Laboratory tests for evaluating thyroid therapy

Appropriate dosage of levothyroxine for the treatment of hypothyroidism is assessed by determining the serum thyroxine (T4) concentration in secondary and tertiary types. In primary hypothyroidism, the optimal thyroid replacement is that which induces a normal thyroid-stimulating hormone level and a normal TSH response to administration of thyrotropin-releasing hormone. Hypothyroidism often occurs in the management of hyperthyroidism. Serial serum TSH measurements help in the early detection of hypothyroidism, whereas serum triiodothyronine (T3) aids in prompt recognition of recurrence of hyperthyroidism.     

Hypothyroidism in the elderly. When symptoms are not a 'normal' part of aging.

Clinical findings alone may not lead to prompt diagnosis of hypothyroidism in elderly patients. Therefore, routine thyroid function tests may be warranted in older patients, especially women. Serum thyrotropin (TSH) is the most sensitive marker for hypothyroidism, although the test is more costly than that for serum thyroxine (T4). Patients with overt hypothyroidism who have elevated TSH and low T4 levels require replacement therapy. In addition, patients who have a TSH level higher than 20 microU/mL or who have a mildly elevated TSH level and high titers of antithyroid antibodies may benefit from prophylactic treatment. The usual recommended replacement dose is 0.05 to 0.1 mg/day of levothyroxine sodium (Levothroid, Synthroid).     

左旋甲状腺素对甲状腺功能减退症患者骨量的影响

目的探讨甲状腺素替代治疗对甲状腺功能减退症（甲减）患者骨量的影响。方法选取2012年1月到11月甲状腺素替代治疗的患者51例,其血清激素水平恢复正常,另选取同一时间段体检的54例为健康组,对每个患者采用双能X线骨密度仪分别测定其腰椎（L1-4）、两侧股骨骨密度,比较两组间骨密度值是否存在差异。结果甲减组患者双侧股骨头的骨密度显著低于健康组;女性患者腰椎及右侧股骨骨密度减低更显著。结论甲状腺素替代治疗后的甲减患者骨密度仍然比健康者低,需要定期测定骨密度。     

头颈部肿瘤放射治疗对甲状腺功能的影响

报道５５例头颈部肿瘤放射治疗（放疗）后甲状腺功能发生的变化。其中１６例放疗后促甲状腺激素（ＴＳＨ）水平高于正常，８例Ｔ_４水平下降，但临床上出现甲状腺功能减退（甲减）者仅２例，多数病人处于亚临床表现。提示临床不能忽视放疗对甲状腺功能的影响。     

妊娠期甲状腺减退患者妊娠期间左旋甲状腺素钠替代剂量探讨

目的 探讨妊娠甲状腺功能减退症(甲减)妊娠期间左旋甲状腺素钠替代剂量。方法 2014年3月至 2015年3月入选在我院分娩的274例妊娠合并甲减孕妇,其中亚临床型甲减组(SHT)207例,临床型甲减组(HT)67 例,以妊娠早期促甲状腺激素(TSH)<2.5mU/L,妊娠中晚期TSH<3.0mU/L为治疗目标,根据TSH 及孕周变化 予调整左旋甲状腺素钠治疗剂量。并根据TSH 水平分为TSH1 组,TSH3~5mU/L,TSH2 组,TSH5~8mU/L, TSH3 组,TSH8~10mU/L,TSH4 组,TSH10~15mU/L,TSH5 组,TSH15~20 mU/L 和TSH6 组,TSH>20 mU/L。结果 各组达治疗目标后,SHT 组T1、T2 和T3 期,左旋甲状腺素钠剂量分别为:(52.26±19.43)μg、 (56.69±20.58)μg和(56.76±19.99)μg;HT组在T1、T2 和T3 期,左旋甲状腺素钠剂量分别为:(64.58±50.26) μg、(66.67±47.64)μg和(65.91±34.06)μg;TSH1 组-TSH6 组左旋甲状腺素钠剂量分别为(45.65±16.08)μg、 (72.32±14.85)μg、(75.00±13.06)μg、(112.5±53.03)μg、(137.5±23.18)μg和(150.00±23.13)μg;T1、T2 和 T3 妊娠期TSH2、TSH3、TSH4 和TSH5 组左旋甲状腺素钠剂量高于TSH1 组(P <0.05);TSH4、TSH5 和TSH6 组 左旋甲状腺素钠片剂量高于TSH2 组(P <0.05);TSH4、TSH5 和TSH6 组高于TSH3 组(P <0.05);TSH5 和 TSH6 组高于TSH4 组(P <0.05);TSH6 组高于TSH5 组(P <0.05)。结论 妊娠期临床型甲减左旋甲状腺素钠 剂量在T1、T2 和T3 妊娠期均高于亚临床型甲减(P <0.05)。随着TSH 水平增高,所需左旋甲状腺素钠明显增加 (P <0.05)。     

