The Natural History of Subclinical Hyperthyroidism in Graves' Disease: The Rule of Thirds

Zhyzhneuskaya, Sviatlana; Addison, Caroline; Tsatlidis,; Weaver, JU; Razvi, Salman

doi:10.1089/thy.2015.0470

Cited by 16 publications

(12 citation statements)

References 17 publications

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“…All these studies were of moderate size (with a mean of around 100 participants). More recent studies have focused mainly on TPOAb positivity, which was found in 76.4% of 802 French patients with GD 15; in 7% of 111 Omani GD patients [11] and in 56.8% of 44 patients with subclinical hyperthyroidism due to GD [29]. Our data of 64% TPOAb-positivity and 36% TgAb positivity show a lower prevalence than those in the listed publications.…”

Section: Discussioncontrasting

confidence: 53%

“…Our fi nding of a positive association of TPOAb levels with serum fT4 is intriguing, but it could be also due to a lower type II deiodinase enzyme activity [36]. In a study addressing the natural history of subclinical hyperthyroidism in GD, positive TPOAb were associated with risk of progression to overt hyperthyroidism -with hazard ratios from 1.06 to 10.15 per year [29]. In a histological study higher TPOAb levels were correlated with intra-thyroidal germinative center development, suggesting a more aggressive immunological attack [37].…”

Section: Discussionmentioning

confidence: 83%

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Clinical, Hormonal, and Ultrasound Characteristics of Patients with Newly Diagnosed Graves’ Disease And Different Thyroid Antibody Profiles

Mekova

Boyanov

2019

Acta Medica Bulgarica

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Objective: Graves’ disease (GD) is characterized by elevated TSH-receptor antibodies (TRAb) and less often – thyroid peroxidase (TPOAb) and thyroglobulin antibodies (TgAb). Our aim was to examine the hormonal and ultrasound characteristics of patients with newly diagnosed GD with differing positive thyroid antibodies. Materials and Methods: This study included 249 patients with newly diagnosed GD (191 women, 58 men). 40.2% of them had Graves’ ophtalmopathy. The serum levels of TSH, free T4, free T3, TRAb, TPOAb, and TgAb were measured with third generation ECLIA assays (Roche Diagnostics, Switzerland). Thyroid ultrasound was performed with a Fukuda-Denshi 550 device (Fukuda Corp., Japan) and an Ultrasonix device (Ultrasonix Medical Corp., Canada). Statistical analyses were done using the SPSS 23.0 statistical package (Chicago, IL). Results: 64% of the patients were TPOAb+ and 36% − TgAb+. One third were only TRAb+, 1/3 had two positive antibodies (TRAb + second antibody) and 1/3 – all three positive antibodies. Patients with more positive antibodies tended to be younger, had higher fT4, TRAb levels, thyroid volume but rarely had nodules on US and accompanying GO. Positive TPOAb antibodies were found in younger patients, with higher fT4 and TRAb levels, higher thyroid volume and lower prevalence of nodules and GO. The same trends were found in patients with positive TgAb. Conclusion: The different characteristics of GD patients with varying thyroid antibody profiles may be due to a variation in the pathogenesis of the disease. An individualized clinical approach may be suitable in those cases.

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Section: Discussioncontrasting

confidence: 53%

Section: Discussionmentioning

confidence: 83%

Clinical, Hormonal, and Ultrasound Characteristics of Patients with Newly Diagnosed Graves’ Disease And Different Thyroid Antibody Profiles

Mekova

Boyanov

2019

Acta Medica Bulgarica

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“…Thyroid diseases, specifically subclinical conditions, can revert to euthyroid status over time (Somwaru et al. 2012; Zhyzhneuskaya et al. 2016).…”

Section: Methodsmentioning

confidence: 99%

Pesticide Use and Incident Hypothyroidism in Pesticide Applicators in the Agricultural Health Study

