Congenital Hypothyroidism and Kidney and Upper Urinary Tract Anomalies in Neonates; Is There Any Association?

Heidarpour, Maryam; Pashnehtalaee, MohammadJavad; Heydari, Arman; Omoomi, Sepehr; Haghighatpanah, Mohammad Ali; Payandeh, Zahra; Mirali, Niloofar; Esmaeilifallah, Mahsa; Rabbanipour, Najmeh; Hovsepian, Silva; Hashemipour, Mahin

doi:10.22038/ijp.2024.82345.5477

Congenital Hypothyroidism and Kidney and Upper Urinary Tract Anomalies in Neonates; Is There Any Association?

Document Type : original article

Authors

Maryam Heidarpour ¹^{, 2}

MohammadJavad Pashnehtalaee ¹^{, 2}

Arman Heydari ¹^{, 2}^{, 3}

Sepehr Omoomi ¹^{, 2}^{, 3}

Mohammad Ali Haghighatpanah ¹^{, 2}

Zahra Payandeh ¹^{, 2}

Niloofar Mirali ¹^{, 2}

Mahsa Esmaeilifallah ¹^{, 2}

Najmeh Rabbanipour ⁴

Silva Hovsepian ¹^{, 2}

Mahin Hashemipour ¹^{, 2}

¹ Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

² Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

³ Cardiology/Heart Failure and Transplantation, Heart Failure Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.

⁴ Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Science, Isfahan, Iran.

10.22038/ijp.2024.82345.5477

Abstract

Background: In the last twenty years, there has been a noticeable rise in the occurrence of extra-thyroidal congenital anomalies in people diagnosed with Congenital Hypothyroidism (CH). This study seeks to investigate the frequency of additional Kidney/Urinary Tract Anomalies (KUTAs) in a group of children with confirmed Permanent Congenital Hypothyroidism (PCH).
Methods: This retrospective study was conducted in Isfahan, Iran, utilizing data from the newborn screening database, where TSH test results from the Guthrie heel pinprick test were accessible. Patients diagnosed with PCH were included in the study. We excluded patients who died before three years and those who migrated to other provinces. All participants underwent ultrasonography and additional diagnostic measures, if necessary, to assess the presence of KUTAs.
Results: The study included 1091 patients with CH, of whom 74 (6.78%) also had additional KUTAs. Specific anomalies included hypospadias (1.5%), undescended testes (UDT) (1.2%), renal agenesis (0.6%), pyelocaliceal system anomalies (1.6%), hydrocele/varicocele (0.7%), and vesicoureteral reflux (0.1%). Regression analysis showed a higher likelihood of KUTAs in cases of Cesarean Section (C/S) delivery and a history of first-degree consanguineous marriage (OR=2.27, 95% CI (0.4-13.04); OR=3.34, 95% CI (0.43, 26.07), respectively). However, these observed associations were not statistically significant (P-value>0.05).
Conclusion: Our findings highlight a significant link between PCH and the occurrence of KUTAs. Therefore, a thorough kidney assessment is necessary for all confirmed PCH patients.

