肾上腺皮质功能减退症的诊治现状
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摘要
<正>从1855年Thomas Addison 首次报道肾上腺皮质功能减退症(adrenal insufficiency,AI),到1949年糖皮质激素(glucocorticoid,GC)替代治疗运用于临床,近100多年AI的诊治取得很多重大成果。肾上腺皮质主要分泌盐皮质激素、GC和性激素。AI是指由于各种原因导致基础或者应激状态下肾上腺皮质激素分泌减少所致的疾病,AI按病因分为原发性肾上腺皮质功能减退症(primary adrenal i
引文
1 Bornstein SR,Allolio B,Arlt W,et al.Diagnosis and treatment of primary adrenal insufficiency:an endocrine society clinical practice guideline[J].J Clin Endocrinol Metab,2016,101(2): 364-389.
2 Husebye ES,Allolio B,Arlt W,et al.Consensus statement on the diagnosis,treatment and follow-up of patients with primary adrenal insufficiency[J].J Intern Med,2014,275(2):104-115.
3 Charmandari E,Nicolaides NC,Chrousos GP.Adrenal insufficiency[J].Lancet,2014,383(9935):2152-2167.
4 Klose M,Lange M,Kosteljanetz M,et al.Adrenocortical insufficiency after pituitary surgery:an audit of the reliability of the conventional short synacthen test[J].Clin Endocrinol,2005,63(5):499-505.
5 Wallace I,Cunningham S,Lindsay J.The diagnosis and investigation of adrenal insufficiency in adults[J].Ann Clin Biochem,2009,46(Pt 5):351-367.
6 Watts NB,Tindall GT.Rapid assessment of corticotropin reserve after pituitary surgery[J].JAMA,1988,259(5):708-711.
7 Hagg E,Asplund K,Lithner F.Value of basal plasma cortisol assays in the assessment of pituitary-adrenal insufficiency[J].Clin Endocrinol,1987,26(2):221-226.
8 Agwu JC,Spoudeas H,Hindmarsh PC,et al.Tests of adrenal insufficiency[J].Arch Dis Child,1999,80(4):330-333.
9 Kazlauskaite R,Evans AT,Villabona CV,et al.Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency:a metaanalysis[J].J Clin Endocrinol Metab,2008,93(11):4245-4253.
10 Yanase T,Tajima T,Katabami T,et al.Diagnosis and treatment of adrenal insufficiency including adrenal crisis:a Japan Endocrine Society clinical practice guideline Opinion][J].Endocr J,2016,63(9):765-784.
11 Struja T,Briner L,Meier A,et al.Diagnostic accuracy of basal cortisol level to predict adrenal insufficiency in cosyntropin testing:results from an observational cohort study with 804 patients[J].Endocr Pract,2017,23(8):949-961.
12 Hsu TH,Bledsoe T.Measurement of urinary free corticoids by competitive protein-binding radioassay in hypoadrenal states[J].J Clin Endocrinol Metab,1970,30(4):443-448.
13 Dullaart RP,Pasterkamp SH,Beentjes JA,et al.Evaluation of adrenal function in patients with hypothalamic and pituitary disorders:comparison of serum cortisol,urinary free cortisol and the human-corticotrophin releasing hormone test with the insulin tolerance test[J].Clin Endocrinol ,1999,50(4):465-471.
14 Marcus-Perlman Y,Tordjman K,Greenman Y,et al.Low-dose ACTH (1 microg) salivary test:a potential alternative to the classical blood test[J].Clin Endocrinol ,2006,64(2):215-218.
15 Raff H.Utility of salivary cortisol measurements in cushing's syndrome and adrenal insufficiency[J].J Clin Endocrinol Metab,2009,94(10):3647-3655.
16 Elder CJ,Harrison RF,Cross AS,et al.Use of salivary cortisol and cortisone in the high- and low-dose synacthen test[J].Clin Endocrinol ,2017.
17 Oelkers W.Adrenal insufficiency[J].N Engl J Med,1996,335(16):1206-1212.
18 Arlt W,Callies F,van Vlijmen JC,et al.Dehydroepiandrosterone replacement in women with adrenal insufficiency[J].N Engl J Med,1999,341(14):1013-1020.
