This articles describe primary adrenal insufficiency or Addison's
disease, including its causes, symptoms, diagnosis, and treatment.
Addison's disease is a condition of primary adrenal insufficiency that affects all age groups. This disease is named after the London physician, Thomas Addison who first described patients affected by this disorder in 1855. At the time, the typical Addison's disease patient had adrenal insufficiency caused by infection with Mycobacterium tuberculosis, an organism that causes tuberculosis (TB). With the introduction of effective treatments for TB, it is now only a rare cause of Addison's disease. Today, the primary cause of Addison's disease is autoimmune destruction of the adrenal glands. Nearly 80 percent of all cases are caused by adrenal cortex autoantibodies that destroy the adrenal cortex, the adrenal gland's outer layer. The adrenal cortex produces about 50 different steroid hormones. The two most important and biologically active of these hormones are cortisol and aldosterone. In classical Addison's disease, the adrenal gland fails to produce adequate amounts of both cortisol and aldosterone.
Cortisol is essential for normal metabolism. Cortisol mobilizes nutrients so that they're available for the body's cells as needed, modifies the immune response to inflammation, stimulates the liver to release glycogen and raise blood sugar levels, and helps control the body's fluid volume. Aldosterone regulates the body's salt and water levels, which, in turn, regulate blood pressure and blood volume.
SYMPTOMS AND SIGNS
Common symptoms of Addison's disease include muscle weakness, apathy, fatigue, loss of appetite, weight loss, nausea, vomiting, diarrhea, abdominal pain, low blood pressure (hypotension) that worsens when standing (orthostatic hypotension), hyperpigmentation or bronzing of skin (this condition is known as melasma suprenale), diminished ability to conserve sodium and excrete water, depression, irritability, salt craving, low blood sugar (hypoglycemia), tetany (muscle spasm caused by high phosphorus levels), diminished attention span, numbness of the extremities due to excess potassium (hyperkalemia), and in complete blood counts, an elevated eosinophil count is noted. Because most androgens in the female are produced in the adrenal cortex, females with Addison's disease may have decreased genital and underarm hair.
In its extreme form, Addison's disease can progress to a potentially fatal condition known as an Addisonian crisis. The most common cause is stopping corticosteroid therapy without first tapering the dose. Other causes in clued stress, infection, and other conditions that increase the body's need for cortisol. Symptoms of Addisonian crisis include brown coating on tongue and teethe due to iron released from blood cell destruction; sudden sharp leg pain, lower back or abdomen; nausea and vomiting resulting in dehydration, severe hypotension, unconsciousness, and severe hypoglycemia.
CAUSES
Besides autoimmunity, Addison's disease has other causes. These include interferon treatment for hepatitis C infection, metastatic cancers, which are cancers that originate in other tissues, primarily breast cancer, and spread to other organs, conditions of amyloidosis or sarcoidosis, treatment or surgery for pituitary or hypothalamic cancers, fungal infections (Histoplasmosis, Candididasis, Coccidiomycosis and others), viral infections, especially cytomegalovirus infection in patients infected with the human immunodeficiency virus (HIV), which causes AIDS, and rarely hemorrhage into the adrenal glands in patients with antiphospholipid syndrome or shock.
Addison's disease may also occur in association with other endocrine and non-endocrine autoimmune disorders in conditions involving multiple glands (autoimmune polyglandular or polyendocrine syndromes). And it may rarely be caused in congenital conditions such as adrenal leukodystrophy, a condition that only affects males, and in triple A syndrome.
DIAGNOSIS
Over time, cortisol insufficiency causes the pituitary gland to continuously secrete the hormone ACTH in an effort to correct the problem. As a result cortisol and aldosterone levels are low and ACTH levels are high. In addition, sodium levels are low, and potassium levels are elevated. Tests of dynamic function such as the ACTH stimulation test can be used to determine if cortisol deficiency is due to a damaged adrenal gland or an impaired pituitary response. Blood tests for dynamic adrenal function are described in my article on Adrenal Insufficiency and tests used to determine if the problem is autoimmune are described in my blog on Adrenal Antibodies.
Imaging tests, usually MRI and CT scans, show diminished adrenal gland tissue in patients with Addison's disease. MRI is superior in distinguishing adrenal masses, and CT is superior in showing calcifications related to tuberculosis infection.
