Discontinuation Of Antithyroid Drugs Research Articles

Efficacy of Anti-Thyroid Medications in Patients with Graves’ Disease

IntroductionGraves’ disease (GD) is an autoimmune disorder characterized by hyperthyroidism due to increased thyroid-stimulating hormone receptor antibodies (TRAb).The treatment of GD often consists of radioactive iodine therapy, anti-thyroid drugs (ATD), or thyroidectomy. Since few studies have collected data on remission rates after treatment with ATD in Saudi Arabia, our study aimed to assess the efficacy and the clinical predictors of GD long-term remission with ATD use.MethodWe conducted a retrospective chart review study of 189 patients with GD treated with ATD between July 2015 and December 2022 at the endocrine clinics in King Abdulaziz Medical City in Riyadh. All GD patients, adults, and adolescents aged 14 years and older who were treated with ATD during the study period and had at least 18 months of follow-up were included in the study. Patients with insufficient follow-up and those who underwent radioactive iodine (RAI) therapy or thyroidectomy as first-line therapy for GD were excluded from the study.ResultsThe study sample consisted of 189 patients, 72% of whom were female. The patients’ median age was 38years (33, 49). A total of 103 patients (54.5%) achieved remission. The median follow-up period for the patients was 22.0 months (9, 36). Patients who achieved remission had lower mean free T4 levels (25.8pmol/l ± 8.93 versus 28.8pmol/l ± 10.82) (P value = 0.038) and lower median TRAb titer (5.1IU/l (2.9, 10.7)) versus (10.5IU/l (4.2, 22.5)) (P value = 0.001) than patients who did not achieve remission. Thirty-five out of 103 patients who achieved remission (34%) relapsed after ATD discontinuation. The patients who relapsed showed higher median thyroid uptake on 99mTc-pertechnetate scan than patients who did not relapse: 10.3% (5.19, 16.81) versus 6.0% (3.09, 12.38), with a P value of 0.03. They also received ATD for a longer period, 40.0 months (29.00, 58.00) versus 25.0 months (19.00, 32.50), with a P value of < 0.0001.ConclusionThe remission of GD was achieved in approximately half of the patients treated with ATD; however, approximately one-third of them relapsed. Lower Free T4 and TRAb levels at diagnosis were associated with remission. Longer ATD use and higher thyroid uptake upon diagnosis were associated with relapse after ATD discontinuation. Future studies are necessary to ascertain the predictors of ATD success in patients with GD.

The need for the GREAT+ score to predict relapse in Graves’ disease: a questionnaire among patients and internal medicine specialists

PurposeGraves’ disease (GD) is an auto-immune cause of hyperthyroidism. First-line treatment often consists of a 12–18 month course of antithyroid drugs (ATD). After discontinuation of ATD, GD relapses in approximately 50% of patients. The ‘Graves recurrent event after therapy+ ’ (GREAT+) score may predict individual relapse chances after ATD discontinuation more accurately based on clinical and laboratory parameters at diagnosis. We investigated the need for the GREAT+ score through an online questionnaire among GD patients and physicians treating GD.MethodsAn anonymous online questionnaire was distributed to patients and physicians between June 2022 and August 2023.ResultsThe questionnaire was completed by 532 patients and 44 physicians. Results showed that 94% of patients were interested in knowing their GREAT+ score at the start of treatment. 55% would consider definite treatment (radioiodine/thyroidectomy) as first-line treatment in case of a high relapse chance. 98% of the physicians indicated the GREAT + score would support patient counseling. 84% may change their advice for first-line treatment if a patient has a high relapse chance based on the score.ConclusionPatients and physicians considered the GREAT+ score as a valuable addition to the current available information which could change treatment decisions. Therefore, external validation of the GREAT+ score is justified to implement this score in clinical practice.

Significance of thyroperoxidase and thyroglobulin antibodies in medically treated Graves' disease.

Thyroperoxidase (TPOAb) and thyroglobulin (TgAb) antibodies are highly prevalent in Graves' disease (GD), but their significance is controversial. We retrospectively analyzed TPOAb and TgAb levels and evolution in 136 patients with newly diagnosed GD between 2000 and 2022, treated with anti-thyroid drugs (ATD) in a block-and-replace (B+R) regimen for at least 12 months and followed up for at least 1 year after ATD discontinuation or until disease relapse. At diagnosis, 98 out of 136 (72%) patients were TPOAb positive and 73 out of 136 (54%) patients were TgAb positive. The presence of TPOAb or TgAb antibodies at diagnosis was generally not related to GD presentation and did not influence the risk of relapse (P = 0.304 and P = 0.348, respectively). There was less TED (thyroid eye disease) in TgAb-positive patients than TgAb-negative patients at diagnosis (11 out of 73 (15.1%) versus 21 out of 63 (33.3%) P = 0.012). In contrast, the presence of TPOAb at diagnosis was not associated with TED (P = 0.354). The absence of TgAb at diagnosis (P = 0.05) and time to euthyroidism (P = 0.009), but not smoking or TRAb levels, were associated with TED in multivariate logistic regression. TPOAb and TgAb levels during treatment and after its discontinuation were not predictive of relapse, except for lower titers of TgAb at 18 months in patients who relapsed (P = 0.034). In GD patients treated with a first course of ATD in a B+R regimen we observed lower titers of TgAb at the end of treatment in patients who relapsed and a significant protection against TED in patients with positive TgAb at diagnosis, irrespectively of TPOAb.

