Tissue-Specific Actions of Thyroid Hormone: Insights From Animal Models

The major developmental targets for thyroid hormone are the brain, small intestine, and bone. Clear defects in gene regulation and tissue function as a consequence of TR gene inactivation can additionally be shown in the pituitary, hypothalamus, heart, and liver. TR gene knockout models show a clear distinction between thyroid hormone requirements for development and those that are required for functions in the adult animal. T3-mediated gene repression appears especially important in a number of tissues including brain, pituitary, and the heart. Preliminary evaluation of the combined TR knockout models suggests that hypothyroidism is associated with more significant abnormalities than receptor deficiency, indicating that the repressive action of the unliganded receptor may have physiological relevance. These various animal models should be very useful to design and test thyroid hormone analogues to selectively stimulate desired thyroid hormone actions.     

糖尿病住院患者434例甲状腺疾病患病率分析

目的 探讨江苏地区糖尿病患者中甲状腺疾病的现患情况.方法 横向断面调查2006年10月至2007年6月于南京医科大学第一附属医院就诊的长期居住于江苏地区的434例糖尿病患者的甲状腺功能,其中109例患者作了甲状腺超声检查.结果 (1)糖尿病患者合并甲状腺疾病的患病率为23.27%,女性多见(P＜0.05),其中甲状腺功能减退者占16.36%(临床甲减4.15%,亚临床甲减12.21%),明显高于甲状腺功能亢进者6.91%(临床甲亢4.61%,亚临床甲亢2.30%),两者差异有统计学意义.(2)糖尿病患者中,甲状腺功能减退的患病率随患者年龄和糖尿病病程的增加而增加(P＜0.01);甲状腺功能亢进的患病率随糖尿病痛程的增加而降低(P＜0.05),随年龄的增加患病率改变无统计学意义.(3)糖尿病患者中甲状腺结节患病率为40.37%,性别差异无统计学意义,患病率随年龄的增加而增加(P＜0.05),不随糖尿病痛程的增加而增加.结论 糖尿病患者合并甲状腺疾病较常见,可能影响糖尿病患者的病情和预后,筛查和随访糖尿病患者的甲状腺功能及形态学状态具有重要的临床意义.     

Medical Management of Thyroid Ectopia: Report of Three Cases

Thyroid ectopia (TE) is an embryological aberration of the thyroid gland migration most commonly observed in the lingual region followed by the sublingual, hyoid, and mediastinal regions. TE is often complicated by local compressive symptoms resulting in dysphagia, dysphonia, and dyspnea. Surgical removal of TE is frequently complicated by difficulties in intubation, increased perioperative bleeding, and severe primary hypothyroidism; on the other hand, I131 ablation is limited by high doses needed and the concern for long-term effects especially in children. We report three children with TE who all presented with compressive symptoms and were managed conservatively with levothyroxine resulting in resolution of compressive symptoms and favorable outcomes. Levothyroxine supplementation is effective and has an important role in managing TE, not only in correcting the associated hypothyroidism but also in resolving the associated compressive symptoms by reducing the size of the ectopic thyroid tissue.Conflict of interest:None declared.     

324例分化型甲状腺癌的临床分析

目的探讨分化型甲状腺癌的诊断和治疗方法。方法回顾性分析324例分化型甲状腺癌的临床资料及随访结果。结果本组病例中,乳头状癌236例(72.84%),滤泡状腺癌88例(27.16%),淋巴结转移者57例(17.59%);手术方式包括单侧病变行患侧腺叶、峡部及对侧大部切除199例,甲状腺全切40例,功能性颈淋巴结清除术62例,姑息性手术或活检7例;术后随访5年,生存率97.53%。结论对于分化型甲状腺癌,应根据临床分期决定手术方式,以提高生存期,改善生活质量。     

The Missense Alteration A5T of the Thyroid Peroxidase Gene is Pathogenic and Associated with Mild Congenital Hypothyroidism

