亚临床甲状腺功能亢进症的研究进展
|
摘要
亚临床甲状腺功能亢进症(Subclinical Hyperthyroidism,以下简称亚临床甲亢)是一种特殊类型的甲状腺功能亢进症,是指血游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)正常,促甲状腺素(TSH)低于正常。依病因可分为内源性和外源性两类。结节性甲状腺肿、潜在的Graves病、甲状腺炎及摄入过量的L-T4是其常见的病因。亚临床甲亢临床症状多不明显,但可较早出现心脏和自主神经调节功能受损;心房纤颤发生率高;绝经后女性亚临床甲亢患者骨质疏松危险性增加。该病的诊断应排除引起暂时性TSH降低的其他原因。亚临床甲亢是否治疗要权衡利弊。TSH显著降低者可相应治疗,TSH轻度降低者应定期随访。
克氏综合征是一种染色体异常的综合征,一般表现为47, XXY的染色体核型,并常伴有其他脏器、系统的异常。现在我们报道一例克氏综合征伴有代谢综合征的青年男性病人。该患者表现为睾丸发育差,低睾酮,高卵泡刺激素、黄体生成素,无精,婚后不育,染色体核型47, XXY,支持克氏综合征诊断。依其肥胖体型、高血压、高血糖、高血脂,诊为代谢综合征。现结合相关文献复习如下。
Subclinical hyperthyroidism is a special kind of hyperthyroidism, as defined by the presence of a low serum TSH level in the face of normal serum free T4 and free T3 levels. According to etiology, it can be divided into two types of endogenous and exogenous subclinical hyperthyroidism. Nodular goiter, the potential Graves disease, thyroiditis, and intake of excessive amount of L-T4 is the common cause of it. Most symptoms of subclinical hyperthyroidism are not obvious, but the heart and autonomic nervous dysfunction can occur early; the incidence of auricular fibrillation raises up; subclinical hyperthyroidism increases risk of osteoporosis in post-menopausal women patients. The diagnosis should be excluded from the disease caused by a temporary reduction in TSH of other causes. The treatment of subclinical hyperthyroidism should be weighed. If there is a noticeable reduction of TSH, we can give the homologous treatment. If TSH has a mild reduction, we should follow up regularly.
Klinefelter’s syndrome, characterised by a 47, XXY chromosomal pattern, has largely been associated with physical abnormalities. Here, we report a case of Klinefelter's syndrome in a 28-year-old man who had metabolic syndrome. We diagnosed him with Klinefelter's syndrome from his atrophic testicles, primary hypogonadism in hormonal examination, infertility, and a chromosomal aberration of 47, XXY. From the fat somatotypes, high level of blood glucose, blood fat and blood pressure, we diagnosed him with metabolic syndrome. In the end, we review some literatures about Klinefelter’s syndrome and metabolic syndrome.
克氏综合征是一种染色体异常的综合征,一般表现为47, XXY的染色体核型,并常伴有其他脏器、系统的异常。现在我们报道一例克氏综合征伴有代谢综合征的青年男性病人。该患者表现为睾丸发育差,低睾酮,高卵泡刺激素、黄体生成素,无精,婚后不育,染色体核型47, XXY,支持克氏综合征诊断。依其肥胖体型、高血压、高血糖、高血脂,诊为代谢综合征。现结合相关文献复习如下。
Subclinical hyperthyroidism is a special kind of hyperthyroidism, as defined by the presence of a low serum TSH level in the face of normal serum free T4 and free T3 levels. According to etiology, it can be divided into two types of endogenous and exogenous subclinical hyperthyroidism. Nodular goiter, the potential Graves disease, thyroiditis, and intake of excessive amount of L-T4 is the common cause of it. Most symptoms of subclinical hyperthyroidism are not obvious, but the heart and autonomic nervous dysfunction can occur early; the incidence of auricular fibrillation raises up; subclinical hyperthyroidism increases risk of osteoporosis in post-menopausal women patients. The diagnosis should be excluded from the disease caused by a temporary reduction in TSH of other causes. The treatment of subclinical hyperthyroidism should be weighed. If there is a noticeable reduction of TSH, we can give the homologous treatment. If TSH has a mild reduction, we should follow up regularly.
