TSH anti-receptor antibodies in Graves' disease

The purpose of this study was to evaluate the sensitivity, specificity and predictive value of thyrotropin receptor antibody (TRAb) in the diagnosis of Graves disease. TRAb was tested by an isotopic receptor assay-TRAK Henning-in 80 newly diagnosed, untreated Graves disease patients (group I), 63 with other thyroid diseases (group II) and 60 controls (group III). In group I, 11 patients were TRAb negative and 7 were considered in the gray area (TRAb between 9 and 14 U/L). In group II, only 2 patients had TRAb 9 U/l and all controls were TRAb negative. For statistical analysis patients with TRAb in gray area were excluded. Sensitivity and specificity for this assay were 84.5 and 100% respectively. Predictive value of 100% affords certainty that a hyperthyroid patient with a positive TRAb has Graves disease, not sequining a scintigram.     

TSH suppression combined with carbimazole for Graves' disease: effect on remission and relapse rates

OBJECTIVE: We studied the influence of TSH suppressive therapy combined with carbimazole (CBZ) on treatment outcome in Graves' disease. DESIGN: Open non-randomized prospective study. SETTING: University Hospital of Montpellier, France. SUBJECTS: Sixty-six consecutive patients without prior treatment were included. All the patients were treated initially with 30 mg of CBZ. After 1 month of treatment, one group continued CBZ alone (n = 23), another group received a combination of CBZ plus T3 (n = 19) and a third group received CBZ and 3,5,3'-triiodothyroacetic acid (Triac, n = 24). Therapy was stopped when remission was obtained based on clinical euthyroidism, normalization of FT4 and of early radioiodine uptake. Nine patients with medical treatment failure or major side effects requiring to stop antithyroid drugs underwent surgery or radioiodine therapy. Nine patients were lost to follow-up. The remaining 48 patients were available for analysis of both remission and relapse. RESULTS: The median duration of therapy was 18 months (range, 4-41 months). Based on clinical examination, goitre size at 4 months decreased more in the CBZ + T3 and CBZ + Triac groups than in the CBZ group (P = 0.02). The overall remission rate tended to be higher in the groups treated with CBZ + T3 and CBZ + Triac than in the group treated with CBZ alone, but the difference did not reach statistical significance (P = 0.17). No difference in the relapse rate was observed between the three groups. CONCLUSION: TSH suppression combined with CBZ has little or no effect on remission and relapse rates in Graves' disease patients.     

Human thyroid adenyl cyclase-stimulating activity in immunoglobulin G of patients with Graves' disease

We have studied the characteristics of the stimulation of adenyl cyclase (AC) activity in human thyroid plasma membranes by thyroid-stimulating hormone (TSH) and by immunoglobulin G (IgG) from the sera of patients with Graves' disease. AC activity was measured as adenosine 3',5'-cyclic monophosphate (cAMP) generated by membranes in a 10 minute incubation. IgG from two patients with Graves' disease possessed particularly potent human thyroid AC-stimulating activity; the dose-response curves with these IgGs were essentially parallel to those obtained with TSH. As little as 30 mug of the IgG of one patient with Graves' disease or 8 muU of TSH caused significant AC stimulation. A Lineweaver-Burk plot of the data suggested similarity in the site of action of both TSH and human thyroid adenyl cyclase stimulator (HTACS) in Graves' IgG. Submaximal doses of HTACS and TSH had additive effects on AC stimulation, but a large dose of a Graves' IgG with potent AC stimulating activity did not enhance AC stimulation by a maximal dose of TSH. The effect of HTACS on AC was slower in onset and longer in duration than an equipotent dose of TSH. HTACS was detectable in IgGs of 9 of 15 untreated hyperthyroid Graves' disease patients; its concentration, however, did not correlate significantly with tests of thyroid function, nor with long-acting thyroid stimulator (LATS) activity. In another 11 treated patients with Graves' disease, selected for the presence of LATS, HTACS and LATS were significantly correlated. We observed no inhibition of LATS activity in a Graves' IgG chosen for such testing because of its high titer of HTACS and no detectable LATS. However, an inhibitor of HTACS was detected in 2 of 4 IgGs; one of these two IgGs also inhibited AC stimulation by TSH. Conclusions: 1) Some Graves' disease IgGs contain a human thyroid AC stimulator (HTACS), probably different from LATS. 2) HTACS may act via a common pathway with TSH; it differs from TSH, however, in having a slower onset and a greater effect during more prolonged incubation with plasma membranes. 3) There is also an inhibitor of HTACS activity in some Graves' disease IgGs.     

