Cortisol and Metabolism
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T3 levels are increased and RT3 decreased in central adrenal insufficiency (Comtois)
Comtois R, Hébert J, Soucy JP. Increase in T3 levels during hypocorticism in patients with chronic
secondary adrenocortical insufficiency. Acta Endocrinol (Copenh). 1992 Apr;126(4):319-24.
The clinical and biochemical manifestations of secondary adrenocortical insufficiency are not well defined in the
medical literature. This study was designed to determine the clinical and laboratory features suggesting the
diagnosis of adrenal insufficiency in 15 chronic ACTH deficiency patients during low and normal cortisol states.
Except for fatigue and weakness, the characteristic clinical manifestations of primary adrenal insufficiency
occurred rarely. ACTH deficiency did not significantly modify blood glucose, serum calcium, sodium, potassium and
differential white blood cell count. However, serum T4 was lower (65 +/- 19 vs 95 +/- 21 nmol/l, p less than 0.001)
during cortisol deficiency, while T3 was higher (2.4 +/- 0.67 vs 2.0 +/- 0.60 nmol/l, p less than 0.001). Furthermore,
rT3 decreased significantly during hypocorticism (0.27 +/- 0.07 vs 0.18 +/- 0.07 nmol/l, p less than 0.001). The
T4/T3 ratio was significantly lower than the normal in 15 out of the 17 episodes of ACTH deficiency (29 +/- 12.5 vs
57 +/- 9.4, p less than 0.0001). We conclude that the increase in T3 and decrease in T4 levels are associated with
chronic secondary adrenocortical insufficiency. This laboratory feature could be due, at least in part, to the
increased peripheral conversion of T4 to T3 during cortisol deficiency. PMID: 1317631
Rizza RA, Mandarino LJ, Gerich JE. Cortisol-induced insulin resistance in man: impaired suppression of
glucose production and stimulation of glucose utilization due to a postreceptor detect of insulin action. J
Clin Endocrinol Metab. 1982 Jan;54(1):131-8.
The present studies were undertaken to assess the mechanisms responsible for cortisol-induced insulin resistance in
man. The insulin dose-response characteristics for suppression of glucose production and stimulation of glucose
utilization and their relationship to monocyte and erythrocyte insulin receptor binding were determined in six
normal volunteers after 24-h infusion of cortisol and 24-h infusion of saline. The infusion of cortisol (2 microgram
kg-1 min-1) increased the plasma cortisol concentration approximately 4-fold (37 +/- 3 vs. 14 +/- 1 microgram/dl;
P less than 0.01) to values observed during moderately severe stress in man. This hypercortisolemia increased
postabsorptive plasma glucose (126 +/- 2 vs. 97 +/- 2 mg/dl; P less than 0.01) and plasma insulin (16 +/- 2 vs. 10
+/- 2 microU/ml; P less than 0.01) concentrations and rates of glucose production (2.4 +/- 0.1 vs. 2.1 +/- -0.1 mg
kg-1 min-1; P less than 0.01) and utilization (2.5 +/- 0.1 vs. 2.1 +/- 0.1 mg kg-1 min -1; P less than 0.01). Insulin
dose-response curves for both suppression of glucose production (half-maximal response at 81 +/- 19 vs. 31 +/ 5
microU/ml; P less than 0.05) and stimulation of glucose utilization (half-maximal response at 104 +/- 9 vs. 64 +/- 7
microU/ml; P less than 0.01) were shifted to the right, with preservation of normal maximal responses to insulin.
Neither monocyte nor erythrocyte insulin binding was decreased. However, except at near-maximal insulin receptor
occupancy, the action of insulin on glucose production and utilization per number of monocyte and erythrocyte
insulin receptors occupied was decreased. These results indicate that the cortisol-induced insulin resistance in man
is due to the decrease in both hepatic and extrahepatic sensitivity to insulin. Assuming that insulin binding to
monocytes and erythrocytes reflects insulin binding in insulin-sensitive tissues, this decrease in insulin action can be
explained on the basis of a postreceptor defect. PMID: 7033265
Christiansen JJ, Djurhuus CB, Gravholt CH, Iversen P, Christiansen JS, Schmitz O, Weeke J, Jørgensen
JO, Møller N. Effects of cortisol on carbohydrate, lipid, and protein metabolism: studies of acute cortisol
withdrawal in adrenocortical failure. J Clin Endocrinol Metab. 2007 Sep;92(9):3553-9.
