The Negative Impact of Levothyroxine Treatment on Urinary Luteinizing Hormone Measurements in Pediatric Patients with Thyroid Disease

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2024 Jan 1

PMID 38161981

Authors

And Demir

Ece Bober

Sukran Darcan

Adem Aydin

Ulf-Hakan Stenman

Atilla Buyukgebiz

Matti Hero

Affiliations

Soon will be listed here.

Abstract

Objectives: Previous studies suggest urinary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements by immunofluorometric assays (IFMA) as noninvasive alternatives to serum assays for puberty assessment. However, these studies excluded patients with other endocrine disorders and those taking medications. Besides, the recent discontinuation of IFMA manufacturing is a concern. We explored the utility of luminometric assays (LIA) for urinary gonadotropins and thyroid-stimulating hormone (TSH) determinations in euthyroid patients with thyroid pathologies.

Methods: We used LIA and IFMA assays to measure serum and first-morning-voided (FMV) urine LH, FSH, and TSH concentrations in euthyroid patients with various thyroid disorders. Of the 47 euthyroid patients with normal serum TSH (S-TSH) levels, 14 were receiving levothyroxine therapy.

Results: FMV total urinary LH (U-LH) concentrations correlated significantly with those measured in serum using either LIA (r=0.67, <.001) or IFMA (r=0.83, =.003) in patients not receiving levothyroxine treatment; however, no significant correlation could be detected in patients receiving levothyroxine regardless of the assay method (for LIA: r=0.50, =.08 and IFMA r=0.44, =.15). Urinary TSH (U-TSH) concentrations correlated poorly with those in serum in both the untreated and the treated groups (r=-0.13, =.49, and r=-0.45, =.11, respectively).

Conclusion: FMV total U-LH determinations by LIA can be used to assess pubertal development in patients with thyroid pathology, provided the euthyroid patient is not on levothyroxine treatment. U-TSH measurements by LIA cannot replace invasive S-TSH measurements at least in patients with normal S-TSH levels. Further research may reveal the utility of U-TSH determinations in patients with elevated S-TSH levels.

References

Demir A, Aydin A, Buyukgebiz A, Stenman U, Hero M . Urinary gonadotropin measurements by enhanced luminometric assays (LIA) for the evaluation of pubertal development. J Pediatr Endocrinol Metab. 2021; 34(7):859-866. DOI: 10.1515/jpem-2020-0598. View

Reiter E, Biggs D, Veldhuis J, Beitins I . Pulsatile release of bioactive luteinizing hormone in prepubertal girls: discordance with immunoreactive luteinizing hormone pulses. Pediatr Res. 1987; 21(4):409-13. DOI: 10.1203/00006450-198704000-00018. View

Kuku S, Harsoulis P, Young J, Fraser T . Concentrations of immunoreactive thyrotrophic hormone in urine of normal subjects, patients with thyroid disorders and hypopituitarism, and after infusion of human thyrotrophic hormone. J Endocrinol. 1974; 62(3):645-55. DOI: 10.1677/joe.0.0620645. View

Bachimanchi B, Vaikkakara S, Sachan A, Praveen Kumar G, Venkatanarasu A, Sai Krishna Chaitanya P . Effect of Adequate Thyroid Hormone Replacement on the Hypothalamo-Pituitary-Gonadal Axis in Premenopausal Women with Primary Hypothyroidism. Eur Thyroid J. 2019; 8(3):152-158. PMC: 6587368. DOI: 10.1159/000495563. View

Zung A, Burundukov E, Ulman M, Glaser T, Rosenberg M, Chen M . The diagnostic value of first-voided urinary LH compared with GNRH-stimulated gonadotropins in differentiating slowly progressive from rapidly progressive precocious puberty in girls. Eur J Endocrinol. 2014; 170(5):749-58. DOI: 10.1530/EJE-14-0010. View

Dunger D, Villa A, Matthews D, Edge J, Jones J, Rothwell C . Pattern of secretion of bioactive and immunoreactive gonadotrophins in normal pubertal children. Clin Endocrinol (Oxf). 1991; 35(3):267-75. DOI: 10.1111/j.1365-2265.1991.tb03534.x. View

