Functional TSH receptor antibodies in children with autoimmune thyroid diseases

Stożek, Karolina; Bossowski, Artur; Ziora, Katarzyna; Bossowska, Anna; Mrugacz, Małgorzata; Noczyńska, Anna; Walczak, Mieczysław; Petriczko, Elżbieta; Pyrżak, Beata; Kucharská, Anna; Szalecki, Mieczysław; Diana, Tanja; Kahaly, George J.

doi:10.1080/08916934.2018.1431776

Cited by 23 publications

(11 citation statements)

References 34 publications

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“…This study demonstrated that TSAb is a sensitive, specific, reliable and reproducible biomarker for pediatric GD/GO and correlates well with disease severity and orbital disease. A further multicenter pediatric study confirmed the above results in European children with GD and GO [74]. Children with GD + GO were TSAb positive in 23/24 (95.8%) samples while children with thyroidal GD only were TSAb positive in 47/53 (88.7%) samples.…”

Section: Pediatric Gd/gosupporting

confidence: 68%

Thyrotropin receptor antibodies and Graves’ orbitopathy

Diana

Ponto

Kahaly

2020

J Endocrinol Invest

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Context and purpose The thyrotropin receptor (TSHR) is the key autoantigen in Graves’ disease (GD) and associated orbitopathy (GO). Antibodies targeting the TSHR (TSHR-Ab) impact the pathogenesis and the course of GO. This review discusses the role and clinical relevance of TSHR-Ab in GO. Methods Review of the current and pertinent literature. Results GO is the most common extrathyroidal manifestation of GD and is caused by persistent, unregulated stimulation of TSHR-expressing orbital target cells (e.g. fibroblasts and pre-adipocytes). Serum TSHR-Ab and more specifically, the stimulatory Ab (TSAb) are observed in the vast majority of patients with GD and GO. TSHR-Ab are a sensitive serological parameter for the differential diagnosis of GO. TSHR-Ab can be detected either with conventional binding immunoassays that measure binding of Ab to the TSHR or with cell-based bioassays that provide information on their functional activity and potency. Knowledge of the biological activity and not simply the presence or absence of TSHR-Ab has relevant clinical implications e.g. predicting de-novo development or exacerbation of pre-existing GO. TSAb are specific biomarkers of GD/GO and responsible for many of its clinical manifestations. TSAb strongly correlate with the clinical activity and clinical severity of GO. Further, the magnitude of TSAb indicates the onset and acuity of sight-threatening GO (optic neuropathy). Baseline serum values of TSAb and especially dilution analysis of TSAb significantly differentiate between thyroidal GD only versus GD + GO. Conclusion Measurement of functional TSHR-Ab, especially TSAb, is clinically relevant for the differential diagnosis and management of GO.

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Section: Pediatric Gd/gosupporting

confidence: 68%

Thyrotropin receptor antibodies and Graves’ orbitopathy

Diana

Ponto

Kahaly

2020

J Endocrinol Invest

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“…In contrast, the highly sensitive cell-based bioassays [26][27][28][29][30][31][32][33] exclusively differentiate between the TSH-R-stimulating Ab (TSAb) and TSH-R-blocking Ab [34,35]. Also, TSAb is a highly sensitive and predictive biomarker for the extrathyroidal manifestations of GD [36][37][38][39][40][41][42] as well as a useful predictive measure of fetal or neonatal hyperthyroidism [43,44]. Finally, the incorporation and early utilization of TSAb into current diagnostic algorithms conferred a 46% shortened time to diagnosis of GD and a cost saving of 47% [45].…”

Section: Serologymentioning

confidence: 99%

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

Kahaly¹,

Bartalena²,

Hegedüs³

et al. 2018

Eur Thyroid J

661

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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“…Further, in euthyroid children with GO, TBII were positive in 24 of 31 (77%) children only, while TSI were detected in all subjects (both p = 0.016). Additionally, in a different trial ( 36 ), children with GD+GO displayed the highest titers of TSAb (SRR% 417±135) in comparison to GD only (SRR% 320±157). Additionally, hyperthyroid children with GD+GO displayed higher TSI levels compared to children with GD only (median SRR%, 481 vs. 395%, both p < 0.001).…”

Section: Clinical Relevance Of Tsab As a Biomarker For Gomentioning

confidence: 93%