Dataset Information

Serum T3 Level and Duration of Minimum Maintenance Dose Therapy Predict Relapse n Methimazole-Treated Graves Disease.

ABSTRACT:

Background

Methimazole (MMI) has been advocated as a preferred option for most Graves disease (GD) patients. However, long-term remission after a course of MMI treatment is achieved in only 20% to 40% of patients, depending on the duration of follow-up.

Objective

To evaluate clinical factors for predicting relapse of GD in Thai patients after MMI treatment.

Methods

A retrospective analysis was performed of newly diagnosed patients with GD who achieved remission of hyperthyroid GD after at least 12 months of MMI treatment. Long-term outcomes were assessed and predictive factors of early and late relapse were evaluated.

Results

A total of 443 patients with newly diagnosed GD who were treated with MMI for at least 12 months from 1985 to 2019, and were able to discontinue medication, were studied. The mean age at diagnosis was 37.0 ± 11.4 years and 81.7% were female. Of the 320 patients (72.2%) who achieved initial remission after MMI treatment for 23 months, 106 patients (33.1%) experienced late relapse during the mean follow-up duration of 9.7 years after MMI withdrawal. The remission rates decreased from 36.4% at the first year after stopping MMI to only 20.7% at 10 years. High initial serum triiodothyronine (T3) level and duration of minimum maintenance dose therapy (MMDT) of <6 months were associated with late disease relapse after remission.

Conclusion

The long-term remission rate of Graves hyperthyroidism was achieved in one-fifth of MMI-treated Thai patients. Predictive markers for late relapse included high initial serum T3 level and a duration of MMDT of <6 months.

SUBMITTER: Thewjitcharoen Y

PROVIDER: S-EPMC7716657 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Hyperthyroidism is related to vascular atherosclerosis. Propylthiouracil (PTU) and methimazole, other than their antithyroid effects, may have different mechanisms in preventing atherogenesis in Graves’ disease. Objective This study aimed to investigate the effect of antithyroid drugs on markers of vascular atherosclerosis in Graves’ hyperthyroidism. Methods This study was a single-blind, randomized clinical trial conducted on 36 patients with Graves’ disease in Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, from June 2019 until July 2020. Graves’ disease was diagnosed from clinical manifestation of hyperthyroidism with diffuse goiter and then confirmed by thyroid stimulation hormone (TSH), free T4 (fT4), and TSH-receptor antibody (TRAb) measurements. Participants were randomly assigned to either a PTU or a methimazole treatment group and followed up for 3 months. Markers of vascular atherosclerosis were represented by adhesion molecules [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin], carotid artery stiffness [pulse wave velocity (PWV)], and thickness [carotid intima media thickness (cIMT)]. Results By the end of the study, 24 participants reached euthyroid condition (13 from the PTU group and 11 from the methimazole group). After 3 months of follow-up, in the PTU group, we noticed an improvement of ICAM-1 [pretreatment: 204.1 (61.3) vs. posttreatment: 141.6 (58.4) ng/ml; p = 0.001], VCAM-1 [837 (707–977) vs. 510 (402–630) ng/ml; p < 0.001] and E-selectin [32.1 (24.1–42.7) vs. 28.2 (21.6–36.8) ng/ml; p = 0.045] in the PTU group. In the methimazole group, only VCAM-1 improvement [725 (565–904) vs. 472 (367–590); p = 0.001] was observed. Meanwhile, we found no significant changes in PWV or cIMT in either group. Conclusion Antithyroid treatment in Graves’ disease leads to improvement in adhesion molecules, with a lesser effect on methimazole, whereas there were no significant changes in PWV or cIMT. PTU may have a better mechanism compared with methimazole in terms of improving adhesion molecules.

Project description:Prompt and stable control of hyperthyroidism is fundamental to avoid the detrimental effects of thyroid hormone excess, and antithyroid drugs, mainly methimazole (MMI), represent the first-line treatment for Graves' disease (GD) hyperthyroidism. Decreased serum concentrations of selenium (Se) and calcifediol (25(OH)D, VitD) have been reported in newly diagnosed GD patients in observational studies. Low Se levels might exacerbate oxidative stress by compromising the antioxidant machinery's response to reactive oxygen species, and low VitD levels might hamper the anti-inflammatory immune response. We performed a randomized controlled clinical trial (EudraCT 2017-00505011) to investigate whether Se and cholecalciferol (VitD) addition to MMI is associated with a prompter control of hyperthyroidism. Forty-two consecutive patients with newly-onset GD and marginal/insufficient Se and VitD levels were randomly assigned to treatment with either MMI monotherapy or MMI combined with Se and VitD. Se treatment was withdrawn after 180 days, while the other treatments were continued. Combination therapy resulted in a significantly greater reduction in serum FT4 concentration at 45 days (-37.9 pg/ml, CI 95%, -43.7 to -32.2 pg/ml) and 180 days (-36.5 pg/ml, CI 95%, -42 to -30.9 pg/ml) compared to MMI monotherapy (respectively: -25.7 pg/ml, CI 95%, -31.6 to -19.7 pg/ml and -22.9 pg/ml, CI 95%, -28 to -17.3 pg/ml, p 0.002). Data at 270 days confirmed this trend (-37.8 pg/ml, CI 95%, -43.6 to -32.1 pg/ml vs -24.4 pg/ml, CI 95%, -30.3 to -18.4 pg/ml). The quality of life (QoL) score was investigated by the validated "Thyroid-related Patient-Reported Outcome" questionnaire (ThyPRO). ThyPRO composite score showed a greater improvement in the intervention group at 45 days (-14.6, CI 95%, -18.8 to -10.4), 180 (-9, CI 95%, -13.9 to -4.2) and 270 days (-14.3, CI 95%, -19.5 to -9.1) compared to MMI group (respectively, -5.2, CI 95%, -9.5 to -1; -5.4, CI 95%, -10.6 to -0.2 and -3.5, CI 95%, -9 to -2.1, p 0-6 months and 6-9 months <0.05). Our results suggest that reaching optimal Se and VitD levels increases the early efficacy of MMI treatment when Se and VitD levels are suboptimal.