Addison's disease is a rare condition caused by insufficient production of hormones by the adrenal glands. It results in a decrease in glucocorticoids and mineralocorticoids. Symptoms include chronic fatigue, weight loss, and hyperpigmentation. While current treatment replaces the missing hormones, research aims to regenerate damaged adrenal cortex cells through stem cell stimulation in order to cure the disease.

1. Addison’s Disease:
The insufficiency of adrenal glands

2. Introduction
Addison’s Disease is a rare and chronic
disease that is characterized by adrenal
insufficiency
There is a decrease in hormones in the
adrenal cortex such as glucocorticoids and
mineralocorticoids
6-110 cases diagnosed per 100,000 in the
world per year.
1.4 million deaths per year around the
world.
Usually effects 30-50 year-olds, but can be
seen in all ages

3. History
First discovered by Thomas Addison in 1855
First described as an infection of the adrenal gland- most
commonly TB.
Now instead of infection, its most commonly characterized
by an autoimmune destruction of the adrenal glands

4. Causes of the Disease
Three different causes of the disease
Adrenal Dysgenesis:
Genetic Causes
Imparied Steriodiogensis:
Congenital Adrenal Hyperplasia
Adrenal Destruction:
Autoimmune destruction

5. Causes of Disease
Adrenal Destruction:
Most common type in industrialized world
Affects humoral and cell-mediated responses
Immune reaction against enzyme 21-hydroxylase, a
cytochrome P450 enzyme.
Normal functioning 21-hydroxylase catalyzes the addition
of an “-OH” on carbon 21 in steroids
Addison’s Disease has an enormous amount of
autoantibodies attack this enzyme and slowly kill off the
adrenal cortex.
82.5% of autoantibodies are adrenal antibodies

6. Symptoms
Chronic fatigue
Muscle Weakness
Weight loss, Nausea, Diarrhea
Hyperpigmentation
Hypercalcemia, Hypoglycemia, Hypoatremia, and
Hyperkalemia
Esinophilia and Lymphocytosis
Metabolic acidosis
Addisonian Crisis:
Severely low blood pressure and potential coma or death

7. How Are the Hormones Affected?
When Addison’s disease goes into affect, the Anterior
pituitary produces excessive but ineffective amounts of
Adrenocorticotropic (ACTH) to the adrenal cortex thus
hindering its ability to produce and release hormones
(Glucocorticoids and Mineralocorticoids).
Since there is no ACTH to stimulate the adrenal cortex
to release its hormones, the adrenal cortex can not
release hormones to regulate processes in the body.

8. Normal Negative Feedback
The hypothalamus releases hypothalamic inhibitory or
releasing hormones to the anterior pituitary.
The anterior pituitary then releases ACTH to the adrenal
cortex.
The adrenal cortex will then release Glucocorticoids (to
raise blood glucose levels or to replenish glucose during
or after stressful situations) or Mineralocorticoids (to
reabsorb sodium and excrete potassium in order to
balance water in the body).
When their functions are completed, the target tissues
of the hormones will release their own hormones back to
the hypothalamus in order to stop the release of
hormones to affect the body.

9. Normal negative feedback loops
Target tissue
Hormone of target
tissue

10. Disrupted Negative Feedback
 The anterior pituitary releases excessive yet ineffective amounts
of ACTH which is supposed to stimulate the adrenal cortex.
 The adrenal cortex as a result is affected negatively and does not
release Glucocorticoids or Mineralocorticoids.
 Since Glucocorticoids are not produced, glucose cannot be
replenished when stressful situations occur.
 Since Mineralocorticoids are not produced, there is a lack of
sodium and water in the body thus leading to severe dehydration.
 Also, because ACTH exists in excessive yet ineffective amounts,
bronzing of the skin occurs because ACTH is linked to melanin
production.

11. Diagram of disrupted negative
feedback
Excessive and ineffective
amounts of
Adrenal cortex
hormones are not
released

12. Diagnosis
Determined by low level of adrenal hormone after
stimulation with synthetic ACTH hormone tetercosactide
Short Test:
Compares blood cortisol levels before and after
250 micrograms of tetracosactide if abnormal go to long test
Long Test:
1 mg of tetracosactide is administered and blood taken at 1, 4, 8,
and 24 hours later

13. Current Treatment
Replacement corticoidsteroids or fludrocortisone
acetate
Doses change according to lifestyle, i.e. stress, infection
or injury
Have to carry emergency injection of hydrocortisone
and card/bracelet indentifying their condition

14. Clinical Trials
Revival of Stem Cells in Addison’s Study
Aims to regenerate adrenocorticol
steroidogenic cell functions by stimulation
proliferation and differentiation of progenitor
cells in order to replace damaged adrenal
cortex cells

15. Conclusion and Future Studies
It’s a rare but detrimental disease if left untreated
Manageable disease through hormone therapy and helps
individuals lead a normal life
Future Studies
Developing a time release capsule to better mimic the
natural fluctuations of the cortisol production