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Haruki Fukuda, Yasuhiro Ito, Ryouji Hirota, Motomu Tsuji, and Hiroshi Mori

Abstract.

Effects of deficiency in ascorbic acid on in vivo production of corticosterone and testosterone were examined using a mutant strain of rats unable to synthesize ascorbic acid. The adrenal weight of scorbutic rats was larger, and corticosterone levels in plasma and adrenal tissues were higher than those of ascorbic acid-supplied (ascorbutic) rats. Acute and chronic stimulation with ACTH increased corticosterone levels in both ascorbutic and scorbutic rats. In contrast, weights of seminal vesicles and ventral prostates in unstimulated scorbutic rats were smaller, and testosterone levels in plasma and testicular tissues were lower than those in ascorbutic rats. Acute stimulation with hCG increased testosterone levels only slightly in plasma and not in testicular tissues of scorbutic rats, when testosterone levels in ascorbutic rats reached a maximum. Chronic stimulation with hCG increased testosterone levels remarkably in both ascorbutic and scorbutic rats. These findings seem to indicate that ascorbic acid is not essential for the synthesis of steroid hormones. The scurvy seems to increase plasma ACTH levels secondary to the stress, resulting in the stimulation of the adrenals. In contrast, a prolonged deficiency in ascorbic acid appears to decrease plasma gonadotropin levels, and may reduce the sensitivity of testes to gonadotropins.

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Motomu Tsuji, Yasuhiro Ito, Nobuyuki Terada, and Hiroshi Mori

Abstract.

Osteogenic disorder syndrome rats are unable to synthesize ascorbic acid owing to the lack of l-gulonolactone oxidase, and become scorbutic within a few weeks without the supply of ascorbic acid. We studied effects of ascorbic acid deficiency on the ovarian aromatase activity in vivo using osteogenic disorder syndrome rats. The ovarian aromatase activity in ascorbic acid-deficient osteogenic disorder syndrome rats was significantly higher than that in normal or ascorbic acid-supplied osteogenic disorder syndrome rats. The activity in hypophysectomized immature rats was extremely low, but increased after treatment with pregnant mare serum gonadotropin, regardless of the presence or absence of ascorbic acid. The extent of the increase was the same among experimental groups. The present results indicate that ascorbic acid at physiological level lowers the ovarian aromatase activity, whereas it does not impair the responsiveness of the aromatase activity to gonadotropins.

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Noboru Hamada, Kunihiko Ito, Takashi Mimura, Naofumi Ishikawa, Naoko Momotani, Jaeduck Noh, Yasuhiro Hosoda, and Hirotoshi Morii

Abstract. The results of treatment were analyzed in relation to serum microsomal antibody (MCAb) titre before treatment in 1185 patients with Graves' disease. The percentage of patients who had ablative therapy because of poor response to antithyroid drug treatment was significantly greater in those with MCAb haemagglutination test (MCHA) titres greater than 1:25 000. With 131I treatment, the patients with MCHA titres greater than 1:6400 responded significantly less to therapy, although the analysis was done in 146 selected patients with certain defined radiation doses and small goitres. With surgical treatment, the percentage of the patients entering into remission was significantly smaller for patients with MCHA titres greater than 1:25 000, because of an increase in both hypothyroidism and relapses. The incidence of hypothyroidism was significantly higher in patients with marked lymphocyte infiltration and/or lymphoid follicles. The degree of these histological findings in Graves' disease was not marked in spite of high MCAb titre and it was significantly different from that in Hashimoto's disease when analyzed in relation to the MCHA titre.

These data indicate that in Graves' patients with high MCAb titre, remission is difficult to obtain by treatment, and suggest that the significance of MCAb is different in Graves' disease and Hashimoto's disease. The titre in Graves' disease may be one expression of the activity of this disease.

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Mitsuru Ito, Akira Miyauchi, Shinji Morita, Takumi Kudo, Eijun Nishihara, Minoru Kihara, Yuuki Takamura, Yasuhiro Ito, Kaoru Kobayashi, Akihiro Miya, Sumihisa Kubota, and Nobuyuki Amino

Objective

Thyroidal production of triiodothyronine (T3) is absent in patients who have undergone total thyroidectomy. Therefore, relative T3 deficiency may occur during postoperative levothyroxine (l-T4) therapy. The objective of this study was to evaluate how the individual serum T3 level changes between preoperative native thyroid function and postoperative l-T4 therapy.

Methods

We retrospectively studied 135 consecutive patients with papillary thyroid carcinoma, who underwent total thyroidectomy. Serum free T4 (FT4), free T3 (FT3), and TSH levels measured preoperatively were compared with those levels measured on postoperative l-T4 therapy.

