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内分泌専門外来では健康成人の甲状腺異常症の頻度は17%と報告されている。今回2007年4月2日から2008年3月31日までの1年間を通して，人間ドック受診時に得られた血清を用いてFT3，FT4，TSHを測定し，それらの分布をみて，成人における甲状腺機能異常症の出現頻度を明らかにするために調査・研究した。男性1,630人，女性1,053人の合計2,683人を対象にした。血清FT3，FT4値では男性群が女性群に比較して高い値が示され，血清TSH値では男性群に比較して女性群で高い値が示された。血清FT3，FT4の基準値より低い値であった個体数が男性例より女性例で高い出現頻度を認めた。血清TSH高値 (>4.91μU/ml) の個体数は男性例より女性例で出現頻度が高いことが示された。男性より女性で甲状腺ホルモン値が低い傾向を示し，甲状腺機能低下症が出現しやすいことが明らかにされた。甲状腺機能低下症を惹起しやすい慢性甲状腺炎が男性例より女性例で出現頻度が高いことが知られているが，今回得られた結果は慢性甲状腺炎の出現頻度と類似した傾向が考えられた。血清甲状腺ホルモン値と甲状腺自己抗体価は密接な関係があることから，今後更なる関係性を明らかにするために甲状腺自己抗体価の調査・研究と併せて検討していきたい。

Summary Background A subset of familial isolated primary hyperparathyroidism (FIHP) is a variant of hyperparathyroidism–jaw tumour syndrome (HPT-JT). Aim/patients and methods We investigated the involvement of the HRPT2, MEN1 and CASR genes in 11 provisional FIHP families and two HPT-JT families. Results Germline mutations of HRPT2 were found in two of the 11 FIHP families and one of the two HPT-JT families. One FIHP family with parathyroid carcinoma and atypical adenomas and another FIHP family with cystic parathyroid adenoma had novel frameshift mutations of 518–521del and 62–66del, respectively. In a patient with HPT-JT, a de novo germline mutation of 39delC was detected. Novel somatic HRPT2 mutations of 70–73del and 95–102del were found in two of five parathyroid tumours in a family with a 518–521del mutation. Biallelic inactivation of HRPT2 by a combination of germline and somatic mutation was confirmed in the parathyroid tumours. The finding that two families diagnosed with FIHP carried HRPT2 mutations suggests that they have occult HPT-JT. In the remaining 10 families, one family had a missense MEN1 mutation. No mutations of CASR were detected. Conclusion Our results confirm the need to test for HRPT2 in FIHP families, especially those with parathyroid carcinomas, atypical adenomas or adenomas with cystic change.

A prospective long-term follow-up study was performed with conventional divided doses (group C: 10 mg 3 times daily, N = 58) and a small single daily dose (group S: 15 mg once daily, N = 54) of methimazole (MMI) for the treatment of Graves' hyperthyroidism. Within 8 weeks, almost 80% of the patients in both groups became euthyroid. The mean time required to achieve a euthyroid state was 5.6 +/- 2.7 weeks in group C and 5.8 +/- 3.1 in group S. TSH binding inhibitor immunoglobulin (TBII) levels before therapy were 44.2 +/- 22.7% and 47.1 +/- 23.9% in group C and group S, respectively. A similar gradual fall in TBII levels was observed in both groups over a two-year period of treatment. MMI doses were gradually reduced to a maintenance dose (5 mg daily) after the patients became euthyroid. The patients were treated for 28 +/- 9 months and were followed up after therapy was stopped (observation period in patients who remained in remission was 12-130 (75 +/- 34) months and the interval to relapse in recurred cases was 1-98 (20 +/- 27) months). The rates of recurrence in group C were 41% at 1 yr, 54% at 2 yrs, 56% at 4 yrs and 61% at 6 yrs. In group S, these were 44%, 53%, 56% and 63%, respectively. No differences between relapse rates were observed with the two different dosage regimens. Adverse effects occurred more frequently in group C patients (24%) than in group S patients (13%). These results show that there is no difference in the clinical and immunological course or in the long-term remission rate of Graves' hyperthyroidism when the treatment is initiated with either a small single daily dose (15 mg) or the conventional regimen (10 mg 3 times daily).

A 41-year-old woman developed primary aldosteronism due to bilateral multiple aldosterone-producing adenomas (APA). She was suspected to have idiopathic hyperaldosteronism (IHA) 7 years previously. Although preoperative data suggest APA and IHA was suspected in a postoperative microscopic specimen, a definite clinical diagnosis could not be made. Cytochrome P-450 and other enzymes involved in aldosterone synthesis were found in the tumor portions but not in the zona glomerulosa of attached adrenals, which histopathologically showed "paradoxical hyperplasia". This was a rare case of bilateral multiple APA, which could be differentiated from IHA by immunohistochemical analysis of adrenal steroidogenic enzymes.