Immunoglobulin A class fibroblast antibodies in patients with Graves' disease and pretibial myxedema

The involvement of autoantibodies in the extrathyroidal manifestations of Graves' disease has been the subject of extensive investigation, with fairly inconclusive results to date. We investigated the presence of immunoglobulin A (IgA) and IgG antibodies in patients with Graves' disease and pretibial myxedema (PTM; n = 21) as well as those with Graves' disease with thyroid-associated ophthalmopathy (TAO; n = 10), Graves' disease with no clinical evidence of extrathyroidal manifestations (n = 11), Hashimoto's thyroiditis (n = 9), type 1 diabetes mellitus (n = 10), systemic lupus erythematosus (n = 9) and normal individuals (n = 17). We looked for antibodies to both retroocular muscle and dermal fibroblasts as well as to thyroid peroxidase, thyroid microsomal antigen, thyroglobulin, and human eye muscle membranes. IgA class antibodies to microsomal antigen (30-50% of patients), thyroid peroxidase (5-20%), and human eye muscle membrane (0-26%) antigens were found in the various groups of patients with Graves' disease. With each of these antigens, serum from patients with PTM showed the greatest binding. Highly significant IgA binding was shown by PTM serum to both dermal (P < 0.001) and retroocular muscle (P < 0.001) fibroblasts from 12 different donors. Serum from Graves' patients with and without TAO and that from Hashimoto's thyroiditis patients reacted significantly with 4 of the 12 fibroblasts lines. In contrast, IgG binding was only found for 3 of the 12 fibroblast lines using patient serum. The IgA binding to fibroblasts shown by PTM patients was predominantly of the IgA2 subclass. The activity was absorbed out by both fibroblasts and thyroid cells. In immunoblotting studies, PTM patient serum reacted with a 54-kilodalton dermal fibroblast antigen and a 66-kilodalton retroocular fibroblast antigen. No binding to these antigens was seen with serum from normal controls or patients without PTM. Further elucidation of the nature of this fibroblast antigen will help to determine the role of IgA autoantibodies in the extrathyroidal manifestations of Graves' disease.     

F-qi-FDG PET of the thyroid gland in Graves' disease

AIM: This study evaluates F-18-FDG PET of the thyroid in Graves' disease. METHODS: Thirty patients were investigated the day before radioiodine therapy, 15 patients 3-10 days after radioiodine therapy. Twenty patients with cancer of the head or neck and normal thyroid function served as controls. RESULTS: F-18-FDG uptake was higher in Graves' disease patients than in controls. Negative correlations of F-18-FDG uptake with half-life of radioiodine and absorbed radiation dose due to radioiodine therapy were found along with a positive correlation to autoantibody levels. CONCLUSION: Thus F-18-FDG PET is likely to give information on the biological activity of Graves' disease as well as on early radiation effects.     

Post-operative thyroid status of patients with Graves'' disease is determined by the responsiveness of thyrocyte to TSH under the present thyroid gland remnant

OBJECTIVE: Differences in the perspectives of severely and persistently ill patients, their family members, and clinical care providers on key aspects of community-based care were examined to help inform community service planning and development. METHODS: A sample of 183 patients being considered for relocation from psychiatric facilities in Alberta, Canada, to community-based care, were interviewed, as were their primary clinical care providers. Family members of 130 patients were also interviewed. RESULTS: Among the 130 patient-family pairs, 41 percent disagreed about the desirability of relocation, with fewer patients favoring relocation than families. Forty-nine percent of the pairs disagreed about the desired proximity to the family of the relocated patient, with the patient desiring closer proximity than the family member in about half of these cases. Fifty-three percent of the pairs disagreed about the amount of financial and emotional support that the family would provide after relocation. In half of these cases, patients believed the family would provide a higher level of support than the family indicated it could. Among the patients, 49 percent preferred independent living, whereas only 10 percent of family members and 17 percent of clinical care providers preferred it. Fifty-five percent of patients expressed a clear desire to work, whereas care providers believed that only 12 percent of patients were employable. CONCLUSIONS: Persistently mentally ill residents of psychiatric facilities express clear preferences about key aspects of community-based care when they are asked, and these preferences often reflect different views from those expressed by either family members or clinical care providers.     

