高频超声与喉镜检查对甲状腺癌侵犯喉返神经的术前评价价值分析

目的:比较高频超声与喉镜检查对甲状腺癌侵犯喉返神经(recurrent laryngeal nerve,RLN)的术前评价价值。方法:选择2012年2月到2019年8月在本院进行诊治的甲状腺癌患者207例,采用高频超声与喉镜进行术前评估侵犯喉返神经情况,记录超声特征并判断诊断价值(以病理检查作为金标准)。结果:在207例甲状腺癌患者中,术后病理学证实喉返神经侵犯52例(侵犯组),转移率为25.1%。侵犯组的性别、年龄、发病位置、体重指数、病程等与非侵犯组患者对比差异无统计学意义(P0.05)。侵犯组超声显示病灶形态、内部回声、边界、钙化、晕环等特征与非侵犯组对比差异有统计学意义(P0.05),主要表现为侵犯组的病灶形态不规则、无晕环、无钙化、边界不清晰、内部高超声均显著高于非侵犯组(P0.05)。侵犯组的峰值强度(Peak intensity,PI)值高于非侵犯组患者(P0.05),两组达峰时间(Peak time,TP)与AUC值对比差异无统计学意义(P0.05)。在207例患者中,高频超声判断为喉返神经侵犯43例,喉镜判断为喉返神经侵犯39例,高频超声与喉镜检查对甲状腺癌侵犯喉返神经的术前诊断敏感性为97.7%和97.4%,特异性为93.9%和91.7%,高频超声诊断的敏感性和特异性比喉镜检查稍优。ROC曲线显示高频超声诊断的AUC为0.903,喉镜检查的AUC为0.860。结论:高频超声与喉镜检查对甲状腺癌侵犯喉返神经的术前评价的应用价值相当,均有很高的敏感性与特异性,能准确反映患者侵犯喉返神经的情况。     

Genetic Factors in Hashimoto's Struma

It has previously been established that there is a significant history of thyroid disorders in families of patients with Hashimoto''s struma or chronic thyroiditis. In the present study, 99 relatives of 20 patients with Hashimoto''s struma or chronic thyroiditis were studied with regard to the incidence of circulating thyroid autoantibodies; 42 of these 99 relatives were found to have such antibodies. Twenty of the 99 relatives were shown to have thyroid abnormalities (chiefly goitre); of this group of 20, antibodies were found in 12. In the remaining 79 persons (who had no clinical evidence of thyroid disease), 30 were found to have circulating antithyroid antibodies. The incidence of such antibodies among these relatives is very significantly greater than in the general population.From these and other similar studies, there is strong evidence favouring a genetic predisposition for Hashimoto''s struma and chronic thyroiditis. The mode of inheritance is not yet established, and the pathogenesis of the disease has not yet been elucidated.     

Hypothyroidism after Thyroidectomy for Graves's Disease: A Search for an Explanation

Out of 38 patients who had undergone subtotal thyroidectomy for Graves''s disease seven to 20 years previously 15 developed hypothyroidism. In these 15 patients autoantibodies against thyroid cytoplasm were significantly more frequent than in the 23 euthyroid patients, though there was no difference in the prevalence of autoantibodies against thyroglobulin. Histological examination of the thyroid tissue removed at operation showed that significantly more plasma cells and lymphoid follicles with germinal centres were present in patients who subsequently developed hypothyroidism than in those who remained euthyroid. No differences in the amount of lymphocytic infiltration were seen in hypothyroid and euthyroid patients.The results suggest that B lymphocytes play a part in the development of postoperative hypothyroidism in Graves''s disease. It is proposed that Graves''s disease and Hashimoto''s disease are different aspects of the same basic autoimmune process.     

