Full text of DOI:10.1111/j.1553-2712.2001.tb00537.x

ACADEMIC EMERGENCY MEDICINE • January 2001, Volume 8, Number 1
1
BASIC INVESTIGATIONS
Adrenocortical Dysfunction Following Etomidate
Induction in Emergency Department Patients
C
HRISTINA L. SCHENARTS, MD, JOHN H. BURTON, MD,
RICHARD R. RIKER, MD
Abstract. Objective: To assess adrenocortical func- results were significantly different between study
tion following intravenous etomidate use in emer- groups, with a normal response in 100% of control
gency department (ED) patients requiring intubation. patients vs 30% of etomidate patients (p = 0.004). The
Methods: This was a prospective, randomized, con- 12- and 24-hour CSTs did not differ significantly be-
trolled trial of consecutive patients presenting to the tween groups: normal CST in 100% of control pa-
ED requiring intubation. Patients were randomized tients at 12 and 24 hours vs 100% and 90% among
to receive a single bolus induction dose of either 0.05– etomidate patients at 12 and 24 hours, respectively
0.1 mg/kg midazolam (control group) or 0.3 mg/kg (p = 1.0 at 12 and 24 hours). Measured cortisol levels
etomidate (etomidate group) during a standardized of patients with abnormal CSTs remained within nor-
rapid-sequence intubation (RSI) with succinylcholine. mal laboratory reference ranges. Conclusion: Use of
The primary outcome variable was adrenocortical etomidate in ED patients requiring RSI results in ad-
function at 4, 12, and 24 hours post-induction as as- renocortical dysfunction. However, cortisol levels re-
sessed by measured serum cortisol response to exog- main within normal laboratory levels during this pe-
enous cosyntropin (cosyntropin stimulation test, riod of dysfunction. Adrenocortical dysfunction
CST). Fisher’s exact test was used to compare CST appears to resolve within 12 hours of a single bolus
results between groups. Results: Thirty-one patients dose of 0.3 mg/kg etomidate. Key words: etomidate;
were enrolled: 8 control, 10 etomidate, and 13 ex- induction; midazolam; rapid-sequence induction; in-
cluded from analysis for either incomplete data or tubation. ACADEMIC EMERGENCY MEDICINE
steroid use during the study period. The 4-hour CST 2001; 8:1–7
NDOTRACHEAL intubation is a common ered to be an appropriate induction agent in the
procedure performed during the stabilization setting of elevated intracranial pressure, hemody-
E
namic instability, and myocardial ischemia.1–7
These features distinguish etomidate as an excel-
lent choice for ED RSI patients. As a consequence,
etomidate is increasingly utilized for ED RSI with
one recent survey documenting its use as the pre-
ferred induction agent in 23% of academic EDs.8
A frequently cited disadvantage to the use of
etomidate during RSI is adrenocortical dysfunc-
tion.2,7 Adrenal dysfunction has been shown to oc-
cur in patients receiving etomidate for sedation
with long-term intravenous (IV) infusions9–12 as
well as with single induction doses.13–16 The use of
continuous etomidate infusion has further been as-
sociated with increased mortality in critically ill
patients.10,11 As a consequence of these findings,
etomidate is no longer used for continuous sedative
infusion.
of emergency department (ED) patients. The ma-
jority of these ED patients will require an induc-
tion agent during rapid-sequence intubation (RSI).
The choice of an appropriate induction agent is a
critical decision in this environment. Numerous
drugs are available: each with characteristics mak-
ing it more or less desirable in specific clinical sce-
narios.
Etomidate, a nonbarbiturate, imidazole hyp-
notic, is notable in the setting of ED induction for
its rapid onset of action, short duration, and min-
imal respiratory depression.1,2 Etomidate is consid-
From the Department of Emergency Medicine (CLS, JHB) and
Department of Pulmonary and Critical Care Medicine (RRR),
Maine Medical Center, Portland, ME.
Received March 22, 2000; revision received August 7, 2000;
accepted August 25, 2000. Presented at the SAEM annual
meeting, Boston, MA, May 1999.
Single bolus dosing of etomidate and its effects
on adrenocortical function have been evaluated in
surgical patients undergoing elective operative
procedures.13–18 The results of these studies have
been conflicting with a strong trend toward the
Address for correspondence and reprints: Christina L. Schen-
arts, MD, Department of Emergency Medicine, Vanderbilt Uni-
versity Medical Center, 703 Oxford House, 1313 21st Avenue,
Nashville, TN 37232-4700. Fax: 615-441-9619.