Outcome of differentiated thyroid cancer in Graves' patients

The clinical behavior and outcome was evaluated in 21 nonoccult differentiated thyroid carcinomas occurring in Graves' patients during the period 1982-94 and compared with that of matched tumors occurring in euthyroid controls (n = 70). At surgery, patients with Graves' disease showed distant metastases more frequently than euthyroid patients (3/21 = 14.3% vs. 1/70 = 1.4%, P = 0.0556). Graves' patients also showed a significantly higher cumulative risk of recurrent/progressive distant metastases or total adverse events (odd ratios = 3.14 and 2.07, respectively) as compared with euthyroid patients. At the last follow-up visit, persistence of distant metastases was also more frequent in the Graves' group (P = 0.007), although the cumulative individual dose of radioiodine administered was higher than in the control group (median dose = 805 mCi vs. 350 mCi). Two patients died in the Graves' group vs. none in the control group. Circulating thyroid stimulating antibodies were present in all patients but one and persisted as long as signs of disease were evident. These findings indicate that differentiated thyroid carcinomas in patients with Graves' disease are more aggressive than those occurring in matched euthyroid controls and should, therefore, be managed accordingly.     

Effect of 1 alpha-hydroxyvitamin D3 on serum levels of thyroid hormones in hyperthyroid patients with untreated Graves' disease

We performed a randomized, open prospective study to determine the effect of 1 alpha-hydroxyvitamin D3 [1 alpha (OH)D3] on hyperthyroidism in patients with untreated Graves' disease. At the time of entry into the study, 30 patients were randomly assigned to receive a daily dose of 30 mg methimazole (MMI) (group A, n = 15) or the same dose of MMI supplemented with 1.5 micrograms 1 alpha (OH)D3 (group B, n = 15). These treatment regimens were continued for 24 weeks, and physicians were allowed to adjust MMI dosage during follow-up visits. Blood samples were collected, and serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), T3, T4, thyrotropin (TSH), alkaline phosphatase (ALP), and TSH-receptor antibody (TRAb) were determined. During the follow-up periods, all patients became euthyroid. The dose of MMI was not significantly different between these two groups. In contrast, decreases in mean serum FT3 and FT4 levels, as well as in mean serum T3 and T4 levels, were greater in group B. Correspondingly, the reciprocal increase in the mean TSH level was more prominent in group B. Mean TRAb levels did not differ between the two groups. Mean serum ALP levels in group B were significantly lower than in group A at 24 weeks. Thus, we suggest that concomitant administration of 1 alpha (OH)D3 is useful for treating hyperthyroidism in patients with Graves' disease.     

Changes in thyroid volume in response to radioactive iodine for Graves' hyperthyroidism correlated with activity of thyroid-stimulating antibody and treatment outcome

This study investigated 1) the relationship between thyroid volume and thyroid function in radioactive iodine (RAI) treatment for Graves' disease, and 2) the activity of thyroid-related Ig in serum on the responsiveness of thyroid tissue to RAI. The changes in thyroid volume per megabecquerel (MBq) of 131I retained in thyroid tissue was calculated by ultrasonography as a quantitative indicator of the effect of RAI on thyroid volume. Of the 52 patients treated with 131I (3.7 MBq retained/g thyroid tissue), 26 patients showed thyrotoxicosis, 20 patients became euthyroid, and 6 patients developed hypothyroidism 6 months after therapy. The change in thyroid volume per MBq 131I was lower (P < 0.01) in the hyperthyroid patients than in the euthyroid or hypothyroid patients. The activity of thyroid-stimulating antibody in serum immediately before the therapy was greater (P < 0.01) in the hyperthyroid patients than in the euthyroid patients and was greater (P < 0.05) in the euthyroid patients than in the hypothyroid patients; it was inversely correlated with the changes in thyroid volume per MBq 131I (r = -0.667; P < 0.01). Accurate measurement of changes in thyroid volume during the course of RAI treatment provides evidence of the responsiveness of Graves' disease thyroid tissue to RAI, which is related to the outcome of thyroid function. Thyroid-stimulating antibody determination may be useful in deciding the appropriate dose of RAI to obtain euthyroidism instead of hyperthyroidism.     

