Investigations for cushing's syndrome- A systematic approach
Investigations for cushings syndrome
Dr. Sanoop Kumar Sherin Sabu
In the background of clinical feature of cushings, after ruling out exogenous intake of
steroids, we have the following important
investigations to be done systematically to reach to the correct cause for
features of cushings.
· Midnight corrtisol
· 8 am corrtisol
· 1mg Dexa suppression test
· Low dose dexa suppression test
· High dose dexa suppression test
· CRH responsiveness
· Inferior petrosal sinsus sampling
· Chest xray
· MRI brain
· Plain/ CECT abdomen
To understand the above investigations we should know:-
·
Why is the test done for
·
What is the physio-anatomical basis
Causes of cushings
syndrome – Exogenous steroid
intake>> ACTH dependant> ACTH independent
|
ACTH dependant
|
ACTH independant
|
Others
|
|
|
Cushings disease
|
Ectopic ACTH
|
·
Adrenal mass- adenoma. Carcinoma
·
Adrenal hyperplasia
·
Carrenys triad
·
Mc-Cune Albright syndrome
|
-
Exogenous
steroid intake
-
Pseudo
cushings
ü Alcoholism
ü Depression
ü Cyclic
cushings
|
|
It is due to a pituitary mass
MC cause of ACTH dependant
|
·
Bronchgogenic carcinoma ( Samll cell)
·
Pancreatic carcinoid
·
Brochial carcinoid
·
Medullary carcinoma thyroid
·
Pheochromocytoma
|
||
·
All the above except ectopic cushings are female
predominant
·
Ectopic cushings show equal sex predominance
From the list of
causes of cushings the investigations are almost clear.
Basic physiology
Hypothalamus-------CRH-----Pituitary------ACTH---- Zona
fasiculata of adrenal cortex ---- Corrtisol
Value points to remember to understand the investigations
·
All pituitary tumors respond to CRH.
·
In normal individuals when exogenous steroids
are given the endogenous cortisol production from the adrenals must decrease
due to suppression of hypo-thalamo pituitary axis.
·
Excess cortisol due to any cause affecting
the above pathway, the Cortisol remains high inspite of exogenous cortisol
admisnistartion. It is because of inadequate suppression of normal hypo-thalmo-pituitary
axis.
·
Source of ACTH can be Pituitary or any where
else ( ECTOPIC) . Never ever ectopic ACTH can be stimulated or suppressed by
CRH.
·
As per the normal diurnal variation, at
midnight corrtisol is least secreated. And maximum at 8am.
Investigations - All these investigations are attempted after
excluding exogenous intake of steroids.
AIM:-
Step 1- show that corrtisol levels in body
is high
Step 2- Prove that corrtisol levels in body is inappropriately
high
Step 3- differentiate
between ACTH dependant or ACTH independent
Step 4- if ACTH
dependant- differentiate between Pituitary cause / ECTOPIC cause
Step 5- Anatomically
locate the lesion
Step 1- show
that corrtisol levels in body is high – screening
·
24 hour urinary excretion of corrtisol levels 3
times greater than normal ( 3.5 to 45mcg per 24 hours)
·
11pm spot Midnight plasma corrtisol > 50 nmol/l (1.8MCG/dl )
·
11pm Midnight salivary cortisol
> 55 nmol /l ( 2mcg/dl)
Step 2- Prove that corrtisol levels in
body is inappropriately high
·
1mg Dexa over night suppression test
Ie. For complete suppression, in normal
individuals , corrtisol levels should go below 1.8mcg/dl or 50nmol/l
·
More specific test is- Low dose dexa suppression test
Step 3- differentiate
between ACTH dependant or ACTH independent
Step 4- if ACTH
dependant- differentiate between Pituitary cause / ECTOPIC cause
2mg dexa suppression test -
·
Use- to differentiate between Pituitary cause for
ACTH dependent and ECTOPIC ACTH
·
Physiological basis- High dose dexamethaose will
be able to suppress the HPA axis.
·
Steps
CRH stimulation
test
·
Use- to differentiate between Pituatary cause
for ACTH dependant and ECTOPIC ACTH
·
Physiological basis- when CRH is given IV it
will stimulate the Pituitary and ACTH levels will increase. The rise in ACTH
will not happen in ECTOPIC ACTH.
Steps
Use of Inferior petrosal
sinsus sampling
In some equivocal cases
of ACTH dependant Cushings with above mentioned 3 tests we will not be able to differentiate
between Pituitary ACTH / ECTOPIC ACTH. In such case we do inferior petrosal
sinus sampling.
What is the role of 8am cortisol in suspected cushings ?
in exogenous cushing's syndrome 8am cortisol will be low , but 11pm cortisol will be high.
What are the causes of highor normal 8am cortisol inspite of exogenous cortisol?
when patient is on hydrocortisone ACTH treatment
What are the causes of low 8am cortisol inspite of endogenous cushigns ?
patient is inactive pahse of cyclic cushings
patient on ketokonazole
pituitary apoplexy
GIP( glucose mediated insulinotropic peptide) mediated ACTH independant Macro nodular adrenal hyperplasia
Value points to note:-
·
All the above investigations are attempted after
excluding exogenous intake of steroids.
·
Never use the normal ranges mentioned in the lab
results of corrtisol
·
In real life situations Donot confuse the units
of the investigations.
·
DEXA is not measureable in the plasma, thus it
donot interfere the corrtisol results
·
Drugs like OCP, rifampicin, anti-epileptics
interferes with Dexa- suppression test due to CYP inhibition.
·
Careful clinical examination and other investigations
are required for other causes like:-
o
Exogenous cushings
o
Pseudo-cushings
·
Mild corrtisol excess is prevalent among type 2
diabetes, central obesity, osteoporotic fractures.
·
Mild corrtisol excess is prevalent
among type 2 diabetes, central obesity, osteoporotic fractures.
·
When psedocushigns is suspected
do LDDST instead of ONDST.
·
Other methods to rule out
pseudo, is do 2 testsà LDSST followed by Midnight S. Cortisol ( more than 1.8mcg/dl) . if
both high, less likely pseudo
·
Other way is loperamide
challenge test, insulin induced hypoglycemia test
.....................................................................9847811159, sanoopkumarsherinsabu2007@gmail.com
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