Predicting the Relapse of Hyperthyroidism in Treated Graves’ Disease with Orbitopathy by Serial Measurements of TSH-Receptor Autoantibodies

Stöhr, Mareile; Oeverhaus, Michael; Lytton, Simon D.; Horstmann, Mareike; Zwanziger, Denise; Möller, Lars; Stark, Achim; Führer-Sakel, Dagmar; Bechrakis, Nikolaos E.; Berchner‐Pfannschmidt, Utta; Banga, J. Paul; Philipp, Svenja; Eckstein, Anja

doi:10.1055/a-1373-5523

Cited by 13 publications

(8 citation statements)

References 39 publications

(57 reference statements)

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“…In addition, unlike binding assays, functional biomarkers have demonstrated remarkable predictive value as indicators of relapse/remission of GD and the clinical phenotype of TAO [27] [43] [44] . This is another feature in favor of bioassays that would greatly facilitate patient monitoring and follow-up.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity of three thyrotropin receptor antibody assays in thyroid-associated orbitopathy

Matutinović¹,

Diana²,

Beleslin³

et al. 2022

J Med Biochemistry

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Background: Thyrotropin receptor autoantibodies (TSH-R-Ab) are indispensable biomarkers in the laboratory assessment of thyroid-associated orbitopathy (TAO). Clinical sensitivity of three different assays for TSH-R-Ab determination was evaluated in patients with TAO. Methods: 87 consecutive TAO patients were enrolled and their serum samples analyzed in parallel with three assays. An ECLIA competitive binding and a chemiluminescent bridge immunoassay were used to measure total and binding TSH-R-Ab concentration, while their functional activity was determined using a stimulatory TSH-R-Ab (TSAb) cell-based bioassay. Results: Compared to the two binding assays (ECLIA p<0.001, bridge p=0.003), the TSAb bioassay was more sensitive pertaining to the positive detection of TSH-R-Ab in TAO patients. No difference (p=0.057) was noted between the ECLIA and bridge assays regarding sensitivity rate. All patients with active and/or moderate-to-severe TAO tested positive in the TSAb bioassay (100% and 100%, respectively), while the positivity rates for bridge and ECLIA binding assays were 89.7% and 82.1% for active TAO, and 90.2% and 86.3% for severe TAO, respectively. Negative predictive values of the bioassay, bridge, and ECLIA assays were 100%, 75%, and 71%, respectively for active TAO, and 100%, 86%, and 71%, respectively for moderate-to-severe TAO. The superiority of the bioassay was most prominent in euthyroid (ET) TAO. Positivity rates of the TSAb bioassay, bridge and ECLIA binding assays were 89.6%, 75%, and 64.6%, respectively for inactive TAO; 86.1%, 69.4%, and 52.8%, respectively for mild TAO; 87.5%, 62.5%, and 12.5%, respectively for euthyroid TAO. The bridge assay correlated better with the ECLIA binding assay (ρ=0.893, p<0.001), compared to the bioassay (ρ=0.669, p<0.001). Conclusions: In patients with TAO of various activity and severity, the TSAb bioassay demonstrates a superior clinical performance compared to both ECLIA and bridge binding assays.

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Section: Discussionmentioning

confidence: 99%

Sensitivity of three thyrotropin receptor antibody assays in thyroid-associated orbitopathy

Matutinović¹,

Diana²,

Beleslin³

et al. 2022

J Med Biochemistry

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“…TRAbs in the serum samples of Graves hyperthyroidism are polyclonal and may contain apparent neutral Abs (or short-acting TBAb) in addition to TSAb and TBAb (long acting). Therefore, the measurement of TSAbs is useful to assess the remission of the patient after treatment with antithyroid drugs [ 25 ]. For a complete understanding of TRAb, the isolation of apparent N-mAb is necessary.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Apparently Paradoxical Thyrotropin Binding Inhibitory Immunoglobulins With Neutral Bioactivity