MHC-extended haplotypes in families of patients with Graves' disease

MHC-extended haplotypes were investigated in multiplex families of patients with hyperthyroid GD. Using a combination of both phenotypic (serology and protein electrophoresis) and genotypic (DNA-RFLP) markers, 159 MHC-extended haplotypes extending from HLA-A across the MHC class III (C2, Bf, C4A, and C4B) toward the HLA-DR/DQ complex were deduced from 217 (51 and 166 affected and unaffected) members of 21 families of patients with GD. Thyroid autoantibodies were measured and found positive in 27.1% of 166 clinically euthyroid unaffected members. Extended haplotypes were classified into four categories--affected (n = 40), Aff/Ab + ve (shared haplotype between affected and Ab + ve members, n = 31), Ab + ve (n = 29), and Ab - ve (n = 59)--based on the presence and absence of these haplotypes in 51 affected members with GD and 45 and 121 unaffected members who were respectively positive and negative for thyroid autoantibodies. Five recombinations were detected: three were found between HLA-A and B and two between HLA-B and the MHC class III. No recombination was found between or within the MHC class III and class II complex. Though the HLA-DR17 (DR beta 17(1) and DR beta 17(2)) allele was found to be significantly increased in both the affected and the Aff/Ab + ve when compared with the Ab - ve haplotypes (p < 0.042 and p < 0.018), the frequency of the HLA-B8, 2.7-kb SstI-4.5-kb TaqI/C2 Bf*S, 6.4-kb TaqI/C4A*Q0C4B*1, HLA-DR beta 17(1)/DQ alpha 2-DQ beta 2a extended haplotype was found to be significantly increased only in the affected haplotype (p < 0.05). These results suggest that while HLA-DR17 is a susceptibility allele shared between GD and individuals with positive thyroid autoantibodies, the HLA-B8, 2.7-kb SstI-4.5-kb TaqI/5'-3'C2 Bf*S, 6.4-kb TaqI/C4A*Q0B*1, DR beta 17(1)/DQ alpha 2-DQ beta 2a is a disease susceptibility-extended haplotype for Graves' disease.     

Neutralizing antibodies to bovine thyrotropin in immunized patients with thyroid cancer

Bovine thyrotropin (bTSH) was administered to 17 patients who had thyroid carcinoma. Anti-bTSH antibodies in the patients' sera were detected by three methods: 1) cross-reaction of sera in a homologous bTSH RIA, 2) [125I]bTSH binding to the patients' sera using charcoal to separate bound from free fractions, and 3) gel filtraton to detect [125I]bTSH bound to anti-bTSH in patients' sera. Immunoreactive anti-bTSH antibodies were thus demonstrated in 14 patients. These patients showed specific binding of their sera to [125I]bTSH with the charcoal separation of free from bound hormone. A high titer of antiserum (1:10,000) was found in those patients whose sera reacted strongly in the bTSH RIA (greater than 50 mu U/ml). The binding capacity of the serum of 1 patient was estimated as 2,600 mu U/ml serum. Ten of the patients' sera which showed immunoreactivity to bTSH neutralized bTSH activity in the McKenzie mouse bioassay but did not neutralize the activity of human TSH in this bioassay. Repeated administration of bTSH to 14 patients resulted in development of immunoreactive and neutralizing anti-bTSH antibodies. Development of immunological resistance to bTSH appears inevitable in patients who receive repeated injections of this hormone. Because of the loss of effectiveness of bTSH by antibody formation, the repeated diagnostic and therapeutic use of bTSH is not recommended.     

TSH receptor antibodies in the recurrent goiter after surgical treatment of Graves-Basedow disease

The serious complication after surgical treatment is goitre renewai. Very important is therefore the correct diagnosis based also on laboratory investigation, enabling early detection of dysthyreosis. The aim of work was assessment of immunological states of thyroid gland of patients with goitre recurrence treated surgically because of Graves-Basedow, based on investigation of TSH receptor antibodies. The time from the surgery to the examination ranged from two to eleven years. The laboratory investigation contained determination of thyroxin, free thyroxin triiodothyronin, thyreotropin and antibodies directed against TSH receptor(TRAb). It has been found that average concentration of TRAb and frequency was significantly higher in recurrent goitre then in group without goitre renewal. The results of investigation indicates usefulness of determination of thyroid antibodies in diagnosis of recurrent goitre after surgical treatment of Graves-Basedow disease.     

