Circulating soluble interleukin 2 receptor concentration is increased in both immunogenic and nonimmunogenic hyperthyroidism.

High serum concentration of soluble interleukin-2 receptor (sIL-2R) is considered a reliable marker of T lymphocyte activation. It has been recently reported that sIL-2R levels are increased in untreated Graves' disease. This finding has been interpreted as the consequence of an active autoimmune state, but the relevance of the thyroid function per se was not investigated. In the present study we assayed sIL-2R by ELISA in 20 normal subjects and in a series of patients with immunogenic (Graves' disease, GD) or nonimmunogenic (toxic adenoma, TA) hyperthyroidism. Significant increased concentrations of sIL-2R were found in 46 patients with untreated hyperthyroid GD (mean +/- SD: 1,683 +/- 1016 U/ml, vs 461 +/- 186 U/ml in normal controls, p less than 0.0001) and in 21 with untreated TA (1,111 +/- 617 U/ml, p less than 0.0001 vs normals). Restoration of the euthyroid state by antithyroid drugs or 131I administration was associated with a normalization of sIL-2R (516 +/- 174 U/ml in 38 patients with GD and 365 +/- 90 U/ml in 12 with TA; p = NS vs normals and p less than 0.001 vs the untreated state for both groups). A highly significant positive correlation between serum sIL-2R and free triiodothyronine (FT3) (r = 0.724, p less than 0.0001) or free thyroxine (FT4) (r = 0.698, p less than 0.0001) concentrations was found in combined sera obtained from all untreated and treated patients, irrespectively of the autoimmune or nonautoimmune nature of the underlying hyperthyroid disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunological features of kala-azar.

Serum immunoglobulins, complement C3c, percentage of T and B cells, and skin reactivity to Leishmania were studied in ten cases of kala-azar. Immunoglobulin G was increased in a majority of these patients. The C3c level in two out of six patients tested was lower than normal. The percentage of T cells in peripheral blood of nine patients tested was reduced and in seven of these patients the percentage of B cells was elevated. After a full course of anti-kala-azar therapy the percentage of T and B cells remained the same in five patients studied. All the patients showed a negative skin reaction when they were tested with Leishmania antigen.     

糖皮质激素抵抗型哮喘的免疫学研究

目的探讨糖皮质激素抵抗型（ＳＲ）哮喘的发生机制及治疗对策。方法检测ＳＲ哮喘及糖皮质激素敏感性（ＳＳ），哮喘患者经强的松（２０ｍｇ／ｄ）治疗前后血清可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）水平的变化，用体外淋巴细胞增殖试验观察地塞米松、氧化苦参碱和胸腺免疫抑制物对外周血Ｔ细胞增殖的抑制作用。结果强的松治疗后，ＳＳ哮喘患者的血清ｓＩＬ－２Ｒ水平显著降低（Ｐ＜０．００１），但ＳＲ哮喘患者的ｓＩＬ－２Ｒ水平无明显变化（Ｐ＞０．５）。地塞米松（１０－７ｍｏｌ／Ｌ）对ＳＲ哮喘患者Ｔ细胞增殖的抑制作用显著低于ＳＳ哮喘患者（Ｐ＜０．００２），但氧化苦参碱和胸腺免疫抑制物对Ｔ细胞增殖的抑制作用在两组患者之间差异无显著性。结论Ｔ细胞对糖皮质激素的反应性降低以及由此引起的Ｔ细胞持续活化是ＳＲ哮喘的免疫学特征。糖皮质激素以外的免疫抑制剂在ＳＲ哮喘治疗中的意义值得进一步探讨。     

Subclinical hyperthyroidism: clinical features and treatment options

Subclinical hyperthyroidism appears to be a common disorder. It may be caused by exogenous or endogenous factors: excessive TSH suppressive therapy with L-thyroxine (L-T4) for benign thyroid nodular disease, differentiated thyroid cancer, or hormone over-replacement in patients with hypothyroidism are the most frequent causes. Consistent evidence indicates that 'subclinical' hyperthyroidism reduces the quality of life, affecting both the psycho and somatic components of well-being, and produces relevant signs and symptoms of excessive thyroid hormone action, often mimicking adrenergic overactivity. Subclinical hyperthyroidism exerts many significant effects on the cardiovascular system; it is usually associated with a higher heart rate and a higher risk of supraventricular arrhythmias, and with an increased left ventricular mass, often accompanied by an impaired diastolic function and sometimes by a reduced systolic performance on effort and decreased exercise tolerance. It is well known that these abnormalities usually precede the onset of a more severe cardiovascular disease, thus potentially contributing to the increased cardiovascular morbidity and mortality observed in these patients. In addition, it is becoming increasingly apparent that subclinical hyperthyroidism may accelerate the development of osteoporosis and hence increased bone vulnerability to trauma, particularly in postmenopausal women with a pre-existing predisposition. Subclinical hyperthyroidism and its related clinical manifestations are reversible and may be prevented by timely treatment.     

