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.
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.
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
