丙基硫氧嘧啶致肺血管炎1例报告及讨论

血管炎是丙基硫氧嘧啶的一种少见的药物不良反应，常累及皮肤和肾脏，肺部合并症罕见。本文报道的一例丙基硫氧嘧啶所致的抗中性粒细胞胞浆抗体(ANCA)阳性血管炎患者却仅有肺部受累表现，并在病程中出现呼吸衰竭。作者对其进行了纤维支气管镜及支气管透壁肺活检等检查。该例患者血中和支气管肺泡灌洗液中均检测到ANCA阳性，且非常见抗原类型，作者又对其抗原特异性进一步进行了分析。经停药并加用糖皮质激素治疗后，该患者症状完全消失。     

丙基硫氧嘧啶致粒细胞减少症64例临床分析

目的 了解丙基硫氧嘧啶（PTU）致粒细胞减少症的发病情况、临床表现及治疗对策。方法 对近2年门诊有完整记录的64例PTU致粒细胞减少症的临床特征及治疗情况进行统计分析。结果 粒细胞减少症多数发生在服药后2～8周，且与PTU的剂量有关。多数病例有头昏、乏力的临床症状。全部病例继续使用PTU，加用口服升白药或皮下注射粒细胞集落刺激因子（G-CSF），粒细胞均恢复正常，无1例发生粒细胞缺乏症。结论 PTU起始剂量不宜超过300mg／d，使用头1、2个月内应密切观察外周血白细胞计数，口服升白药或注射G-CSF对白细胞恢复是有效的，并可避免粒细胞缺乏症的发生。     

Effect of hyperthyroidism and propylthiouracil treatment on liver biochemical tests

Liver biochemical test (LBT) changes can be commonly observed in hyperthyroid patients. Those kinds of changes could also be observed because of propylthiouracil (PTU) therapy. We prospectively evaluated LBT changes because of PTU use for 1 year in patients who had been diagnosed with hyperthyroidism first. We studied 64 patients who had been diagnosed with hyperthyroidism. These patients took at least 1-year PTU treatment. We analysed LBT at diagnosis and after 2 and 12 months of treatment with PTU. Prior to PTU treatment, 30 (46.8%) of the 64 patients had at least one LBT abnormality. We observed at least one LBT abnormality in 11 (32%) patients after 2 months and nine (26%) patients after 12 months of treatment with PTU in 34 patients whose CBT were normal before treatment. We did not observe any deterioration in clinical picture and bilirubin levels. Elevated serum LBT during the pretreatment and PTU treatment period is common and usually transient and asymptomatic. PTU could be used for long times by lowering the dose and close follow-up in patients who have elevated LBT during the pretreatment and after PTU treatment period.     

Effects of thyroid state on serotonin, 5-hydroxyindoleacetic acid and substance P contents in discrete brain nuclei of adult rats

The effects of chemical thyroidectomy produced by propylthiouracil treatment or hyperthyroidism produced by daily injections of thyroxine on the content of serotonin, its metabolite 5-hydroxyindoleacetic acid and of substance P in discrete brain nuclei of adult rats have been studied. Brain nuclei were removed by punches of frozen brain slices. The serotonin and 5-hydroxyindoleacetic acid contents were measured by high performance liquid chromatography with electrochemical detection while substance P was assayed by radioimmunoassay. The serotonin level was significantly increased in 11 nuclei of the hypothyroid and in 12 nuclei of the hyperthyroid rats. The 5-hydroxyindoleacetic acid levels were higher in 16 nuclei of the hypothyroid and 7 nuclei of the hyperthyroid animals. The state of the thyroid gland in adult rats also affected the substance P system but less consistently than the serotonin pathway. Thus, the substance P content in the brain of propylthiouracil-treated animals increased significantly in 4 nuclei while it decreased in the septum lateralis and the striae terminalis. Following the chronic thyroxine injections, the substance P level was increased in the nucleus caudatus putamen and the tractus diagonalis and was decreased in the area ventralis tegmenti. We previously reported that neonatal thyroidectomy caused a general increase of the substance P and serotonin contents in many brain nuclei of young rats.