2
ETOMIDATE
Schenarts et al. • ETOMIDATE AND ADRENAL DYSFUNCTION
conclusion that etomidate causes adrenocortical prior to ED RSI. Patients and families who could
dysfunction after a single induction dose.14,15,17,18 not be consented prior to ED RSI were consented
However, there is currently no literature docu- immediately following intubation and prior to ob-
menting the clinical significance of adrenal dys- taining baseline cortisol measurements. In the lat-
function in this patient population.
ter circumstance, patients were randomized to in-
The authors are unaware of any previous study duction agent prior to RSI and consent. This
that has addressed the question of adrenocortical practice was deemed appropriate by the study au-
dysfunction in ED patients receiving single etom- thors and the IRB, given the accepted use of IV
idate doses during RSI. This drug’s increasing ED etomidate and midazolam in the study setting.
utilization demands a consideration of this issue.
Patients were assigned to an induction agent
The potential morbidity or mortality associated via a computer-generated randomization table and
with the use of single induction doses could become enrollment log maintained in the ED. Patients re-
significant as increasing numbers of emergency ceived either a single, nonblinded dose of IV etom-
physicians (EPs) use this agent.
idate (0.3 mg/kg) or IV midazolam (0.05–0.1 mg/
The study hypothesis was that adrenocortical kg). Neuromuscular blockade was accomplished
dysfunction would be observed following the use of with succinylcholine (1–1.5 mg/kg) in all patients.
a single bolus dose of etomidate in ED RSI pa- Use of a ‘‘priming dose’’ of a nondefasciculating
tients. The null hypothesis was that adrenocortical agent or use of IV lidocaine during RSI took place
function, as assessed by response to exogenous co- at the discretion of the attending EP. Initial base-
syntropin (synthetic ACTH) administration, would line data included patient sex, age, indication for
be unaffected by the use of a single bolus dose of ED RSI, vital signs, and oxygen saturation
etomidate when compared with a group of control through pulse oximetry.
patients receiving midazolam as an induction
Following consent of patient or family, a base-
agent. The cosyntropin stimulation test (CST), in line cortisol level was obtained. Medical providers
preference to random cortisol levels, served as the were encouraged to obtain the baseline cortisol
means of assessment of adrenocortical function.
level prior to administration of induction agent.
However, need for rapid airway intervention or de-
lay in obtaining consent dictated a delay in re-
trieval of the baseline cortisol until after RSI in a
majority of patients. All CST evaluation took place
in the medical center’s intensive care unit (ICU).
Medical staff in the ICU received instructions re-
garding the study protocol for CST evaluation at
the trial’s inception.
Collected patient data included length of ICU
and hospital admission, duration of intubation,
mortality, and need for exogenous steroid therapy
during hospitalization.
Adrenocortical function, assessed by CST, pro-
vided the primary outcome measure in the study.
Each CST, performed at 4, 12, and 24 hours post-
receipt of the study induction agent, consisted of a
pre-cosyntropin cortisol level followed by adminis-
tration of 250 ␮g exogenous IV cosyntropin. A cor-
tisol level obtained 1 hour following cosyntropin
administration completed the CST assessment
(Fig. 1).
METHODS
Study Design. The study used a prospective,
randomized, placebo-controlled design for consec-
utive patients requiring ED RSI. Physicians and
medical providers administering the randomized
induction agent were not blinded to the study drug
identity. The medical center institutional review
board (IRB) approved the study protocol.
Study Setting and Population. Study enroll-
ment took place during a five-month period of
1998. This institution is a university-affiliated, ter-
tiary care center with approximately 62,000 an-
nual ED visits.
Rapid-sequence induction and intubation of all
patients took place in the ED. All adult patients
requiring emergent or urgent intubation within
the ED were considered for study enrollment. Ex-
clusion criteria included age less than 18 years,
steroid use within four weeks prior to ED presen-
tation, steroid use during the first 24 hours of hos-
pital admission, and any medical history sugges-
tive of adrenocortical dysfunction.
