A1 Refereed original research article in a scientific journal
Congenital Hypothyroidism and Hyperthyroidism Alters Adrenal Gene Expression, Development, and Function
Authors: Patyra Konrad, Löf Christoffer, Jaeschke Holger, Undeutsch Hendrik, Zheng Huifei Sophia, Tyystjärvi Sofia, Puławska Kamila, Doroszko Milena, Chruściel Marcin, Loo Britt-Marie, Kurkijärvi Riikka, Zhang Fu-Ping, Huang Chen-Che Jeff, Ohlsson Claes, Kero Andreina, Poutanen Matti, Toppari Jorma, Paschke Ralf, Rahman Nafis, Huhtaniemi Ilpo, Jääskeläinen Jarmo, Kero Jukka
Publisher: Mary Ann Liebert Inc.
Publication year: 2022
Journal: Thyroid
Journal name in source: Thyroid
Volume: 32
Issue: 4
First page : 459
Last page: 471
eISSN: 1557-9077
DOI: https://doi.org/10.1089/thy.2021.0535
Web address : http://doi.org/10.1089/thy.2021.0535
Background
The human adrenal cortex undergoes several rapid remodeling steps during its lifetime. In rodents, similar remodeling occurs postnatally in the “X-zone” layer through unknown mechanisms. Furthermore, little is known regarding the impact of thyroid hormone (TH) on adrenal glands in humans.
Methods
To investigate the impact of TH on adrenal pathophysiology, we created two genetic murine models mimicking human nonautoimmune hypothyroidism and hyperthyroidism. Moreover, we analyzed serum thyrotropin (TSH) and steroid hormone concentrations in patients diagnosed with congenital hypothyroidism and premature adrenarche (PA).
Results
We found that TH receptor beta-mediated hypertrophy of the X-zone significantly elevated the adrenal weights of hyperthyroid women. In the hypothyroid model, the X-zone was poorly developed in both sexes. Moreover, large reciprocal changes in the expression levels of genes that regulate adrenal cortical function were observed with both models. Unexpectedly, up- and downregulation of several genes involved in catecholamine synthesis were detected in the adrenal glands of the hypothyroid and hyperthyroid models, respectively. Furthermore, TSH and adrenal steroid concentrations correlated positively in pediatric patients with congenital hypothyroidism and PA.
Conclusions
Our results revealed that congenital hypothyroidism and hyperthyroidism functionally affect adrenal gland development and related steroidogenic activity, as well as the adrenal medulla.
