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Objective: Iodinated contrast media (ICMs) are widely used in a variety of examinations and procedures. The aim of the current study was to investigate the efficacy of methimazole (MMI) in prevention of thyrotoxicosis after ICM exposure., Methods: A retrospective cohort study included patients aged ≥18 years admitted to a tertiary medical center who underwent ICM examination or procedure and received MMI prior to iodine exposure., Results: A total of 179 patients with 202 hospitalizations were included. The mean age was 72.3 ± 13.5 years (female, 64%). Nearly all patients (99%) had a history of thyroid disease, and 91% were treated with MMI prior to admission. Seventy-five patients had low thyroid-stimulating hormone (TSH) levels prior to ICM exposure. In this high-risk group, MMI led to normalization of TSH after discharge in 19%, and 64% remained with low TSH levels after discharge but with a small median difference in free thyroxine levels of -0.5 (interquartile range [IQR], -5.9 to 5.2) pmol/L. In the 8 patients with dose increase during hospitalization, treatment with MMI was beneficial with a median free thyroxine decrease of -6.2 (IQR, -9.2 to -1) pmol/L and TSH increase of 0.2 (IQR, 0.02-0.7) mIU/L. In 110 patients with normal TSH levels before admission, with MMI treatment, most (71%) remained euthyroid after discharge, 13% had low TSH levels, and 9% had high TSH levels. In the 15 patients with high TSH levels prior to admission, the TSH levels of only 2 patients normalized, 47% remained with high TSH levels, and 27% had low TSH levels after discharge., Conclusion: In patients with pre-existing thyrotoxicosis treated with antithyroid drugs, MMI therapy before ICM exposure prevented exacerbations. In patients with low TSH levels before admission, increasing the dose of MMI before exposure led to improvement in thyroid functions after discharge., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Objective: To assess response predictors to radioactive iodine (RAI) therapy without using thyroid uptake for dose estimate in patients pretreated with methimazole., Methods: Retrospective analysis was performed of patients with Graves' disease treated with RAI doses determined without using uptake studies., Results: In 242 patients (median age, 41.9 years; 66.1% female), initial mean free thyroxine (FT4) level was 4.7 ng/dL with an estimated thyroid size of 49.15 g. Prior to RAI therapy, average methimazole dose was 22.7 mg/day. Mean RAI dose was 737.0 ±199.4 MBq (19.9 ± 5.4 mCi). Two hundred eight patients (85.9%) responded to RAI therapy; 185 (88.9%) became hypothyroid and 23 (11.1%) became euthyroid. The majority (90.4%) responded within 6 months of therapy with a quicker response (13.9 ± 8.3 vs 17.5 ± 13.5 weeks) for those treated with doses per gram of ≥14.8 MBq (0.4 mCi). Thirty-four nonresponders had a higher initial FT4 level and larger thyroid size with a lower RAI dose per gram of thyroid tissue. In multivariate analysis, the independent response predictor to therapy was dose per gram of thyroid tissue of ≥14.8 MBq (0.4 mCi) (hazard ratio, 3.18; 95% CI, 1.1-9.7). Doses per gram of 14.8 to 18.1 MBq (0.4-0.5 mCi) achieved maximal response rate without added advantage of higher doses. Thyroid size prior to RAI therapy, FT4 levels at diagnosis, and age were inversely related to response., Conclusion: RAI therapy for Graves' disease without uptake studies for dose estimates is an effective treatment method. In patients pretreated with methimazole, an RAI dose per gram of thyroid tissue of ≥14.8 MBq (0.4 mCi) showed high response rate. Prospective studies are needed to confirm the viability of this simplified and cost-effective approach., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Objective: Iodine 131 (I-131) radioactive iodine (RAI) therapy has been the preferred treatment for Graves disease in the United States; however, trends show a shift toward antithyroid drug (ATD) therapy as first-line therapy. Consequently, this would favor RAI as second-line therapy, presumably for ATD refractory disease. Outcomes of RAI treatment after first-line ATD therapy are unclear. The purpose of this study was to investigate treatment failure rates and potential risk factors for treatment failure, including ATD use prior to RAI treatment., Methods: A retrospective case control study of Graves disease patients (n = 200) after I-131 RAI therapy was conducted. Treatment failure was defined as recurrence or persistence of hyperthyroidism in the follow-up time after therapy (mean 2.3 years). Multivariable regression models were used to evaluate potential risk factors associated with treatment failure., Results: RAI treatment failure rate was 16.5%. A majority of patients (70.5%) used ATD prior to RAI therapy, predominantly methimazole (MMI) (91.9%), and approximately two-thirds of patients used MMI for >3 months prior to RAI therapy. Use of ATD prior to RAI therapy (P = .003) and higher 6-hour I-123 thyroid uptake prior to I-131 RAI therapy (P<.001) were associated with treatment failure. MMI use >3 months was also associated with treatment failure (P = .002)., Conclusion: More patients may be presenting for RAI therapy after failing first-line ATD therapy. MMI use >3 months was associated with RAI treatment failure. Further studies are needed to investigate the association between long-term first-line ATD use and RAI treatment failure., (© 2020 American Association of Clinical Endocrinologists. Published by Elsevier, Inc. All rights reserved.)

