Running head: THE OPTIMAL TREATMENT FOR ADDISON S DISEASE 1 Kelly Wetmore Merrimack College
2 Introduction Addison s disease is a rare autoimmune disorder caused by the body s destruction of its own adrenal glands. This destruction ultimately leads to the kidneys inability to produce two vital hormones, cortisol and aldosterone. This malfunction of the immune system results in the body viewing the adrenal glands as a foreign body or invader that it must attack. The resulting attack leads to damage to the adrenal cortex and glands; which system has the specific role of secreting hormones ( Napier & Pearce, 2012 ). Thus, Addison s disease is considered a chronic condition due both to the extensive and irreversible damage to the adrenal cortex and the risk of further damage absent treatment. This autoimmune disease affects 1 in every 100,000 people and is almost twice as prevalent in adult females compared to adult males in the population ( Addison's Disease Self Help Group ). Etiology & Pathophysiology Addison s disease is classified as both one of the autoimmune diseases as well as a congenital condition. In the autoimmune classification, an environmental trigger leads to an immune system or pituitary gland failure in a person who is predisposed. Addison s disease can also be identified at birth. In those non-autoimmune cases, Addison s disease is genetically predetermined; when the adrenal glands in utero are undeveloped or not developed at all, known as adrenal dysgenesis. The cause of autoimmune Addison s disease is unknown, similar to most other autoimmune diseases but certain classes of people such as those with cancer, those taking blood thinners, suffering from chronic
3 infections or those with type 1 diabetes may have a higher risk of developing the disease. These links correlate to the theory that a stressor triggers the disease. Autoimmune Addison s disease makes up 80-90% of diagnoses; whereas the genetic mutation inherited for the rare condition is present in only 5-10% of cases ( Batten, Schummer, & Selden, 2017 ). However, both forms of the disease cause the same type of harm to adrenal function. The functional impairment to the adrenal cortex disrupts the production and secretion of steroid hormones from the adrenal glands, triangle-shaped glands that sit on top of each kidney. One of the hormones that the adrenal glands produce, cortisol, helps the body to respond to stresses such as disease and infection. This hormone helps utilize macronutrients, such as carbohydrates and proteins, and sugars for energy. Without cortisol, the body s immune function and metabolism begin to shut down. Another key hormone secreted by the adrenal glands is aldosterone. This hormone signals the kidneys to regulate the balance of salt and water in the body. The function of regulating the correct concentrations of salt and water is vital for survival. An imbalance can lead to dangerously low levels of blood pressure. Absence of both of these hormones can lead to detrimental effects on the body. Thomas Addison was the first to discover Addison s disease. In the 1800s, when the prevalence of tuberculosis was high, one of the consequences of this infection was damage to the adrenal cortex, and therefore insufficient production of adrenal gland secretions ( Batten, Schummer, & Selden, 2017 ). Due to advances in medicine related to treatment of tuberculosis, it is now rare for tuberculosis to manifest itself in this way.
4 However, as noted above, Addison s disease can develop from other stressors such as chronic infections, but the exact genetic component and trigger causes remain unknown. Although damage to the adrenal cortex, and the inability to secrete hormones is clear upon testing, signs and symptoms are still difficult to identify. This disease has a slow and insidious onset of unfavorable symptoms. The signs and symptoms are so gradual, that only 75% of individuals are aware they have the condition ( Addison's Disease Self Help Group ). It is common for individuals to discover this disease when they seek medical help or testing for another reason. Clinical Presentation Individuals with Addison s disease present a range of symptoms related to the absence of cortisol and aldosterone hormones. These symptoms include dizziness because of low blood pressure, fatigue, nausea, vomiting, depression, muscle and joint pain, sensitivity to temperature, and cravings for salty foods. It is evident that these symptoms can relate to a wide range of other issues and diseases. Addison s disease symptoms are more easily identified when coupled with other noticeable signs, such as, the development of dark patches on the skin, and weight loss due to decreased appetite. Diagnosis and Management Symptoms are insufficient to establish a diagnosis as official diagnosis relies on a blood test for abnormal hormone levels. A blood workup will indicate low sodium levels, high potassium levels, and an elevated white blood cell count. This workup also identifies other conditions often associated with Addison s disease. These conditions can include vitamin B-12 deficiency, type II insulin-dependent diabetes, hypothyroidism, etc.
