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Three euthyroid patients with Hashimoto's thyroiditis developed hypothyroidism after the administration of rifampin. We studied 67 patients with tuberculosis. All of them were treated with rifampin. Of the 67 patients, 42 had negative tests for anti-thyroid antibodies (ATA) and 25 had positive tests for ATA. The diagnosis of Hashimoto's thyroiditis was made on the basis of positive tests for ATA. After the administration of rifampin, TSH levels were not significantly altered in all of the former 42 ATA-negative patients and in 22 of the latter 25 ATA-positives, but TSH levels increased in the other three (Patients 1, 2 and 3) of the latter 25 ATA-positives. Three euthyroid Hashimoto's patients (Patients 1, 2 and 3) developed hypothyroidism after the administration of rifampin. This rifampin-induced hypothyroidism resolved in each, once rifampin was discontinued. A) Patient 1: a 62-yr-old man with lymphoma had pulmonary tuberculosis. After the administration of rifampin, serum TSH increased to 170 mU/l; B) Patient 2: a peritoneal-biopsy specimen containing Langhans' giant cells led to a diagnosis of tuberculous peritonitis in a 66-yr-old woman with ascites. After the administration of rifampin, TSH increased to 12.4 mU/l; C) Patient 3: a 56-yr-old woman with a liver abscess and lymphadenopathy underwent lymph-node biopsy that showed Mycobacterium tuberculosis with caseating granulomas. After the administration of rifampin, TSH increased to 21.3 mU/l. After its administration, Patients 1, 2 and 3 developed hypothyroidism, and received T4. When rifampin was discontinued, the hypothyroidism resolved. After the course of rifampin-therapy had been completed, T4 was discontinued. At-risk patients who receive rifampin may become hypothyroid.

There are two types of TSH receptor antibodies (TRAb); thyroid stimulating antibody (TSAb) and TSH-stimulation blocking antibody (TSBAb). TSAb causes Graves' hyperthyroidism. TSBAb causes hypothyroidism. Both TSAb and TSBAb block TSH-binding to thyroid cells as TSH receptor antibodies (TRAb). TSBAb-positive patients with hypothyroidism and Graves' patients with hyperthyroidism may have both TSBAb and TSAb. We studied TSBAb and TSAb in 43 TSBAb-positive patients with hypothyroidism and in 55 untreated Graves' patients with hyperthyroidism. TSBAb-activities were expressed as percentage inhibition of bovine (b) TSH-stimulated cAMP production by test IgG. Two formulas were used to calculate TSBAb-activities; TSBAb-A (%) = [1 - (c - b)/(a - b)] x 100 and TSBAb-B (%) = [1 - (c - d)/(a - b)] x 100, where a: cAMP generated in the presence of normal IgG and bTSH, b: cAMP generated in the presence of normal IgG, c: cAMP generated in the presence of test IgG and bTSH, and d: cAMP generated in the presence of test IgG. TSAb (%) = [d/b] x 100. All of the 43 TSBAb-positive patients with hypothyroidism had strongly positive TSBAb-A and -B. Some of them had weakly positive TSAb (<240%). All 55 untreated Graves' patients had positive TSAb (205-2509%). Some of them had both TSAb and TSBAb. TSBAb-positive patients with hypothyroidism had a limited distribution of TSBAb- and TSAb-activities (TSBAb-A + 75 - + 103%, TSBAb-B + 87 - + 106%, TSAb 92-240%), but Graves' patients with hyperthyroidsim had a wide distribution of TSAb- and TSBAb-activities (TSAb 205-2509%, TSBAb-A - 158 - + 43%, TSBAb-B - 14 - + 164%). TSBAb-A ignores TSAb activity in serum, and might give low TSBAb activity. However, TSBAb-A clearly differentiates TSBAb-positive patients with hypothyroidism from Graves' patients with hyperthyroidism; thus, we favor TSBAb-A over TSBAb-B. Some of TSBAb-positive patients with hypothyroidism and Graves' patients with hyperthyroidism have both TSBAb and TSAb.

