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Addison’s Disease: Overview of Antibodies & Genetic Links

Addison’s disease, also known as primary adrenal insufficiency, is an endocrine condition involving destruction of parts of the adrenal gland (which sits atop the kidney), resulting in a deficiency of the steroid hormones produced by this gland, including cortisol and aldosterone.  It can have many causes, though the two most common are autoimmune (in developed countries) and infectious (in developing nations) in nature.  Good info can be found from National Adrenal Diseases Foundation and MedicineNet.com.  Below we discuss some important aspects of this disease, as regards genetics, inheritance and common antibodies.

Which antibody tests are positive in Addison’s disease?

It has been postulated for quite some time that organ-specific antibodies, directed mistakenly against one’s own tissues – in this case, the adrenal cortex – are responsible for the manifestations of autoimmune disease according to studies published by the Journal of Translational Immunology and the Journal of Clinical Endocrinology and Metabolism.

There are three known potential adrenal proteins targeted by anti-cortical antibodies (ACAs):

  • 21-hydroxylase (21-OH)
  • 17-hydroxylase (17-OH)
  • Cytochrome P-450

Of these, the most commonly used test is for antibodies to 21-OH, since the other two proteins are also found in non-adrenal tissues, making them less specific and confirmatory for Addison’s.  The test will likely be called an adrenal (21-OH) antibody test, or something similar.  When positive, there are antibodies in the bloodstream directed against only adrenal cortex tissue, which confirms the presence of autoimmune disease.

Is it possible to test negative for the antibodies and still have Addison’s?

Yes.  Because Addison’s is not always autoimmune in nature – it can also be caused by infection, trauma, cancer and other etiologies – it is possible to have the disease without the presence of any antibodies.

That said, most cases are usually a result of an autoimmune mechanism, and thus a test should reveal some or all of the aforementioned antibodies.  Still, laboratory science is not perfect, being impacted by human and methodological errors as well as sensitivity and specificity issues, which means that it is still possible (though less likely) to test negative, even while having autoimmune Addison’s disease.

If they are asymptomatic, at what age could/should I have my children tested for the antibodies to determine whether they inherited a predisposition for Addison’s?

This is an individual issue that should be decided on a case-by-case basis, after consultation with your endocrinologist and your children’s pediatrician.  Since there is currently no genetic test for Addison’s, it is impossible to know whether they have inherited this predisposition until (if and when) antibodies are formed, which is not generally predictable.  Also, there are several other tests often used prior to antibody testing to determine the diagnosis and treatment of endocrine disorders, and these would probably be administered first.

In most cases, without any indication to do so, doctors would likely be hesitant to perform any such adrenal testing until there are clinical manifestations warranting it.  However, this is again a matter that depends on the suspected cause of your disease, any other disorders present in you or your children, and case-specific circumstances.  For instance, most children with type-1 diabetes will get tested, since having this disease is mildly predictive of developing Addison’s in the future.  All of this should be discussed thoroughly with your physicians.

How is Addison’s disease inherited (e.g., from mother, from father, from both)?

It is not known exactly how Addison’s is passed from one generation to the next.  Most current thinking is that this adrenal disease, when genetically influenced, is a result of something called “polygenic inheritance”, whereby a trait or disease is a consequence of inheriting several genes that code for it.  This results in something called a complex genetic trait or disease, which is thought to be directed and affected by more than one gene, possibly on different chromosomes.

Addison’s is believed to be mostly a genetically complex disease, which makes elucidating the mechanisms of inheritance more challenging.  As with other autoimmune conditions, it is believed that this disorder involves a genetic predisposition that is somehow triggered, resulting in the ensuing autoimmune process.

However, there is a small subset of patients for whom the disease appears to be X-linked, meaning it is passed on by the mother, usually skipping a generation, and only affects male children per an article on DiabetesDaily.com.  And certain forms of Addison’s – when part of a larger endocrine syndrome – do appear to be inherited on a single autosomal recessive gene; meaning both parents must contribute copies for the disease to manifest itself.

Questions for your doctor:

  • Is it necessary for me to have the antibody tests if I’ve already been diagnosed and am receiving treatment?
  • Are there any new studies indicating a greater understanding of Addison’s inheritance or specific genes inherited?
  • If my disease is not autoimmune, what do you think is the cause?
  • What are the chances that the antibody test is negative but I still have autoimmune Addison’s?
  • Should I be concerned about the possibility of my children developing this disorder in the future?  If so, what can I do and when?

 

About the Author
Dr. Rothbard is a professional medical writer and consultant based in New York City, specializing in medical education articles targeted at a variety of audiences, from children through clinicians.  After leaving medicine, he worked as a biology and medical science educator for several years, before deciding to pursue writing full-time.  He may be reached at [email protected].

 

This post contains opinions of the author.  AutoimmuneMom.com is not a medical practice and does not provide medical advice, diagnosis, or treatment.  It is your responsibility to seek diagnosis, treatment, and advice from qualified providers based on your condition and particular circumstances.  Camino Real Ventures, Inc., the company that makes AutoimmuneMom.com available to you, does not endorse nor recommend any products, practices, treatment methods, tests, physicians, service providers, procedures, clinical trials, opinions or information available on this website.  Your use of the website is subject to our Terms of Use and Privacy Policy

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