1. Dr. Tariq Waseem
Professor of Medicine
King Edward Medical University
Mayo Hospital Lahore.
Prof. Tariq Waseem

2. Prof. Tariq Waseem
Munich 2011

3. Adrenal Cortex
Adrenal Medulla
Prof. Tariq Waseem

4.  Salt
 Sugar
 Sex
Prof. Tariq Waseem

5.  Mineralocorticoids
Fluid & Electrolytes balance
 Aldosterone (renin from kidneys controls adrenal
cortex production of aldosterone)
 Na retention
 Water retention
 K excretion
Prof. Tariq Waseem

6.  GLUCOCORTICOIDS
Regulate metabolism & are critical in stress
response
 CORTISOL responsible for control and &
metabolism of:
a. CHO (carbohydrates)
 amount of glucose formed
 amount of glucose released
Prof. Tariq Waseem

7. b. FATS-control of fat metabolism
 stimulates fatty acid mobilization from
adipose tissue
c. PROTEINS-control of protein metabolism
 stimulates protein synthesis in liver
 protein breakdown in tissues
Prof. Tariq Waseem

8. Inflammatory and allergic
response
Immune system therefore
Prone to infection
Prof. Tariq Waseem

9.  ANDROGENS
 hormones which male characteristics
release of testosterone
 Seen more in women than men
Prof. Tariq Waseem

10.  A 40 years old man presents to his primary care
physician with a month long history of FATIGUE,
LIGHT HEADEDNESS, and MUSCLE WEAKNESS. He
noticed 5 kg WEIGHT LOSS, over this time, as well
as darkening of skin over his knees. The light
headedness is particularly severe when he gets
out of bed in morning or rises from seated
position. During the entire interview, patient
appears irritable and agitated.
Prof. Tariq Waseem

11.  O/E blood pressure in supine is 115/75, and
standing is 90/60 mmHg.
 Other positive physical signs : cachexia,
pigmentation in palmar creases, elbows,
knees, gums and buccal mucosa.
Prof. Tariq Waseem

12.  Adrenal insufficiency
 Chronic fatigue syndrome
 Depression
 Eating disorders
Prof. Tariq Waseem

13. Prof. Tariq Waseem
Eosinophilia,
Na – 125, K – 5.9,
BSF – 64mg/dl

14. Addison’s Disease
Prof. Tariq Waseem

15.  Addison disease is adrenocortical insufficiency
due to the destruction or dysfunction of the
entire adrenal cortex. It affects both
glucocorticoid and mineralocorticoid function.
The onset of disease usually occurs when
90% or more of both adrenal cortices are
dysfunctional or destroyed.
Prof. Tariq Waseem

16. Disease tends to be more common in females
and children.
Age at onset:
Mostly in adults at 30-50 years
Prof. Tariq Waseem

17. Idiopathic Autoimmune.
The most common cause, accounts for more than 80% of reported cases.
Associations.
Schmidt syndrome:
AD + Hashimoto thyroiditis.
Polyglandular Autoimmune Syndrome Type 1:
AD + hypoparathyroidism + mucocutaneous candidiasis.
Polyglandular Autoimmune Syndrome Type2:
AD + type 1 DM + Hashimoto thyroiditis or Graves disease.
Prof. Tariq Waseem

18. Chronic Granulomatous Diseases:
Tuberculosis
Sarcoidosis,
Histoplasmosis,
Blastomycosis,
and Cryptococcosis
Could involve the adrenal glands.
Prof. Tariq Waseem

19. Malignancies Metastasis:
Infiltrative metabolic disorders :
Amyloidosis and hemochromatosis could involve
the adrenal glands and lead to primary
adrenocortical insufficiency.
HIV
Prof. Tariq Waseem

20.  Onset of symptoms often is insidious.
Hyperpigmentation of the skin and
mucous membranes often precedes all
other symptoms by months to years.
Excess of (ACTH) stimulates the melanocytes
to produce melanin.
Appears on the sun-exposed areas of the
skin, extensor surfaces, knuckles, elbows and
knees in addition to mucous membranes;
dentogingival margins and buccal areas.
Vitiligo:In autoimmune Addison due to
melanocytes destruction.
Prof. Tariq Waseem

