Thyroid hormones mainly include thyroxine (T 4) and 3, 5, 3′-triiodothyronine (T 3). About 75% of T 4 and 70% of T 3 in circulating blood bind to serum thyroxine binding globulin (TBG). Hereditary TBG abnormalities is caused by SERPINA7 mutation, which are classified into three types according to serum TBG levels in male patients: complete TBG deficiency (TBG-CD), partial TBG deficiency (TBG-PD), and TBG excess (TBG-E). The decrease of serum TBG level often leads to decreased level of total T 4 and total T 3, while the serum free thyroid hormone are normal. If the diagnosis of hereditary TBG abnormalities can be confirmed in such patients, no treatment is required. When hereditary TBG abnormalities are combined with other thyroid diseases, the thyroid function test will become more complicated, which will easily lead to misdiagnosis, missed diagnosis, and even mistreatment. Therefore, enhancing the understanding of this disease can avoid misdiagnosis, mistreatment, reduce unnecessary laboratory tests, or inappropriate treatment.

Background: In humans, resistance to thyroid hormone (RTH) caused by mutations in the thyroid hormone receptor alpha (THRA) gene, RTHα, manifests as tissue-specific hypothyroidism and circulating thyroid hormone levels exhibit hypothyroid-like clinical features. Before the identification of patients with RTHα, several Thrα1 knock-in mouse models were generated to clarify the function of TRα1. However, the phenotypes of these mice were not consistent with the clinical presentation of RTHα in humans. For the present study, we generated an RTHα mouse model that carries the Thra1E403X mutation found in human RTHα patients. Here, we report the gross phenotypes of this mouse RTHα model. Methods: Traditional homologous recombination gene targeting techniques were used to introduce a mutation (Thra1E403X) in the mouse Thra gene. The phenotypes of the resulting mice were studied and compared with clinical features observed for RTHα with THRAE403X. Results: Thrα1E403X/E403X homozygous mice exhibited severe neurological phenotypes, such as spasticity and motor ataxia, which were similar to those observed in endemic cretinism. Thrα1E403X/+ heterozygous mice reproduced most clinical manifestations of patient with RTHα, such as a normal survival rate and male fertility, as well as delayed postnatal growth and development, neurological and motor coordination deficits, and anemia. The mice had typical thyroid function with a modest increase in serum triiodothyronine (T3) levels, a low thyroxine (T4)/T3 ratio, and low reverse T3 (rT3) levels. Conclusions: The Thrα1E403X/+ mice faithfully recapitulate the clinical features of human RTHα and thus can provide a useful tool to dissect the role of TRα1 in development and to determine the pathological mechanisms of RTHα.

背景 β型甲状腺激素抵抗综合征(RTHβ)属于罕见内分泌疾病,临床极易误诊、误治.目的 总结RTHβ患者的临床特点,为临床医师了解本病提供帮助.方法 选取2013—2016年于中国医科大学附属第一医院内分泌与代谢病科诊断为RTHβ的患者6例.回顾性分析6例RTHβ患者的临床资料,包括性别、诊断年龄、发病年龄、家族史、主诉、心电图检查结果、甲状腺触诊结果、甲状腺超声检查结果、甲状腺核素静态显像结果、甲状腺功能指标〔游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)〕、促甲状腺素受体抗体(TRAb)、性激素结合蛋白(SHBG)、血清铁蛋白、脂代谢指标、骨代谢指标、骨密度、基因测序情况等.结果 6例RTHβ患者的诊断年龄均高于发病年龄,患者在确诊RTHβ之前均被误诊为甲状腺功能亢进症,长期服用抗甲状腺药物治疗.患者主诉均存在心悸、多汗,3例伴心房颤动.6例患者甲状腺核素静态显像均显示甲状腺双叶摄取率增高.5例RTHβ患者甲状腺超声显示有甲状腺肿大,4例显示多发结节.6例RTHβ患者血清FT3、FT4水平升高,TSH水平在参考范围,且TRAb均为阴性;血清SHBG和血清铁蛋白均在参考范围;甲状腺激素受体(TR)β基因测序均存在点突变.结论 RTHβ的临床表现存在高度异质性,临床诊断时需注意与甲状腺功能亢进症和甲状腺功能减退症区分,同时注意并非所有的RTHβ患者能检测出TRβ基因突变.对于高度怀疑为RTHβ的患者,可以采用促甲状腺素释放激素(TRH)兴奋试验、左旋-三碘甲腺原氨酸(L-T3)抑制试验或TRH兴奋试验联合L-T3抑制试验进行临床诊断.

Objective:To search for the clinical indicators in differentiating Graves′ disease from subacute thyroiditis (SAT).Methods:Retrospective analysis was performed on thyroid function measurement of 265 cases of newly diagnosed Graves′ disease, 76 cases of SAT with thyrotoxicosis, 100 cases of non-toxic thyroid nodules, 105 cases of autoimmune thyroid diseases with normal thyroid function, and 151 cases of outpatients with normal thyroid function and without thyroid diseases.Results:Free triiodothyronine(FT 3)/free thyroxine(FT 4) ratio of Graves′ disease patients was significantly higher than that of SAT patients with thyrotoxicosis (0.65±0.29 vs 0.32±0.75, P<0.05). Receiver operating characteristic curve(ROC curve) analysis of FT 3/FT 4 ratio between Graves′ disease group and SAT group showed that FT 3/FT 4 ratio greater than 0.4 with a sensitivity of 98.11% and a specificity of 83.81% for diagnosis of Graves′ disease. Conclusion:FT 3/FT 4 ratio greater than 0.4 is helpful for differentiating Graves′ disease from subacute thyroiditis with thyrotoxicosis.

BACKGROUND Thyroxine-binding globulin (TBG; the gene product of SERPINA7) is the main transporter of thyroid hormones in humans. Mutations in the TBG gene may lead to inherited TBG deficiency. There have been 28 reported mutations that associate with complete TBG deficiency (TBG-CD). Here we identified a novel frameshift mutation causing early termination of the TBG protein and TBG-CD in a Chinese family. CASE SUMMARY A 46-year-old Chinese man was referred to our hospital with normal free thyroxine, free triiodothyronine, thyrotropin, but lower total thyroxine and total triiodothyronine, and undetectable serum TBG, indicative of TBG-CD. Blood samples were obtained from the patient’s family members and thyroid function and serum TBG were evaluated. Genomic DNA from peripheral blood was sequenced to detect possible TBG mutation(s). Quantitative PCR high-resolution melting curve analysis was used to screen TBG-Poly (L283F) among 117 Chinese men. A novel mutation of TBG (p.Phe135Alafs*21), a 19-nucleotide insertion in exon 1, was identified, which resulted in a truncated TBG protein product and caused TBG-CD. The other mutation, identified in the proband’s father, is a known polymorphism, TBG-Poly (L283F). The frequency of the TBG-Poly allele among 117 unrelated Han Chinese men from northeast China was 21.37%. CONCLUSION A novel mutation in the TBG gene associated with the TBG-CD phenotype was identified in a Chinese family. Additionally, it was found that 21.37% of Chinese males had TBG-Poly (L283F).

The diagnosis and treatment of 1 patient with hypokalemia and rhabdomyolysis caused by Glycyrrhiza uralensis is reviewed. The related literature and its pathogenesis are reviewed, so as to improve clinicians' understanding of hypokalemia and rhabdomyolysis caused by Glycyrrhiza uralensis..