Evidence that antithyroid drugs induce remissions in Graves' disease by modulating thyroid cellular activity.
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Antithyroid Agents↗
Biomedical subjects
R Jansson
Publications and source records attributed to R Jansson.
Subacute thyroiditis: activated HLA-DR and interferon-gamma expressing T cytotoxic/suppressor cells in thyroid tissue and peripheral blood.
Using a two-colour direct immunofluorescence staining technique, we investigated activated HLA-DR-expressing T helper and T cytotoxic/suppressor cells in peripheral blood of six patients with subacute thyroiditis at referral and at follow-up and in blood from 20 controls. In three of the patients, thyroid fine-needle aspirates were examined as well. At referral, all patients had elevated blood levels of activated T helper and T cytotoxic/suppressor cells 2 (2-4)%, median and range, vs 0 (0-2)%, P less than 0.001 and 12.5 (2-24)%, vs 0 (0-1)% P less than 0.001). At follow-up, the activated proportion of T helper cells had become normal whereas some activated T cytotoxic/suppressor cells remained, 7 (0-8)%. No significant changes in total T cell number were detected when data at referral and at follow-up were compared. In thyroid aspirates, HLA-DR expressing thyrocytes were observed; the total proportion of T cytotoxic/suppressor cells was elevated (70% compared with 35% in blood) and 70% of the T cytotoxic/suppressor cells were HLA-DR+. Furthermore, 55% of the thyroid-infiltrating lymphoid cells were positive for interferon (IFN-gamma+). The finding of activated T cytotoxic/suppressor cells in the blood and thyroid tissue in subacute thyroiditis is consistent with a viral aetiology. Furthermore, intrathyroidal IFN-gamma+ lymphocytes are likely to contribute to expression of major histocompatibility complex (MHC) class II antigens on thyrocytes. No autoantibodies, however, were detected, which suggests that aberrant expression of MHC class II molecules alone is not sufficient to provoke an autoimmune response.
Adult↗
Cholecystokinin secretion after oral Emtobil, a gallbladder-contracting formula.
Oral Emtobil, a liquid preparation of sorbitol and peanut oil, has been used in roentgenological practice for several years. Emptying of an opacified gallbladder is seen within 15 min after intake of 100 ml of this solution. The main physiological factor responsible for contraction of the gallbladder is cholecystokinin (CCK). In the present study plasma concentrations of CCK in fasting, healthy subjects were studied in response to oral Emtobil. The radioimmunoassay used measures sulphated CCK-8 and CCK-33 with equimolar potency. Neither non-sulphated CCK nor any gastrins are measured. The average concentration, after an overnight fast in nine healthy subjects without gallstones, was 1.2 pmol/l. A peak concentration was seen within 30 min after 'the test meal' and averaged 8 pmol/l. It is suggested that oral Emtobil contracts the gallbladder by release of CCK. Since Emtobil induces a fast and marked rise in the plasma concentration of CCK, it may be used in test procedures to estimate the secretion of CCK.
Administration, Oral↗
Rubella-specific IgM determination of heat-treated sera.
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Antibodies, Viral↗
Postpartum thyroid disease.
Recent epidemiological studies in Japan and Sweden have disclosed a high prevalence of transient thyroid dysfunction in women following delivery. These changes seem to reflect an immunoregulatory "rebound" following pregnancy-induced immunosuppression. Thyroid microsomal antibody titers characteristically decrease during pregnancy and increase again after delivery to maximum levels around six months postpartum. At this time some microsomal antibody-positive women develop goitrous hypothyroidism. Subsequently, the microsomal antibody titers fall, reaching the early pregnancy values one year postpartum by which time hypothyroidism subsides. The severity of hypothyroidism is closely related to the titer of microsomal antibody, especially the immunoglobulin G1 subclass of microsomal antibody, and partly predictable from the titer in early pregnancy. The HLA-DR4 antigen was observed in 58% of microsomal antibody-positive Swedish women as compared to 33.7% in the general population (relative risk = 2.71). This association was even stronger in microsomal antibody-positive women who developed postpartum hypothyroidism (69%; relative risk = 4.36). Finally, postpartum thyrotoxicosis with a high radioiodine uptake may occur in women with latent Graves' disease. In these cases changes of TSH-receptor-stimulating antibodies analogous to microsomal antibodies seem to occur.