5 (CareNotes, Truven Health Analytics, 2017). In addition, an X-ray image or CT scan may be helpful to visually detect damage to the adrenal cortex and glands. A short Synacthen test, also known as the ACTH stimulation test also provides a definitive diagnosis. This test measures the amount of cortisol in the blood, thus indicating adrenal failure, if none is present. Once a final diagnosis for Addison s disease is confirmed, lifelong treatment is required in order to prevent further damage and sustain life. Those diagnosed will require steroid replacement therapy. Although patient dependent, most individuals start with 15mg to 25mg of Hydrocortisone in 2 to 3 daily doses to replace cortisol. Most patients will also receive 50mcg to 200mcg of Fludrocortisone to replace aldosterone. Fludrocortisone is usually taken in 1 to 2 daily doses; however, exact dosage will depend upon such factors as blood pressure, renin plasma levels, exercise frequency or intensity, and metabolism. One optional treatment some patients try is DHEA. DHEA is a sex hormone produced by the kidneys, which would otherwise occur naturally in the body, to aid testosterone and estrogen production ( Gurnell et al., 2008 ). This is an unlicensed or experimental treatment. Those diagnosed must be made aware of their prognosis and the importance of treatment. It is a life-long or chronic disorder and one missed steroid replacement is potentially fatal. In addition, blood pressure, metabolism, electrolyte levels, etc. must be closely monitored for interaction. After diagnosis, patients will receive a medical bracelet for emergency situations to let technicians and doctors know of their condition. Emergencies most commonly occur when patients forget their steroid replacement
6 therapy by pill or injection ( Batten, Schummer, & Selden, 2017 ). Patients should make others aware of, and educate them about, their condition. These action steps are vital especially in adrenal crisis when an Addison s disease patient may be unable to self-inject a steroid replacement. In emergencies, it is crucial to have someone available to help. Current Research Steroid replacement therapy, also known as Conventional Glucocorticoid Replacement therapy, is the most common treatment for Addison s disease. However, long-term use can cause possible adverse effects on mortality, morbidity and overall quality of life. In 2014, Clinical Endocrinology, released a study entitled, Circadian hormone profiles and insulin sensitivity in patients with Addison s disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy. This study s aim was to compare the Conventional, most commonly taken as an Oral Hydrocortisone (OHC) therapy, with a Continuous Subcutaneous Hydrocortisone Infusion (CSHI) in Addison s patients ( Bjornsdottir, et al. 2015). The research was conducted to help improve patient symptoms that generally include a reduced glucose intolerance, greater central adiposity, and dyslipidemia. In addition, since all of these factors contribute to a greater risk of heart disease, a better intervention technique could decrease that risk. The study included a treatment course for 12 weeks in two small groups; a 10 patient OHC treatment group and a 15 patient CSHI treatment group. The two groups were closely monitored at night, and each individual had their cortisol level, glucose
7 level, and circadian rhythm measured ( Bjornsdottir, et al. 2015). At the end of the trial, it was evident that the CSHI treatment was more effective than the OHC treatment. Especially at night, the Continuous Subcutaneous Hydrocortisone Infusion (CSHI) treatment resulted in a more stable glucose level and normalized nighttime cortisol levels. This data is consistent with the understanding that a constant subcutaneous administration, through a pump, of glucocorticoid replacement is more effective during overnight sleep especially when compared to a conventional glucocorticoid replacement of an oral therapy that is taken just 2-3 times during the day. Conclusion Addison s Disease is a rare chronic disease, which is difficult to diagnosis because of the slow onset of symptoms, which mimic problems in other disorders, and diseases. However, since there are available blood tests and diagnostic tools that allow for definitive diagnosis practitioners should be more attuned to patients complaints since earlier intervention can help prevent damage and improve daily living. In addition, since regulation of doses is vital to treatment more research is needed on treatment modalities such as the pump for constant administration of replacement hormones. References Napier, C., & Pearce, S. H. (2012, December). Autoimmune Addison's disease. Retrieved October 23, 2017, from https://www.ncbi.nlm.nih.gov/pubmed/23177474 Addison's Disease Self Help Group. (1984). What is Addison's Disease? Retrieved October 23, 2017, from http://www.addisons.org.uk/ Batten, D., Schummer, P., & Selden, H. (2017). Addison's Disease (3rd ed., Vol. 1, Human Diseases and Conditions). Retrieved October 22, 2017, from http://go.galegroup.com/ps/retrieve.do?tabid=t003&resultlisttype=result_l
8 IST&searchResultsType=SingleTab&searchType=BasicSearchForm tposition=1 &docid=gale%7ccx3630000012&doctype=disease%2fdisorder overview&sort=relevance&contentsegment=&prodid=gvrl&contentset= GALE%7CCX3630000012&searchId=R2&userGroupName=mlin_n_merrcol&in PS=true&u=mlin_n_merrcol&authCount=1#notes CareNotes, Truven Health Analytics. (2017). Addison disease (Health & Wellness Resource Center) Retrieved October 22, 2017, from proxy3.noblenet.org/login?url=http://go.galegroup.com/ps/i.do?p=hwrc&sw=w &u=mlin_n_merrcol&v=2.1&id=gale%7ca503762082&it=r&asid=9fa4ad4a8 3ec1fbb8ca5e8b2b4cf9a2f Gurnell, E. M., Hunt, P. J., Curran, S. E., Conway, C. L., Pullenayegum, E. M., Huppert, F. A.,... Chatterjee, V. K. (2008, February). Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial. Retrieved October 23, 2017, from https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2729149/ Bjornsdottir, S., Oksnes, M., Isaksson, M., Methlie, P., Nilsen, R.M., Hustad, S., Bensing S. (2015). Circadian hormone profiles and insulin sensitivity in patients with Addison s disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy (Clinical Endocrinology). Retrieved October 23, 2017, from http://web.b.ebscohost.com.proxy3.noblenet.org/ehost/detail/detail?vid=4&sid=0 1d1ce10-83c8-42e4-8225-9c8c1d6ff143%40sessionmgr103&bdata=JkF1dGhUe XBlPWlwJnNpdGU9ZWhvc3QtbGl2ZSZzY29wZT1zaXRl#AN=103341199&db =hch