Context:Patients with TSH-secreting pituitary adenomas (TSHoma) show inappropriate secretion of TSH; serum TSH levels are not suppressed despite high serum free thyroid hormone levels. The mechanism of a defect in negative regulation of TSH in a TSHoma is still unclear.Objective:Recently, we cloned a novel thyroid hormone receptor β isoform (TRβ4) from a human pituitary library. To elucidate the clinical significance of TRβ4, we investigated the expression of this isoform in TSHoma.Methods:RT-PCR was performed to detect TRβ isoforms such as TRβ1, TRβ2, and TRβ4 using RNA obtained from surgically resected TSHoma. The effects of TRβ4 on the TSH gene expression were examined in the transient gene expression experiments.Results:Quantitative analysis using a real-time PCR revealed that relative expression of TRβ4 to TRβ1+2 was higher in three TSHoma than in a prolactinoma or a nonfunctioning pituitary adenoma. TRβ4 construct did not mediate T3-dependent gene regulation but inhibited the negative regulation of TSHα mediated by TRβ1 or TRβ2.Conclusions:Aberrant expression of TRβ4 may partly contribute to the inappropriate secretion of TSH in a TSHoma.

We report a patient with Graves' disease in whom thyroid function was changed from initial hyperthyroidism to transient hypothyroidism and back to hyperthyroidism during interferon (IFN) therapy. A 43-year-old man was admitted to our hospital to receive IFN treatment for chronic active hepatitis (type C) in June 1998. His thyroid function was normal and testing for thyroid gland antibodies (TSH binding inhibitor immunoglobulins; TBII, anti-thyroglobulin antibodies; TgAb and anti-thyroid peroxidase antibodies; TPOAb) was negative before IFN therapy. The patient had neither history of thyroid disease nor any particular family history. He developed hyperthyroidism four months after its initiation of IFN therapy. When he was hyperthyroid, TBII, the activity of thyroid-stimulating antibodies (TSAb) and thyroid stimulation-blocking antibodies (TSBAb) were 40.2% (normal range, -15 approximately +15.0%), 1201% (normal range,or=180%) and 52.0% (normal range,or=45.6%), respectively. Thyroid 99mTc(technetium)-uptake ratio (Tc-UTR) was 1.07% (normal range, 0.5-3.0%). He transiently developed hypothyroidism in December 1998 and recurrent hyperthyroidism in February 1999. When he was hypothyroid, TBII, TSAb and TSBAb were 74.3%, 769% and 95.9%, respectively. To investigate the mechanism of his fluctuating thyroid status, we serially assessed the serum levels of cytokines (TNF-alpha, IFN-gamma, IL-1beta, IL-2, IL-4) and the soluble form of ICAM-1 (sICAM-1) as well as the activities of two types of TSH receptor antibodies (TRAb), TSAb and TSBAb, before and after IFN therapy. There were no characteristic changes of cytokines or sICAM-1 during the follow-up period. The transient hypothyroid state may be explained by two possible mechanisms: one may be due to the shift in the balance between the stimulating and blocking types of TRAb, and the other may be due to the complication of destructive thyroiditis that developed during IFN therapy.

We report a case of Graves' hyperthyroidism induced by long-term interferon (IFN) therapy.A 52-year-old woman suffered from chronic active hepatitis type C and was treated with a total of 456×106 units of IFN-α for 23 weeks. During the 12th week of treatment she showed transient thyrotoxicosis. One week after the termination of IFN therapy, TSH-receptor antibodies became positive and subsequently she showed Graves' hyperthyroidism. This case showed sequential manifestation from transient thyrotoxicosis to the appearance of TSH-receptor autoantibodies, and then the occurrence of Graves' hyperthyroidism during IFN therapy. The course of this case may be useful in the understanding of the pathogenesis of autoimmune hyperthyroidism.(Internal Medicine 34: 58-60, 1995)

A prospective randomized trial with the conventional divided doses (10 mg 3 times daily, N = 29) and a small single daily dose (15 mg once daily, N = 25) of methimazole for the treatment of Graves' hyperthyroidism was performed. Within 8 weeks, almost 80% of the patients in both groups became euthyroid. The mean time required to achieve the euthyroid state was 6.0 ± 2.8 and 6.0 ± 3.8 weeks, respectively. TSH binding inhibitor immunoglobulin was found in about 90% of the patients in both groups before methimazole treatment. However, a gradual fall of its levels was observed in nearly all patients after treatment. There was no difference in the mean levels of TSH binding inhibitor immunoglobulin between the two groups during therapy. We conclude that the single daily dose regimen of 15 mg of methimazole will control Graves' hyperthyroidism in most patients, and TSH binding inhibitor immunoglobulin levels decrease in this regimen in the same way as with the conventional divided dose regimen (10 mg 3 times daily).

19才男性.視力障害・左不全麻痺等にて1985年11月入院.血中PRL 16600ng/ml, CTscanにて鞍上部から周囲に浸潤性に発育した巨大腫瘍(容積: 124cm3)を認めた. bromocriptine投与1週後に血中PRL・腫瘍容積ともに著明に低下し,症状は消失.投薬中止時一時的に腫瘍の再増大を認めたが,経蝶形骨洞的手術後投与を再開し再び急速な腫瘍の縮小を認め,以後3年余にわたり継続投与中でありCT上腫瘍は殆ど認められなくなっている.