Preclinical Cushing 1 ACTH alendronate 5 mg alfacalcidol. Cushing. Preclinical Subclinical Cushing 2

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1 Subclinical Cushing Preclinical Cushing 1 ACTH Preclinical Subclinical Cushing 2 Subclinical Cushing Cushing alendronate 5 mg alfacalcidol 1.0 µ g CT Cushing cm 46 kg BMI mmhg enalapril 5 mg amlodipine 5mg Cushing

2 Table WBC 4520 µ l Neutro 68.6 Iymph 24.8 Eos 0.9 RBC µ l Hb g dl Ht Plt 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 PaO torr PaCO torr HCO mmol l BE 5.9 mmol l CVR R 3.68 Shellong test Ccr 90.1 ml min 1.9 mg day ABI PWV 1352 cm s 1409 cm s C µ g day g cmyam nm mmcr DPD Table mg dl HbA1c 5.7 C 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 Hardy ACTH 2 CRH Table 3 ACTH hydrocortisone 20 mg DDAVP 22.5 µ g mmhg C µ g µ g 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.

3 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 Urine cortisol Urine 17 OHCS Urine 17 KS PRA Aldosterone Urine adrenalin Urine noradrenalin urine dopamine 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 µ g day Dex mg 7 7 8mg CRH dynamic MRI T1 ACTH pg ml Table 3 DDAVP ACTH ACTH hydrocortisone 1mg ACTH MRI Cushing Cushing Preclinical Cushing 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

4 Table CRH Na K Cl DPD LH FSH GH PRL TSH FT 4 ACTH Cortisol sosm uosm ADH µ g day 132 meq l 3.5 meq l 97 meq l g cmyam nm mmcr 3.5 miu ml miu ml ng ml ng ml µ lu ml ng dl pg ml µ g dl pg ml ACTH Dex 1mg µ g dl DDAVP ACTH 1.5 CRH ACTH MRI Subclinical Cushing Subclinical Cushing Cushing 5, 6 7 Cushing 8 β 9 in vitro 10 Table Table 1 3 Hardy 2 5 Cushing 12 4 µ g dl CRH ACTH 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

5 Subclinical Cushing 2 1 Table 4 Subclinical Cushing Subclinical Cushing BMI 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 ND 5.7 HbA1c ND ND Nagai et al Subclinical Cushing BMI 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 Takao et al ND HT DM IGT 793

6 Table 4 Subclinical Cushing Hardy mg 5 17 Hardy 7 Hardy 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 mg 12 9 CRH ACTH DDAVP ACTH CT 5 5 MRI Subclinical Cushing CT ACTH cortisol 1mgCRH DDAVP ACTH MRI Subclinical Cushing 2 1 Subclinical Cushing CT CRH DDAVP 1,, 1994 Preclinical Cushing. 70 : Takao T, Mimoto T, Yamamoto M, Hashimoto K 2001 Preclinical Cushing disease. Arch Intern Med 161 : ,,,,,,,,,,,,, 2000 Preclinical Cushing s syndrome Overt Cushing s syndrome 76 : Pre Subclinical Cushing. 79 suppl. Aug Nosadini R, Del Prato S, Tiengo A, Valerio A, Muggeo 794

7 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 : 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 : 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 : 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 : 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 : 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 : : ,,,,,,,,,, 2001 Cushing, γ knife 77 suppl : , : ,,,,,, : Preclinical Cushing 1. ACTH RELATED PEPTIDES 8 : ,,, 2002 CRH preclinical Cushing disease. 51 : Nagai T, Imamura M, Misumi S, Mori M 2002 Subclinical Cushing s disease accompanied by malignant hypertension and diabetes mellitus. Internal medicine 41 : , 2001 preclinical Cushing : Tomlinson JW, Stewart PM 2001 Cortisol metabolism and the role of 11 β hydroxysteroid dehydrogenase. Best practice and clinical endocrinology and metabolism 15 : 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 :

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