1. Lab test and treatment
ofAddison's disease
Eman abd el raouf ahmad

2. The content
Addison disease
investigation
Lab test
treatment

3. Note: Addison Disease
Also called:
Adrenal insufficiency
Adrenocortical hypo function,
Hypocortisolism

4. Defect in Addison's disease
Auto antigen:21-oH,P450,17OH
Tissue cells: enzymes of the adrenal cortex

5. Investigation:
General: K+ ↑ Na+ ↓
glucose ↓ uraemia, mild
acidosis, Ca2+ ↑
eosinophilia , neutropenia
lymphocytosis and anaemia .

6. Lab test
Blood test.: Measuring your blood levels of sodium,
potassium, cortisol and ACTH gives your doctor an initial
indication of whether adrenal insufficiency may be causing
your signs and symptoms. A blood test can also measure
antibodies associated with autoimmune Addison's disease.
ACTH stimulation test. This test involves measuring the level
of cortisol in your blood before and after an injection of
synthetic ACTH. ACTH signals your adrenal glands to produce
cortisol. If your adrenal glands are damaged, the ACTH
stimulation test shows that your output of cortisol in response
to synthetic ACTH is limited or nonexistent.

7. Corticotrophin-releasing hormone (CRH) stimulation test. This test is used
when the ACTH test is abnormal, to help determine the cause of adrenal
insufficiency. CRH is a hormone released by the hypothalamusthat stimulates
ACTH production by the pituitary gland, which in turn stimulates cortisol
production by the adrenal glands. For this test, synthetic CRH is injected
intravenously and blood cortisol and ACTH levels are measured at timed
intervals after the injection, for example, at 30 and 60 minutes. The normal
response is a peak in ACTH levels followed by a peak in cortisol levels.
People with Addison disease (underactive or damaged adrenal glands)
produce a high level of ACTH but no cortisol.
People with secondary adrenal insufficiency have absent or delayed ACTH
responses. If someone has a damaged pituitary, CRH will not stimulate
ACTH secretion and an absent ACTH response indicates the pituitary is the
cause. If ACTH response is delayed, that indicates the hypothalamus is the
cause.

8. Aldosterone. Blood or urine aldosterone levels are measured to
help diagnose Addison disease, to determine whether the adrenal
gland is producing aldosterone. If the level is low, it is another
indication that an individual may have a primary adrenal
insufficiency.
Electrolytes. Electrolytes (sodium, potassium, chloride and carbon
dioxide) are measured to help detect and evaluate the severity of
an existing electrolyte imbalance and to monitor the effectiveness
of treatment. Electrolytes may be affected by many conditions;
with Addison disease, the sodium, chloride, and carbon dioxide
levels are often low, while the potassium level may be very high.
BUN and Creatinine are tests done to monitor kidney function.
Glucose levels may be very low during an adrenal crisis. Glucose
may be ordered in order to help monitor the individual during a
crisis.

9. Occasionally Used Tests
Insulin-induced hypoglycemia test. Occasionally, a doctor will
order this test to learn if pituitary disease (secondary adrenal
insufficiency) is the cause of adrenal insufficiency. Glucose
and cortisol levels are measured at predetermined intervals
after an injection of insulin is used to stress the pituitary
gland. In healthy people, blood glucose levels fall and
cortisol concentrations increase.
In those with adrenal insufficiency, cortisol levels will remain
low and glucose levels will fall, then recover slowly.

10. Renin. Renin activity is elevated in primary
adrenal insufficiency because a lack of
aldosterone causes increased renal sodium
losses. This lowers blood sodium levels and
decreases the amount of fluid in the blood
(which lowers blood volume and pressure),
which in turn stimulates renin production by
the kidney.
21-hydroxylase autoantibodies are
sometimes ordered as part of the diagnostic
process when autoimmune Addison disease
is suspected. The test is considered a good
indicator of autoimmune Addison disease
but is not widely used at this time.

11. Which antibody tests are positive
in Addison’s disease?
There are three known potential adrenal proteins targeted by anticortical antibodies (ACAs):
21-hydroxylase (21-OH)
17-hydroxylase (17-OH)
Cytochrome P-450
Of these, the most commonly used test is for antibodies to 21-OH, since
the other two proteins are also found in non-adrenal tissues, making
them less specific and confirmatory for Addison’s. The test will likely be
called an adrenal (21-OH) antibody test, or something similar. When
positive, there are antibodies in the bloodstream directed against only
adrenal cortex tissue, which confirms the presence of autoimmune
disease.