Comparison between TRH-stimulated TSH and basal TSH measurement by a commercial immunoradiometric assay in the management of thyroid disease

In order to assess the current diagnostic role of the TRH test following the introduction of more sensitive "second generation" TSH assays, we studied a series of 259 outpatients, 237 women and 22 men, mean age 44.7 years (range 12-82), 91 of whom (35%) with untreated simple goiter, 133 (51%) with simple nodular goiter on steady state I-thyroxine treatment, 18 (7%) with overt or subclinical hyperthyroidism and 17 (7%) with overt or subclinical hypothyroidism, compared to a control group of 26 euthyroid healthy subjects. Serum TSH was measured by a commercial immunoradiometric assay (clinical sensitivity 0.1 microU/ml). TSH response to TRH was evaluated 30 minutes after giving 200 micrograms TRH i.v. bolus, the results being analyzed both as absolute increase (delta-TSH=stimulated TSH minus basal TSH) and as relative increase (R-TSH stimulated TSH/basal TSH). Using cut-off values of 0.3-3.2 microU/ml, basal TSH measurement was able to detect hypothyroidism (specificity = 100%) and to exclude hyperthyroidism (sensivity = 96.9%), but failed to accurately prove hyperthyroidism (specificity = 93.4%) and, above all, to exclude hypothyroidism (sensitivity = 35.3%) in our ambulatory patients. The delta-TSH values showed a basal TSH dependent linear increase (r = + 0.87, p < 0.001) both including only patients (n = 139) with basal TSH level in the euthyroidism range and including all patients (n = 223) having TSH responsive to TRH. All the patients with detectable basal TSH level displayed detectable TSH response to TRH, as did 19 (= 23.5%) of 81 patients with undetectable (< 0.1 microU/ml) basal value. In particular: a) for subnormal but detectable basal TSH ranging between 0.1 and 0.2 microU/ml, TSH was always hyporesponsive (delta-TSH < or = 2.5 microU/ml), while between 0.2 and 0.3 microU/ml TSH was hyporesponsive in 72.2% and normoresponsive (delta-TSH > 2.5 and < or = 11.9 microU/ml) in the remaining 27.8%; b) for basal TSH values within the normal range (0.3-3.2 microU/ml). TSH was hyporesponsive in 13.7%, normoresponsive in 74.8% and hyperresponsive in 11.5%; c) for high basal TSH values TSH was always hyperresponsive. The analysis of R TSH showed relatively constant values in the range of euthyroidism and hypothyroidism (m +/- SD: 7.4 +/- 2.3 and 7.7 +/- 3.1, respectively), and a marked differentiation of hyperthyroid patients whose R-TSH values were significantly lower (4.2 +/- 3.4) but had a wide individual variability. Linear regression analysis of basal or stimulated TSH and circulating thyroid hormones showed a close negative relationship, being highly significant between delta-TSH and T4 (r = 0.57, p < 0.001) and delta-TSH and FT4 (r = 0.46, p < 0.001). In conclusion, after the introduction of current second generation TSH immunoradiometric assay, the diagnostic role of the TRH test is greatly limited but not to be excluded: it can provide additional information to that obtained with simple basal TSH measurement in the diagnosis of subclinical hypothyroidism and in the precise evaluation of the degree of TSH suppression in patients with a subnormal basal TSH, either for endogenous thyrotoxicosis or I.-thyroxine treatment.     

Antibody-dependent cell-mediated cytotoxicity in autoimmune thyroid disease: relationship to antithyroperoxidase antibodies