In-vitro Inhibition of Leucocyte Migration in Crohn's Disease by a Sarcoid Spleen Suspension

A Kveim suspension has been shown to inhibit the migration of leucocytes in vitro from 12 out of 18 patients with Crohn''s disease but to have no comparable effect on leucocytes from patients with ulcerative colitis or from a group of patients with other diseases. These findings provide further evidence of cross-reactivity or of a possible aetiological link between Crohn''s disease and sarcoidosis and suggest a further immunological distinction between Crohn''s disease and ulcerative colitis.     

Optimum duration of antithyroid drug treatment determined by assay of thyroid stimulating antibody in patients with Graves' disease.

OBJECTIVE--To determine the optimal duration of antithyroid drug treatment by monitoring serum thyroid stimulating antibody values in patients with Graves'' disease. DESIGN--Prospective longitudinal trial of patients with Graves'' disease followed up for 24 months after withdrawal of treatment. SETTING--Tertiary referral centre. PATIENTS--A total of 64 consecutive patients with untreated Graves'' disease, eight of whom were subsequently excluded. Fifty six patients completed the study. INTERVENTIONS--All patients were treated initially with carbimazole 40 mg, then with decreasing doses that maintained a euthyroid state. Treatment was scheduled to continue for 18 months but was withdrawn earlier if serum thyroid stimulating antibody became undetectable. END POINT--Serum values of thyroid stimulating antibody (assayed by stimulation of human thyroid cells in vitro) and thyroid hormones and thyroid state every three months during treatment and afterwards every six months for 24 months. MEASUREMENTS AND MAIN RESULTS--In 44 patients serum thyroid stimulating antibody became undetectable during treatment and treatment was withdrawn (median duration of treatment nine months, range 3-18 months). In 12 patients the antibody could be detected during 18 months of treatment. Among the first group of 44 patients initial values of the antibody before treatment were significantly lower than in the second group of 12 patients (median 225% (range 138-1236%) v 570% (250-1480%), p less than 0.001); the incidence of relapse was also lower (41% v 92%, p less than 0.001); and among those who did relapse the disease free interval after treatment was longer (median 12 months v 1 month, p less than 0.001). Moreover, the initial median serum values of thyroid stimulating antibodies were not related to the occurrence of relapse or remission as these did not differ between patients who did and did not have a relapse (median 267% (range 139-1480%) v 220% (range 138-1236%). CONCLUSION--Monitoring of serum thyroid stimulating antibody was a good guide to the duration of treatment as it allowed the treatment period to be considerably shortened in a large group of patients with no loss of efficiency.     

Effects of Long-acting Thyroid Stimulator (LATS) and LATS Protector on Human Thyroid Adenyl Cyclase Activity

The long-acting thyroid stimulator (LATS) has been thought to be responsible for the hyperthyroidism of Graves''s disease. It is detected by its effect on the mouse thyroid gland but cannot be found in all patients with hyperthyroidism. In an attempt to clarify the problem of LATS-negative hyperthyroidism, serum was obtained from untreated patients and its effect in vitro on human thyroid tissue examined, using the activation of adenyl cyclase as a measure of stimulation. Human thyroid adenyl cyclase was activated by both thyroid-stimulating hormone (TSH) and LATS. Thyroid tissue obtained from patients with Graves''s disease was relatively less responsive to LATS than was non-toxic thyroid tissue. Of the 24 samples studied five contained LATS and all of these activated adenyl cyclase. The presence of LATS protector in LATS-negative hyperthyroid patients was confirmed but LATS-negative sera had no effect on human thyroid adenyl cyclase activity.     

