Goitre and thyroid dysfunction during chronic amiodarone treatment

We measured thyroid function in a cross-sectional survey of 37 unselected patients receiving chronic amiodarone treatment. Palpable goitre was presented in 17 patients and was a new finding in ten. Despite frequent elevations of serum free T4 (67%) or free T4 index (43%), all 37 patients were clinically euthyroid with a normal or decreased serum free T3 or free T3 index. Mean urine iodide/creatinine excretion was increased 13-fold. Three patterns of thyroid function were seen; in 21 patients with normal TRH responses, the mean basal serum TSH was significantly elevated. Five patients had biochemical hypothyroidism which did not require treatment. Eleven patients had evidence of thyroid autonomy and the three patients with absent TRH responses each gave a past history of goitre or thyrotoxicosis; a trial of carbimazole treatment in these three was without clinical benefit. The observed spectrum of subclinical goitre and thyroid dysfunction may result from an unpredictable thyroid response to excessive free iodide combined with a weak goitrogenic effect of amiodarone mediated by increased TSH secretion.     

Subtotal thyroidectomy for thyrotoxicosis: a reassessment, including TRH responsiveness.

Thyroid function was assessed in patients treated surgically for thyrotoxicosis in Christchurch between 1965 and 1972. Seventy-eight of the 89 thyrotoxic patients were available for reassessment. Seventy-one were clinically and biochemically euthyroid. Seven patients had received radioiodine therapy for post-operative relapse and 10 patients were receiving thyroxine replacement therapy. At the time of the survey five patients were clinically thyrotoxic and two patients were hypothyroid and an additional nine patients had grossly elevated TSH levels. TRH tests performed on 31 clinically euthyroid patients with normal baseline thyroid parameters demonstrated that more than a third had excessive TSH responses consistent with reduced thyroid reserve and only one patient showed a lack of response consistent with persistent thyroid autonomy.     

Thyrotoxicosis: relations between clinical state and biochemical changes during carbimazole treatment.

The relation between clinical and biochemical changes in thyrotoxicosis were studied in 12 patients with Graves's disease who were being treated with carbimazole. Clinical assessment (using the Crooks-Wayne index) was combined with the measurement of free thyroxine and triiodothyronine indices (FT4I and FT3I) and the assessment of two tissue markers of thyroid hormone action--sex-hormone-binding globulin (SHBG) levels and the thyrotrophin responses to TRH. In general the FT4I and FT3I fell rapidly once treatment was started, and returned to normal in one to four weeks, followed shortly by SHBG levels. The thyrotrophin response returned at this time in two patients, who still had borderline high levels of FT3I and SHBG. The clinical score fell more slowly and variably and was less closely related to any of the biochemical indices than these were to each other. During the early phase of treatment with antithyroid drug the clinical evaluation may be an unreliable indicator of persisting thyroid hormone excess, and when the patient seems clinically but not biochemically thyrotoxic the symptoms should be treated on their own merits with beta-blocking drugs and not with increased doses of antithyroid drugs.     

Ophthalmic Graves's disease: natural history and detailed thyroid function studies

Of 27 patients with ophthalmic Graves's disease (OGD) who had been clinically euthyroid three years previously, one became clinically hyperthyroid and seven overtly hypothyroid. Improvement in eye signs was associated with a return to normal of thyroidal suppression by triiodothyronine (T3) and of the response of thyroid-stimulating hormone (TSH) to thyrotrophin-releasing hormone (TRH). Of a further 30 patients with OGD who had not been studied previously, three were overtly hypothyroid. Of the combined series, 46 patients were euthyroid, 18 (40%) of whom had an impaired or absent TSH response to TRH, and 3(6-7%) an exaggerated response. Eleven out of 37 patients (29-7%) had abnormal results in the T3 suppression test. There was a significant correlation between thyroidal suppression by T3 and the TSH response to TRH. Total serum concentrations of both T3 and thyroxine (T4) were closely correlated with T3 suppressibility and TRH responsiveness. Free T4 and T3 (fT3) concentrations were normal in all but three patients, in whom raised fT3 was accompanied by abnormal TSH responses and thyroidal suppression. The presence of normal free thyroid hormone concentrations in patients with impaired or absent TSH responses to TRH is interesting and challenges the concept that free thyroid hormones are the major controlling factors in the feedback control of TSH.     

