Long-term treatment of children with epilepsy with valproate or carbamazepine may cause subclinical hypothyroidism

PURPOSE: The aim of the study was to evaluate serum thyroid hormone balance in children receiving long-term therapy with carbamazepine (CBZ), valproate (VPA), and phenobarbital (PB). METHODS: We determined serum levels of triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), thyroxine-binding globulin (TBG), and thyroid-stimulating hormone (TSH) in 148 healthy children and 141 children with epilepsy who had been receiving CBZ (61 patients), VPA (51 patients), or PB (29 patients) for 12-161 months. In view of TSH values, three categories of subclinical hypothyroidism were considered: I, TSH greater than the control-group mean + 2 SD (4.37 mIU/L in our study) and <6 mIU/L; II, TSH between 6 and 12 mIU/L; and III, TSH >12 mIU/L. RESULTS: In all treated groups, mean T4 and FT4 levels were lower than in the control group, whereas the CBZ- and VPA-treated children additionally showed reduced mean T3 and TBG levels and increased mean TSH levels. In the group receiving CBZ, 8.2% had TSH values higher than the normal-range maximum, by comparison with only 3.6% of healthy children. The increase in TSH levels was particularly marked in VPA-treated children, accounting for 26% of patients with subclinical hypothyroidism. CONCLUSIONS: Our results, in contrast to previous reports, suggest that CBZ and particularly VPA may induce subclinical hypothyroidism. This suggests a need for careful monitoring of TSH levels in children receiving CBZ or VPA.     

Sinemet and thyroid function in Parkinson disease

Patients on chronic carbidopa-levodopa (Sinemet) therapy underwent thyroid function testing that included measurement of serum thyroxine (T4), triiodothyronine (t3), thyrotropin (TSH), T3 uptake (T3U), free T4 index (FT4I), and free T3 index (FT3I). The subjects were studied both in a random sampling and in a controlled manner, fasting and 2 hours after receiving the drug. All subjects were euthyroid by testing, and there was no significant difference in thyroid hormone levels of patients and controls or in fasting values and values 2 hours after the drug. However, there was a small but significant reduction in serum TSH levels after Sinemet. Therapeutic doses of Sinemet have no significant effect on thyroid function in euthyroid patients with Parkinson disease.     

氯氮平对血清甲状腺素和血糖、血脂水平的影响

目的 探讨氯氮平对精神分裂症患者糖、脂代谢与血清甲状腺素水平的影响.方法 对60例接受氯氮平治疗的住院精神分裂症患者分别在治疗前和治疗8周末检测血糖（FPG）、胆固醇（TC）和甘油三脂（TG）及甲状腺相关激素水平.并对以上检测指标做统计分析.结果 氯氮平治疗8周后血清T4水平显著下降（P＜0.01）,TSH水平显著升高（P＜0.01）;血糖、甘油三脂显著升高（P＜0.01）;治疗8周末血糖分别与血清FT3、FT4、T3及T4水平呈显著负相关;甘油三脂与TSH水平呈显著正相关.结论 氯氮平导致糖、脂代谢紊乱和甲状腺功能改变,而糖、脂代谢紊乱与其血清甲状腺素水平变化有-定的相关性.     

急性颅脑损伤后血清甲状腺素的改变及其意义

目的探讨急性颅脑损伤后血清甲状腺素水平的改变及其意义。方法应用磁性酶联免疫定量分析法检测１５６例急性颅脑损伤患者伤后２４～７２小时及存活者伤后２周的血清Ｔ３、游离Ｔ３（ＦＴ３）、Ｔ４、游离Ｆ４（ＦＴ４）及促甲状腺激素（ＴＳＨ）水平的改变,并与１００名正常对照者比较。结果伤后患者早期血清Ｔ３、ＦＴ３水平显著降低（Ｐ〈０．００１）,而Ｔ４、ＦＴ４显著升高（Ｐ〈０．０１）;颅脑损伤愈重,昏迷程度愈深,上     