老年人甲亢性肝损害临床特点分析

原发性甲状腺功能亢进症并发肝脏功能损害(简称:甲亢性肝损害,HLI)临床上并不少见,而老年HLI患者由于症状多不典型,尤其在并发症表现较突出时易造成漏诊、误诊。我们回顾分析26例确诊的老年HLI患者的住院病史资料,对其发病特点、临床相关因素、防治策略进行总结,现将结果报道如     

Severe hyperthyroidism: aetiology,clinical features and treatment outcome

Background Severe hyperthyroidism (SH) is a serious medical disorder that can compromise life. There have not been systematic studies in which SH has been evaluated in detail. Here, our aims were: (1) to analyse both clinical and analytical features and outcome in patients with SH and (2) to compare these data with those found in more usual forms of hyperthyroidism. Patients and methods All patients diagnosed of SH (free thyroxine, FT4 > 100 pmol/l, NR: 11–23) seen in our endocrinology clinic in the last 15 years were studied and compared with a sample of patients with mild (mH; FT4, 23–50 pmol/l) and moderate (MH; FT4, 51–100 pmol/l) hyperthyroidism. Aetiology, clinical analytical and imaging data at diagnosis, therapeutic response and outcome were registered. Results A total of 107 patients with overt hyperthyroidism (81 females, mean age ± SD 46·9 ± 16·1 years) were evaluated. We studied a historic group with SH (n = 21; 14 females, 40·9 ± 17·2 years) and, as a comparator group, we analyszed the data of 86 hyperthyroid patients (67 females, 48·4 ± 15·5·6 years, NS) comparable in age and gender. The comparator group was classified in MH (n = 37, 26 females, 47·2 ± 16·6 years) and mH (n = 49, 41 females, 49·4 ± 14·8 years). In comparison with mH group, SH patients were significantly (P < 0·05) younger and showed a greater proportion of first episode of thyroid hyperfunction (P < 0·05). Graves’ disease was the main aetiology in the three groups, but patients with SH showed the highest titre of TSH‐receptor antibodies (TRAb) (P < 0·001). Heart rate and size of goitre were higher in SH group than in mH and MH groups (P < 0·01). Atrial fibrillation was more frequently reported in SH group than in MH and mH groups (15·8%vs. 5·4% and 0%, respectively, P < 0·05). Results from logistic regression analysis showed that younger age [OR 0·958 (95% CI, 0·923–0·995), P = 0·026], presence of asthenia [OR 4·35 (1·48–12·78), P = 0·008] and higher heart rate [OR 1·03 (1·01–1·06), P = 0·013] were independent clinical variables associated to SH. SH patients showed similar biochemical parameters in comparison with mH group, except for increased serum aspartate aminotransferase (AST) (P < 0·01) and calcium (P < 0·05) levels, and decreased serum cholesterol (P < 0·05) and albumin (P < 0·05) concentrations. Logistic regression analysis showed that only AST [OR 1·07 (1·02–1·11), P = 0·005] was an independent biochemical variable associated to SH. No differences in the type of therapy, cure rate and time in achieving cure were found in SH subjects in relation to patients with milder forms of hyperthyroidism. FT4 was the only independent predictor of cure [OR 0·98 (CI 95%, 0·97–0·99), P < 0·05]. Conclusions Graves’ disease is the most common aetiology in patients with SH. This type of hyperthyroidism is usually de novo and is accompanied by more clinical signs, symptoms, and analytical derangements, as well as higher titres of TRAb at diagnosis than milder forms of hyperthyroidism. The present data are not able to show differences in treatment modality, time to achieve cure, and remission rate among patients with mild, moderate and severe hyperthyroidism.     

Immunological features of fibrodysplasia ossificans progressiva and the dysregulated BMP4 pathway

Dysregulation of the bone morphogenic protein (BMP)4-signaling pathway can explain many developmental and postnatal features of fibrodysplasia ossificans progressive (FOP). However, many puzzling clinical features of the disease strongly implicate an underlying immunological component to the disorder. In this article, we review features of the BMP4 signaling pathway that regulate the immune system, and suggest an integrated hypothesis for FOP that accounts for both BMP-related abnormalities and immunological features of the condition.     

