Physiological linkage of thyroid and pituitary sensitivities.

OBJECTIVES: The sensitivities of the pituitary to thyroxine feedback, and the thyroid to thyrotropin stimulation determine the free thyroxine /thyrotropin feedback loop and can be described mathematically by two curves. It is not well understood how the two curves combine in a healthy population with normal thyroid function to express the individual balance points that are observed. This study was directed at this issue testing the possibilities of random combination and directed linkage between the two curves. METHODS: We reverse-engineered two sets of population data, on the assumption of independent combinations of thyroid and pituitary sensitivities, to obtain estimates of the curve describing thyroid sensitivity. Sensitivity studies were performed. RESULTS: No analysis resulted in a physiologically feasible estimate of the curve describing thyroid sensitivity. There was evidence of linkage of the two curves in terms of their combination throughout the normal range. Thyroid response curves reflecting a low free thyroxine response to thyrotropin tended to be combined in individuals with thyrotropin curves reflecting a high thyrotropin response to free thyroxine, and vice versa. CONCLUSIONS: Thyroid and pituitary sensitivities are linked, being combined in individuals in a non-random directed pattern. Direct mutual interaction may contribute to this linkage. This linkage precludes the derivation of the curves describing these sensitivities from population data of the free thyroxine and thyrotropin relationship and complicates their derivation by physiological experimentation. This linkage and probable interaction may also bestow evolutionary advantage by minimising inter-individual variation in free thyroxine levels and by augmenting homeostasis.

Thyroid stimulating hormone (TSH) autoregulation reduces variation in the TSH response to thyroid hormones.

The physiological functions of Thyroid Stimulating Hormone (TSH) autoregulation, the ultra-short feedback loop inhibition of TSH by TSH itself, have not been determined. In this work we explored the role of TSH autoregulation in thyroid homeostasis. We synthesized the known physiology of autoregulation with theknown physiological relationships between thyroid hormones; in particular between free thyroxine and TSH. We analysed the implications of TSH autoregulation, on the generation of the TSH response to free thyroxine (the 'TSH curve'), and on the variation inthis response, which might result from variations in hypothalamopituitary or thyroid gland function. Our analysis demonstrated that, in the circumstances of inter-individual and intra-individual variations to hypothalamo-pituitary function TSH autoregulation lessens variation in the TSH curve. This in turn enhances the probability of generating and maintaining a euthyroid free thyroxine value. This contribution of TSH autoregulation to the stabilisation of thyroid physiology offers a logical explanation for the evolutionary selection of this physiological process.

Corrigendum to "The Relationship between Population T4/TSH Set Point Data and T4/TSH Physiology".

[This corrects the article DOI: 10.1155/2016/6351473.].

The Relationship between Population T4/TSH Set Point Data and T4/TSH Physiology.

Context. Population studies of the distribution of T4/TSH set points suggest a more complex inverse relationship between T4 and TSH than that suggested by physiological studies. The reasons for the similarities and differences between the curves describing these relationships are unresolved. Methods. We subjected the curve, derived from empiric data, describing the TSH suppression response to T4, and the more mathematically derived curve describing the T4 response to TSH, to the different possible models of population variation. The implied consequences of these in terms of generating a population distribution of T4/TSH equilibrium points (a "population curve") were generated and compared to the empiric population curve. The physiological responses to primary hypothyroidism and hyperthyroidism were incorporated into the analysis. Conclusions. Though the population curve shows a similarly inverse relationship, it is describing a different relationship than the curve describing the suppression of TSH by T4. The population curve is consistent with the physiological studies of the TSH response to T4 and implies a greater interindividual variation in the positive thyroid T4 response to TSH than in the central inhibitory TSH response to T4. The population curve in the dysthyroid states is consistent with known physiological responses to these states.