Recurrent Differentiated Thyroid Cancer

ObjectiveTo discuss the risk of recurrence in patients with differentiated thyroid cancer and emphasize the importance of risk-group stratification.MethodsCommon risk factors associated with recur rent thyroid cancer are outlined, and appropriate manage ment strategies are reviewed.ResultsThe overall prognosis in patients with dif ferentiated thyroid cancer is excellent. Factors associated with recurrent thyroid cancer include extrathyroidal exten sion of the primary tumor, bulky nodal metastatic lesions, macroscopic local invasion, and aggressive histologic subtypes. The locoregional recurrence and mortality are higher in patients with high-risk thyroid cancers. Patients initially presenting with locally aggressive and advanced thyroid cancer have a higher incidence of recurrent disease in the thyroid bed or nodal metastasis. These patients also have a high incidence of distant metastatic lesions. Locally recurrent thyroid cancer may be seen in more than 25% of patients with aggressive differentiated thyroid cancer. Recurrent disease in the thyroid bed can be a difficult prob lem to manage because of the proximity of the tumor to the recurrent laryngeal nerve, visceral structures in the central compartment, and occasional involvement of the trachea or larynx. External beam radiation therapy after surgical treatment may be important for better local control in the thyroid bed region, especially in patients with poorly dif ferentiated histologic features. The role of additional radio iodine therapy remains undefined at this stage.ConclusionManagement of patients with recur rent thyroid cancer necessitates a true multidisciplinary approach. These patients require close follow-up, with cross-sectional imaging and positron emission tomo graphic scanning in selected individuals. (Endocr Pract. 2012;18:600-603)     

Persistent or Recurrent Disease in Thyroid Cancer Survivors Who Have Elevated Serum Antithyroglobulin Antibodies

ObjectiveDetection of residual differentiated thyroid cancer is important but difficult. A variety of imaging modalities and biochemical markers has been used with moderately good success. We hypothesized that elevated perioperative serum antithyroglobulin antibody (TgAb) levels would also be a predictive marker for persistent or recurrent thyroid cancer.MethodsWe performed a retrospective analysis of 277 differentiated thyroid cancer survivors divided into 2 groups: (1) those with low or normal serum TgAb (TgAb−) and (2) those with elevated serum TgAb (TgAb+). All patients were seen at one major academic medical center. Patients were followed for a median of 7.54 years.ResultsPatients in the TgAb+ group were more likely to have positive lymph nodes at initial surgery, to be assigned to a higher American Joint Committee on Cancer stage, and to have significantly higher incidence of persistent/recurrent disease. The higher incidence of persistent/recurrent cancer was significant under univariable and multivariable (including TgAb status, age, and sex) Cox proportional hazards model analysis.ConclusionWe conclude that individuals with elevated serum TgAb at the outset should be followed with a higher index of suspicion for persistent/recurrent thyroid cancer.     

The role of surgery in the management of thyroid cancer.

This is a review of one surgeon''s personal experience with 85 patients with thyroid cancer treated over a 20-year period. The data confirm that for papillary thyroid tumours, with rare exceptions, the prognosis is excellent. Anaplastic lesions, however, are consistently lethal. Follicular carcinoma and medullary carcinoma fall between these extremes. A simple clinical classification is offered as a guide to operative management and a reliable index of prognosis. Patients with clinically apparent, "manifest cancer" have serious, life-threatening disease; many such patients die of their disease. Patients with "neck lumps not yet diagnosed" usually have papillary carcinoma; their prognosis is excellent. Patients whose thyroid tumours fall into the category of "malignant nodule" or "pathologist''s cancer" are particularly fortunate: in this series no such patient has died. The importance of age in relation to thyroid cancer is also confirmed: non of the patients first treated before the age of 40 years has died of cancer. For young patients with favourable disease the author recommends conservative surgical treatment, which avoids cosmetic deformity or functional disability, to be followed by administration of levothyroxine to suppress production of thyroid=stimulating hormone. For patients with "unfavourable" thyroid cancer valuable palliation can often be achieved by a combination of surgery and irradiation. Survival rates for the total series are 76% at 5 years and 60% at 10 years.     

