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group_3_presentation_2_-_addison_s_disease [2017/03/10 22:50]
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group_3_presentation_2_-_addison_s_disease [2018/01/25 15:18] (current)
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    ​Figure 1: Overview of Addison'​s Disease    ​Figure 1: Overview of Addison'​s Disease
 Image from: http://​www.organsofthebody.com Image from: http://​www.organsofthebody.com
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 ====== Signs and Symptoms ====== ====== Signs and Symptoms ======
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 +   Table 1: Michels & Michels, 2014
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 <style justify>​The symptoms of Addison’s disease begin gradually. As the disease progresses and more of the adrenal glandular tissue is destroyed, symptoms tend to worsen from mild to severe. This can take up to a few years, and because these symptoms are generalized and similar to many other health conditions, Addison’s disease may not even be diagnosed until the patient suffers from an Addisonian crisis (Sarkar et al., 2012). <style justify>​The symptoms of Addison’s disease begin gradually. As the disease progresses and more of the adrenal glandular tissue is destroyed, symptoms tend to worsen from mild to severe. This can take up to a few years, and because these symptoms are generalized and similar to many other health conditions, Addison’s disease may not even be diagnosed until the patient suffers from an Addisonian crisis (Sarkar et al., 2012).
  
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 Because these symptoms are slow to progress and very generalized,​ an event of illness or accident can spontaneously worsen the condition and lead to an Addisonian crisis. The crisis is characterized by sudden, penetrating pains in the lower back, abdomen, or legs, combined with severe vomiting and diarrhea (Sarkar et al., 2012). This leads to severe dehydration,​ drastic drop in blood pressure, and loss of consciousness. Other associated symptoms include pale, cold, and clammy skin, sweating, and rapid, shallow breathing (Sarkar et al., 2012). It is important that a patient suffering from an Addisonian crisis seeks emergency medical assistance. If left untreated, it can lead to shock, seizures, coma, or even death (Sarkar et al., 2012). ​ Because these symptoms are slow to progress and very generalized,​ an event of illness or accident can spontaneously worsen the condition and lead to an Addisonian crisis. The crisis is characterized by sudden, penetrating pains in the lower back, abdomen, or legs, combined with severe vomiting and diarrhea (Sarkar et al., 2012). This leads to severe dehydration,​ drastic drop in blood pressure, and loss of consciousness. Other associated symptoms include pale, cold, and clammy skin, sweating, and rapid, shallow breathing (Sarkar et al., 2012). It is important that a patient suffering from an Addisonian crisis seeks emergency medical assistance. If left untreated, it can lead to shock, seizures, coma, or even death (Sarkar et al., 2012). ​
  
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-   Table 1: Michels & Michels, 2014 +
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    ​Figure 3: Sarkar et al., 2012    ​Figure 3: Sarkar et al., 2012
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 ====== Diagnosis ====== ====== Diagnosis ======
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 +   ​Figure 4: Michels & Michels, 2014
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 <style justify>​Due to the subtlety and non-specificity of Addison’s disease, early diagnosis can be difficult. Presentation of the symptoms relates to the degree of cortisol, mineralocorticoid,​ and adrenal androgen deficiency (higher degree of deficiency equates to more severe symptoms) (Michels & Michels, 2014). There are three main types of tests that are used in combination to diagnose Addison’s:​ <style justify>​Due to the subtlety and non-specificity of Addison’s disease, early diagnosis can be difficult. Presentation of the symptoms relates to the degree of cortisol, mineralocorticoid,​ and adrenal androgen deficiency (higher degree of deficiency equates to more severe symptoms) (Michels & Michels, 2014). There are three main types of tests that are used in combination to diagnose Addison’s:​
  
