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Adrenal Insufficiency (AI) in
the Septic Patient
Fady Youssef, MD PGY-2 2014
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Objectives
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Define adrenal insufficiency
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Understand who gets Relative adrenal insufficiency
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Review the current evidence
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Understand how to manage “Relative adrenal insufficiency” in the
setting of sepsis.
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Case Problem
68 yo male with PMH of HTN, HL and COPD presents to ER with AMS
and cough with productive sputum for 1 day. T 39 degrees C, BP 70/35,
HR 121, RR 21. He has been given 4L of NS and has been started on
norepinephrine, with no improvement in his vitals. Which of the
following next steps is most appropriate?
A: Draw a
B:
random cortisol level
Perform a high dose ACTH stimulation test
C: Administer
hydrocortisone
D: Administer
hydrocortisone with fludrocortisone
E:
None of the above
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Definition
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Acute reversible dysfunction of the HPA axis in the setting of
physiologic stress (e.g. sepsis, intra/post operative state)
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It is estimated that ___ % of critically ill patients suffer from
HPA axis dysfunction
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
30%
Symptoms of AI
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shock, abdominal pain, fever, nausea and vomiting, electrolyte
disturbances and, occasionally, hypoglycemia
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Who gets AI?
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Any patient in the setting of physiologic stress
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Etiology:
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Adrenal ACTH resistance
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Decreased responsiveness of the target tissue to
glucocorticoids (GC)
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Secondary AI: 2/2 chronic steroid therapy (dose dependent)
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Certain meds: Etomidate, Phenytoin, Ketoconazole
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HPA Axis
2ry AI
Where is the dysfunction occurring in secondary AI?
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Diagnosing Relative Adrenal
Insufficiency
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Diurnal variation is LOST during physiological stress
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Lab assays of plasma cortisol concentration and ACTH stimulation test
are unreliable in critically ill patients
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Random serum cortisol: Varies widely in critically ill patients.
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Increased mortality with both very low and very high cortisol levels
There is are no reliable tests for diagnosing relative adrenal
insufficiency.
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So when to start steroid therapy?
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Low MAP or SBP: requiring vasopressors
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All meta-analyses confirmed improved shock reversal with
low-dose corticosteroid use (trials listed below for further
reference)
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Response to vasopressors is irrelevant to whether steroids should be
started or not
Responsiveness is defined as: maintaining MAP > 65 mmHg
without vasopressor use within 1 day of starting hydrocortisone
Don’t delay treatment for ACTH stim test
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Treatment in sepsis
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Hydrocortisone: total of 200 – 300 mg over 24 hrs
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50 – 100 mg q6-8h for 5-7 days with taper
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Patients receiving higher doses of steroids had worse outcomes (citation
below)
Fludrocortisone (a mineralocorticoid) has not been shown to help in
relative adrenal insufficiency.
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Hydrocortisone seems to have sufficient mineralocorticoid activity
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COIITSS trial
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Case Problem
68 yo male with pmxh of HTN, HL and COPD presents to ER with AMS
and cough with productive sputum for 1 day. T 39 degrees C, BP 70/35,
HR 121, RR 21. He has been given 4L of NS and has been started on
norepinephrine, with no improvement in his vitals. Which of the
following next steps is most appropriate?
A: Draw a
B:
random cortisol level
Perform a high dose ACTH stimulation test
C: Administer
hydrocortisone
D: Administer
hydrocortisone with fludrocortisone
E:
None of the above
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Summary
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No diagnostic test is reliable for relative adrenal insufficiency.
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Low threshold to treat relative adrenal insufficiency in patients with
septic shock
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Use low dose hydrocortisone/physiologic dosing for a limited time
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Fludrocortisone has not been shown to help in relative AI
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Interested? Here is more …
HPA axis – Normal response
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Physiological stress activates the HPA axis which in turn increases
serum cortisol levels
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Serum Cortisol levels remain elevated during stress due to several
factors:
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Reduced activity of cortisol metabolizing enzymes
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Renal dysfunction prolonging the half life
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Decrease in cortisol-binding globulin and albumin which brings > 90% of
cortisol
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Inflammatory cytokines: Increase GC receptor affinity and increase the
peripheral conversion of precursors to cortisol