How to Diagnose Addison’s disease (مرض أديسون)
Addisons Disease (primary adrenal insufficiency, مرض قصور الغدة الكظرية الاولي) is an endocrine disorder of the adrenal cortex that is commonly caused by autoimmune glandular injury, it is characterized by hypocortisolism, hypoaldosteronism, and hypoadrenalism.
Autoimmune adrenal insufficiency affects the three cortical layers, it is usually caused by impaired function of autoreactive T cells and 21-hydroxylase autoantibodies.
Cortisol is a glucocorticoid produced in response to stress or hypoglycemia by the zona fasciculata, which is the largest of the three cortical layers accounting for nearly 80% of the volume of the cortex. The zona fasciculata is located between the zona reticularis and zona glomerulosa.
Aldosterone is a mineralocorticoid produced by the zona glomerulosa, which is the outer layer of the adrenal cortex.
Pathogenesis of hypocortisol
Low blood cortisol levels can be caused by the following disorders:
Primary adrenal insufficiency is a condition characterized by impaired adrenal function and the inability to produce enough amounts of cortisol hormone. Adrenal failure is characterized by decreased serum Na and increased serum K, Ca. 
Secondary adrenal insufficiency is a condition caused by ACTH insufficiency. ACTH is a hormone messenger that moves brain signals to the adrenals instructing them to secrete more cortisol. Moreover, decreased amounts of ACTH often impairs the secretion of aldosterone and results in hypoaldosteronism.
Main symptoms of addisons disease include:
Weakness, hypocortisol leads to carbohydrate insufficiency and hypoglycemia due to increased gluconeogenesis, which increases glycogen deposition; however, chronic increased gluconeogenesis increases protein catabolism, where the body breaks down its own muscle and converts it into glucose for quick energy.
Fatigue, mitochondrial myopathy and low blood pressure reduces the mean time mitochondrial perfusion, while the mean response time of mitochondrial oxygen consumption is increased due to stress, which provokes lactic acidosis and induces cellular hypoxia and dyspnea, which in turn may lead to reduced ability to work hard.
Abdominal pain, hypoaldosteronism reduces fluid retention in the kidneys and can lead to low fluid levels in the body (decreased levels of extracellular and intracellular fluid), thus increasing the thickness of your stool, which may make it harder to defecate and waste will not promptly pass out of the intestines, especially with low blood pressure or impaired tonus, constipation is a common issue in most patients with addisons disease.
Nausea, constipation and abdominal bloating may cause nausea and vomiting.
Weight loss, loss of appetite, chronic stress, and low fluid levels (due to frequent urination) can lead to weight loss.
Low blood pressure, hypoaldosteronism leads to low fluid levels in the body, which may cause low blood pressure.
Hyperpigmentation (Darkened skin), is a common pathological dermatological disorder in which patches of skin become darker, which occurs when an excess of melanin forms deposits in the skin. Hypocortisolism leads to hyperactivity in the hypothalamic-pituitary-adrenal axis. The overactive pituitary gland secretes excess amounts of ACTH (that regulates the secretion of cortisol in the adrenals) and β-Melanocyte-stimulating hormone (responsible for the synthesis of melanin or skin pigment). Increased β-MSH promotes an increase in melanin pigment and causes increased pigmentation of the skin. Moreover, hypocortisol decreases glycogen storage in adipose tissue (fat tissue under the skin), which reduces the inner surface of the skin. Furthermore, low aldosterone level leads to low intracellular fluid volume (the cytoplasm is made of ~90% water), which results in cellular collapse, and for this reason, the skin, which is rich in melanin will look much darker.
Dizziness when standing up (light-headedness), which is caused by postural hypotension, it occurs as a result of abnormal blood pressure regulation. Normally, blood pressure drops to the feet and trunk due to gravity, but in hypotensive patients, dizziness may be felt for just a few seconds or minutes before it subsides, as the body compensates by secreting adrenaline that stimulates extra contractions of the heart muscles.
Adrenaline and stress response, the process of adrenaline secretion
Stressors stimulate the epinephrine secretory command center (ESCC) in the brain, which in turn stimulates the adrenal medulla to release adrenaline or epinephrine into blood.
Stress or anxiety stressors (life problems, dark thoughts, work issues, house trouble, etc.) trigger the hypothalamus to secrete CRH, which stimulates the pituitary to release ACTH. The cells of the adrenal cortex produce cortisol hormone (a glucocorticoid) in response to ACTH.
The adrenals secrete cortisol to coup with stress in two steps:
By increasing blood sugar levels quickly, thus providing the body with enough energy. 
Regulating the level of fat deposition by converting androstenedione to oestrone, which is a weak endogenous estrogen capable of altering stress. Women are more anxious than men, but since oestradiol is a much stronger estrogen, they are less susceptible to depression and other health problems related to stress than men. Patients suffering of cortisol deficiency are more likely to develop stress and depression.
Diagnostic Laboratory Tests
Laboratory Tests to measure Cortisol and ACTH levels in blood
1- Acth stimulation test (cosyntropin test), is the test of choice for diagnosis of primary adrenal insufficiency or addisons disease. The physician draws a sample of blood and measures the levels of cortisol and Acth before injecting the patient with cosyntropin (*), then he draws another sample of blood 30-60 minutes after injection of cosyntropin to recheck the levels of Cortisol and ACTH. In normal people, an increase in cortisol levels is observed.
2- Insulin tolerance test, is a test used to diagnose primary and secondary adrenal insufficiency; however, it is contraindicated in patients with ischemic heart disease and epilepsy.
The physician injects insulin to reduce blood glucose level, then he draws blood periodically to measure cortisol as glucose level drops. More specifically, Low blood glucose level stimulates the pituitary to secrete more ACTH, which in turn stimulates the adrenal glands to secrete cortisol. In normal people, an increase in cortisol levels is observed.
Other common responses to this test include sweating, rapid heart rate (pulse), and excessive hunger.
3- CRH stimulation test, is a test used to diagnose primary adrenal insufficiency (crh acth cortisol negative feedback). The physician injects Corticotropin Releasing Hormone (CRH) (a). CRH stimulates the pituitary gland to secrete ACTH (b), which in turn stimulates the adrenals to secrete cortisol hormone (c).
Interpretation of Results
The presence of excessive ACTH levels (b), in the absence of high serum cortisol levels (c) suggests primary adrenal insufficiency (addison’s disease).
The absence of reaction (b) suggests secondary adrenal insufficiency, whereas a delayed CRH response (b) suggests a problem in the hypothalamus.
4- Imaging tests provide a picture of the body’s internal organs and tissue. CT of the abdomen and MRI of the brain are often used to rule out tumors, atrophy, and other functional abnormalities.
5- Blood tests show high serum potassium level (hyperkalemia), low serum sodium level (hyponatremia), and increased BUN (blood urea nitrogen).
Addison’s Disease etiology pathogenesis and diagnosis