Data Analysis. A normal CST assumed either a
pre-cosyntropin cortisol level of more than 18 ␮g/
100 mL or a rise of the 1-hour post-cosyntropin cor-
tisol level of more than 7 ␮g/100 mL (when com-
Study Protocol. After the attending EP con- pared with the precosyntropin level).19 Comparison
firmed the need for ED RSI, patients were consid- of CST results between study groups used two-
ered for study inclusion. When clinical circum- tailed Fisher’s exact test. This test was deemed ap-
stances permitted, the patient or patient’s family propriate given the clinical relevance of cortisol
were introduced to the study protocol with objec- levels within the CST. Although serum cortisol
tives, risks of participation, and consent discussed levels suggest a quantitative evaluation, the CST

ACADEMIC EMERGENCY MEDICINE • January 2001, Volume 8, Number 1
3
Figure 1. Study clinical pathway. ED = emergency department; RSI = rapid-sequence intubation.
clinical interpretation is qualitative in clinical power calculations, and statistical analysis in-
practice. The investigators undertook this deter- cluded Microsoft Excel 97 (Microsoft Corporation,
mination a priori in the study design.
Redmond, WA), PASS 6.0 (NCSS, Kaysville, UT),
Review of prior studies investigating elective and NCSS 97 (NCSS), respectively.
surgical patients receiving etomidate suggests self-
Sample Size Determination. Previous studies
limited adrenocortical dysfunction with resolution
within 24 hours.13–16 For this reason, three CST
assessments were performed during the first 24-
hour period of hospitalization. The initial CST was
undertaken at 4 hours as an attempt to permit
adequate time for patient stabilization and trans-
fer to the ICU.
Comparison of baseline cortisol means between
groups and continuous demographic and outcome
data were analyzed by Student’s t-test with a two-
sample test assuming unequal variances or Mann-
Whitney U test as appropriate. Between-group
gender comparison used Fisher’s exact test.
have differed in evaluating the incidence of adren-
ocortical dysfunction following single-dose etomi-
date induction.14,15 Evaluation of previous data
suggested an abnormal CST response up to 8 hours
post-induction to be more than 75%. These obser-
vations are dependent on the time to CST follow-
ing induction and the definition of abnormal CST
used by previous authors.14,15 Based on these cal-
culations, we estimated a need for eight patients
enrolled in each of the two treatment groups to de-
tect a 75% difference in 4-hour CST. An alpha level
of 0.05 was used with a beta of 0.20 to yield a
Ninety-five percent confidence intervals (95% CIs) power of 80% given this sample size.
about the differences between the means are re-
Outcome data and protocol compliance review,
ported for selected outcome and demographic data. at the completion of enrollment of 20 patients, re-
Two-tailed test analyses were used for ordinal and vealed incomplete CST data as well as use of ex-
continuous data.
ogenous steroids in selected patients. As a conse-
Software packages used for data collection, quence, randomized study enrollment was

4
ETOMIDATE
Schenarts et al. • ETOMIDATE AND ADRENAL DYSFUNCTION
No difference was detected in length of stay, pe-
riod of intubation, or length of ICU admission be-
tween the study groups (Table 1). One patient in
the midazolam group died on hospital day 7 after
withdrawal of support. No patient in the treatment
group died during the hospital course. One patient
in the etomidate-treated group required prolonged
intubation and ICU management. This was a
head-injured patient who underwent tracheotomy
on hospital day 19 and subsequent ICU discharge
on day 23 of hospitalization.
4-hour CST. Patients without 4-hour CST re-
sults were excluded from analysis. Complete 4-
hour CST data existed for ten etomidate patients.
Complete 4-hour CST data were obtained for seven
midazolam patients. An eighth midazolam patient
had a post-ACTH level of 35.8 ␮g/100 mL and was
included in data analysis given the study criteria
used for normal CST.
Figure 2. Percent normal cosyntropin stimulation test.
Midaz = midazolam; Etom = etomidate.
continued to the endpoint of a minimum of eight
patients per study group with satisfactory data col-
lection and protocol compliance.
A significant difference in observed normal
CSTs between groups was observed at 4 hours:
100% and 30% for the control and study groups
(difference between group means = 70%, 95% CI =
35% to 105%), respectively (Fig. 2). Pre- and post-
ACTH cortisol levels of all etomidate patients were
within or above the normal cortisol laboratory ref-
erence range, 10–25 ␮g/100 mL (Fig. 3).