Tissue studies vary depending on the type of adrenal gland destruction. In autoimmune Addison's disease, the adrenal glands are characterized by infiltration of lymphocytic white blood cells. Surviving tissue shows atypical cell nuclei due to the prolonged ACTH stimulation. In patients with adrenal destruction caused by sarcoidosis or malignancy, granulomatous lesions are seen.
TREATMENT
Patients with Addison's disease are treated with synthetic cortisol preparations, such as cortisone (Cortone) or hydrocortisone (Hydrocortone, Cortef) and synthetic preparations of Fludrocortisone (Florinef) in patients with reduced aldosterone levels. Dexamethasone (Decadron, Baldex, and Dexone) may also be used for patients with adrenocorticol deficiency in patients with hypersensitivity to cortisone or who have viral, fungal or tubercular skin infections. Correct dosing of cortisol is accomplished by monitoring urine cortisol levels, and mineral status due to low aldosterone is measured with serum potassium levels and plasma rennin concentrations. Treatment may need to be adjusted during times of stress or infection.
The copyright of the article Addison's Disease in Endocrine Disorders is owned by Elaine Moore. Permission to republish Addison's Disease in print or online must be granted by the author in writing.
Can the blood levels of cortisol show that a person is suffering from
Addison's disease? Would the levels be low or high?
Oct 26, 2008 9:47 AM
Elaine Moore :
Hi, A low cortisol level can suggest adrenal insufficiency, and
Addison's disease is a type of adrenal insufficiency. If cortisol is low,
other tests, such as the cortysn stimulation test and tests for adrenal
antibodies are used to diagnose Addison's.
Nov 2, 2008 2:59 AM
Guest :
Hi, I have been tested for Addison'd disease, the baseline was 44 30
minutes was 309 and 60 minutes 409, I have not had any of this explained to
me and was wondering if anyone knows the what the levels should be. I have
been told these are low but my Doctor was reluctant to send me onto a
Specialist...Thanks S
Jan 15, 2009 5:59 PM
Guest :
Can brain lesions be present with Addisons?
Can Addisons be
misdiagnosed as MS?
My wife was diagnosed with MS but is now
being tested for Addisons? Could there be a connection?
Jan 15, 2009 6:37 PM
Elaine Moore :
Hi, Addison's doesn't typically cause brain lesions. It's possible to
have both MS and Addison's, and people with one autoimmune disorder have an
increased risk for developing a second autoimmune disorder. Addison's is
easy to diagnose with blood tests for adrenal hormone levels. Best,
Elaine
Jan 16, 2009 9:22 PM
Guest :
Elaine...thanks, I had read online that occassionally Addisons was
misdiagnosed as MS. Is that even possible? Have you ever heard of
this?
We hope to take the blood tests for Addison in the next
week.
Jan 17, 2009 7:54 AM
Elaine Moore :
Hi, I hadn't heard of Addison's being misdiagnosed as MS, but it's
certainly possible. I meet many people who are diagnosed incorrectly. MS is
often misdiagnosed and frequently turns out to be Lyme disease, CIDP,
Guillain-Barre syndrome or a variant of MS such as Devic's syndrome. Most of the people I know with Addison's disease do have the bronze skin
tone or hyperpigmentation mentioned above. President John Kennedy had
Addison's and his son may have also had it. Typically, Addison's causes low
blood pressure, weight loss and increased sweating. These symptoms cause it
often to be confused with hyperthyroidism although many people with
Addison's have hypothyroidism once the final diagnosis is in. Best, Elaine
Jan 26, 2009 7:53 PM
Guest :
Hi Elaine: In 2005 I was diagnosed with Fibromyalgia. Adrenal
Insufficiency was then diagnosed in April of 2007; IGg Insufficiency in
August of 2007; and Sarcoidosis in September of 2008. Can Sarcoidosis be
the cause of the other disorders? Also, CT and MRIs show "a cyst-like
lesion" on my left adrenal gland. Might this "cyst" be a
granuloma instead? Any help would be greatly appreciated.
-
Marcia
Jan 27, 2009 7:18 AM
Elaine Moore :
Hi, According to this article
www.pulmonologychannel.com/sarcoidosis/symptoms.shtml sarcoidosis can
affect almost any organ except the adrenal gland.
