Name the enzyme responsible for converting cortisol to cortisone in the kidney
Why is this ezyme important/protective?
It prevents over-activation of the mineralcorticoid receptor by excess cortisol (cortisone is the inactive form)
What causes deficient cortisol in secondary adrenal insufficiency?
What is the clinical presentation of adrenal insufficiency?
- Fatigue, malaise, lack of energy
- GI: nausea, vomiting, anorexia leading to weight loss
- Hypotension leading to dizziness and orthostasis
- Increased pigmentation
- Salt craving
What is the key lab abnormality in adrenal insufficiency?
Why is hyperkalemia seen in only primary adrenal insifficiency?
Hyperkalemia is seen in primary due to deficient aldosterone production, leading to deficient excretion of potassium
Give two genetic conditions that present with adrenal insufficiency
- Congenital adrenal hyperplaia
Give some drug-related causes of adrenal insufficiency
- Withdrawal from corticosteroid therapy
- Narcotics (suppress CRH/ACTH)
- Adrenostatic/lytic therapy (ketoconazole, etomidate, mitotane)
- Glucocorticoid receptor antagonists: mifepristone
What is the cosyntropin test?
Synthetic ACTH test
Evaluation of maximum adrenocortical secretory capacity. Used to detect adrenal destruction (primary insufficiency) or atrophy (secondary insufficiency)
In either form of insufficiency, cortisol will fail to rise adequately (<18ug/dL response at 30-60 minute mark, or basal cortisol <5ug/dL)
True or false: plasma ACTH is always increased in patients with primary adrenal insufficiency
What should plasma ACTH levels be in secondary adrenal insufficiency?
secondary: low or normal (inappropriately not increased)
Measurement of what arenal androgen is a sensitive marker of adrenal reserve? Why is this important?
A normal DHEAS level is very unusual in a patient with any type of adrenal insufficiency
Why might chronically/critically ill patients and women on oral contraceptives present with misleading cortisol levels?
Alterations in CBG (cortisol binding proteins) will be present in both
Critically/chronically ill: decreased CBG. These patients may have low total cortisol due to lack of CBG, but still have normal levels of biologically active cortisol
Women taking oral contraceptives may have higher total cortisol due to an increase in CBG. Increased total cortisol does not reflect an increase or alteration in adrenal function in these patients.
Name (7) broad etiologies for primary adrenal insufficiency
- Adrenal hemorrhage (bilateral)
- Inflitrative disorders (amyloidosis, etc)
- Drugs - including ketoconazole, metyrapone, mitotane, etomidate
Why does withdrawal from exogenous corticosteroid therapy cause secondary adrenal insufficiency?
The adrenals are atrophied due to long-standing negative feedback inhibition of ACTH by the exogenous corticosteroids. As medication is withdrawn, the atrophied adrenals may not be able to produce sufficient cortisol in response to rising ACTH levels.
Explain the therapeutic approach for acute adrenal crisis
- Administer hydrocortisone (100mg IV every 6 hours for 24 hours)
- When stable, decrease dose to 50mg every 6 hours and taper to maintenence levels (10mg?)
- Support with isotonic glucose/containing fluids
Explain the treatment strategy for primary adrenal insufficiency
How does this differ from the management of secondary adrenal insufficiency?
Primary Adrenal insufficiency
- Give hydrocortisone (corticosteroid replacement) 10-15mg in the morning and 5-10mg in the afternoon
- monitor sense of well-being, plasma ACTH, give injectable hydrocortisone for emergencies
- Give fludrocortisone (mineralcorticoid replacement) 50-100mch daily
- monitor electrolyte composition and plasma renin activity
Secondary adrenal insufficiency
- Hydrocortisone 7.5-15mg daily in divided doses - lower doses than primary because there is some cortisol secretion from the adrenals
- Mineralcorticoid replacement is not needed
- Sick day management, adrenal crisis, and surgical steroid coverage still apply
Explain approach to steroid coverage in a adrenal insufficient patient undergoing surgery