难治性抑郁症患者甲状腺激素水平的分析

目的 探讨难治性抑郁症患者的甲状腺激素水平。方法 按性别、年龄1：1匹配选取难治性抑郁症患者和健康对照各30例，采用放射免疫法测定患者组治疗前和对照组血清TSH、T3、T4、FT3、FT4水平。结果 患者组异常者17例，占56．7％，对照组异常者2例，占6．7％，两组比较，患者组甲状腺激素水平出现异常的比率明显高于对照组，主要表现为TSH升高、T3降低、FT4降低，差异均有统计学意义（P〈0．05）。结论 难治性抑郁症患者中有56．7％的患者存在亚临床型甲状腺功能的减退。     

急性脑梗死患者甲状腺激素变化及其临床意义

目的探讨急性脑梗死患者甲状腺激素水平的变化及其临床意义。方法采用化学发光法检测65例急性脑梗死患者治疗前后和50例健康对照者血清三碘甲状腺原氨(T3)、游离三碘甲状腺原氨(FT3)、甲状腺素(T4)、游离甲状腺素(FT4)、促甲状腺激素(TSH)水平,并对2组进行比较。结果甲状腺激素水平T4、FT4、TSH在治疗前后各组与对照组相比差异无统计学意义(P>0.05)。T3在治疗前较对照组明显降低(P<0.05),FT3治疗前与对照组相比降低更显著(P<0.01),在治疗后T3、FT3与对照组相比差异无统计学意义(P>0.05)。结论脑梗死患者急性期的保护性应激反应可引起T3和FT3下降,并且T3和FT3的降低与病情严重程度及预后密切相关,随着病情好转逐渐恢复;对于治疗前后甲状腺激素水平的变化,有助于监测治疗和判断预后有一定临床意义。     

Carbamazepine and risk of hypothyroidism: a prospective study

OBJECTIVES - While carbamazepine (CBZ) decreases thyroid hormone concentrations it rarely causes hypothyroidism. We assessed prospectively the early effect of CBZ on thyroid status in thyroxine-supplemented hypothyroid patients, when compared with patients without a thyroid disorder. METHODS - In 29 patients, thyrotropin (TSH), total thyroxine (TT4) and free thyroxine (FT4) serum levels were assayed before starting CBZ, and then weekly for 7 weeks. Nineteen patients with no thyroid disorder (group A) were compared with 10 thyroxine-supplemented hypothyroid patients, stable before CBZ treatment (group B). RESULTS - In group A, TT4 decreased significantly by ca. 15-25%, starting from the first week (Friedman, P < 0.001). FT4 decline was smaller (ca. 10-15%) and delayed till the second week. FT4/TT4 ratio increased significantly (P < 0.001), while TSH only slightly (P = 0.073), never exceeding normal range. In group B, similar TT4 and FT4 decline was followed by significantly increasing TSH (P = 0.011), while the FT4/TT4 ratio was not significantly changed. In 3 of 10 patients TSH rose over 5 mIU/l, necessitating treatment adjustment. CONCLUSIONS - In patients with no thyroid disorder, CBZ causes hormonal changes of no clinical relevance, due to adaptive response. In T4-supplemented hypothyroid patients this adaptation is lacking, CBZ may precipitate subclinical or overt hypothyroidism, and early thyroid function monitoring seems advisable.     

抑郁症首次发病与复发患者甲状腺激素水平的研究

目的:探讨甲状腺激素水平与首发和复发抑郁症之间的相关性及临床意义。方法:采用电化学发光免疫分析法,分别测定127例抑郁症患者(其中首发抑郁组66例、复发抑郁组61例)和53名正常者(正常对照组)的血清三碘甲状腺原氨酸(T3)、甲状腺素(T4)、游离甲状腺激素(FT3、FT4)和促甲状腺激素(TSH)水平;采用汉密尔顿抑郁量表(HAMD)评估患者抑郁程度。结果:复发抑郁组血清FT3水平显著低于正常对照组(P=0.009),血清T3、T4、FT4、TSH水平与正常对照组差异无统计学意义;首发抑郁组血清T3、T4、FT3、FT4、TSH水平与正常对照组差异无统计学意义。相关分析显示,首发抑郁组血清T3水平与HAMD总分呈负相关(r=-0.250,P=0.043);复发抑郁组血清T3、T4、FT3、FT4、TSH与HAMD总分均无相关(r=0.014~0.204,P均0.05)。结论:抑郁症首次发病与复发患者血清甲状腺激素水平存在一定变化,复发较首发抑郁者可能存在更严重的甲状腺功能减退。     