Although the factors that cause developments or exacerbations of autoimmune thyroid dysfunction are not known, the changes of glucocorticoids might modulate the autoimmune responses. We compared the postoperative changes in thyroid function in one patient with Carney's complex with primary adrenocortical nodular dysplasia (PAND) and 19 patients with Cushing's disease due to ACTH-producing pituitary adenoma. Thyroid dysfunction developed after surgery for glucocorticoid excess in two patients; one with Carney's complex had transient hypothyroidism after bilateral adrenalectomy for PAND, and the other had transient hyperthyroidism due to thyroiditis after removal of ACTH-producing pituitary adenoma for Cushing's disease. Both patients had no thyroid autoantibodies at the time of surgery. None of the remaining 18 patients had clinically evident thyroid disease or increased antithyroidantibody titers. Development of autoimmune thyroid dysfunction may be observed after surgery for glucocorticoid excess in the patients with any forms of Cushing's syndrome, even who do not have thyroid antibodies.

Background: Hypothyroidism may result from the production of antibodies that block the actions of thyrotropin. How often these thyrotropin-blocking antibodies are a cause of hypothyroidism and whether their production may cease, causing hypothyroidism to disappear, have not been extensively studied., Methods: We determined the frequency with which thyrotropin-blocking antibodies were present in 172 hypothyroid patients with goitrous autoimmune thyroiditis (Hashimoto's disease) and 64 hypothyroid patients with atrophic autoimmune thyroiditis (idiopathic primary hypothyroidism). For 6 to 11 years we then followed 21 of these patients who were found to have thyrotropin-blocking antibodies. They received levothyroxine therapy for 3.5 to 8 years, after which it was discontinued. At frequent intervals during this time we measured the patients' serum concentrations of thyroxine, triiodothyronine, thyrotropin, and thyrotropin-blocking antibodies (measured as immunoglobulins that inhibit thyrotropin binding and immunoglobulins that inhibit thyrotropin bioactivity)., Results: Thyrotropin-blocking antibodies were detected in 9 percent of the patients with goitrous autoimmune thyroiditis and in 25 percent of those with atrophic autoimmune thyroiditis. Among the 21 patients studied serially while receiving levothyroxine, thyrotropin-blocking antibodies disappeared in 15 (group 1), 7 of whom had goiter initially, and persisted in 6 (group 2), none of whom had goiter initially. Levothyroxine therapy was subsequently discontinued in these 21 patients. Six of those in group 1 (four with goiter) remained euthyroid (mean follow-up after discontinuation of therapy, 2.1 years), and nine became hypothyroid again within 3 months. All six patients in group 2 remained hypothyroid., Conclusions: Hypothyroidism in some patients with autoimmune thyroiditis may be due to thyrotropin-blocking antibodies. The production of thyrotropin-blocking antibodies may subside, producing remissions of hypothyroidism. Chronic autoimmune thyroiditis may therefore cause transient as well as permanent hypothyroidism.

Hashimoto's and Graves' diseases represent the main two types of autoimmune thyroid disease. The combination of these two is well known. However, occurrence of Graves' disease after primary hypothyroidism is rare. We report seven patients with hypothyroidism due to Hashimoto's disease, who developed Graves' disease with hyperthyroidism. We also report one patient with hypothyroidism due to Hashimoto's disease, who continued to be hypothyroid even in the presence of TSAb (thyroid stimulating antibody). These patients were divided into three groups according to the changes in thyroid function and clinical course: (1) transient hyperthyroidism due to Graves' disease following hypothyroidism; (2) persistent hyperthyroidism due to Graves' disease following hypothyroidism; and (3) persistent hypothyroidism with positive TSAb. Such changes in thyroid function and clinical course seem to be decided by three factors: (1) TSAb and (2) TSBAb (thyroid stimulation blocking antibody) activities in the blood and (3) the responsiveness of the thyroid gland to TSAb. Seven patients had hyperthyroidism, when they had TSAb, which stimulated the thyroid gland; one of these seven patients had TSBAb during the hypothyroid state and TSAb during the hyperthyroid state, indicating that the alterations in the thyroid state related to the balance between the activities of TSAB and TSBAb. Another patient continued to be hypothyroid despite the presence of TSAb; his thyroid gland was not palpable and could not respond to TSAb.

