Effects of Altered Thyroid States on Myelinogenesis

Abstract: Myelinogenesis was studied in controls and in rats treated since birth with Methimazole (hypothyroid) or thyroxine (hyperthyroid). The amount of myelin in forebrain and its protein composition were determined between 13 and 40 days of age, the period of most rapid myelin accumulation. Hypothyroid rats had reduced body and brain weights relative to controls and the yield of myelin was reduced on both a per brain and a per milligram brain protein basis. Developmental changes in the protein composition of isolated myelin followed the pattern of control animals (the percentage of total myelin protein present as proteolipid protein, large basic protein, and small basic protein increased, as did the ratio of proteolipid/large basic protein) but were delayed temporally by 1–2 days. Hyperthyroid rats also had reduced body and brain weights. At 13 days myelin accumulation was greater than that of controls, corresponding to an earlier initiation of myelination. At later ages myelin yield was reduced on a per brain basis but not on a per milligram brain protein basis. The developmental pattern of myelin protein composition was accelerated temporally by 1–2 days. Myelination in optic nerve, assayed by proteolipid protein content, also was slightly delayed in hypothyroid animals and somewhat accelerated in hyperthyroid animals. The relative synthesis of myelin proteins (determined as incorporation of intracranially injected [³H]glycine into myelin protein relative to incorporation into whole brain protein), as well as distribution of radioactivity among individual myelin proteins, was determined. The results supported the conclusion of the myelin protein accumulation study; hypothyroidism retards the developmental program for myelinogenesis, whereas in the hyperthyroid state myelin synthesis is initiated earlier but is also terminated earlier.     

Potentiation of humoral immune response and activation of NF-kappaB pathway in lymphocytes in experimentally induced hyperthyroid rats

This study explored the effect of hyperthyroid state on humoral immune response and NF-kappaB signaling in lymphocytes. Male Wistar rats were treated with l-thyroxin for four weeks. Animals were immunized with sheep red blood cells (SRBC) after three weeks of l-thyroxin treatment. After one week of immunization, serum anti-SRBC titer was measured and NF-kappaB signaling was studied in lymphocytes by Western blot analysis of p-IKB-alpha, IKB-alpha, and p65. These results were compared with that of control rats. Antibody response and density of p-IKB-alpha and p65 were significantly higher in l-thyroxin treated rats in comparison to controls. The antibody response was found to have significant correlation with density of p-IKB-alpha and p65. Our results indicate that NF-kappaB signaling pathway in lymphocytes is activated in hyperthyroid state which might play a role in potentiation of antibody response.     

甲状腺功能亢进性心脏病患者血清BNP及CRP水平及其与心功能的关系

目的:研究甲亢性心脏病患者血清BNP(B-type natriuretic peptide)与CRP(C-reaction protein)水平及其与心功能的关系。方法:选择2015年10月至2017年3月在我院进行治疗的甲亢性心脏病患者68例作为观察组,同期选择在我院进行常规体检的健康者35例作为对照组。采用免疫放射法检测血清BNP水平,免疫比浊法检测血清CRP水平。比较两组血清BNP、CRP水平的差异及不同心功能甲亢性心脏病患者血清BNP、CRP水平,分析血清BNP、CRP水平与甲亢性心脏病患者心功能的相关性。结果:观察组血清BNP、CRP水平明显高于对照组,差异具有统计学意义(P0.05);观察组心功能Ⅱ级患者血清BNP、CRP水平明显高于心功能Ⅰ级患者(P0.05);心功能Ⅲ级患者血清BNP、CRP水平明显高于心功能Ⅱ级患者(P0.05);心功能Ⅳ级患者血清BNP、CRP水平明显高于心功能Ⅲ级患者(P0.05);观察组治疗后血清BNP、CRP水平较治疗前显著降低,差异具有统计学意义(P0.05)。甲状性功能亢进性心脏病患者血清BNP、CRP水平均与其心功能等级呈显著正相关(r=0.742,P=0.037;r=0.857,P=0.011)。结论:甲亢性心脏病患者血清BNP与CRP水平均显著升高,可能用于甲亢并发甲亢性心脏病的早期诊断及心功能评估的重要参考指标。     