甲状腺功能正常2型糖尿病患者的机体甲状腺轴微紊乱情况研究

目的 观察甲状腺功能正常的2型糖尿病(T2DM)患者甲状腺轴激素微紊乱及其对胰岛素抵抗的影响.方法 选择2014年7月至2016年7月确诊的初诊T2DM患者80例作为T2DM组;选择同期被OGTT实验证实为糖耐量异常的健康体检者40例作为IGT组;同期体检血糖在正常范围的40例作为健康对照组.观察T2DM组,IGT组和健康对照组3组机体三碘甲状腺原氨酸(FT3),游离甲状腺素(FT4),促甲状腺素(TSH),稳态模型评价胰岛素抵抗(HOMA-IR)和糖化血红蛋白(HbA1c)水平的变化,T2DM患者的T3,FT4,TSH水平与HOMA-IR和HbA1c水平的相关性,及其治疗后水平的变化.结果 T2DM组和IGT组的FT3和FT4水平明显低于健康对照组(P<0.01),T2DM组水平明显低于IGT组(P<0.01),治疗后T2DM机体的FT3和FT4水平较治疗前明显提高(P<0.01);而TSH,HOMA-IR和HbA1c水平明显高于健康对照组(P<0.01),T2DM组水平明显高于IGT组(P<0.01),治疗后T2DM患者机体的TSH,HOMA-IR和HbA1c水平明显较治疗前降低(P<0.01).T2DM患者机体的FT3,FT4和HO-MA-IR水平随着HbA1c水平的升高而出现明显升高(P<0.01),而TSH水平随着HbA1c水平的升高而降低(P<0.01).胰岛素抵抗组的FT3和FT4水平明显低于非胰岛素抵抗组(P<0.01),而TSH和HbA1c水平明显高于非胰岛素抵抗组(P<0.01).结论 甲状腺功能正常的T2DM患者机体存在甲状腺轴功能的微紊乱,其紊乱程度与糖尿病严重程度和胰岛素抵抗指数相关,控制T2DM后机体的甲状腺轴紊乱得到纠正.     

甲状腺激素与甲状腺结节良恶性的关系

【摘要】目的 观察甲状腺结节（TN）患者血清甲状腺激素的水平并探讨其与TN良恶性的关系。方法随机抽取TN患者245例,根据甲状腺相关抗体水平及术后病理结果分为结节性甲状腺肿组（NG组）、甲状腺腺瘤组（TA 组）和甲状腺癌组（TC组）,TC组进一步分为甲状腺相关抗体升高组（TC-Ab +组）和甲状腺相关抗体正常组(TC-Ab - 组)。检测患者术前血清游离T3（FT3）、游离T4（FT4）和促甲状腺激素（TSH）。分析各组患者甲状腺激素水平的差异。结果以NG组、TA组和TC组3组比较时,TC组血清TSH水平高于其他2组（P＜0.05）。TC-Ab +组血清FT3水平低于NG组和TC-Ab -组,FT4水平低于NG组,TSH水平明显高于其他各组（P＜0.05）。结论部分TC患者出现血清TSH水平升高,其原因可能是由于伴有自身免疫性甲状腺炎并继发了甲状腺功能减退。血清TSH水平升高未必是TC的固有特征。     

The effects of ranitidine on pituitary-thyroid function.

Although several studies have examined the effects of cimetidine on pituitary-thyroid function, few have investigated ranitidine in this respect. We found no changes in thyroid-stimulating-hormone (TSH) or prolactin responses to TSH-releasing-hormone (TRH) in 10 patients with peptic ulcer disease given oral ranitidine. Serum total and free thyroxine (TT4 and FT4) concentrations declined slightly, whereas total and free triiodothyronine (TT3 and FT3) increased slightly following ranitidine. None of these changes achieved statistical significance. Both the ratio of TT4/TT3 and FT4/FT3, however, declined (P less than 0.05) following ranitidine. Thus ranitidine may have a minor influence on peripheral deiodination of thyroxine but has little effect on hormone production from the thyroid gland. The diagnostic value of biochemical tests of thyroid function is not seriously compromised in patients receiving ranitidine.     

