Mendel C M, Cavalieri R R
J Clin Endocrinol Metab. 1984 Sep;59(3):499-504. doi: 10.1210/jcem-59-3-499.
We studied two families with familial dysalbuminemic hyperthyroxinemia (FDH), a recently described entity characterized by marked elevation of serum T4 due to increased binding of T4 to albumin. The seven affected subjects had elevated serum total T4 levels (range, 15.3-25.2 micrograms/dl; normal, 4.5-11.0 micrograms/dl), but normal serum free T4 levels, as measured by equilibrium dialysis. Their serum T3 levels ranged from 1.40-2.46 ng/ml (normal, 0.9-2.0 ng/ml). The proportion of T4 associated with serum albumin was increased approximately 4-fold in the affected subjects, as shown both by reverse flow paper electrophoresis and immunoprecipitation of albumin-bound T4 with antihuman serum albumin. In vivo T4 kinetic studies were performed in the two index subjects to assess the effects of the increased binding of T4 to albumin on the in vivo transport, distribution, and disposal of T4. Compared to values in normal subjects, the MCR of T4 was decreased by about 50%, and its total body (extrathyroidal) pool size was increased by approximately 50%; the T4 production rate was normal. The extracellular T4 pool size was increased by about 100% in the FDH subjects, but the rapidly exchangeable intracellular T4 pool size was normal. The unidirectional T4 clearance rate from plasma into the rapidly exchangeable cellular compartment was reduced by approximately 50%, but the absolute rate of T4 flux from plasma into the cellular compartment was normal. Thus, the in vivo kinetic data indicate that the increased plasma binding of T4 in FDH alters the distribution of T4 in favor of the extracellular compartment, retards the fractional rate of transfer of T4 into cells, and slows the metabolic clearance of T4. However, the absolute rate of T4 flux into the rapidly exchangeable cellular compartment, the intracellular T4 pool size, and the T4 disposal rate are all normal in FDH, consistent with the normal serum concentrations of free T4 and the eumetabolic state of these individuals.
我们研究了两个患有家族性异常白蛋白血症性高甲状腺素血症（FDH）的家庭，这是一种最近描述的病症，其特征是由于甲状腺素（T4）与白蛋白的结合增加，导致血清T4显著升高。7名受影响的受试者血清总T4水平升高（范围为15.3 - 25.2微克/分升；正常为4.5 - 11.0微克/分升），但通过平衡透析测定的血清游离T4水平正常。他们的血清T3水平在1.40 - 2.46纳克/毫升之间（正常为0.9 - 2.0纳克/毫升）。通过逆流纸电泳以及用抗人血清白蛋白对白蛋白结合的T4进行免疫沉淀均显示，受影响受试者中与血清白蛋白结合的T4比例增加了约4倍。对两名索引受试者进行了体内T4动力学研究，以评估T4与白蛋白结合增加对T4在体内的转运、分布和代谢的影响。与正常受试者的值相比，T4的代谢清除率（MCR）降低了约50%，其全身（甲状腺外）池大小增加了约50%；T4产生率正常。FDH受试者的细胞外T4池大小增加了约100%，但快速可交换的细胞内T4池大小正常。从血浆到快速可交换细胞区室的单向T4清除率降低了约50%，但从血浆到细胞区室的T4通量绝对速率正常。因此，体内动力学数据表明，FDH中T4与血浆结合增加改变了T4的分布，有利于细胞外区室，延缓了T4进入细胞的分数速率，并减慢了T4的代谢清除。然而，在FDH中，T4进入快速可交换细胞区室的绝对通量速率、细胞内T4池大小和T4代谢率均正常，这与这些个体的游离T4血清浓度正常和代谢状态正常一致。
