1. Adrenal Gland
Cortisol

2. corticosteroids

3. HPA axis
ACTH secretion from the anterior pituitary is controlled by both a classical negative feedback control mechanism and CNS-stress mediated control system.
Various types of stress or pain perceived in higher levels of the brain modulate secretion of the hypothalamic neurosecretory hormone, corticotropin releasing hormone (CRH), a 41-amino acid peptide. CRH stimulates pituitary ACTH secretion.
The second peptide that modulates ACTH secretion is vasopressin (AVP)= ADH. AVP secretion is also stimulated by stress and acts synergistically with CRH to increase ACTH secretion in the pituitary portal circulation.

4. ACTH ACTH (Adrenocorticotropic hormone) or corticotropin.
Is a 39 amino acid peptide hormone (mwt=4500) secreted by the pituitary to regulate the production of steroid hormones by the adrenal cortex.
ACTH is secreted in irregular pulses throughout the day which cause parallel increases in plasma cortisol. Both the frequency and the amplitude of the pulses are the greatest in the early morning.
Steroid hormons by adrenal cortex

5. Cortisol and cortisone?

6. ACTH increases the synthesis and release of all adrenal cortex steroids, aldosterone, cortisol and adrenal androgens(corticosteroids).
It is the principal modulator of cortisol, the most important glucocorticoid in man. As the cortisol level in blood increases, release of ACTH is inhibited directly at the pituitary level. Through this same mechanism, decreasing cortisol levels lead to elevated ACTH levels.

7. The determination of ACTH should be performed on EDTA plasma.
To assay the specimen in duplicate, μL of EDTA plasma is required.

8. Primary aldosteronism is being increasingly investigated as a possible secondary cause of hypertension in adults.
From the laboratory perspective, this usually involves measuring both aldosterone and renin and calculating aldosterone to renin ratio.

9. Also called Hydrocortisone
Cortisol the glucocorticoid found in the largest concentration in the serum, is the one usually measured to gain information about the functioning of the adrenal cortex.
Also called Hydrocortisone
Plasma cortisol has a diurnal variation, its levels being higher in the morning than in the evening. Baseline readings are taken in the morning with the client at rest.
تغير التركيز خلال ساعات النهار

10. Levels peak in the early morning and drop to the lowest concentration at night.
Levels rise independently of circadian rhythm in response to stress.
Increased cortisol production is associated with Cushing’s syndrome and adrenal tumors, while decreased cortisol production is associated with adrenal insufficiency (e.g., Addison’s disease) and adrenocorticotropic hormone (ACTH) deficiency.

11. Increased amounts of ACTH and cortisol are secreted independently of the circadian rthyme in response to physical and psychological stress.
Elevated cortisol levels and lack of diurnal variation have been identified in patients with cushing’s disease
Elevated circulating cortisol levels have also been identified in patients with adrenal tumors
Low cortisol levels are found in primary adrenal inufficiency as adrenal hypoplasia, congenital adrenal hyperplasia or addisson’s disease and in ACTH defeciency.

12. Due to the normal circadian variation of cortisol levels distinguishing normal and abnormally low cortisol levels can be difficult.
Therefore, various tests to evaluate the pituitary adrenal axis ACTH-cortisol, including insulin-induced hypoglycemia, short and long term ACTH stimulation, CRF stimulation and artificial blockage of cortisol synthesis with metronome have been performed.
Saliva measure free preferred
ممكن من اليورن

13. Cortisol function Stress hormone
Physiologically effective in anti-inflammatory activity and blood pressure maintainace, cortisol is also involved in gluconeogensis.
Cortisol is probably the most measured analyte for evaluating adrenal function although aldosterone and rennin are also ordered frequently.

14. ?