THU670 Serum TSI Concentration In Patients With Graves’ Disease Undergoing Maintenance-dose Of Antithyroid Drug (ATD) And Its Relationship With Disease Relapse After ATD Withdrawal

Abstract Disclosure: P.V. Nguyen: None. K.T. Nguyen: None. Background: Graves' disease (GD) is an autoimmune disorder in which thyroid-stimulating immunoglobulin (TSI) plays a key role in its pathogenesis. TSI assays have been recently optimized in their accuracy, and the procedure has also been simplified, which can potentially replace TRAb measured by conventional TSH-binding inhibitory immunoglobulins (TBII) assays in routine clinical practice. Objectives: Our objective was to study the serum TSI concentration in patients with Graves’ disease undergoing maintenance-dose ATD. We also aimed to assess the predictive value of TSI immunoassay, as well as the clinical signs and thyroid function tests in predicting Graves’ disease relapse following ATD discontinuation. Finally, follow-up would be continued to check for relapse or long term euthyroid status. Methods: Retrospective follow-up study of 352 patients with hyperthyroidism due to GD, treated at the endocrine outpatient clinic of Medic Medical Center, Ho Chi Minh City from January 2000 to April 2021. TSI was measured several times during the course of treatment when planning to stop the medication (at the discretion of the attending physician). ATD withdrawal would be considered when the patients achieved clinical euthyroidism with normal FT4 tests for at least 3 months with minimal dose of ATD. The decision to withdraw ATD was also based on TSI concentration, as well as the goiter’s characteristics and parenchymal vascularity observed via thyroid Doppler ultrasound. Results: The median TSI concentration of patients with GD undergoing maintenance-dose ATD was 1.45 IU/L (normal range &amp;lt;0.10 IU/L), and their thyroid function measured at the same time tended to be euthyroid in our study. TSI cut-off level at ATD withdrawal to predict the recurrence of GD was 1.31 IU/L which corresponded with the sensitivity, specificity, positive and negative predictive values of 63.64%, 78,79%, 50% and 86.67%, respectively. Multiple logistic regression analysis showed that the following factors were associated with an increased risk of relapse after the end of medical treatment: Graves' ophthalmopathy (GO), OR 3.69 (95% CI: 1.06-12.87; p=0.04), treatment duration less than 18 months, OR 7.77 (95% CI: 1.92-31.42; p&amp;lt;0.01), TSI level before ATD withdrawal ≥1.31 IU/L, OR 9.92 (95% CI: 2.77-35.42; p&amp;lt;0.01). Conclusion: At the time of ATD withdrawal, while normal FT4 levels were observed, high TSI levels were indicative of an ongoing immune process. These findings suggest that TSI measurements, in addition to clinical and ultrasound evaluations, may aid in the prediction of GD relapse after ATD discontinuation. In addition, GO, treatment duration of less than 18 months and TSI level before ATD withdrawal ≥1.31 IU/L were associated with an increased risk of relapse of GD after ATD discontinuation. Our study contributes to the expanding literature supporting the clinical utility of TSI assay in the management of GD. Presentation: Thursday, June 15, 2023

FRI569 A Therapeutic Dilemma: Spontaneous Oscillating Graves' Disease And Hypothyroidism

Abstract Disclosure: D. Suravajjala: None. J. Case: None. S. Kolli: None. V. Eranki: None. Spontaneous recurrent conversions between hyperthyroidism and hypothyroidism in Graves’ disease (GD) is very rare. We present a case of GD with spontaneous oscillation since diagnosis. From our review, less than 10 cases have been reported in the literature with alternating hyper and hypothyroidism. The patient is a 68-year-old female diagnosed with GD 4 years back with TSH &amp;lt;0.01 (0.4 - 4.5 uIU/mL) and TSI 25.70 (0.00-0.5 IU/L). She denied viral illness, radiation exposure, Lithium or Amiodarone use. Ultrasound thyroid was consistent with GD. Thyroid uptake scan was also consistent with GD. Eventually, Methimazole (MMI) 10 mg daily was initiated. About five months after MMI treatment, she was found to be hypothyroid with TSH 9.030 (0.4-4.5 uIU/mL) and FT4 0.99 (0.9-2.2 ng/dl) which led to discontinuation of MMI. 2 months later, she was clinically hyperthyroid with TSH 0.026, FT4 2.93 (0.9-2.2 ng/dl), TSI 9.59 (0-0.55 IU/L). MMI 5 mg daily was resumed, and as she preferred medical management, other treatment options for GD were not considered. Six months after low dose MMI, patient again reverted to hypothyroidism with TSH 21.420, FT4 0.82. MMI 5 mg was changed to every other day. After 8 months, she was found to be clinically and biochemically hypothyroid with TSH 147, FT4 0.41 (0.9-2.2 ng/dl), TSI 7.98 (0-0.55 IU/L). With the suspicion that she had burnt out GD, she was started on Levothyroxine (LT4) 100 mcg daily. Two months after LT4 initiation, she became clinically hyperthyroid with TSH 0.010 (0.4-4.5 uIU/mL) and FT4 1.91 (0.9-2.2 ng/dl). When trial of LT4 dose reduction failed to alleviate patient hyperthyroid symptoms, it was discontinued and MMI was resumed at 2.5 mg qd. Within 3 months she reverted to hypothyroidism. HAMA interference was as well ruled out. Although the patient's thyroid function ranged spontaneously from hyperthyroidism to hypothyroidism, she was still reluctant for definitive treatment options for GD, including RAI ablation and total thyroidectomy. As GD patients may have definitive treatment early, spontaneous conversion between hyperthyroidism and hypothyroidism is usually not seen in GD and most episodes usually occur several years after discontinuation of antithyroid drugs. It is known that both TSH receptor stimulating antibodies (TSAb) and TSH receptor blocking antibodies (TBAb) can be produced at the same time. The presence of hyper or hypothyroidism may depend on the equilibrium between stimulating and blocking antibodies. Switching of TSH receptor antibodies between stimulation and blockage is uncommon. Diagnosis demands careful clinical and biochemical assessments. Alternatively, the case may be easily mistaken for excessive thyroid suppression or replacement. This condition is difficult to manage, and definitive treatment options could be considered with I-131 ablation, thyroidectomy, or pharmacological treatment (block and replace). Presentation: Friday, June 16, 2023

