Subclinical Cushing 2 1 1 1 1 1 1 1 1 1 1 2 Preclinical Cushing 1 ACTH Preclinical Subclinical Cushing 2 Subclinical Cushing 2 1 58 Cushing 1992 2002 1991 1999 2001 alendronate 5 mg alfacalcidol 1.0 µ g 2002 5 CT Cushing 2002 9 50 149 cm 46 kg BMI 20.7 118 66 mmhg enalapril 5 mg amlodipine 5mg 53 36.4 Cushing 1 930 0194 2630 2 939 0741 677 930 0194 2630 2005 1 12 2005 6 19 789
Table 1 48 11 2005 1 WBC 4520 µ l Neutro 68.6 Iymph 24.8 Eos 0.9 RBC 376 10 4 µ l Hb. 12.4 g dl Ht. 38.20 Plt. 15.8 10 4 µ l TP 5.6 g dl Alb 3.3 g dl GOT 20 IU l GPT 28 IU l γ GTP 32 U l ALP 223 IU l LDH 198 IU l T Bil 0.5 mg dl D Bil 0.1 mg dl AMY 102 IU l ChE 0.86 ph CPK 39 IU l BUN 13 mg dl Cre 0.4 mg dl Na 145 meq l K 3.2 meq l Cl 108 meq l Ca 9.0 mg dl IP 3.0 mg dl UA 4.0 mg dl T Cho 169 mg dl TG 72 mg dl FBS 160 mg dl HbA1c 5.7 ph 7.517 PaO2 96.6 torr PaCO2 35.4 torr HCO3 28.6 mmol l BE 5.9 mmol l CVR R 3.68 Shellong test Ccr 90.1 ml min 1.9 mg day ABI 1.11 1.11 PWV 1352 cm s 1409 cm s C 11 26 µ g day 0.583 g cmyam 2 55 11.5 nm mmcr DPD Table 1 30 160 mg dl HbA1c 5.7 C 11 26 µ g DPD alendronate 5 mg alfacalcidol 1.0 µ g Table 2 ACTH 17 OHCS ACTH ACTH CRH ACTH CT 2cm 131 I dynamic MRI Table 2 T1 4mm venous sampling ACTH ACTH ACTH Cushing Subclinical Cushing 2002 10 Hardy ACTH 2 CRH Table 3 ACTH hydrocortisone 20 mg DDAVP 22.5 µ g 120 130 70 80 mmhg C 11 26 µ g 35 42 µ g 2003 4 0.5 mg HbA1c 6 Table 3 alendronate 5 mg, alfacalcidol 1.0 µ g DPD 2 790
Subclinical Cushing 2 1 Table 2 LH FSH GH PRL TSH FT 3 FT 4 ACTH Cortisol 18.2 miu ml 65.4 miu ml 1.63 ng ml 28.7 ng ml 0.22 µ IU ml 2.2 pg ml 0.9 ng dl 19 pg ml 18.1 µ g dl 7.5 56.2 9.2 124.7 0.0 3.0 3.8 24.5 0.35 3.73 2.2 4.1 0.9 1.8 60 5.6 21.3 Urine cortisol Urine 17 OHCS Urine 17 KS PRA Aldosterone Urine adrenalin Urine noradrenalin urine dopamine 125.2 µ g day 15.1 mg day 5.3 mg day 0.4 ng ml hr 3.1 ng dl 8.0 µ g day 63.0 µ g day 613.8 µ g day 11.2 80.3 3.4 12.0 4.6 18.0 0.3 2.9 2 13 3 15 26 121 190 740 8 33 23.4 16 21.2 15.2 24 15.2 17.6 Dex 19 18.1 1mg 7 7 8mg 10 2.8 CRH 16 30 73 60 41 120 17 dynamic MRI T1 ACTH pg ml 14 14 15 20 18 68 98 29 176 1 2004 4 Table 3 DDAVP ACTH ACTH hydrocortisone 1mg ACTH MRI Cushing Cushing Preclinical Cushing 2.9 12.0 1 ACTH Preclinical Subclinical Cushing 12 Table 4Preclinical Cushing Subclinical Cushing Cushing 3 Preclinical Cushing Cushing Subclinical Cushing 4 1 Cushing 2 ACTH ACTH DHEA S 1mg 791
48 11 2005 Table 3 2002 11 CRH Na K Cl 2004 4 DPD LH FSH GH PRL TSH FT 4 ACTH Cortisol sosm uosm ADH 5 1.7 30 9 3.0 60 9 3.1 120 5 2.6 35 42 µ g day 132 meq l 3.5 meq l 97 meq l 0.595 g cmyam 2 57 2.7 nm mmcr 3.5 miu ml 7.5 56.2 15.3 miu ml 9.2 124.7 0.9 ng ml 0.0 3.0 14.7 ng ml 6.1 30.5 0.5 µ lu ml 0.4 4.0 1.0 ng dl 0.8 1.9 13.0 pg ml 9 52 10.4 µ g dl 4.5 21.3 282 533 0.4 pg ml 0.3 4.2 ACTH 30 60 14.3 32.1 35.7 Dex 1mg 13 5.3 10.4 1.9 3 µ g dl DDAVP ACTH 1.5 CRH ACTH 1.5 3 MRI Subclinical Cushing Subclinical Cushing Cushing 5, 6 7 Cushing 8 β 9 in vitro 10 Table 1 3 11 Table 1 3 Hardy 2 5 Cushing 12 4 µ g dl CRH ACTH 23 2 18 1 12 2 Table 3 hydrocortisone 20 mg CRH ACTH 2 MRI ACTH Cushing 0.5 mg HbA1c 6 2 Cushing DPD 13 Cushing Table 1 3 Cushing 792