People with
one autoimmune disorder are at higher risk for developing other autoimmune
disorders. In the case of adrenal insufficiency the glandular deficit is
corrected but the immune dysfunction isn't usually addressed. For instance,
people aren't told to watch for environmental triggers or follow diets that
would help with immune system healing.
Cysts are usually easy to
distinguish from solid masses like granulomas. And with adrenals not
usually affected by sarcoidosis it probably is a cyst.
Fibromyalgia is trickier to diagnose since there aren't any specific
blood tests. Trigger points are used for diagnosis but this can be a vague
approach since people can have pain in trigger points caused by other
conditions. Best, elaine
see my website at www.elaie-moore.com
Jan 29, 2009 3:53 PM
Guest :
I was diagnosed in '07 with Addisons disease and breast cancer exactly one
year later. I just completed a double mastsectomy. Ouch!!!! Two weeks later
went into a Addisonian crisis due to lack of corteff. Do you think the two
diagnosises are related? Am I a candidate for more cancer?
Jan 29, 2009 8:15 PM
Elaine Moore :
Hi, See this link from Web MD:
http://www.webmd.com/a-to-z-guides/understanding-addisons-disease-basics
Cancer cells can spread and injure the adrenal glands so there
could be a link here. This shouldn't cause a risk of other cancers. Best,
Elaine
Jan 30, 2009 6:18 PM
Guest :
Re: Addison's and brain MRI result
I had auto/allo stem cell
transplants in 2001 for multiple myeloma. I am in complete clinical
remission, but was diagnosed with Addison's in 2003 after trying to wean
off of the treatment steroids for over two years. MRI showed smaller than
normal adrenals. Multiple cortisol stim test results indicated adrenal
insufficiency. I am on 20 mg of hydrocortisone per day and have extreme
muscle weakness, muscle pain, and fatigue. Since being discharged as a
transplant patient, I have been unable to get any medical support for my
Addison's other than the hydrocortisone prescriptions. Now, an MRI (taken
due to a TIA) has indicated there are "microvascular" changes in
my brain--the neurologist pointed out"clouds" of pale grey areas
spread out over what apparently should have been darker grey.
Question: 1) Is 20 mg of cortisol sufficient for some kind of quality of
life? I have never had a urine test to monitor my level. 2) Are you
aware of an correlation between Addison's and an MRI as described above?
Thank you for such incredible and much needed information.
Jan 31, 2009 3:33 PM
Elaine Moore :
Hi, I'm sorry to hear that you're not feeling well. My background is
in laboratory medicine so I can help with test interpretations but I'm
limited when it comes to MRI. If you do a search on PubMed,
www.ncbi.nlm.nih.gov/pubmed/ you'll find abstracts for a number of
journal articles. Most suggest that changes are seen when leukodystrophy is
present or during changes associated with Addisonian crisis. You're
correct in that more lab tests are needed. You'd need an aldosterone level
to see if you need to be on Florinef as well as hydrocortisone and better
monitoring of blood and urine cortisol levels. It's almost important to
determine the cause of Addison's. For instance, tests for adrenal
antibodies would tell if the condition is autoimmune. Best to you, Elaine
Feb 13, 2009 4:00 AM
Guest :
Hi, I have low borderline thyroid, deficent estrogen (33years),
chronic candida, low cortisol, seizures and my right side of body in muscle
spasm / weakness came on sudden with stress a year ago and stayed the
same. I am under Barts and wanted to know if this low cortisol could
cause my spasm weakness on the right side and if it will get better.. My neckis taught, lower facual weakness but i notice its worse at
times.. I have hypoglycemia and suffered a seizure aswell, anxiety,
cant handle stress, nausea, when family crisis and weakness came on i lost
1/2 a stone quickly with dioreah, and was shaking for a week and change
personality.. LOads more i could say but dont want to bore anyone..so
sick of it all Mandy Thanks
Feb 13, 2009 8:11 AM
Elaine Moore :
Hi Mandy, You might want to read this article on polyglandular
syndrome http://www.suite101.com/blog/daisyelaine/1534
and
this article on the thyroid adrenal connection http://endocrine-disorders.suite101.com/article.cfm/the_thyroid_and_adren
al_connection
Also, do a search for APECED.