甲状腺功能亢进性心脏病临床特点及相关危险因素分析

目的:探讨甲状腺功能亢进性心脏病的临床特点及相关危险因素.方法:选取2008年9月至2011年9月收治112例甲状腺功能亢进患者为单纯甲亢组,另选取同期的甲状腺功能亢进性心脏病61例为甲心组.对两组患者性别、年龄、病程、FT3和FT4 进行比较,并采用Logistic回归方法对其危险因素进行分析.结果:①甲心组患者年龄较大,病程较长,FT3和FT4水平较高,与单纯甲亢组比较差异有统计学意义(P＜0.05).②经Logistic回归分析,患者的年龄大、病程长及FT4水平较高为甲状腺功能亢进性心脏病发生的危险因素.结论:对于年龄大、病程长、病情重的甲状腺功能亢进患者应予以充分重视,临床医生应予积极治疗,减少甲状腺功能亢进性心脏病的发病率和死亡率.     

Long-Term Follow-up of Graves Orbitopathy After Treatment With Short- or Long-Term Methimazole or Radioactive Iodine

ObjectiveThe aim of this study was to compare long-term outcomes in terms of new onset or worsening of Graves orbitopathy (GO) in patients with Graves disease treated with different therapeutic modalities for hyperthyroidism.MethodsA total of 1163 patients with Graves disease were enrolled in this study; 263 patients were treated with radioiodine and 808 patients received methimazole (MMI) therapy for a median of 18 months, of whom 178 patients continued MMI for a total of 96 months (long-term methimazole [LT-MMI]). The thyroid hormonal status and GO were evaluated regularly for a median of 159 months since enrollment.ResultsThe rates of relapse, euthyroidism, and hypothyroidism at the end of follow-up were as follows: radioiodine treatment group: 16%, 22%, and 62%, respectively; short-term MMI group: 59%, 36%, and 5%, respectively; and LT-MMI group: 18%, 80%, and 2%, respectively. During the first 18 months of therapy, worsening of GO (11.5% vs 5.7%) and de novo development of GO (12.5% vs 9.8%) were significantly more frequent after radioiodine treatment (P <.004). Overall worsening and de novo development of GO from >18 to 234 months occurred in 26 (9.9%) patients in the radioiodine group and 8 (4.5%) patients in the LT-MMI group (P <.037). No case of worsening or new onset of GO was observed in patients treated with LT-MMI from >60 to 234 months of follow-up.ConclusionProgression and development of GO were associated more with radioiodine treatment than with MMI treatment; GO may appear de novo or worsen years after radioiodine treatment but not after LT-MMI therapy.     

Time to Normalization and Sustainable Normal Serum Thyrotropin Concentrations in Patients with Hyperthyroidism: Comparison of Methimazole and Radioactive Iodine Treatments

ObjectiveThe aim of this study was to compare the “time to euthyroidism” and “time spent in euthyroidism” following methimazole (MMI) and radioactive iodine (RAI) treatments.MethodsThree hundred fifty-eight patients with hyperthyroidism, 178 who underwent long-term MMI treatment and 180 patients who underwent RAI treatment, were analyzed. The time to normalization of increased serum values of free thyroxine and triiodothyronine and suppressed serum thyroid-stimulating hormone (TSH) values as well as the percentage of time that the thyroid hormone levels remained within normal ranges during a mean follow-up time of 12 years were compared.ResultsThe mean time to euthyroidism was 4.59 ± 2.63 months (range, 2-16 months) in the MMI group and 15.39 ± 12.11 months (range, 2-61 months) in the RAI group (P < .001). During follow-up, the percentage of time spent in euthyroidism was 94.5% ± 7.3% and 82.5% + 11.0% in the MMI and RAI groups, respectively (P < .001). Serum TSH values above and below the normal range were observed in 5.3% and 0.2% of patients, respectively, in the MMI group and 9.8% and 7.7% of patients, respectively, in the RAI group (P < .001). The time to euthyroidism and the percentage of time spent in euthyroidism in 40 RAI-treated patients with euthyroidism were similar to those in the MMI group and significantly shorter than those in the RAI-treated hypothyroid and relapsed subgroups. In patients who continued MMI therapy for >10 years, the percentage of time spent in euthyroidism was >99%.ConclusionIn our cohort of selected patients, MMI therapy was accompanied by faster achievement of the euthyroid state and more sustained normal serum TSH levels during long-term follow-up compared with RAI therapy.