Klinefelter’s syndrome, characterised by a 47, XXY chromosomal pattern, has largely been associated with physical abnormalities. Here, we report a case of Klinefelter's syndrome in a 28-year-old man who had metabolic syndrome. We diagnosed him with Klinefelter's syndrome from his atrophic testicles, primary hypogonadism in hormonal examination, infertility, and a chromosomal aberration of 47, XXY. From the fat somatotypes, high level of blood glucose, blood fat and blood pressure, we diagnosed him with metabolic syndrome. In the end, we review some literatures about Klinefelter’s syndrome and metabolic syndrome.
引文
1 Cooper DS. Approach to the patient with subclinical hyperthyroidism. J Clin Endocrinol Metab, 2007, 92: 3-9
2 Boelaert K, Franklyn JA. Thyroid hormone in health and disease. J Endocrinol, 2005, 187: 1-15
3 Pinchera A. Subclinical thyroid disease: to treat or not to treat? Thyroid, 2005, 15: 1-2
4 Hoogendoorn EH, den Heijer M, van Dijk AP, et al. Subclinical hyperthyroidism: to treat or not to treat? Postgrad Med J, 2004, 80: 394-398
5 Biondi B, Palmieri EA, Klain M, et al. Subclinical hyperthyroidism: clinical features and treatment options. Eur J Endocrinol, 2005, 152: 1-9
6 Al Abadi AC. Subclinical thyrotoxicosis. Postgrad Med J, 2001, 77(903): 29-32
7 Toft AD. Clinical prautice. Subclinical hyperthyroidism. N Engl J Med, 2001, 345(7): 512-516
8 Atzmon G, Barzilai N, Hollowell JG, et al. Extreme longevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab, 2009, 94: 1251-1254
9 Munte TF, Radamm C, Johannes S, et al. Alteration of cognitive function induced by exogenous application of thyroid hormones in healthy men: a double-blind cross-over study using event-related brain potential. Throid, 2001, 11: 385-391
10 Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA, 2004, 291: 228-238
11 Parle JV, Maisonneuve P, Sheppard MC, et al. Prediction of all cause and cardiovascular mortality in elderly people from one low serum thyrothropin result: a 10 year cohort study. Lancet, 2001, 358: 861-865
12 Auer J, Scheibner P, Mische T, et al. Subclinical hyperthroidism as a riskfactor for atrial fibrillation. Am Heart J, 2001, 142: 835-842
13 Sawin CT. Subclinical hyperthyroidism and atrial fibrillation. Thyroid, 2002, 12: 501-503
14 Boelaert K, Franklyn JA. Thyroid hormone in health and disease. J Endo- crinol, 2005, 187: 1-15
15 Osman F, Franklyn JA, Daykin J, et al. Heart rate variability and turbulence in hyperthyroidism before, during, and after treatment. Am J Cardiol, 2004, 94: 465-469
16 Aras D, Maden O, Ozdemir O, et al. Simple electrocardiographic markers for the prediction of paroxysmal atrial fibrillation in hyperthyroidism. Int J Cardiol, 2005, 99: 59-64
17 Biondi B, Palmieri EA, Fazio S, et al. Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middle-aged patients. J Clin Endocrinol Metab, 2000, 85: 4701-4705
18 Sgarbi JA, Villaca FG, Garbeline B, et al. The effects of early anti-thyroid for endogenous subclinical hyperthyroidism in clinical and heart abnormalities. J Clin Endocrinol Metab, 2003, 88: 1672-1677
19 Tamer I, Sargin M, Sargin H, et al. The evaluation of left ventricular hypertrophy in hypertensive patients with subclinical hyperthyroidism. Endocr J, 2005, 52: 421-425
20 Shargorodsky M, Serov S, Gavish D, et al. Long-term thyrotropin- supperssive therapy with levothyroxine impairs small and large artery elasticity and increases left ventricular mass in patients with thyroid carcinoma. Thyroid, 2006, 16: 381-386
21 Cappola AR, Fried LP, Arnold AM, et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA , 2006, 295: 1033-1041
22 Smit JW, Eustatia Rutten CF, Corssmit EP, et al. Reversible diastolic dysfunction after long-term exogenous subclinical hyperthyroidism: a randomized, placebo-controlled study. J Clin Endocrinol Metab, 2005, 90: 6041-6047
