Santini F, Chiovato L, Bartalena L, Lapi P, Palla R, Panichi V, Velluzzi F, Grasso L, Chopra I J, Martino E, Pinchera A
Institute of Endocrinology, University of Pisa, Italy.
Eur J Endocrinol. 1996 Jan;134(1):45-9. doi: 10.1530/eje.0.1340045.
Sulfation is an important pathway of triiodothyronine (T3) metabolism. Increased serum T3 sulfate (T3S) values have been observed during fetal life and in pathological conditions such as hyperthyroidism and selenium deficiency. Similar variations have also been reported in a small number of patients with systemic non-thyroidal illness, but the underlying mechanisms have not been elucidated. In this study, serum T3S concentrations have been measured by a specific radioimmunoassay in 28 patients with end-stage neoplastic disease (ESND) and in 44 patients with chronic renal failure (CRF); 41 normal subjects served as controls. Both ESND and CRF patients had lower serum total T4 (TT4) and total T3 (TT3) than normal controls, while serum reverse T3 (rT3) was increased significantly in ESND (0.7 +/- 0.5 nmol/l; p < 0.001 vs. controls) but not in CRF (0.3 +/- 0.1 nmol/l). The TT3/rT3 ratio, an index of type I iodothyronine monodeiodinase (type I MD) activity, was reduced significantly in both groups of patients. Serum T4-binding globulin (TBG) was decreased in CRF but not in ESND patients. Serum T3S was significantly higher both in ESND (71 +/- 32 pmol/l) and CRF (100 +/- 24 pmol/l) than in controls (50 +/- 16 pmol/l, p < 0.001). Serum T3S values showed a positive correlation with rT3 values and a negative correlation with both TT3 and FT3 values in ESND, but not in CRF. In the latter group a positive correlation was observed between T3S and TBG values. The T3S/FT3 ratio was higher both in CRF (18 +/- 5) and in ESND (23 +/- 18) as compared to controls (10 +/- 4). Serum inorganic sulfate was increased and correlated positively with T3S values in CRF patients. In conclusion, the results of this study in a large series of patients confirm that patients with systemic non-thyroidal illness have increased serum T3S levels. The mechanisms responsible for these changes appear to be different in ESND and CRF patients. In ESND the increase in serum T3S levels is mainly related to reduced degradation of the hormone by type I MD, whereas in CRF it might be driven by the enhanced sulfate ion concentration, and could be partially dependent on the impaired renal excretion of T3S. Because T3S can be reconverted to T3, it is possible that increased T3S concentrations contribute to maintenance of the euthyroid state in systemic non-thyroidal disease.
硫酸化是三碘甲状腺原氨酸（T3）代谢的重要途径。在胎儿期以及甲状腺功能亢进和硒缺乏等病理状况下，已观察到血清硫酸化三碘甲状腺原氨酸（T3S）值升高。在少数患有全身性非甲状腺疾病的患者中也报告了类似变化，但潜在机制尚未阐明。在本研究中，通过特异性放射免疫测定法测量了28例终末期肿瘤疾病（ESND）患者和44例慢性肾衰竭（CRF）患者的血清T3S浓度；41名正常受试者作为对照。ESND和CRF患者的血清总T4（TT4）和总T3（TT3）均低于正常对照，而ESND患者的血清反三碘甲状腺原氨酸（rT3）显著升高（0.7±0.5 nmol/l；与对照相比，p<0.001），但CRF患者中未升高（0.3±0.1 nmol/l）。TT3/rT3比值是I型碘甲状腺原氨酸脱碘酶（I型MD）活性的指标，在两组患者中均显著降低。CRF患者的血清甲状腺素结合球蛋白（TBG）降低，但ESND患者未降低。ESND（71±32 pmol/l）和CRF（100±24 pmol/l）患者的血清T3S均显著高于对照组（50±16 pmol/l，p<0.001）。在ESND患者中，血清T3S值与rT3值呈正相关，与TT3和游离T3（FT3）值呈负相关，但在CRF患者中并非如此。在后一组中，观察到T3S与TBG值之间呈正相关。与对照组（10±4）相比，CRF（18±5）和ESND（23±18）患者的T3S/FT3比值均较高。CRF患者的血清无机硫酸盐增加，且与T3S值呈正相关。总之，本研究在大量患者中的结果证实，全身性非甲状腺疾病患者的血清T3S水平升高。ESND和CRF患者中导致这些变化的机制似乎不同。在ESND中，血清T3S水平升高主要与I型MD对激素的降解减少有关，而在CRF中，可能是由硫酸根离子浓度升高驱动的，并且可能部分依赖于T3S肾脏排泄受损。由于T3S可再转化为T3，因此T3S浓度升高可能有助于维持全身性非甲状腺疾病中的甲状腺功能正常状态。
