Salivary Cortisol and Cortisone do not Appear to be Useful Biomarkers for Monitoring Hydrocortisone Replacement in Addison's Disease.
Salivary cortisol has been used to monitor hydrocortisone replacement in patients with Addison's disease (AD). Since salivary cortisol is metabolised to salivary cortisone, it may be an adjunctive analyte to assess adequacy of hydrocortisone replacement in patients with AD. We aimed to characterise the exposure of salivary cortisol and cortisone in patients and healthy controls. We measured salivary cortisol and cortisone by liquid chromatography-tandem mass spectrometry and constructed a day curve (08:00 until 24:00 h) with 16 time points in 25 AD patients taking their usual hydrocortisone dose and in 26 healthy controls. The median (interquartile range) area under the curve (AUC) for cortisol was not different for patients, compared with controls [55.63 (32.91-151.07) nmol*min*l-1vs. 37.49 (27.41-52.00) nmol*min*l-1; p=0.098, respectively], whereas the peak cortisol Cmaxwas higher in patients [32.61 (5.75-146.19) nmol/l vs. 8.96 (6.96-12.23) nmol/l; p=0.013], compared with controls. The AUC for cortisone [23.65 (6.10-54.76) nmol*min*l-1vs. 227.73 (200.10-280.52) nmol*min*l-1; p≤ 0.001, respectively], and peak cortisone Cmaxwas lower in patients than in controls [11.11 (2.91-35.85) nmol/l vs. 33.12 (25.97-39.95) nmol/l; p=0.002]. The AUC for salivary cortisol and salivary cortisone were not correlated with any measures of hydrocortisone dose. The time-course and AUC of salivary cortisol were similar between Addison's patients and healthy controls. Patients had substantially lower salivary cortisone AUC, compared to healthy controls. Salivary cortisol AUC and pharmacokinetics were not related to hydrocortisone dose and thus are not likely useful markers for the adequacy of hydrocortisone replacement.
Division of Endocrinology, Department of Medicine University of Cape Town, Cape Town, South Africa.
I L
IL
Ross
Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa.
M
M
Lacerda
Department of Chemical Pathology & NHLS Tshwane Academic Division, University of Pretoria, Pretoria, South Africa.
T S
TS
Pillay
Division of Lipidology, Department of Medicine, University of Cape Town, South Africa.
D J
DJ
Blom
Department of Endocrinology, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
G
G
Johannsson
Division of Endocrinology, Department of Medicine University of Cape Town, Cape Town, South Africa.
J A
JA
Dave
Division of Endocrinology, Department of Medicine University of Cape Town, Cape Town, South Africa.
N S
NS
Levitt
Ampath Laboratories Pomona, Gauteng Province, South Africa.
D
D
Haarburger
Eli Lilly Windlesham, Surrey GU20 6PH, UK.
J-S
JS
van der Walt
D000224:Addison Disease / Q000188:drug therapy*; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003348:Cortisone / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000378:metabolism*; D013997:Time Factors; D055815:Young Adult
D015415:Biomarkers; D003348:Cortisone; D006854:Hydrocortisone