甲状腺全切除术与半切除术治疗甲状腺癌的临床效果分析

目的:比较甲状腺全切除术与半切除术治疗甲状腺癌的临床效果。方法:选取我院收治的90例甲状腺癌患者,对所有患者行甲状腺全切除术或近全切除术,同时应用I131以及甲状腺激素抑制治疗作为辅助治疗,并对所有患者进行随访。结果:两组患者的术中出血量、喉返神经显露率比较差异无统计学意义(P0.05),观察组的手术切口以及手术时间均明显长于对照组(P0.01),甲状旁腺显露率高于对照组(P0.01)。两组患者暂时性、永久性喉返神经损伤,暂时性、永久性甲状旁腺功能低下发生率比较差异无统计学意义(P0.05)。复发率为13.33%(6/45),观察组无复发,两组患者术后复发率比较差异具有统计学意义(P0.05)。结论:甲状腺全切除术治疗甲状腺癌的效果优于半切除术,且能够有效降低术后复发率。     

Diazepam and Tests of Thyroid Function

The effect of diazepam on thyroid function tests was examined in 12 euthyroid patients requiring the drug for psychiatric reasons and in six patients with thyrotoxicosis. Assessment was made before and after four weeks'' therapy.There was no significant difference in results from tests of thyroid iodide trapping and binding (thyroid radioiodine uptake, thyroid clearance, and absolute iodine uptake) except in the one-hour thyroid uptake in the euthyroid group, which was increased after diazepam. This increase occurred without alteration in serum thyroid stimulating hormone levels. No change occurred in either group in tests of thyroid hormone release (protein-bound iodine, T-3 resin uptake, or Thyopac-3 and free thyroxine index).Patients with suspected thyroid disease who are taking diazepam do not need to stop therapy while their thyroid status is being determined.     

Primary malignant lymphoma of the thyroid in a patient with long-standing Graves' disease

We have recently encountered a patient with rapidly enlarging thyroid masses histologically diagnosed as diffuse histiocytic lymphoma which developed in the active course of Graves' disease. The primary thyroid lymphoma has been in complete remission after local radiation therapy. The association of Hashimoto's thyroiditis and thyroid lymphoma has well been recognized. Meanwhile, data have accumulated to demonstrate that Hashimoto's thyroiditis and Graves' disease share possible similar causal immunological abnormalities and are closely related entities. However, the association of Graves' disease and primary thyroid lymphoma has never been reported, as far as we know. Therefore, this case may be the first one that supports the natural concept that thyroid lymphoma develops from pre-existing Graves' disease secondary to the similar immunological abnormalities in Hashimoto's thyroiditis.     

Recurrent Herpetic Stromal Keratitis in Mice,a Model for Studying Human HSK

Herpetic eye disease, termed herpetic stromal keratitis (HSK), is a potentially blinding infection of the cornea that results in over 300,000 clinical visits each year for treatment. Between 1 and 2 percent of those patients with clinical disease will experience loss of vision of the infected cornea. The vast majority of these cases are the result of reactivation of a latent infection by herpes simplex type I virus and not due to acute disease. Interestingly, the acute infection is the model most often used to study this disease. However, it was felt that a recurrent model of HSK would be more reflective of what occurs during clinical disease. The recurrent animal models for HSK have employed both rabbits and mice. The advantage of rabbits is that they experience reactivation from latency absent any known stimulus. That said, it is difficult to explore the role that many immunological factors play in recurrent HSK because the rabbit model does not have the immunological and genetic resources that the mouse has. We chose to use the mouse model for recurrent HSK because it has the advantage of there being many resources available and also we know when reactivation will occur because reactivation is induced by exposure to UV-B light. Thus far, this model has allowed those laboratories using it to define several immunological factors that are important to this disease. It has also allowed us to test both therapeutic and vaccine efficacy.     

High TSH concentrations in "euthyroidism": explanation based on control-loop theory.

High concentrations of thyroid-stimulating hormone (TSH) in the serum have often been reported in apparently euthyroid patients with damaged thyroids. We have confirmed this finding in 14 patients 18 months after subtotal thyroidectomy for Graves''s disease (group 1) and in 14 patients with manic-depressive psychosis (group 2) receiving lithium carbonate, which reduces thyroid reserve. One factor common to groups 1 and 2 but not to the controls was reduced thyroid reserve or functioning capacity, and, using established physical principles of servo-control, we have tried to define the mechanism. A series of curves were projected to indicate how TSH might be expected to vary with functioning thyroid capacity.     