With the
new ranges for TSH (recommended 0.3-3.0) you may have subclinical rather
than borderline hypothyroidism. This can cause some of the symptoms you're
mentioning. Best, Elaine
Feb 16, 2009 7:10 PM
Guest :
Hi, I have bee ill for the past 11 months since the birth of my baby. But
I've always had a slight fatigue feeling most of my life early in the day.I
have hyperpigmentation which I've had for about 15 years and about a year
ago when I began feeling really bad I found a few hypigmentations on my
gums that was confirmed today it is hyperpigmentation by a dentist. I have
extreme fatigue, low blood pressure,loss of appetite, and so many other
symptoms. I am curious does Addisons symptoms get worse with menstrual
cycle in any way? Also if your cortisol is low does your aldosterone level
get low also? One more thing if my cortisol was tested when I 1st became
sick and it was normal with basic serum test does it take a certain amount
of time to show up with just a basic cortisol blood test, or is that not an
accurate reading? thanks
Feb 16, 2009 7:32 PM
Elaine Moore :
Hi, I'm sorry to hear you haven't been feeling well. Hyperpigmentation and low blood pressure are common symptoms of Addison's
although they can also be symptoms of other disorders.
It's true
that symptoms and signs in autoimmune disease such as Addison's can occur
before blood tests show changes characteristic of Addison's. Usually, if
the cortisol level is low, other confirmatory tests are ordered. And along
with a cortisol level, an aldosterone level is usually run. Some, but not
all people with Addison's, have low levels of mineralocorticoids and
require Florinef. An endocrinologist can help you get a proper diagnostic
workup.
Feb 28, 2009 5:06 PM
Guest :
Please, please, PLEASE I need some help! I live on Long Island, in New
York. I have been diagnosed with Addison's for about three years. Quite
honestly, the endocrinologist is still tinkering with my meds to get levels
to an acceptable level. I am presently taking Florinef and Cortef.
On top of this, however, I was diagnosed with breast cancer in
September 2008. I underwent a left breast lumpectomy and sentinel node
removal on November 13, 2008. Post-surgically, I developed an infection
(MRSA), that has been resistant to any antibiotic except vancomicin. I
have been hospitalized twice for IV Vanco, and each time the infection has
returned. I started radiation therapy February 2, 2009, but on February 23
I had to stop because the infection was back, even though I was taking
Augmentin. I have developed blisters on my breast that have opened. I
also have ongoing cellulitis and edema.
The radiation oncologist
says it's not related to radiation. The surgeon says it's not related to
surgery, but to my Addison's. My endocrinologist is refraining from
comment because he doesn't have privileges at the hospital at which I'm
being treated. The infectious disease specialist says it has to do with my
immune system.
Needless to say, each specialist seems to point a
finger at another specialty as the cause for my condition. They all seem
to be at a loss for an answer. All the while, my condition gradually
worsens, and my frustration level has reached near-panic proportions. All
I want is to get rid of the infection and finish my cancer treatment so I
can move on. Can you point me in a direction where I might find some
answers? Thank you. Fran
Mar 1, 2009 9:40 AM
Elaine Moore :
Hi Fran, I'm sorry to hear all of the problems you've had of late. Here's a link to an article I wrote last week on MRSA and other
superbugs. www.emaxhealth.com/1035/39/29397/mrsa-other-superbugs-continue-threaten-h
ealth.html
Your MRSA infection is most likely a hospital
acquired, rather than a community acquired, infection. It doesn't sound
like your infection is as resistant to Vancomycin as it should be. MRSA
can also mutate and you could be infected with multiple strains. It seems
that your priority is in getting the infection in control.
The
problem is that specialists often only what to deal with their area of
specialty. Of all your doctors, your surgeon and your primary care
physician are the ones most likely to help you eradicate the infection
unless they're too busy trying to avoid blame or point at others. You
might also call the infection control department at the hospital you
stayed at if you were an inpatient. Tell them how long you've been dealing
with the infection and get the hospital's infection control doctor
involved. He or she can work with your doctor to take a more aggressive
approach at treating your infection.
It's true that certain
drugs, particularly chemotherapeutic drugs, suppress or slow down your
immune system. This makes infections more likely. Your oncologist should
also be working with the infection control doctor to adjust your meds
appropriately so that MRSA doesn't take hold.
