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Adenylate Cyclase Activity in Thyroid Tissue from Patients with Untreated Graves' Disease^*

Departments of Nuclear Medicine and Otorhinopharyngolaryngology, Kyoto University School of Medicine, Kyoto, and the Department of Internal Medicine, Kobe Central City Hospital and Kuma Hospital Kobe, Japan

Address requests for reprints to: Kanji Kasagi, M.D., Department of Nuclear Medicine, Kyoto University School of Medicine, Shogoin, Sakyo-ku, Kyoto 606, Japan.

Both basal and TSH-stimulated (10 mU/ml) adenylate cyclase (AC) activities were measured in a crude plasma membrane function (800–10,000 x g) prepared from 3–10 mg (wet wt) thyroid tissue, which was obtained from patients with Graves disease and thyroid adenoma and from normal subjects. Twelve thyroid tissues of patients with untreated Graves disease and 4 adenoma tissues were obtained by needle biopsy, while 15 normal thyroid tissues, 20 tissues of patients with Graves disease under treatment, and 8 adenoma tissues were obtained at the time of operation. AC activities measured in 4 thyroid adenoma tissues obtained by needle biopsy did not differ significantly from those in 8 adenoma tissues obtained at the time of operation.

In normal thyroid tissue the basal AC activity and the percent stimulation by TSH were 1.25 ± 0.46 (mean ± SD) pmol cAMP generated/mg wet wt-10 min and 134.0 ± 23.8%, respectively. In untreated Graves thyroid tissue, the mean basal AC activity (2.76 ± 0.57) was significantly higher (P< 0.001) and the percent stimulation by TSH (111.5 ± 18.3%) was significantly lower (P < 0.02) than these values in normal thyroid tissue. Thyroid tissue from treated Graves patients showed a mean basal AC activity of 1.68 ± 0.65, which was significantly higher than that in normal thyroid tissue (P < 0.05) and lower than that in untreated Graves' thyroid tissue (P < 0.001). The difference between treated Graves and normal thyroid tissues, however, was not significant when expressed per mg membrane protein.

In adenoma tissue, the basal AC and the percent stimulation were 2.89 ±1.84 and 261.1 ± 145.3%, both of which were significantly higher than these values in normal thyroid tissue (P < 0.01). Human thyroid adenylate cyclase stimulator (HTACS) was detected in 7 (58.3%) of the 12 patients with untreated Graves' disease. Mean basal AC activity in the thyroid tissue from patients with positive HTACS was significantly higher (P < 0.02) than that in tissue from patients without detectable HTACS. These results suggest that Graves' thyroid tissue has been actually stimulated by abnormal thyroid stimulators such as HTACS.

^* This work was supported in part by a Research Grant for the Intractable Diseases from the Ministry of Health and Welfare of Japan.

Received January 26, 1979.