Acute lymphoblastic leukaemia in adults: Immunological subtypes and clinical features at presentation

Summary In 91 of 106 adult patients with acute lymphoblastic leukemia (ALL) enrolled in the treatment protocol ALL HOVON-5 between May 1988 and October 1991, the immunophenotype of the leukemia was determined and correlated with clinical characteristics at presentation. The immunological marker analysis was performed in ten laboratories, all members of the Dutch Study Group on Immunophenotyping of Leukemias and Lymphomas (SIHON). Undifferentiated blasts were found in four patients, 67 had B-lineage ALL, 18 had T-lineage ALL, and two had biphenotypic ALL. The age of T-lineage ALL patients was lower (mean 29.3) than that of B-lineage ALL patients (mean 35.5). Tumor mass, as expressed by leukocyte count, organomegaly, and LDH, was more pronounced in T-lineage ALL. Hemoglobin and platelet count was similar in all (sub)types. CD34 was expressed in 58% of the leukemias, but most frequently in the common B-ALL (70%). Thirteen percent of the leukemias expressed one or more markers not associated with their lineage. In this prospective study immunological data were not evaluable for 15 patients. On four of them data were not available because of dry tap, for six patients the typing was technically insufficient, and for four patients the results were unclassifiable; with one patient the marker analysis was not performed.The following persons participated in the immunophenotyping studies:E. van der Schoot, Central Laboratory Red Cross Blood Transfusion Service, Amsterdam;A. E. G. Kr. von dem Borne, Acad. Medical Center, Amsterdam; J.J.M. Hoffmann, Catharina Hospital, Eindhoven; P. Wijermans, Leyenburgh Hospital, The Hague; J. Mulder, Regional Immunologic Lab., Leeuwarden; J. C. Kluin-Nelemans, University Hospital, Leiden; D. J. van Rheenen, University Hospital Annadal, Maastricht; H. J. Adriaansen, Erasmus Univ., Rotterdam; M. B. van't Veer, Dr. Daniel den Hoed Cancer Center, Rotterdam; H. Lokhorst, University Hospital, Utrecht; The Netherlands.     

Prevalence of incidental thyroid cancer and its ultrasonographic features in subcentimeter thyroid nodules of patients with hyperthyroidism

In patients, who undergo surgery for hyperthyroidism, many cases of incidental thyroid cancer (ITC) have been detected. In the literature, there is no study about ITC in subcentimeter nodules in these patients. We performed this study to determine the frequency of ITC in subcentimeter nodules and ultrasonographic features that can predict malignancy in the patients with hyperthyroidism. We retrospectively reviewed our database about 3114 patients, who underwent thyroidectomy in our hospital. Among 869 patients (27.9%), who were operated because of hyperthyroidism, we enrolled 337 patients, who underwent total thyroidectomy and had subcentimeter nodule [59 Graves’ disease (GD) 98 subcentimeter nodule; 278 toxic multinodular goitre (TMNG), 359 subcentimeter nodule], in this study. Twenty-five nodules with ITC and 432 benign nodules have been detected and compared for ultrasonographic (US) features. Incidental thyroid cancer detection ratio was 5.4% [10.2% (10/98) in subcentimeter thyroid nodules in individuals with GD, and 4.1% (15/359) in individuals with TMNG, P = 0.018)]. Significant differences have been observed between the groups in terms of microcalcification in US examination of malign and benign subcentimeter thyroid nodules and the ratio of anterioposterior diameter to transverse diameter (A/T) ≥1 [(OR = 5.172; 95% CI: 1.495–17.886, P = 0.015), and (OR = 5.930; 95% CI: 1.531–22.971, P = 0.007), respectively]. We detected a higher incidence of ITC in subcentimeter thyroid nodules in GD compared to TMNG. US examination of subcentimeter nodules in hyperthyroid individuals has indicated that microcalcification and ratio of A/T ≥1 are the parameters that predict malignancy.     

甲状腺功能亢进症的治疗

甲状腺毒症(thyrotoxicosis)是指血循环中甲状腺激素过多,引起以神经、循环、消化等系统兴奋性增高和代谢亢进为主要表现的一组临床综合征。其中由于甲状腺腺体本身功能亢进,合成和分泌甲状     

Therapy of hyperthyroidism

The symptoms called hyperthyroidosis are caused by a thyroid hormone intoxication, which may have various causes. More than 95% of the hyperthyroidosis are caused by an autoimmune thyropathy (Basedow's disease) or autonomy (autonomous adenoma, disseminated autonomy). Other causes are rare. The therapy has 2 aims: the normalisation of the supply of the thyroid hormone and the removal or influence of the cause. Thus apart from an exact functional diagnostics the etiopathogenetic coordination must be done which has an essential influence on the differential-therapeutic decision. Beside the general therapeutic measures the thyrostatic long-term therapy, the subtotal thyroid resection and the radioiodine therapy are at our disposal. Diagnosis, performance, advantages and disadvantages are demonstrated.