摘要
BACKGROUND: It has been demonstrated that traditional antiepileptics, such as phenytoin, carbamazepine (CBZ), phenobarbital, etc., can result in the decrease of thyroid hormone of epileptic patients. However, there is still no sufficient evidence for the studies about the effect of new-type antiepileptics, such as topiramate (TPM), on thyroid hormones. OBJECTIVE: To observe the effects of TPM and CBZ on the level of thyroid hormones in serum of adults with epilepsy. DESIGN: A comparative observation. SETTING: Department of Neurology, Sichuan Provincial People's Hospital. PARTICIPANTS: Totally 100 outpatients or inpatients newly diagnosed to have epilepsy were selected from the Department of Neurology, Sichuan Provincial People's Hospital from July 2003 to August 2005, including 60 males and 40 females, aged 18-70 years. All the patients were accorded with the standard for the classification of epilepsy set by International League Against Epilepsy (ILAE) in 1981; Had been Informed and agreed with the detection; Had no history of thyroid gland disease; Had not taken any drugs could affect the thyroid function. Meanwhile, 40 adult healthy examinees were selected from our hospital as the control group, including 24 males and 16 females, aged 18-65 years. METHODS: ① The 100 epileptic patients were randomly divided into TPM group (n =50) and CBZ group (n =50), and they were treated with TPM (Xian-Janssen Pharmaceutical, Ltd.; Batch number: 03AS032, Norm: 25 mg/tablet) and CBZ (Shanghai Sunve Pharmaceutical Co., Ltd.; Batch number: 030201, Norm: 100 mg/tablet) respectively. The initial dosage of TPM was 25 mg per day, increased by 25 mg every week, the objective dosage of 100-200 mg per day was maintained when the symptoms were satisfactorily controlled. The dosage of CBZ was 6-8 mg/kg per day. All the patients were administrated for 1 year. ② The serum levels of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3) and thyroid stimulating hormone (TSH) in the epileptic patients were detected by means of chemiluminescence before treatment and at 3, 6 and 12 months after treatment respectively. ③Standards for judging curative effects: Controlled by without seizure, the frequency of seizure reduced by ≥ 75% was taken as significant effect, reduced by 50%-74% as effect, and reduced by < 49% as invalid, whereas increased by more than 20% was taken as aggravation. ④ The intergroup and intragroup differences of the measurement data were compared by the analysis of variance and paired t test respectively. MAIN OUTCOME MEASURES: Serum levels of thyroid hormones before treatment and at different time points after treatment of TPM and CBZ. RESULTS: All the 100 epileptic patients and 40 healthy subjects were involved in the analysis of results. ① Changes of serum levels of thyroid hormones: The serum levels of TT3, TT4, FT3, FT4 and TSH were close between the epileptic patients and normal subjects before treatment (P > 0.05). In the CBZ group, the serum levels of FT4 at 3, 6 and 12 months after treatment [(16.87±3.77), (16.34±3.98) , (16.97±3.95) pmol/L] were significantly decreased as compared with those before treatment [(18.00±3.54) pmol/L, t =2.74, 3.50, 2.26, P < 0.05]; The levels of TT3 at 3, 6 and 12 months [(2.09±0.54), (1.99±0.49), (1.84±0.47) nmol/L] were significantly decreased as compared with those before treatment [(2.22±0.63) nmol/L, t =2.73, 2.78, 5.18, P < 0.05]. The levels of TT3 at 6 and 12 months [(109.65±23.98), (107.72±23.90) nmol/L] were significantly decreased as compared with those before treatment [(118.98±28.48) nmol/L, t =3.11, 3.30, P < 0.05]. TT4 level in serum at 3 months and the levels of FT3 and TSH at each time point after CBZ treatment had no obvious changes as compared with those before treatment (P > 0.05). In the TPM group, the levels of thyroid hormones at each time point had no obvious changes as compared with those before treatment (P > 0.05). ② Curative effects: Of the 100 epileptic patients, it was controlled in 12 cases, significantly effective in 30 cases, effective in 39 cases and invalid in 19 cases, the total effective rate was 81% (81/100). CONCLUSION: CBZ treatment can lead to the decreases of thyroid hormones in adult epileptic patients. Epilepsy itself and TPM treatment cannot change the thyroid hormones in adult epileptic patients, which suggests that TPM treatment is safer for the thyroid function of adult epileptic patients.
