Jeremy Cohan took us on an Adrenal Function journey at SMACC Chicago with his talk Raging Hormones in Critical Care. Cohan explores the natural roll of cortisol in the human body, various schools of thought and recent research in the areas of sepsis and cortisol resistance.

1. Jeremy Cohen
Royal Brisbane & Women’s Hospital
Queensland, Australia
Raging Hormones
in the Critically Ill

2. “An Expert is someone who has made all the mistakes that can be made, in a
narrow field.”
–Niels Bohr

4. “Buck up, it’s probably just a virus”
–An Expert

6. Severe Stress
Moderate Stress
Mild Stress

7. RAI

8. CIRCI

9. Cortisolnmol/l
0
1000
2000
3000
4000
Rothwell Annane Schein Sibbald Bollaert Sam Bouachour Schroeder Beishuizen Aygen Jarek De Jong Dimopoulou Oppert
Survivors Non Survivors
Cortisol values in Sepsis

10. “There is no greater tragedy in Science than to witness the slaying of a beautiful
hypothesis by an ugly fact”
–Thomas Huxley

11. Glucocorticoid Mechanism of Action

13. GR-ALPHA
GR-BETA
GR-GAMMA,A,P

14. FIG. 2. Quantitation of GR fluorescence in cytoplasm and nucleus of
cells treated with IL-1␣ in the presence or absence of Dex. Cells were
treated as indicated in Fig. 1. Quantitative analysis of fluorescence
was performed in blindly selected regions from the cytoplasm and
nucleus using digital image analysis. Results are based on quanti-
tation of approximately 460 cells from three to five independent ex-
periments and are expressed as the mean Ϯ SEM percentage of the
signal in vehicle-treated cells. *, Significant (P Ͻ 0.05) difference vs.
vehicle; ϩ, significant (P Ͻ 0.05) difference vs. Dex (10 nM), using
Student-Newman-Keuls post-hoc analysis.
FIG. 3. Increased cytosolic GR binding and GR-mediated gene tran-
scription after treatment with IL-1␣ alone. A, L929 cells were treated
with vehicle (Ⅺ) or IL-1␣ (1000 U/ml; f) for 24 h. Cell lysates were
centrifuged, and the supernatant-cytosol was added to incubation
solutions containing radiolabeled (3
H) Dex for the exchange assay.
Values are presented as the mean Ϯ SEM GR binding in vehicle- and
IL-1␣-treated cells from five independent experiments. *, Significant
(P Ͻ 0.05) difference vs. vehicle, using Student’s t test [t(23) ϭ 3.27;
P ϭ 0.003]. B, LMCAT cells were grown in steroid-free medium and
treated with vehicle (Ⅺ) or IL-1␣ (1000 U/ml; f) for 24 h. Cells were
fractionated, and lysates were analyzed for relative CAT enzyme
activity (presented as a percentage of vehicle activity). The results are
4362 IL-1␣ INHIBITS GR TRANSLOCATION AND FUNCTION Endo • 1999
Vol 140 • No 9
FIG. 4. Inhibition of Dex-induced GR-mediated gene transcription
after pretreatment with IL-1␣. LMCAT cells were grown in steroid-
free medium and treated with vehicle plus Dex (10 nM to 1 ␮M) for 1.5 h
(Ⅺ), or IL-1␣ (1000 U/ml) for 24 h followed by coincubation of IL-1␣
(1000 U/ml) and Dex (10 nM to 1 ␮M) for 1.5 h (f). Cell lysates were
analyzed for relative CAT enzyme activity (presented as a percentage
of vehicle activity). The results are shown as the mean Ϯ SEM from five
independent experiments. There was a significant [F(2,1) ϭ 32.1; P Ͻ
0.0001] main effect of IL-1␣ plus Dex treatment vs. Dex alone using
two-way ANOVA. *, Significant (P Ͻ 0.05) difference using Student’s
t test [t(3) ϭ 5.3; P ϭ 0.013].
FIG. 5. Inhibition of GR-m
incubation of Dex and IL
LMCAT cells were grown
vehicle (Ⅺ), Dex (10 nM) for
U/ml) for 24 h ( ), or Dex
24 h ( ); in panel B only).
analyzed for relative CAT
IL-1␣ INHIBITS GR TRANSLOCATION AND FUNCT
Inhibition of GR translocation and function by IL-1
Pariante et al 1999

15. Webster et al, PNAS 2000

16. 11-bHSD-1Activity
0
7.5
15
22.5
30
Liver Adipose
Sepsis Control
11-Beta HSD-1 Activity in Rats with Experimentally Induced Sepsis
p < 0.03
p < 0.02

17. Boonen et al, NEJM 2013

18. “I think you’ll find its a bit more complicated than that”
–An Expert

19. LPS
LPS
Dexamethasone
Cytokine Release
Cytokine Release

20. Cardinal et al , JCEM 2010

21. Cohen et al ,
unpublished
data

22. TNFa
0.0
0.2
0.4
0.6
0.8
1.0
Ra&o((Dex./Max.s&mulated)
Pa&ents Controls
IL#6
0.0
0.2
0.4
0.6
0.8
1.0
Ra'o)(Dex./Max.s'mulated)
Pa'ents Controls
Cohen et al , unpublished data

23. Relative mRNA expression in patients and controls
Cohen et al , unpublished data

25. Queensland
Princess Alexandra
Royal Brisbane & Womens
Ipswich
Logan
Mater Health-Public
Mater Private Hospital
Nambour
Redcliffe
Toowoomba
Wesley
NSW
Blacktown
Calvary Mater – Newcastle
John Hunter
Liverpool
Nepean
Prince of Wales
Royal North shore
Royal Prince Alfred
St George
St Vincent’s Sydney
Tamworth
Woollongong
Victoria
Austin
Bendigo
Dandenong
Geelong
Monash
Northern
Royal Melbourne
St Vincent’s Melbourne
Western
South Australia
Lyell McEwin
Queen Elizabeth
Western Australia
Fremantle
Royal Perth
Northern Territory
Darwin
New Zealand
Auckland DCCM
Auckland CVICU
Christchurch
Middlemore
North Shore
Tauranga
Wellington
Waikato
ADRENAL
42 SITES IN AUSTRALIA &
NEW ZEALAND

26. Republic of Ireland
Cork University Hospital
United Kingdom
St Georges NHS + 7 sites
Denmark
Righospitalet
India
Christian Medical College
Manipal Hospital
Columbia Asia
Saudia Arabia
King Abdul Aziz Medical City
King Fahad Medical City
King Faisal Medical City
ADRENAL
ETHICS APPROVAL INTERNATIONALLY

27. “The time you perform a Google Image search for “Raging Hormones”on your
work computer will be the same time your Director enters unannounced”
–An Expert