R
ESULTS
Thirty-one patients were enrolled during the study
period: 16 randomized to receive etomidate (treat-
ment group) and 15 to receive midazolam (control
group). Thirteen patients were excluded from anal-
ysis: nine for incomplete data, four for steroid uti-
lization. Of the four patients excluded for steroids,
one had been found after enrollment to be taking
chronic steroids and three had an admission di- 12-hour CST. Complete 12-hour CST data ex-
agnosis warranting steroid utilization during the isted for seven etomidate patients. An eighth pa-
first 24 hours of their hospital courses.
tient had a pre-ACTH level of 33.8 ␮g/100 mL. No
No statistically significant difference existed in post-ACTH level was obtained for this patient due
age or gender of patients between the two groups to nursing error. However, given the pre-ACTH
(Table 1). Emergency department cortisol levels of level in excess of 18 ␮g/100 mL, this patient was
the control and treatment group were 38.4 ␮g/100 included in data analysis as a normal CST re-
mL (Ϯ7.3, range: 30.1–49.1) and 28.8 ␮g/100 mL sponse. Two other etomidate patients included in
(Ϯ8.6, range: 11.5–39.7), respectively (p = 0.03). the 4-hour CST analysis had no 12-hour CST data.
Blood was drawn for ED cortisol levels after in- One of these patients had an abnormal 4-hour CST
duction drug administration in 71% of the control and a normal 24-hour CST. The second patient had
group (median time to draw after midazolam = 20 abnormal 4-hour and 24-hour CSTs. This patient
min, range 0–50) and 78% of the study group pa- weighed approximately 185 kg and consequently
tients (median time to draw after etomidate = 17 received a 55-mg etomidate induction bolus.
min, range 0–44).
Complete 12-hour CST data were obtained for
TABLE 1. Demographic, Baseline, and Hospital Course Comparison between Study Groups
Sex
Intital
Cortisol
Age
(years)
Male
(%)
Female
No. Hours
Intubated
No. Hours
in ICU
No. Total
Hospital Days
(%)
(␮g/100 mL)
Etomidate (n = 10)
Midazolam (n = 8)
58.4
71.0
60.0
37.5
40.0
62.5
28.8
38.4
68.6
28.4
96.8
42.2
12.0
10.0
Between-group
difference
(95% CI)
12.6 (Ϫ13, 38)
Ϫ22.5 (Ϫ75, 30)
Ϫ9.7 (Ϫ18, Ϫ1) 40.2 (Ϫ62, 143) 54.6 (Ϫ68, 177)
0.03 0.35 0.21
2.0 (Ϫ7, 11)
p
0.31
0.64
0.82

ACADEMIC EMERGENCY MEDICINE • January 2001, Volume 8, Number 1
5
gland, in contrast to suppression of intrinsic
ACTH.
Adrenocortical dysfunction associated with
etomidate use has been found to occur in the set-
9–12
ting of continuous IV infusion.
This adrenal
axis dysfunction adversely affects patient outcome
in the setting of long-term sedative infusions.10,11
Dysfunction has also been found following a single
bolus induction dose.13–16 No literature has docu-
mented a relevant clinical significance with the
blunted adrenal response observed following a sin-
gle etomidate dose in patients undergoing elective
surgical procedures.13–16
This investigation has demonstrated adreno-
cortical dysfunction following single-dose etomi-
date induction in ED RSI patients. Cosyntropin
stimulation testing was used at 4, 12, and 24 hours
to evaluate adrenal axis function. Cosyntropin
stimulation testing has been used in this setting
by other investigators.14,15,18 In contrast to previous
Figure 3. 4-hour cosyntropin stimulation test.
seven control group patients. An eighth midazolam
patient had a post-ACTH level of 50.3 ␮g/100 mL.
This patient was included in data analysis.
The percentages of normal CST results were
equivalent between the etomidate and midazolam
patients at 12 hours: 100% normal tests for each
group (Fig. 2 and Fig. 4).
24-hour CST. Complete 24-hour CST data ex-
isted for nine etomidate patients. A tenth patient
had a pre-ACTH level of 30.6 ␮g/100 mL. This pa-
tient was included in data analysis, although no
post-ACTH level was obtained. One etomidate pa-
tient had an abnormal CST at 24 hours post-etom-
idate induction as discussed above.