Thyroid antibody-dependent cell-mediated cytotoxicity (ADCC) has been reported in autoimmune thyroid disease, and its relationship with antithyroperoxidase antibodies (TPOAb) questioned. We studied the effect of highly purified human thyroperoxidase (TPO) on thyroid ADCC activity elicited by serum from patients with autoimmune thyroid disease. ADCC promoted by a pool of Graves' disease sera could be inhibited by the addition of TPO in a dose-dependent manner. TPO at 40 micrograms/mL decreased the ADCC observed in the presence of this serum pool by 50%. In the presence of 40 micrograms/mL TPO, ADCC was significantly reduced (P < 0.0005) from 39.6 +/- 10.6% (mean +/- SD) to 14.0 +/- 12.9% for the 18 Graves' disease sera tested and from 39.1 +/- 10.5% to 6.1 +/- 1.7% for the 16 thyroiditis sera tested. Purified thyroglobulin had no effect. Immunoaffinity-purified TPOAb could mediate ADCC in a dose-dependent manner, whereas purified antithyroglobulin antibodies could not. Three TPOAb-positive, but ADCC-negative, sera appear to contain an activity able to protect thyroid cells from ADCC. This protective effect is also observed on human fibroblasts. In conclusion, TPO is the major antigen involved in thyroid ADCC.     

Recurrence of thyrotoxicosis after attack of allergic rhinitis in patients with Graves' disease

Graves' disease is frequently aggravated during antithyroid drug therapy; however, little is known of its aggravating factors. We studied 83 patients with Graves' disease who were euthyroid for at least 6 months under antithyroid maintenance therapy, and we examined the relationship between thyrotoxicosis relapse, attack of allergic rhinitis, and peripheral eosinophil increase. Forty-one patients showed thyrotoxicosis relapse; of these, 22 (54%) showed peripheral eosinophil increase, and 14 (34%) had attacks of allergic rhinitis. In the remaining 42 patients without thyrotoxicosis relapse, only 4 (10%, P < 0.001) showed an increase in peripheral eosinophils, and only 3 (7%, P < 0.01) had allergic rhinitis. Recurrence of thyrotoxicosis was observed with the increase in serum levels of TSH-receptor antibodies and increase in eosinophils 2 months after the attack of allergic rhinitis. Three patients with seasonal allergic rhinitis showed thyrotoxicosis relapse at the same time of year within 2 consecutive years. Our findings indicate that allergic rhinitis can be an aggravating factor of Graves' disease and suggest that the preceding increase in peripheral eosinophils can be a predictive indicator of recurrence of thyrotoxicosis during antithyroid drug therapy.     

Relationship of thyroid states and serum thrombomodulin (TM) levels in patients with Graves' disease: TM, a possible new marker of the peripheral activity of thyroid hormones

Thrombomodulin (TM) is a thrombin receptor glycoprotein that functions as an anticoagulant on the surface of endothelial cells. Serum TM is regarded as a new marker of generalized endothelial cell damage. Serum TM concentrations were measured in 75 patients with Graves' disease and 75 age- and sex-matched healthy subjects. Serum TM levels in patients in the hyperthyroid state were significantly increased, while those in patients in the hypothyroid state due to treatment were significantly decreased compared with levels in control subjects. All patients with untreated Graves' disease had markedly elevated TM levels. Serum TM levels correlated closely with thyroid hormone concentration (TM vs. free T4, r = 0.858; P = 0.001). Serial measurement of individual patients revealed that serum TM levels paralleled thyroid hormone concentration, reaching normal control values upon attainment of euthyroidism. On the other hand, there was no significant correlation between serum TM concentration and titer of antithyroglobulin antibodies, titer of antimicrosomal antibodies, serum thyroglobulin level, or goiter size, and serum TM was not directly influenced by TSH receptor antibodies or resting pulse rates. The close correlation between serum TM and thyroid hormone concentration suggests that thyroid hormones might influence the synthesis or metabolism of TM on the surface of endothelial cells in patients with Graves' disease.     

Evidence for the presence of immunoglobulin E antibodies specific to the cell wall phosphomannoproteins of Candida albicans in patients with allergies