Dose-response studies with thyrotropin-releasing hormone (TRH) in abstinent male alcoholics: evidence for selective thyrotroph dysfunction?

A reduced thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) has been reported in subjects with a history of alcoholism whereas prolactin (PRL) responses have generally been normal. One hypothesis proposed to explain the reduced TSH response is down-regulation of pituitary TRH receptors. If this is correct, PRL response should also be diminished. To account for the different dose-response characteristics of TSH/PRL we have given four dosages of TRH (25, 100, 500 and 800 micrograms) to eight noncirrhotic, male alcoholics abstinent from ethanol a minimum of 28 days and to seven male control subjects. Across the TRH dose range the alcoholic subjects exhibited reduced basal TSH (p = .01) and a reduced TSH response (p = .0023) but no differences in basal and stimulated PRL levels. Alcoholic subjects had higher basal T4, T3 and FT4I values than did control subjects but covarying for T4, T3 and FT4I did not change the significance of either TSH or PRL findings. No significant differences in estradiol, estrone, testosterone, cortisol or glucose were noted between groups. The present study confirms the observation of a lower TSH response to TRH in abstinent alcoholics and indicates that the lower response cannot be overcome by increasing TRH dosage. The similar PRL response between groups suggests normal lactotroph function in noncirrhotic abstinent alcoholics and argues against the pituitary TRH receptor down-regulation hypothesis.     

The effects of delta 9-tetrahydrocannabinol on serum thyrotropin levels in the rat

The effects of acute treatment with delta 9-tetrahydrocannabinol (delta 9-THC) on serum levels of thyrotropin (TSH) and the thyroid hormones triiodothyronine (T3) and thyroxine (T4) were determined in the rat. Intraperitoneal doses of delta 9-THC greater than 3 mg/kg reduced serum TSH levels to less than 10% of control. The ED50 for delta 9-THC was approximately 0.3 mg/kg. After a 10 mg/kg dose of delta 9-THC, the maximum decrease in serum TSH occurred at one hour. Both serum T3 and serum T4 levels were decreased by a single 10 mg/kg delta 9-THC injection with maximal decreases at 6 hr post-injection. The effects of delta 9-THC on the ability of thyrotropin releasing hormone (TRH) to increase serum TSH and T3 were determined. TRH produced a 10-fold increase in serum TSH levels and this increase was unaffected by delta 9-THC pretreatment. Serum T3 levels were slightly increased by TRH and this increase was also unaffected by delta 9-THC. These findings indicate that acute treatment with delta 9-THC results in a decrease in circulating TSH, T3 and T4 levels but has no effect on the pituitary or thyroid response to exogenous TRH.     

2型糖尿病患者甲状腺功能异常的临床特征分析

目的分析2型糖尿病患者甲状腺功能异常的临床特征。方法检测2010年1月~2011年6月于我院住院的1299例2型糖尿病患者的血清游离T3(FT3)、游离T4(FT4)、促甲状腺激素(TSH)。结果①2型糖尿病合并甲状腺功能异常的发生率为25.2%,其中亚临床甲状腺功能减退占50.1%。②与甲状腺功能正常的糖尿病患者相比,糖尿病合并甲状腺功能异常的患者女性多见,HbA1c较高。结论 2型糖尿病合并甲状腺功能异常较常见,应筛查和随访糖尿病患者的甲状腺功能。     

糖尿病合并甲状腺功能亢进患者血清胰岛素抵抗和脂联素表达水平及其与甲状腺激素的相关性分析

目的 探讨糖尿病合并甲状腺功能亢进(甲亢)患者血清胰岛素抵抗(IR)指数和脂联素表达水平及其与甲状腺激素的相关性.方法 选择2012年6月-2014年10月收治的50例糖尿病合并甲亢患者作为研究组,选取同期50例单纯糖尿病作为对照组.观察2组IR指数、脂联素、游离三碘甲状腺原氨酸(FT3)、促甲状腺激素(TSH)、游离甲状腺素(FT4)水平,并分析其相关性.结果 研究组IR、脂联素、TSH、FT3、FT4水平均高于对照组(P＜0.05).研究组血清FT3和脂联素、IR指数呈正相关(r=0.4579、0.5874,P=0.015、0.026),血清FT4与脂联素和IR指数呈正相关(r=0.3578、0.4325,P=0.010、0.013),TSH与脂联素和IR指数呈正相关(r=0.4342、0.5012,P=0.014、0.021),IR指数与脂联素也呈正相关(r=0.5745,P=0.024).结论 IR指数和脂联素在糖尿病合并甲亢患者中存在异常增高表达,且其与甲状腺激素水平呈正相关,表明糖尿病合并甲亢患者IR指数及脂联素与甲亢的病变过程有相关关系.     