Objective: The present study aimed to investigate the adverse effects of the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI)/carbimazole (CMZ) in treating hyperthyroidism. Methods: Qualitative analysis was performed for studies identified in a literature search up to April 20, 2019, and 30 studies were selected for meta-analysis. The study designs included case-control, randomized controlled, and retrospective cohort. Patients were in four age groups: childhood, gestating mothers, older adults, and other ages, and all were receiving PTU or MMI/CMZ. Adverse reactions to MMI/CMZ and PTU were evaluated and compared. Results: Odds of liver function injury were higher in the PTU group than in the MMI/CMZ group (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.16 to 4.96; P = .02). Odds of elevated transaminase were much higher in the PTU group than in the MMI/CMZ group (OR, 3.96; 95% CI, 2.49 to 6.28; P <.00001). No significant between-group differences were found in odds of elevated bilirubin, agranulocytosis, rash, or urticaria; incidence of other adverse events; or in children. Odds of birth defects during the first trimester of pregnancy were higher in the MMI/CMZ group than in the PTU group (OR, 1.29; 95% CI, 1.09 to 1.53; P = .003). Conclusion: The impact of PTU on liver injury and transaminase levels is greater than that of MMI/CMZ, but no significant between-group differences are found in the drugs' effects on bilirubin, agranulocytosis and rash, urticaria, or in children. In treating pregnancy-related hyperthyroidism, PTU should be used in the first trimester and MMI reserved for use in late pregnancy. Abbreviations: ALT = alanine aminotransferase; ATD = antithyroid drug; CI = confidence interval; CMZ = carbimazole; GD = Graves disease; MMI = methimazole; MTU = methylthiouracil; NOS = Newcastle-Ottawa Scale; OR = odds ratio; PTU = propylthiouracil; RAI = radioactive iodine.