To determine the major antigenic component of Candida albicans against immunoglobulin E (IgE) antibodies in the sera of patients with allergies who were positive for IgE antibodies to C. albicans crude antigen in a CAP system, phosphomannoproteins (CAMP/A or CAMP/B for serotype A or B strain, respectively) and their acid-stable portions (CAMP-S/A or CAMP-S/B) were isolated from beta-mercaptoethanol (2-ME) extracts of C. albicans cells of serotypes A and B, and IgE antibodies against these components were compared with those against protein complex and enolase (CAE) fractions isolated from C. albicans cells. The dot blot test, which was used to detect IgE antibodies to the C. albicans antigens, showed that IgE antibodies to the 2-ME extract and phosphomannoprotein fractions were present in the sera of 98.0% (2-ME extract), 96.8% (CAMP/A), 93.2% (CAMP-S/A), 97.2% (CAMP/B), and 81.5% (CAMP-S/B) of the patients, whereas IgE antibodies to the protein complex and CAE fractions were found in the sera of 73.6 and 48.8% of the patients, respectively. The extent of IgE binding to the 2-ME extract and phosphomannoproteins was well correlated with the fluorescence intensities estimated with the CAP system. Furthermore, the results obtained from the inhibition experiment with the CAP system indicated that the binding of IgE antibodies to Candida antigens is strongly inhibited by the phosphomannoprotein fraction and is an indication that the serum of the patients contained IgE antibodies specific to the cell wall phosphomannoproteins of C. albicans. Finally, an initial chemical analysis indicated that the epitopes for IgE antibodies on the phosphomannoproteins is a carbohydrate portion, since the ability of CAMP/A to inhibit the binding of IgE antibodies to the homologous CAMP/A was destroyed after oxidation by sodium periodate but not after digestion with proteinase K.     

Determination of factors affecting the therapeutic outcome of radioiodine therapy in patients with Graves' disease

AIM: Of this study was to determine whether success of radioiodine therapy (RIT) in Graves' disease depends on thyroid volume, function, thyroideal receptor antibodies (TRAK), thyreostasis, therapeutic dosage, 131I uptake, or effective half-life. METHOD: 78 patients received an average of 626 +/- 251 MBq of iodine-131 orally for thyroid ablation. 60 were assessed for successful therapy 3 months after RIT. RESULTS: In patients showing hyperthyreosis or a TRAK value > 11 U/l at the beginning of RIT, a significantly lower therapeutic dosage and effective iodine half-life were found than in non-hyperthyreotic patients or patients with TRAK < or = 11 U/l. Patients with a thyroid volume < or = 25 ml showed a significantly lower 131I uptake, but a significantly higher relative uptake (131I uptake/ volume) than patients with a thyroid volume > 25 ml. All failures were treated thyreostatically during RIT and showed a significantly lower therapeutic iodine dosage and relative uptake, as well as a significantly higher thyroid volume than patients with a successful therapy. RIT caused a thyroid volume reduction of 44%, with therapy failures showing a significantly lower volume reduction. Patients who received a therapeutic dosage of < or = 250 Gy showed significantly worse results than did those who had received > 250 Gy. Only one case of therapy failure received a dosage > 250 Gy, while 50% of failures received dosages > 200 Gy but < 250 Gy. Multivariate analyses (MANOVA, factor analyses) showed thyreostasis as the decisive negative factor for a successful course of therapy. CONCLUSIONS: Since most treatment failures occurred in patients under thyreostatic medication we recommend raising the target dosage to 250 Gy for these cases.     

Evidence for abnormal calcium homeostasis in patients with adynamic bone disease

To investigate whether the derangements in calcium kinetics in patients with renal osteodystrophy are similar in the various histologic forms of this metabolic bone disease, 43 patients on chronic maintenance dialysis underwent calcium kinetic studies using the double isotope technique, iliac crest bone biopsies for mineralized bone histology and histomorphometry and determinations of serum indices of calcium and bone metabolism. Intestinal calcium absorption was not different among the three histologic groups. However, women exhibited lower calcium absorption in each histologic form (P < 0.01). Patients with predominant hyperparathyroid bone disease showed plasma calcium efflux, calcium accretion rate and calcium retention markedly above normal values. Patients with low turnover bone disease exhibited a normal or slightly decreased plasma calcium efflux and calcium accretion rate together with a disproportionately low calcium retention. Patients with mixed uremic osteodystrophy presented with a calcium kinetic profile intermediary to the two other forms. Good relationships existed between plasma calcium efflux, calcium accretion rate, calcium retention and histomorphometric parameters of bone turnover as well as serum levels of parathyroid hormone. However, no serum parameter could indicate with certainty the underlying bone disease. These findings demonstrate that adynamic bone disease does not merely represent an academic finding but is characterized by a very low bone capacity to buffer calcium and inability to handle an extra calcium load. This is particularly relevant for the daily care of end-stage renal failure patients presently receiving higher than ever amounts of vitamin D and calcium salts.