Age-dependent response to T4 overtreatment and recovery on systemic and organ level.
Helena RakovKostja RenkoGeorg Sebastian HönesKlaudia BrixJosef KöhrleLars Christian MoellerDagmar FührerPublished in: Journal of molecular endocrinology (2021)
Thyroid hormone (TH) metabolism and cellular TH action are influenced by ageing. To investigate the response to thyroxine (T4) overtreatment, a kinetic study was conducted in young and aged mice with chronic hyperthyroidism and hormone withdrawal. Five and 22 months old male mice were treated with T4 or PBS over 5 weeks, followed by observation for up to 12 days. Serial analysis was performed for thyroid function parameters, transcript levels of TH target genes, deiodinase type 1 (DIO1) activity as well as serum lipids at 12, 24, 72, 144, 216, and 288 h after cessation of T4 administration. Higher FT3 concentrations and higher renal DIO1 activities were noted in aged mice 12 h after T4 withdrawal and marked thyroid-stimulating hormone elevation was found in aged mice after 12 days compared to respective controls. A biphasic expression pattern occurred for TH target genes in all organs and a hypothyroid organ state was observed at the end of the study, despite normalization of TH serum concentrations after 72 h. In line with this, mirror-image kinetics were detected for serum cholesterol and triglycerides in aged and young mice. Recovery from TH overtreatment in mice involves short- and medium-term adaption of TH metabolism on systemic and organ levels. Increased renal DIO1 activity may contribute to higher T3 concentrations and prolonged thyrotoxicosis followed by hypothyroidism in an aged-mouse organism. Translation of these findings in the clinical setting seems warranted and may lead to better management of hyperthyroidism and prevention of T4 overtreatment in aged patients.
Keyphrases
- high fat diet induced
- end stage renal disease
- chronic kidney disease
- newly diagnosed
- ejection fraction
- type diabetes
- gene expression
- metabolic syndrome
- poor prognosis
- dna methylation
- drug induced
- long non coding rna
- peritoneal dialysis
- fatty acid
- transcription factor
- preterm birth
- low density lipoprotein
- patient reported outcomes
- smoking cessation