非典型抗精神病药对精神分裂症患者血清甲状腺激素水平的影响

目的探讨非典型抗精神病药利培酮、奥氮平对精神分裂症患者甲状腺功能的影响。方法将符合《中国精神障碍分类与诊断标准(第3版)》(CCMD-3)的54例精神分裂症患者,采用随机数字表法分成服用利培酮和奥氮平两组,其中利培酮组29例,给药初始剂量为4 mg/d,2周内逐渐加至6 mg/d,观察至8周末;奥氮平组25例,给药初始剂量为10 mg/d,2周内逐渐加至15mg/d,观察至8周末。分别在治疗前、治疗第8周末测血清总三碘甲状腺原氨酸(TT3)、血清总甲状腺素(TT4)、游离三碘甲状腺原氨酸(FT3)、血清游离甲状腺素(FT4)及促甲状腺激素(TSH)水平。结果利培酮组治疗前后血清TT3、TT4、FT3、FT4、TSH水平差异均无统计学意义(P0.05),奥氮平组治疗前后血清TT3、TT4、TSH水平差异无统计学意义(P0.05),治疗前后FT3、FT4差异有统计学意义[(3.01±0.28)pg/mlvs.(2.81±0.26)pg/ml,(0.91±0.2)pg/mlvs.(0.77±0.14)pg/ml,P0.05]。利培酮组治疗后血清TT3、FT3水平升高,较奥氮平组差异有统计学意义(P0.05)。结论利培酮对精神分裂症患者甲状腺功能无实质影响,奥氮平能影响精神分裂症患者血清FT3、FT4的水平,在治疗中应注意监测服用奥氮平的精神分裂症患者的甲状腺激素水平。     

女性抑郁症患者血清甲状腺激素水平研究

目的:探讨女性血清甲状腺激素水平与抑郁症的关系.方法:采用免疫化学发光法对58例女性抑郁症患者及对照组40例健康女性的血清游离三碘甲状腺原氨酸(FT3),游离甲状腺素(FT4),促甲状腺素(75H)进行了检测.结果:女性抑郁症患者治疗前血清FP4,TSH较对照组低(P均<0.01),而FT3与对照组差异无显著性(P>0...     

Grades 1 and 2 hypothyroidism in a state mental hospital: Risk factors and clinical findings

Thirty-six chronically psychotic patients (nine men and 27 women, mean age 56.7 +/- S.D. 13.4 years) were found to have elevated thyroid stimulating hormone (TSH) levels during review of thyroid function screening tests of 1150 patients over a 15 month period in a 700 bed state mental hospital. This study population of 36 patients was more likely to be female and older than the general hospital population. The spectrum and frequency of psychiatric diagnoses included dementia (3); schizoaffective disorder (12); bipolar disorder (6); schizophrenic disorder (4); organic affective disorder (7); major depression (3); and mental retardation (1). Only nine of these 36 patients failed to receive the goitrogens lithium (LI), carbamazepine (CBZ) and/or phenytoin (PTN) and five of those nine patients had a history of thyroid disease. Sex did not predict age, thyroxine (T4) level, triiodothyronine (T3) uptake, or TSH. The distribution of psychiatric diagnoses were the same for both sexes. Expectedly, there was an inverse relationship between TSH and T4 and T3 uptake. Using T4 to separate grades 1 and 2 hypothyroidism revealed that six (17%) patients had grade 1 disease. Men were more likely to have a seizure disorder and receive LI, CBZ, and PTN. Women were more likely to have a history of thyroid disease. The goitrogenic effects of LI + CBZ seemed additive compared with patients receiving LI alone. While T4, T3 uptake, and LI levels were the same for the two groups, patients receiving LI + CBZ had higher TSH values (p = 0.028) than did patients receiving LI alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thyroid Function with Antiepileptic Drugs