Immunoradiometric assay for basal thyroid-stimulating hormone levels: strategy for the management of thyroxine replacement

Basal levels of thyroid-stimulating hormone (TSH) as determined by a highly sensitive immunoradiometric assay (IRMA) were evaluated in 30 clinically euthyroid patients receiving levothyroxine (T4) replacement therapy for primary hypothyroidism. In each patient, the serum TSH level had been normal as determined by conventional TSH radioimmunoassay while the patient had been receiving a constant dosage of T4 for at least three months before the study. Correlation of the TSH levels by IRMA with the concurrent concentrations of serum T4 and triiodothyronine (T3) showed that basal TSH levels by IRMA were not predictable from the serum T4 and/or T3 levels. We observed a relatively high frequency of suppression of basal TSH levels (8/30, 27%), a finding compatible with, though not necessarily indicative of, overmedication with T4. In view of the reasonable suspicion that modest but protracted overmedication with T4 may be detrimental and that suppressed TSH levels are commonly observed in conventionally managed patients, and since suppression of TSH levels is now identifiable, it seems prudent to revise the guidelines of T4 replacement therapy accordingly. In addition to maintaining clinical euthyroidism, we propose that titrating the T4 dosage to establish lower normal TSH concentrations without suppression (eg, 0.1 to 3.0 microU/ml) would assure the resolution of frank hypothyroidism, reduce the likelihood of persistent goiter, and minimize the potential for subtle but chronic overmedication.     

Management of primary hypothyroidism

Primary hypothyroidism is a common condition requiring lifelong treatment and monitoring. The type and amount of thyroid hormone replacement, selection of laboratory tests, and timing of office visits are all important for optimizing patient well-being and reducing the costs of medical care. The aim of treatment is to bring the patient to the euthyroid state. Currently this is defined as a normal serum concentration of TSH by recently developed sensitive and specific immunometric assays, and is accomplished by titrating the dose of levothyroxine and changing it not more often than at 4- to 6-week intervals. As an indicator of euthyroidism, the sensitive TSH assay has advantages over tests of serum T4, FT4I, T3, FT4, and TSH by RIA because it is independent of TBG changes that result from pregnancy, birth-control pills, and estrogen replacement, is not spuriously elevated by the levothyroxine treatment itself, and is the only test that detects both subclinical hypothyroidism and subclinical hyperthyroidism. Additional serum tests are not usually necessary but have advantages under special circumstances. Once the optimal replacement dose is determined, monitoring can be done yearly or even bi-yearly, depending on the adequacy of patient education and patient compliance.     

Noncompliance with medical treatment: pseudomalabsorption of levothyroxine

Euthyroidism could not be achieved in a 41-year-old woman with primary hypothyroidism despite escalating doses of oral levothyroxine as high as 600 microg and 100 microg of triiodothyronine daily. Clinical and biochemical evidence of hypothyroidism persisted even with the administration of intramuscular levothyroxine. There was no history compatible with drug-induced malabsorption of levothyroxine. Evaluation of serum showed no thyroid hormone autoantibodies. After hospitalization, intravenous levothyroxine therapy returned thyroid hormone to normal concentrations. Moreover, thyroid hormone loading tests revealed normal oral absorption of both levothyroxine and triiodothyronine. Noncompliance with medical treatment leading to pseudomalabsorption of levothyroxine should be considered in patients who have persistent hypothyroidism with high-dose replacement therapy.     