Hypothyroid patients with Hashimoto's thyroiditis usually receive lifelong thyroxine therapy. Some are known to recover thyroid function, but identification of these patients during continued thyroxine therapy has been impossible. 92 patients with hypothyroidism after Hashimoto's thyroiditis and 70 normal controls were studied. All controls but not patient before thyroxine was started had a normal thyroid response to thyroid stimulating hormone (TSH), circulating concentrations of which were increased by administration of 500 micrograms thyrotropin releasing hormone (TRH). During treatment with thyroxine, 22 patients recovered thyroid responsiveness to TSH, and when treatment was stopped these patients have remained euthyroid for 1-8 years, whereas all 70 who did not recover thyroid TSH responsiveness became hypothyroid within 3 months. Over 20% of patients with hypothyroidism after Hashimoto's thyroiditis may recover satisfactory thyroid function, and can be identified during thyroxine treatment by their thyroid response to TSH in a TRH test.

In an attempt to re-evaluate a possible high incidence of hypertension in hypothyroid patients, blood pressure was measured in 38 slightly hypothyroid patients, in 17 moderate hypothyroid patients, and in 26 severe hypothyroid patients. The data were then compared with the findings in 73 known euthyroid subjects and in 1,601 possibly euthyroid subjects. Blood pressure and incidence of hypertension increased progressively with age in known euthyroid subjects and in possibly euthyroid subjects. Similarly, blood pressure increased progressively with age in slight and moderate hypothyroid patients, but the incidence of hypertension was high in the sixth decade in slightly hypothyroid patients for some unknown reason. In contrast, blood pressure and the incidence of hypertension were low in the fifth and sixth decades in severe hypothyroid patients. This low blood pressure was elevated slightly when Sv1 + Rv5 and C/T were shifted toward normal by T4 treatment for 3 to 4 months. It is suggested that the hypothyroid state does not accelerate the development of hypertension.

The status of TSH secretion in hypothalamic hypothyroidism was evaluated by using rats with anterior medial basal hypothalamic deafferentation as the experimental model of the disorder. In the deafferented rats, the basal serum thyroid hormone concentrations as well as that of TSH was significantly lower than normal and cold exposure failed to increase serum TSH, indicating they were in fact in a hypothalamic hypothyroid state. The minimum effective dose of TRH to elicit an increase in serum TSH was smaller in the deafferented rats than in the controls, whereas the response to the maximum dose of TRH was similar in both groups. Although the radioimmunoassayable TSH of the adenohypophysis was significantly decreased in the deafferented rats, it was qualitatively similar to that of the control rats, since the peak of TSH immunoreactivity was eluted at exactly the same position on the gel filtration column in the pituitaries from normal and deafferented rats. When the adenohypophysis was perifused in vitro with Krebs-Ringer solution buffered with Hepes, the minimum effective dose of TRH was similar in both cases. This finding suggests that the exposure to the perifusion medium completely devoid of thyroid and hypothalamic hormones erased the difference in sensitivity to TRH between the two groups as observed in vivo, although in vivo experiments on deafferented rats with normal thyroid hormone induced by exogenous thyroid hormone were not performed. Our results indicate that in hypothalamic hypothyroid rats: 1) the sensitivity but not the responsiveness of the thyrotroph to TRH is increased; and 2) the readily releasable fraction of pituitary TSH pool in response to exogenous TRH is increased. It is also suggested that the difference in the milieu between the pituitary of normal and deafferented rats in vivo is critically important for the latter to retain hypersensitivity to TRH.