Exotropia is rarely reported in thyroid eye disease (TED). We report the case of an 18-year-old patient with TED who developed exotropia and hypotropia as an initial presentation of TED., (Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Objective: Overt hyperthyroidism and methimazole (MMI) treatment are frequently associated with abnormal liver function tests (LFTs). We describe the serial changes of LFTs in MMI-treated hyperthyroid patients., Methods: We retrospectively analyzed all 77 patients presenting with newly diagnosed overt hyperthyroidism (59 Graves diseases, 11 toxic nodular goiters, 4 toxic adenomas, 3 amiodarone-induced thyrotoxicosis) between 2012 and 2014. All patients started MMI at 10 to 60 mg/day that was gradually tapered. We measured thyroid-stimulating hormone, free thyroxine, alanine aminotransferase (ALT) and aspartate aminotrasnferase (AST) at baseline and at 6 weeks, 4.5 months and 10 months after starting the MMI treatment. The concomitant medication was stable during MMI treatment., Results: At baseline, 25 patients (32.5%) had abnormal LFT, of which 5 had ALT or AST levels >2× the upper limit of normal (ULN). In most patients with baseline abnormal LFT, MMI treatment resulted in a normalization of serum ALT and AST. Thirteen patients with normal baseline LFT had <2× the ULN elevations of LFT sometime during treatment. There was a case of significant hepatotoxicity. During treatment, there were no significant differences in LFT levels between patients with initially normal or abnormal LFT. In a Cox proportional hazard regression model, abnormal LFT at baseline, abnormal thyroid function at the last evaluation, and MMI dose were not predictors of abnormal LFT at the final evaluation., Conclusion: MMI treatment can induce insignificant LFT elevation, <2× the ULN. MMI can be safely administered in hyperthyroid patients with abnormal LFT, and normalization of increased AST and ALT levels should be anticipated., Abbreviations: ALT = alanine aminotransferase AST = aspartate aminotransferase fT4 = free thyroxine HCV = hepatitis C virus LFT = liver function test LOCF = last observation carried forward MMI = methimazole PTU = propylthiouracil TSH = thyroid-stimulating hormone ULN = upper limit of normal.

Objective: To demonstrate that drug-induced agranulocytosis can occur after a very prolonged period of low-dose treatment with antithyroid medications., Methods: We present the history and long-term follow-up of a patient with Graves disease, including clinical and laboratory findings, and provide a brief review of the related literature., Results: A 53-year-old woman with a history of Graves disease presented with an absolute neutrophil count of zero, body temperature of 38.7°C, and symptoms of an upper respiratory tract infection. She had been treated continuously with low doses of antithyroid drugs for the preceding 11 years-propylthiouracil (100 to 150 mg daily) from February 1998 until July 2003 and methimazole (5 to 30 mg daily) from July 2003 until her presentation with severe neutropenia in March 2009. The daily dose of methimazole had been stable at 15 mg for 1 year before the current presentation. A thorough hematologic evaluation, including bone marrow biopsy, did not reveal an alternative cause for the agranulocytosis. After discontinuation of methimazole treatment and a short course of granulocyte colony-stimulating factor, she responded successfully with clinical improvement of her symptoms and resolved neutropenia., Conclusion: Although this case is atypical, it reinforces the importance of remaining vigilant for signs of agranulocytosis throughout the course of treatment with antithyroid drugs, even at low doses and after years of continuous administration.

Objective: To alert clinicians about the risk of vasculitis and cross-reactivity of antithyroid medication., Methods: We describe the clinical course and medical management of the study patient., Results: A 25-year-old woman with hyperthyroidism developed antineutrophil cytoplasmic antibody-positive vasculitis after 15 months of propylthiouracil therapy. Her condition improved when propylthiouracil was withdrawn, but recurred when she was prescribed methimazole. Propylthiouracil and methimazole are commonly used antithyroid medications, and propylthiouracil is a well-recognized cause of drug-induced vasculitis. Cross-reactivity between the 2 drugs is likely, but it has not been reported previously with regard to vasculitis. Many patients with propylthiouracil-induced vasculitis have been switched to methimazole., Conclusions: Awareness of this rare, but potentially serious, adverse drug reaction is important because prompt discontinuation of medication is essential. Cross-reactivity between propylthiouracil and methimazole must be considered when selecting alternative therapies.