BACKGROUND: It has been demonstrated that traditional antiepileptics, such as phenytoin, carbamazepine (CBZ), phenobarbital, etc., can result in the decrease of thyroid hormone of epileptic patients. However, there is still no sufficient evidence for the studies about the effect of new-type antiepileptics, such as topiramate (TPM), on thyroid hormones. OBJECTIVE: To observe the effects of TPM and CBZ on the level of thyroid hormones in serum of adults with epilepsy. DESIGN: A comparative observation. SETTING: Department of Neurology, Sichuan Provincial People's Hospital. PARTICIPANTS: Totally 100 outpatients or inpatients newly diagnosed to have epilepsy were selected from the Department of Neurology, Sichuan Provincial People's Hospital from July 2003 to August 2005, including 60 males and 40 females, aged 18-70 years. All the patients were accorded with the standard for the classification of epilepsy set by International League Against Epilepsy (ILAE) in 1981; Had been Informed and agreed with the detection; Had no history of thyroid gland disease; Had not taken any drugs could affect the thyroid function. Meanwhile, 40 adult healthy examinees were selected from our hospital as the control group, including 24 males and 16 females, aged 18-65 years. METHODS: ① The 100 epileptic patients were randomly divided into TPM group (n =50) and CBZ group (n =50), and they were treated with TPM (Xian-Janssen Pharmaceutical, Ltd.; Batch number: 03AS032, Norm: 25 mg/tablet) and CBZ (Shanghai Sunve Pharmaceutical Co., Ltd.; Batch number: 030201, Norm: 100 mg/tablet) respectively. The initial dosage of TPM was 25 mg per day, increased by 25 mg every week, the objective dosage of 100-200 mg per day was maintained when the symptoms were satisfactorily controlled. The dosage of CBZ was 6-8 mg/kg per day. All the patients were administrated for 1 year. ② The serum levels of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3) and thyroid stimulating hormone (TSH) in the epileptic patients were detected by means of chemiluminescence before treatment and at 3, 6 and 12 months after treatment respectively. ③Standards for judging curative effects: Controlled by without seizure, the frequency of seizure reduced by ≥ 75% was taken as significant effect, reduced by 50%-74% as effect, and reduced by < 49% as invalid, whereas increased by more than 20% was taken as aggravation. ④ The intergroup and intragroup differences of the measurement data were compared by the analysis of variance and paired t test respectively. MAIN OUTCOME MEASURES: Serum levels of thyroid hormones before treatment and at different time points after treatment of TPM and CBZ. RESULTS: All the 100 epileptic patients and 40 healthy subjects were involved in the analysis of results. ① Changes of serum levels of thyroid hormones: The serum levels of TT3, TT4, FT3, FT4 and TSH were close between the epileptic patients and normal subjects before treatment (P > 0.05). In the CBZ group, the serum levels of FT4 at 3, 6 and 12 months after treatment [(16.87±3.77), (16.34±3.98) , (16.97±3.95) pmol/L] were significantly decreased as compared with those before treatment [(18.00±3.54) pmol/L, t =2.74, 3.50, 2.26, P < 0.05]; The levels of TT3 at 3, 6 and 12 months [(2.09±0.54), (1.99±0.49), (1.84±0.47) nmol/L] were significantly decreased as compared with those before treatment [(2.22±0.63) nmol/L, t =2.73, 2.78, 5.18, P < 0.05]. The levels of TT3 at 6 and 12 months [(109.65±23.98), (107.72±23.90) nmol/L] were significantly decreased as compared with those before treatment [(118.98±28.48) nmol/L, t =3.11, 3.30, P < 0.05]. TT4 level in serum at 3 months and the levels of FT3 and TSH at each time point after CBZ treatment had no obvious changes as compared with those before treatment (P > 0.05). In the TPM group, the levels of thyroid hormones at each time point had no obvious changes as compared with those before treatment (P > 0.05). ② Curative effects: Of the 100 epileptic patients, it was controlled in 12 cases, significantly effective in 30 cases, effective in 39 cases and invalid in 19 cases, the total effective rate was 81% (81/100). CONCLUSION: CBZ treatment can lead to the decreases of thyroid hormones in adult epileptic patients. Epilepsy itself and TPM treatment cannot change the thyroid hormones in adult epileptic patients, which suggests that TPM treatment is safer for the thyroid function of adult epileptic patients.