Tagami

Moriyama

2022

Journal of the Endocrine Society

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Context The thyrotropin (TSH) receptor (TSH-R) autoantibody activity is clinically measured by inhibition of labeled ligand (TSH or M22) binding to the TSH-R [TSH-binding inhibitory immunoglobulin (TBII)] or by stimulation [TSH-R stimulating antibody (TSAb)] or inhibition [TSH-R blocking antibody (TSBAb)] of cAMP production in isolated cells. Objective We experienced a patient with hypothyroid Graves’ disease (GD) having strong positive TBII, but with almost neutral bioactivities on the TSH-R. The aim of this study is characterization of this apparently paradoxical TBII (sera S). Design We first compared the TBII, TSAb and TSBAb activities of sera S with mixtures of stimulating (S-mAb) and blocking monoclonal Ab (B-mAb). Next, we serially measured cAMPs stimulated by various sera in the presence or absence of TSH. Results Mixtures of S-mAb and B-mAb did not reproduce the characteristics of sera S. Instead, the sera S had a unique feature which blocked the TSH-stimulated cAMP initially but disappeared the blocking activity thereafter to reach the control level. Conclusions We present here the TBIIs with neutral bioactivities found in the patient with autoimmune thyroid disease, which strongly inhibit TSH-binding to the TSH-R but exerts neither TSAb nor TSBAb activity. Differences in the methods to detect TRAb between TBII in vitro and bioassay may cause the discrepancy. Although the sera S may be an extreme example, a variety of TRAb, not only stimulating or blocking but also interfering with TSH-R binding only for a short time, may exist in the sera of GD patients.

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“…In the course of the treatment of the GO, decisions have to be made again and again for the patients. Identification of relapsing hyperthyroidism was possible with automated immunoassays and cell-based bioassay especially with serial TRAb measurements during the course of ATD therapy [40] . Bartalena et al (2017) has shown in the dose finding study for i. v. glucocorticoid treatment that after 6 weeks treatment one can already see a trend whether i. v. glucocorticoid treatment will deliver the desired treatment success [41].…”

Section: Discussionmentioning

confidence: 99%

Predicting the Course of Graves’ Orbitopathy Using Serially Measured TSH-Receptor Autoantibodies by Automated Binding Immunoassays and the Functional Bioassay

Stöhr

Oeverhaus

Lytton³

et al. 2021

Horm Metab Res

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The aim of the study was to investigate the use of serial measurements of TSH-receptor autoantibodies (TRAb) with the newest available assay technology to predict the course of Graves’ Orbitopathy (GO) during the first 24 months from disease onset. Serial serum samples from patients with GO (103 mild/135 severe) were collected between 2007 and 2017 and retrospectively analyzed. The course of GO were classified into mild/severe 12 months after manifestation (severe: NOSPECS≥5; mild<5). TRAb were measured with automated binding immunoassays (IU/l): TRAb Elecsys (Cobas, Roche), TRAb bridge assay (IMMULITE, Siemens), and a cell-based bioassay (percent of specimen to reference ratio - SRR%) (Thyretain, Quidel). Variable cut off levels of measured TRAb were calculated at specificity of 90% from receiver operator curve (ROC) analysis for several timepoints during the course of GO. To select one: 5–8 months after first GO symptoms, which is the timepoint for usual referals for treatment mild course could be predicted at cut offs of 1.5 IU/l (Elecsys), 0.8 IU/l (Immulite) and 402% SRR (Thyretain) and the risc of severe course has to be anticipated if TRAb are above 11.6 IU/l (Elecsys), 6.5 IU/l (Thyretain), and 714% SRR (Thyretain). The Thyretain bioassay showed the highest diagnostic sensitivity (using the commercial cut off’s) over the entire follow up period. TRAb measurements during the 24-month follow up of GO provide added value to the GO clinical activity and severity scores and should be used especially in the event of an unclear decision-taking situation with regard to therapy.

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Predicting the Relapse of Hyperthyroidism in Treated Graves’ Disease with Orbitopathy by Serial Measurements of TSH-Receptor Autoantibodies

Cited by 13 publications

References 39 publications

Sensitivity of three thyrotropin receptor antibody assays in thyroid-associated orbitopathy

Sensitivity of three thyrotropin receptor antibody assays in thyroid-associated orbitopathy

Characterization of Apparently Paradoxical Thyrotropin Binding Inhibitory Immunoglobulins With Neutral Bioactivity

Predicting the Course of Graves’ Orbitopathy Using Serially Measured TSH-Receptor Autoantibodies by Automated Binding Immunoassays and the Functional Bioassay

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