Demir A, Hero M, Holopainen E, Juul A . Quantification of urinary total luteinizing hormone immunoreactivity may improve the prediction of ovulation time. Front Endocrinol (Lausanne). 2022; 13:903831. PMC: 9581300. DOI: 10.3389/fendo.2022.903831. View

Kolby N, Busch A, Aksglaede L, Sorensen K, Petersen J, Andersson A . Nocturnal Urinary Excretion of FSH and LH in Children and Adolescents With Normal and Early Puberty. J Clin Endocrinol Metab. 2017; 102(10):3830-3838. DOI: 10.1210/jc.2017-01192. View

Ulloa-Aguirre A, MIDGLEY Jr A, Beitins I, Padmanabhan V . Follicle-stimulating isohormones: characterization and physiological relevance. Endocr Rev. 1995; 16(6):765-87. DOI: 10.1210/edrv-16-6-765. View

10.

Vanderpump M, Tunbridge W, French J, Appleton D, Bates D, Clark F . The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf). 1995; 43(1):55-68. DOI: 10.1111/j.1365-2265.1995.tb01894.x. View

11.

Mann D, Plant T . The role and potential sites of action of thyroid hormone in timing the onset of puberty in male primates. Brain Res. 2010; 1364:175-85. PMC: 2992600. DOI: 10.1016/j.brainres.2010.09.082. View

12.

Demir A, Buyukgebiz A, Aydin A, Hero M . Quantification of overnight urinary gonadotropin excretion predicts imminent puberty in girls: a semi-longitudinal study. Hormones (Athens). 2023; 23(1):141-150. PMC: 10847198. DOI: 10.1007/s42000-023-00499-7. View

13.

Demir A, Hero M, Juul A, Main K . Sex-independent timing of the onset of central puberty revealed by nocturnal luteinizing hormone concentrations. Clin Endocrinol (Oxf). 2023; 99(6):552-558. DOI: 10.1111/cen.14974. View

14.

Yoshida K, Sakurada T, Kaise K, Kaise N, Nomura T, ITAGAKI Y . Measurement of thyroid stimulating hormone (TSH) in human urine. Endocrinol Jpn. 1988; 35(5):733-9. DOI: 10.1507/endocrj1954.35.733. View

15.

Vanderpump M, Tunbridge W . Epidemiology and prevention of clinical and subclinical hypothyroidism. Thyroid. 2002; 12(10):839-47. DOI: 10.1089/105072502761016458. View

16.

Zung A, RAISIN A, Zadik Z, Chen M . Nocturnal integrated gonadotropin concentrations in evaluating pubertal transition in girls. J Pediatr Endocrinol Metab. 2000; 13(4):417-23. DOI: 10.1515/jpem.2000.13.4.417. View

17.

Rabkin R, Kitaji J . Renal metabolism of peptide hormones. Miner Electrolyte Metab. 1983; 9(4-6):212-26. View

18.

Saran S, Gupta B, Philip R, Singh K, Bende S, Agroiya P . Effect of hypothyroidism on female reproductive hormones. Indian J Endocrinol Metab. 2016; 20(1):108-13. PMC: 4743370. DOI: 10.4103/2230-8210.172245. View

19.

Goldberg M, Ciesielski Jones A, McGrath J, Barker-Cummings C, Cousins D, Kipling L . Urinary and salivary endocrine measurements to complement Tanner staging in studies of pubertal development. PLoS One. 2021; 16(5):e0251598. PMC: 8118248. DOI: 10.1371/journal.pone.0251598. View

20.

Zhan S, Huang K, Wu W, Zhang D, Liu A, Dorazio R . The Use of Morning Urinary Gonadotropins and Sex Hormones in the Management of Early Puberty in Chinese Girls. J Clin Endocrinol Metab. 2021; 106(11):e4520-e4530. PMC: 8530706. DOI: 10.1210/clinem/dgab448. View