Subclinical hyperthyroidism: possible danger of overzealous thyroxine replacement therapy

Many patients taking customary doses of levothyroxine have slightly elevated serum thyroxine (T4), apparently normal serum triiodothyronine, suppressed serum thyrotropin (thyroid-stimulating hormone; TSH) concentrations, and no clinical symptoms of hyperthyroidism. Recent reports suggest that these patients may have adverse effects from subclinical hyperthyroidism, including abnormally short systolic time intervals, elevations in liver enzymes, and reductions in bone density. Controversy exists about which thyroid function tests should be used to monitor patients taking levothyroxine. A review of currently available data suggests that replacement doses of levothyroxine given to hypothyroid patients should be adjusted so that serum TSH measured by the new sensitive assays is within the normal range. Patients requiring suppressive doses of levothyroxine to shrink goitrous thyroid tissue or to prevent growth of abnormal tissue should be given the minimal dose needed to accomplish the desired clinical or biochemical response.     

How to detect hypothyroidism when screening tests are normal. Use of the TRH stimulation test

In this study, 65 women and two men were examined because of symptoms suggesting hypothyroidism (eg, tiredness, lack of energy, weight gain, dry skin, cold intolerance, constipation, galactorrhea, menstrual disturbances). Some also demonstrated biochemical abnormalities (eg, hyperlipoproteinemia, elevation of creatine phosphokinase). Serum thyroxine (T4) and triiodothyronine (T3) and T3 uptake were normal in all patients. The thyrotropin-releasing hormone (TRH) test differentiated the patients into two groups: Group 1 (47 patients) had an exaggerated response of thyroid-stimulating hormone (TSH) to TRH; group 2 (20 patients) had a normal TSH response. Compared with group 2, the group 1 patients had a higher incidence of typical hypothyroid symptoms and goiter and responded more readily to levothyroxine therapy. We concluded that these patients had borderline hypothyroidism. Results of basal thyroid function tests may be within normal limits in such a condition. The TRH test, then, appears to increase diagnostic accuracy and should be routinely performed in patients who have symptoms suggesting hypothyroidism but normal results of basal thyroid function tests.     

左甲状腺素钠对妊娠早期甲状腺过氧化物酶抗体阴性的亚临床甲状腺功能减退患者围产结局的影响

目的 探讨左甲状腺素钠(L-T4)对妊娠早期伴甲状腺过氧化物酶抗体(TPoAb)阴性的亚临床甲状腺功能减退(甲减)患者围产结局的影响。方法 选择就诊的妊娠早期亚临床甲减伴TPoAb阴性患者1 140例,随机分为L-T4组(n=570)和对照组(n=570),L-T4组给予L-T4治疗并达到目标值[促甲状腺素(TSH)<2.5 mU/L],对照组不进行相应治疗。观察两组患者妊娠高血压、贫血、流产、早产及新生儿体质量等相关指标。结果 对照组妊娠高血压、贫血、流产率及早产率等指标显著高于L-T4组(P＜0.05),顺产率显著低于L-T4组,并且L-T4组患者治疗达目标值所需L-T4剂量与患者的TSH水平呈明显正相关(r=0.763,P＜0.05)。结论 L-T4可以明显改善妊娠早期伴TPoAb抗体阴性的亚临床甲状腺功能减退患者的围产结局。     

Possible hypothyroidism associated with quetiapine

OBJECTIVE: To report a case of hypothyroidism occurring after the addition of quetiapine to an existing drug regimen. CASE SUMMARY: A 46-year-old African-American woman diagnosed with schizoaffective disorder, bipolar type, and a four-year history of successfully treated hyperthyroidism, was suboptimally responsive to olanzapine treatment. Transition from olanzapine to quetiapine was initiated and, approximately two months after adding quetiapine to a standing pharmacotherapeutic regimen, the patient developed an elevated thyroid-stimulating hormone (TSH) concentration of 8.45 microU/L. A diagnosis of hypothyroidism was subsequently made, treatment with levothyroxine was initiated, and the patient's thyroid function became stable. DISCUSSION: Drug induced hypothyroidism is known to occur with several medications. Quetiapine is an atypical antipsychotic with the potential to decrease thyroid hormone concentrations in some patients; this effect may be dose related. Despite this known adverse effect, the manufacturer of quetiapine reports that elevated TSH concentrations and subsequent treatment with thyroid hormone supplementation have occurred only rarely. We report the development of hypothyroidism in a patient who had previously received successful radioactive iodine treatment for hyperthyroidism in 1994, but who had no detected thyroid abnormalities until treatment with quetiapine was started four years later. CONCLUSIONS: Patients with compromised thyroid function who receive treatment with quetiapine may develop hypothyroidism. Appropriate care for these patients may include an increased awareness of possible hypothyroidism and consideration of thyroid function monitoring.     