Results

Serum TSH levels during postoperative l-T4 therapy were significantly decreased compared with native TSH levels (P<0.001). Serum FT4 levels were significantly increased (P<0.001). Serum FT3 levels were significantly decreased (P=0.029). We divided the patients into four groups according to postoperative serum TSH levels: strongly suppressed (less than one-tenth of the lower limit); moderately suppressed (between one-tenth of the lower limit and the lower limit); normal limit; and more than upper limit. Patients with strongly suppressed TSH levels had serum FT3 levels significantly higher than the native levels (P<0.001). Patients with moderately suppressed TSH levels had serum FT3 levels equivalent to the native levels (P=0.51), and patients with normal TSH levels had significantly lower serum FT3 levels (P<0.001).

Conclusions

Serum FT3 levels during postoperative l-T4 therapy were equivalent to the preoperative levels in patients with moderately suppressed TSH levels. Our study indicated that a moderately TSH-suppressive dose of l-T4 is required to achieve the preoperative native serum T3 levels in postoperative l-T4 therapy.

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Mitsuru Ito, Akira Miyauchi, Shino Kang, Mako Hisakado, Waka Yoshioka, Akane Ide, Takumi Kudo, Eijun Nishihara, Minoru Kihara, Yasuhiro Ito, Kaoru Kobayashi, Akihiro Miya, Shuji Fukata, Hirotoshi Nakamura, and Nobuyuki Amino

Objective

We and others recently reported that in total thyroidectomy (TT), serum triiodothyronine (T3) levels during levothyroxine (l-T4) therapy were low compared to the preoperative levels, suggesting that the presence of the thyroid tissue affects the balances of serum thyroid hormone levels. However, the effects of remnant thyroid tissue on these balances in thyroidectomized patients have not been established.

Methods

We retrospectively studied 253 euthyroid patients with papillary thyroid carcinoma who underwent a TT or hemithyroidectomy (HT). We divided the cases into the TT+supplemental l-T4 (+l-T4) group (n=103); the HT+l-T4 group (n=56); and the HT-alone group (n=94). We compared the postoperative serum levels of free T4 (FT4) and free T3 (FT3) and the FT3/FT4 ratio in individual patients with those of controls matched by serum TSH levels.

Results

The TT+l-T4 group had significantly higher FT4 (P<0.001), lower FT3 (P<0.01) and lower FT3/FT4 (P<0.001) levels compared to the controls. The HT+l-T4 group had FT4, FT3 and FT3/FT4 levels equivalent to those of the controls. The HT-alone group had significantly lower FT4 (P<0.01), equivalent FT3 (P=0.083), and significantly higher FT3/FT4 (P<0.001) ratios than the controls.

Conclusions

The presence of the remnant thyroid tissue was associated with different thyroid hormone balances in thyroidectomized patients, suggesting that T3 production by remnant thyroid tissue has a substantial effect on the maintenance of postoperative serum T3 levels.

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Fumitoshi Satoh, Ryo Morimoto, Kazumasa Seiji, Nozomi Satani, Hideki Ota, Yoshitsugu Iwakura, Yoshikiyo Ono, Masataka Kudo, Masahiro Nezu, Kei Omata, Yuta Tezuka, Yoshihide Kawasaki, Shigeto Ishidoya, Yoichi Arai, Kei Takase, Yasuhiro Nakamura, Keely McNamara, Hironobu Sasano, and Sadayoshi Ito

Objective and design

Adrenal venous sampling (AVS) is critical to determine the subtype of primary aldosteronism (PA). Central AVS (C-AVS) – that is, the collection of effluents from bilateral adrenal central veins (CV) – sometimes does not allow differentiation between bilateral aldosterone-producing adenomas (APA) and idiopathic hyperaldosteronism. To establish the best treatment course, we have developed segmental AVS (S-AVS); that is, we collect effluents from the tributaries of CV to determine the intra-adrenal sources of aldosterone overproduction. We then evaluated the clinical utility of this novel approach in the diagnosis and treatment of PA.

Methods

We performed C-AVS and/or S-AVS in 297 PA patients and assessed the accuracy of diagnosis based on the results of C-AVS (n=138, 46.5%) and S-AVS (n=159, 53.5%) by comparison with those of clinicopathological evaluation of resected specimens.

Results

S-AVS demonstrated both elevated and attenuated secretion of aldosterone from APA and non-tumorous segments, respectively, in patients with bilateral APA and recurrent APA. These findings were completely confirmed by detailed histopathological examination after surgery. S-AVS, but not C-AVS, also served to identify APA located distal from the CV.

Conclusions

Compared to C-AVS, S-AVS served to identify APA in some patients, and its use should expand the pool of patients eligible for adrenal sparing surgery through the identification of unaffected segments, despite the fact that S-AVS requires more expertise and time. Especially, this new technique could enormously benefit patients with bilateral or recurrent APA because of the preservation of non-tumorous glandular tissue.