Karine Bech

Thyroid function in patients with breast cancer

Thyroid function was evaluated in 58 patients with breast cancer and compared with data obtained from an age-matched control group of healthy women. Thyroid antibodies at low levels were present in 29 patients (50%): 21 patients (36%) had thyroid stimulating antibodies at low activity. Ten patients (17%) had thyroglobulin antibodies compared with 3 in the control group (P less than 0.05). Nine of 10 patients with thyroglobulin antibodies had microsomal antibodies as well. Two patients had only microsomal antibodies. Additionally 10 autoimmune antibodies were determined. These were, however, either absent or present in low concentrations in serum. Independent of the stage of disease, no differences were demonstrated between patients and controls in serum levels of triiodothyronine, thyroxine, free T3 index, free T4 index, thyroid stimulating hormone, and thyroglobulin. In conclusion, we found an increased frequency of thyroid autoantibodies in euthyroid patients with breast cancer compared with healthy controls suggesting a possible relation between this disease and autoimmune thyroid disease.

INTERLEUKIN-6 PRODUCTION BY THYROID EPITHELIAL CELLS. ENHANCEMENT BY INTERLEUKIN-1

Interleukin-1 is a potent inhibitor of thyroglobulin and cAMP production in human thyroid cells and the inhibitory effect is enhanced by tumor necrosis factor-alpha and interferon-gamma. In the present study secondary cultures of human thyroid cells produced interleukin-6 and the production was significantly increased after exposure of the cells to recombinant interleukin-1 alpha and -1 beta. This increase was dose-dependent and concomitant of the IL-1 induced decrease in cAMP and thyroglobulin production. Both tumor necrosis factor-alpha and -beta also augmented interleukin-6 production, but less potently than interleukin-1. Interferon-gamma did not affect the production of interleukin-6. The rat thyroid cell line FRTL-5 produced interleukin-6 spontaneously, and the production was enhanced after addition of recombinant interleukin-1 beta. A pathogenetic role of interleukin-6 in autoimmune thyroid disease is suggested.

Thyroid function in patients with Pendred's syndrome

Thyroid function was studied in 17 unrelated patients with Pendred’s syndrome. Fourteen patients had been treated with L-thyroxine, which was withdrawn during the investigation. Eight of the patients had previously had a thyroid resection. Thirteen patients had goiter at the time of study. The serum total thyroxine and serum total triiodothyronine concentrations were normal in 8, of whom 3 had elevated serum TSH concentrations. In the remaining 9 cases the thyroxine levels were below normal with elevated TSH. Serum reverse triiodothyronine concentrations were decreased in 8 out of 11. Median serum thyroglobulin was 973 μg/l (range 10.9–3200 μg/1) and increased in 13. Three patients had slightly positive thyroglobulin antibodies and one with normal level was thyrodectomized. Thyroid stimulating antibodies as measured by adenylate cyclase stimulation (median 114%, range 85–137%) were slightly increased in 11. When measured as TSH binding inhibiting immunoglobulins none were positive. Thyroid microsomal antibodies were negative in all. All patients with a detectable 131I uptake (n = 15) showed a pathological iodide perchlorate discharge test (median 32%, range 16–46%). These findings indicate an organification defect with impaired hormone synthesis.

Circulating immune complexes in Hashimoto's thyroiditis. Correlation to HLA and autoantibodies

Circulating immune complexes (IC) were determined in sera from 41 patients with Hashimotos thyroiditis by a polyclonal rheumatoid factor (pRF) assay based on the inhibition of the agglutination of IgG‐coated latex particles. Elevated levels of IC were found in 63% (26/41) of the sera. There was a significant correlation (Rho = 0.91, P < 0.001) between results obtained before and after treatment of sera with dithiothreitol (DTT). By precipitation with 2.5% polyethylene glycol (PEG) before pRF inhibition assay, the activity of IC was found in only 7% (3/41) of the sera. Size chromatography studies of the sera showed the inhibitory activity predominantly in the intermediary region. When found in the IgM‐region the activity was not reduced by DTT. By use of a polyethylene glycol complement consumption test (PEG‐CC) the occurrence of IC was 10% (4/41). It was not possible to find any correlation between the detectable IC and the presence of microsomal, thyroglobulin, or thyroid‐stimulating antibodies. Based on our studies the sizes of IC seemed to be heterogeneously distributed and the majority were not precipitated by PEG (2.5%, final concentration). The antibodies involved in the formation of complexes seemed to be of IgG or IgA classes. HLA‐D typing of the patients showed a non‐significant association between HLA‐Dw5 and low levels of IC while the presence of HLA‐Dw4 was significantly associated with a high level of IC (P < 0.05).

Thyroid‐stimulating immunoglobulins in insulin‐dependent diabetes mellitus

Abstract. Increased frequencies of thyroid diseases and thyroid microsomal antibodies have been observed in insulin‐dependent diabetes mellitus. However, the exact prevalence of thyroid‐stimulating immunoglobulins has not been established. In the present study these antibodies were measured by both a radioreceptor and an adenylate‐cyclase stimulation assay.

Thyroid stimulating antibodies in rheumatoid arthritis: an in vitro phenomenon

The purpose of the study was to evaluate the frequency of thyroid stimulating immunoglobulins and their possible effect in vivo in patients with rheumatoid arthritis. Thyroid stimulating antibodies (TSAb) were present in 17 (68%) of 25 patients with rheumatoid arthritis, whereas only 2 (8%) had thyrotropin binding inhibiting immunoglobulins (TBII). The groups with and without TSAb were comparable with regard to sex, age, anti-inflammatory drugs, serum thyroglobulin levels, antithyroglobulin and antimicrosomal antibodies, rheumatoid factor, as well as to the serum levels of thyroxine and 3, 5, 3′-triiodothyronine. A possible stimulating effect of TSAb in vivo was evaluated by an ultrasensitive immunoradiometric assay for TSH. Both groups had normal serum TSH levels, and no significant difference was found between the two groups suggesting that the demonstration of TSAb in vitro is not always associated with a stimulation of the thyroid gland in vivo.

The prognostic value of parallel measurements of thyrotropin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cyclase stimulating antibodies (TSAb) in Graves’ disease after longterm antithyroid treatment

Thyroid stimulating immunoglobulins were measured in 43 patients with Graves’ disease both before and at the end of longterm antithyroid treatment. Parallel determinations were performed of thyrotropin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cyclase stimulating antibodies (TSAb). Before treatment 33 patients were TBII positive and 32 TSAb positive, and at the end of treatment 19 remained TBII positive and 14 TSAb positive. The frequency of relapse was about 70% in the positive patients and about 40% in the patients, who became negative in either test for thyroid stimulating immunoglobulins. By combination of the two assays 23 patients were positive in both before treatment. In these patients 5 relapsed of the 6 who remained positive for both, while none relapsed of the 5 patients, who became negative during treatment. In the remaining 12 patients either TBI I or TSAb became negative during treatment and 7 of these relapsed. It is concluded, that the combined measurement of TBII and TSAb in this study seemed superior to the separate determinations of either activity in predicting relapse after medical treatment of Graves’ disease, though this evaluation was only possible in part of the patients.