Complete 24-hour CST data were obtained for
six midazolam patients. No data existed at 24
hours post-induction for the remaining two mida-
zolam patients included in the initial 4-hour CST
data analysis.
The percentages of normal CST results were
similar between groups at 24 hours: 100% and 90%
for the control and study groups, respectively (dif-
ference between group means = 10%, 95% CI =
12% to 32%) (Fig. 2 and Fig. 5).
Figure 4. 12-hour cosyntropin stimulation test.
DISCUSSION
Previous investigation has elucidated the mecha-
nism of etomidate-induced adrenocortical dysfunc-
tion. Etomidate has been demonstrated to inhibit
11-beta-hydroxylase, an enzyme that facilitates the
conversion of 11-deoxycortisol to cortisol.20,21 De-
spite high levels of circulating ACTH and 11-deoxy-
cortisol (a precursor to deoxycortisol), cortisol mea-
surements appear to remain depressed relative to
controls. These observations indicate a direct
mechanism for adrenocortical dysfunction with
cortisol suppression at the site of the adrenal
Figure 5. 24-hour cosyntropin stimulation test.

6
ETOMIDATE
Schenarts et al. • ETOMIDATE AND ADRENAL DYSFUNCTION
authors, we used a previously described and ac- ence range, remains a topic of debate in the use of
cepted definition of CST response to evaluate CST etomidate. To the best of our knowledge, no patient
results.19 One advantage to CST assessment is the has been reported to have required exogenous ster-
evaluation of cortisol production at the level of the oid administration, nor have there been reports de-
adrenal gland. Other medications, particularly scribing adverse outcomes attributed to these find-
opioids, are known to suppress adrenal function ings in ED RSI patients.
through reduced levels of circulating ACTH.22
Findings of adrenocortical dysfunction associ-
Stimulation testing evaluation thus removes the ated with one-time ED induction doses of etomi-
complication of suspected opioid-induced suppres- date emphasize the need for an assessment of the
sion.
clinical importance of this effect. The need for re-
Previous investigators have described dimin- moval of this agent from this setting, in preference
ished random cortisol levels indicative of adreno- to other available induction agents, or a routine
cortical dysfunction following etomidate induc- utilization of exogenous steroids might also prove
tion.13,16,17 In these and other studies,14,15 the advisable should clinical significance be demon-
observed depressed cortisol levels remain within strated. However, if no meaningful deleterious out-
normal laboratory reference ranges, confusing the come is found to be associated with the use of
interpretation of these findings. The present group etomidate, the merits of the unique etomidate pro-
of etomidate ED RSI patients had similar de- file in this and similar settings might further be
pressed cortisol levels at 4 hours post-induction. exploited.
Cortisol levels were uniformly within normal lab-
oratory reference range, despite the demonstrated
adrenocortical dysfunction evident by abnormal
CSTs at 4 hours post-induction. At 12 and 24 hours
post-induction, no further evidence of adrenocor-
tical dysfunction was seen as assessed by CSTs.
In the current study, 30% of the etomidate-
treated group maintained a normal response to ex-
ogenous ACTH at 4 hours post-induction. Although
these patients had lower cortisol levels than their
control counterparts, cortisol levels in excess of 20
␮g/100 mL were found in these patients. Addition-
ally, all patients with 4-hour abnormal CST re-
sponses corrected to normal 12-hour CST re-
sponses, with the exception of one patient. For this
patient, the 12-hour CST was not available due to
collection error. The abnormal 24-hour CST for this
patient suggests that the 12-hour CST was prob-
ably abnormal. This patient was unique in that the
induction etomidate dose received was approxi-
mately twice the normal dose. This dosing occurred
as a consequence of the patient’s excessive weight.
Etomidate continues to gain favor with EPs as
a first-line agent during emergent RSI. Etomidate
has been cited as the drug of choice for emergent
RSI in patients who have or are at risk for hemo-
dynamic instability.6,7 Additionally, one recent re-
port has noted etomidate’s value as a sedative
agent in brief, painful ED procedures.23 These re-
ports serve as indications that etomidate will con-
tinue to have an expanding role in the ED setting.
Given the available data regarding the adre-
nocortical effects following a single bolus dose of
0.3 mg/kg etomidate, we suspect that the period of
adrenal axis dysfunction resolves within 4–8
hours in the majority of patients. The clinical im-
portance of this brief period of adrenal dysfunction
L
IMITATIONS AND FUTURE QUESTIONS
This study was not designed for interpretation of
clinical significance of adrenocortical dysfunction.