The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves' Disease.

To determine whether baseline thyroid-stimulating immunoglobulin (TSI) bioassay or its early response upon treatment with an anti-thyroid drug (ATD) can predict prognosis of Graves' disease (GD) in real-world practice. This retrospective study enrolled GD patients who had previous ATD treatment with TSI bioassay checked at baseline and at follow-up from April 2010 to November 2019 in one referral hospital. The study population were divided into two groups: patients who experienced relapse or continued ATD (relapse/persistence), and patients who experienced no relapse after ATD discontinuation (remission). The slope and area under the curve at 1st year (AUC1yr) of thyroid-stimulating hormone receptor antibodies including TSI bioassay and thyrotropin-binding inhibitory immunoglobulin (TBII) were calculated as differences between baseline and second values divided by time duration (year). Among enrolled 156 study subjects, 74 (47.4%) had relapse/persistence. Baseline TSI bioassay values did not show significant differences between the two groups. However, the relapse/persistence group showed less decremental TSI bioassay in response to ATD than the remission group (-84.7 [TSI slope, -198.2 to 8.2] vs. -120.1 [TSI slope, -204.4 to -45.9], P=0.026), whereas the TBII slope was not significantly different between the two groups. The relapse/persistence group showed higher AUC1yr of TSI bioassay and TBII in the 1st year during ATD treatment than the remission group (AUC1yr for TSI bioassay, P=0.0125; AUC1yr for TBII, P=0.001). Early changes in TSI bioassay can better predict prognosis of GD than TBII. Measurement of TSI bioassay at beginning and follow-up could help predict GD prognosis.

Long-Term, Low-Dose Methimazole Therapy Is Effective in Protecting against Relapses in Graves’ Disease

Clinical ThyroidologyVol. 35, No. 02 HyperthyroidismFree AccessLong-Term, Low-Dose Methimazole Therapy Is Effective in Protecting against Relapses in Graves’ DiseaseGiuseppe BarbesinoGiuseppe BarbesinoThyroid Unit, Division of Endocrinology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, U.S.A.Search for more papers by this authorPublished Online:8 Feb 2023https://doi.org/10.1089/ct.2023;35.54-56AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Review of: Lertwattanarak R, Kunavisarut T, Sriussadaporn S 2022 Benefits of Long-term continuation of low-dose methimazole therapy in the prevention of recurrent hyperthyroidism in Graves' hyperthyroid patients: A randomized prospective controlled study. Int J Endocrinol 2022:1705740. PMID: 36267362.SUMMARYBackgroundThe management of Graves’ disease (GD) hyperthyroidism has been evolving over the past two decades. The traditional standard of care suggested treatment with methimazole for 12 to18 months followed by radioactive iodine (RAI) treatment or surgery (1) in patients not achieving remission, where remission is defined as the ability to maintain euthyroidism after discontinuation of methimazole. This recommendation is supported by the recognition that longer courses of antithyroid drugs do not increase the rate of lasting remissions after discontinuation (2). This strategy has become less attractive owing to increasing evidence that RAI can cause or worsen thyroid eye disease (3) on the one hand and on the other to concerns about quality of life with hypothyroidism, even when thyroid hormone is optimally replaced (4). This study (5) was conducted to understand whether long-term therapy with low-dose methimazole could protect GD patients from relapses of hyperthyroidism.MethodsThis was a randomized controlled study in adult GD patients who had been euthyroid while taking methimazole for at least 6 months prior to randomization. The patients were randomly assigned to either continue methimazole at low doses (2.5–5 mg daily) or discontinue methimazole. The subjects’ thyroid function was then monitored every 6 months for 36 months. Standard diagnostic criteria for GD were adopted for inclusion. Patients who had already experienced a relapse were excluded. The primary outcome measured was the cumulative incidence of relapsing hyperthyroidism in the two groups.ResultsNinety-two patients were randomly assigned to the discontinuation group and 92 to the low-dose treatment group. Except for minor differences, the two groups were very similar for most epidemiologic parameters (86% female vs. 84% and mean [±SD] age, 39.9±10.9 vs. 42.2±14.9 years), indicating a reliable randomization process. The average duration of methimazole therapy prior to randomization was 37 months in the discontinuation group and 32 months in the low-dose group (not statistically different). In the discontinuation group, the number of relapses increased progressively and uniformly during the study time, reaching 41.2% at 36 months. In the low-dose group, the rate of relapse was 11%, and it was reached 18 months after randomization, with no additional relapses after that time. There were no recorded side effects during the study period.ConclusionsIn patients with GD, long-term treatment with 2.5 to 5 mg of methimazole daily is safe and effective in preventing the relapse of hyperthyroidism. This strategy is a valid alternative to RAI therapy and thyroidectomy in patients who want neither and yet worry about relapses of hyperthyroidism.COMMENTARYGraves’ disease, like many other autoimmune diseases, is often characterized by flares and remissions (6). Patients taking methimazole are typically treated for 12 to 18 months, after which a discontinuation trial is performed, in the hope of a lasting remission. Measuring serum TSH receptor antibodies (TRAbs) before antithyroid drug discontinuation helps to identify patients who are at high risk for early relapses in the 3 to 6 months after discontinuation (7). However, 20 to 30% of patients negative for TRAbs will still relapse months to years after the discontinuation (8,9). This observation, and mounting diffidence towards RAI therapy and surgery, has led to increased interest for long-term methimazole treatment. The data so far available have been mostly retrospective, or have addressed only select patient groups (for example, patients who already have experienced a relapse) (10). Like other endocrinologists, I have been advising some of my patients with GD who appear to be “currently” in remission, to continue methimazole indefinitely at very low doses, typically 2.5 mg daily. This article provides good-quality evidence to support such a practice, which I will continue to apply, especially to older patients and patients who had experienced particularly intense symptoms from the hyperthyroidism at the time of its first presentation.Disclosures: The author has no relevant conflicts of interest to declare.