Your cortisol and
aldosterone levels are affected by stress, medications, and your immune
system. The immune system, endocrine system and nervous system all work
together. Anything that affects your immune system like antibiotics and
infection and immunosuppressant drugs will affect your endocrine levels.
Stress affects your nervous system and this also affects your cortisol and
aldosterone levels.
I would think your endocrinologist would
have to make regular changes while you're battling infection and
undergoing radiation and other cancer treatments. I don't see your
adrenals as causing the other problems. Rather your Addison's is being
affected by all that's going on. Because these same factors can influence
thyroid function and people with Addison's often develop hypothyroidism,
you should make sure you're having thyroid function tests at least
annually. Hypothyroidism can make infections harder to treat and affect
your overall health. You might want to ask about this the next time your
other endocrine levels are checked.
Best, Elaine
Mar 17, 2009 10:37 AM
Guest :
Hi Elaine, I'm somewhat of a medical mystery, so I've been told by many
doctors I've seen over the years. I was diagnosed w/Addisons at age 19,
Rhematoid Arthritis at 24, Diabetis at 30, Hypothyroidism at 35, and high
cholesteral at 40. I have two questions: 1. Any idea as to what
might go wrong next in my immune system? 3. How can I strengthen my
immune system? Thank you!
Mar 17, 2009 11:59 AM
Elaine Moore :
Hi, You might want to read my articles on polyglandular syndromes
(also known as polyendocrine disorders) and on multiple autoimmune syndrome
autoimmunedisease.suite101.com/article.cfm/multiple_autoimmune_ syndrome
The high cholesterol, while not an autoimmune condition, is a key
feature in hypothyroidism. Often, restoring adequate FT4 and FT3 levels
helps reduce elevated cholesterol levels.
You're correct in that
your goal is to strengthen and not stimulate the immune system.
Immunomodulators like the plant sterols and sterolins and low dose
naltrexone help. And it can help to avoid environmental triggers such as
aspartame in nutrasweet, environmental toxins, processed foods, and any
known or suspected allergens. Many people have found improvement following
a nutrient-rich whole foods diet, using fish oil supplements to correct the
omega-3 and omega-6 balance and incorporating light exercise such as yoga
or pilates. Best, Elaine
Mar 30, 2009 9:44 PM
Guest :
Hi, I have been experiencing health problems for years, and have been
in and out of doctor offices since I was 14 (I am not 24). I was always
told it was probably hormonal, puberty, depression, etc. No matter what I
did, my symptoms got worse. At age 21, out of desperation, I went to the
Mayo Clinic and the doctors found that I had numerous health problems. I
went back a couple times and was supposed to go back one more time, but the
dreaded age 22 came around where I was no longer covered on my father's
health insurance. Since then, I cannot get insurance due to pre-existing
conditions, otherwise I would go to a doctor for this. So instead, for
now, I'm relying on my own research. I have been diagnosed with a
number of problems, but what is missing is a direct "link"
between them. The last thing I was tested for before losing my insurance
was my cortisol level. They took it on a few different dates, and it was
always low. I was supposed to have further testing, but that never
happened due to insurance problems. My problems are: low blood
pressure (they diagnosed me with neurally mediated syncope, but never
checked for an underlying problem), hypoglycemia, super low body
temperature, anemia (low iron and b12), extreme fatigue (my biggest
complaint), excessive sweating, my thyroid has tested low before but the
levels have been inconsistent, my hair falls out in clumps, I'm
underweight, salt cravings, and of course, low cortisol. My ANA is also
positive, which I know is an indication of a potential auto-immune problem.
Anything a rheumatologist might specialize in has been ruled out, as I was
able to see one consistently before I lost my insurance. Lupus, rheumatoid
arthritis, etc have all been rules out. I have not yet followed up with an
endocrinologist after my initial Mayo Clinic visit. However, I am
missing one key sign for this disease, which is hyperpigmentation. My
sister, on the other hand, has all the same symptoms and problems that I
have, and she has dark spots and "splotches" all over her face.
She's had this for years and always assumed it was sun-related, but it does
not look like normal freckling. My question is, is it possible to have
this disease without hyperpigmentation? I'm debating on paying cash for an
appointment with an endocrinologist, but I can't waste time and multiple
appointments on something I couldn't possibly have due to lack of
hyperpigmentation.