19 Nasrallah MP,Arafah BM.The value of dehydroepiandrosterone sulfate measurements in the assessment of adrenal function[J].J Clin Endocrinol Metab,2003,88(11):5293-5298.
20 Sayyed Kassem L,El Sibai K,Chaiban J,et al.Measurements of serum DHEA and DHEA sulphate levels improve the accuracy of the low-dose cosyntropin test in the diagnosis of central adrenal insufficiency[J].J Clin Endocrinol Metab,2012,97(10):3655-3662.
21 Grinspoon SK,Biller BM.Clinical review 62:laboratory assessment of adrenal insufficiency[J].J Clin Endocrinol Metab,1994,79(4):923-931.
22 Oelkers W.Dose-response aspects in the clinical assessment of the hypothalamo-pituitary-adrenal axis,and the low-dose adrenocorticotropin test[J].Eur J Endocrinol,1996,135(1):27-33.
23 Barth JH,Seth J,Howlett TA,et al.A survey of endocrine function testing by clinical biochemistry laboratories in the UK[J].Ann Clin Biochem,1995,32 ( Pt 5):442-449.
24 Gonzalbez J,Villabona C,Ramon J,et al.Establishment of reference values for standard dose short synacthen test (250 microgram),low dose short synacthen test (1 microgram) and insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in normal subjects[J].Clin Endocrinol ,2000,53(2):199-204.
25 Speckart PF,Nicoloff JT,Bethune JE.Screening for adrenocortical insufficiency with cosyntropin (synthetic ACTH)[J].Arch Intern Med,1971,128(5):761-763.
26 Giordano R,Picu A,Bonelli L,et al.Hypothalamus-pituitary-adrenal axis evaluation in patients with hypothalamo-pituitary disorders:comparison of different provocative tests[J].Clin Endocrinol ,2008,68(6):935-941.
27 Salvatori R.Adrenal insufficiency[J].JAMA,2005,294(19):2481-2488.
28 Arlt W,Allolio B.Adrenal insufficiency[J].Lancet,2003,361(9372):1881-1893.
29 Dorin RI,Qualls CR,Crapo LM.Diagnosis of adrenal insufficiency[J].Ann Intern Med,2003,139(3):194-204.
30 Nieman LK.Dynamic evaluation of adrenal hypofunction[J].J Endocrinol Invest,2003,26(7 Suppl):74-82.
31 Pfeifer M,Kanc K,Verhovec R,et al.Reproducibility of the insulin tolerance test (ITT) for assessment of growth hormone and cortisol secretion in normal and hypopituitary adult men[J].Clin Endocrinol ,2001,54(1):17-22.
32 Dolman LI,Nolan G,Jubiz W.Metyrapone test with adrenocorticotrophic levels.Separating primary from secondary adrenal insufficiency[J].JAMA,1979,241(12):1251-1253.
33 Berneis K,Staub JJ,Gessler A,et al.Combined stimulation of adrenocorticotropin and compound-S by single dose metyrapone test as an outpatient procedure to assess hypothalamic-pituitary-adrenal function[J].J Clin Endocrinol Metab,2002,87(12):5470-5475.
34 Fiad TM,Kirby JM,Cunningham SK,et al.The overnight single-dose metyrapone test is a simple and reliable index of the hypothalamic-pituitary-adrenal axis[J].Clin Endocrinol ,1994,40(5):603-609.
35 Courtney CH,McAllister AS,McCance DR,et al.The insulin hypoglycaemia and overnight metyrapone tests in the assessment of the hypothalamic-pituitary-adrenal axis following pituitary surgery[J].Clin Endocrinol,2000,53(3):309-312.
36 Oelkers W,Diederich S,Bahr V.Diagnosis and therapy surveillance in addison's disease:rapid adrenocorticotropin (ACTH) test and measurement of plasma ACTH,renin activity,and aldosterone[J].J Clin Endocrinol Metab,1992,75(1):259-264.
37 Courtney CH,McAllister AS,McCance DR,et al.Comparison of one week 0900 h serum cortisol,low and standard dose synacthen tests with a 4 to 6 week insulin hypoglycaemia test after pituitary surgery in assessing HPA axis[J].Clin Endocrinol ,2000,53(4):431-436.
