Congenital hypothyroidism: Space-time clustering of thyroid dysgenesis indicates a role for environmental factors in disease etiology

McNally, R., Jones, J. H., Shaikh, M. G., Donaldson, M., Blakey, K. and Cheetham, T. (2021) Congenital hypothyroidism: Space-time clustering of thyroid dysgenesis indicates a role for environmental factors in disease etiology. Thyroid, 31(6), pp. 876-883. (doi: 10.1089/thy.2020.0005) (PMID:33183175) (PMCID:PMC8215409)

Abstract

Background: The etiology of most cases of congenital hypothyroidism (CHT) due to thyroid dysgenesis (DG) is unknown. If transient environmental factors can impact on thyroid gland development, then clustering of cases in time and/or space may occur, and this would be more likely in thyroid DG than dyshormonogenesis (DHG). Methods: The newborn screening program for CHT in Scotland is linked to a central database that includes case details such as postcode. The etiology of CHT is investigated in many cases of CHT using scintigraphy and/or ultrasonography. We looked for evidence of a change in CHT incidence with year of birth and according to season of the year. We then undertook space–time clustering analysis (using a method based on K-functions, with nearest neighbor thresholds) of CHT in Scotland between 1979 and 2015. We also looked for evidence of overall changes associated with sex and area-based birth density. Results: Of 531 cases with CHT during the study period, 290 cases had been categorized as DG (n = 229) or DHG (n = 61) following more detailed investigation. The incidence of CHT increased with year of birth and was in part linked to changing methodology, but there was no seasonality. There was no evidence of overall space–time clustering (p = 0.06), but there was evidence of clustering in babies with DG (p = 0.007). This picture appeared to be most closely linked to underlying thyroid gland hypoplasia rather than thyroid gland agenesis or ectopia. There was significant space–time clustering for both males and females, but clustering was restricted to lesser birth density areas. There was also evidence of clustering for unknown cases (p < 0.001). Clustering of these cases was restricted to females but was present for cases from both greater and lesser birth density areas. There was no evidence of clustering in cases of DHG. Conclusions: These data suggest that an unidentified environmental factor or factors may be involved in the etiology of thyroid DG in Scotland. The variation in CHT incidence observed internationally may reflect environmental as well as genetic factors.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Shaikh, Dr Mohammed Guftar and Donaldson, Dr Malcolm
• Authors: McNally, R., Jones, J. H., Shaikh, M. G., Donaldson, M., Blakey, K., and Cheetham, T.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Thyroid
• Publisher: Mary Ann Liebert
• ISSN: 1050-7256
• ISSN (Online): 1557-9077
• Published Online: 29 December 2020
• Copyright Holders: Copyright © Richard J.Q. McNally et al., 2020
• First Published: First published in Thyroid 31(6):876-883
• Publisher Policy: Reproduced under a Creative Commons licence