after administration of the tracer) in 34 healthy human volunteers. Fourteen of these subjects were kept on carbimazole for four weeks. A gradual recovery of the radioiodine uptake was observed in every individual. By the end of the fourth week the 24 h uptake had risen by 100% over the value observed with acute suppression in the 15 mg carbimazole group (i. e. from 5.7 to 11.4%) and by 500% in the 45 mg carbimazole group (i.e. from 2.7 to 15.8%). The corresponding figures for the 8 h uptake were 100 to 250% and for the 2 h uptake 40 to 60%. In three individuals the uptake in the fourth week of carbimazole treatment was distinctly higher than the pretreatment control values. Thus the acute suppression of a complete blocking dose of carbimazole on thyroidal radioiodine uptake is partially or even totally overcome within a few weeks of chronic treatment. It is therefore possible, in human subjects, to produce experimentally a high thyroidal radioiodine uptake by antithyroid drug treatment alone, in the absence of concomitant severe iodine deficiency. This finding may have a bearing on the interpretation of radioiodine studies carried out on endemic goitre. Comparable findings were obtained in 23 hyperthyroid patients treated with carbimazole for a mean of 28 weeks. In order to elucidate the mechanisms responsible for the later rise of an acutely carbimazole suppressed uptake, the serum PB127I and TSH concentration was measured at weekly intervals. Whereas the PBI fell both in this and in another series of volunteers by the end of the fourth week of carbimazole treatment, no significant change in serum TSH concentration was measurable by radioimmunoassay. Nevertheless, the hypothesis is put forward that a biologically significant increase in serum TSH concentration had occurred, which was not detectable by the radioimmunoassay techniques available at the present time. There are indeed reasons to suspect that biologically important variations in TSH secretion may occur which fail to bring the serum TSH concentration beyond the normal range defined by radioimmunoassay.

CHILDHOOD HYPERTHYROIDISM

ABSTRACT Thirty-nine patients with childhood hyperthyroidism were treated during the period 1950-1964, most of them after 1955. The youngest patient was 3 years old. Thyroid nodules occurred in 55 per cent of the cases. In 25 patients long-term anti-thyroid treatment was instituted. This therapy was considered as successful in 7 instances (29 per cent). Four patients (17 per cent) are still under treatment, while in 13 (54 per cent) operation was later regarded as advisable owing to unsuccessful anti-thyroid treatment. The failure of thyrostatic therapy may have had some connection with the presence or appearance of thyroid nodules. In eight instances operation was carried out, primarily owing to compressive and/or nodular goitre. The results of operation (21 cases in all) are that 10 patients are euthyroid (48%) and 4 hypothyroid (19%) whilst 7 had a relapse or persistence of the disease (33%) of whom 5 are still under treatment and two have subsequently been rendered euthyroid by reoperation in one case and radioactive iodine (at the age of 19) in another case. There also seems to be a small group of patients (6 cases in this series) in whom, in spite of evident »biochemical disease« although with slight clinical signs and symptoms, the condition seems to resolve spontaneously and nothing but close observation appears to be needed. A primarily conservative attitude seems advisable. The presence of nodules in the thyroid initially, however, seems to indicate that a surgical approach will be required later on.