Capulong, Aya L.

Premed2 8:00-9:00 TTh

Section:LCA

Addison’s disease

Pathogenesis
Autoimmune Addison disease affects the function of the adrenal
glands, which are small hormone-producing glands located on top
of each kidney. It is classified as an autoimmune disorder because
it results from a malfunctioning immune system that attacks the
adrenal glands. As a result, the production of several hormones is
disrupted, which affects many body systems.
Signs and Symptoms
*The signs and symptoms of autoimmune Addison disease can
begin at any time, although they most commonly begin between
ages 30 and 50.

-extreme tiredness (fatigue)

-nausea
-decreased appetite
-weight loss
-low blood pressure (hypotension)
-dark areas of skin
(hyperpigmentation)
-low levels of sugar (hypoglycemia)
-sodium (hyponatremia)
- high levels of potassium
(hyperkalemia)
 

Autoimmune Addison disease can lead to a life-threatening adrenal crisis, characterized by

vomiting, abdominal pain, back or leg cramps, and severe hypotension leading to shock. The
adrenal crisis is often triggered by a stressor, such as surgery, trauma, or infection.

Individuals with autoimmune Addison disease or their family members can have another
autoimmune disorder, most commonly autoimmune thyroid disease or type 1 diabetes.
Risk Factors
-Swelling (inflammation) of the thyroid gland that often results in reduced thyroid function
(chronic thyroiditis)
-Thyroid gland produces too much thyroid hormone (overactive thyroid, Graves disease)
-Itchy rash with bumps and blisters (dermatitis herpetiformis)
-Parathyroid glands in the neck do not produce enough
parathyroid hormone (hypoparathyroidism)
-Pituitary gland does not produce normal amounts of some or
all of its hormones (hypopituitarism)
-Autoimmune disorder that affects the nerves and the muscles
they control (myasthenia gravis)
-Body does not have enough healthy red blood cells
(pernicious anemia)
-Testicles cannot produce sperm or male hormones (testicular failure)
-Type I diabetes
-Loss of brown color (pigment) from areas of the skin (vitiligo)

Causes
*The cause of autoimmune Addison disease is complex and not completely understood. A
combination of environmental and genetic factors plays a role in the disorder, and changes in
multiple genes are thought to affect the risk of developing the condition.
*The genes that have been associated with autoimmune Addison disease participate in the
body's immune response. The most commonly associated genes belong to a family of genes
called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune
system distinguish the body's own proteins from proteins made by foreign invaders (such as
viruses and bacteria). Each HLA gene has many different normal variations, allowing each
person's immune system to react to a wide range of foreign proteins. The most well-known risk
factor for autoimmune Addison disease is a variant of the HLA-DRB1 gene called HLA-
DRB1*04:04. This and other disease-associated HLA gene variants likely contribute to an
inappropriate immune response that leads to autoimmune Addison disease, although the
mechanism is unknown.

Inheritance pattern: unknown.

Diagnosis:
*Genetic Testing
What is genetic testing?
Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or
proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or
help determine a person’s chance of developing or passing on a genetic disorder. More than
1,000 genetic tests are currently in use, and more are being developed.
Several methods can be used for genetic testing:
a. Molecular genetic tests (or gene tests) study single genes or short lengths of DNA to identify
variations or mutations that lead to a genetic disorder.
b. Chromosomal genetic tests analyze whole chromosomes or long lengths of DNA to see if
there are large genetic changes, such as an extra copy of a chromosome, that cause a genetic
condition.
c.Biochemical genetic tests study the amount or activity level of proteins; abnormalities in either
can indicate changes to the DNA that result in a genetic disorder.
Genetic testing is voluntary. Because testing has benefits as well as limitations and risks, the
decision about whether to be tested is a personal and complex one. A geneticist or genetic
counselor can help by providing information
about the pros and cons of the test and
discussing the social and emotional aspects of
testing.
*Blood test. Tests can measure your blood
levels of sodium, potassium, cortisol and
adrenocorticotropic hormone (ACTH), which
stimulates the adrenal cortex to produce its
hormones. A blood test can also measure
antibodies associated with autoimmune Addison's disease.
*ACTH stimulation test. ACTH signals your adrenal glands to produce cortisol. This test
measures the level of cortisol in your blood before and after an injection of synthetic ACTH.
*Insulin-induced hypoglycemia test. You may be given this test if doctors think you may have
adrenal insufficiency as a result of pituitary disease (secondary adrenal insufficiency). The test
involves checking your blood sugar (blood glucose) and cortisol levels after an injection of
insulin. In healthy people, glucose levels fall and cortisol levels increase.
In certain situations doctors may do alternative tests for secondary adrenal insufficiency, such
as a low-dose ACTH stimulation test, prolonged ACTH stimulation test or glucagon stimulation
test.
*Imaging tests. You may undergo a computerized tomography (CT) scan of your abdomen to
check the size of your adrenal glands and look for other abnormalities. You may also undergo
an MRI scan of your pituitary gland if testing indicates you might have secondary adrenal
insufficiency.
Treatment
All treatment for Addison's disease involves medication. You will be given hormone replacement
therapy to correct the levels of steroid hormones your body isn't producing. Some options for
treatment include oral corticosteroids such as:

 Hydrocortisone (Cortef), prednisone or methylprednisolone to

replace cortisol. These hormones are given on a schedule to
mimic the normal 24-hour fluctuation of cortisol levels.

 Fludrocortisone acetate to replace aldosterone.

Other treatment recommendations include:

-Carry a medical alert card and bracelet at all times. A steroid emergency card and medical
alert identification will let emergency medical personnel know what kind of care you need. Also
have a written action plan.
-Keep extra medication handy. Missing even one day of medication may be dangerous, so
keep a small supply of medication at work and with you whenever you travel.
-Carry a glucocorticoid injection kit. The kit contains a needle, syringe and injectable form of
corticosteroids to use in case of emergency.
-Stay in contact with your doctor. Keep an ongoing relationship with your doctor to make sure
that the doses of replacement hormones are adequate, but not excessive. If you're having
ongoing problems with your medications, you may need adjustments in the doses or timing of
the medications.
-Have annual checkups. See your doctor or an endocrinology specialist at least once a year.
Your doctor may recommend annual screening for a number of autoimmune diseases.
References:
-Gombos Z, Hermann R, Kiviniemi M, Nejentsev S, Reimand K, Fadeyev V, Peterson P, Uibo R,
Ilonen J. Analysis of extended human leukocyte antigen haplotype association with Addison's
disease in three populations. Eur J Endocrinol. 2007 Dec;157(6):757-61. Citation on PubMed
-Husebye E, Løvås K. Pathogenesis of primary adrenal insufficiency. Best Pract Res Clin
Endocrinol Metab. 2009 Apr;23(2):147-57. doi: 10.1016/j.beem.2008.09.004. Review. Citation
on PubMed
-Mitchell AL, Pearce SH. Autoimmune Addison disease: pathophysiology and genetic
complexity. Nat Rev Endocrinol. 2012 Jan 31;8(5):306-16. doi: 10.1038/nrendo.2011.245.
Review. Citation on PubMe
-Genetics Home Reference, ghr.nlm.nih.gov/condition/autoimmune-addison-
disease#sourcesforpage.
-Addison’s Disease, Mayo Clinic: https://www.mayoclinic.org/diseases-conditions/addisons-
disease/diagnosis-treatment/drc-20350296