Week 2: Addison's disease

Question 1

Etiology of adrenal insufficiency

Answer 1

1. Primary: adrenal gland destruction
   - autoimmune- 70%
   - tuberculosis -20%
   - other - 10%
2. Secondary: loss of ACTH/CRH
   - exogenous glucocorticoids
   - cure of Cushing’s syndrome
   - hypothalamic/pituitary disease

Question 2

Actions of glucocorticoids: Type 1 and Type 2 responses

Answer 2

1. Type I GC receptor (aka MC receptor)
   - health/wellbeing. High affinity and low capacity.
   - promotes anabolism, sustains response to catecholamines, maintains lean body mass, preserves normal vascular tone, cognitive function, clearance of free water, reproductive function
2. Type 2 GC receptor
   - illness/fasting, low affinity, high capacity
   - high energy mobilization: increase blood glucose, promotes muscle catabolism, hepatic glycogenolysis and gluconeogensis
   - increases insulin resistance
   - modulates immune response: prevents overshooting through various mechanisms, e.g. blocking cytokines, block WBC egress from circulation, decrease lymphocytes, increase neutrophils

Question 3

Clinical features of adrenal insufficiency

Answer 3

1. Chronic
   - weakness, weight loss, fatigue, anorexia, nausea, vague ab pain, diarrhea, orthostatic dizziness, salt craving, depression, decrease in libido
   - hyperpigmentation of skin, scars, areas of repeated trauma, vitiligo, (patients look dirty)
2. Acute
   - myalgias/arthralgias, severe abdominal pain, nausea, vomiting, postural hypotension,
   - fever, dehydration, marked hypotension, altered sensorium

Question 4

Laboratory findings in adrenal insufficiency

Answer 4

• hyponatremia
• metabolic acidosis
• hypoglycemia
• anemia: normochromic, normocytic
• eosinophilia
• hyperkalemia
• prerenal azotemia
• hypercalcemia- rare
• neutropenia
• lymphocytosis

Question 5

Diagnosis of adrenal insufficiency

Answer 5

1. Acute
   - clinical signs and symptoms
   - serum cortisol level9 mg rise is normal. 15 normal
   - cortisol15 normal, <15=AI

Question 6

Therapy for acute and chronic adrenal insufficiency

Answer 6

ACUTE
-IV hydration with normal saline
-IV glucocorticoids
CHRONIC
-glucocorticoid replacement, hydrocortisone 15mg/5mg
-mineralocorticoid replacement, fludrocortisone 0.1mg
-medalert and education: serum K= levels for adequency of fludrocortisone dose, symptoms for adequacy of hydrocortisone dose, double daily hydrocortisone dose with stress

Question 7

Primary vs secondary adrenal insufficiency: symptoms+labs

Answer 7

PRIMARY
-weight loss
-wasting
-hyperpigmentation
-hyper K+
-elevated ACTH w/ low cortisol
-low cortisol with 3 day ACTH stimulation test
SECONDARY
-weight gain
-obesity
-normal pigmentation
-normal K+
-low ACTH+low cortisol
-normal cortisol after ACTH stimulation test for 3 days