Research Article

Measurement of free fraction, total concentration and protein binding for testosterone, triiodothyronine and thyroxine

Albany College of Pharmacy & Health Sciences, Department of Pharmaceutical Sciences, 106 New Scotland Avenue, Albany, NY 12208, USA

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Michael P Kane

Albany College of Pharmacy & Health Sciences, Department of Pharmacy Practice, 106 New Scotland Avenue, Albany, NY 12208, USA

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Florin M Musteata

*Author for correspondence: Tel.: +1 518 694 7883;

E-mail Address: marcel.musteata@acphs.edu

https://orcid.org/0000-0001-6143-2171

Albany College of Pharmacy & Health Sciences, Department of Pharmaceutical Sciences, 106 New Scotland Avenue, Albany, NY 12208, USA

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Published Online:17 Oct 2023https://doi.org/10.4155/bio-2023-0126

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Abstract

Aims: Measuring the total and free concentrations of hormones is useful, but the technology to do this simultaneously is lacking. Methods: A new method offers the ability to measure these parameters concurrently for testosterone, thyroxine and triiodothyronine. Results: The free concentrations showed significant correlations with patients’ vital statistics. Overall, 67% of correlations for total concentration showed that the new and classical methods had equal accuracy, or that comprehensive ultrafiltration was more accurate. The protein binding term was found to correlate significantly with the patients’ luteinizing hormone, prostate-specific antigen and height. Conclusion: Comprehensive ultrafiltration for measuring the total concentration, free concentration and protein binding term uses less sample and is much faster than measuring these parameters with three separate methods.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Cibotaru D, Celestin MN, Kane MP, Musteata FM. Method for simultaneous determination of free concentration, total concentration, and plasma binding capacity in clinical samples. J. Pharm. Sci. 110(3), 1401–1411 (2021). •• Describes two sample preparation approaches and two calculation approaches for simultaneous measurement of free and total concentrations in the same sample; further describes how to measure both concentrations with and without using isotopically labeled analytes.
Medline CASGoogle Scholar
2. Summerfield SG, Fairman DA. Free drug theory – no longer just a hypothesis? Pharm. Res. 39(2), 213–222 (2022). •• Recent analysis of the importance of measuring free drug concentrations; points out that the importance of free concentrations is not a hypothesis anymore, but has been proven.
Medline CASGoogle Scholar
3. Bikle DD. The free hormone hypothesis: when, why, and how to measure the free hormone levels to assess vitamin D, thyroid, sex hormone, and cortisol status. JBMR Plus 5(1), e10418 (2021). • Thorough discussion of the importance of measuring free hormone concentrations.
Medline CASGoogle Scholar
4. Goldman AL, Bhasin S, Wu FCW, Krishna M, Matsumoto AM, Jasuja R. A reappraisal of testosterone’s binding in circulation: physiological and clinical implications. Endocr. Rev. 38(4), 302–324 (2017).
MedlineGoogle Scholar
5. Illamola SM, Hirt D, Tréluyer JM, Urien S, Benaboud S. Challenges regarding analysis of unbound fraction of highly bound protein antiretroviral drugs in several biological matrices: lack of harmonisation and guidelines. Drug Discov. Today 20(4), 466–474 (2015). • Comprehensive overview of challenges and approaches for monitoring free concentrations.
Medline CASGoogle Scholar
6. Tanoue R, Kume I, Yamamoto Y et al. Determination of free thyroid hormones in animal serum/plasma using ultrafiltration in combination with ultra-fast liquid chromatography-tandem mass spectrometry. J. Chromatogr. A 1539, 30–40 (2018).
Medline CASGoogle Scholar
7. Thienpont LM, Van Uytfanghe K, Poppe K, Velkeniers B. Determination of free thyroid hormones. Best Pract. Res. Clin. Endocrinol. Metab. 27(5), 689–700 (2013).
Medline CASGoogle Scholar
8. Kurniawan AL, Hsu CY, Chao JC et al. Association of testosterone-related dietary pattern with testicular function among adult men: a cross-sectional health screening study in Taiwan. Nutrients 13(1), 259 (2021).
Medline CASGoogle Scholar
9. Page ST, Mohr BA, Link CL, O’Donnell AB, Bremner WJ, McKinlay JB. Higher testosterone levels are associated with increased high-density lipoprotein cholesterol in men with cardiovascular disease: results from the Massachusetts Male Aging Study. Asian J. Androl. 10(2), 193–200 (2008).
Medline CASGoogle Scholar