Long-term outcomes of anti-thyroid drug treatment in childhood-onset Graves' disease.

Outcomes of childhood-onset Graves' disease (GD) and suggested duration of anti-thyroid drug (ATD) therapy have been controversial. This study aimed to determine long-term outcomes following ATD therapy, including remission and relapse rates. A retrospective study of 265 paediatric patients with GD who were initially treated with ATD was conducted. Long-term outcomes were analysed. Median (IQR) age at diagnosis was 11.5 (9.4, 13.7) years. Duration of ATD treatment was 4.3 (2.3, 6.7) years and time since diagnosis to the enrolment was 7.1 (3.8, 10.9) years. There were 77, 93 and 95 patients who underwent definitive treatment, had ATD discontinuation, and were still being treated with ATD, respectively. The remission rate was 21% (56 out of 265 patients) and relapse rate was 40% (37 out of 93 patients). Cumulative incidence of first remission increased with the duration of ATD treatment with maximum remission rate at 5.3 years following ATD therapy. Among patients who experienced relapse, approximately 50% had disease relapse which occurred within 1 year after ATD discontinuation. Patients with goitre size of less than 3.5 cm, thyroid-stimulating hormone receptor antibody of less than 10 IU/L, no ophthalmopathy at diagnosis and methimazole dose requirement of less than 0.25 mg/kg/day at 1 year after treatment were more likely to achieve remission. Remission rate of childhood-onset GD was relatively low following ATD treatment. Longer-term ATD therapy was associated with increased remission rate. Approximately 50% of patients with relapse had disease relapse within 1 year following ATD discontinuation.

Successful Treatment with Radioiodine for Antithyroid Drug-Induced Agranulocytosis in Graves' Disease

Background: Graves’ disease (GD) is an autoimmune disorder and the leading cause of hyperthyroidism. Antithyroid drugs (ATDs) are available treatment option. Agranulocytosis is a rare but potentially fatal complication of ATD in hyperthyroidism management. The study's objectives include clinical symptoms of ATD-induced agranulocytosis in Graves' illness and the difficulties in clinical care in addition to radioactive iodine therapy (RAIT). Methods: Twelve patients with ATD induced agranulocytosis referred to NINMAS between 2021to 2022 for RAIT therapy were included in this study. All the patients with hyperthyroidism and agranulocytosis or leukopenia were taken in this study. Results: The age of the 12 patients (female: male = 10:3) was 26 to 56 years (mean SD: 38.41±13.9 years). Among the twelve patients 10 were treated with carbimazole and two with PTU for Graves’ disease. Initial dose of ATD was 15-30 mg daily. The most common clinical manifestations were fever (100%), sore throat (41.6%), oral ulcer (16%), rash (41.66%), loose motion (16.66%) and atrial fibrillation (8.33%) with deep vein thrombosis (DVT). Agranulocytosis developed between 7th and 547th days after initiation of ATD; all of them developed early onset except one who developed agranulocytosis after 1.5 years of initiation of ATD. All 12 patients were treated immediately after diagnosis of agranulocytosis following prompt discontinuation of ATD, they were treated with antibiotic with 12 cases, G CSF in one case, KI in one case, glucocorticoid in two cases, and beta blocker in all cases. After intensive and supportive treatment in hospital, all the patients recovered with absolute neutrophil counts of more than 500/mm3 in 5 to 15 days (mean SD: 7.6 3.4 days). Nine patients were treated with lithium carbonate supplement to reduce FT3 level. Average dose of lithium carbonate was 600 mg. After that patients were referred for RAIT. TRAb were positive in seven patients and average were 4.2 U/L. Plasmapheresis was done in three patients and one patient in two times due to high FT4 level before RAIT. Lithium carbonate supplementation reduce thyroid hormone level but not to the optimum level. All the 12 patients were treated with RAIT. Average dose RAI 10.9 mCi, average follow up period 2.3 years. Two patients required second dose of RAIT due to persistent hyperthyroidism. Six patients became hypothyroid, two were in hyperthyroid state (on plan for second therapy), four patients are euthyroid at present and they are on follow up. No fatal condition was found in this study. Conclusion: The most cost-effective method of managing agranulocytosis induced by thionamide-derived ATD is that all patients with thyrotoxicosis must be informed that their white blood cells and differential counts should be checked immediately whenever the “common cold” symptoms occur during treatment, especially within the first three months of medication. Contraindication to ATDs; RAI is a safe and effective alternative. Bangladesh J. Nuclear Med. 26(1): 39-43, 2023

