Objective: We previously reported increasing free T3 (FT3) to free T4 (FT4) ratios as thyroid-stimulating hormone (TSH) increases within the normal range in children. It is not known if this phenomenon is age-related among humans, as previously reported in rats. This study examines the relationships between TSH and FT3/FT4 ratios in different ages. Design: Retrospective examination of thyroid tests from patients without thyroid disease from community clinics. Methods: Free T3, free T4, and TSH levels from 527 564 sera collected from patients aged 1 year or greater were studied. Exclusion criteria were the following: missing data, TSH greater than 7.5 mIU/L, and medications that may interfere with thyroid hormone activity. A total of 27 940 samples remaining after exclusion were stratified by age. Samples with available anthropometric data were additionally stratified for body mass index (BMI). Correlations of TSH to FT4, FT3, and FT3/FT4 ratios by age group were examined. Results: Up to age 40, for each increasing TSH quartile, FT3 and the FT3/FT4 ratio increased and FT4 decreased significantly (for both FT3, FT4 and FT3/FT4 ratio, P < 0.05 for every TSH quartile when compared with the 1st quartile, except FT3 in the 30-40 age group). In older age groups, increasing TSH was not associated with increased FT3/FT4 ratio. Conclusion: As TSH levels increase, FT3/FT4 ratios increase until age 40, but this differential increase does not occur in older age groups. This may reflect a decrease in thyroxine (T4) to triiodothyronine (T3) conversion with age, which may be part of the aging process.

These findings suggest that deletion of VCX-A and NLGN4 can result in variable phenotypic features and that normal mental development can be achieved despite this deletion, emphasizing the importance of environmental factors and possible modifier genes.

The GnRH-agonist test and the repeated-injection hCG test are reliable diagnostic tools for differentiating CDP from GD in boys.