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 A metabolic panel is a complete blood analysis that serves as a broad-spectrum medical screening tool. This type of test provides a rough evaluation of kidney and liver function, and the balance of serum electrolytes and fluid, using a blood sample drawn from the patient in question (2005). Along with this, the physician also requests serum cortisol levels to be tested early in the morning (8 a.m.). Low cortisol levels are the most evident clinical feature of Addison’s (Michels & Michels, 2014). If the results demonstrate low serum cortisol concentrations (<83 nmol/L), hyponatremia (<135 mmol/L) (Simon, 2016), and hyperkalemia (>5.5 mEq/L) (Lederer, 2016), the physician then requests a cosyntropic stimulation test (Michels & Michels, 2014). This type of test measures cortisol response to ACTH levels. An abnormal rise in ACTH levels (>11 pmol/L) is indicative of underlying cortisol deficiency (Michels & Michels, 2014). Therefore, this type of test is the first-line test for confirming diagnosis of Addison’s disease. Initially, plasma levels of cortisol, ACTH, aldosterone,​ and renin should be measured, followed by administration of 250 mcg of synthetic ACTH (Michels & Michels, 2014). After 30-60 minutes of intravenous ACTH administration,​ serum cortisol levels are measured again (Michels & Michels, 2014). Less than 497-552 nmol/L peak cortisol levels in the blood is diagnostic for adrenal insufficiency (Michels & Michels, 2014). A summary of the metabolic panel is shown in Figure 4. A metabolic panel is a complete blood analysis that serves as a broad-spectrum medical screening tool. This type of test provides a rough evaluation of kidney and liver function, and the balance of serum electrolytes and fluid, using a blood sample drawn from the patient in question (2005). Along with this, the physician also requests serum cortisol levels to be tested early in the morning (8 a.m.). Low cortisol levels are the most evident clinical feature of Addison’s (Michels & Michels, 2014). If the results demonstrate low serum cortisol concentrations (<83 nmol/L), hyponatremia (<135 mmol/L) (Simon, 2016), and hyperkalemia (>5.5 mEq/L) (Lederer, 2016), the physician then requests a cosyntropic stimulation test (Michels & Michels, 2014). This type of test measures cortisol response to ACTH levels. An abnormal rise in ACTH levels (>11 pmol/L) is indicative of underlying cortisol deficiency (Michels & Michels, 2014). Therefore, this type of test is the first-line test for confirming diagnosis of Addison’s disease. Initially, plasma levels of cortisol, ACTH, aldosterone,​ and renin should be measured, followed by administration of 250 mcg of synthetic ACTH (Michels & Michels, 2014). After 30-60 minutes of intravenous ACTH administration,​ serum cortisol levels are measured again (Michels & Michels, 2014). Less than 497-552 nmol/L peak cortisol levels in the blood is diagnostic for adrenal insufficiency (Michels & Michels, 2014). A summary of the metabolic panel is shown in Figure 4.
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-   ​Figure 4: Michels & Michels, 2014 
  
  
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-   ​Figure ​3: The three zones of the adrenal cortex.+   ​Figure ​5: The three zones of the adrenal cortex.
 Image from https://​www.britannica.com/​science/​adrenal-gland. Image from https://​www.britannica.com/​science/​adrenal-gland.
  
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-   ​Figure ​4: The hypothalamus,​ pituitary gland & adrenal glands make up the HPA axis. +   ​Figure ​6: The hypothalamus,​ pituitary gland & adrenal glands make up the HPA axis. 
 Image from http://​www.integrativepro.com/​Resources/​Integrative-Blog/​2016/​The-HPA-Axis. Image from http://​www.integrativepro.com/​Resources/​Integrative-Blog/​2016/​The-HPA-Axis.
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-   ​Figure ​5: Comparing Primary Adrenal Insufficiency to Secondary/​Tertiary Adrenal Insufficiency. ​+   ​Figure ​7: Comparing Primary Adrenal Insufficiency to Secondary/​Tertiary Adrenal Insufficiency. ​
 Image from: http://​www.prn.org/​index.php/​complications/​article/​hiv_osteoporosis_adrenal_insufficiency_85. Image from: http://​www.prn.org/​index.php/​complications/​article/​hiv_osteoporosis_adrenal_insufficiency_85.
  
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-   ​Figure ​6: Molecular Immunopathogenesis of Primary Adrenal Insufficiency.+   ​Figure ​8: Molecular Immunopathogenesis of Primary Adrenal Insufficiency.
 Image from: (Charmandari,​ Nicolaides & Chrousos, 2014) Image from: (Charmandari,​ Nicolaides & Chrousos, 2014)
  
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-   ​Figure ​7: Oral tablets which replenish bodily hormones. ​+   ​Figure ​9: Oral tablets which replenish bodily hormones. ​
 Image from: http://​www.mcguffmedical.com,​ http://​www.drsfostersmith.com Image from: http://​www.mcguffmedical.com,​ http://​www.drsfostersmith.com
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 **Injection Alternatives** **Injection Alternatives**
    