Objective: To report an unusual case of hyperthyroidism from Graves' disease that was coexistent with malignant struma ovarii., Methods: We summarize the clinical history, physical findings, laboratory data, imaging studies, pathologic features, and treatment in a patient with recurrent hyperthyroidism and discuss the incidence of ovarian tumors of various histologic origins, including thyroid tissue (that is, struma ovarii)., Results: Five years after diagnosis of Graves' disease and resolution of symptoms with 1 year of antithyroid drug therapy, a 53-year-old woman had recurrence of palpitations, tremors, and weight loss. Results of thyroid function tests showed high total and free thyroxine levels and a low thyrotropin level. Thyroid radioiodine uptake was high (69% at 24 hours). Abdominal ultrasound studies disclosed a cystic mass in the right adnexal area. Total abdominal hysterectomy and bilateral oophorectomy revealed a 7.5-cm cystic right ovary that contained a 1.0-cm struma ovarii with a 0.4-cm nodule of follicular variant papillary thyroid carcinoma within it. The patient was treated with methimazole and radioiodine ablation of the thyroid. Three months later, a massive myocardial infarction resulted in her death., Conclusion: The concomitant presence of Graves' disease complicates the management of struma ovarii and raises interesting questions about treatment and prognosis.

Objective: To describe the case of a young woman who had severe osteoporosis due to the compounding effects of pregnancy, lactation, and hyperthyroidism and who had a presumed metastatic lesion in the lumbar spine., Methods: We present the clinical, pathologic, radiologic, and laboratory findings and describe the clinical course of our patient., Results: A 31-year-old Arabic woman was referred to the M. D. Anderson Cancer Center because of a lytic lesion in her lumbar spine, presumed to be metastatic deposits. She had a history of two consecutive pregnancies and intermittently treated hyperthyroidism. Our initial evaluation revealed that the patient had clinical and biochemical thyrotoxicosis, and we treated her with thionamides, corticosteroids, and radioiodine ablation. Radiologic studies disclosed a complex renal cyst that had increased uptake on a bone scan, which was highly suggestive of a primary malignant lesion. Ultimately, however, it proved benign on pathologic analysis after a left nephrectomy. Bone mineral density measurements identified severe osteoporosis (T-scores: lumbar spine, -3.3; right hip, -2.2; and left hip, -2.0), which had led to vertebral collapse and was misinterpreted as malignant metastatic disease. The bone mineral densities improved (+5 to +11% at the various sites) within 4 months after definitive treatment and cure of the hyperthyroidism., Conclusion: The effect of pregnancies and prolonged lactation, in the milieu of other risk factors for bone depletion such as hyperthyroidism, may cause severe osteoporosis in a young patient. The resulting osteoporosis may manifest as a lesion suggestive of malignant metastatic involvement.

We performed a randomized, open prospective study to determine the effect of 1 alpha-hydroxyvitamin D3 [1 alpha (OH)D3] on hyperthyroidism in patients with untreated Graves' disease. At the time of entry into the study, 30 patients were randomly assigned to receive a daily dose of 30 mg methimazole (MMI) (group A, n = 15) or the same dose of MMI supplemented with 1.5 micrograms 1 alpha (OH)D3 (group B, n = 15). These treatment regimens were continued for 24 weeks, and physicians were allowed to adjust MMI dosage during follow-up visits. Blood samples were collected, and serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), T3, T4, thyrotropin (TSH), alkaline phosphatase (ALP), and TSH-receptor antibody (TRAb) were determined. During the follow-up periods, all patients became euthyroid. The dose of MMI was not significantly different between these two groups. In contrast, decreases in mean serum FT3 and FT4 levels, as well as in mean serum T3 and T4 levels, were greater in group B. Correspondingly, the reciprocal increase in the mean TSH level was more prominent in group B. Mean TRAb levels did not differ between the two groups. Mean serum ALP levels in group B were significantly lower than in group A at 24 weeks. Thus, we suggest that concomitant administration of 1 alpha (OH)D3 is useful for treating hyperthyroidism in patients with Graves' disease.

