Addison disease is a chronic primary adrenal insufficiency which can be due to atrophy from exogenous cortisol intake, or due to destruction.
Atrophy of the adrenal glands can occur due to exogenous intake of high dose corticosteroids. After roughly a week of glucocorticoid intake, CRH and ACTH secretion decreases, and prolonged intake leads to physical atrophy of the adrenals. Beyond this point, it may take months to restore adrenal function, and patients may suffer from adrenal insufficiency.
Destruction of the adrenal gland can be due to many etiologies. One common cause is autoimmune adrenalitis, while others include metastases of cancer from other organs, hemorrhage from Waterhouse-Friderichsen syndrome, amyloidosis or infection (TB, coccidiomycosis).
Due to adrenal deficiency, hormones regularly produced are no longer secreted. Thus, patients have deficiencies in aldosterone and cortisol.
A common manifestation of Addison disease is skin flexure and mucous membrane hyperpigmentation. John F. Kennedy's bronzed skin was attributed to being afflicted with Addison disease.
In Addison disease, there is a decrease of adrenal hormone secretion, but a large increase in ACTH. The precursor to ACTH is POMC (proopiomelanocortin), and is also a precursor to MSH (Melanocyte stimulating hormone). As the demand for ACTH increases, an increase in its precursor also leads to excess MSH production, leading to hyperpigmentation.
Decreased aldosterone leads to hypotension, or a decrease in blood pressure. Aldosterone works on Na+/K+ pumps to resorb Na+, which is followed by water, leading to decreased blood volume, and subsequently, pressure.
As aldosterone works on Na+/K+ pumps in the distal tubule and collecting ducts, it works to maintain homeostasis of K+, Na+, and fluids. In this disease, a lack of aldosterone means that excess K+ is not secreted into the tubular lumen. This can lead to hyperkalemia in patients.
Metabolic acidosis occurs because Na+ resorption in the distal tubule is linked with H+ secretion under the influence of aldosterone. Low levels of aldosterone in the renal distal tubule leads to sodium wasting in the urine, and more importantly, excess H+ retention in the serum. This leads to acidosis.
Severe adrenal insufficiency leads to Addisonian crisis, which is a potentially life-threatening medical emergency which needs intervention. Patients can display coma, fever, convulsions, hypoglycemia, lethargy, and eventually death.
Diagnosis of Addison disease is supported with the ACTH stimulation test. A synthetic ACTH analog known as cosyntropin is administered either intramuscularly or intravenously. Serum cortisol levels are measured before and after this. If cortisol levels remain low after the injection, patients can be diagnosed with the disease.
Treatment for this disease is to replace the missing cortisol to mimic normal physiologic levels.
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