It appears that the effects of chemical thyroidectomy on mature and immature rat brain are different for the substance P system, suggesting that thyroxine plays an important role in the maturation of substance P-containing neurons.     

Uptake,metabolism and action of triiodothyronine in calf-thyroid slices

T₃ and T₄ at 10^?6M caused a significant inhibition on [³H]uridine incorporation into RNA in calf-thyroid slices. This effect was not altered by addition of 10^?3M PTU or MMI. The metabolism of ¹²⁵I-T₃ was studied under the same conditions. There was a very slight dehalogenation after 60 min (less than 5%) which was inhibited by PTU.The time course of the uptake of labeled T₃ showed a temperature dependence, and this uptake was not altered by 10^?6M KI, 1-T₄, DIT or MIT, thus indicating specificity. The early phase of labeled T₃ entrance into the cell was inhibited by the addition of cold T₃ in a dose-dependent manner from 10^?9 to 10^?5M. Slices previously stimulated by cAMP or cGMP showed a significant increase in the uptake of labeled T₃. ATPase activity or ATP, protein or RNA synthesis does not seem to play a role in this process.The relationship between substitutions in the thyronine molecule and its biological action on RNA synthesis was also studied, and some preliminary conclusions were drawn.These studies demonstrate that T₃ has a direct action on the thyroid.     

The effects of postnatal hyper- and hypothyroidism on the development of D-amino acid oxidase in rat cerebellum and brain stem.

Treatment of rats with propylthiouracil for the first 30 days of postnatal life drastically retards the ontogenesis of D-amino acid oxidase in the brain stem and cerebellum. There is a marked terminal deficit of D-AAO in both the brain stem (--64%) and cerebellum (--67%) at 94 days (adults) despite the near euthyroid status at this age. If initiated early enough, thyroxine replacement therapy reverses the effects of PTU on the development of D-AAO. Hyperthyroidism significantly accelerates the development of D-AAO in both brain stem and cerebellum. Nonetheless, animals treated with thyroxine the first month of life display a net deficit of cerebellar D-AAO content in adulthood. The results are discussed in terms of the localization of D-AAO in cell types especially sensitive to thyroid hormone: (1) a cell type which is among the last to derive from the external germinal zone in the developing cerebellum, and which in the adult is located adjacent to the Purkinje cell soma; and (2) mossy fiber neurons and cerebellar glomeruli.     

A role for luteinizing hormone and follicle-stimulating hormone in the etiology of simple goiters in the pediatric population

In light of the progressive, pubertal increases in serum gonadotropin (FSH, LH) levels coinciding with the peak incidence of simple goiters; the common alpha subunits associated with the gonadotropins, TSH and hCG; the ability of LH and hCG to bind to thyroid TSH receptors and affect thyroid function; and, the probable interactions between thyroid hormones and gonadotropins, a role for gonadotropins in the etiology of simple goiters merits consideration.     

Neurofilaments in Thyrotrophs of Hypothyroid Rats: An Immunohistochemical Study

We examined by immunohistochemistry the expression of 200-kDa (NF-H) neurofilaments in pituitary thyrotrophs of rats, made hypothyroid by propylthiouracil (PTU) administration. Rats were sacrificed at 3, 7, 14, and 28 d of PTU administration as well as at 3, 7, and 14 d after interruption of a 14-d PTU treatment. The pituitaries were fixed, dehydrated, and embedded in paraffin. Consecutive sections were prepared for the immunohistochemical demonstration of thyroid-stimulating hormone and NF-H. NF-H were found in some thyrotrophs of the adenohypophysis of control rats. NF-H were expressed in thyroidectomy cells of hypothyroid rats. Discontinuation of PTU treatment led to recovery from cytologic alterations in the thyroidectomy cells expressing NF-H.