Gland composed from outer to inner:
Zona Glomerulosa producing aldosterone in response to Angio II, ACTH, and serum Na/K levels
Zona Fasiculata producing glucocorticoids in response to corticotropin-releasing hormone (CRH)
Zona Reticularis producing androgens in response to ACTH
GFR=salt, sugar, sex
Inner medulla produces catecholamines
circulating cortisol is usually increased in the morning hours.
The stress response is characterized by continuous ACTH release despite levels of cortisol and increases cortisol production regardless of time of day
Primary adrenal insufficiency can be caused by autoimmune disease, infections such as TB or histoplasma, AIDS, neoplasms, medications such as ketoconazole, etomidate, dilantin, and rifampin, adrenal hemorrhage,
Secondary from pituitary disorders or exogenous steroids
Weakness, fatigue, n/v, weight loss, anorexia, nausea, diarrhea, vomiting, abdominal pain. If primary, hyperpigmentation may be seen, especially in skin creases.
Labs show hyponatremia, acidosis, prerenal azotemia, hyperkalemia, hypoglycemia,
Waterhouse-Friedrichson Syndrome-after overwhelming septicemia
Dexamethasone will not affect cortisol stimulation test/levels (2 mg=100 mg of hydrocortisone)
IV Fluids and dextrose replacement
Hydrocortisone 100 mg IVP x1 and add 2nd 100 mg to first liter of fluids then 100-200 IVPB Q6-8 hours (Parrillo recommends 100 Q8) Has both gluco- and mineralocorticoid activity.
Random cortisol at any time of day (critically ill patients lose diurnal variation) <25 indicates insufficiency and these patients should receive supplemental steroids
· Give hydrocortisone 100 mg IV Q8 or Dex 4 mg then 2 mg IV Q8 (allows ACTH stim, but has no mineralocorticoid activity) If hydrocortisone is tapered to less than 100 mg/day, can add Fludrocortisone 0.05-0.20 mg/day
(Chest 122:5, 2002)
Other algorithm:
ACTH Stim test
can be performed at any time of day in the critically ill as the diurnal variation is lost
draw a cortisol level and then give Cosyntropin 250 mcg IV. Draw cortisol at 30 and 60 minutes. A normal response is an increase of 9 and a total poststim cortisol of >20
At STC, they use cosyn 1 mcg
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Measurements of Serum Free Cortisol in Critically Ill Patients
Amir H. Hamrahian, M.D., Tawakalitu S. Oseni, M.D., and Baha M. Arafah, M.D.
etomidate may cause relative adrenal insuffic. even after
one dose (Inten Care Med 2005;31:388) and (Chest 2005;127:1031)
Endocrinology
Critical Care
Related Chapters at Harrison's Online
ABSTRACT
Background Because more than 90 percent of circulating cortisol in human serum
is protein-bound, changes in the binding proteins can alter measured serum total
cortisol concentrations without influencing free concentrations of this hormone.
We investigated the effect of decreased amounts of cortisol-binding proteins on
serum total and free cortisol concentrations during critical illness, when
glucocorticoid secretion is maximally stimulated.
Methods Base-line serum total cortisol, cosyntropin-stimulated serum total
cortisol, aldosterone, and free cortisol concentrations were measured in 66
critically ill patients and 33 healthy volunteers in groups that were similar
with regard to sex and age. Of the 66 patients, 36 had hypoproteinemia (albumin
concentration, 2.5 g per deciliter or less), and 30 had near-normal serum
albumin concentrations (above 2.5 g per deciliter).
Results Base-line and cosyntropin-stimulated serum total cortisol concentrations
were lower in the patients with hypoproteinemia than in those with near-normal
serum albumin concentrations (P<0.001). However, the mean (±SD) base-line serum
free cortisol concentrations were similar in the two groups of patients (5.1±4.1
and 5.2±3.5 µg per deciliter [140.7±113.1 and 143.5±96.6 nmol per liter]) and
were several times higher than the values in controls (0.6±0.3 µg per deciliter
[16.6±8.3 nmol per liter], P<0.001 for both comparisons). Cosyntropin-stimulated
serum total cortisol concentrations were subnormal (18.5 µg per deciliter [510.4
nmol per liter] or less) in 14 of the patients, all of whom had hypoproteinemia.
In all 66 patients, including these 14 who had hypoproteinemia, the base-line
and cosyntropin-stimulated serum free cortisol concentrations were high-normal
or elevated. Volume 350:1629-1638 April 15, 2004 Number 16
Conclusions During critical illness, glucocorticoid secretion markedly
increases, but the increase is not discernible when only the serum total
cortisol concentration is measured. In this study, nearly 40 percent of
critically ill patients with hypoproteinemia had subnormal serum total cortisol
concentrations, even though their adrenal function was normal. Measuring serum
free cortisol concentrations in critically ill patients with hypoproteinemia may
help prevent the unnecessary use of glucocorticoid therapy. NEJM Volume
350:1629-1638 April 15, 2004 Number 16
Non-responders to cosynotropin stim benefited from steroids (JAMA Aug 21, 2002 288:7)
50 mg Hydrocortisone Q6 and 50 mcg of fludrocortisone QD
Crit Care Med 2005;33(11):2457
Low-dose hydrocortisone improves shock reversal and reduces cytokine levels
in early hyperdynamic septic shock
Conclusions: Treatment with low-dose hydrocortisone accelerates shock reversal
in early hyperdynamic septic shock. This was accompanied by reduced production
of proinflammatory cytokines, suggesting both hemodynamic and immunomodulatory
effects of steroid treatment. Hemodynamic improvement seemed to be related to
endogenous cortisol levels, whereas immune effects appeared to be independent of
adrenal reserve.
showed mortality benefit if steroids are given to non-responders (<9) regardless of cortisol levels. (JAMA 2002;288(7):862)
N Engl J Med 2008;358:111-24.
Editorial N Engl J Med 2008;358:188
The rate of death in the control group was
lower than expected, and this factor, combined
with early stopping of the study, meant that the
study had a power of less than 35% to detect a
20% reduction in the relative risk of death. With
this caveat, the primary conclusion of the study
was that treatment with corticosteroids had no
effect on the rate of death at 28 days, a finding
that was consistent in the overall population (relative
risk, 1.09; 95% confidence interval [CI], 0.84
to 1.41), in patients who had a response to corticotropin
(relative risk, 1.00; 95% CI, 0.68 to 1.49),
and in those who did not have a response to
corticotropin (relative risk, 1.09; 95% CI, 0.77 to
1.52). The lack of treatment effect was also consistent
regardless of the duration of septic shock
before recruitment. Also notable is that shock
was reversed more rapidly in patients receiving
hydrocortisone but that this factor did not result
in reduced mortality.
Liver failure pts have an exceedingly high incidence of adrenal failure (Crit Care Med 2005;33:1254)
Special Note
[GC = glucocorticoid]
index drug: hydrocortisone 20 mg
[MC = mineralocorticoid]
index drug: fludrocortisone 0.1 mg
betamethasone
[GC 0.6 mg; MC n/a]
cortisone
[GC 25 mg; MC 20 mg]
dexamethasone
[GC 0.75 mg; MC n/a]
fludrocortisone
[GC 1.3 mg; MC 0.1 mg]
hydrocortisone
[GC 20 mg; MC 20 mg]
methylprednisolone
[GC 4 mg; MC n/a]
prednisolone
[GC 5 mg; MC 50 mg]
prednisone
[GC 5 mg; MC 50 mg]
triamcinolone
[GC 4 mg; MC n/a]