12. Is it possible to test negative for the
antibodies and still have Addison’s?
Yes. Because Addison’s is not always
autoimmune in nature – it can also be
caused by infection, trauma, cancer and
other etiologies – it is possible to have the
disease without the presence of any
antibodies.
.

13. Genetic test for HLA
Addison’s disease is associated with DRB1*03:01-DQB1*02 (DR17, DQ2)
and DRB1*04-DQB1*03:02 (DR4, DQ8). The most strongly associated
DRB1*04 allele is DRB1*04:04. The major histocompatibility complex
class I related chain – A (MICA) is an additional risk factor. MICA genes
are highly polymorphic with over 70 alleles described.
Autoantibody testing for anti-21-hydroxylase is more diagnostic in
Addison’s disease than genetic testing. Genetic testing does however
contribute to a better understanding of the etiology of the disease.

14. Non lab test
X-rays may be used to look for calcification on the adrenal cortex that
may be due to a tuberculosis infection.
CT (computerized tomography) or MRI (magnetic resonance imaging)
scans are sometimes used to look at the size and shape of the adrenal
glands and the pituitary. The adrenal glands can be enlarged with
infections and cancers. With autoimmune diseases and secondary
adrenal insufficiency, the adrenal glands are often normal or small.

15. treatment
1-hormone replacement is used to
correct the insufficient levels of
steroids.
2-increase in sodium intake
Fludrocortisone
Hydrocortisone
Prednisone
Oral injection
Hydrocortisone oral
Cortisone oral
Dexamethasone oral

16. treatment
All patients with adrenal insufficiency should
receive specific hormone replacement.
Replacement therapy should correct both
glucocorticoid and mineralocorticoid deficiencies.
Hydrocortisone ( cortisol ) is the mainstay of
treatment. Patients are advised to take
glucocorticoids with meals or, if that is impractical,
with milk or an antacid, because the drugs may
increase gastric acidity and exert direct toxic effects
on the gastric mucosa.

17. TREATMENT: Since the replacement dosage
of hydrocortisone does not replace the
mineralocorticoid component of the
adrenal hormones, mineralocorticoid
supplementation is usually needed.
This is accomplished by the administration of
0.05 to 0.1 mg fludrocortisone per day by
mouth. Patients should also be instructed to
maintain an ample intake of sodium (3 to 4 g/d).

18. TREATMENT: In female patients
with adrenal insufficiency,
androgen levels are also low. Thus,
some physicians believe that daily
replacement with 25 to 50 mg of
DHEA orally may improve quality of
life and skeletal density

19. Special Therapeutic Problems: During periods of
intercurrent illness, especially in the setting of
fever, the dose of hydrocortisone should be
doubled. With severe illness it should be
increased to 75 to 150 mg/d..

20. Hydrocortisone tablets
indication: used to treat endocrine Indication
(hormonal) disorders (adrenal insufficiency,
Addison's disease).

21. Pharmacological action
Hydrocortisone is the most important human glucocorticoid. It is essential for life and
regulates or supports a variety of important cardiovascular, metabolic, immunologic
and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or
immunosuppressive properties to treat inflammation due to corticosteroid-responsive
dermatoses. Glucocorticoids are a class of steroid hormones characterised by an
ability to bind with the cortisol receptor and trigger a variety of important
cardiovascular, metabolic, immunologic and homeostatic effects.

22. Mechanism of action:
1. Hydrocortisone binds to the cytosolic glucocorticoid receptor.
2. the receptor the newly formed receptor-ligand complex
translocate itself into the cell nucleus, where it binds to many
glucocorticoid response elements (GRE) in the promoter region
of the target genes.
3. The DNA bound receptor then interacts with basic transcription
factors, causing the increase in expression of specific target
genes. The anti-inflammatory actions of corticosteroids are
thought to involve lipocortins, phospholipase A2 inhibitory
proteins which, through inhibition arachidonic acid, control the
biosynthesis of prostaglandins and leukotriene.

23. Prednisone
Prednisone is a glucocorticoid. Glucocorticoids are
adrenocortical steroids, both naturally occurring
and synthetic, which are readily absorbed from
the gastrointestinal tract. The molecular formula
for prednisone is C21H26O5. Chemically, it is
17,21-dihydroxypregna-1, 4-diene-3,11, 20-trione
and has the following structural formula:

24. CLINICAL PHARMACOLOGY
Glucocorticoids, such as prednisone, cause profound
and varied metabolic effects. In addition, they modify
the body’s immune response to diverse stimuli.