Mar 30, 2009 9:45 PM
Guest :
Hi, I have been experiencing health problems for years, and have been
in and out of doctor offices since I was 14 (I am now 24). I was always
told it was probably hormonal, puberty, depression, etc. No matter what I
did, my symptoms got worse. At age 21, out of desperation, I went to the
Mayo Clinic and the doctors found that I had numerous health problems. I
went back a couple times and was supposed to go back one more time, but the
dreaded age 22 came around where I was no longer covered on my father's
health insurance. Since then, I cannot get insurance due to pre-existing
conditions, otherwise I would go to a doctor for this. So instead, for
now, I'm relying on my own research. I have been diagnosed with a
number of problems, but what is missing is a direct "link"
between them. The last thing I was tested for before losing my insurance
was my cortisol level. They took it on a few different dates, and it was
always low. I was supposed to have further testing, but that never
happened due to insurance problems. My problems are: low blood
pressure (they diagnosed me with neurally mediated syncope, but never
checked for an underlying problem), hypoglycemia, super low body
temperature, anemia (low iron and b12), extreme fatigue (my biggest
complaint), excessive sweating, my thyroid has tested low before but the
levels have been inconsistent, my hair falls out in clumps, I'm
underweight, salt cravings, and of course, low cortisol. My ANA is also
positive, which I know is an indication of a potential auto-immune problem.
Anything a rheumatologist might specialize in has been ruled out, as I was
able to see one consistently before I lost my insurance. Lupus, rheumatoid
arthritis, etc have all been rules out. I have not yet followed up with an
endocrinologist after my initial Mayo Clinic visit. However, I am
missing one key sign for this disease, which is hyperpigmentation. My
sister, on the other hand, has all the same symptoms and problems that I
have, and she has dark spots and "splotches" all over her face.
She's had this for years and always assumed it was sun-related, but it does
not look like normal freckling. My question is, is it possible to have
this disease without hyperpigmentation? I'm debating on paying cash for an
appointment with an endocrinologist, but I can't waste time and multiple
appointments on something I couldn't possibly have due to lack of
hyperpigmentation.
Mar 31, 2009 9:39 AM
Elaine Moore :
Hi, With autoimmune diseases patients usually have a cluster of
predominant symptoms but they don't have every single symptom. Also,
symptoms can change over time. Some of the people I know with Addison's
look tan (think President JFK Kennedy) rather than hyperpigmented. The skin
can have a bronze tinge but it's not necessarily noticeable. I see that
rather than blotchy hyperpigmentation. If you're uncertain and don't
have insurance you might find a doctor in your area who doesn't take
insurance but bills minimally for an office visit. Or you could call to see
the price of an endo visit and the price of a GP visit. Anyone can order
the tests you need and in most states you can arrange the lab tests through
www.healthcheckusa.com. best, elaine
Jun 15, 2009 8:43 AM
Elaine Moore :
Hi, The cortisol is a good test for diagnosing adrenal insufficiency.
Adrenal insufficiency is a very rare disorder compared to hypothyroidism,
which is the most common autoimmune disorder. Many of the symptoms of
adrenal insufficiency mimic symptoms of hypothyroidism. People with
long-standing severe untreated hypothyroidism can have some symptoms of
adrenal insufficiency that are corrected when thyroid replacement hormone
is started.
You might want to see how you feel after starting
thyroid replacement hormone. In true adrenal insufficiency having adequate
replacement hormone can make adrenal insufficiency more pronounced. If you
have the typical bronze skin coloring seen in Addison's patients you could
ask your doctor to repeat the cortisol in a few months. Best, Elaine
Aug 11, 2009 7:45 PM
Elaine Moore :
Hi, It's possible that the ACTH injection caused an increase in
cortisol and that reduced your son's symptoms. The cortisol results will
show if there is there is adrenal insufficiency. Here's a link to some info
on the test from the national library of medicine. www.nlm.nih.gov/medlineplus/ency/article/003696.htm
Best,
Eaine
Aug 24, 2009 5:22 PM
Elaine Moore :
Hi, I'd probably get another opinion on bariatric surgery from a
surgeon experienced in this procedure. There have been several recent
studies published showing that bariatric surgery is much safer now than it
was a decade ago. You probably also want to ask your endo about his
or her objections. Are your adrenal function tests wildly erratic or are
you in pretty good control on meds? Best, elaine