23 Kvetny J. Subclinical hyperthyroidism in patients with nodular goiter represents a hypermetabolic state. Exp Clin Endocrinol Diabetes, 2005, 113: 122-126
24 Yonem O, Dokmefas HS, Aslan SM, et al. Is anti-thyroid treatment really relevant of young patients with subclinical hyperthyroidism? Endocr J, 2002, 49: 307-314
25 Kisakol G, Kaya A, Gonen S, et al. Bone and calcium metabolism in subclinical autoimmune hyperthyroidism and hypothyroidism. Endocr J, 2003, 50: 657-661
26 Lee WY, Oh KW, Rhee EJ, et al. Relationship between subclinical thyroid dysfunction and femoral neck bone mineral density in women. Arch Med Res, 2006, 37: 511-516
27 Sheppard MC, Holder R, Franklyn JA. Levothyroxine treatment and occurrence of fracture of the hip. Arch Int Med, 2002, 162: 338-343
28 Al-Adsani H, Hoffer LJ, Silva J E. Resting expenditure is sensitive to small dose changes in patients on chronic thyroid replacement. J Clin Endocrinol Metab , 1997, 82: 1118-1125
29 Marqusee E, Haden ST, Utiger RD. Subclinical thyrotoxicosis. Endocrinol Metab Clin Nor Am, 1998, 27: 37-49
30 Col NF, Surks MI, Daniels GH. Subclinical thyroid disease: clinical application. JAMA, 2004, 291: 239-243
31 Smallridge RC. An approach to mild laboratory abnormalities and vague or absent symptoms. Postgrad Med, 2000, 107(1): 143-152
32 Nyirenda MJ, Clark DN, Finlayson AR, et al. Thyroid disease and increased cardiovascular risk. Thyroid, 2005, 15: 718-724
33 Franklyn JA, Sheppard MC, Maisonneuve P. Thyroid function and mortality in patients treated for hyperthyroidism. JAMA, 2005, 294: 71-80
1 Arnedo N,Templado C,Sanchez-Blanque X,et a1.Sperm aneuploidy in fathers of Klinefelter syndrome offspring assessed by muhicolour fluorescence in situ hybridization using probe for chromosome 6, 13, 18, 21, 22, X and Y. Ham Reprod, 2006, 21: 524-528
2 Vidal F.Synaptonemal complex studies in a mosaic.46, XY/47, XXY male.Human Genet, 1984, 66: 306-306
3 Visootsak J, Graham JM jr. Klinefelter syndrome and other sex chromosomal aneuploidies. Orphant J Rare Dis, 2006, 1, 42-45
4 Stuart SW, King CH, Pai GS. Autism spectrum disorder, Klinefelter syndrome and chromosome 3P21. 31 duplication: A case report. Med Gen Med, 2007, 9: 60-63
5 Mansfield C, Hopfer S, Marteau Tm. Termination rates after prenatal diagnosis of Down syndrome, spina bifida, anencephaly, and Turner and Klinefelter syndromes: a systematic literature review. Prenat Diagn, 1999, 19(9): 808-812
6 Berlin BM, Norton ME, Sugarman EA, et al. Cystic fibrosis and chromosome abnormalities associated with echogenic fetal bowel. Obstet Gynecol, 1999, 94(1): 135-138
7 Ramaker J, Goerdt S, Zouboulis CC, et al. Recurrent thrombophlebitis and ulcera crurum as manifestations of hereditary blood coagulation disorders and Klinefelter syndrome. Hautarzt, 1997, 48(9): 634-639
8 Prall JA, McGavran L, Greffe BS, et al. Intracranial malignant germ cell tumor and the Klinefelter syndrome: case report and review of the literature. Pediatr Neurosurg, 1995, 23(4): 219-224
9 Yamamoto T, Tamura J, et al. Rhabdomysarcoma in a patient with mosaic Klinefelter syndrome and transformation of immature teratoma. J Int Med Res, 1999, 27(4): 196-200
10狄福松,张桂元.十一酸睾酮对Klinefeter综合征患者垂体-性腺轴系功能的影响.中国男科学杂志,1999,13:152-152
11 Visootsak J, Aylstock M, Graham JM. Klinefelter syndrome and itsvariants: An update and review for the primary pediatrician. Clin Pediatr (Phila), 2001, 40: 639-642
12 Reaven G. The metabolic syndrome or the insulin resistance syndrome? Different names, different concepts, and different goals. Endocrinol Metab Clin North Am, 2004, 33 (2): 283-303
13 Kapoor D, Malkin CJ, Canner KS, et al. Androgens, insulin resistance and vascular disease in men. Clin Endocrinol (Oxf ), 2005, 63: 239-250
14 Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med, 1998, 15 (7): 539-553.