The effects of hyperthyroidism on uric acid metabolism were investigated. First, the serum uric acid level was measured in 92 patients with hyperthyroidism due to Graves' disease, eight patients with subacute thyroiditis, six patients with hypothyroidism, and 70 sex- and age-matched controls. Second, the correlation between serum thyroxine (T4) and serum uric acid was obtained in hyperthyroid Graves' disease patients before and during antithyroid drug therapy. Finally, uric acid clearance (CUA) was determined in untreated patients with hyperthyroidism due to Graves' disease. Serum uric acid was significantly elevated in patients with hyperthyroidism, and the elevation correlated well with serum T4 before treatment as a group and during treatment in each patient. A significant elevation of serum uric acid was not present in patients with a transient mild thyrotoxicosis due to subacute thyroiditis. Serum uric acid was significantly decreased in patients with hypothyroidism. Renal excretion of uric acid clearly increased in hyperthyroid patients, and CUA also increased. The increase in CUA corresponded to the increase in renal plasma flow (RPF), which was measured by p-aminohippuric acid clearance. The fractional excretion of uric acid as determined by CUA/glomerular filtration rate (GFR) was similar and within the normal range in hyperthyroid patients and normal controls. A significant inverse correlation between CUA and serum uric acid concentration was present in hyperthyroid patients as in normal controls, indicating that the renal handling of uric acid in the tubule affected uric acid excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective study was conducted to evaluate the effect of prolonged treatment of hyperthryoid Graves' disease with methimazole (MMI) for 12 months or Na ipodate for only 6.6 +/- 1.1 months, since the drug had to be discontinued because of persistent or recurrent hyperthyroidism during treatment. The eight patients who were treated with MMI alone for 12 months became euthyroid, and seven remained in remission for at least 6 months after MMI was discontinued. In contrast, only two of 10 patients treated with Na ipodate alone became euthyroid and remained so during therapy. No ipodate was discontinued in the eight patients who did not respond, and they were then treated with MMI. One patient had recurrent hyperthyrodism after NA ipodate was discontinued, and she was then treated with MMI. MMI was efficacious in treating these nine patients, and all patients were euthyroid by the third month of MMI administration. Five of these nine patients remained euthyroid for at least 6 months after MMI was discontinued, a remission rate that was not significantly different from that observed in the eight patients treated only and initially with MMI (Fisher's Exact Test). There was no significant change in serum thyroid peroxidase antibodies during treatment with MMI alone, Na ipodate alone, or Na ipodate followed by MMI.(ABSTRACT TRUNCATED AT 250 WORDS)

In 77 untreated patients (16 males and 61 females, aged 12 to 65 years) with hyperthyroid Graves' disease, and in 107 control subjects (36 males and 71 females, aged 13 to 78 years), blood urea nitrogen (BUN), serum creatinine (Scr) levels, and BUN to Scr ratios (BUN/Scr) were determined. In 53 patients, the determinations were performed before treatment and after restoration of euthyroidism by treatment with an antithyroid drug. In addition, in seven untreated patients and seven normal subjects, renal clearances of creatinine (Ccr), urea nitrogen (Cun), inulin (Cin), and p-aminohippurate (CPAH) were also determined. The distal tubule delivery of chloride (DTD) and the distal fractional chloride reabsorption (DFCR) were also measured in these subjects: DTD = (CH2O + Ccl)/Cin x 100, and DFCR = CH20/(H20 + Ccl) x 100, where CH20 and Ccl stand for clearances of H2O and chloride, respectively. BUN was significantly elevated, while Scr was significantly depressed, in untreated patients with hyperthyroid Graves' disease. Accordingly, the BUN/Scr was markedly elevated. Restoration of euthyroidism accompanied the normalization of all these abnormalities. Ccr and Cun were significantly elevated, but Cin (glomerular filtration rate [GFR]) was slightly, but insignificantly, elevated in the patients. As a result, the ratios Ccr/Cin and Cun/Cin were significantly greater in the patients than in controls (Ccr/Cin, 1.42 v 1.00; Cun/Cin, 0.92 v 0.68). The amounts of urinary creatinine and urea nitrogen (UN) excretion were decreased and increased, respectively, and DTD was significantly depressed, but DFCR was unchanged in the patients. We conclude that BUN is elevated, Scr is depressed, and the BUN/Scr is increased in hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

