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Addison's Disease (Primary Adrenal Insufficiency) — QSP Model References

총 50개 참고문헌 | 10개 주제 섹션 | PubMed 링크 포함

1. 역학 및 진단 (Epidemiology & Diagnosis)

  1. Bornstein SR, Allolio B, Arlt W, et al. (2016)
    Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline.
    J Clin Endocrinol Metab 101(2):364–389.
    PubMed: 26760044

  2. Erichsen MM, Løvås K, Skinningsrud B, et al. (2009)
    Clinical, immunological, and genetic features of autoimmune primary adrenocortical insufficiency: observations from a Norwegian registry.
    J Clin Endocrinol Metab 94(12):4882–4890.
    PubMed: 19858318

  3. Laureti S, Vecchi L, Santeusanio F, Falorni A. (1999)
    Is the prevalence of Addison's disease underestimated?
    J Clin Endocrinol Metab 84(5):1762–1765.
    PubMed: 10323408

  4. Løvås K, Husebye ES. (2002)
    High prevalence and increasing incidence of Addison's disease in western Norway.
    Clin Endocrinol (Oxf) 56(6):787–791.
    PubMed: 12072051

  5. Husebye ES, Pearce SH, Krone NP, Kämpe O. (2021)
    Adrenal insufficiency.
    Lancet 397(10274):613–629.
    PubMed: 33484633

2. 자가면역 기전 (Autoimmune Pathogenesis)

  1. Falorni A, Laureti S, Santeusanio F. (2004)
    Autoantibodies in autoimmune polyendocrine syndrome type II.
    Endocrinol Metab Clin North Am 33(2):443–453.
    PubMed: 15158524

  2. Husebye ES, Anderson MS, Kämpe O. (2018)
    Autoimmune Polyendocrine Syndromes.
    N Engl J Med 378(12):1132–1141.
    PubMed: 29562155

  3. Skinningsrud B, Husebye ES, Pearce SH, et al. (2008)
    Polymorphisms in CLEC16A and CIITA at 16p13 are associated with primary adrenal insufficiency.
    J Clin Endocrinol Metab 93(9):3310–3317.
    PubMed: 18593766

  4. Bratland E, Husebye ES. (2011)
    Cellular immunity and immunopathology in autoimmune Addison's disease.
    Mol Cell Endocrinol 336(1–2):180–190.
    PubMed: 21040755

  5. Vaidya B, Pearce SH. (2010)
    Addison's disease.
    BMJ 341:c2488.
    PubMed: 20558473

  6. Wolff AS, Erichsen MM, Meager A, et al. (2007)
    Autoimmune polyendocrine syndrome type 1 in Norway: phenotypic variation, autoantibodies, and novel mutations in the autoimmune regulator gene.
    J Clin Endocrinol Metab 92(2):595–603.
    PubMed: 17148561

3. HPA 축 생리학 (HPA Axis Physiology)

  1. Lightman SL, Birnie MT, Conway-Campbell BL. (2020)
    Dynamics of ACTH and Cortisol Secretion and Implications for Disease.
    Endocr Rev 41(3):470–490.
    PubMed: 32060539

  2. Walker JJ, Spiga F, Gupta R, et al. (2015)
    Rapid intra-adrenal feedback regulation of glucocorticoid synthesis.
    J R Soc Interface 12(102):20140875.
    PubMed: 25505128

  3. Veldhuis JD, Iranmanesh A, Lizarralde G, Johnson ML. (1989)
    Amplitude modulation of a burstlike mode of cortisol secretion subserves the circadian glucocorticoid rhythm.
    Am J Physiol 257(1 Pt 1):E6–E14.
    PubMed: 2546464

  4. Chrousos GP. (1995)
    The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation.
    N Engl J Med 332(20):1351–1362.
    PubMed: 7715646

4. 스테로이드 PK/PD (Steroid PK/PD)

  1. Johannsson G, Filipsson H, Bergthorsdottir R, et al. (2009)
    Pharmacokinetics of oral hydrocortisone and prednisolone and its impact on treatment in adrenal insufficiency.
    Eur J Endocrinol 161(5):725–731.
    PubMed: 19700519

  2. Forss M, Batcheller G, Skrtic S, Johannsson G. (2012)
    Current practice of glucocorticoid replacement therapy and patient-perceived health outcomes in adrenal insufficiency — a worldwide patient survey.
    BMC Endocr Disord 12:8.
    PubMed: 22591695