15 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA, 2001, 285 (19): 2486-2497.
16中华医学会糖尿病学分会代谢综合征研究协作组.中华医学会糖尿病学分会关于代谢综合征的建议.中华糖尿病杂志,2004,12(3):156-161
17 Zimmet P, MM Alberti KG, Serrano Ríos M. A new international diabetes federation worldwide definition of the metabolic syndrome: the rationale and the results. Rev Esp Cardiol, 2005, 58(12): 1371-1376.
18陈家伟.代谢综合征正在威胁人类健康.中华医学杂志,2004,84(7): 529-530
19 Okamoto E, Motegi M, Imai K, et al. A case of Klinefelter’s syndrome associated with insulin dependent diabetes mellitus. Kitakantou Igaku, 1991, 41: 697-701
20 Takeuchi Y, Murata Y, Sintani J, et al. Klinefelter’s syndrome accompanied by mixed connective tissue disease and diabetes mellitus. Intern Med, 1999, 38: 875-881
21 Aoki N. Klinefelter's syndrome, autoimmunity, and associated endocrinepathies. Intern Med, 1999, 38: 838-839
22 Kocar IH, Yesilova Z, Ozata M, Turan M, Sengul A, Ozdemir I. The effect of testosterone replacement treatment on immunological features of patients with Klinefelter’s syndrome. Clin Exp Immunol, 2000, 121: 448-452
23 Kikuko Ota, Tadashi Suehiro, Yukio Ikeda, et al. Diabetes mellitus associated with Klinefelter’s syndrome: a case report and review in Japan. Internal medicine, 2002, 41: 842-847
2 Boelaert K, Franklyn JA. Thyroid hormone in health and disease. J Endocrinol, 2005, 187: 1-15
3 Pinchera A. Subclinical thyroid disease: to treat or not to treat? Thyroid, 2005, 15: 1-2
4 Hoogendoorn EH, den Heijer M, van Dijk AP, et al. Subclinical hyperthyroidism: to treat or not to treat? Postgrad Med J, 2004, 80: 394-398
5 Biondi B, Palmieri EA, Klain M, et al. Subclinical hyperthyroidism: clinical features and treatment options. Eur J Endocrinol, 2005, 152: 1-9
6 Al Abadi AC. Subclinical thyrotoxicosis. Postgrad Med J, 2001, 77(903): 29-32
7 Toft AD. Clinical prautice. Subclinical hyperthyroidism. N Engl J Med, 2001, 345(7): 512-516
8 Atzmon G, Barzilai N, Hollowell JG, et al. Extreme longevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab, 2009, 94: 1251-1254
9 Munte TF, Radamm C, Johannes S, et al. Alteration of cognitive function induced by exogenous application of thyroid hormones in healthy men: a double-blind cross-over study using event-related brain potential. Throid, 2001, 11: 385-391
10 Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA, 2004, 291: 228-238
11 Parle JV, Maisonneuve P, Sheppard MC, et al. Prediction of all cause and cardiovascular mortality in elderly people from one low serum thyrothropin result: a 10 year cohort study. Lancet, 2001, 358: 861-865
12 Auer J, Scheibner P, Mische T, et al. Subclinical hyperthroidism as a riskfactor for atrial fibrillation. Am Heart J, 2001, 142: 835-842
13 Sawin CT. Subclinical hyperthyroidism and atrial fibrillation. Thyroid, 2002, 12: 501-503
14 Boelaert K, Franklyn JA. Thyroid hormone in health and disease. J Endo- crinol, 2005, 187: 1-15
15 Osman F, Franklyn JA, Daykin J, et al. Heart rate variability and turbulence in hyperthyroidism before, during, and after treatment. Am J Cardiol, 2004, 94: 465-469
