Stephen Paul Fitzgerald1,2, Nigel G Bean3, Henrik Falhammar4,5, Rudolf Hoermann6,7. 1. The Departments of General Medicine and Endocrinology, The Royal Adelaide Hospital, Adelaide, SA, Australia. stephen.fitzgerald2@sa.gov.au. 2. The University of Adelaide, School of Medicine, Adelaide, SA, Australia. stephen.fitzgerald2@sa.gov.au. 3. School of Mathematical Sciences and ARC Centre of Excellence for Mathematical and Statistical Frontiers, University of Adelaide, Adelaide, SA, 5000, Australia. 4. Department of Endocrinology, Karolinska University Hospital, 171 76, Stockholm, Sweden. 5. Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76, Stockholm, Sweden. 6. Klinikum Lüdenscheid, Paulmannshöherstr. 14, 58515, Lüdenscheid, Germany. 7. 113 Andersons Road, Yandina, QLD, 4561, Australia.
Abstract
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.
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.
Authors: Antonio C Bianco; Alexandra Dumitrescu; Balázs Gereben; Miriam O Ribeiro; Tatiana L Fonseca; Gustavo W Fernandes; Barbara M L C Bocco Journal: Endocr Rev Date: 2019-08-01 Impact factor: 19.871