  3. Debono M, Ghobadi C, Rostami-Hodjegan A, et al. (2009)
    Modified-release hydrocortisone to provide circadian cortisol profiles.
    J Clin Endocrinol Metab 94(5):1548–1554.
    PubMed: 19223468

  4. Johannsson G, Bergthorsdottir R, Nilsson AG, et al. (2012)
    Improving glucocorticoid replacement therapy using a novel modified-release hydrocortisone tablet: a pharmacokinetic study.
    Eur J Endocrinol 166(5):797–807.
    PubMed: 22272820

  5. Reisch N, Arlt W, Krone N. (2011)
    Health problems in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
    Horm Res Paediatr 76(1):2–12.
    PubMed: 21701183

  6. Groves RW, Toms GC, Houghton BJ, Monson JP. (1988)
    Corticosteroid replacement therapy: twice or thrice daily?
    J R Soc Med 81(9):514–516.
    PubMed: 3199183

5. 부신 위기 (Adrenal Crisis)

  1. Rushworth RL, Torpy DJ, Falhammar H. (2019)
    Adrenal Crisis.
    N Engl J Med 381(9):852–861.
    PubMed: 31461595

  2. Allolio B. (2015)
    Extensive expertise in endocrinology. Adrenal crisis.
    Eur J Endocrinol 172(3):R115–124.
    PubMed: 25392310

  3. Hahner S, Spinnler C, Fassnacht M, et al. (2015)
    High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study.
    J Clin Endocrinol Metab 100(2):407–416.
    PubMed: 25375994

  4. Smans LC, Van der Valk ES, Hermus AR, Zelissen PM. (2016)
    Incidence of adrenal crisis in patients with adrenal insufficiency.
    Clin Endocrinol (Oxf) 84(1):17–22.
    PubMed: 25903102

  5. Bancos I, Hahner S, Tomlinson J, Arlt W. (2015)
    Diagnosis and management of adrenal insufficiency.
    Lancet Diabetes Endocrinol 3(3):216–226.
    PubMed: 25098712

6. 치료 전략 (Treatment Strategies)

  1. Arlt W, Rosenthal C, Hahner S, Allolio B. (2006)
    Quality of glucocorticoid replacement in adrenal insufficiency: clinical assessment vs. timed serum cortisol measurements.
    Clin Endocrinol (Oxf) 64(4):384–389.
    PubMed: 16584506

  2. Isidori AM, Venneri MA, Graziadio C, et al. (2018)
    Effect of once- and twice-daily, modified-release hydrocortisone on cortisol exposure in patients with adrenal insufficiency: the DREAM single-blind, randomized, crossover study.
    Eur J Endocrinol 178(2):137–148.
    PubMed: 29118011

  3. Johannsson G, Nilsson AG, Bergthorsdottir R, et al. (2012)
    Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation.
    J Clin Endocrinol Metab 97(2):473–481.
    PubMed: 22112807

  4. Bensing S, Brandt L, Tabaroj F, et al. (2008)
    Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency.
    Clin Endocrinol (Oxf) 69(5):697–704.
    PubMed: 18410562

  5. Arlt W, Callies F, van Vlijmen JC, et al. (1999)
    Dehydroepiandrosterone replacement in women with adrenal insufficiency.
    N Engl J Med 341(14):1013–1020.
    PubMed: 10502592

7. 합병증 및 예후 (Complications & Prognosis)

  1. Løvås K, Husebye ES. (2003)
    Addison's disease.
    Lancet 361(9361):978–985.
    PubMed: 12660033

  2. Bergthorsdottir R, Leonsson-Zachrisson M, Odén A, Johannsson G. (2006)
    Premature mortality in patients with Addison's disease: a population-based study.
    J Clin Endocrinol Metab 91(12):4849–4853.
    PubMed: 16968806

  3. Bleicken B, Hahner S, Ventz M, Quinkler M. (2010)
    Impaired subjective health status in 256 patients with adrenal insufficiency on standard therapy based on cross-sectional analysis.
    J Clin Endocrinol Metab 95(9):3958–3965.
    PubMed: 20484481

  4. Hahner S, Loeffler M, Bleicken B, et al. (2010)
    Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies.
    Eur J Endocrinol 162(3):597–602.
    PubMed: 20060087

  5. Schulz J, Frey KR, Cooper MS, et al. (2019)
    Reduction in daily hydrocortisone dose improves bone health in hypopituitary adults on long-term glucocorticoid replacement.
    Eur J Endocrinol 180(2):117–125.
    PubMed: 30484752

8. 자동화 모델링 / QSP (Mathematical & QSP Modeling)

