Corticosteroid Insufficiency

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Current conceptCorticosteroid Insufficiency in

Acutely ill Patients

Mark S. Cooper, M.D., and Paul M. Stewart, M.D.

NEJM Volume 348:727-734

February 20, 2003 Number 8

By Ri 93-04-05


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Questions

How to make a diagnosis of adrenal

insufficiency in patient under stress?

Treatment?


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Hypothesis

The normal range of cortisol level (plasma,

morning: 6 ~ 30 g/dl)

But it should be adjust in patient with stress.


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Knowledge

Fight or Fright

The need of corticosteroid increases in patient

with stress


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Whats known or unknown

The s/s of adrenal insufficiency are usuallynonspecific.

Adrenal crisis can cause fetal outcome.

The role of using corticosteroid in pt withinfection is still unclear.

If the diagnosis of adrenal insufficiency is

established, how long should corticosteroid beused?


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The HypothalamicPituitaryAdrenal

Axis in Acute illness

The Hypothalamic-Pituitary-Adrenal Axis

A diurnal pattern cortisol secretion

corticotropin (pituitary gland)

hypothalamic corticotropin-releasinghormone

Negative feedback


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The HypothalamicPituitaryAdrenal Axis in

Acute illness

Stress: severe infection,trauma, burns, illness,

surgerycortisol

Roughlyproportional to the severity.

Diurnal variation: vanished.

Stimulation of the hypothalamicpituitary

adrenal

axis: elevated levels of circulating

cytokines and other factors.


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Acute illness

During severe illness, many factors can impair

the normal corticosteroidresponse.


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Head injury;CNS depressants

Pituitary infarction

Ketoconazole

Adrenal hemorrhage insepticemia orcoagulopathy

High level ofinflammatory cytokinesin sepsis pt directly

inhibit adrenal cortisolsynthesis

Extensivedestruction by

tumor orinfection


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Acute illness

The metabolism of cortisol: Liver, can be

enhanced by drugs such as rifampin or

phenytoin

Excessive inflammatory cytokines during

sepsis: systemic or tissue-specific resistance to

cortisol

The need of corticosteroid increases in

patient with stress


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Acute illness

Develop during an illness

Transient

Functional adrenal insufficiency

-- no obvious structral defects in HPA axis

Relative adrenal insufficiency

-- insufficient to control the inflammatoryresponse


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Diagnosis of Corticosteroid Insufficiency during

Acute illness

Corticosteroid insufficiency associated withacute illness

-- difficult to discern clinically, but there are

some featuresthat suggest the diagnosis.


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Diagnosis of Corticosteroid Insufficiency during

Acute illness

It still remains extremely difficult torecognizeadrenal insufficiency in the ICU.

Important diagnostic clues

Hemodynamic instability

despite adequate fluidresuscitation

Ongoing evidence of inflammation without an

obvious source that does not respond to empirical

treatment.


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Laboratory Investigations

Randomly measured cortisol levels

More usefulwould be the identification of aminimal threshold level and a maximal

thresholdlevel. 15 g/dl (10 g/dl to 34 g/dl) best identifies

persons with clinical featuresof corticosteroid

insufficiency or who would benefit fromcorticosteroid replacement


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Corticotropin stimulation test

IV or IM250 g of Cosyntropin

Check plasma cortisol levels

0, 30, ( 60 ) mins after administration


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Corticotropin stimulation test

Prognostic implications

-- < 9g /dl

increased risk of death.


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The authors opinion

> 34 g /dl:unlike.


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Methylprednisolone2 mg/kg/day


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When to recheck ?

Development of new clinical features

Deterioration in clinical condition


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Treatment of Acute Adrenal

Insufficiency

Critically ill patients with established

hypoadrenalism: IV or IM Hydrocortisone

(solu-cortef) 50 mg q6h.

Patients in shock: 5 percent dextrose in

normal saline shouldbe given IV initially.


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Treatment of

Acute Adrenal Insufficiency(in septic shock)

Evidence-based support the use of supplementalcorticosteroid in septic shock pt, esp. in ICU.

3 randomized,controlled trials of hydro-cortisonereplacement in patientswith septic shock

Improvements in hemodynamics

Reduction in the need for vasopressor therapy.


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Treatment of


In the largestrandomized, placebo-controlled

trial, treatment of300 medicaland surgical

patients with 200 mg of hydrocortisone per

dayand 50 g of fludrocortisone once daily for7 dayssignificantly reduced mortality and the

duration of vasopressortherapy.


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Treatment of


Supplemental corticosteroid treatment in

septic shock pt should be initiated ASAP.


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Treatment of

Acute Adrenal Insufficiency(in other critical illness)

It may be beneficial in patients with other

criticalillnesses such as trauma, burns, and

medical and surgical conditions.

But no evidence now


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Conclusions

Diagnose corticosteroid insufficiencyinpatients with critical illnesses: still difficult.

Recent trials confirmed corticosteroid

replacement in septic shock pt havesubstantial benefits.


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Conclusions

Treatment with physiologic levelsof cortico-

steroid appears to carry few risks.

low threshold to testing of the hypothalamic

pituitaryadrenalaxis and corticosteroid-

replacement therapyin acutely ill patients.


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Prospect

Further studies are needed to clarify

specific situations: in which corticosteroid

replacement is beneficial

optimal dose

optimal duration


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Take Home Message

Supplemental corticosteroid treatment in septic

shock pt should be initiated ASAP.


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Thanks for your attention !!

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Corticosteroid Insufficiency