Remission in pediatric Graves' disease treated with antithyroid drug and the risk factors associated with relapse.

To evaluate the characteristics and frequency of remission in pediatric patients with Graves' disease (GD) treated with antithyroid drug (ATD) and to identify factors that may be associated with relapse. Medical records of patients younger than 19 years who presented to the Department of Pediatrics of Queen Elizabeth Hospital Hong Kong with newly diagnosed GD from 1st January 2007 to 31st December 2017 were retrospectively reviewed. Remission was defined as euthyroidism for 12 months or more after discontinuation of ATD treatment and no relapses during the follow-up period. Patients who successfully achieved remission were compared to those who suffered relapse. Factors that may predict occurrence of relapse after ATD treatments were studied, and their odds ratios (ORs) were calculated. A total of 101 patients was included in this study. Eighty-one patients completed one course of ATD. Eighteen patients (17.8%) successfully achieved remission, and 58 patients (57.4%) experienced relapse after discontinuation of ATD. The remission group received a significantly longer course of ATD therapy than the relapse group (median, 28 months; interquartile range [IQR], 18-48 months in remission group vs. median, 21 months; IQR, 17-26; p=0.024). The OR for relapse was 0.971 (95% confidence interval [CI], 0.946-0.997) in univariate analysis and remained significant after adjustments in the multivariate regression model (OR, 0.961; 95% CI, 0.933-0.989; p=0.008). The remission rate in pediatric patients with GD treated with ATD was low. A longer ATD course was associated with a greater chance of remission in this population.

PSAT344 Zeroing In: Methimazole Induced Agranulocytosis in Amiodarone Induced Thyrotoxicosis

Abstract Background Agranulocytosis, defined as absolute neutrophil count (ANC) &amp;lt; 500/µL due to antithyroid drugs (ATDs), methimazole, carbimazole, and propylthiouracil (PTU), is a rare but serious complication with an occurrence of 0.1- 0.5%. ATDs induced agranulocytosis occurs abruptly, usually in the first three months of treatment but can occur any time after initiation of treatment, and although it is more common with a higher dose of methimazole &amp;gt; 30 mg/day, it can also occur with lower dosages. We present a rare case of agranulocytosis in a patient with Amiodarone-induced Thyrotoxicosis (AIT) with an ANC of 0/µL. Clinical Case A 68-year-old male with atrial fibrillation and heart failure was diagnosed with AIT when he presented to ED with thyrotoxicosis. Amiodarone was discontinued. Methimazole 40 mg daily with prednisone 20 mg daily was initiated. The ANC was 4360/µL. After nine weeks on methimazole, he presented with fever and tremors. The laboratory tests during this admission revealed WBC 1310/µL (4000-11000/µL) with granulocytes 0% (35%-80%), ANC 0/µL (1820-7420/µL), TSH &amp;lt; 0.01 (0.45-5.3mIU/mL), free T4 5.5 (0.58-1.64 ng/dL), free T3 4.4 (2.8-4.4 pg/dL). Methimazole was discontinued and antibiotics started. He received six doses of Granulocyte colony-stimulating factor (G-CSF) Filgrastim 480 mcg with an improvement of WBC to 6370/µL with a granulocyte count of 60% on the 6th day of admission. He eventually underwent thyroidectomy for treatment of the thyrotoxicosis. Discussion The proposed mechanism of agranulocytosis with ATDs is twofold. First, there is a direct toxic effect on mature circulating neutrophils and stem cells. The second is complement-mediated antibodies against granulocytes. Furthermore, AIT is associated with a higher risk for ATD induced agranulocytosis, although the mechanism remains elusive. The most common manifestations are fever and sore throat. The management includes discontinuation of ATD and starting antibiotics. G-CSF is used to treat agranulocytosis as it decreases the recovery time, the rate of infectious complications, and the mortality rate. Patients with ANC &amp;lt; 100/µL have a greater risk of infectious and fatal complications than patients with ANC &amp;gt; 100/µL. After resolution of agranulocytosis, methimazole or any other thionamides are generally not recommended due to concern for recurrence due to cross-reactivity among thionamides. Thyroidectomy or radioiodine therapy should be considered for definitive treatment of the hyperthyroidism in this circumstance. Conclusion Due to the low incidence and abruptness of agranulocytosis from ATDs, controversy exists over the value of routine monitoring of WBC count. This case emphasizes routine WBC monitoring could be considered in patients on higher doses of methimazole, especially in the first three months, due to the increased risk of agranulocytosis. Patient education on the life-threatening complication of ATD induced agranulocytosis is vital. It helps patients recognize early symptoms and seek medical care promptly, which aids in early intervention and reduces morbidity and mortality. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Outcomes of Early-Pregnancy Antithyroid Drug Withdrawal in Graves' Disease: A Preliminary Prospective Follow-Up Study.

