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Ken Okamura, Kenjiro Inoue and Teruo Omae

ABSTRACT

An interesting case of iodide induced goitre with immunological abnormalities is described. The patient who was sensitive to synthetic penicillin had previously been treated for exudative pleuritis, congestive heart failure and acute renal failure. Following recovery, he began to ingest large amounts of seaweed after which he developed goitrous hypothyroidism. It was of interest that the serum level of gamma-globulin increased, and subsequently the antithyroid microsomal antibody became strongly positive, suggesting that thyroidal autoimmune processes had been precipitated. Biopsy of the thyroid gland revealed chronic thyroiditis, with evidence suggesting extreme stimulation by TSH. High thyroidal uptake of 131I, positive perchlorate discharge test and biochemical analysis of the thyroidal soluble protein showed severe impairment of hormone synthesis following continuous accumulation of excess iodide. While there is evidence suggesting that increased iodide may be an important factor in the initiation of Hashimoto's thyroiditis, this may result from the marked increased sensitivity of Hashimoto's gland to the effects of iodine. Thus an occult lesion could be unmasked in this manner. The mechanism by which iodide mediates this effect is not clear.

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Ken Okamura, Kenjiro Inoue, Toshiro Nakashima, Akiyo Shiroozu and Mototaka Yoshinari

ABSTRACT

Thyroid lobes of male Sprague-Dawley rats on an iodine-sufficient diet were incubated in our improved in vitro system with 0.01 μm 127I and 5 mU/ml of bovine TSH. Thyroidal 131I-uptake and the relative incorporation of iodine into iodothyronines increased with time. The average yield of each iodoamino acid after 8 h of incubation was: monoiodotyrosine 28.0 %, diiodotyrosine 46.5 %, triiodothyronine 1.9 % and thyroxine 13.9 %, which showed a striking resemblance to the values obtained in vivo. The yields of iodotyrosines and iodothyronines, the latter in particular, were strikingly high, and this system is considered to be useful in the study of thyroidal iodine metabolism.

Effects of TSH, temperature and pH of the medium were examined and a unique effect of pH was observed on the iodoamino acid synthesis. As the pH was elevated from 6.8 to 7.9, 131I-uptake, MIT/DIT ratio, T4/DIT ratio and T3/T4 ratio increased. The effect of slightly alkaline pH was considered to be similar to that observed in iodine-deficiency.

It was found that the rubber stoppers which are commonly used in shortterm incubation contain a kind of potent inhibitor of thyroid hormone synthesis. The pattern of inhibition was similar to that of thionamide compounds.

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Takeo Kuroda, Ken Okamura, Mototaka Yoshinari, Hiroshi Ikenoue, Kaori Sato, Yoshiaki Yamashita, Shuichi Takishita and Masatoshi Fujishima

Abstract.

A 55-year-old man with normotensive primary aldosteronism, hypopituitarism, epilepsy, and medullary sponge kidney is reported. Seventeen years before admission, he had been noted to have hypokalemia associated with high potassium clearance, suppressed plasma renin activity, metabolic alkalosis, and normal blood pressure as well as low urinary excretion of 17-hydroxycorticosteroids. He kept normotensive in spite of hyperaldosteronism until nine months after the initiation of replacement therapy with glucocorticoid and thyroxine for hypopituitarism, when he became hypertensive. Hypopituitarism seemed to play a role in keeping a normal blood pressure despite long-standing hyperaldosteronism.

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Hiroshi Ikenoue, Ken Okamura, Kaori Sato, Takeo Kuroda, Mototaka Yoshinari, Takashi Tokuyama, Mizuho Nakagawa and Masatoshi Fujishima

Abstract.

Thyroid stimulation indices such as high thyroidal radioactive iodine uptake, increased estimated thyroid weight, presence of TSH-binding inhibitor immunoglobulin or thyroid-stimulating antibody, and elevated serum thyroglobulin level, were evaluated in 148 patients with Graves' disease who had been treated with antithyroid drugs for two years or more before the drugs were withdrawn. In all 19 patients in whom three or more indices were positive, early relapse, within 12 months, occurred after reducing the dosage of antithyroid drugs. Other 129 patients were followed after the drug was withdrawn and in 77 patients with one or two positive indices, early relapse occurred in 65-71% and late relapse, after 12 months or later, occurred in 2-11%. In 52 patients in whom none of the indices were positive, 86% remained in remission, but 10% developed an early relapse, and 4% a late relapse. We conclude that a combined analysis of thyroid stimulation indices is useful in predicting relapse in Graves' disease whereas it remains difficult to predict permanent remission.

