Addison's disease

Question 1

Addison’s disease

Answer 1

• Adrenal insufficiency, can be 1o or 2o
• 1o adrenal insufficiency is usually autoimmune, sometimes TB, or other diseases (fungal infection, AIDS, metastatic disease)
• 2o adrenal insufficiency is usually due exogenous GCCs or hypothalamic/pituitary disease

Question 2

Physiology of GCCs 1

Answer 2

• GCCs (cortisol) is released from zona fasciculata when ACTH is released from pituitary (stored as POMC), which is released when CRH is released from hypothalamus
• GCCs can bind to 2 types of receptors
• T1 receptors (MCCR: during health/well fed) are high affinity, low capacity receptors (permissive for normal function) that promote general anabolism, sustains response to catecholamines, preserved normal vascular tone, regulates free H2O clearance, boosts reproductive function, supports mentation

Question 3

Physiology of GCCs 2

Answer 3

-T2 receptors (GCCR: fast/illness) are low affinity, high capacity (turns off normal function for times of stress) that increase blood glc, promote muscle catabolism, hepatic GNG and glycogenolysis, increases insulin resistance and lipolysis, blocks cytokines/lyphocytes/eosinophils but increases PMNs, increases CO in response to catecholamines

Question 4

Signs and Sx of adrenal insufficiency

Answer 4

• Chronic Sx: weakness, weight loss, fatigue, anorexia, nausea, ab pain, diarrhea, orthostatic dizziness, salt craving
• Chronic signs: hyperpigmentation (dirty look- esp of mucous membranes), scars, vitiligo
• Acute Sx: muscle and joint pain, severe ab pain, nausea/vomiting, postural hypotension
• Acute signs: fever, dehydration, marked hypotension, altered sensorium, decreased bowel sounds
• These pts look sick and are often hemodynamically unstable

Question 5

Lab findings

Answer 5

• Normochromic, normocytic anemia (ACD)
• Neutropenia w/ eosinophilia and lymphocytosis
• Metabolic acidosis and prerenal azotemia
• Hypoglycemia, hyponatremia (can’t clear free water), hyperkalemia

Question 6

Dx of acute addison’s

Answer 6

• Pt has signs/Sx (10-20) w/ unexplained hypotension, hyponatremia +/- hyperkalemia then do serum cortisol
• Serum cortisol can be drawn at any time of day (diurnal variation doesn’t matter), because if its some other acute stress the cortisol level will be high
• If addison’s the cortisol level will be <20

Question 7

Dx of chronic addison’s

Answer 7

• Must draw serum cortisol in the morning when the levels are supposed to be high (if they are drawn at night the levels are supposed to be low so won’t tell you anything)
• If serum cortisol is 15 no AI
• Can also do ACTH stimulation test, same as acute: give cosyntropin (acts like ACTH) after getting baseline cortisol, then re-measure cortisol
• If cortisol increases >9mg there is normal adrenal function, if not then suspect addison’s (doesn’t tell you if its secondary or primary due to atrophy of the adrenal gland in both)

Question 8

Distinguishing btwn 2o and 1o AI

Answer 8

• Fasting ACTH/cortisol: in primary the ACTH will be elevated and the cortisol low (appropriate)
• In secondary the ACTH will be low and cortisol low (inappropriate)
• Can also do cortisol stimulation (longer test, 3 days of 8 hour ACTH infusions, then measure AM cortisol): cortisol rises then the AI is 2o (adrenals are intact and responding appropriately)
• If cortisol doesn’t rise then the AI is 1o and adrenals are the problem

Question 9

Signs/Sx of 2o vs 1o AI

Answer 9

• Primary: weight loss/wasting, hyperkalemia, hyper pigmentation
• Secondary: weight gain/obesity, normal K, normal pigmentation

Question 10

Rx of AI

Answer 10

• Acute: need to meet demands of the stress so give 300mg of hydrocortisone in 3 doses (1 100mg dose every 8 hrs)
• Chronic: physiologic hydrocortisone replacement of 20-30mg in 2 10-15mg doses (AM and PM) + mineralcorticoid replacement (depending on serum K and BP)
• VERY IMPORTANT: pts must double their doses then they get sick (during stress)