Serum thyroid hormone balance was assessed in 108 patients receiving chronic antiepileptic drug (AED) therapy. Forty-five patients were receiving carbamazepine (CBZ), 26 phenytoin (PHT), 16 CBZ-PHT, 11 valproate (VPA), and 10 CBZ-VPA. Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in patient groups receiving CBZ and/or PHT. Serum T4 concentrations were below the normal range in 24 (53.3%) CBZ patients, 11 (42.3%) PHT patients, 12 (75%) CBZ-PHT patients, and in all 10 patients (100%) receiving CBZ-VPA. Furthermore, serum levels of FT4 were below the normal range in 13 (28.9%) CBZ patients, 6 PHT (23.1%) patients, 5 (31.3%) CBZ-PHT patients, and 5 (50%) CBZ-VPA patients. Despite the decreased serum T4 and FT4 levels in these patients, serum basal and stimulated thyrotropin (TSH) concentrations were normal, except for the slightly increased basal TSH in the CBZ-VPA group. In the VPA group, the findings were different from those in other patients: T4 serum levels were unchanged and FT4, T3, and basal TSH levels increased, but stimulated TSH levels did not differ from those of the control group. The decrease in serum thyroid hormone levels during CBZ and/or PHT medication probably is caused by an accelerated hepatic plasma clearance of these hormones due to induction of hepatic microsomal enzyme systems by these AEDs. VPA, an AED with no liver enzyme-inducing properties, does not cause similar changes. The feedback mechanism is not activated, possibly because of a hypothalamic interference by CBZ and PHT.(ABSTRACT TRUNCATED AT 250 WORDS)     

An evaluation of basal hypothalamic-pituitary-thyroid axis function in depression: Results of a large-scaled and controlled study

In order to evaluate the function of the hypothalamic-pituitary-thyroid (HPT)-axis in unipolar depression, the authors measured basal 0800h plasma levels of free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) by means of the new, ultrasensitive assays (TSH-IRMA) in 69 healthy controls, 62 minor, 101 simple major, and 57 melancholic depressed subjects. Basal HPT-axis hormone levels of almost all (96.8%) unipolar depressed patients fell within the normal, euthyroid range. None of the major depressed subjects showed subclinical hypothyroidism. It was found that 8.8% of the melancholic subjects exhibited some degree of subclinical hyperthyroidism. Basal TSH-IRMA values were significantly lower in melancholic patients than in healthy controls, minor and simple major depressed patients, and in major vs. minor depressed subjects. FT4 circulating levels were significantly higher in melancholic patients than in all other subjects. Basal TSH-IRMA and FT4 levels were significantly correlated with severity of illness. In depression, there was a significant and negative correlation between basal TSH-IRMA values and FT4 concentrations. No significant gender- or age-related differences in TSH-IRMA or thyroid hormones were detected in depression. It is argued that—in depression research—the assays of basal TSH-IRMA should replace thyrotropin releasing hormone tests.     

Thyroid dysfunction in children with autism spectrum disorder is associated with folate receptor α autoimmune disorder

Folate receptor α (FRα) autoantibodies (FRAAs) are prevalent in autism spectrum disorder (ASD). FRAAs disrupt folate transport across the blood‐brain barrier by binding to the FRα. Thyroid dysfunction is frequently found in children with ASD. We measured blocking and binding FRAAs and thyroid‐stimulating hormone (TSH), free thyroxine (T4) (FT4), total triiodothyronine (T3) (TT3), reverse T3 (rT3), thyroid‐releasing hormone (TRH) and other metabolites in 87 children with ASD, 84 of whom also underwent behaviour and cognition testing and in 42 of whom FRAAs, TSH and FT4 were measured at two time points. To better understand the significance of the FRα in relation to thyroid development, we examined FRα expression on prenatal and postnatal thyroid. TSH, TT3 and rT3 were above the normal range in 7%, 33% and 51% of the participants and TRH was below the normal range in 13% of the participants. FT4 was rarely outside the normal range. TSH concentration was positively and the FT4/TSH, TT3/TSH and rT3/TSH ratios were inversely related to blocking FRAA titres. On repeated measurements, changes in TSH and FT4/TSH ratio were found to correspond to changes in blocking FRAA titres. TSH and the FT4/TSH, TT3/TSH and rT3/TSH ratios were related to irritability on the Aberrant Behavior Checklist and several scales of the Social Responsiveness Scale (SRS), whereas TT3 was associated with SRS subscales and TRH was related to Vineland Adaptive Behavior Scale subscales. The thyroid showed significant FRα expression during the early prenatal period, although expression decreased significantly in later gestation and postnatal thyroid tissue. The results of the present study suggest that thyroid dysfunction in ASD may be related to blocking FRAA. The high expression of FRα in the early foetal thyroid suggests that foetal and neonatal exposure to maternal FRAAs could affect the development of the thyroid and may contribute to the pathology in ASD.     