二仙汤加芪海消瘿汤治疗慢性淋巴细胞性甲状腺炎伴甲状腺功能减退症的临床研究

目的：观察二仙汤加芪海消瘿汤治疗慢性淋巴细胞性甲状腺炎（慢甲炎）伴甲状腺功能减退症的临床疗效。方法选择慢甲炎伴甲状腺功能减退症70例,皆用左旋甲状腺素片维持甲状腺激素正常,分为两组,治疗组在左旋甲状腺素基础上加二仙汤和芪海消瘿汤方,对照组单用左旋甲状腺素。治疗前后观察两组临床疗效,并检测两组血清总甲状腺素（T4）、血清总三碘甲腺原氨酸（T3）、促甲状腺激素（TSH）、游离三碘甲腺原氨酸（FT3）、血清游离甲状腺素（FT4）、甲状腺球蛋白抗体（TGAb）、甲状腺过氧化物酶抗体（TPOAb）、血常规、肝肾功。结果治疗前两组T3、T4、TSH、FT3、FT4、TGAb、TPOAb、血常规比较差异无统计学意义（P＞0．05）,肝肾功能皆正常,具可比性。经治疗后治疗组有效率为91．4％,对照组为74．3％,两组比较差异有统计学意义（ P＜0．05）。治疗后两组T3、T4、FT3、FT4、TSH皆正常,治疗组TGAb、TPOAb降低,与治疗前相比差异有统计学意义（P＜0．05）,与对照组相比差异有统计学意义（P＜0．05）。治疗组左旋甲状腺素用量明显减少,与治疗前相比差异有统计学意义（P＜0．05）。治疗组肿大的甲状腺较治疗前缩小,相比差异有统计学意义（P＜0．05）;对照组治疗前、后甲状腺大小变化不大,与治疗组相比差异有统计学意义（P＜0．05）。结论二仙汤加芪海消瘿汤能调节慢甲炎伴甲状腺功能减退患者免疫功能,降低抗体水平,减少左旋甲状腺素用量,缩小肿大的甲状腺。     

TSH may not be a good marker for adequate thyroid hormone replacement therapy

The objective of this study was to evaluate parameters of thyroid function and indices of peripheral thyroid hormone action (such as SHBG) in patients whose hypothyroidism was considered well controlled under current criteria. Eighty-five patients with T4-treated hypothyroidism, 28 of whom had athyria, were compared with 114 normal individuals with the same TSH levels. T3 levels were significantly lower in hypothyroidism although mean T4 and fT4 levels were significantly higher. Furthermore, mean SHBG levels were significantly lower in hypothyroidism independently of age. The difference remained when stricter criteria for adequate treatment were applied (TSH < 2.5 microgU/ml). Significant negative correlations were found between logTSH and T3. The slopes of the regression lines of T3 to TSH were significantly different in the control group and the hypothyroid group: thus, for the same TSH levels, T3 levels were lower in the hypothyroid group. We conclude that patients with T4-treated hypothyroidism have lower T3 levels, lower T3/T4 ratio and lower SHBG than normal individuals with the same TSH, perhaps indicating relative tissue hypothyroidism in the liver. TSH levels used to monitor substitution, mostly regulated by intracellular T3 in the pituitary, may not be such a good indicator of adequate thyroid hormone action in all tissues. The co-administration of T3 may prove more effective in this respect, provided novel suitable preparations are developed. Until this is accomplished, substitution in hypothyroidism should aim at low normal TSH, to ensure normal T3 levels.     

