Plasma Beta-Glucuronidase Activity: A Novel Tool to Distinguish Type 1 from Type 2 Amiodarone-Induced Thyrotoxicosis?

• Published in: European thyroid journal Vol. 8; no. 4; pp. 215 - 220
• Main Authors: Markantes, Georgios K., Michalaki, Marina A., Vagenakis, George A., Lamari, Fotini N., Pitsi, Efthymia, Eliopoulou, Maria, Beratis, Nicholas G., Markou, Kostas B.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01-07-2019
• Subjects: Clinical Thyroidology / Original Paper; Plasma beta-glucuronidase activity; Destructive thyroiditis; Amiodarone-induced thyrotoxicosis; Beta-glucuronidase
• ISSN: 2235-0640; 2235-0802
• DOI: 10.1159/000500355

Background: Amiodarone-induced thyrotoxicosis (AIT) is a common and deleterious side effect of amiodarone use. There are two types of AIT, characterized by distinct pathogenic mechanisms and, hence, different treatments. Discriminating between type 1 (AIT1) and type 2 (AIT2) AIT is often very challenging. Beta-glucuronidase (β-G) is a lysosomal enzyme released into the extracellular fluid during inflammation. Objectives: To examine whether the determination of the plasma activity of β-G is useful in distinguishing AIT1 from AIT2. Methods: The study included 67 subjects: 9 with AIT1, 9 with AIT2, 14 with hyperthyroidism due to Grave’s disease or toxic multinodular goiter, 14 with subacute thyroiditis, and 21 euthyroid controls. Thyroid function tests and plasma β-G activity were determined in all participants, while thyrotoxic patients also underwent thyroid ultrasound/scintigraphy and urine iodine excretion assessment. Results: Plasma β-G activity (expressed as mean ± SD in nmol 4-methylumbelliferone [4-MU]/mL plasma/h) in AIT2 was higher compared to AIT1 (2,263.6 ± 771 vs. 1,101.8 ± 201.9, p < 0.05) and similar to subacute thyroiditis (2,263.6 ± 771 vs. 2,083.2 ± 987.5, p = ns). β-G activity did not differ significantly between AIT1 and controls (1,101.8 ± 201.9 vs. 954.6 ± 248.6, p = ns). ROC curve analysis revealed that β-G activity had a high predictive value for destructive processes, namely AIT2 and subacute thyroiditis (AUC 0.846, 95% CI 0.748–0.943) and a cut-off value of 1,480.5 nmol 4-MU/mL plasma/h was able to discriminate between destructive and non-destructive thyroid conditions with 74% sensitivity and 82% specificity. Conclusion: In our study, plasma β-G activity performed well in distinguishing AIT1 from AIT2. Further studies are warranted to establish its usefulness as a discriminator between the two AIT types.