急性脑出血患者血清甲状腺激素水平的变化及其意义

目的探讨急性脑出血患者血清甲状腺激素水平的变化及其意义。方法 65例急性脑出血患者于入院第1 d、第3 d、第7 d、第15 d,52名正常对照者于体检日进行血清三碘甲状腺原氨酸(T3)、甲状腺素(T4)、游离T3(FT3)、游离T4(FT4)和促甲状腺激素(TSH)水平检测和比较。并对不同病情及预后的急性脑出血患者入院第3 d的血清甲状腺激素水平进行比较。结果与正常对照组比较,急性脑出血组入院第1 d、第3 d、第7 d时血清T3、FT3水平明显降低,血清T4、FT4水平明显增高(均P<0.05)。与急性脑出血轻度亚组比较,中度亚组及重度亚组血清T3、FT3水平明显降低,血清T4、FT4及TSH水平明显增高(均P<0.05);与急性脑出血中度亚组比较,重度亚组血清T3、FT3水平明显降低,血清T4、FT4及TSH水平明显增高(均P<0.05)。与急性脑出血显著进步亚组比较,进步亚组及死亡亚组血清T3、FT3水平明显降低,血清T4、FT4及TSH水平明显增高(均P<0.05);与急性脑出血进步亚组比较,死亡亚组血清T3、FT3水平明显降低,血清T4、FT4及TSH水平明显增高(均P<0.05)。结论急性脑出血...     

Thyrotropin-releasing hormone (TRH) in abstinent alcoholic men

Chronic alcoholics who had been abstinent from alcohol for more than 2 years were evaluated with the thyrotropin-releasing hormone (TRH) test. The findings suggest the following profound disturbances in the hypothalamic-pituitary-thyroid axis: 1) a "euthyroid sick syndrome," evidenced by low levels of triiodothyronine (T3), high levels of reverse T3, and normal levels of thyroxine (T4) (this syndrome implies a decreased 5'-deiodination of T4 to T3 and of reverse T3 to its lesser iodinated metabolites), 2) an increased binding capacity for thyroid hormones, evidenced by a decreased T3-uptake value and an increased level of T4-binding globulin, and 3) thyroid-stimulating hormone (TSH) blunting in 31% of patients. Paradoxically, there was a positive correlation between basal T4 and delta max TSH in subjects with blunted TSH, but baseline TSH levels were reduced in subjects with and without blunted TSH.     

甲状腺功能水平与双相情感障碍相关性的对照研究

目的 探索甲状腺功能与双相情感障碍的相关性.方法 以符合美国精神疾病分类与诊断标准第4版修订本(DSM-Ⅳ-TR)的双相情感障碍诊断标准的患者59例为研究对象,并选取41名健康人作为对照,应用酶联免疫吸附法(ELISA)分别测定所有研究对象的血清甲状腺激素水平,包括TT3、FT3、TT4、FT4及TSH.选用HAMD、HAMA及Bech-Rafaelsen躁狂量表评估患者组临床症状.结果 双相躁狂组中TT4、FT4水平明显高于对照组,FT3水平明显高于抑郁组,差异有统计学意义(P<0.01).双相抑郁组中TT3、FT3水平明显低于对照组,FT4水平则明显高于对照组,差异有统计学意义(P<0.01).按性别分层比较,女性双相躁狂组FT4水平与对照组相比明显升高,差异有统计学意义(P<0.05);女性双相抑郁组TT3明显低于对照组或双相躁狂组,FT4明显高于对照组,FT3则明显低于对照组,差异均有统计学意义(P<0.05),而男性躁狂组中仅TT4水平显著高于对照组(P<0.05).在双相抑郁患者中,HAMD总分与FT4呈负相关(r=-0.34,P=0.03).结论 双相情感障碍患者的甲状腺功能存在一定的改变,不同临床相甲状腺功能改变亦不相同,且这种变化以女性患者明显.     