38 Marik PE,Pastores SM,Annane D,et al.Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients:consensus statements from an international task force by the American College of Critical Care Medicine[J].Crit Care Med,2008,36(6):1937-1949.
39 Moraes RB,Czepielewski MA,Friedman G,et al.Diagnosis of adrenal failure in critically ill patients[J].Arq Bras Endocrinol Metabol,2011,55(5):295-302.
40 Hahner S,Loeffler M,Bleicken B,et al.Epidemiology of adrenal crisis in chronic adrenal insufficiency:the need for new prevention strategies[J].Eur J Endocrinol,2010,162(3):597-602.
41 Arlt W.Society for endocrinology clinical c.society for endocrinology endocring emergency guidance::emergency management of acute adrenal insufficiency (adrenal crisis) in adult patients[J].Endocr Connect,2016,5(5):G1-G3.
42 Hahner S,Loeffler M,Fassnacht M,et al.Impaired subjective health status in 256 patients with adrenal insufficiency on standard therapy based on cross-sectional analysis[J].J Clin Endocrinol Metab,2007,92(10):3912-3922.
43 Kampmeyer D,Haas CS,Moenig H,et al.Self-management in adrenal insufficiency - towards a better understanding[J].Endocr J,2017,64(4):379-385.
44 Reisch N,Arlt W.Fine tuning for quality of life:21st century approach to treatment of Addison's disease[J].Endocrinol Metab Clin North Am,2009,38(2):407-418.
45 Murray RD,Ekman B,Uddin S,et al.Management of glucocorticoid replacement in adrenal insufficiency shows notable heterogeneity - data from the EU-AIR[J].Clin Endocrinol ,2017,86(3):340-346.
46 Bleicken B,Hahner S,Loeffler M,et al.Influence of hydrocortisone dosage scheme on health-related quality of life in patients with adrenal insufficiency[J].Clin Endocrinol ,2010,72(3):297-304.
47 Howlett TA.An assessment of optimal hydrocortisone replacement therapy[J].Clin Endocrinol ,1997,46(3):263-268.
48 Ekman B,Bachrach-Lindstrom M,Lindstrom T,et al.A randomized,double-blind,crossover study comparing two- and four-dose hydrocortisone regimen with regard to quality of life,cortisol and ACTH profiles in patients with primary adrenal insufficiency[J].Clin Endocrinol ,2012,77(1):18-25.
49 Lovas K,Husebye ES.Continuous subcutaneous hydrocortisone infusion in Addison's disease[J].Eur J Endocrinol,2007,157(1):109-112.
50 Bleicken B,Hahner S,Loeffler M,et al.Impaired subjective health status in chronic adrenal insufficiency:impact of different glucocorticoid replacement regimens[J].Eur J Endocrinol,2008,159(6):811-817.
51 Quinkler M,Ekman B,Marelli C,et al.Prednisolone is associated with a worse lipid profile than hydrocortisone in patients with adrenal insufficiency[J].Endocr Connect,2017,6(1):1-8.
52 Smith DJF,Prabhudev H,Choudhury S,et al.Prednisolone has the same cardiovascular risk profile as hydrocortisone in glucocorticoid replacement[J].Endocr Connect,2017,6(8):766-772.
53 Chikada N,Imaki T,Hotta M,et al.An assessment of bone mineral density in patients with Addison's disease and isolated ACTH deficiency treated with glucocorticoid[J].Endocr J,2004,51(3):355-360.
54 Mazziotti G,Formenti AM,Frara S,et al.Management of endocrine disease:risk of overtreatment in patients with adrenal insufficiency:current and emerging aspects[J].Eur J Endocrinol,2017,177(5):R231-R248.
55 Esposito D,Pasquali D,Johannsson G.Primary adrenal insufficiency:managing mineralocorticoid replacement therapy[J].J Clin Endocrinol Metab,2017.
56 Binder G,Weber S,Ehrismann M,et al.Effects of dehydroepiandrosterone therapy on pubic hair growth and psychological well-being in adolescent girls and young women with central adrenal insufficiency:a double-blind,randomized,placebo-controlled phase III trial[J].J Clin Endocrinol Metab,2009,94(4):1182-1190.
