Endocrine Abstracts (2006) 11 P749

Hydrocortisone replacement therapy- the controversy continues…

M Freel1, A Thomson3, M Devers1, K Campbell1, D Grant1, M Wallace2 & J Connell1

1Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; 2Department of Clinical Biochemistry, Glasgow Royal Infirmary, Glasgow, United Kingdom; 3Department of Clinical Pharmacokinetics, Western Infirmary, Glasgow, United Kingdom.

Although hydrocortisone is the standard replacement therapy for primary or secondary adrenal insufficiency (AI), there are limited data on dosage requirements and the value of salivary monitoring in this patient group. We assessed inter-individual variability in cortisol metabolism and relationships between plasma and salivary cortisol profiles in 27 patients. Ten (3 male) patients had primary AI and 17 (8 male) secondary AI. Salivary and plasma cortisol levels were measured at regular intervals following intravenous (IV, 20 mg bolus) and oral (10–20 mg) hydrocortisone. Local Ethics Committee approval was obtained. Cortisol levels were measured in saliva by radioimmunoassay (125I-cortisol) and in plasma by HPLC following solvent extraction.

Wide variability in plasma cortisol profiles was observed after IV administration (Cmax range 715–8313 nmol/l; AUC 1367–11658 nmol.h/l). Cortisol clearance was calculated as an indirect measure of inter-individual variability. This had a mean value (S.D.) of 20.5 (9.1) l/h and was influenced by weight (mean (S.D.) 0.273 (0.107) l/h/kg), with no additional effect of age, height, body surface area or sex. After oral administration, Cmax ranged from 422–1554 nmol/l, AUC 1160–4511 nmol.h/l and oral clearance had a mean (S.D.) of 0.245 (0.082) l/h/kg.

There was no clear relationship between paired saliva and plasma cortisol concentrations after IV or oral dosing. There was a significant correlation between plasma and salivary AUC2–8 h after IV administration (r=0.87, P=0.00) but differences between predicted and measured plasma AUCs ranged from 3–90% (median 18%). There was a poor correlation between plasma and saliva AUC2–-6 h after oral administration (r=0.4, P=0.08).

Wide inter-individual variability was identified in the handling of hydrocortisone in patients with AI making it difficult to recommend a standard ‘dose’ of hydrocortisone. Poor correlation between limited sample salivary and plasma AUCs suggests that salivary monitoring is unlikely to be a useful determinant of dosage requirements in patients with AI.

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