Relationship between thyroid hormone levels and regional cerebral blood flow in Alzheimer disease

Subclinical thyroid disease and even variations in thyroid function within the normal range is associated with cognitive function and a risk of Alzheimer disease (AD). Several studies reported the effect of thyroid hormones on cerebral blood flow. The aim of this study was to objectively evaluate regional cerebral blood flow (rCBF) in association with thyroid hormone levels within the normal range in patients with AD. Serum thyroid-stimulating hormone (TSH), free T3, and free T4 levels were measured in 62 patients with AD (23 men and 39 women; age 56 to 91 y; mean age 77.3 y) and 27 control subjects (9 men and 18 women; age 61 to 93 y; mean age 75.8 y). The 99mTc ethylcysteinate dimer single photon emission computed tomography was performed in all subjects. The rCBF in the region of interest was measured by the noninvasive Patlak plot method and calculated using FineSRT, which is a fully automated region of interest technique. No significant correlation was found between thyroid hormone levels and Mini-Mental State Examination scores or global CBF values. Serum levels of TSH, but not free T3 or free T4, were significantly inversely correlated with rCBF in the middle and inferior temporal regions of right cerebral hemisphere in patients with AD. Control subjects showed no significant correlation between thyroid hormone levels and rCBF. Although these findings of a regional relationship must be considers preliminary, this study proposed the hypothesis that altered TSH levels within the normal range may be related to brain perfusion in right temporal region.     

首发精神分裂症患者的血清甲状腺相关激素水平变化及其与临床关系对照研究

目的探讨首发精神分裂症患者血清甲状腺相关激素（Ｔ３、Ｔ４、ＴＳＨ、ＦＴ３及ＦＴ４）水平的动态变化及其与临床关系。方法４１例患者分别于疗前、疗后进行ＢＰＲＳ评定及血清Ｔ３、Ｔ４、ＴＳＨ、ＦＴ３、ＦＴ４测定，并与正常对照组作比较。结果研究组疗前血清甲状腺素（Ｔ４）显著高于对照组，并随治疗及病情改善而恢复正常。但游离甲状腺素（ＦＴ４）在疗前、疗后均低于正常对照组。患者的ＢＰＲＳ得分高低与其疗前血清Ｔ３、Ｔ４水平显著正相关（Ｐ＜０．０５）。结论精神分裂症患者血清Ｔ４、ＦＴ４水平变化可能与其疾病本身有关。血清Ｔ３，Ｔ４水平似乎可预测精神分裂症的严重度。     

Influence of carbamazepine on serum thyroxine and triiodothyronine in patients with epilepsy

Hypothyroidism induced by anti-epileptic drug treatment gave rise to thyroid function test studies in patients treated with carbamazepine (CBZ) only. In 42 patients on long-term CBZ treatment thyroxine (T4), free T4-index (FT4I), and triiodothyronine (T3) concentrations in serum were significantly lower than in controls, while triiodothyronine uptake (T3U) and thyrotropin (TSH) concentrations did not differ between patients and controls. In 12 patients starting on CBZ, means T4, calculated FT4 and thyroxine binding globulin (TBG) were 1-5 months later reduced compared to the initial levels. Thus, CBZ reduced thyroid hormones, TBG and FT4I. A CBZ-induced increase in conversion and metabolism of the thyroid hormones could explain this effect. The normal T3U values and decreased concentrations of TBG make a competitive CBZ binding to TBG less probable. Although the thyroid hormones levels were found lowered in the patients, all remained clinically euthyroid during the study.