57 Alkatib AA,Cosma M,Elamin MB,et al.A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA treatment effects on quality of life in women with adrenal insufficiency[J].J Clin Endocrinol Metab,2009,94(10):3676-3681.
58 Lovas K,Gebre-Medhin G,Trovik TS,et al.Replacement of dehydroepiandrosterone in adrenal failure:no benefit for subjective health status and sexuality in a 9-month,randomized,parallel group clinical trial[J].J Clin Endocrinol Metab,2003,88(3):1112-1118.
2 Husebye ES,Allolio B,Arlt W,et al.Consensus statement on the diagnosis,treatment and follow-up of patients with primary adrenal insufficiency[J].J Intern Med,2014,275(2):104-115.
3 Charmandari E,Nicolaides NC,Chrousos GP.Adrenal insufficiency[J].Lancet,2014,383(9935):2152-2167.
4 Klose M,Lange M,Kosteljanetz M,et al.Adrenocortical insufficiency after pituitary surgery:an audit of the reliability of the conventional short synacthen test[J].Clin Endocrinol,2005,63(5):499-505.
5 Wallace I,Cunningham S,Lindsay J.The diagnosis and investigation of adrenal insufficiency in adults[J].Ann Clin Biochem,2009,46(Pt 5):351-367.
6 Watts NB,Tindall GT.Rapid assessment of corticotropin reserve after pituitary surgery[J].JAMA,1988,259(5):708-711.
7 Hagg E,Asplund K,Lithner F.Value of basal plasma cortisol assays in the assessment of pituitary-adrenal insufficiency[J].Clin Endocrinol,1987,26(2):221-226.
8 Agwu JC,Spoudeas H,Hindmarsh PC,et al.Tests of adrenal insufficiency[J].Arch Dis Child,1999,80(4):330-333.
9 Kazlauskaite R,Evans AT,Villabona CV,et al.Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency:a metaanalysis[J].J Clin Endocrinol Metab,2008,93(11):4245-4253.
10 Yanase T,Tajima T,Katabami T,et al.Diagnosis and treatment of adrenal insufficiency including adrenal crisis:a Japan Endocrine Society clinical practice guideline Opinion][J].Endocr J,2016,63(9):765-784.
11 Struja T,Briner L,Meier A,et al.Diagnostic accuracy of basal cortisol level to predict adrenal insufficiency in cosyntropin testing:results from an observational cohort study with 804 patients[J].Endocr Pract,2017,23(8):949-961.
12 Hsu TH,Bledsoe T.Measurement of urinary free corticoids by competitive protein-binding radioassay in hypoadrenal states[J].J Clin Endocrinol Metab,1970,30(4):443-448.
13 Dullaart RP,Pasterkamp SH,Beentjes JA,et al.Evaluation of adrenal function in patients with hypothalamic and pituitary disorders:comparison of serum cortisol,urinary free cortisol and the human-corticotrophin releasing hormone test with the insulin tolerance test[J].Clin Endocrinol ,1999,50(4):465-471.
14 Marcus-Perlman Y,Tordjman K,Greenman Y,et al.Low-dose ACTH (1 microg) salivary test:a potential alternative to the classical blood test[J].Clin Endocrinol ,2006,64(2):215-218.
15 Raff H.Utility of salivary cortisol measurements in cushing's syndrome and adrenal insufficiency[J].J Clin Endocrinol Metab,2009,94(10):3647-3655.
16 Elder CJ,Harrison RF,Cross AS,et al.Use of salivary cortisol and cortisone in the high- and low-dose synacthen test[J].Clin Endocrinol ,2017.
17 Oelkers W.Adrenal insufficiency[J].N Engl J Med,1996,335(16):1206-1212.
18 Arlt W,Callies F,van Vlijmen JC,et al.Dehydroepiandrosterone replacement in women with adrenal insufficiency[J].N Engl J Med,1999,341(14):1013-1020.
19 Nasrallah MP,Arafah BM.The value of dehydroepiandrosterone sulfate measurements in the assessment of adrenal function[J].J Clin Endocrinol Metab,2003,88(11):5293-5298.
20 Sayyed Kassem L,El Sibai K,Chaiban J,et al.Measurements of serum DHEA and DHEA sulphate levels improve the accuracy of the low-dose cosyntropin test in the diagnosis of central adrenal insufficiency[J].J Clin Endocrinol Metab,2012,97(10):3655-3662.
