The role of functional thyroid capacity in pituitary thyroid feedback regulation

BackgroundThyroid feedback regulation and equilibria between thyroid hormones differ in the presence or absence of a functioning thyroid remnant. Materials and MethodsThis study examines the relationship between the sensitivity of TSH feedback and thyroid capacity in untreated patients with thyroid autoimmune disease (n=86) and healthy controls (n=271). Functional capacity was estimated at maximum TSH stimulation, and pituitary TSH response was FT4-standardised with two established indices, the TSH index and the thyrotroph thyroid hormone resistance index. ResultsThe two indices correlated inversely with thyroid volume and functional thyroid capacity. Relationships were shifted upwards in patients with thyroid autoimmune disease. This positioned patients with thyroid autoimmune disease predominantly at the lower capacity range and upper part of TSH index. The relationship was modulated by serum FT3 concentrations, shifting 0.19 [95%CI: 0.12, 0.26] mIU/L per pmol FT3 increase. FT3 correlated with TSH index in total group (=0.09, P=0.009) and both subgroups. FT3 levels were maintained despite a substantial capacity loss by progressively increasing conversion rates of T3 from T4, only collapsing at capacities below <1.5pmol/s. ConclusionFunctional thyroid capacity and preferential T3 generation are essential elements in adjusting the sensitivity of hypothalamic-pituitary-thyroid feedback control and balancing system equilibria. This suggests that the indirect regulatory role of glandular T3 co-secretion exceeds its quantitative contribution to the thyroid hormone pool. Implications for clinical practice extend to the diagnostic use of TSH in patients with impaired thyroid reserve.