Evidence of a correlation between thyrotrophin receptor binding inhibition and thyroid adenylate cyclase activation by immunoglobulins in Graves' disease before and during long-term antithyroid treatment

1982 ◽  
Vol 101 (1) ◽  
pp. 35-40 ◽  
Author(s):  
Henning Bliddal ◽  
Karine Bech ◽  
Per Hyltoft Petersen ◽  
Kaj Siersbæk-Nielsen ◽  
Thorkild Friis
Keyword(s):  
Adenylate Cyclase ◽  
Statistical Model ◽  
Receptor Binding ◽  
Graves Disease ◽  
Adenylate Cyclase Activation ◽  
Binding Inhibition ◽  
Antithyroid Treatment ◽  
Analytical Variation ◽  
Stimulation Of

Abstract. In the present study we have measured in parallel thyrotrophin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cyclase stimulating immunoglobulins (TACSI) in patients with Graves' disease (GD) both before and during long-term antithyroid treatment. A statistical model based on the calculation of the differences (TACSI-TBII) is presented, comparing the changes in this parameter to the analytical variation. The correlation between TBII and TACSI in 52 patients with GD before treatment was: r = 0.58, P < 0.0001. During long-term antithyroid treatment of GD the 2 activities changed in parallel in 39 of 45 patients followed. In a few patients discrepancies were observed, and 1 patient, initially TACSI positive, developed adenylate cyclase inhibiting IgG during treatment but without detectable TBII. In conclusion, 1) TBII and TACSI are significantly correlated in patients with GD both before and during long-term antithyroid treatment, 2) in some patients discrepancies between TBII and TACSI suggest, that these IgGs are heterogeneous with varying capacity for stimulation of the adenylate cyclase and receptor binding, and 3) adenylate cyclase inhibitory IgG without TBII activity was demonstrated in GD.

Thyroid stimulating immunoglobulins in Graves' disease with goitre growth, low thyroxine and increasing triiodothyronine during PTU treatment

1984 ◽  
Vol 107 (4) ◽  
pp. 482-488 ◽  
Author(s):  
Laszlo Hegedüs ◽  
Jens M. Hansen ◽  
Karine Bech ◽  
Jens P. Kampmann ◽  
Keld Jensen ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Thyroid Volume ◽  
Subtotal Thyroidectomy ◽  
Graves Disease ◽  
Normal Range ◽  
Thyroid Stimulating Immunoglobulins ◽  
Maximum Value ◽  
Adenylate Cyclase Activation ◽  
Group 2 ◽  
Group 1

Abstract. In 50 consecutive patients with Graves' disease treated with PTU, 7 (group 1) developed increasing goitre in spite of unmeasurable TSH. Thyroid variables were compared with those from 10 controls with an ordinary response to PTU (group 2). Serum T4 decreased in group 1 from 246 ± 47 nmol/l (mean ± sd) to 40 ± 9 nmol/l after 6 weeks of PTU treatment and continued to be below the normal range during the next 4 months. In group 2 serum T4 decreased from 190 ± 35 to 88 ± 47 nmol/l and stayed in the normal range. Serum T3 was normalized in both groups after 6 weeks but increased to values above the normal range in group 1 after that time. In spite of unmeasurable TSH during the 6 months of treatment in group 1, thyroid volume, determined ultrasonically, increased significantly from 60 ± 29 to 93 ± 68 ml (P < 0.05), but was unaltered in group 2 about 25 ml. Thyroid stimulating antibodies (TSAb) measured by adenylate cyclase activation (normal below 109%) decreased in group 2 from 117 ± 23 to 90 ± 17% (P <0.01) (6 months of therapy), but increased significantly in group 1, from 201 ± 47% to a maximum value of 234 ± 69% (P < 0.05). TSH binding inhibitory immunoglobulins (TBII) (given as per cent inhibition, normal below 26%) decreased in group 2 from 43 ± 29 to 29 ± 27% (P < 0.05) but were unaltered high in group 1,66 ± 25% before therapy and 57 ± 26% after 6 months of therapy. A positive correlation was found between thyroid volume and TSAb and TBII levels (P < 0.05, P < 0.05) before treatment as well as during the treatment period of 6 months. In 5 of 7 patients of group 1 either 131I therapy or subtotal thyroidectomy were necessary to control the disease. It is proposed that TSAb and TBII remaining abnormal in this subgroup of patients with Graves' disease, might in part explain the unusual response to PTU-treatment.