21 Grinspoon SK,Biller BM.Clinical review 62:laboratory assessment of adrenal insufficiency[J].J Clin Endocrinol Metab,1994,79(4):923-931.
22 Oelkers W.Dose-response aspects in the clinical assessment of the hypothalamo-pituitary-adrenal axis,and the low-dose adrenocorticotropin test[J].Eur J Endocrinol,1996,135(1):27-33.
23 Barth JH,Seth J,Howlett TA,et al.A survey of endocrine function testing by clinical biochemistry laboratories in the UK[J].Ann Clin Biochem,1995,32 ( Pt 5):442-449.
24 Gonzalbez J,Villabona C,Ramon J,et al.Establishment of reference values for standard dose short synacthen test (250 microgram),low dose short synacthen test (1 microgram) and insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in normal subjects[J].Clin Endocrinol ,2000,53(2):199-204.
25 Speckart PF,Nicoloff JT,Bethune JE.Screening for adrenocortical insufficiency with cosyntropin (synthetic ACTH)[J].Arch Intern Med,1971,128(5):761-763.
26 Giordano R,Picu A,Bonelli L,et al.Hypothalamus-pituitary-adrenal axis evaluation in patients with hypothalamo-pituitary disorders:comparison of different provocative tests[J].Clin Endocrinol ,2008,68(6):935-941.
27 Salvatori R.Adrenal insufficiency[J].JAMA,2005,294(19):2481-2488.
28 Arlt W,Allolio B.Adrenal insufficiency[J].Lancet,2003,361(9372):1881-1893.
29 Dorin RI,Qualls CR,Crapo LM.Diagnosis of adrenal insufficiency[J].Ann Intern Med,2003,139(3):194-204.
30 Nieman LK.Dynamic evaluation of adrenal hypofunction[J].J Endocrinol Invest,2003,26(7 Suppl):74-82.
31 Pfeifer M,Kanc K,Verhovec R,et al.Reproducibility of the insulin tolerance test (ITT) for assessment of growth hormone and cortisol secretion in normal and hypopituitary adult men[J].Clin Endocrinol ,2001,54(1):17-22.
32 Dolman LI,Nolan G,Jubiz W.Metyrapone test with adrenocorticotrophic levels.Separating primary from secondary adrenal insufficiency[J].JAMA,1979,241(12):1251-1253.
33 Berneis K,Staub JJ,Gessler A,et al.Combined stimulation of adrenocorticotropin and compound-S by single dose metyrapone test as an outpatient procedure to assess hypothalamic-pituitary-adrenal function[J].J Clin Endocrinol Metab,2002,87(12):5470-5475.
34 Fiad TM,Kirby JM,Cunningham SK,et al.The overnight single-dose metyrapone test is a simple and reliable index of the hypothalamic-pituitary-adrenal axis[J].Clin Endocrinol ,1994,40(5):603-609.
35 Courtney CH,McAllister AS,McCance DR,et al.The insulin hypoglycaemia and overnight metyrapone tests in the assessment of the hypothalamic-pituitary-adrenal axis following pituitary surgery[J].Clin Endocrinol,2000,53(3):309-312.
36 Oelkers W,Diederich S,Bahr V.Diagnosis and therapy surveillance in addison's disease:rapid adrenocorticotropin (ACTH) test and measurement of plasma ACTH,renin activity,and aldosterone[J].J Clin Endocrinol Metab,1992,75(1):259-264.
37 Courtney CH,McAllister AS,McCance DR,et al.Comparison of one week 0900 h serum cortisol,low and standard dose synacthen tests with a 4 to 6 week insulin hypoglycaemia test after pituitary surgery in assessing HPA axis[J].Clin Endocrinol ,2000,53(4):431-436.
38 Marik PE,Pastores SM,Annane D,et al.Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients:consensus statements from an international task force by the American College of Critical Care Medicine[J].Crit Care Med,2008,36(6):1937-1949.
39 Moraes RB,Czepielewski MA,Friedman G,et al.Diagnosis of adrenal failure in critically ill patients[J].Arq Bras Endocrinol Metabol,2011,55(5):295-302.