Adolescent↗
Association between thyroid microsomal antibodies of subclass IgG-1 and hypothyroidism in autoimmune postpartum thyroiditis.
The potential role of thyroid microsomal (Mic) antibodies in the development of postpartum hypothyroidism was investigated in 34 euthyroid women, whose sera were found to contain Mic antibodies in pregnancy. Additional serum samples were obtained 2. 5 and 10-12 months after delivery and analysed for IgG class and IgG subclass levels of Mic antibodies by ELISA techniques. Characteristically, Mic antibodies decreased from early pregnancy to 2 months postpartum, increased two-fold 5 months postpartum and had returned 10-12 months postpartum to the early pregnancy level. Mic antibodies were predominantly subclass IgG-1 or IgG-4 with only minor contributions from IgG-2 and IgG-3. In each individual the percentage contribution made by each IgG subclass to Mic antibody was essentially similar in early pregnancy and the postpartum period despite changes in total IgG class Mic antibody. During the year following delivery, thyrotoxicosis alone (Graves' disease) developed in 5 women. In the remaining 29 patients the absolute levels of Mic antibodies of IgG-4 subclass were similar 5 months postpartum in women with maximal serum thyrotropin (TSH) greater than 20 mU/1 (mean optical density in ELISA +/- s.d.; 0.84 +/- 0.538; n = 13) and in women with maximal TSH less than 10 mU/l (0.69 +/- 0.457; n = 16). In contrast, significantly higher values were observed for Mic antibody of IgG-1 subclass in patients with TSH greater than 20 mU/l (1.14 +/- 0.440) compared with women with maximal TSH less than 10 mU/l (0.65 +/- 0.289) (P less than 0.001 by t-test for groups). These results imply that the magnitude of Mic antibody levels of subclass IgG-1 but not IgG-4 is associated with the development of postpartum hypothyroidism and possibly with tissue destruction in autoimmune thyroid disease in general.
Adult↗
Thyroxine, methimazole, and thyroid microsomal autoantibody titres in hypothyroid Hashimoto's thyroiditis.
Ten hypothyroid patients with Hashimoto's thyroiditis were treated with methimazole 30 mg in addition to thyroxine 0.15 mg daily. Another 10 hypothyroid patients with Hashimoto's thyroiditis were given thyroxine 0.15 mg alone. After 22 weeks of treatment significant decreases in thyroid microsomal autoantibody titres were observed in both groups (p less than 0.01). There was no difference in the mean change in titre between the two groups. When the patients treated with methimazole were subsequently given thyroxine 0.15 mg alone for a further 22 weeks no additional change in titre was observed. The data suggest that thyroxine, by normalising serum thyroid stimulating hormone concentrations, may reduce the autoantigenic properties of the thyrocytes with a subsequent decrease in autoantibody titres.
Adult↗
Influence of endogenous T3-autoantibodies on thyroid hormone measurements in a woman with transient postpartum thyroiditis.
Unreliable estimates of serum total T3 due to the presence of autoantibodies against T3 were observed in a woman who developed thyrotoxicosis followed by transient hypothyroidism after childbirth (postpartum thyroiditis). The T3 autoantibody levels changed during the postpartum period in a similar way to the thyroid microsomal antibodies. The total T3 values were constantly low, whereas the measurement of free T3 by the Amerlex analogue method deviated from the expected only at the time of maximal antibody levels. Thus, evaluation of thyroid function may be complicated by the simultaneous presence of thyroid hormone autoantibodies and transient postpartum thyroiditis.
Adult↗
Influence of the HLA-DR4 antigen and iodine status on the development of autoimmune postpartum thyroiditis.
HLA-A, -B, and -DR antigens were determined in all 50 women with a serum thyroid microsomal hemagglutination antibody (MsAb) titer equal to or greater than 1:100 in the first trimester of pregnancy in a population of 733 pregnant women. The DR4 antigen was found in 58.0% of the women compared to 33.7% in control subjects, which corresponds to a relative risk of 2.71 (P less than 0.01 by X2 test). The MsAb-positive women were examined regularly during the year after delivery for the development of thyroid dysfunction. The DR4 antigen frequency was found to be even higher, 69.0% (relative risk = 4.36; P less than 0.001), among the 29 women who developed hypothyroidism in the postpartum period. No other HLA antigen deviations were found among those 15 hypothyroid women in whom an initial thyrotoxic phase occurred before hypothyroidism. The B8, DR3 haplotype was found in 3 of 5 women who developed Graves' thyrotoxicosis alone. Urinary iodine excretion measured in some MsAb-positive women 3 (n = 19) or 6 months (n = 29) postpartum, respectively, was compatible with leakage of thyroid iodine during the initial destruction-induced thyrotoxic phase of postpartum thyroiditis, followed by low iodine excretion during the subsequent hypothyroid phase. We conclude that genes coding for the DR4 antigen may have a regulatory influence on MsAb production, which in turn affects the development of postpartum hypothyroidism. Thyroid iodine content and iodine intake also may have an impact on the severity of the thyrotoxic and the hypothyroid phases of autoimmune postpartum thyroiditis.