Shrestha

Parks

Goldner

et al. 2018

Environ Health Perspect

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Background: Though evidence suggests that some pesticides may have thyroid-disrupting properties, prospective studies of associations between specific pesticides and incident thyroid disease are limited. Objective: We evaluated associations between use of specific pesticides and incident hypothyroidism in private pesticide applicators in the Agricultural Health Study (AHS). Methods: Self-reported incident hypothyroidism ( cases) was studied in relation to ever-use and intensity-weighted cumulative days of pesticide use at study enrollment. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CI) using Cox proportional hazards models applied to 35,150 male and female applicators followed over 20 y. All models were stratified by state and education to meet proportional hazards assumptions ( for age x covariate interactions). Models of pesticides that did not meet proportional hazards assumptions were stratified by median attained age (62 y). Results: Hypothyroidism risk was significantly increased with ever- vs. never-use of four organochlorine insecticides (aldrin, heptachlor, and lindane among participants with attained age ; chlordane in all participants), four organophosphate insecticides (coumaphos in those ; diazinon, dichlorvos, and malathion in all participants) and three herbicides (dicamba, glyphosate, and 2,4-D in all participants). HRs ranged from 1.21; 95% CI: 1.04, 1.41 (chlordane) to 1.54; 95% CI: 1.23, 19.4 (lindane in those ). Hypothyroidism risk was greatest among those with higher intensity-weighted lifetime days of using chlordane, lindane, coumaphos (over age 62), diazinon, permethrin, and 2,4-D. Conclusions: Our findings support associations between exposure to several pesticides and increased hypothyroidism risk. These findings are generally consistent with prior analyses of prevalent hypothyroidism in the AHS. https://doi.org/10.1289/EHP3194

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“…In addition, in the presence of TSH-R-Ab indicating "subclinical" GD, the rate of progression to overt hyperthyroidism is up to 30% in the subsequent 3 years [83]. Therefore, despite the absence of randomized trials, treatment is indicated in patients older than 65 years with a TSH that is persistently < 0.1 mIU/L to potentially avoid these serious adverse events and the risk of progression to overt hyperthyroidism.…”

Section: ∅∅∅○mentioning

confidence: 99%

2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism

Kahaly¹,

Bartalena²,

Hegedüs³

et al. 2018

Eur Thyroid J

656

650

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Graves’ disease (GD) is a systemic autoimmune disorder characterized by the infiltration of thyroid antigen-specific T cells into thyroid-stimulating hormone receptor (TSH-R)-expressing tissues. Stimulatory autoantibodies (Ab) in GD activate the TSH-R leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with biochemically confirmed thyrotoxicosis, positive TSH-R-Ab, a hypervascular and hypoechoic thyroid gland (ultrasound), and associated orbitopathy. In GD, measurement of TSH-R-Ab is recommended for an accurate diagnosis/differential diagnosis, prior to stopping antithyroid drug (ATD) treatment and during pregnancy. Graves’ hyperthyroidism is treated by decreasing thyroid hormone synthesis with the use of ATD, or by reducing the amount of thyroid tissue with radioactive iodine (RAI) treatment or total thyroidectomy. Patients with newly diagnosed Graves’ hyperthyroidism are usually medically treated for 12–18 months with methimazole (MMI) as the preferred drug. In children with GD, a 24- to 36-month course of MMI is recommended. Patients with persistently high TSH-R-Ab at 12–18 months can continue MMI treatment, repeating the TSH-R-Ab measurement after an additional 12 months, or opt for therapy with RAI or thyroidectomy. Women treated with MMI should be switched to propylthiouracil when planning pregnancy and during the first trimester of pregnancy. If a patient relapses after completing a course of ATD, definitive treatment is recommended; however, continued long-term low-dose MMI can be considered. Thyroidectomy should be performed by an experienced high-volume thyroid surgeon. RAI is contraindicated in Graves’ patients with active/severe orbitopathy, and steroid prophylaxis is warranted in Graves’ patients with mild/active orbitopathy receiving RAI.

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The Natural History of Subclinical Hyperthyroidism in Graves' Disease: The Rule of Thirds

Cited by 16 publications

References 17 publications

Clinical, Hormonal, and Ultrasound Characteristics of Patients with Newly Diagnosed Graves’ Disease And Different Thyroid Antibody Profiles

Clinical, Hormonal, and Ultrasound Characteristics of Patients with Newly Diagnosed Graves’ Disease And Different Thyroid Antibody Profiles

Pesticide Use and Incident Hypothyroidism in Pesticide Applicators in the Agricultural Health Study

2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism

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