Role of Genetic Variants of Autophagy Genes in Susceptibility for Non-Medullary Thyroid Cancer and Patients Outcome

Autophagy is a central process in regulation of cell survival, cell death and proliferation and plays an important role in carcinogenesis, including thyroid carcinoma. Genetic variation in autophagy components has been demonstrated to influence the capacity to execute autophagy and is associated with disease susceptibility, progression and outcome. In the present study, we assessed whether genetic variation in autophagy genes contributes to susceptibility to develop thyroid carcinoma, disease progression and/or patient outcome. The results indicate that patients carrying the ATG5 single nucleotide polymorphisms rs2245214 have a higher probability to develop thyroid carcinoma (OR 1.85 (95% CI 1.04–3.23), P = 0.042). In contrast, no significant differences could be observed for the other genetic variants studied in terms of thyroid carcinoma susceptibility. Furthermore, none of the selected genetic variants were associated with clinical parameters of disease progression and outcome. In conclusion, genetic variation in ATG5, a central player in the autophagy process, is found to be associated with increased susceptibility for thyroid carcinoma, indicating a role for autophagy in thyroid carcinogenesis.     

Scintigraphy with [111In]octreotide and 201Tl in a Hürthle cell thyroid carcinoma without detectable radio-iodine uptake. Report of a case and review of the literature

AIM: To describe the visualization of recurrent disease by [111In]octreotide and 201Tl scintigraphy in a patient with Hürthle cell thyroid carcinoma, increased thyroglobulin levels, and a negative radio-iodine total-body scan. METHODS: Scintigraphy with [111In]octreotide and 201Tl was performed, and a local recurrence in the thyroid bed was detected which was excised by surgery. RESULTS: On histology, the tumour proved to be a Hürthle cell carcinoma, and within the tumour somatostatin receptors were detected by RT-PCR. CONCLUSION: Scintigraphy with [111In]octreotide and 201Tl is an alternative imaging method for the detection of residual disease in patients with a differentiated thyroid carcinoma having increased thyroglobulin levels and a negative radio-iodine total-body scan.     

Place of thyroglobulin antibodies assay in laboratory diagnostic of autoimmune thyroid diseases

Tyroglobulin and thyroid peroxidase antibodies have been estimated in patients with thyroid autoimmune diseases. In a group of 109 patients with Hashimoto's thyroidities 85.53% and 78.89% were positive for Tyroglobulin antibodies and anti-TPO antibodies respectively. The anti-Tg antibodies has not been detected in 14.67% and anti-TPO in 21.1% patients. Both antibodies have not been detected in 1.83% of patients. In a group of 79 patients with Graves' disease 62.02 and 91.13% were positive for anti-Tg and anti-TPO antibodies respectively. The anti-Tg antibodies has not been detected in 37.97% and anti-TPO in 8.66% patients. Both antibodies have not been detected in one patients with exophtalmos (1.26%). Our results indicate that anti-tyroglobulin antibodies should be estimated only in patients suspected for thyroid autoimmune disease and negative for thyroid peroxidase antibodies.     

On-levothyroxine measurement of thyroglobulin is not a reliable test for the follow-up of patients at high risk for remnant/recurrent differentiated thyroid carcinoma