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Ken Okamura, Kaori Sato, Hiroshi Ikenoue, Mizuho Nakagawa, Takeo Kuroda, Mototaka Yoshinari and Masatoshi Fujishima

Okamura K, Sato K, Ikenoue H, Nakagawa M, Kuroda T, Yoshinari M, Fujishima M. Primary hypothyroidism manifested in childhood with special reference to various types of reversible hypothyroidism. Eur J Endocrinol 1994;131:131–7. ISSN 0804–4643

The clinical courses of 15 patients with overt primary hypothyroidism manifested in childhood were studied. Nine female patients with goitrous hypothyroidism due to chronic thyroiditis showed almost normal height and became euthyroid spontaneously during iodine restriction. The other 6 non-goitrous patients (3M and 3F) (atrophic thyroiditis in 2, lingual goiter in 2 and probable hypoplastic thyroid in 2) showed physical growth retardation and remained irreversibly hypothyroid requiring replacement therapy. In the reversible group, the characteristic findings were high thyroidal radio-active iodine uptake (58 ± 19%/24 h, N = 8) and positive perchlorate discharge test. Serum non-hormonal iodine levels were high in 4 of 6 patients measured. During the long-term follow-up period of 6 years in 6 patients, 2 patients remained euthyroid with normal growth and regular menstrual cycle and 4 patients became hypothyroid again (after eating seaweed in 1, despite iodine restriction in 2 and after the episode of painless thyroiditis in 1). Transient retardation of growth was observed during the second episode of hypothyroidism. In the irreversible group, one patient with blocking type TSH binding inhibitor immunoglobulin (TBII) became thyrotoxic 4 years later with the decrease in activity of blocking type TBII. These results suggested that reversible recovery of the thyroid function could be expected in patients with juvenile hypothyroidism due to chronic thyroiditis after (1) iodine restriction, (2) improvement of immunological perturbation, or (3) disappearance of blocking type TBII. However, careful follow-up is necessary, because hypothyroidism would recur again with transient retardation of growth in children.

Ken Okamura, Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812, Japan

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Ken Okamura, Kaori Sato, Mototaka Yoshinari, Hiroshi Ikenoue, Takeo Kuroda, Mizuho Nakagawa, Hiroshi Tsuji, Masakazu Washio and Masatoshi Fujishima

Abstract

The prognosis of atrophic hypothyroidism with blocking type TSH-binding inhibitor immunoglobulin was studied. Among 45 patients (16 males and 29 females) with overt hypothyroidism (serum TSH >40 mU/l) without goitre, thyroid autoantibody to microsomal antigen was positive in 38 or 84.4%, and 4 or 8.9% had TSH-binding inhibitor immunoglobulin, which was shown to be a TSH-stimulation blocking antibody by cAMP production assay using cultured porcine thyroid cells. Thyroidal radioactive iodine uptake was low and thyroid hormone replacement therapy was required. Long-term follow up of 2 patients with strongly positive TSH-binding inhibitor immunoglobulin for 2 to 7 years, however, revealed recovery of the thyroid function after steroid therapy or spontaneously with iodide restriction, respectively, correlating with decrease in both TSH-binding inhibitor immunoglobulin and TSH-stimulation blocking antibody activities. Thyroidal radioactive iodine uptake became normal and histological examination of the thyroid in one patient revealed well-preserved thyroid follicles with lymphocytic infiltration. Recovery of thyroid function can be expected with a decrease in TSH-binding inhibitor immunoglobulin activity in atrophic hypothyroidism, which is not necessarily the end stage of chronic thyroiditis.

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Kaori Sato, Ken Okamura, Mototaka Yoshinari, Takeo Kuroda, Hiroshi Ikenoue, Kaeko Okazawa, Tetsuya Mizokami, Kaoru Onoyama and Masatoshi Fujishima

Recovery of thyroid function in patients with both thyroid and renal dysfunction was studied. Among 245 patients with primary hypothyroidism (serum TSH >10 mU/l), 36 had mild to severe renal dysfunction (serum urea nitrogen >7.1 mmol/l and creatinine >106 μmol/l). Of these 36 patients, recovery of the thyroid function after iodine restriction was observed in 30(83%), in whom an elevated serum non-hormonal iodine level (median 236, range 67–15591 μg/l, N=19) and a high thyroidal radioactive iodine uptake (51.5±29.3%at24h, N = 26) were observed. The perchlorate discharge test was positive in 7 of 13 patients examined, suggesting an iodide organification defect rather than an atrophic or destructive change in the thyroid. Antithyroid antibodies were negative in 22 patients (73%) and an almost normal thyroid gland or colloid goitre was confirmed histologically in 8 of them. After a 13.2 mg potassium iodide loading test, 24 h urinary excretion of iodine was about 60% in normal controls, but only 10% in a different group of six euthyroid patients with renal dysfunction. These findings suggest that impaired renal handling of iodine rather than autoimmune mechanism may have a significant role in the pathogenesis of reversible hypothyroidism found in patients with renal dysfunction, probably through a prolonged Wolff-Chaikoff effect.