Subclinical Cushing 2 1 Table 4 Subclinical Cushing Subclinical Cushing 1 2 3 4 5 6 7 17 53 63 74 53 53 58 BMI 21 32 20.6 29 22.9 22.5 20.7 DM ND ND ND DM DM DM DM DM IGT DM HT MRI empty sella ND ND ND ND ND Dex 1 mg CRH ACTH DDAVP ACTH ND ND ND ND Hardy Hardy Hardy Hardy HT DM HT DM HT DM HT IGT DM HT ND insulin insulin 20 U ND insulin 30 U ND 40 mg ND 0.5 mg HbA1c ND 5.6 9.2 11 ND 5.7 HbA1c ND 5.1 6.2 ND 5.8 14 3 15 16 Nagai et al. 17 18 Subclinical Cushing 8 9 10 11 12 75 67 74 72 77 BMI 23 28.4 21.6 ND ND DM ND ND ND ND ND ND HT MRI ND ND Dex 1 mg CRH ACTH DDAVP ACTH ND ND ND Hardy Hardy ND ND Kageyama et al. 2003 Takao et al. 2 1999 2001 2001 ND HT DM IGT 793
48 11 2005 Table 4 Subclinical Cushing 2003 12 14 18 7 2 4 5 Hardy 4 1 5 4 3 15 40 mg 5 17 Hardy 7 Hardy 1 30 0.5 mg Subclinical Cushing 7 5 Table 4 BMI 11β HSD 19 11β HSD1 cortisone cortisol 11β HSD2 cortisol cortisone cortisol 19 11β HSD1 11β HSD2 19 Tomlinson 20 ACTH cortisol 11β HSD1 Cushing 1 Table 4 Cushing 11β HSD1 11β HSD1 Cushing 11β HSD1 K 11β HSD2 cortisol 12 Subclinical Cushing ACTH cortisol Table 4 12 10 1mg 12 9 CRH ACTH 1.5 12 10 DDAVP ACTH 1.5 5 5 CT 5 5 MRI 12 11 Subclinical Cushing CT ACTH cortisol 1mgCRH DDAVP ACTH MRI Subclinical Cushing 2 1 Subclinical Cushing CT CRH DDAVP 1,, 1994 Preclinical Cushing. 70 : 25 30 2 Takao T, Mimoto T, Yamamoto M, Hashimoto K 2001 Preclinical Cushing disease. Arch Intern Med 161 : 892 893 3,,,,,,,,,,,,, 2000 Preclinical Cushing s syndrome Overt Cushing s syndrome 76 : 109 111 42003 Pre Subclinical Cushing. 79 suppl. Aug. 27 28 5 Nosadini R, Del Prato S, Tiengo A, Valerio A, Muggeo 794
Subclinical Cushing 2 1 M, Opocher G, Mantero F, Duner E, Marescotti C, Mollo F, Belloni F 1983 Insulin resistance in Cushing s syndrome. J Clin Endocrinol Metab 57 : 529 536 6 Robert RA, Mandarino LJ, Gerich JE 1982 Cortisol induced insulin resistance in man : Impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor defect of insulin action. J Clin Endocrinol Metab 54 : 131 138 7 Heaney AP, Harper R, Ennis C, Rooney DP, Sheridan B, Atkinson AB, Bell PM 1997 Insulin action and hepatic glucose cycling in cushings syndrome. Clin Endocrinol 46 : 735 743 8 Friedman TC, Mastorakos G, Newman TD, Mullen NM, Horton EG, Costello R, Papadopoulos NM, Chrousos GP 1996 Carbohydrate and lipid metabolism in endogenous hypercortisolism : shared features with metabolic syndrome X and NIDDM. Endocrine J 43 : 645 655 9 Matsumoto K, Yamasaki H, Akasawa S, Sakamaki H, Ishibashi M, Abiru N, Uotani S, Matsuo H, Yamaguchi Y, Tokuyama K, Nagataki S 1996 High dose but not low dose dexamethazone impaires glucose tolerance by inducing compensatory failure of pancreatic β cells in normal men. J Clin Endocrinol Metab 81 : 2621 2626 10 Lambillotte C, Gilon P, Henquin JC 1997 Direct glucocorticoid inhibition of insulin secretion : an in vitro study of dexamethazone effects in mouse islets. J Clin Invest 99 : 414 423 111996 54 : 2709 2714 12,,,,,,,,,, 2001 Cushing, γ knife 77 suppl : 33 36 13, 2000. 30 : 871 876 14,,,,,, 1994 1. 70 : 726 151997 Preclinical Cushing 1. ACTH RELATED PEPTIDES 8 : 189 196 16,,, 2002 CRH preclinical Cushing disease. 51 :6 9 17 Nagai T, Imamura M, Misumi S, Mori M 2002 Subclinical Cushing s disease accompanied by malignant hypertension and diabetes mellitus. Internal medicine 41 : 566 570 18, 2001 preclinical Cushing 1. 70 : 144 19 Tomlinson JW, Stewart PM 2001 Cortisol metabolism and the role of 11 β hydroxysteroid dehydrogenase. Best practice and clinical endocrinology and metabolism 15 : 61 78 20 Tomlinson JW, Draper N, Mackie J, Johnson AP, Holder G, Wood P, Stewart PM 2002 Abscence of cushingoid phenotype in a patient with Cuhing s disease due to defective cortisone to cortisol conversion. J Clin Endocrinol Metab 87 : 57 62 795