Thyroid function and psychiatric morbidity in patients with manic disorder receiving lithium therapy

Euthyroid hyperthyroxinemia as a result of a transient increase in thyroid-stimulating hormone (TSH) levels may contribute to the development of manic disorder. Lithium has a potent short-term antithyroidal effect that may account for its antimanic action. The thyroid function and psychiatric morbidity of 46 adult patients with manic disorder were assessed prospectively before and 1 and 6 months after lithium treatment. At baseline, the free thyroxine level (FT4, 16.23 +/- 3.11 pmol/L) was at the high end of the normal range, whereas the free triiodothyronine (FT3, 4.24 +/- 0.65 pmol/L) and TSH (1.47 +/- 0.73 mIU/L) levels were within the normal range. All patients were clinically euthyroid, but five of them (11%) had elevated FT4 levels. Baseline FT3 and FT4 levels were positively correlated with past psychiatric morbidity. The FT4 level at baseline and after 1 month of treatment was positively correlated with scores on the Brief Psychiatric Rating Scale (p < 0.02) and negatively correlated with scores on the Global Assessment Scale (p < 0.005). During the first month of treatment, the reduction of FT3 and FT4 levels was significantly correlated with a decrease in psychiatric symptoms. By 6 months, the FT3 level was no longer significantly different from that at the baseline, but FT4 levels remained significantly lower. The TSH level increased progressively from baseline to 6 months. Multilevel models showed that FT4 and serum lithium levels were positively and negatively associated with psychiatric symptoms, respectively. The findings of the study lend support to the notion that euthyroid hyperthyroxinemia contributes to acute mania and suggest that lithium's short-term antimanic action may be mediated by its antithyroid effect.     

Thyroid indices and response to fluoxetine and nortriptyline in major depression

We investigated: (i) the status of thyroid hormones and their clinical correlates in patients with major depression; (ii) changes in thyroid hormone status after treatment with fluoxetine versus nortriptyline; and (iii) whether blunted thyrotropin-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) challenge predicts improvement after 6 weeks of fluoxetine versus nortriptyline treatment. Patients with major depression entering a treatment trial were assessed with the Structured Clinical Interview for DSM-III-R and were rated on the Montgomery-Asberg Depression Rating Scale (MADRS). Blood samples were taken for TSH, thyroxine (T4) and free thyroxine (FT4) measurement, and the maximum TSH response (deltamaxTSH) to a TRH challenge test was undertaken. Patients were then randomly assigned to receive fluoxetine or nortriptyline for six weeks. At 6 weeks, patients repeated the thyroid hormone assessment and completed the MADRS. Mean concentrations of TSH, T4, FT4 and deltamaxTSH were within reference ranges. T4 and FT4 levels decreased significantly after treatment in responders, but not in nonresponders. After treatment, deltamaxTSH concentrations decreased significantly in patients who responded to fluoxetine, and increased in patients who responded to nortriptyline. Patients with deltamaxTSH blunting at pretreatment were more likely to be male, to have higher MADRS scores and have a history of alcohol and drug dependence. Patients with a pretreatment deltamaxTSH of < 3.0 microm/ml showed greater improvement on the MADRS when treated with fluoxetine than if treated with nortriptyline. We observed a decrease in T4 and FT4 in responders to treatment with fluoxetine or nortriptyline. Positive relationships between deltamaxTSH blunting and alcohol and drug abuse and severity of depression were found. Patients with blunted deltamaxTSH responded better to fluoxetine than to nortriptyline. It is suggested that a blunted DmaxTSH may reflect a predominantly serotonergic disturbance in this group of patients with major depression.     