Optimisation of thyroid hormone replacement using an automated thyroid register

The high prevalence of thyroid dysfunction requires an efficient and effective means of monitoring and adjustment. We compared the current network of 12,524 patients with thyroid dysfunction with register data prior to 1991 to examine the precision of thyroxine replacement in patients with hypothyroidism and assess locally changing trends in treatment of hyperthyroidism. Since 1991, due to the associated adverse effects of a suppressed thyroid-stimulating hormone (TSH) (<0.03 mU/l), the network has facilitated a significant reduction in the proportion of thyroxine-treated patients with TSH suppression from 58.5% before 1991 to 9.2 +/- 3.8% thereafter. Since 1991, there has been an increased use of radioiodine by 14.3% [95% confidence interval (95% CI): 10.6-17.8] and a reduced use of thyroidectomy by 12.3% (95% CI: 8.8-15.8) to treat hyperthyroid patients compared with before 1991. Between the two treatments, there were no differences in subsequent rates of hypothyroidism or mean thyroxine dosage.     

Cardiac systolic time intervals and thyroid hormone levels during treatment of hypothyroidism.

This study was undertaken to compare results of modern serum thyroid hormone assays with cardiac systolic time intervals (STI) during thyroxine treatment in hypothyroid patients. The patients were assessed clinically (Billewicz index) and the STI and serum thyrotropin (TSH), total and free thyroxine (T4) and total and free triiodothyronine (T3) were determined in 16 hypothyroid women (Group I) treated with 50 micrograms increments of thyroxine, and in 13 women who had a history of thyroid carcinoma and high-dose thyroxine replacement therapy and had elevated thyroid hormone concentrations (Group II). The STI of 24 matched healthy female controls were used for reference of STI. The pre-ejection period (PEP) index and the PEP/LVET ratio (left ventricular ejection period) were greater in untreated overtly and mildly hypothyroid patients (p less than 0.05) than in the controls. During stable thyroxine therapy [mean daily dosage for Group I 137.5 (7.3) micrograms and for Group II 220 (61) micrograms] the PEP correlated with serum free T4 (FT4), as measured by a two-step method (SpectriaR) (r = -0.55, p less than 0.01, n = 29) and total T4 (r = -0.51, p less than 0.05, n = 29), but not with TSH, T3, FT3 or FT4 measured by an analogue method Amerlex-M(R). The TRH test was not valuable in follow-up because of the strong correlation between basal TSH and stimulated TSH values (r = 0.95). In conclusion, STI are useful for assessment of the thyroid state in untreated hypothyroid patients. Serum TSH becomes normal in the same time as STI and is the best for follow-up. If serum TSH is low and the patient is on stable thyroxine therapy, we recommend serum FT4 for monitoring thyroxine replacement. Two-step FT4 assays had the best correlation with STI, which has significance in patients with non-thyroidal illness.     

舒尼替尼致转移性肾细胞癌患者甲状腺功能异常的临床分析

目的 总结接受舒尼替尼治疗的转移性肾细胞癌患者的甲状腺功能变化规律,评价舒尼替尼对甲状腺功能的影响.方法 前瞻性收集北京大学第一医院泌尿外科2008 年6 月至2010 年4 月37 例转移性肾细胞癌接受舒尼替尼治疗的患者的临床资料,其中22 例患者于基线及每个治疗周期第28 天进行甲状腺功能检测.对甲状腺功能异常发生情况进行分析.结果 22 例患者接受舒尼替尼的中位治疗时间为7 个周期(10.5 个月),共18 例(81.8%)患者出现甲状腺功能减低,其中亚临床甲状腺功能减低14 例(63.6%),临床甲状腺功能减低4 例(18.2%),予左旋甲状腺素片替代治疗;6 例(27.3%)患者出现一过性亚临床甲状腺毒症后转为甲状腺功能减退,无持续甲状腺功能亢进患者.甲状腺功能减低的风险随舒尼替尼用药时间延长而增加,出现甲状腺功能减退的中位时间为3 个周期(1 ～7个周期).治疗3 个周期内,50.0%(11/22 例)的患者出现甲状腺功能减退;4 ～6个周期时,约72.7%(16/22 例)患者出现甲状腺功能减退.结论 舒尼替尼致甲状腺功能减退的发生率较高,程度可较严重,应引起临床重视.舒尼替尼相关性甲状腺功能减退可以用激素替代进行治疗,因此应避免舒尼替尼减量或停药.     