Adult↗
Thyrotropin-releasing hormone testing during antithyroid drug treatment of Graves' disease as an indicator of remission.
In 74 patients with hyperthyroid Graves' disease, TRH tests were undertaken every third month during the course of a standardized antithyroid drug and T4 treatment program. The antithyroid drug dose was reduced gradually and finally withdrawn when persistently normal TSH responses were obtained. In 46 patients (62%), such normal responses occurred and therapy was discontinued after a mean treatment period of 13 months (range, 5-24 months). In the remaining unresponsive 28 patients (38%), therapy was gradually withdrawn after 2 yr of treatment (mean treatment period, 27 months; range, 25-36 months; P = 0.0001 vs. the other group). The mean overall follow-up period after cessation of treatment was 65 months (range, 32-100 months) and did not differ between the TRH-responsive and TRH-unresponsive group. In the TRH-responsive group, 12 relapses (26%) occurred 23 months (range, 6-45 months) after discontinuation of therapy, in contrast to 20 relapses (71%) after 6 months (range, 0-12 months) in the TRH-unresponsive group. The differences in relapse rates and time duration until relapse are highly significant (P = 0.0003 and P = 0.0001, respectively). Small but significant differences in serum T3 and T4 levels were found between the groups throughout the treatment periods, emphasizing the importance of thyroid hormone levels in regulating the pituitary responsiveness to TRH. It is concluded that regular TRH tests during antithyroid drug treatment are useful in deciding the dose and duration of therapy and in predicting the likelihood of remission.
Adult↗
Indomethacin reduces raised intraluminal gallbladder pressure in acute cholecystitis.
Indomethacin was recently shown to have a potent analgesic effect on biliary pain. The underlying mechanism is not fully clear, although reduction of increased gallbladder pressure by inhibition of prostaglandin synthesis had been suggested. For further clarification of this mechanism, the effect of intravenous indomethacin on the intraluminal gallbladder pressure was investigated in patients undergoing operation for acute cholecystitis. After laparotomy, gallbladder pressure was measured continuously during 25 min in 20 patients, 10 of whom received 100 mg indomethacin intravenously, while 10 were untreated controls. High intraluminal gallbladder pressure was found in all patients. Indomethacin reduced the average pressure by 11% in 20 min, whereas the corresponding pressure in the controls was constant. The results indicate that acute cholecystitis is associated with substantially raised intraluminal pressure, and that the analgesic action of indomethacin on biliary pain may be attributable to a local effect on gallbladder function, resulting in reduction of intraluminal pressure.
Acute Disease↗
[Autoimmune postpartum thyroiditis].
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Autoimmune Diseases↗
Long-term ECG recordings in hyperthyroid patients before and after antithyroid treatment.
Heart rate and heart rhythm were studied in 19 hyperthyroid patients before and after antithyroid treatment inducing a euthyroid state. The mean 24-hour heart rate in patients with sinus rhythm and without drugs influencing heart rate was 100 beats/min before and 80 after antithyroid treatment. The difference was greatest in the sleeping hours. The heart rate, especially in the sleeping hours, correlated significantly with serum triiodothyronine but not with serum thyroxine concentrations.
Adult↗
Autoimmune thyroid dysfunction in the postpartum period.
The prevalence of thyroid disease was investigated in 460 Caucasian women after delivery. Thyroid microsomal antibodies (MsAb) were found in 44 (9.6%) of the women. These women appeared to have autoimmune thyroiditis. The changes in MsAb titers followed a predictable pattern with maximal values around 5-7 months postpartum. At this time 20 of these women had transient hypothyroidism and in some this was preceded by a thyrotoxic episode. The extent of postpartum hypothyroidism correlated well with the titers of MsAb in early pregnancy and in the postpartum period. Transient thyrotoxicosis occurred in eight women 5-7 months postpartum. TSH-receptor stimulating antibodies and/or high radioiodine uptake, suggesting Graves' disease, were detected in four of these women. Thus, after delivery, manifestations of autoimmune thyroid disorders, are remarkably common. In patients with autoimmune thyroiditis measurements of MsAb provide a good prognostic marker for the development of transient hypothyroidism.
