Lee H Y, Suhl J, Pekary A E, Hershman J M
Endocrine and Intensive Care Sections, Wadsworth Veterans Administration Medical Center, University of California School of Medicine, Los Angeles 90073.
J Clin Endocrinol Metab. 1987 Nov;65(5):942-5. doi: 10.1210/jcem-65-5-942.
Patients with nonthyroid illness (NTI) often have reduced serum T3, free T3, T4, and free T4 concentrations. Paradoxically, serum TSH is usually in the normal range. The data suggest a diagnosis of hypothalamic hypothyroidism, in which TSH may have reduced biological activity because TRH, which is necessary for key steps in the glycosylation of TSH, is deficient. To study the glycosylation of TSH in patients with NTI, we measured the serum TSH concentration in 36 such patients hospitalized on our intensive care units and compared the results with those from a group of 18 normal subjects. Serum TSH was measured in 2 assays: 1) a sensitive TSH RIA of unextracted serum (TSH-RIA) and 2) a RIA of serum TSH after its extraction with Concanavalin-A (Con-A), a lectin which binds glycoproteins containing mannose residues in their oligosaccharide side-chains (TSH-Con-A). The ratio of TSH-Con-A to TSH-RIA was significantly reduced in the NTI patients [0.61 +/- 0.03 (+/- SE) vs. 0.89 +/- 0.05 in the normal subjects] due to reduced binding of the TSH to the Con-A. This change was not dependent on the extent of the abnormalities of thyroid hormone levels. The data suggest that the TSH secreted in NTI has altered glycosylation which is associated with reduced biological activity. This finding may explain in part the low serum T4 level in NTI patients in the face of an apparently normal immunoreactive TSH level.
患有非甲状腺疾病（NTI）的患者通常血清三碘甲状腺原氨酸（T3）、游离T3、甲状腺素（T4）和游离T4浓度降低。矛盾的是，血清促甲状腺激素（TSH）通常在正常范围内。这些数据提示诊断为下丘脑性甲状腺功能减退，其中TSH的生物活性可能降低，因为促甲状腺激素释放激素（TRH）缺乏，而TRH是TSH糖基化关键步骤所必需的。为了研究NTI患者TSH的糖基化，我们测量了36例入住我们重症监护病房的此类患者的血清TSH浓度，并将结果与18名正常受试者组成的对照组进行比较。用两种检测方法测定血清TSH：1）未提取血清的敏感TSH放射免疫分析（TSH-RIA）和2）用伴刀豆球蛋白A（Con-A）提取血清TSH后的放射免疫分析，Con-A是一种凝集素，可结合其寡糖侧链中含有甘露糖残基的糖蛋白（TSH-Con-A）。由于TSH与Con-A的结合减少，NTI患者中TSH-Con-A与TSH-RIA的比值显著降低[0.61±0.03（±标准误），而正常受试者为0.89±0.05]。这种变化不依赖于甲状腺激素水平异常的程度。数据提示NTI患者分泌的TSH糖基化改变，这与生物活性降低有关。这一发现可能部分解释了NTI患者在免疫反应性TSH水平明显正常的情况下血清T4水平较低的原因。