探讨碳酸锂联合131I在治疗妇女Graves病的疗效

目的探讨碳酸锂联合131I在治疗妇女Graves病的疗效。方法 51例女性Graves病患者随机分为研究组(30例)及对照组(21例)。两组均一次性口服131I量;研究组治疗当日开始加服碳酸锂250mg,2次/天,连服4周。检测不同时间的游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)水平。记录不良反应,随访疗效。结果 131I治疗后15、30、60d,研究组FT3、FT4水平低于对照组(P<0.01)。研究组30、60和90dFT3和FT4较治疗前明显下降;而对照组FT3、FT4较治疗前明显升高。研究组治疗60d时甲状腺大小恢复正常者28例(93.3%),明显多于对照组的11例(52.4%)(P<0.01)。研究组治愈率高于对照组(93.3%vs.57.1%)(P<0.01)。结论碳酸锂联合131I治疗妇女Graves病,能早期降低血清甲状腺激素水平,快速缩小甲状腺,减轻131I治疗的不良反应。     

Cobas601对中年非甲状腺疾病患者血清FT3、FT4、TSH测定结果分析

目的：通过研究中年人群患者血清当中存留的血清游离三碘甲状腺原氨酸（ FT3）、血清游离甲状腺素（FT4）以及促甲状腺激素（TSH）含有量探讨中年人群甲状腺功能情况。方法使用电化学发光的检测手段对130名无甲状腺疾病的中年患者进行FT3、FT4和TSH检测,并对非正常情况出现率、不同性别、年龄（30～36岁、37～40岁、41～45岁）测定值及非正常情况出现率进行分析。结果 FT3以及FT4含量减少的发生机率分别为19 j．9％和7．7％,TSH升高的发生机率为34．3％。女性FT3含量要比男性偏高（ P ＜0．05）,FT4在不同性别间差异无统计学意义（ P ＞0．05）,不同性别FT3、TSH非正常发生率比较,差异有统计学意义（ P ＜0．05）。 FT3会伴随着年龄的增加含量会逐渐减少（ P ＜0．05）,不同年龄组TSH含量比较,差异有统计学意义（ P ＜0．05）。不同的年龄FT3出现含量降低发生率比较,差异有统计学意义（ P ＜0．05）,而FT4不会随着年龄的改变出现变化（ P ＞0．05）。结论在中年患者当中,随着年龄的逐渐增加,其甲状腺功能出现异常的情况会比较容易发生,其重点表现在FT3含量降低,以及TSH含量增加。     

JNK pathway decreases thyroid hormones via TRH receptor: A novel mechanism for disturbance of thyroid hormone homeostasis by PCB153

PCBs, widespread and well-characterized endocrine disruptors, cause the disruption of thyroid hormone (TH) homeostasis in humans and animals. In order to verify the hypotheses that MAPK pathways would play roles in disturbance of TH levels caused by PCBs, and that TH-associated receptors could function in certain MAPK pathway, Sprague-Dawley rats were dosed with PCB153 intraperitoneally (i.p.) at 0, 4, 16 and 32mg/kg for 5 consecutive days, and Nthy-ori 3-1 cells were treated with PCB153 (0, 1, 5, 10μM) for 30min. Results showed that after the treatment with PCB153, serum total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3) and thyrotropin releasing hormone (TRH) were decreased, whereas free triiodothyronine (FT3) and serum thyroid stimulating hormone (TSH) were not altered. In vivo and in vitro studies indicated that JNK pathway was activated after PCB153 exposure. Moreover, TRH receptor (TRHr) level was suppressed after the activation of JNK pathway and was elevated after the inhibition of JNK pathway, but TSH receptor (TSHr) level was not affected by the status of JNK pathway though it was reduced after PCB153 treatment. The activated signs of ERK and P38 pathways were not observed in this study. Taken together, observed effects suggested that JNK pathway could decrease TH levels via TRHr, and that would be one novel mechanism of PCB153-mediated disruption of THs.     

