Mass spectrometry in the diagnosis of thyroid disease and in the study of thyroid hormone metabolism

Abstract

The importance of thyroid hormones in the regulation of development, growth, and energy metabolism is well known. Over the last decades, mass spectrometry has been extensively used to investigate thyroid hormone metabolism and to discover and characterize new molecules involved in thyroid hormones production, such as thyrotropin-releasing hormone. In the earlier period, the quantification methods, usually based on gas chromatography-mass spectrometry, were complicated and time consuming. They were mainly focused on basic research, and were not suitable for clinical diagnostics on a routine basis. The development of the modern mass spectrometers, mainly coupled to liquid chromatography, enabled simpler sample preparation procedures, and the accurate quantification of thyroid hormones, of their precursors, and of their metabolites in biological fluids, tissues, and cells became feasible. Nowadays, molecules of physiological and pathological interest can be assayed also for diagnostic purposes on a routine basis, and mass spectrometry is slowly entering the clinical laboratory. This review takes stock of the advancements in the field of thyroid metabolism that were carried out with mass spectrometry, with special focus on the use of this technique for the quantification of molecules involved in thyroid diseases. | INTRODUCTIONThyroid hormones (TH), namely triiodothyronine (3,5, 3′-triiodothyronine, T 3 ) and thyroxine (3,5,3′,5′-tetraiodothyronine, T 4 ), regulate development, energy metabolism, and growth, and their blood levels are controlled by complex central and peripheral signals mainly mediated by hypothalamic thyrotropin-releasing hormone (TRH) and pituitary thyrotropin (thyroid-stimulating hormone, TSH). The hypothalamic-pituitary-thyroid axis determines the set

Determination of 3-monoiodotyrosine and 3,5-diiodotyrosine in newborn urine and dried urine spots by isotope dilution tandem mass spectrometry

“…13 Isotopically labelled MIT and DIT have not been employed to develop analytical methods for these compounds and only the possible use of 13 C 9 -iodothyroxines has been indicated. 3…”

“…Newborn screening (NBS) programs typically measure the concentration of thyrotropin stimulating hormone (TSH) in blood by inmunometric methods 1 alone or in combination with the hormone thyroxine (T4). Recently, a new type of congenital hypothyroidism was described 2 which can be missed by current NBS programs: 3,4 Iodotyrosine dehalogenase 1 deficiency (ITDD). This is a type of congenital hypothyroidism related to the failure of the thyroid enzyme iodotyrosine dehalogenase 1 (DEHAL1).…”

“…This enzyme deiodinates 3-mono-and 3,5-diiodotyrosine (MIT and DIT, respectively) and recycles iodide for the efficient synthesis of thyroid hormones. 3 Thus, mutations in the gene encoding DEHAL1 (IYD, OMIM #612025) result in iodide deficiency, which is associated with hypothyroidism, gout and childhood mental and developmental disorders. [5][6][7] High levels of iodine in the form of MIT and DIT have been observed in patients with overt hypothyroidism due to DEHAL 1 malfunction.…”

“…15 Thyroid hormone metabolites (THMs) have been determined in a variety of clinical samples using LC-MS 8,9,[16][17][18][19][20][21][22][23][24][25][26] and GC-MS. 27,28 These methods reported different sample treatment procedures in order to: (i) avoid ion suppression in the electrospray ionization source, (ii) remove high abundant compounds which may interfere in the measurement and (iii) enhance MS detection by means of preconcentration or derivatization. However, a recent review on THMs methods 3 stressed that, the lack of commercially available stable isotopically labelled internal standards for some THMs does not guarantee the proper correction of matrix effects and the reliable evaluation of extraction and/or derivatization efficiencies during sample preparation. 13 Isotopically labelled MIT and DIT have not been employed to develop analytical methods for these compounds and only the possible use of 13 C 9 -iodothyroxines has been indicated.…”

Thyroid Hormones in Sediment and Water: Method Validation and Detection in Taihu Lake of China

“…Several genetic defects of this enzyme, as well as its inhibition by xenobiotics, are known to be associated with primary hypothyroidism (Moreno et al, 2008). MIT and DIT assay is under consideration as a clinical test in neonatal screening and/or in the evaluation of potential endocrine disruptors (Borsò et al, 2020). These observations raised interest in the quantitative detection of the wider spectrum of thyroid hormones (including MIT and DIT) in serum, tissues and various environmental matrices.…”