Objective: The use of antithyroid drugs (ATDs) carries potential risk for teratogenic effects. For women with well-controlled hyperthyroidism on a low dose of ATDs, drug withdrawal upon pregnancy is recommended by international medical guidelines. Therefore, it is necessary to determine the characteristics of patients suitable for ATD withdrawal, subsequent changes in thyroid function after ATD discontinuation, and its impact on pregnancy and offspring outcomes. Methods: This prospective study recruited 63 pregnant women with well-controlled Graves' hyperthyroidism who had stopped ATDs during early pregnancy. Patients were followed up until the end of pregnancy and data on pregnancy outcomes were collected. Results: Overall, 20 patients (31.7%) had rebound of hyperthyroidism. Patients with either subnormal thyrotropin (TSH) levels (TSH <0.35 mIU/L, odds ratio [OR] = 5.12, confidence interval [CI = 1.29-20.34], p = 0.03) or positive thyrotropin receptor antibody (TRAb) (TRAb >1.75 IU/L, OR = 3.79, [CI = 1.17-12.30], p = 0.02) at the time of ATDs withdrawal presented a higher risk of rebound than those with either normal TSH levels or negative TRAb. Patients with both subnormal TSH and positive TRAb at the time of ATD withdrawal were more likely to experience rebound (83.3%, 5/6) than those with both normal TSH and negative TRAb (13%, 3/23, OR = 33.33, [CI = 2.83-392.60], p = 0.003). The prevalence of adverse pregnancy outcomes was significantly higher in patients who experienced rebound compared with those who did not (55.0% vs. 9.3%, OR = 11.92, [CI = 3.08-46.18], p = 0.0002). Conclusions: Subnormal TSH levels and TRAb positivity at the time of ATD withdrawal in early pregnancy may be associated with rebound of Graves' hyperthyroidism. Rebound of hyperthyroidism during pregnancy may increase the risk of adverse pregnancy outcomes. Larger prospective studies are needed to confirm these findings.

Appropriate duration of antithyroid drug treatment as a predictor for relapse of Graves' disease: a systematic scoping review.

Following the conventional 12-18month antithyroid drug (ATD) treatment in Graves' disease (GD), 50% of patients experience relapse of hyperthyroidism. The aim of this systematic scoping review was critical appraisal of duration of ATD therapy in the last 80years. Articles were identified through the search of PubMed from January 1, 1941 to April 30, 2021. All study types were included. Articles were eligible if they reported data on the length of ATD treatment, particularly thyroid hormones and TSH receptor antibodies (TRAb) concentrations and specifically those with data on the remission and/or relapse rates. We described major progress regarding the duration of ATD therapy and related outcomes at every 20years. Articles of 1941-1960 were mainly concerned with determination of favorable treatment, minimal effective dose, side effects and rate of remission after < 12-month ATD therapy. Studies with larger number of patients and longer follow-ups appeared in 1961-1980; higher remission rate after 18-24months versus 6months of ATD therapy was reported. Articles of 1981-2000 focused on identification of factors associated with high relapse rates after discontinuation of ATD. In 2001-2021, ATD became the first choice of treatment in many countries. However, 12-18months of ATD therapy was arbitrarily chosen as the appropriate option. According to recent studies, persistent normalization of TRAb occurs after 5years of methimazole therapy and ATD treatment of > 60months could offer a 4-year remission rate of 85%. Long-term ATD treatment for more than 60months is safe and effective, has the highest remission rate and cures most patients with GD; hence, it should be considered as the most appropriate duration for ATD therapy in these patients.

Predictive effect of antithyroid antibody for relapse of Graves' disease.

The remission rate in children with Graves' disease (GD) after 2-6 years of antithyroid drug (ATD) treatment is 40-50%. It has been reported that it is difficult to predict the GD prognosis based on the thryroid stimulating hormone (TSH) receptor antibody (TRAb) level at the cessation of ATD treatment. We studied whether the persistence of negative TRAb at ATD treatment cessation increased the remission rate in pediatric patients with GD. We included 22 patients diagnosed with GD who discontinued ATD treatment after confirmation of negative TRAb on two or more consecutive tests. Remission was defined as the maintenance of normal thyroid function, including serum TSH level, with negative TRAb more than 2 years after ATD discontinuation. Of the 22 patients, 12 achieved remission (remission rate 54.5%), with no significant between-group difference in the median duration of ATD treatment in the remission and relapse groups (4.4 vs 3.9 years). Of the 10 patients who relapsed, four (40.0%) relapsed within 2 years after ATD discontinuation, and 4 (40.0%) relapsed more than 5 years after ATD discontinuation. The persistence of negative TRAb at ATD treatment cessation might indicate prolonged duration of remission but does not increase the final remission rate in patients with childhood-onset GD.