CONTEXT: Cortisol is an important catabolic hormone, but little is known about the metabolic effects of acute
cortisol deficiency. OBJECTIVE: The objective of the study was to test whether clinical symptoms of weight loss,
fatigue, and hypoglycemia could be explained by altered energy expenditure, protein metabolism, and insulin
sensitivity during cortisol withdrawal in adrenocortical failure. DESIGN, PARTICIPANTS, AND INTERVENTION:
We studied seven women after 24-h cortisol withdrawal and during replacement control during a 3-h basal period
and a 3-h glucose clamp. RESULTS: Cortisol withdrawal generated cortisol levels close to zero, a 10% decrease in
basal energy expenditure, increased TSH and T(3) 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 6-h study period. CONCLUSIONS: Cortisol
withdrawal increased insulin sensitivity in terms of increased glucose oxidation and decreased endogenous glucose
production; this may induce hypoglycemia 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. PMID: 17609300
Desantis AS, Diezroux AV, Hajat A, Golden SH, Jenny NS, Sanchez BN, Shea S, Seeman TE.
Associations of Salivary Cortisol Levels with Metabolic Syndrome and Its Components: the Multi-Ethnic
Study of Atherosclerosis. J Clin Endocrinol Metab. 2011 Aug 31. [Epub ahead of print]
Context:Prior research has identified associations between social-environmental factors and metabolic syndrome
(MetS) components. The physiological mechanisms underlying these associations are not fully understood, but
alterations in activity of the hypothalamic-pituitary-adrenal axis, a stress-responsive biological system, have been
hypothesized to play a role.Objective:The aim of the study was to determine whether MetS diagnosis and specific
clusters of MetS components (waist circumference, high-density lipoproteins, glucose, and blood pressure) are
associated with cortisol levels.Design and Setting:We conducted cross-sectional analyses of data from the MultiEthnic Study of Atherosclerosis (MESA) study in the general community.Patients or Other Participants:We studied a
population-based sample of 726 adults (ages 48 to 89 yr) who do not have clinical diabetes.Intervention(s):There
were no interventions.Main Outcome Measure(s):Cortisol awakening response, cortisol decline across the waking
day, and total cortisol output were analyzed (using 18 timed measures of salivary cortisol over 3 d).Results:Overall,
we found little evidence that the presence of MetS or its components is related to cortisol output or patterns.
Contrary to expectation, the presence of MetS was associated with lower rather than higher area under the curve,
and no consistent pattern was observed when MetS components or subsets of components were examined in relation
to cortisol. Conclusions:Our findings do not support the hypothesis that differences in level or diurnal pattern of
salivary cortisol output are associated with MetS among persons without clinical diabetes. PMID: 21880797
Shipunova NN, Petinati NA, Drize NI. Effect of hydrocortisone on multipotent human mesenchymal
stromal cells. Bull Exp Biol Med. 2013 May;155(1):159-63.
We studied the effect of natural glucocorticosteroid hydrocortisone on total cell production, cloning efficiency, and
expression of genes important for the function of mesenchymal stromal cells. Addition of hydrocortisone to the
culture medium reduces the total cell yield by 2 times and significantly increased cloning efficiency by 2-3 times;
this effect was more pronounced in multipotent mesenchymal stromal cells obtained from female donors.
Hydrocortisone had no effect on the expression of immunomodulatory factors produced by multipotent mesenchymal
stromal cells. Hydrocortisone inhibits the expression of bone differentiation markers, increases the expression of the
early adipocyte differentiation marker at the beginning of culturing, and dramatically stimulates the expression of
the late adipocyte differentiation marker throughout the culturing period. The findings suggest that hydrocortisone
activates multipotent mesenchymal stromal cells. PMID: 23667895
Tremblay MS, Copeland JL, Van Helder W. Influence of exercise duration on post-exercise steroid
hormone responses in trained males. Eur J Appl Physiol. 2005 Aug;94(5-6):505-13.
The purpose of this study was to systematically evaluate the effect of endurance exercise duration on hormone
concentrations in male subjects while controlling for exercise intensity and training status. Eight endurance-trained
males (19-49 years) completed a resting control session and three treadmill runs of 40, 80, and 120 min at 55% of
VO2max . Blood samples were drawn before the session and then 1, 2, 3 and 4 h after the start of the run. Plasma
was analyzed for luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), cortisol, and free and total
testosterone. LH was significantly greater at rest compared to the running sessions. Both free and total testosterone
generally increased in the first hour of the 80 and 120 min runs and then showed a trend for a steady decline for the
next 3 h of recovery. Dehydroepiandrosterone sulfate increased in a dose-response manner with the greatest
increases observed during the 120-min run, followed by the 80-min run. Cortisol only increased in response to the
120-min run and showed a decline across time in all other sessions. The ratios of anabolic hormones (testosterone
and DHEAS) to cortisol were greater during the resting session and the 40-min run compared to the longer runs.
The results indicate that exercise duration has independent effects on the hormonal response to endurance exercise.
At a low intensity, longer duration runs are necessary to stimulate increased levels of testosterone, DHEAS and
cortisol and beyond 80 min of running there is a shift to a more catabolic hormonal environment. PMID: 15942766