L ABORATORY APPROACH TOWARDS

HYPOCORTISOLISM
AND INTERPRETATION OF
SHORT SYNACTHEN TEST

D r. Wa r a A r s ha d
R es id e nt – C hem ica l Pat ho lo g y
OBJECTIVES

Brief Introduction​

Hypocortisolism

Short Synacthen Test

Interpretation

2
 CORTISOL
Cortisol is a steroid hormone, widely
known as the body’s stress hormone.

steroid hormones
: any of numerous hormones (such as estrogen, testosterone, and cortisol) that are produced in the body from cholesterol especially in the adrenal glands, testes, 3
and ovaries and that have the chemical ring structure characteristic of steroids
 CORTISOL
It is the main glucocorticoid released
from the zona fasciculata layer of the
adrenal cortex.

glucocorticoid
: any of a group of corticosteroids (such as cortisol) that are involved especially in carbohydrate, protein, and fat metabolism, that are anti-inflammatory and 4
immunosuppressive, and that are used widely in medicine (as to alleviate the symptoms of rheumatoid arthritis)
CORTISOL
The hypothalamus-pituitary-
adrenal axis regulates both
production and secretion of
cortisol.

5
CORTISOL
Cortisol exhibits a proper 24-h
circadian rhythm that affects the
brain, the autonomic nervous
system, the heart, and the
vasculature that prepares the
cardiovascular system for optimal
function during these anticipated
behavioral cycles.
6
CORTISOL
Lower levels of cortisol are seen
at the beginning of sleep, while a
rise towards the end of sleep is
observed, with the highest level
reaching at the moment the
individual wakes up.

7
CORTISOL
Loss of regulation can lead to
cortisol excess disorders, such as
Cushing syndrome, or cortical
insufficiency, such as Addison
disease.

8
WHAT IS
HYPOCORTISOLISM??
HYPOCORTISOLISM/
ADRENAL INSUFFICIENCY
• Adrenal insufficiency is the decreased production of adrenocortical
hormones (glucocorticoids, mineralocorticoids, and adrenal androgens).

• It is classified as primary, secondary, or tertiary.

HYPOCORTISOLISM/
ADRENAL INSUFFICIENCY
• Primary adrenal insufficiency (Addison disease) is caused by a disorder of the
adrenal glands such as autoimmune adrenalitis, which can occur sporadically
or as a manifestation of polyglandular autoimmune syndromes.

• Secondary adrenal insufficiency is the result of decreased production of

ACTH (adrenocorticotropic hormone) by the pituitary gland.

• Tertiary adrenal insufficiency is the result of decreased production of CRH

(corticotropin-releasing hormone) by the hypothalamus.
HYPOCORTISOLISM/
ADRENAL INSUFFICIENCY
• Patients with long-standing adrenal insufficiency can present with
• postural hypotension
• nausea, vomiting
• weight loss, anorexia
• lethargy
• depression
• chronic hyponatremia

• Patients with primary adrenal insufficiency tend to additionally develop

hyperpigmentation of the skin, mild hyperkalemia, and metabolic acidosis.
HYPOCORTISOLISM/
ADRENAL INSUFFICIENCY
• Decreased levels of ACTH or CRH are seen following sudden cessation of
prolonged glucocorticoid therapy and in pituitary/hypothalamic diseases.

• Serum cortisol levels that remain low even after the administration of
exogenous ACTH (ACTH stimulation test) confirm the diagnosis of primary
adrenal insufficiency.
HYPOCORTISOLISM/
ADRENAL INSUFFICIENCY
• Most common electrolyte imbalance  HYPONATREMIA

• Serum Cortisol levels: LOW

• Serum ACTH levels: HIGH

• Short Synacthen Test: INADEQUATE RESPONSE

SHORT SYNACTHEN TEST
SHORT SYNACTHEN TEST
The short Synacthen test is a test of adrenal
insufficiency which can be used as a
screening procedure in the non-critically ill
patient.

The test is based on the measurement of

serum cortisol before and after an injection of
synthetic ACTH.

17
SHORT SYNACTHEN TEST
No dietary preparation is required.

Current or recent steroid therapy may make

result interpretation difficult.

Estrogen containing medications should be

stopped for six weeks prior to measuring
serum cortisol.
This is because estrogen induces cortisol
binding globulin and leads to elevations in
measured serum cortisol.

18
SHORT SYNACTHEN TEST
Glucocorticoid replacement on the day of the
test invalidates the test.

Prednisolone should be stopped 24 hours

before the Short Synacthen test.

Hydrocortisone should be omitted on the

morning of the Short Synacthen test.

19
SHORT SYNACTHEN TEST
1. Take a baseline blood sample for cortisol
at 9:00 AM - label with the patient's name,
Lab order number, as well as the date and
actual clock time of the blood sample.

2. Give the 250 ug of Synacthen by

intramuscular (i.m.) injection.

20
SHORT SYNACTHEN TEST
3. Take another blood sample for cortisol at
30 and 60 minutes post injection. Label
with the date and actual clock time the
samples were taken.

4. Send all samples to the laboratory for

processing with clinical details and any
history of relevant drugs (especially
steroid treatment).

21
22
 INTERPRETATION

Adrenal insufficiency is excluded by a 30 min value >18ug/dL.

Failure to meet the above criteria indicates probable Addison's disease or very marked adrenal
atrophy secondary to prolonged absence of ACTH stimulation. Further tests are required to
differentiate between the two.

A normal response does not exclude ACTH deficiency.

23
 INTERPRETATION

If impaired cortisol response, and ACTH >200 pg/mL the diagnosis is primary adrenal failure.
If ACTH <10 pg/mL then diagnosis is secondary adrenal failure.

Borderline cases are difficult to interpret and patients with low normal basal levels or minimal
responses to Synacthen may still have adrenal insufficiency.

24
 THANK YOU

F O R YOU R VA LUA B LE TI M E
References:
h t t p s : / / w w w. n c b i . n l m . n i h . g o v / b o o k s / N B K 5 3 8 2 3 9 /
h t t p s : / / m f t . n h s . u k / a p p / u p l o a d s / 2 0 2 3 / 0 2 / S h o r t- s y n a c t h e n - t e s t- A d u l t s . p d f
h t t p s : / / w w w. n c b i . n l m . n i h . g o v / p m c / a r t i c l e s / P M C 7 8 3 0 9 8 0 /

28