Effects of oral erythrosine (2',4',5',7'-tetraiodofluorescein) on the pituitary-thyroid axis in rats

Erythrosine (FD&C Red Dye No.3) is a tetraiodinated derivative of fluorescein. Rats fed a 4% erythrosine diet for 30 months beginning in utero have an increased incidence of thyroid adenomas and adenocarcinomas. These tumors may be secondary to increased stimulation of the thyroid gland by TSH. This study was undertaken to determine if dietary erythrosine disrupts the pituitary-thyroid axis thereby altering serum thyroid hormone levels. TSH levels, or the pituitary's response to TRH. Rats were fed diets containing erythrosine (0.5, 1.0, 4.0%), sodium iodide (0.16%), or fluorescein (1.6%) for 3 weeks after which TRH testing was performed in vivo. Erythrosine produced a dose-dependent increase in serum T4 levels. With the 4% erythrosine diet, serum T4 and T3 levels and the free-T4 index were significantly increased, whereas the free-T3 index were significantly increased, whereas the free-T3 index was unchanged. Rats fed the 4.0% erythrosine diet had an exaggerated TSH response to TRH; 10 min after the TRH injection, serum TSH levels were 80% greater than TSH levels of control rats. Short-term administration of erythrosine to rats decreased hepatic T3 production by decreasing its conversion of T4 to T3, indicating that erythrosine decreases hepatic 5'-deiodinase activity. These data demonstrate that dietary ingestion of 4% erythrosine disrupts the pituitary-thyroid axis as evidenced by an increased TSH response to TRH. This effect is mediated by erythrosine or an iodinated metabolite, since ingestion of its fluorescein nucleus had no effect. Erythrosine's effects were not likely mediated by iodide, because serum T4 and T3 levels were elevated and iodide administration did not increase the TSH response to TRH. These data suggest that erythrosine increases the pituitary's TSH response to TRH by altering thyrotroph cell conversion of T4 to T3. Chronic erythrosine ingestion may promote thyroid tumor formation in rats via chronic stimulation of the thyroid by TSH.     

垂体促甲状腺素腺瘤的诊断和处理

目的探讨垂体促甲状腺素(TSH)腺瘤的临床特点及治疗方法。方法垂体TSH腺瘤患者4例,男1例,女3例,年龄25-47岁,中位病程7.5年,延误诊断4.2年。4例患者均有不同程度的甲状腺增大和甲亢症状,血浆FT3、FT4、T3、T4增高,3例患者TSH增高。1例对促甲状腺激素释放激素(TRH)激发试验有反应。头部鞍区MRI检查显示3例为大腺瘤,1例为微腺瘤。确诊后4例患者行经鼻-蝶窦入路垂体瘤切除术,其中1例术后辅以放疗。结果术后病理均证实为垂体腺瘤。随访至今(术后约5-7年),鞍区MRI检查未见肿瘤复发,甲状腺激素水平基本控制在正常范围。结论垂体TSH腺瘤发病率极低,甲亢患者血清TSH水平不被抑制时应警惕垂体TSH腺瘤的存在;鞍区影像学检查有助于垂体TSH腺瘤的早期诊断和治疗。     

脑卒中急性期情感障碍患者甲状腺功能变化的临床研究

目的探讨脑卒中急性期情感障碍患者甲状腺功能的变化。方法对109例急性脑卒中患者进行分组(卒中后无情感障碍组55例和卒中后情感障碍组54例)。收集两组发病第2天及第14天两次空腹血清,采用化学发光法进行甲状腺功能测定,并与40名正常对照组比较分析。结果第2天甲状腺功能变化情况:两观察组比对照组血清游离三碘甲状腺原氨酸(FT3)水平明显下降,而血清游离甲状腺素(FT4)水平显著增高,脑卒中后情感障碍组比无情感障碍组的变化程度更显著;卒中后无情感障碍组血清促甲状腺素(TSH)水平比对照组显著增高,但脑卒中后情感障碍组TSH水平升高不明显。第14天甲状腺功能变化情况:卒中后无情感障碍组FT3、FT4、TSH均恢复接近正常,与对照组比较差异无统计学意义;卒中后情感障碍组FT3、FT4虽有恢复但不明显,与对照组比较差异有统计学意义;3组的TSH水平比较差异均无统计学意义。结论卒中患者甲状腺功能都发生变化,而卒中后情感障碍患者比无情感障碍患者FT3、FT4变化更明显,且恢复慢。