40 Hahner S,Loeffler M,Bleicken B,et al.Epidemiology of adrenal crisis in chronic adrenal insufficiency:the need for new prevention strategies[J].Eur J Endocrinol,2010,162(3):597-602.
41 Arlt W.Society for endocrinology clinical c.society for endocrinology endocring emergency guidance::emergency management of acute adrenal insufficiency (adrenal crisis) in adult patients[J].Endocr Connect,2016,5(5):G1-G3.
42 Hahner S,Loeffler M,Fassnacht M,et al.Impaired subjective health status in 256 patients with adrenal insufficiency on standard therapy based on cross-sectional analysis[J].J Clin Endocrinol Metab,2007,92(10):3912-3922.
43 Kampmeyer D,Haas CS,Moenig H,et al.Self-management in adrenal insufficiency - towards a better understanding[J].Endocr J,2017,64(4):379-385.
44 Reisch N,Arlt W.Fine tuning for quality of life:21st century approach to treatment of Addison's disease[J].Endocrinol Metab Clin North Am,2009,38(2):407-418.
45 Murray RD,Ekman B,Uddin S,et al.Management of glucocorticoid replacement in adrenal insufficiency shows notable heterogeneity - data from the EU-AIR[J].Clin Endocrinol ,2017,86(3):340-346.
46 Bleicken B,Hahner S,Loeffler M,et al.Influence of hydrocortisone dosage scheme on health-related quality of life in patients with adrenal insufficiency[J].Clin Endocrinol ,2010,72(3):297-304.
47 Howlett TA.An assessment of optimal hydrocortisone replacement therapy[J].Clin Endocrinol ,1997,46(3):263-268.
48 Ekman B,Bachrach-Lindstrom M,Lindstrom T,et al.A randomized,double-blind,crossover study comparing two- and four-dose hydrocortisone regimen with regard to quality of life,cortisol and ACTH profiles in patients with primary adrenal insufficiency[J].Clin Endocrinol ,2012,77(1):18-25.
49 Lovas K,Husebye ES.Continuous subcutaneous hydrocortisone infusion in Addison's disease[J].Eur J Endocrinol,2007,157(1):109-112.
50 Bleicken B,Hahner S,Loeffler M,et al.Impaired subjective health status in chronic adrenal insufficiency:impact of different glucocorticoid replacement regimens[J].Eur J Endocrinol,2008,159(6):811-817.
51 Quinkler M,Ekman B,Marelli C,et al.Prednisolone is associated with a worse lipid profile than hydrocortisone in patients with adrenal insufficiency[J].Endocr Connect,2017,6(1):1-8.
52 Smith DJF,Prabhudev H,Choudhury S,et al.Prednisolone has the same cardiovascular risk profile as hydrocortisone in glucocorticoid replacement[J].Endocr Connect,2017,6(8):766-772.
53 Chikada N,Imaki T,Hotta M,et al.An assessment of bone mineral density in patients with Addison's disease and isolated ACTH deficiency treated with glucocorticoid[J].Endocr J,2004,51(3):355-360.
54 Mazziotti G,Formenti AM,Frara S,et al.Management of endocrine disease:risk of overtreatment in patients with adrenal insufficiency:current and emerging aspects[J].Eur J Endocrinol,2017,177(5):R231-R248.
55 Esposito D,Pasquali D,Johannsson G.Primary adrenal insufficiency:managing mineralocorticoid replacement therapy[J].J Clin Endocrinol Metab,2017.
56 Binder G,Weber S,Ehrismann M,et al.Effects of dehydroepiandrosterone therapy on pubic hair growth and psychological well-being in adolescent girls and young women with central adrenal insufficiency:a double-blind,randomized,placebo-controlled phase III trial[J].J Clin Endocrinol Metab,2009,94(4):1182-1190.
57 Alkatib AA,Cosma M,Elamin MB,et al.A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA treatment effects on quality of life in women with adrenal insufficiency[J].J Clin Endocrinol Metab,2009,94(10):3676-3681.
58 Lovas K,Gebre-Medhin G,Trovik TS,et al.Replacement of dehydroepiandrosterone in adrenal failure:no benefit for subjective health status and sexuality in a 9-month,randomized,parallel group clinical trial[J].J Clin Endocrinol Metab,2003,88(3):1112-1118.