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26.  Dizziness & Syncope
Due to postural hypotension
Due to the combined effects of volume
depletion, loss of the mineralocorticoid effect of
aldosterone, and loss of the permissive effect
of cortisol in enhancing the vasopressor effect
of the catecholamines.
 Myalgias and flaccid muscle paralysis
may occur due to hyperkalemia.
 Progressive weakness, fatigue, poor
appetite, and weight loss.
 Gastrointestinal symptoms may include
nausea, vomiting, and occasional diarrhea.
Prof. Tariq Waseem

27.  SECONDARY adrenal insufficiency:
Many of the signs and symptoms seen in
primary adrenal insufficiency are also
present here
EXCEPT:
NO HYPERPIGMENTATION
GI: less common
NO salt craving
Prof. Tariq Waseem

28.  Serum Cortisol
 ACTH
PRIMARY ADDISONS
A random plasma cortisol value of 25 mcg/dL or
greater effectively excludes adrenal insufficiency of
any kind.
Prof. Tariq Waseem

29.  Rapid ACTH stimulation test:
1-Blood is drawn in 2 separate tubes for baseline
cortisol and aldosterone values.
2. Synthetic ACTH (1-24 amino acid sequence) in
a dose of 250 mcg (0.25 mg) is given IM or IV.
Thirty or 60 minutes after the ACTH injection, 2
more blood samples are drawn; one for cortisol
and one for aldosterone.
Prof. Tariq Waseem

30.  Interpreting rapid ACTH stimulation test:
 -Two criteria are necessary for diagnosis:
1. An increase in the baseline cortisol value of 7
mcg/dL or more and
2. The value must rise to 20 mcg/dL or more in
30 or 60 minutes, establishing normal adrenal
glucocorticoid function.
 In patients with Addison disease, both cortisol
and aldosterone show minimal or no change in
response to ACTH.
Prof. Tariq Waseem

31.  CHRONIC
ADDISON’S
Hyponatremia,
Hyperkalemia,
Hypercalcemia
Azotemia
Eosinophilia
Anemia
Low Cortisol
Unresponsive to
Exogenous ACTH
 SECONDARY
ADRENAL
INSUFFICIENCY
NO hyperkalemia
Hyponatremia often
present
Low cortisol
LOW ACTH
Hypoglycemia is
more common
Prof. Tariq Waseem

32.  CBC ( eosinophilia, anemia)
 S/E ( hyponatremia, hyperkalemia, hypercalcemia,
 Hypoglycemia
 Low cortisol unresponsive to synthetic ACTH
( ACTH STIMULATION TEST – cortisol level fail to
increase in response to exogenous ACTH)
 ACTH LEVEL TO differentiate primary and
secodnary
 If autoimmune suspected – adrenal antibodies
 Tuberculosis causes adrenal calcification
 X-ray or CT scan abdomen.
Prof. Tariq Waseem

33.  Patients with adrenocortical insufficiency
always need glucocorticoid replacement
therapy and usually, but not always,
mineralocorticoid. Other treatments on the
underlying cause.
Prof. Tariq Waseem

34. Cortisol ( hydrocortisone 15-20 mg PO every
am and 5-10 mg every pm)
or
Prednisolone 5 mg am and 2.5 mg pm
Fludrocortisone 0.05-0.2 mg PO daily if
mineralocorticoid deficient
Increase dose of steroid 2 to 3 fold for a few
days during illness or for surgery
Prof. Tariq Waseem

35.  Closely monitor patients for any signs of
inadequate replacement (e.g., morning
headaches, weakness, and dizziness) and
any signs of over-replacement (e.g.,
cushingoid features).
 A periodic bone dual-energy x-ray
absorptiometry (DEXA) detecting early
osteoporosis in patients who are over-
replaced with maintenance steroids.
 Patients should be instructed to double or
triple their steroid replacement doses in
stressful situations such as a common cold or
tooth extraction.
Prof. Tariq Waseem