Adult↗
Intrathyroidal and circulating lymphocyte subsets in different stages of autoimmune postpartum thyroiditis.
Postpartum thyroiditis (PPT) is a reversible form of lymphocytic thyroiditis which has been attributed to an aggravation of preexisting subclinical autoimmune thyroiditis. In this study no differences in circulating lymphocyte subsets were found between 9 thyrotoxic and 18 hypothyroid PPT patients and normal subjects. We obtained sufficient numbers of thyroid-infiltrating lymphocytes for surface marker characterization in 3 women in the thyrotoxic phase and in 10 women in the hypothyroid phase of PPT. Cells were identified by conventional T and B cell markers as well as by monoclonal antibodies (OKT) directed against different T cell subsets in a microscale immunofluorescence assay. In the hypothyroid patients a relative accumulation of B cells (31% vs. 17%; P less than 0.01 by the Wilcoxon signed rank test) was found within the thyroid when compared to peripheral blood. A relative decrease in intrathyroidal supressor-cytotoxic (OKT 8+) T cells (19% vs. 28%; P less than 0.01) resulted in an increased intrathyroidal helper to suppressor-cytotoxic (OKT 4+/OKT 8+) T cell ratio (3.0 vs. 2.0; P less than 0.01). Intrathyroidal lymphocyte subsets in the thyrotoxic patients were comparable to those in the hypothyroid patients. These findings, which are similar to those we previously obtained in patients with chronic Hashimoto's thyroiditis, may indicate that local synthesis of thyroid-directed autoantibodies is of primary importance in all stages of autoimmune thyroiditis.
Adult↗
Postpartum thyroid dysfunction.
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Antibodies↗
Intrathyroidal HLA-DR expression and T lymphocyte phenotypes in Graves' thyrotoxicosis, Hashimoto's thyroiditis and nodular colloid goitre.
Thyroid surgical biopsies from 21 individuals were examined by a double immunoenzymatic technique with respect to HLA-DR expression and lymphocytic infiltration. HLA-DR positive thyrocytes were observed in two examined Hashimoto goitres and in nine of 11 specimens from patients with Graves' disease. HLA-DR positive thyrocytes were localized to areas harbouring infiltrating lymphocytes, whereas regions with no lymphocytes only rarely expressed HLA-DR antigens. In two specimens of nodular goitre HLA-DR positive thyrocytes were observed in the vicinity of lymphocytic infiltration. Tissues from another three nodular goitres, from one follicular adenoma and from two normal individuals contained no HLA-DR positive thyrocytes and no or only a few lymphocytes. The lymphocytic infiltrates were dominated by cells with the Leu 3a helper/inducer phenotype irrespective of underlying disease, although most pronounced in Hashimoto's thyroiditis. The results indicate that HLA-DR antigens is expressed on thyrocytes in thyroid disorder. The extent of expression correlated with lymphocytic infiltration, which suggests that the two findings are related and of importance for the development of thyroid autoimmunity.
Adolescent↗
The concentrating function of the feline gallbladder after truncal vagotomy.
Truncal vagotomy is associated with a raised incidence of cholesterol gallstone disease and increase in the size of the gallbladder and of the bile acid pool. Investigations of hepatobiliary function in man and mammals after truncal vagotomy have not established if the enlarged gallbladder is simply dilated, or if the absorptive capacity of the mucosa has changed. We studied the concentrating function of the gallbladder with a perfusion technique in anaesthetized cats three weeks and three months after intrathoracic truncal vagotomy and compared the results with a control group. The histology of the gallbladder was studied with light microscopy. Three weeks after vagotomy the gallbladder size, histologic picture and concentrating function did not differ from observations in the control cats. Three months after the vagotomy the gallbladder was slightly enlarged, sludge was found in the luminal contents, an inflammatory response was seen in the mucosa and the net rate of water absorption was increased two to three times compared with the controls. Possible mechanisms in the increased rate of net water absorption are tentatively discussed.
Animals↗