Congenital hypothyroidism (CH) occurs with a prevalence of approximately 1:4000 live births. Defects of thyroid hormone synthesis account for 15-20% of these cases. Thyroid peroxidase (TPO) gene is the most common cause for dyshormonogenesis. So far, more than 60 mutations in the TPO gene have been described, resulting in a variable decrease in TPO bioactivity. We present an 8-day-old male with mild CH who was identified to have a G to A transition in the fifth codon of the TPO gene (c.13G>A; p.Ala5Thr). The unaffected family members were heterozygous carriers of the mutation, whereas 400 healthy individuals of the same ethnic background did not have the mutation. Mutation analysis of 11 known causative CH genes and 4 of our own strong candidate genes with next-generation sequencing revealed no mutations in the patient nor in any other family members. The results of in silico functional analyses indicated partial loss-of-function (LOF) in the resulting enzyme molecule due to mutation. The patient’s clinical finding s were consistent with the effect of this partial LOF of the mutation. In conclusion, we strongly believe that A5T alteration in the TPO gene is actually pathogenic and suggest that it should be classified as a mutation.     

Multiple simple cystic metastases in the lateral neck at presentation with papillary thyroid microcarcinoma: A case report

Introduction:Metastasis of a papillary thyroid microcarcinoma (PTMC) in the lateral neck is characterized primarily by solid lymphadenopathy, although some cases may rarely present with a cervical cystic mass. We report a case of lateral cervical lymph node metastases of PTMC that appeared as a cystic lymphangioma of the lateral neck.Patient concerns:A 55-year-old man with a painless egg-sized mass in the right side of the neck that had been present for 1 month underwent physical examination, ultrasonography, computed tomography (CT), fine needle aspiration biopsy (FNAB), and intraoperative fast-frozen pathological examination, which indicated that the cystic masses in the neck were benign. However, the final pathology report identified the lateral neck masses as lymph node metastases of thyroid carcinoma.Diagnosis:The patient was diagnosed with PTMC of the right lobe of the thyroid gland with lateral neck metastases.Interventions:The patient underwent right cervical neck dissection together with a right thyroidectomy, followed by levothyroxine therapy and routine follow-up.Outcomes:No postoperative complications were reported, and the thyroid-stimulating hormone inhibition target was <0.1 mmol/L; there was no detectable tumor recurrence on routine clinical follow-up for up to 16 months.Conclusions:This case report emphasizes the need to consider cervical lymph node metastases of thyroid carcinoma in the differential diagnosis for patients with large, multiple, simple cystic neck masses.     

Lingual thyroid with severe hypothyroidism: A case report

Introduction:Ectopic thyroid tissue presenting at the base of the tongue, called lingual thyroid, is a clinical rarity. Clinical presentation varies depending upon either the severity of regional symptoms associated with the enlargement of gland size, or the features related to thyroid dysfunction.Patient concerns:We reported a case of a 29-year-old female who presented with symptoms of easy fatigue and depression for 3 months.Diagnosis:After a series of diagnostic workup, the lingual thyroid with severe hypothyroidism was diagnosed.Intervention and outcome:She received conservative treatment with thyroid hormone replacement and the symptoms improved significantly.Lessons:Lingual thyroid is a rare entity that needs careful diagnostic workup including clinical examination, biochemical tests, imaging methods such as ultrasonography, scintigraphy, computed tomography, magnetic resonance imaging, and fine-needle aspiration cytology to plan the management. Lingual thyroid with hypothyroidism and no neck regional symptoms can be conservatively treated and requires regular follow-up for the prevention of potential risk of malignant transformation.     

血清甲状腺球蛋白测定与甲状腺疾病

甲状腺球蛋白(Tg)是自身免疫性甲状腺疾病(AITD)的主要自身抗原.各种甲状腺疾病均可出现Tg浓度异常.血清Tg测定对分化型甲状腺癌(DTC)复发或转移的诊断和疗效的监测有重要意义.但是Tg的测定受多种因素影响,其中甲状腺球蛋白抗体(TgAb)的干扰在临床上最常见.另外,不同甲状腺疾病Tg抗原表位不同,Tg基因多态性与甲状腺疾病也有一定关系.     