36.  Ketoconazole inhibits the adrenal cytochrome P450
steroidogenic enzymes.
 Aminoglutethimide blocks the early conversion of
cholesterol to pregnenolone by inhibiting the 20,22-desmolase
enzyme.
 Mitotane (O,P'-DDD) blocks adrenal mitochondrial steroid
biosynthesis.
 Busulphan, etomidate, and trilostane inhibit or
interfere with adrenal steroid biosynthesis.
 Methadone, perhaps by depleting pituitary ACTH, may cause
secondary adrenocortical insufficiency in some patients.
Prof. Tariq Waseem

37. Prof. Tariq Waseem
Which famous American President
had Addison’s Disease???

38. Prof. Tariq Waseem

39. Prof. Tariq Waseem

40.  A 15 year old boy presented with 3 days H/O
fever, headache and altered consciousness.
On 5th day purpuric rash developed over legs,
he had repeated vomiting, oliguria and
became agitated. BP recorded at that time
was 80/50 mmHg. Two liters of 0.9% saline
infusion failed to improve the blood
pressure.
 What’s the diagnosis?
 What Complication has occurred?
Prof. Tariq Waseem

41.  Adrenal Crisis is not to be confused with
Addison’s disease which results from long-
term adrenal insufficiency that develops over
months to years, with weakness,
fatigue, anorexia, weight loss, and
hyperpigmentation as the primary symptoms.
 In contrast, an acute adrenal crisis can manifest
with vomiting, abdominal pain, and hypovolemic
shock.
Prof. Tariq Waseem

42.  Adrenal crisis and severe acute
adrenocortical insufficiency are often elusive
diagnoses that may result in severe morbidity
and mortality when undiagnosed or
ineffectively treated.
Prof. Tariq Waseem

43.  In every patient presenting with hypotension
and hypovolemic shock and not responding to
IV fluid replacement alone Acute Adrenal
crisis should be considered especially in
those on long term steroid therapy for
various indications.
Prof. Tariq Waseem

44.  Maintain normal vascular response to
vasoconstrictors
 Resist increases in capillary permeability
 Inhibit interleukin-2 (IL-2) production by
macrophages
 Stimulate of neutrophil (PMN) leukocytosis
 Reduce adherence of macrophages to
endothelium
 Deplete circulating eosinophils and
lymphocytes
 Reduce circulating lymphocytes (primarily T
cells)
Prof. Tariq Waseem

45.  Suppression of the hypothalamic-pituitary axis
from chronic exogenous steroid use is the most
common cause of secondary adrenal
insufficiency.
 Steroid Withdrawl.
 Sepsis
 Surgical stress
 Acute Adrenal hemorrhage
Waterhouse Fredrickson’s Syndrome
 Acute Pituitary Necrosis
Sheehan’s Syndrome
Prof. Tariq Waseem

46.  Left untreated, a patient with acute adrenal
insufficiency has a dismal prognosis for
survival. Therefore, treatment upon clinical
suspicion is mandatory. Any delay in
management while waiting for diagnostic
confirmation cannot be justified.
Prof. Tariq Waseem

47.  Maintain ABC
 Coma protocol (ie, glucose, thiamine, naloxone).
 Aggressive volume replacement therapy
(dextrose 5% in normal saline solution [D5NS]).
 Correct electrolyte abnormalities :
 Hypoglycemia (67%)
 Hyponatremia (88%)
 Hyperkalemia (64%)
 Hypercalcemia (6-33%)
 Use dextrose 50% as needed for hypoglycemia.
Prof. Tariq Waseem

48.  Administer hydrocortisone 100 mg
intravenously (IV) every 6 hours. During
adrenocorticotropic hormone (ACTH)
stimulation testing, dexamethasone (4 mg IV)
can be used instead of hydrocortisone to
avoid interference with testing of cortisol
levels.
 Administer fludrocortisone acetate
(mineralocorticoid) 0.1 mg every day.
 Always treat the underlying problem that
precipitated the crisis.
Prof. Tariq Waseem

49. Prof. Tariq Waseem
Nymphemberg Palace
Munich 2011