Diagnostic testing for Graves' or non-Graves' hyperthyroidism: A comparison of two thyrotropin receptor antibody immunoassays with thyroid scintigraphy and ultrasonography.
OBJECTIVE
Graves' disease (GD) is the most common cause of hyperthyroidism. In many cases, when the aetiological diagnosis of GD is not evident based on the clinical evaluation and thyroid function testing, it may become challenging to distinguish Graves' hyperthyroidism from other forms of thyrotoxicosis. The current study was primarly carried out to compare the diagnostic effectiveness of two TSH receptor antibody immunoassays (IMAs), ultrasonography and thyroid scintigraphy in hyperthyroidism scenario.


METHODS
We retrospectively analysed consecutive patients with newly diagnosed and untreated thyrotoxicosis who underwent thyroid functional tests, both TRAb and TSI measurements, thyroid scintigraphy and ultrasonography. TRAb assessment was carried out by Kryptor® compact PLUS, while TSI by Immulite® . Echo pattern 3 corresponded to 'thyroid inferno', and the final diagnosis of GD vs non-Graves' hyperthyroidism was made according to the thyroid scan (qualitative scintigraphy). Receiver operating characteristic (ROC) curves were drawn using the final diagnosis as reference. Clinical sensitivity and specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for all the tests.


RESULTS
A total of 124 untreated hyperthyroid patients were included in our study (GD, n = 86 vs non-Graves' hyperthyroidism, n = 38). ROC curves showed that the optimal cut-off values associated with the highest diagnostic sensitivity and specificity was 0.7 IU/L for TRAb Kryptor® (93 [85.4-97.4] and 86.8 [71.9-95.5]) and 0.1 IU/L for TSI Immulite® (94.2 [86.9-98.1] and 84.2 [68.7-93.9]), respectively. For the echo pattern 3, we found a good sensitivity (92.1%) and a high PPV (95.2%) but a quite low specificity value (69.8%) and a relative low NPV (57.5%). For thyroid scintigraphy, the TcTU cut-off value of 1.3% corresponded to the best limit for sensitivity and specificity in our patients (95.3 [88.5-98.7] and 96.4 [81.6-99.4]). The Passing-Bablok regression equation and the Bland-Altman test showed a great degree of correlation and agreement existed between TRAb Kryptor® and Immulite® TSI results.


CONCLUSIONS
Thyroid scintigraphy remains the most accurate method to differentiate causes of thyrotoxicosis. However, TRAb assays can be alternatively adopted in this setting, limiting the use of thyroid scintigraphy (TcTU evaluation) to TRAb-negative patients. Thyoid US is less accurate than both TRAb/TSI and thyroid scintigraphy, but the 'thyroid inferno' pattern provides a high PPV for GD.
['Scappaticcio|Lorenzo|L|0000-0003-2972-9551', 'Trimboli|Pierpaolo|P|', 'Keller|Franco|F|', 'Imperiali|Mauro|M|', 'Piccardo|Arnoldo|A|0000-0002-6779-1471', 'Giovanella|Luca|L|0000-0003-0230-0974']
D000328:Adult D000368:Aged D003937:Diagnosis, Differential D005260:Female D006111:Graves Disease D006801:Humans D006980:Hyperthyroidism D007118:Immunoassay D018828:Immunoglobulins, Thyroid-Stimulating D008297:Male D008875:Middle Aged D011877:Radionuclide Imaging D015203:Reproducibility of Results D012189:Retrospective Studies D012680:Sensitivity and Specificity D013670:Sodium Pertechnetate Tc 99m D013960:Thyroid Function Tests D013961:Thyroid Gland D013971:Thyrotoxicosis D018615:Ultrasonography, Doppler, Color
hyperthyroidism thyroid scintigraphy thyroid ultrasonography thyroid-stimulating immunoglobulins (TSI) thyrotropin receptor antibodies (TRAb)