Imatinib induces hypothyroidism in patients receiving levothyroxine

Interactions of imatinib with other drugs have been scarcely reported. We report a previously unknown effect of imatinib on levothyroxine therapy. Eleven patients (1 with gastrointestinal stromal tumor and 10 with medullary thyroid carcinoma) received imatinib. Eight had undergone thyroidectomy and used levothyroxine, and 3 had the thyroid in situ. Thyroid function was measured before, during, and within 2 weeks after any change in either imatinib or levothyroxine dosage. We observed symptoms of hypothyroidism in all patients who had undergone thyroidectomy, whereas patients with the thyroid in situ remained clinically and biochemically euthyroid. On average, thyrotropin (INN, thyrotrophin) levels increased to 384% +/- 228% of the upper limit in patients after thyroidectomy, whereas free thyroxine (fT4) and free tri-iodothyronine (fT3) values remained within the reference range (59% +/- 17% of the upper limit for fT4 and 63% +/- 4% of the upper limit for fT3). Clinicians should be aware that hypothyroid subjects receiving imatinib have a high likelihood for increased levothyroxine replacement and should be closely monitored for elevations in thyrotropin indicating worsening hypothyroidism.     

Short‐term overt hypothyroidism induces discrete diastolic dysfunction in patients treated for differentiated thyroid carcinoma

Background Thyroid hormone has important effects on the cardiovascular system. The consequences of episodes of acute hypothyroidism on cardiac function have been investigated in only a few studies, and their results are inconclusive. Our objective was to investigate the effects of acute hypothyroidism on cardiac function in patients with iatrogenically induced subclinical hyperthyroidism after treatment for differentiated thyroid carcinoma. Material and methods Fourteen patients with a history of differentiated thyroid carcinoma on thyroid‐stimulating hormone (TSH)‐suppressive thyroxine replacement therapy were studied. We assessed cardiac function before, and 1 and 4 weeks after withdrawal of thyroxine substitution. We measured serum levels of free thyroxine, triiodothyronine and TSH and used a new sophisticated Doppler echocardiography technique, tissue Doppler imaging (TDI), to assess detailed and quantitative assessment of systolic and diastolic cardiac function. Echocardiographic parameters in patients were compared to controls. Results Compared to controls, patients had higher left ventricular mass and wall thickness and decreased diastolic function during TSH‐suppressive l ‐thyroxine substitution therapy. Thyroxine withdrawal resulted in a decrease in both early (E) and late (A) diastolic mitral inflow velocities, without impact on E/A ratio. Using TDI, late diastolic velocity (A′) decreased without impact on E′/A′ ratio. Left ventricular dimensions, wall thickness and mass did not change during thyroxine withdrawal. Conclusions Subclinical hyperthyroidism is accompanied by diastolic dysfunction. Subsequent acute hypothyroidism induces only subtle changes in diastolic function.     

131I治疗Graves'病后早发甲低甲状腺功能指标及摄锝率测定的意义

目的进一步探讨甲状腺功能指标和摄锝率测定在^131Ⅰ治疗Graves’病后早发甲低中的临床价值。方法66例Graves’病经^131Ⅰ治疗后早发临床甲低患者，在左甲状腺素钠片替代治疗前后进行甲状腺功能检查及20min摄锝率测定。结果替代治疗前暂时性甲低和永久性甲低FT3、FT4及摄^99mTc率均低于健康对照组，TSH高于健康对照组，差异均有统计学意义（P〈0．01），而暂时性甲低组与永久性甲低组差异无统计学意义（P〉0．05）；替代治疗后暂时性甲低组各项指标恢复正常，永久性甲低组FT3、FT。和摄^99mTc率分别低于健康对照组和暂时性甲低组，TSH高于健康对照组和暂时性甲低组，差异有统计学意义（P〈0．01）。结论甲状腺功能和摄锝率测定早期不能鉴别暂发性甲低和永久性甲低。短时间替代治疗后暂时性甲低可恢复正常，而永久性甲低不能恢复。