16 Aras D, Maden O, Ozdemir O, et al. Simple electrocardiographic markers for the prediction of paroxysmal atrial fibrillation in hyperthyroidism. Int J Cardiol, 2005, 99: 59-64
17 Biondi B, Palmieri EA, Fazio S, et al. Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middle-aged patients. J Clin Endocrinol Metab, 2000, 85: 4701-4705
18 Sgarbi JA, Villaca FG, Garbeline B, et al. The effects of early anti-thyroid for endogenous subclinical hyperthyroidism in clinical and heart abnormalities. J Clin Endocrinol Metab, 2003, 88: 1672-1677
19 Tamer I, Sargin M, Sargin H, et al. The evaluation of left ventricular hypertrophy in hypertensive patients with subclinical hyperthyroidism. Endocr J, 2005, 52: 421-425
20 Shargorodsky M, Serov S, Gavish D, et al. Long-term thyrotropin- supperssive therapy with levothyroxine impairs small and large artery elasticity and increases left ventricular mass in patients with thyroid carcinoma. Thyroid, 2006, 16: 381-386
21 Cappola AR, Fried LP, Arnold AM, et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA , 2006, 295: 1033-1041
22 Smit JW, Eustatia Rutten CF, Corssmit EP, et al. Reversible diastolic dysfunction after long-term exogenous subclinical hyperthyroidism: a randomized, placebo-controlled study. J Clin Endocrinol Metab, 2005, 90: 6041-6047
23 Kvetny J. Subclinical hyperthyroidism in patients with nodular goiter represents a hypermetabolic state. Exp Clin Endocrinol Diabetes, 2005, 113: 122-126
24 Yonem O, Dokmefas HS, Aslan SM, et al. Is anti-thyroid treatment really relevant of young patients with subclinical hyperthyroidism? Endocr J, 2002, 49: 307-314
25 Kisakol G, Kaya A, Gonen S, et al. Bone and calcium metabolism in subclinical autoimmune hyperthyroidism and hypothyroidism. Endocr J, 2003, 50: 657-661
26 Lee WY, Oh KW, Rhee EJ, et al. Relationship between subclinical thyroid dysfunction and femoral neck bone mineral density in women. Arch Med Res, 2006, 37: 511-516
27 Sheppard MC, Holder R, Franklyn JA. Levothyroxine treatment and occurrence of fracture of the hip. Arch Int Med, 2002, 162: 338-343
28 Al-Adsani H, Hoffer LJ, Silva J E. Resting expenditure is sensitive to small dose changes in patients on chronic thyroid replacement. J Clin Endocrinol Metab , 1997, 82: 1118-1125
29 Marqusee E, Haden ST, Utiger RD. Subclinical thyrotoxicosis. Endocrinol Metab Clin Nor Am, 1998, 27: 37-49
30 Col NF, Surks MI, Daniels GH. Subclinical thyroid disease: clinical application. JAMA, 2004, 291: 239-243
31 Smallridge RC. An approach to mild laboratory abnormalities and vague or absent symptoms. Postgrad Med, 2000, 107(1): 143-152
32 Nyirenda MJ, Clark DN, Finlayson AR, et al. Thyroid disease and increased cardiovascular risk. Thyroid, 2005, 15: 718-724
33 Franklyn JA, Sheppard MC, Maisonneuve P. Thyroid function and mortality in patients treated for hyperthyroidism. JAMA, 2005, 294: 71-80
1 Arnedo N,Templado C,Sanchez-Blanque X,et a1.Sperm aneuploidy in fathers of Klinefelter syndrome offspring assessed by muhicolour fluorescence in situ hybridization using probe for chromosome 6, 13, 18, 21, 22, X and Y. Ham Reprod, 2006, 21: 524-528
2 Vidal F.Synaptonemal complex studies in a mosaic.46, XY/47, XXY male.Human Genet, 1984, 66: 306-306