Keywords

Congenital Hypothyroidism

Congenital Abnormalities

Kidney

Urinary Tract

Van Trotsenburg, P., Stoupa, A., Léger, J., Rohrer, T., Peters, C., Fugazzola, L., et al. Congenital Hypothyroidism: A 2020–2021 Consensus guidelines update—An ENDO-European reference network initiative endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology. Thyroid, 31(3), pp.387-419.
Hashemipour M, Rabbani A, Rad AH, Dalili S. The consensus on the diagnosis and management of congenital hypothyroidism in term neonates. International Journal of Preventive Medicine. 2023 Jan 1;14(1):11.
Hashemipour M, Rad AH, Dalili S. Guideline for the Treatment of Hypothyroidism in Prematurity. International Journal of Preventive Medicine. 2021 Jan 1;12(1):123.
Wassner AJ, Brown RS. Congenital hypothyroidism: recent advances. Current Opinion in Endocrinology, Diabetes and Obesity. 2015 Oct 1;22(5):407-12.
Dalili S, Rezvany SM, Dadashi A, Medghalchi A, Mohammadi H, Dalili H, et al. Congenital hypothyroidism: a review of the risk factors. Acta Medica Iranica. 2012:735-9.
Therrell BL, Hannon WH. National evaluation of US newborn screening system components. Mental retardation and developmental disabilities research reviews. 2006;12(4):236-45.
Olivieri A, Fazzini C, Medda E, Italian Study Group for Congenital Hypothyroidism. Multiple factors influencing the incidence of congenital hypothyroidism detected by neonatal screening. Hormone Research in Paediatrics. 2015 Mar 1;83(2):86-93.
Dilli D, Özbaş S, Acıcan D, Yamak N, Ertek M, Dilmen U. Establishment and development of a national newborn screening programme for congenital hypothyroidism in Turkey. Journal of clinical research in pediatric endocrinology. 2013 Jun;5(2):73.
Skordis N, Toumba M, Savva SC, Erakleous E, Topouzi M, Vogazianos M, et al. High prevalence of congenital hypothyroidism in the Greek Cypriot population: results of the neonatal screening program 1990-2000. Journal of Pediatric Endocrinology and Metabolism. 2005 May;18(5):453-62.
Harris KB, Pass KA. Increase in congenital hypothyroidism in New York State and in the United States. Molecular genetics and metabolism. 2007 Jul 1;91(3):268-77.
Veisani Y, Sayehmiri K, Rezaeian S, Delpisheh A. Congenital hypothyroidism screening program in iran; a systematic review and metaanalysis. Iranian journal of pediatrics. 2014 Dec;24(6):665.
Yarahmadi S, Azhang N, Salesi M, Rahmani K. Familial-related risks for congenital hypothyroidism in iranian newborns: A population-based case-control study. International Journal of Endocrinology and Metabolism. 2021 Jan;19(1).
Hemati Z, Hashemipour M, Hovsepian S, Mansourian M, Zandieh M, Ahmadian M, et al. Congenital hypothyroidism in different cities of the Isfahan province: A descriptive retrospective study. Journal of Education and Health Promotion. 2019 Jan 1;8(1):137.
Dalili S, Rezvani SM, Dalili H, Amiri ZM, Mohammadi H, Kesh SA, et al. Congenital hypothyroidism: etiology and growth-development outcome. Acta Medica Iranica. 2014:752-6.
Castanet M, Polak M, Bonaïti-Pellié C, Lyonnet S, Czernichow P, Léger J, Afdphe. Nineteen years of national screening for congenital hypothyroidism: familial cases with thyroid dysgenesis suggest the involvement of genetic factors. The Journal of Clinical Endocrinology & Metabolism. 2001 May 1;86(5):2009-14.
Perry R, Heinrichs C, Bourdoux P, Khoury K, Szöts F, Dussault JH, et al. Discordance of monozygotic twins for thyroid dysgenesis: implications for screening and for molecular pathophysiology. The Journal of Clinical Endocrinology & Metabolism. 2002 Sep 1;87(9):4072-7.
Uthayaseelan K, Kadari M, Subhan M, Parel NS, Krishna PV, Gupta A, et al. Congenital Anomalies in Infant With Congenital Hypothyroidism: A Review of Pathogenesis, Diagnostic Options, and Management Protocols. Cureus. 2022 May;14(5).
Gheissari A, Hashemipour M, Khosravi P, Adibi A. Different aspects of kidney function in well-controlled congenital hypothyroidism. Journal of Clinical Research in Pediatric Endocrinology. 2012 Dec;4(4):193.
Tanase-Nakao K, Muroya K, Adachi M, Abe K, Hasegawa T, Narumi S. A patient with congenital hypothyroidism due to a PAX8 frameshift variant accompanying a urogenital malformation. clinical pediatric endocrinology. 2022;31(4):250-5.
Sap J, Muñoz A, Damm K, Goldberg Y, Ghysdael J, Leutz A, et al. The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature. 1986 Dec 18;324(6098):635-40.
Singh BK, Yen PM. A clinician’s guide to understanding resistance to thyroid hormone due to receptor mutations in the TRα and TRβ isoforms. Clinical diabetes and endocrinology. 2017 Dec;3:1-1.
Ortiga-Carvalho TM, Sidhaye AR, Wondisford FE. Thyroid hormone receptors and resistance to thyroid hormone disorders. Nature Reviews Endocrinology. 2014 Oct;10(10):582-91.
Yousefichaijan P, Dorreh F, Rafeie M, Sharafkhah M, Safi F, Amiri M, et al. Congenital anomalies of kidney and upper urinary tract in children with congenital hypothyroidism; a case-control study. Journal of Renal Injury Prevention. 2015;4(4):120.
Kumar J, Gordillo R, Kaskel FJ, Druschel CM, Woroniecki RP. Increased prevalence of renal and urinary tract anomalies in children with congenital hypothyroidism. The Journal of pediatrics. 2009 Feb 1;154(2):263-6.
Cassio A, Tato L, Colli C, Spolettini E, Costantini E, Cacciari E. Incidence of congenital malformations in congenital hypothyroidism. Screening. 1994 Dec 1;3(3):125-30.
Reddy PA, Rajagopal G, Harinarayan CV, Vanaja V, Rajasekhar D, Suresh V, et al. High prevalence of associated birth defects in congenital hypothyroidism. International journal of pediatric endocrinology. 2010 Dec;2010(1):1-5.
El Kholy M, Fahmi ME, Nassar AE, Selim S, Elsedfy HH. Prevalence of minor musculoskeletal anomalies in children with congenital hypothyroidism. Hormone research. 2007 Nov 1;68(6):272-5..
Wędrychowicz A, Furtak A, Prośniak A, Żuberek M, Szczerkowska M, Pacut P, et al. Extrathyroidal congenital defects in children with congenital hypothyroidism–observations from a single paediatric centre in Central Europe with a review of literature. Pediatric Endocrinology Diabetes and Metabolism. 2019 Jan 1;25(3):114-21.
Rose SR, Wassner AJ, Wintergerst KA, Yayah-Jones NH, Hopkin RJ, Chuang J, et al. Congenital hypothyroidism: screening and management. Pediatrics. 2023 Jan 1;151(1).
Abbasi F, Janani L, Talebi M, Azizi H, Hagiri L, Rimaz S. Risk factors for transient and permanent congenital hypothyroidism: A population-based case-control study. Thyroid Research. 2021 May 5;14(1):11.