Thyroid cytology and histology

Fine needle aspiration (FNA) is an economical procedure that allows prompt evaluation of a thyroidal mass. Careful attention to each step of the aspiration will allow good specimens to be obtained. The cytopathologist should obtain the aspirates or else should accompany the clinician performing the aspirations. Unsatisfactory specimens should constitute less than 5% of the total. Reliable diagnoses can be made of papillary carcinoma, medullary carcinoma, anaplastic carcinoma, chronic lymphocytic thyroiditis, benign cystic lesions and the usual colloid-rich adenomatoid nodules. The diagnosis of follicular neoplasms and some cellular adenomatoid nodules remains problematical. Therefore, some thyroid operations inevitably yield benign follicular lesions.     

Thyroid hormone resistance: the role of mutational analysis

The finding of increased thyroxine (T4) and tri-iodothyronine (T3) levels in a patient with normal or increased thyroid-stimulating hormone is unexpected and presents a differential diagnosis between a thyroid-stimulating hormone-secreting pituitary adenoma, generalized resistance to thyroid hormone (RTH) and laboratory artefact. Without careful clinical and biochemical evaluation, errors may occur in patient diagnosis and treatment. In the case of RTH, mutation of the thyroid hormone receptor beta gene results in generalized tissue resistance to thyroid hormone. As the pituitary gland shares in this tissue resistance, euthyroidism with a normal thyroid-stimulating hormone is usually maintained by increased thyroid hormones. To date, we have identified eight pedigrees in New Zealand with mutations in the thyroid hormone receptor beta gene, including two novel mutations. Mutational analysis of the thyroid hormone receptor beta gene allows definitive diagnosis of RTH, potentially avoiding the need for protracted and expensive pituitary function testing and imaging. Mutational analysis also enables family screening and may help to avoid potential misdiagnosis and inappropriate treatment.     

Abnormal thyroid function in older men with or at risk for HIV infection

Objectives

The aim of the study was to evaluate the prevalence of and factors associated with abnormal thyroid function in older men with or at risk for HIV infection.

Methods

A cross‐sectional analysis of 636 men ≥49 years old was carried out using data obtained from interviews, from measurements of body mass index (BMI), HIV‐1 serology and viral load, CD4 cell count, hepatitis C virus (HCV) assays, thyroid‐stimulating hormone (TSH) and free thyroid hormone levels.

Results

Participants were 54% black, 57% overweight/obese, 57% HIV seropositive, and 72% HCV seropositive; 38% reported recent cocaine or heroin use. Decreased TSH was found in 56 men (8.8%) and raised TSH in 23 men (3.6%). Only three men had abnormal free thyroxine levels.

Conclusions

Abnormal TSH levels were noted in 12.4% of older men with or at risk for HIV infection, but nearly all reflected subclinical hyperthyroidism or subclinical hypothyroidism.     

血清甲状腺球蛋白测定与甲状腺疾病

甲状腺球蛋白(Tg)是自身免疫性甲状腺疾病(AITD)的主要自身抗原.各种甲状腺疾病均可出现Tg浓度异常.血清Tg测定对分化型甲状腺癌(DTC)复发或转移的诊断和疗效的监测有重要意义.但是Tg的测定受多种因素影响,其中甲状腺球蛋白抗体(TgAb)的干扰在临床上最常见.另外,不同甲状腺疾病Tg抗原表位不同,Tg基因多态性与甲状腺疾病也有一定关系.     

Is hepatitis C virus a risk factor for thyroid autoimmunity?

The role of hepatitis C virus (HCV) in inducing thyroid autoimmunity is still under discussion and to assess the prevalence of thyroid autoantibodies and thyroid disease in the general population and to analyse the role of HCV in inducing thyroid autoimmunity. We studied 697 subjects residing in Arsita (a small town in central Italy). Thyroid autoantibodies and nonorgan-specific autoantibodies (NOSAs) were tested in each subject, who were also screened for anti-HCV antibodies; all subjects found positive to HCV-RNA were considered as being HCV-infected. Thyroid function tests were performed in all subjects positive for thyroid autoantibody. Seventy-one subjects were found HCV-positive; four of these (5.6%) were positive for at least one thyroid autoantibody, as opposed to 7 (4.9%) of the 142 sex- and age-matched controls of the same population (P = n.s.). Thyroid dysfunction was found in 2/4 HCV-positive, and in 1/7 HCV-negative subjects with thyroid autoantibodies (P = n.s.). NOSAs were significantly more common in HCV-positive than in HCV-negative subjects (P < 0.0001). Hence HCV per se is not responsible for thyroid autoimmune dysfunction, whereas HCV does seem to induce NOSAs. It should be taken into account, however, that the phenotypic expression of autoimmune diseases is obviously influenced by a number of risk factors, including genetic predisposition, female sex and infectious agents, that could trigger the onset of the disease.     