3 Visootsak J, Graham JM jr. Klinefelter syndrome and other sex chromosomal aneuploidies. Orphant J Rare Dis, 2006, 1, 42-45
4 Stuart SW, King CH, Pai GS. Autism spectrum disorder, Klinefelter syndrome and chromosome 3P21. 31 duplication: A case report. Med Gen Med, 2007, 9: 60-63
5 Mansfield C, Hopfer S, Marteau Tm. Termination rates after prenatal diagnosis of Down syndrome, spina bifida, anencephaly, and Turner and Klinefelter syndromes: a systematic literature review. Prenat Diagn, 1999, 19(9): 808-812
6 Berlin BM, Norton ME, Sugarman EA, et al. Cystic fibrosis and chromosome abnormalities associated with echogenic fetal bowel. Obstet Gynecol, 1999, 94(1): 135-138
7 Ramaker J, Goerdt S, Zouboulis CC, et al. Recurrent thrombophlebitis and ulcera crurum as manifestations of hereditary blood coagulation disorders and Klinefelter syndrome. Hautarzt, 1997, 48(9): 634-639
8 Prall JA, McGavran L, Greffe BS, et al. Intracranial malignant germ cell tumor and the Klinefelter syndrome: case report and review of the literature. Pediatr Neurosurg, 1995, 23(4): 219-224
9 Yamamoto T, Tamura J, et al. Rhabdomysarcoma in a patient with mosaic Klinefelter syndrome and transformation of immature teratoma. J Int Med Res, 1999, 27(4): 196-200
10狄福松,张桂元.十一酸睾酮对Klinefeter综合征患者垂体-性腺轴系功能的影响.中国男科学杂志,1999,13:152-152
11 Visootsak J, Aylstock M, Graham JM. Klinefelter syndrome and itsvariants: An update and review for the primary pediatrician. Clin Pediatr (Phila), 2001, 40: 639-642
12 Reaven G. The metabolic syndrome or the insulin resistance syndrome? Different names, different concepts, and different goals. Endocrinol Metab Clin North Am, 2004, 33 (2): 283-303
13 Kapoor D, Malkin CJ, Canner KS, et al. Androgens, insulin resistance and vascular disease in men. Clin Endocrinol (Oxf ), 2005, 63: 239-250
14 Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med, 1998, 15 (7): 539-553.
15 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA, 2001, 285 (19): 2486-2497.
16中华医学会糖尿病学分会代谢综合征研究协作组.中华医学会糖尿病学分会关于代谢综合征的建议.中华糖尿病杂志,2004,12(3):156-161
17 Zimmet P, MM Alberti KG, Serrano Ríos M. A new international diabetes federation worldwide definition of the metabolic syndrome: the rationale and the results. Rev Esp Cardiol, 2005, 58(12): 1371-1376.
18陈家伟.代谢综合征正在威胁人类健康.中华医学杂志,2004,84(7): 529-530
19 Okamoto E, Motegi M, Imai K, et al. A case of Klinefelter’s syndrome associated with insulin dependent diabetes mellitus. Kitakantou Igaku, 1991, 41: 697-701
20 Takeuchi Y, Murata Y, Sintani J, et al. Klinefelter’s syndrome accompanied by mixed connective tissue disease and diabetes mellitus. Intern Med, 1999, 38: 875-881
21 Aoki N. Klinefelter's syndrome, autoimmunity, and associated endocrinepathies. Intern Med, 1999, 38: 838-839
22 Kocar IH, Yesilova Z, Ozata M, Turan M, Sengul A, Ozdemir I. The effect of testosterone replacement treatment on immunological features of patients with Klinefelter’s syndrome. Clin Exp Immunol, 2000, 121: 448-452
23 Kikuko Ota, Tadashi Suehiro, Yukio Ikeda, et al. Diabetes mellitus associated with Klinefelter’s syndrome: a case report and review in Japan. Internal medicine, 2002, 41: 842-847