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 Since some individuals experience nausea leading to vomiting as a symptom, intravenous or intramuscular cortisol injections can replace the oral tablets (Mayo Clinic, 2015). ​ Since some individuals experience nausea leading to vomiting as a symptom, intravenous or intramuscular cortisol injections can replace the oral tablets (Mayo Clinic, 2015). ​
  
    
 It is strongly recommended that individuals with the disease carry a cortisol injection kit with them in case of Addisonian/​Adrenal Crisis (Canadian Addison Society, 2017). In the appropriate hospital setting, receiving an intravenous dose of hydrocortisone and dextrose sugar in saline solution would be an ideal treatment for the adrenal crisis (Mayo Clinic, 2015). Otherwise, the individual or family member can follow the appropriate instructions to inject the hydrocortisone intramuscularly into a large muscle, typically the thigh (quadricep muscle) (Canadian Addison Society, 2017).  ​ It is strongly recommended that individuals with the disease carry a cortisol injection kit with them in case of Addisonian/​Adrenal Crisis (Canadian Addison Society, 2017). In the appropriate hospital setting, receiving an intravenous dose of hydrocortisone and dextrose sugar in saline solution would be an ideal treatment for the adrenal crisis (Mayo Clinic, 2015). Otherwise, the individual or family member can follow the appropriate instructions to inject the hydrocortisone intramuscularly into a large muscle, typically the thigh (quadricep muscle) (Canadian Addison Society, 2017).  ​
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-   ​Figure ​8: Injection kit should be carried on the person in case of Addisonian crisis. ​+   ​Figure ​10: Injection kit should be carried on the person in case of Addisonian crisis. ​
 Image from: http://​www.addisons.org Image from: http://​www.addisons.org
  
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-  Figure ​9: Intramuscular injection into a large muscle is usually recommended;​ typically the thigh. ​+  Figure ​11: Intramuscular injection into a large muscle is usually recommended;​ typically the thigh. ​
 Image from: www.addisonsociety.ca Image from: www.addisonsociety.ca
  
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-Oral tablets, intravenous injections and intramuscular injections are current hormone replacement therapies for Addison’s Disease, however, there have been many clinical trials considering continuous subcutaneous hydrocortisone infusions (CSHI) as a better treatment option. A 2014 study investigated the efficacy of CSHI versus conventional oral hydrocortisone (OHC) replacement and the subcutaneous infusions showed improvements in normalization of ACTH and cortisol levels and improvements in quality of life (Oksnes et al., 2014). As shown in figure ​10, the infusions got the morning blood cortisol levels back to normal ranges as opposed to the oral tablets (Oksnes et al., 2014). Cortisol levels should be high in the morning and the infusions reestablished this to the normal range (Oksnes et al., 2014). ​+Oral tablets, intravenous injections and intramuscular injections are current hormone replacement therapies for Addison’s Disease, however, there have been many clinical trials considering continuous subcutaneous hydrocortisone infusions (CSHI) as a better treatment option. A 2014 study investigated the efficacy of CSHI versus conventional oral hydrocortisone (OHC) replacement and the subcutaneous infusions showed improvements in normalization of ACTH and cortisol levels and improvements in quality of life (Oksnes et al., 2014). As shown in figure ​12, the infusions got the morning blood cortisol levels back to normal ranges as opposed to the oral tablets (Oksnes et al., 2014). Cortisol levels should be high in the morning and the infusions reestablished this to the normal range (Oksnes et al., 2014). ​ 
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-  Figure ​10: Morning cortisol levels in the CSHI condition are up to normal circadian levels; OHC condition levels are still low.+  Figure ​12: Morning cortisol levels in the CSHI condition are up to normal circadian levels; OHC condition levels are still low.
 Image from: (Oksnes et al., 2014) Image from: (Oksnes et al., 2014)
  
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-   ​Figure ​11: All-cause mortality in Addison'​s patients, between 1987-2001, in Sweden.+   ​Figure ​13: All-cause mortality in Addison'​s patients, between 1987-2001, in Sweden.
 Image from: Bergthorsdottir et al., 2006 Image from: Bergthorsdottir et al., 2006
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-   ​Figure ​12: Medical bracelets help convey information.+   ​Figure ​14: Medical bracelets help convey information.
 Image from: http://​www.myidentitydoctor.com Image from: http://​www.myidentitydoctor.com
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