25. fludrocortisone
Fludrocortisone (also called 9α-fluorocortisol or 9α-fluorohydrocortisone) is a synthetic
corticosteroid with moderate glucocorticoid potency and much greater mineralocorticoid
potency.
. Fludrocortisone has been used in the treatment of cerebral salt wasting.[1] It is used
primarily to replace the missing hormone aldosterone in various forms of adrenal
insufficiency such as Addison's disease and the classic salt wasting (21-hydroxylase
deficiency) form of congenital adrenal hyperplasia. Due to its effects on increasing Na+
levels, and therefore blood volume.

26. Fludrocortisone is available in 0.1 mg tablets. Typical daily doses for mineralocorticoid
replacement are between 0.05 mg - 0.2 mg. Renin plasma, sodium, and potassium is
checked through blood tests in order to verify that the correct dosage is reached.

27. Chemically, fludrocortisone is
identical to cortisol except for the
substitution of fluorine in place of
one hydrogen. Fluorine is a good
bioisostere for hydrogen because it
is similar in size. The major
difference is in its electronegativity.

28. Dexamethasone
Dexamethasone is a potent synthetic member of
the glucocorticoid class of steroid drugs that has
anti-inflammatory and immunosuppressant
effects. It is 25 times more potent than cortisol in
its glucocorticoid effect, while having minimal
mineralocorticoid effect.

29. A Classic Case of Addison's
Disease
A 23-year-old female presented to the Emergency Department complaining of
nausea and vomiting for one week. She also reported 8 months of progressively
worsening fatigue. The patient was previously very active as a ballet student, but
for the past 8 months she stopped participating in ballet because of lack of
energy. She was now living with her mother and sleeping or watching television
most of the day. One week prior to admission, she developed nausea and had
several episodes of vomiting which provoked her visit to the Emergency
Department. She also reported a poor appetite for months and had lost 5 to 10
pounds. In addition, she endorsed poor concentration, dry skin and "darkening
"of the skin in several areas. She repeatedly denied purposefully restricting food
intake or binging and purging behaviors. There was no abdominal pain, diarrhea,
fevers, dysuria or headache.

30. Past medical history was significant for hypothyroidism diagnosed several
months prior. The patient was prescribed levothyroxine and subsequently
Amour Thyroid but had stopped taking them a month prior because "they
made her feel ill." Her only current medication was progesterone to regulate
her menstrual cycle. There was no family history of autoimmune or endocrine
disorders. Initial examination was remarkable for a blood pressure of 93/50
mmHg and heart rate of 104 beats/min. There were significant orthostatic
changes. The patient was a thin, nontoxic appearing Caucasian female in no
distress. She was alert, oriented and cooperative. Her examination was
otherwise unremarkable except for mild skin hyperpigmentation over the
knuckles, elbows and knees. The thyroid, abdominal, and neurological
examinations were normal.

31. Laboratory testing revealed a normal complete blood count. A basic
metabolic panel showed a sodium of 111 mmol/L (normal range 135-145),
potassium 4.5 mmol/L, chloride 78 mmol/L, bicarbonate 23 mmol/L, glucose
85 mg/dL and creatinine 0.7 mg/dL. Further testing showed serum osmolality
at 234 mosm/kg (normal range 275-295), urine osmolality of 162 mosm/kg,
and urine sodium less than 20 mmol/L consistent with severe hypovolemic
hyponatremia.

32. A random cortisol level was less than 0.2 μg/dL and a subsequent cortisol
level following the administration of 250 mcg of Cosyntropin (Cosynstropin
stimulation testing) remained less than 0.2 μg/dL.
The plasma adrenocorticotropic hormone (ACTH) level was elevated at 882
pg/dL (normal range 5-27) and adrenal antibody testing (antibodies against
the enzyme 21-hydroxylase) was positive with a 1:40 titer (normal<1:10).
Further endocrine testing showed an elevated thyroid-stimulating hormone
level of 29.2 μIU/mL (normal 0.3-4.7), and a thyroid peroxidase
autoantibody level greater than 600 IU/ml (normal<20). Estradiol, folliclestimulating hormone, luteinizing hormone, and prolactin levels were all
within normal limits.

33. references
http://www.nlm.nih.gov/medlineplus/addisondisea
se.html#cat28
http://www.netdoctor.co.uk/liver-and-kidneyproblems/medicines/hydrocortisone-tablets.html
http://ucsdlabmed.wikidot.com/chapter-10

34. thanx