TY  - JOUR
ID  - discovery10198894
AV  - public
A1  - Ji, Cindy Xinyu
A1  - Zonias, Danae
A1  - Djumaeva, Nafisa
A1  - Cheng, Ranchu
A1  - Salim, Kawther
A1  - Alikhani, Pouya
A1  - Oyelade, Tope
A1  - Moore, Kevin P
A1  - Moreno, José C
A1  - Mani, Ali R
SN  - 0006-291X
KW  - Iodotyrosine deiodinase
KW  - 
Iodotyrosine dehalogenase
KW  - 
Metabolites
KW  - 
Urine
KW  - 
Mass spectrometry
UR  - http://dx.doi.org/10.1016/j.bbrc.2024.150854
Y1  - 2024/10//
PB  - Elsevier BV
N2  - Background: Congenital hypothyroidism screening traditionally relies on detecting elevated thyroid-stimulating
hormone levels, yet this approach may not detect a specific type of congenital hypothyroidism caused by
iodotyrosine dehalogenase-1 (Dehal1) deficiency. The deficiency of this enzyme prevents the deiodination of
mono-iodotyrosine (MIT) and di-iodotyrosine (DIT) in the process of iodine recycling. This underscores the
potential use of iodotyrosine or its metabolites as non-invasive urinary biomarkers for early diagnosis of
congenital hypothyroidism. However, the urinary metabolites of MIT/DIT have not yet been discovered. Thus,
this study aimed to identify the urinary metabolites of iodotyrosine in experimental models.
Method: Gas chromatography mass spectrometry was used to identify the urinary metabolites of iodotyrosine
following intraperitoneal injection of MIT in rats. An isotope dilution mass spectrometric assay was developed for
assessment of identified metabolites. Urine samples from Dehal1 knockout mice were used to confirm the results.
Results: We identified novel iodotyrosine metabolites, 3-iodo-4-hydroxyphenylacetic acid (IHPA), and 3,5-diiodo4-hydroxyphenylacetic acid (Di-IHPA) as the primary urinary metabolites of MIT and DIT respectively. The
concentrations of urinary IHPA and Di-IHPA were significantly higher in Dehal1 knockout mice.
Conclusion: Our findings suggest that IHPA is detected in larger quantities and may hold more clinical significance than previously identified biomarkers like MIT and DIT, making it a promising candidate for diagnosing
congenital hypothyroidism or other conditions associated with iodine recycling inhibition.
TI  - Identification and determination of the urinary metabolite of iodotyrosine in vivo
JF  - Biochemical and Biophysical Research Communications
N1  - © 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/bync/4.0/).
ER  -