INTRODUCTION: At present the most widely accepted tool for follow-up management of differentiated thyroid cancer (DTC) patients is serum thyroglobulin (Tg) measurement. It is not uncommon for the serum Tg level to be measured while the patient is taking thyroid hormones (on-treatment Tg measurement). The purpose of the study was to evaluate the accuracy of on-treatment measurement of serum Tg in detecting remnant/recurrent or metastatic disease in high-risk DTC patients. MATERIAL AND METHODS: We retrospectively analysed the medical records of 26 high-risk DTC patients and compared the on-treatment and off-treatment Tg levels of these patients. All patients were anti-Tg negative. Using off-treatment measurement of Tg as the gold standard, the results of on-treatment measurement of Tg in the diagnosis of remnant/recurrent disease were analysed for sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). RESULTS: The median serum Tg level under thyroid hormone suppressive therapy (on-treatment Tg) was 16.5 ng/ml and after withdrawal of thyroid hormone suppressive therapy (off-treatment Tg) was 95.0 ng/ml (P value = 0.001). In 6 patients (23%) the on-treatment Tg level missed the recurrence of the disease. Regarding the off-treatment Tg as the gold standard, the sensitivity, specificity, PPV and NPV of the on-treatment Tg measurement were 72.7%, 100%, 100%, and 40% respectively. CONCLUSION: Normal serum Tg level without TSH-stimulation (on-treatment) is not diagnostically reliable in the follow-up of DTC patients with a high probability of residual/recurrent or metastatic disease.     

Unknown and Already Known Thyroid Abnormalities in Primary Hyperparathyroidism

Objective: Primary hyperparathyroidism (PHPT) and thyroid diseases are highly prevalent in the general population, but the putative link between the 2 conditions remains unclear.Methods: A monocentric consecutive series of 434 patients with PHPT was retrospectively evaluated by lab and ultrasonography to look for thyroid abnormalities. Patients were classified in 3 groups: without thyroid abnormalities (group 1, n = 171), with thyroid diseases not previously known (group 2a, n = 69), and thyroid diseases previously known (group 2b, n = 194).Results: In terms of thyroid disease, no significant difference was found between groups 2a and 2b, except for the significantly larger number of patients with toxic nodular goiter in group 2b. PHPT was more frequently symptomatic in group 2a than in group 2b, despite no differences in serum calcium, creatinine, parathyroid hormone (PTH), or 25-hydroxyvitamin D (25OHD) levels.Conclusion: A total of 60% of PHPT patients had a thyroid disease that was unknown prior to PHPT diagnosis in almost one-third of cases. The newly diagnosed and previously known thyroid diseases were similar, both mostly affecting postmenopausal females.Abbreviations: Ab = antibody; aPHPT = asymptomatic PHPT; 25OHD = 25-hydroxyvitamin D; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; Tg = thyroglobulin; TPO = thyroperoxidase; TSH = thyroid-stimulating hormone; US = ultrasound     

Autoimmune Thyroid Disease in the Use of Alemtuzumab for Multiple Sclerosis: A Review

ObjectiveThe monoclonal antibody alemtuzumab has been demonstrated to reduce the risks of relapse and accumulation of sustained disability in multiple sclerosis (MS) patients when compared to β-interferon. The development of autoimmune diseases, including thyroid disease, has been reported in the literature with a frequency of 20 to 30%. In this article, we describe 4 cases of alemtuzumab-induced thyroid disease in patients with MS. We also performed a systematic review of the available literature.MethodsFour patients who had received alemtuzumab for MS and subsequently developed thyroid dysfunction are presented. We compared our patients' clinical courses and outcomes to established disease patterns. We also undertook a systematic review of the published literature.ResultsAll 4 patients presented with initial hyperthyroidism associated with elevated thyroid-stimulating hormone (TSH) receptor antibodies (TRAb). In 2 cases, hyperthyroidism did not remit after a total of 24 months of carbimazole therapy, and they subsequently underwent subtotal thyroidectomy. The third case subsequently developed biochemical hypothyroidism and required thyroxine replacement, despite having a markedly raised initial TRAb titer. Autoimmunity following alemtuzumab therapy in MS appears to occur as part of an immune reconstitution syndrome and is more likely in smokers who have a family history of autoimmune disease.ConclusionManagement of alemtuzumab-induced thyroid disease is similar to the management of “wild-type” Graves’ disease. The use of alemtuzumab in this setting will necessitate close monitoring of thyroid function and early intervention when abnormalities are developing. (Endocr Pract. 2013;19:821-828)