15. While the assessment of cortisol in sweat or tears is only of theoretical importance and urinary cortisol of decreasing interest, salivary cortisol has become an invaluable tool for both basic scientists and clinicians.
A number of significant advantages over the assessment of cortisol in blood has resulted in an steadily increasing interest in salivary cortisol.
In the blood only 1 to 15% of cortisol is in its unbound or biologically active form. The remaining cortisol is bound to serum proteins.Unbound serum cortisol enters the saliva via intracellular mechanisms, and in saliva the majority of cortisol remains unbound to protein.
Free cortisol in saliva

16. Q: Does the concentration of cortisol in saliva accurately reflect the level in blood?
A:Yes, when compared to the amount of unbound cortisol in serum or plasma samples. A number of studies have revealed correlations between the two specimen of r > However, the correlation between the total cortisol levels in blood and salivary cortisol is usually weaker due to different amounts of CBG found in blood (e.g., high levels of CBG due to oral contraceptive use results in high total cortisol levels; free cortisol levels are usually unaltered in states of increased CBG).
Unbound= free

17. Q: Does the salivary cortisol levels depend on saliva flow rate?
A:No. Studies looking at salivary cortisol levels obtained under minimal and maximal flow rate clearly showed that the cortisol levels in saliva do not depend on flow rate
لا يوجد علاقة بين كمية اللعاب التي يتم انتاجها و تركيز الكورتيزول

18. Preparation of client:
The specimen is usually drawn in the morning after the client has been fasting. Evening samples may also require about 3 hour of fasting. Water is allowed. Because activity increases the level, the client needs to be supine for 2 hour before the test.
Cortisol is excreted primarily in urine in an unbound free form
Salivary cortisol:
For research studies, salivary cortisol is simple noninvasive way to obtain a physiological index of stress.

19. You may be asked to avoid strenuous physical activity the day before the test.
Be sure to drink enough fluids during the 24-hour urine test. This prevents dehydration .
Many medicines may change the results of this test. Be sure to tell your doctor about all the non-prescription and prescription medicines you take.
Talk to your doctor about any concerns you have regarding the need for the test, its risks, how it will be done, or what the results will mean
L dopa affect cortisol conc

20. Serum cortisol levels
Increased serum cortisol level significance: an increase in cortisol can either ACTH-dependent or ACTH- independent.
The specific medical treatment of elevated cortisol levels depends on the cause.
The client may undergo a pattern of tests to determine whether there is a tumor of the pituitary gland or of the adrenal gland.
Decrease serum cortisol level clinical significance: the lack of cortisol in the serum may be due to primary hypofunction of the adrenal cortex, or it may be secondary to hypo functioning of the pituitary gland.

21. Once the symptoms of a lack of cortisol and aldosterone are recognized and confirmed, replacement therapy is started. Until the hormones are replaced, or when the need is greater than the supply, these clients may have problems related to the lack of cortisol and aldosterone.

22. Cortisone
In adipose tissue liver, muscle, brain, and other organs, Cortisone, an inactive glucocorticoid, is converted to cortisol
The amount of cortisol found to be produced in this conversion is approximately 25 percent of the amount produced by the adrenal cortex
Cortisol and cortisone are both steroids. They share a similar core chemical structure which is common to all the cholesterol-like molecules. The difference between cortisol and cortisone lies in the difference of the functional groups present in the two molecules.
When the adrenal glands do not make enough cortisol, this is called adrenal insufficiency, the treatment is hydrcortison
الادوية الستيرويدية تؤثر على تركيز الكورتيزول

24. Clinical significance of cortisol
Measurement of cortisol is used primarily to diagnose and monitor the  treatment of Addison’s  disease and Cushings syndrome
CUSHING’S DISEASE
ADDISON’S DISEASE
Hypersecretion of adrenocortical hormone
Hyposecretion of adrenocortical hormones 
Definition
Elevated Cortisol
FBS elevated
Elevated Na
Decreased K
Plasma cortisol decreased
FBS decreased (N= mg/dl)
Serum Na decreased (N= )
Serum K elevated (N= meq/L)
Diagnostics

26. Reference ranges
The reference ranges for serum cortisol are as follows:
Morning μg/dL
Afternoon μg/dL
Stimulated* - ≥ 18 μg/dl
Suppressed** - < 2 μg/dl
*Low-dose ACTH stimulation test: before or after (anytime, but usually one hour) ACTH 250 μg (one ampule) intravenous injection
**Overnight low-dose dexamethasone suppression test: 8 AM serum cortisol after oral dexamethasone 1 mg taken in late evening (11 PM)
The cortisol conversion factor is To convert from μg/dl to the nmol/L, multiply by the conversion factor; to convert from nmol/L to the μg/dl, divide by the conversion factor.