10. Reinhardt W, Mülling N, Behrendt S et al. Association between albuminuria and thyroid function in patients with chronic kidney disease. Endocrine 73(2), 367–373 (2021).
Medline CASGoogle Scholar
11. Alwani M, Al-Zoubi RM, Al-Qudimat A et al. The impact of long-term testosterone therapy (TTh) in renal function (RF) among hypogonadal men: an observational cohort study. Ann. Med. Surg. 69, 102748 (2021).
MedlineGoogle Scholar
12. Selva DM, Hammond GL. Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4alpha. J. Mol. Endocrinol. 43(1), 19–27 (2009).
Medline CASGoogle Scholar
13. Dumoulin SC, Perret BP, Bennet AP, Caron PJ. Opposite effects of thyroid hormones on binding proteins for steroid hormones (sex hormone-binding globulin and corticosteroid-binding globulin) in humans. Eur. J. Endocrinol. 132(5), 594–598 (1995).
Medline CASGoogle Scholar
14. Rudorff KH. [Thyroxine-binding globulin (TBG). Clinical studies on the regulation of TBG concentration in serum and the value of TBG for the evaluation of thyroid function]. Fortschr. Med. 97(44), 2038–2045 (1979).
Medline CASGoogle Scholar
15. Rizos CV, Elisaf MS, Liberopoulos EN. Effects of thyroid dysfunction on lipid profile. Open Cardiovasc. Med. J. 5, 76–84 (2011).
Medline CASGoogle Scholar
16. Kabodmehri R, Sharami SH, Sorouri ZZ et al. The relationship between thyroid function and ovarian reserve: a prospective cross-sectional study. Thyroid Res. 14(1), 22 (2021).
Medline CASGoogle Scholar
17. Romano RM, Bargi-Souza P, Brunetto EL et al. Triiodothyronine differentially modulates the LH and FSH synthesis and secretion in male rats. Endocrine 59(1), 191–202 (2018).
Medline CASGoogle Scholar
18. Viguié C, Battaglia DF, Krasa HB, Thrun LA, Karsch FJ. Thyroid hormones act primarily within the brain to promote the seasonal inhibition of luteinizing hormone secretion in the ewe. Endocrinology 140(3), 1111–1117 (1999).
Medline CASGoogle Scholar
19. Ashok T, Palyam V, Azam AT et al. Relationship between vitamin D and thyroid: an enigma. Cureus 14(1), e21069 (2022).
MedlineGoogle Scholar
20. Aboelnaga MM, Abdullah N. The correlation between 25-hydroxyvitamin D levels and testosterone levels in type 2 diabetic male patients. Endocr. Metab. Immune Disord. Drug Targets doi:10.2174/1871530322666220524104929 (2022) (Epub ahead of print).
MedlineGoogle Scholar
21. Henderson CM, Fink SL, Bassyouni H et al. Vitamin D-binding protein deficiency and homozygous deletion of the GC gene. N. Engl. J. Med. 380(12), 1150–1157 (2019).
Medline CASGoogle Scholar
22. Koga M, Murai J, Saito H, Matsumoto S, Kasayama S. Effects of thyroid hormone on serum glycated albumin levels: study on non-diabetic subjects. Diabetes Res. Clin. Pract. 84(2), 163–167 (2009).
Medline CASGoogle Scholar
23. Cetinkaya E, Aslan A, Vidinlisan S, Ocal G. Height improvement by L-thyroxine treatment in subclinical hypothyroidism. Pediatr. Int. 45(5), 534–537 (2003).
Medline CASGoogle Scholar
24. Srivastava S, Rajput J, Shrivastava M, Chandra R, Gupta M, Sharma R. Correlation of thyroid hormone profile with biochemical markers of renal function in patients with undialyzed chronic kidney disease. Indian J. Endocrinol. Metab. 22(3), 316–320 (2018).
Medline CASGoogle Scholar
25. Kotwal A, Cortes T, Genere N et al. Treatment of thyroid dysfunction and serum lipids: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 105(12), dgaa672 (2020).
MedlineGoogle Scholar
26. Cakir E, Sahin M, Topaloglu O et al. The relationship between LH and thyroid volume in patients with PCOS. J. Ovarian Res. 5(1), 43 (2012).
Medline CASGoogle Scholar
27. Larsen PR. Salicylate-induced increases in free triiodothyronine in human serum. Evidence of inhibition of triiodothyronine binding to thyroxine-binding globulin and thyroxine-binding prealbumin. J. Clin. Invest. 51(5), 1125–1134 (1972).
Medline CASGoogle Scholar

Vol. 15, No. 22

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History

Received 22 June 2023

Accepted 20 September 2023

Published online 17 October 2023

Published in print November 2023

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.future-science.com/doi/suppl/10.4155/bio-2023-0126

Financial disclosure

The authors acknowledge funding from the US National Institutes of Health (1R15GM126510). The article will be deposited on the NIHMS system/PMC. The authors’ work was independent of the funders. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Albany College of Pharmacy and Health Sciences (23 September 2019, no. 18-016-19). Written informed consent was obtained from all participants prior to conducting any study procedures.

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