2056例成人甲状腺功能及其自身抗体分析

目的　探讨亚临床甲状腺功能异常的早期诊断和确定筛查对象 ,分析一般人群中TSH、甲状腺自身抗体 (TAA)、年龄和性别间的关系。方法　对西安地区某单位全体职工 2 0 5 6人进行血清TSH、总甲状腺素 (TT4)、总三碘甲酰原氨酸 (TT3 )、甲状腺球蛋白抗体 (TGAb)和甲状腺微粒体抗体 (TMAb) 5项指标检测 ,排除甲状腺疾病家族史、怀孕、服用性激素及锂剂等影响因素后确定亚临床甲状腺功能异常的患病率。结果　未诊断组中 (即研究总体中去除有甲状腺疾病史和家族史、怀孕、服用性激素、锂剂等药物者 )甲减患病率为 8.0 % ,甲亢患病率为 6.0 % ,其中 95 %以上为亚临床甲状腺功能异常。TSH值随年龄增长而增高 ;60～ 69岁组TSH值达峰 ,女性和男性的TSH值中位数分别达 2 .47mU /L和 3 .3 1mU/L ;TSH值性别间差异不显著。TSH值明显异常时 (TSH≥ 10mU /L或≤ 0 .13mU/L) ,仅有 <2 0 %个体TT3和 (或 )TT4值超出正常值。TAA阳性存在明显的性别间差异 ,女性较高 (P <0 .0 5 ) ,但各年龄组间分布较一致。TAA阳性率与TSH值有相关性 ,当TSH值明显异常时TAA阳性率也显著增高。结论　一般成年人群中亚临床甲状腺功能异常的患病率较高 ,应重视亚临床甲状腺功能异常的早期诊断和防治。     

育龄期妇女肥胖与甲状腺异常的相关分析

目的在育龄期妇女中探讨肥胖与甲状腺异常的相互影响。方法通过整群抽样进行横断面调查,经筛选最终入选受试者116例。受试者均进行问卷调查、体格测量、甲状腺B超检查和血清甲状腺功能及抗体检测。结果以体质量指数（BMI）分组,肥胖组中促甲状腺激素（TSH）的平均水平略高于非肥胖组（P=0.054）,虽然没有统计学意义,但是肥胖组中TSH超过正常上限的比例显著高于非肥胖组（P〈0.01）。以腰围分组,腹型肥胖组的甲状腺体积显著高于非腹型肥胖组（P〈0.05）。高TSH组的BMI和腰围都显著高于正常TSH组（P〈0.05）。结论育龄期妇女肥胖与TSH水平之间存在相互影响;腹型肥胖可引起甲状腺体积增加,内脏脂肪可能在其中发挥重要作用。     

Thyroid Function after Surgical Treatment of Nontoxic Goitre: A Randomized Study of Postoperative Thyroxine Administration

ABSTRACT Following thyroid resection for nontoxic goitre, 29 euthyroid patients were randomly allocated to no medication or to 0.2 mg levothyroxine daily (17 and 12 patients). The two groups were comparable in age, sex, extent of surgery and thyroid pathology. The patients were free from other endocrine disorders and had no other medication. Serum TSH, T₄ and T₃ were measured and T₃-resin test performed preoperatively and 14 days and 3, 6, 12 and 18 months postoperatively. All values were within normal range. Only at the 3-month follow-up could statistically significant intergroup differences be observed, with T₄ higher in the thyroxine-treated and TSH higher in the untreated group, but the outset values were thereafter regained. The T₃ values in both groups were slightly reduced immediately after the operation. There was no recurrence of goitre in the 18-month observation period, and none of the findings suggested that routine thyroxine treatment is of value after resection of nontoxic goitre “in Denmark”.