title: Salivary cortisol day curves in assessing glucocorticoid replacement therapy in Addison's disease.
abstract: OBJECTIVE
  Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects. The aim of this study was to investigate the use of salivary cortisol day curves (SCDC) in the individual adjustment of GRT in order to approach normal cortisol levels as closely as possible, reduce over- and underreplacement and study the short-term effects on quality of life (QoL).
  
  
  METHODS
  Twenty patients with Addison's disease were included in this prospective study. A SCDC was obtained and compared to normal controls; general and disease specific QoL-questionnaires were completed. Based on SCDC assessment of over- and undertreatment (calculated as duration (h) × magnitude (nmol/L) at different time points, glucocorticoid dose and regime were adjusted. After 4 weeks SCDC and QoL assessment were repeated and the effect of adjusting GRT was analysed.
  
  
  RESULTS
  At baseline, underreplacement was present in 3 and overreplacement in 18 patients; total calculated overreplacement was 32.8 h.nmol/L. Overreplacement decreased significantly to 13.3 h. nmol/L (p =0.005) after adjustment of GRT. Overreplacement was found particularly in the afternoon and evening. After reducing overreplacement in the evening, complaints about sleep disturbances significantly decreased.
  
  
  CONCLUSIONS
  Individual adjustment of GRT based on SCDC to approach normal cortisol concentrations during the day can reduce overreplacement, especially in the evening. This can lead to a reduction of sleep disturbances and fatigue in patients with Addison's disease. A SCDC is a simple and patient-friendly tool for adjusting GRT and can be useful in the follow-up of patients with Addison's disease.
authors.affiliation: Department of Internal Medicine and Endocrinology, University Medical Center Utrecht, Utrecht, The Netherlands. L.C.C.J.Smans@umcutrcht.nl
authors.forename: Lisanne
authors.initials: L
authors.lastname: Smans
authors.forename: Eef
authors.initials: E
authors.lastname: Lentjes
authors.forename: Ad
authors.initials: A
authors.lastname: Hermus
authors.forename: Pierre
authors.initials: P
authors.lastname: Zelissen
mesh_terms: D000224:Addison Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002940:Circadian Rhythm; D003348:Cortisone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D006854:Hydrocortisone / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011788:Quality of Life; D012463:Saliva / Q000378:metabolism*; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D003348:Cortisone; D006854:Hydrocortisone