Although no clinical significance of a brief period
of adrenocortical dysfunction has previously been
demonstrated, the true implications of this effect
can only be hypothesized. Future investigation
should evaluate well-defined, objective, clinical
outcomes in patients receiving etomidate for ED
RSI. This project would require a prolonged en-
rollment at a large center or potentially through a
multicenter design. Close collaboration with inves-
tigators within the ICU setting would facilitate
such an investigation.
This study enrolled a consecutive series of pa-
tients requiring ED intubation, which represents
the reality of ED practice with a wide variety of
indications for airway intervention. The absence of
a well-defined, more homogeneous population of
patients would have removed the complications in-
herent in evaluating data within a diverse, heter-
ogeneous population of adult patients. The possi-
bility exists that the two patient groups may not
have been comparable in this important regard.
Further, the small population size may lend cer-
tain elements of comparison between the two
groups to have no statistical significance while
clinically relevant differences may exist.
The dosage of midazolam equivalent to 0.3 mg/
kg of etomidate is generally understood to be 0.1
mg/kg. However, EPs use midazolam for induction
at a dose of 0.05–0.1 mg/kg to achieve successful
intubation conditions while avoiding risks of hy-
potension. Theoretically, a subtherapeutic dosage
of midazolam may have resulted in a more difficult
and subsequent depressed cortisol levels, though intubation or excessive agitation resulting in ad-
the levels remain in the normal laboratory refer- renal stimulation and confounding the results of

ACADEMIC EMERGENCY MEDICINE • January 2001, Volume 8, Number 1
7
3. Harris CE, Murray AM, Anderson JL, Grounds RM, Morgan
M. Effects of thiopentone, etomidate, and propofol on the he-
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Br J Anaesth. 1979; 51:347–51.
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Pre-induction cortisol levels were unable to be
obtained for all study patients. This proved diffi- 5. Modica PA, Tempelhoff R. Intracranial pressure during in-
duction of anaesthesia and tracheal intubation with etomidate-
cult given the clinical setting. However, this mod-
ification would be an improvement in the current
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41.
study design. The observed difference in the base- 6. Woodard LL, Wolfson AB, Iorg EC, Peitzman AB. Hemody-
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difference between groups achieved statistical sig-
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A significant percentage of patients were ex-
cluded from analysis secondary to protocol non-
8. Smith DC, Smithline HA. Intubation practices in US EDs.
Ann Emerg Med. 1997; 30:401.
9. Allolio B, Stuttmann R, Fischer H, Leonhard W, Winkel-
mann W. Long-term etomidate and adrenocortical suppression.
Lancet. 1983; 1:626.
compliance. This occurrence may have engendered 10. Ledingham IM, Watt I. Influence of sedation on mortality
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1:1270.
11. Ledingham IM, Finlay WE, Watt I, McKee JI. Etomidate
was problematic in both treatment groups. Al- and adrenocortical function [letter]. Lancet. 1983; 1:1434.
12. Fellows IW, Bastow MD, Byrne AJ, Allison SP. Adreno-
though unfortunate, the severity of illness neces-
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Assessing response to exogenous ACTH at ear-
14. Zurick AM, Sigurdsson H, Koehler LS, et al. Magnitude
lier and more frequent intervals may elucidate a and time course of perioperative adrenocortical suppression
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more precise timing of the onset and duration of
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CONCLUSIONS
Use of etomidate as a single bolus dose in ED pa-
tients requiring RSI results in adrenocortical dys-
function. This dysfunction appears to resolve
within 12 hours of the administration of a 0.3-mg/
kg etomidate bolus. During this period of adreno-
cortical dysfunction, cortisol levels remain within
normal laboratory reference ranges.
19. Speckart PF, Nickloff JT, Bethune JE. Screening for ad-
renocortical insufficiency with cosyntropin. Arch Intern Med.
1971; 128:761–3.
20. Fraser R, Watt I, Gray CE, Ledingham IM, Lever AF. The
effect of etomidate on adrenocortical function in dogs before
and during hemorrhagic shock. Endocrinology. 1984; 115:
2266–70.
21. Boidin MP. Modification of corticosteroid synthesis be
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