The prognostic value of thyroid-stimulating immunoglobulin in the management of Graves' disease.

Background:The bioassay of thyroid-stimulating immunoglobulin was reported to have a similar performance to the commonly used thyroid-stimulating hormone binding inhibition assay, also known as thyroid receptor antibody assay. The normal reference range of thyroid receptor antibody levels indicates the withdrawal of anti-thyroid drugs in the recent clinical guidelines.Methods:A prospective, longitudinal observational study was conducted to evaluate the prognostic value of thyroid-stimulating immunoglobulin in patients with Graves’ disease.Results:A total of 77 patients with Graves’ disease treated with anti-thyroid drugs were in a continuous follow-up until 1 year after anti-thyroid drugs discontinuation. Commercial kits of thyroid-stimulating immunoglobulin and M22-thyroid-stimulating hormone binding inhibition assay were used and compared. Thyroid-stimulating immunoglobulin was all negative in healthy controls, Hashimoto thyroiditis, and subacute thyroiditis. Thyroid-stimulating immunoglobulin value was highest in untreated patients with Graves’ disease (p < 0.001). Under anti-thyroid drugs treatment, thyroid-stimulating immunoglobulin value decreased gradually. A total of 21 patients had positive thyroid-stimulating immunoglobulin at the end of treatment. According to clinical fate of patients with Graves’ disease after withdrawal of anti-thyroid drugs, thyroid-stimulating immunoglobulin value and positivity in patients with relapse were significantly higher than that reported in patients with remission (p = 0.001, p < 0.001). After adjustment for age, gender, initial thyroid receptor antibody, initial thyroid-stimulating immunoglobulin, and thyroid receptor antibody at the end of treatment, the odds ratio of positive thyroid-stimulating immunoglobulin for the risk of relapse was 33.271 (95% confidence interval: 4.741–233.458, p < 0.001) and odds ratio of quantitative thyroid-stimulating immunoglobulin was 1.009 (95% confidence interval: 1.002–1.015, p < 0.001).Conclusion:Thyroid-stimulating immunoglobulin is a good predictor of relapse in patients with Graves’ disease treated with anti-thyroid drugs. It might be safer to discontinue anti-thyroid drugs when thyroid-stimulating immunoglobulin and thyroid receptor antibody were both negative.

Influence of Short-Term Dietary and Therapeutic Iodine Restriction on the Therapeutic Effects of Radioactive Iodine Therapy in Patients with Graves' Disease.

Background: Several studies have investigated the factors affecting the effects of radioactive iodine (131I) treatment (RAIT) in patients with Graves' disease. However, the influence of dietary or therapeutic iodine on the effect of RAIT has not been fully elucidated yet. The aim of this study was to investigate whether dietary or therapeutic iodine before RAIT influences the therapeutic effects of RAIT with a fixed-dose regimen and a short-term restriction of iodine intake in an iodine-sufficient area. Materials and Methods: We retrospectively analyzed 81 Japanese patients with Graves' disease treated with the following RAIT regimen: dietary iodine restriction for 7 days as well as discontinuation of antithyroid drugs (ATDs), potassium iodine (KI), or both for 5 days before RAIT. On the day of RAIT, we measured urinary iodine content to estimate daily iodine intake. After RAIT, we adjusted the dose of ATDs, KI, or both according to serum thyroid hormone levels every 1-2 months. Using the data from these patients, we investigated the effect of dietary and therapeutic iodine on the therapeutic effects of RAIT. The therapeutic effects at 1 year after RAIT were evaluated based on the necessity of ATDs, KI, or both. Results: Dietary iodine intake was weakly correlated with 131I uptake (RAIU), but the dose of therapeutic iodine was not correlated with RAIU. The therapeutic effects of RAIT were strongly negatively associated with estimated thyroid volume before RAIT. Neither dietary iodine intake nor therapeutic iodine before RAIT affected this association. Conclusion: This study did not find an association between short-term dietary or therapeutic iodine restriction before RAIT and the therapeutic effects of RAIT in an iodine-sufficient area.

Corticosteroid Pulse Therapy for Graves' Ophthalmopathy Reduces the Relapse Rate of Graves' Hyperthyroidism.

Background: A course of anti-thyroid drugs (ATD) is the most common first line treatment for Graves' hyperthyroidism. However, hyperthyroidism relapse is frequent (30–70%). Due to the autoimmune nature of Graves' disease, the immunosuppressive treatment used for active Graves' orbitopathy (GO) may reduce the relapses after ATD discontinuation.Objective: To evaluate the recurrence rate in Graves' patients who, in addition to standard ATD, were treated or not treated with parenteral methylprednisolone (MPDS) for GO.Methods: Single-center retrospective study in a continuous series of 162 newly diagnosed Graves' patients, with or without GO, all gone into remission and followed-up until hyperthyroidism recurrence or at least 4 years after ATD discontinuation. Patients with moderate-severe active GO underwent middle dose MPDS treatment according to the EuGoGo guidelines. Cox proportional-hazard model was used to comparatively evaluate the risk of recurrence and the predictive factors in patients treated or not treated with MPDS pulse therapy.Results: MPDS treatment was the most significant factor that independently correlated with a reduced risk of hyperthyroidism relapse (HR = 0.53, 95% C.I. = 0.31–0.89). FT3 and female sex were also independent protective factors, while age almost reached the significance level, p = 0.062. The efficacy of MPDS was very high in patients aged <40 years (42.1% decrease in relapses, p < 0.01) but it was not significant in older patients.Discussion: Our study found that after ATD discontinuation the frequency of Graves' hyperthyroidism relapse was reduced in patients treated with MPDS pulse therapy for GO. This effect was more marked in young patients.

