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This version published online on July 3, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-0445
A more recent version of this article appeared on September 1, 2007
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Submitted on March 5, 2007
Accepted on June 26, 2007

Effects of cortisol on carbohydrate, lipid, and protein metabolism; studies of acute cortisol withdrawal in adrenocortical failure

Jens Juel Christiansen*, Christian B. Djurhuus, Claus H. Gravholt, Per Iversen, Jens Sandahl Christiansen, Ole Schmitz, Jørgen Weeke, Jens Otto Lunde Jørgensen, and Niels Møller

Medical Department M, Aarhus Sygehus and Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Denmark

* To whom correspondence should be addressed. E-mail: Juel{at}dadlnet.dk.

CONTEXT: Cortisol is an important catabolic hormone, but little is known about the metabolic effects of acute cortisol deficiency.

OBJECTIVE: To test whether clinical symptoms of weight loss, fatigue and hypoglycaemia could be explained by altered energy expenditure, protein metabolism and insulin sensitivity during cortisol withdrawal in adrenocortical failure.

DESIGN, PARTICIPANTS and INTERVENTION: We studied 7 women after 24h cortisol withdrawal (CW) and during replacement control (CTR) during a 3h basal period and a 3h glucose clamp.

RESULTS: Cortisol withdrawal generated cortisol levels close to zero, a 10% decrease in basal energy expenditure, increased TSH and T3 levels and increased glucose oxidation. Whole body glucose and phenylalanine turnover were unaltered, but forearm phenylalanine turnover was increased.

During the clamp glucose infusion rates rose by 70%, glucose oxidation rates increased and endogenous glucose production decreased. Urinary urea excretion decreased by 40% over the 6h study period.

CONCLUSIONS: Cortisol withdrawal increased insulin sensitivity, in terms of increased glucose oxidation and decreased endogenous glucose production; this may induce hypoglycaemia in adrenocortical failure. Energy expenditure and urea loss decreased, indicating that weight and muscle loss in Addison's disease, is caused by other mechanisms, such as decreased appetite. Increased muscle protein breakdown may amplify the loss of muscle protein.
Key words: Cortisol • adrenal insufficiency • glucose • protein and lipid metabolism • insulin sensitivity






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