We have recently reported that, in patients with hyperthyroidism, the red blood cell (RBC) carbonic anhydrase I (CAI) and zinc (Zn) concentrations both reflect the patient's integrated thyroid hormone level over the preceding few months. In this study, we evaluated the clinical usefulness of determining the RBC CAI and Zn concentrations in patients with various types of thyroid disease. Six patients with painless thyroiditis (PT) had normal RBC CAI concentrations and the two patients tested had normal RBC Zn levels. In four patients with syndromes of inappropriate thyrotropin (TSH) secretion (SITSH) two euthyroid patients had normal RBC CAI and two hyperthyroid patients had subnormal RBC CAI and Zn. In a patient with Graves' disease whose plasma thyroxine (T4) and triiodothyronine (T3) concentrations changed remarkably because of poor compliance with the regimen, the change in plasma thyroid hormone levels preceded the change in the RBC CAI and Zn concentrations by 2 to 3 months. These observations suggest that the measurement of RBC CAI and Zn concentrations may be useful clinically as follows: (1) in differentiating hyperthyroid Graves' disease from transient hyperthyroidism due to destructive thyroiditis; and (2) in obtaining an accurate estimate of the extent of elevated thyroid hormone levels in hyperthyroid patients over time.

Red blood cell (RBC) zinc (Zn) concentration was measured by atomic absorption spectrophotometry in 28 healthy volunteers, in 46 patients with hyperthyroidism, and in 6 patients with hypothyroidism. The mean (+/- SD) RBC Zn concentration in euthyroid controls was 11.4 +/- 1.5 mg/L RBC, and the normal range defined as the mean +/- 2 SD was 8.5 to 14.3 mg/L RBC. The mean RBC Zn in patients with hyperthyroidism was decreased to 6.4 +/- 1.6 mg/L RBC, and 43 (93%) had low values. The mean RBC Zn in patients with hypothyroidism was not different from that in the controls. There was a significant negative correlation between the concentrations of RBC Zn and those of both plasma thyroxine (T4; r = -0.73) and plasma 3,5,3'-triiodothyronine (T3; r = -0.70). After the treatment of 17 hyperthyroid patients with antithyroid drugs, both mean plasma T4 and T3 levels became normal within 4 weeks, but the normalization of RBC Zn lagged about 2 months behind them. The RBC Zn levels significantly correlated with both the plasma T4 and T3 levels obtained 0, 4, 8, and 12 weeks prior to the RBC sampling, and the highest correlation was observed between the RBC Zn levels and plasma T4 and T3 levels measured 8 weeks previously. These data suggest that RBC Zn concentration in hyperthyroid patients reflects a patient's mean thyroid hormone level over the preceding several months as glycosylated hemoglobin level does in diabetic patients.

Although the activity of lysosomal protease in Graves' thyroid is considered to be increased, there has been no quantitative method to estimate the protease activity in the thyroid tissue due to the contamination of thyroglobulin (Tg) which varies in susceptibility to the protease. In the present study, the proteolytic activity (PA) of thyroid lysosomal protease preparation (P25) separated from Tg was assayed using 125I labeled rat Tg. More than 95% of 125I-Tg was hydrolyzed at pH 4.0 without deiodination, and the pattern of liberated iodoamino acids resembled that of pronase digest except for a higher T3/T4 ratio. Thirty-seven Graves' thyroids and 15 paranodular thyroid tissues were assayed. PA, the specific PA (SPA; calculated as PA per mg P25 protein) and PA per DNA content in Graves' thyroids were significantly higher than those in controls. There were good correlations among PA, SPA and PA per DNA content of the thyroid tissue. PA and SPA in the thyroid from 29 patients with Graves' disease treated with propylthiouracil or methimazole did not correlate with serum thyroid hormone level immediately before surgery. In 8 patients treated with KI, PA from 5 patients whose serum thyroid hormone levels had been normalized were significantly lower than those from 3 patients who were still thyrotoxic.(ABSTRACT TRUNCATED AT 250 WORDS)