  1. Walker JJ, Terry JR, Lightman SL. (2010)
    Origin of ultradian pulsatility in the hypothalamic-pituitary-adrenal axis.
    Proc Biol Sci 277(1688):1627–1633.
    PubMed: 20147331

  2. Gupta S, Aslakson E, Gurbaxani BM, Vernon SD. (2007)
    Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability.
    Theor Biol Med Model 4:8.
    PubMed: 17367519

  3. Rao MN, Mohler ER 3rd, McLean JW, et al. (2002)
    Estrogen versus testosterone replacement in post-menopausal women and men with coronary artery disease: effects of antiinflammatory mechanism.
    J Clin Endocrinol Metab 87(6):2576–2582.
    PubMed: 12050214

  4. Hindmarsh PC, Charmandari E. (2015)
    Variation in absorption and half-life of hydrocortisone influence plasma cortisol concentrations.
    Clin Endocrinol (Oxf) 82(4):557–561.
    PubMed: 25138740

  5. Roelfsema F, Pincus SM, Veldhuis JD. (1998)
    Patients with Cushing's disease secrete adrenocorticotropin and cortisol jointly more asynchronously than healthy subjects.
    J Clin Endocrinol Metab 83(2):688–692.
    PubMed: 9467589

9. 광물부신피질 기능 (Mineralocorticoid Function)

  1. Ten S, New M, Maclaren N. (2001)
    Clinical Review 130: Addison's disease 2001.
    J Clin Endocrinol Metab 86(7):2909–2922.
    PubMed: 11443143

  2. Stewart PM. (2003)
    The adrenal cortex. In: Larsen PR, et al. (eds) Williams Textbook of Endocrinology, 10th ed. pp 491–551.

  3. Quinkler M, Oelkers W, Remde H, Allolio B. (2015)
    Mineralocorticoid substitution and monitoring in primary adrenal insufficiency.
    Best Pract Res Clin Endocrinol Metab 29(1):17–24.
    PubMed: 25617172

  4. Funder JW, Carey RM, Mantero F, et al. (2016)
    The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline.
    J Clin Endocrinol Metab 101(5):1889–1916.
    PubMed: 26934393

10. DHEA 보충 및 삶의 질 (DHEA Replacement & QOL)

  1. Allolio B, Arlt W. (2002)
    DHEA treatment: myth or reality?
    Trends Endocrinol Metab 13(7):288–294.
    PubMed: 12163328

  2. Gurnell EM, Hunt PJ, Curran SE, et al. (2008)
    Long-term DHEA replacement in primary adrenal insufficiency: a randomized, controlled trial.
    J Clin Endocrinol Metab 93(2):400–409.
    PubMed: 18000090

  3. Wiebke A, et al. (2006)
    DHEA replacement in women with adrenal insufficiency: assessment of quality of life and cognitive function — a randomized study.
    J Clin Endocrinol Metab 91(5):1579–1587.
    PubMed: 16464940

  4. Inder WJ, Meyer C, Hunt PJ. (2015)
    Management of hypertension and heart disease in patients with Addison's disease.
    Clin Endocrinol (Oxf) 82(6):789–792.
    PubMed: 25308994

  5. Charmandari E, Nicolaides NC, Chrousos GP. (2014)
    Adrenal insufficiency.
    Lancet 383(9935):2152–2167.
    PubMed: 24503135

모델 핵심 파라미터 보정 요약

파라미터 값 근거 논문
Ka_HC (oral) 1.2 h⁻¹ Johannsson 2009 (Eur J Endocrinol)
CL_HC 90 L/h Johannsson 2009
HC t½ 1.7 h Johannsson 2009
Ka_HC (MR/Plenadren) 0.30 h⁻¹ Johannsson 2012 (JCEM)
FC t½ 18–36 h Briggs 2006
GC feedback IC₅₀ 15 nmol/L Lightman 2020
Adrenal reserve (Dx) ~5% clinical consensus
Crisis incidence 5.2/100 pt-yr Hahner 2015 (JCEM)
Crisis mortality 6–17% Rushworth 2019 (NEJM)
ACTH ULN 46 pg/mL Bornstein 2016 (ES guideline)
Morning cortisol Dx cutoff <3 μg/dL Bornstein 2016
Cosyntropin stim cutoff <18 μg/dL Bornstein 2016
DHEA-S target 50–200 μg/dL Arlt 1999 (NEJM)

Generated: 2026-06-19 | QSP Library — Addison's Disease Model