scholarly journals Experimental Reproduction of Dynamic Fluctuation of TSH Receptor–Binding Antibodies Between Stimulation and Inhibition

2019 ◽  
Vol 3 (12) ◽  
pp. 2361-2373
Author(s):  
Tetsuya Tagami ◽  
Kaho Hiroshima-Hamanaka ◽  
Hironobu Umakoshi ◽  
Mika Tsuiki-Naruse ◽  
Toru Kusakabe ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Tsh Receptor ◽  
Graves Disease ◽  
Camp Production ◽  
Isolated Cells ◽  
Human Mabs ◽  
Experimental Reproduction ◽  
Dynamic Fluctuation ◽  
Stimulation Of

Abstract Context Hyperthyroidism in Graves disease (GD) is caused by autoantibody stimulation of the TSH receptor (TSHR). TSHR autoantibody (TSHR-Ab) activity is measured routinely by inhibition of labeled ligand (TSH or M22) binding to the TSHR [TSH-binding inhibitory immunoglobulins (TBIIs)] or by stimulation of cAMP production in isolated cells [TSH receptor–stimulating antibodies (TSAbs)]. Usually, measurements of TSHR-Abs by TBIIs agree reasonably well with TSAb values at least in the setting of hyperthyroidism, and both measurements tend to change in parallel during treatment with some exceptions. In this study, we describe three unusual cases, which illustrate nearly pure stimulating, blocking, or neutral properties of TSHR-Abs. Objective Whether patient serum TSHR-Abs can be reproduced by mixtures of human monoclonal autoantibodies to the TSHR was studied because the sera in most patients show moderate properties having both of TBII and TSAb activities. Design We compared the TBII and TSAb activities of serum from four unusual patients in detail with mixtures of human monoclonal TSHR-Abs (mAbs) M22 (stimulating), K1-18 (stimulating), and K1-70 (blocking). Results Characteristic of a patient’s serum was similar to M22 or K1-18, another was similar to K1-70, whereas another was similar to a mixture of K1-70 and M22 (or K1-18). Additionally, some patients seemed to have neutral TSHR-Abs in their sera. Conclusions Our studies suggest that the characteristics of TSHR-Abs in the patient serum can be mimicked by mixtures of human mAbs to the TSHR, stimulating, blocking, and neutral if any.

Comparison of renal and osseous binding of parathyroid hormone and hormonal fragments

1985 ◽  
Vol 249 (5) ◽  
pp. E437-E446 ◽  
Author(s):  
M. Demay ◽  
J. Mitchell ◽  
D. Goltzman
Keyword(s):  
Parathyroid Hormone ◽  
Adenylate Cyclase ◽  
Osteosarcoma Cells ◽  
Binding Studies ◽  
Intact Pth ◽  
Amino Terminal ◽  
Adenylate Cyclase Activation ◽  
Adenylate Cyclase Stimulation ◽  
Bovine Parathyroid Hormone ◽  
Stimulation Of

We compared receptor binding and adenylate cyclase stimulation of intact bovine parathyroid hormone (bPTH)-(1-84) and the synthetic amino-terminal fragments, bPTH-(1-34) and rat PTH (rPTH)-(1-34). Radioligands for binding studies were prepared by the lactoperoxidase technique and purified by high-pressure liquid chromatography. In both canine renal membranes and cloned rat osteosarcoma cells the amino-terminal fragments bound to a single order of sites; the affinity of rPTH-(1-34) exceeded that of bPTH-(1-34), correlating with its higher potency in stimulating adenylate cyclase. In studies with oxidized bPTH-(1--84), the middle and carboxyl regions of intact PTH were found to bind to both tissues but with higher affinity to osteosarcoma cells than to renal membranes. Our results demonstrate that rPTH-(1--34) is the most favorable probe of amino-terminal PTH binding and the most potent of the PTH peptides in stimulating renal and osseous adenylate cyclase. The results also show that midregion and carboxyl determinants within intact PTH contribute to hormone binding, which does not correlate with adenylate cyclase activation and appears more significant for skeletal than for renal binding.

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