Addison’s Disease:The insufficiency of adrenal glands
IntroductionAddison’s Disease is a rare and chronicdisease that is characterized by adrenalinsufficiencyThere is a decrease in hormones in theadrenal cortex such as glucocorticoids andmineralocorticoids6-110 cases diagnosed per 100,000 in theworld per year.1.4 million deaths per year around theworld.Usually effects 30-50 year-olds, but can beseen in all ages
HistoryFirst discovered by Thomas Addison in 1855First described as an infection of the adrenal gland- mostcommonly TB.Now instead of infection, its most commonly characterizedby an autoimmune destruction of the adrenal glands
Causes of the DiseaseThree different causes of the diseaseAdrenal Dysgenesis:Genetic CausesImparied Steriodiogensis:Congenital Adrenal HyperplasiaAdrenal Destruction:Autoimmune destruction
Causes of DiseaseAdrenal Destruction:Most common type in industrialized worldAffects humoral and cell-mediated responsesImmune reaction against enzyme 21-hydroxylase, acytochrome P450 enzyme.Normal functioning 21-hydroxylase catalyzes the additionof an “-OH” on carbon 21 in steroidsAddison’s Disease has an enormous amount ofautoantibodies attack this enzyme and slowly kill off theadrenal cortex.82.5% of autoantibodies are adrenal antibodies
SymptomsChronic fatigueMuscle WeaknessWeight loss, Nausea, DiarrheaHyperpigmentationHypercalcemia, Hypoglycemia, Hypoatremia, andHyperkalemiaEsinophilia and LymphocytosisMetabolic acidosisAddisonian Crisis:Severely low blood pressure and potential coma or death
How Are the Hormones Affected?When Addison’s disease goes into affect, the Anteriorpituitary produces excessive but ineffective amounts ofAdrenocorticotropic (ACTH) to the adrenal cortex thushindering its ability to produce and release hormones(Glucocorticoids and Mineralocorticoids).Since there is no ACTH to stimulate the adrenal cortexto release its hormones, the adrenal cortex can notrelease hormones to regulate processes in the body.
Normal Negative FeedbackThe hypothalamus releases hypothalamic inhibitory orreleasing hormones to the anterior pituitary.The anterior pituitary then releases ACTH to the adrenalcortex.The adrenal cortex will then release Glucocorticoids (toraise blood glucose levels or to replenish glucose duringor after stressful situations) or Mineralocorticoids (toreabsorb sodium and excrete potassium in order tobalance water in the body).When their functions are completed, the target tissuesof the hormones will release their own hormones back tothe hypothalamus in order to stop the release ofhormones to affect the body.
Normal negative feedback loopsTarget tissueHormone of targettissue
Disrupted Negative Feedback The anterior pituitary releases excessive yet ineffective amountsof ACTH which is supposed to stimulate the adrenal cortex. The adrenal cortex as a result is affected negatively and does notrelease Glucocorticoids or Mineralocorticoids. Since Glucocorticoids are not produced, glucose cannot bereplenished when stressful situations occur. Since Mineralocorticoids are not produced, there is a lack ofsodium and water in the body thus leading to severe dehydration. Also, because ACTH exists in excessive yet ineffective amounts,bronzing of the skin occurs because ACTH is linked to melaninproduction.
Diagram of disrupted negativefeedbackExcessive and ineffectiveamounts ofAdrenal cortexhormones are notreleased
DiagnosisDetermined by low level of adrenal hormone afterstimulation with synthetic ACTH hormone tetercosactideShort Test:Compares blood cortisol levels before and after250 micrograms of tetracosactide if abnormal go to long testLong Test:1 mg of tetracosactide is administered and blood taken at 1, 4, 8,and 24 hours later
Current TreatmentReplacement corticoidsteroids or fludrocortisoneacetateDoses change according to lifestyle, i.e. stress, infectionor injuryHave to carry emergency injection of hydrocortisoneand card/bracelet indentifying their condition
Clinical TrialsRevival of Stem Cells in Addison’s StudyAims to regenerate adrenocorticolsteroidogenic cell functions by stimulationproliferation and differentiation of progenitorcells in order to replace damaged adrenalcortex cells
Conclusion and Future StudiesIt’s a rare but detrimental disease if left untreatedManageable disease through hormone therapy and helpsindividuals lead a normal lifeFuture StudiesDeveloping a time release capsule to better mimic thenatural fluctuations of the cortisol production