Long-Term Treatment of Hyperthyroidism with Antithyroid Drugs: 35 Years of Personal Clinical Experience.

Background: None of the current therapeutic approaches for management of Graves' disease has been able to re-establish normal thyroid function in all patients. Objective: To describe the author's 35 years of personal experience in the management of Graves' hyperthyroidism and, in doing so, review current articles published on the long-term medical treatment of hyperthyroidism. Methods: All published articles related to ≥4 years of continuous antithyroid drug (ATD) treatment were searched. Findings were added and compared with studies published by the authors on the same topic. Results: Long-term ATD treatment is effective and safe, both in children and adults, for treatment of hyperthyroidism. Treatment of Graves' patients with ATDs >60 months causes euthyroidism up to 4 years after discontinuation of ATDs in the majority of patients. Long-term ATD therapy is not inferior to radioiodine therapy and may sometimes even be superior in some aspects, when considering serum lipid profile, cardiac function, mood, and cognition. Conclusions: Long-term ATD therapy for Graves' hyperthyroidism is efficient and safe and induces control of hyperthyroidism, without rendering the patient hypothyroid in the majority of patients.

Thyroid storm after coronary artery bypass surgery: a case report

BackgroundThyroid storm is a rare, life-threatening disease triggered by an acute event or trauma, such as surgery of the thyroid or another area, and infection. However, recent studies have shown that irregular use or discontinuation of antithyroid drugs is the most common cause of thyroid storm. A cardiovascular event caused by thyroid storm following coronary artery bypass graft (CABG) is high output heart failure with extreme tachycardia, which can be fatal. Thyroid storm after nonthyroidal surgery, especially CABG, has been rarely reported, with only one reported case until now. Herein, we present a case of thyroid storm onset in a patient who underwent CABG.Case presentationA 74-year-old woman with a history of antithyroid medication discontinuation against medical advice underwent urgent CABG. The patient exhibited extreme tachycardia postoperatively, which is highly suggestive of thyroid storm. Although a higher infection risk is an important consideration, a high-dose steroid was used to control the intractable tachycardia that did not respond to beta-blocker administration. Despite appropriate antibiotic treatment, the patient’s condition was exacerbated, and she developed multiple organ failure resulting from adult respiratory distress syndrome progression, and she died on day 8 after surgery.ConclusionsRisk factors for thyroid storm after CABG and its treatment outcomes are rarely reported. Patients with a history of inappropriate antithyroid medication prescription should be in a euthyroid state before surgery. If surgery is imminent, anticipating thyroid storm and its treatment as well as a euthyroid state can improve recovery outcomes postoperatively.

Thyroid Storm in the ICU: A Retrospective Multicenter Study.

Thyroid storm represents a rare but life-threatening endocrine emergency. Only rare data are available on its management and the outcome of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management and in-ICU and 6-month survival rates of patients with those most severe thyroid storm forms requiring ICU admission. Retrospective, multicenter, national study over an 18-year period (2000-2017). Thirty-one French ICUs. The local medical records of patients from each participating ICU were screened using the International Classification of Diseases, 10th Revision. Inclusion criteria were "definite thyroid storm," as defined by the Japanese Thyroid Association criteria, and at least one thyroid storm-related organ failure. Ninety-two patients were included in the study. Amiodarone-associated thyrotoxicosis and Graves' disease represented the main thyroid storm etiologies (30 [33%] and 24 [26%] patients, respectively), while hyperthyroidism was unknown in 29 patients (32%) before ICU admission. Amiodarone use (24 patients [26%]) and antithyroid-drug discontinuation (13 patients [14%]) were the main thyroid storm-triggering factors. No triggering factor was identified for 30 patients (33%). Thirty-five patients (38%) developed cardiogenic shock within the first 48 hours after ICU admission. In-ICU and 6-month postadmission mortality rates were 17% and 22%, respectively. ICU nonsurvivors more frequently required vasopressors, extracorporeal membrane of oxygenation, renal replacement therapy, mechanical ventilation, and/or therapeutic plasmapheresis. Multivariable analyses retained Sequential Organ Failure Assessment score without cardiovascular component (odds ratio, 1.22; 95% CI, 1.03-1.46; p = 0.025) and cardiogenic shock within 48 hours post-ICU admission (odds ratio, 9.43; 1.77-50.12; p = 0.008) as being independently associated with in-ICU mortality. Thyroid storm requiring ICU admission causes high in-ICU mortality. Multiple organ failure and early cardiogenic shock seem to markedly impact the prognosis, suggesting a prompt identification and an aggressive management.