Thyroid-cytotoxic antibodies (thyroid-cytotoxic Abs) have been described in patients with autoimmune thyroiditis, but their role in the development of hypothyroidism remains to be clarified. In this study, we evaluated the pathogenetic role of thyroid-cytotoxic Abs in 20 patients with atrophic thyroiditis (idiopathic myxedema; AT) and 94 patients with goitrous Hashimoto's thyroiditis (HT). Among patients with HT, 27 were euthyroid (HT-E), 27 had subclinical hypothyroidism (HT-SH), and 40 had overt hypothyroidism (HT-H). Seventeen normal subjects and 8 patients with nonthyroidal illnesses were used as controls (C). To detect thyroid-cytotoxic Abs, human thyroid cells expressing thyroid peroxidase (TPO) were labeled with 51Cr and challenged with the immunoglobulin G (IgG) fraction of serum plus rabbit complement. The cytotoxic effect of IgGs was calculated as the percent specific lysis (% SL), taking into account the lytic effect of complement alone and the maximal lysis produced by a detergent. Most C-IgGs decreased the cytotoxic effect of complement (median % SL, -3.3). IgGs from hypothyroid patients with thyroiditis had a greater cytotoxic effect than C-IgGs, either as a whole group (P < 0.001), or when subdivided according to clinical diagnosis: HT-SH (median % SL, 4.8; P < 0.005), HT-H (%SL, 2.2; P < 0.0001), or AT (%SL, 0.9; P < 0.01). Among patients with HT, the lytic activity of IgGs from patients with subclinical and overt hypothyroidism was higher than that of IgGs from euthyroid patients (P < 0.05). The results of IgGs from euthyroid patients with HT (median % SL, -0.9) did not significantly differ from those of C-IgGs. By taking a cut-off over the upper range of % SL produced by C-IgGs (> 2), the prevalence of thyroid-cytotoxic Abs was 30% in AT, 59% in HT-SH, and 55% in HT-H. However, 37% of euthyroid patients with HT also had thyroid-cytotoxic Abs. No IgG containing TPO antibodies (TPOAb) at low titer (< 40(2)) was cytotoxic. However, the levels of thyroid-cytotoxic Abs did not correlate with TPOAb titers, and preabsorption with TPO only partially abolished the lytic effect of some HT-IgG. These findings suggest that TPO is a target of thyroid-cytotoxic Abs, but other thyroid antigens are also involved in the cytotoxic reaction.(ABSTRACT TRUNCATED AT 400 WORDS)

Autoantibodies blocking the TSH-dependent production of cAMP in thyroid cells (TSH-BAb) have been described in atrophic thyroiditis (AT; idiopathic myxedema) and in neonates with transient hypothyroidism, but their incidence in autoimmune thyroiditis in relation to thyroid status remains to be completely established. To this purpose TSH-BAb were evaluated in a group of 140 consecutive patients with autoimmune thyroiditis, which included 26 cases of AT and 114 subjects with goitrous Hashimoto's thyroiditis (HT); among the goitrous group 27 were euthyroid (HT-E), 32 had subclinical hypothyroidism (HT-SH), and 55 had clinical hypothyroidism (HT-H). TSH-BAb were measured in immunoglobulin G prepared by DEAE-Sephadex A-50 by determining their ability to inhibit TSH-dependent cAMP production in a differentiated strain of cultured rat thyroid cells (FRTL-5). Using this sensitive and reproducible method, TSH-BAb were detected in 12 of 26 (46%) patients with AT, in 1 of 27 (3.7%) subjects with HT-E, in 3 of 32 (9.4%) with HT-SH, and in 20 of 55 (36%) with HT-H. The prevalence of TSH-BAb was higher in AT vs. HT-H (P less than 0.001), HT-SH (P less than 0.001), or HT-E (P less than 0.001), and in HT-H vs. HT-SH (P less than 0.001) or HT-E (P less than 0.001). Mean TSH-BAb levels in AT were higher than those in HT-H (P less than 0.005) and HT-SH (P less than 0.025); the difference was not significant between HT-H and HT-SH. An inverse correlation was found between TSH-BAb levels and estimated goiter weight (P less than 0.005). The results of the present study indicate that 1) in autoimmune thyroiditis TSH-BAb are detectable almost exclusively in hypothyroid patients, their prevalence being higher in overt hypothyroidism than in subclinical thyroid failure; 2) the prevalence of TSH-BAb and their mean levels are higher in hypothyroid patients with AT than in those with HT; and 3) therefore, the presence of circulating TSH-BAb appears to be related to the development of hypothyroidism and thyroid atrophy.

The influence of steroid hormones on lipoprotein metabolism has been investigated in menstruating women undergoing oophorectomy; indeed, by this procedure, it is possible to alter selectively the secretion of the hormones and thus to determine the influence of their withdrawal on blood lipids. Within 3 months of surgery we observed significant rapid changes in cholesterol levels of total and HDL-bound components (early decrease and subsequent increase) without alteration of the triglyceride component of the lipoproteins. Similar biphasic changes were observed for the apolipoproteins A and B, determined by immunological methods. These results are suggestive of an action of sex hormones on the lipoprotein metabolism, both on the lipid and the protein moieties. They can be explained by a primary action of the hormones on the apolipoprotein metabolism and a secondary apoprotein-mediated effect on the lipid component of the lipoproteins.

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FRTL-5 cells were shown to be suitable for the measurement of thyroid stimulating antibody (TSAb) present in sera of patients with Graves' disease. Current methods for the assay of TSAb require the separation of immunoglobulin G (IgG) from patient sera. In this report the possibility to measure TSAb directly on serum was evaluated using FRTL-5 cells. To this purpose cells were seeded in 96-well plates and cultured for 4 days in medium deprived of TSH. Using this system bovine TSH was able to produce a significant stimulation of cAMP production at 1 microU/ml. Whole normal serum completely inhibited the stimulation of TSH as well as that of TSAb, while diluted serum was devoid of any effect. Heat inactivated sera and IgGs, prepared by DEAE Sephadex separation, were diluted in hypotonic medium and incubated with cells for 1 h at 37 C. After incubation cAMP was measured in the assay medium by RIA. In some experiments the effects of graded dilutions of sera and IgGs with known TSAb activity were compared. Sera as well as IgGs increased the cAMP production, but, at the highest concentrations, an inhibitory effect was evident. For this reason sera were tested after appropriate dilution. Thirteen/27 (48%) sera and 22/27 (81%) IgGs from patients with Graves' disease were TSAb positive. The effect of Graves' sera on adenylate cyclase stimulation was completely inhibited by an anti-human IgG. The results of stimulation produced by Graves' sera and IgGs were highly correlated (r = 0.97, p less than 0.001). In conclusion it is possible to measure TSAb directly in serum using FRTL-5 cells.(ABSTRACT TRUNCATED AT 250 WORDS)