What are the layers of the adrenal gland (superficial to deep)?
- Zona Glomerulosa (Cortex)
- Zona Fasciculata (Cortex)
- Zona Reticularis (Cortex)
In what portion of the adrenal are the following steroids made?
Aldo - Zona Glomerulosa
Andro - Zona Reticularis
Cortisol - Zona Fasiculata and Reticularis
What are the naturally occuring glucocorticoids, mineralocorticoids, and sex hormones made w/i the adrenal?
- Gluc - Cortisol
- Mineral - Aldosterone and Deoxycorticosterone
- Sex Hormones - Testosterone, Estradiol, Estrone
Describe the general mechanism of glucocorticoid action
Describe the hypothalamic-pituitary-adrenal axis
Describe glucocorticoid metabolic effects. What is the overarching goal of these metabolic effects?
- Increase gluconeogenesis
- Release amino acids through muscle catabolism
- Inhibit peripheral glucose uptake
- Stimulate lipolysis
GOAL: Maintain adequate glucose for the brain
What are the glucocorticoid effects on inflammation?
Overall anti-inflammatory effects
- Upreg. of anti-inflamm proteins
- Downreg. of pro-inflamm proteins
- Decreased WBC presence and function at sites of inflamm
Four major effects of excess cortisol?
- Inhibition of bone formation (osteoporosis)
- Suppression of calcium absorption
- Delayed wound healing
- Catabolic effects on skin, connective tissue, msucle, peripheral fat, lymphoid tissue
What two proteins (mentioned in lecture) are upregulated by aldosterone?
- Epithelial Na+ channel expression
Blood concentrations of cortisol are 2000x higher than aldosterone. How then does aldo exhibit any tissue specific effect whatsoever?
In aldo-specific cells, 11Beta-Hydroxysteroid Dehydrogenase Type 2 converts active cortisol into inactive cortisone.
What are the two most significant regulators of aldosterone secretion?
- Extracellular K+ concentration
- Angiotensin II
What are the general goals of modifying molecular structure of corticosteroids?
- Affinity of steroid for mineralocorticoid vs. glucocorticoid receptors
- Extent of protein binding
What is the most commonly used synthetic mineralocorticoid? What is its mineralocortioid activity compared to cortisol?
Fludrocortisone; 125x > cortisol
A patient has decreased levels of cortisol and aldosterone. ACTH is elevated. Dx?
Primary adrenocortical insufficiency
A patient has low cortisol and low ACTH. Dx?
Secondary adrenocortical insufficiency
What are two major causes of secondary adrenal insufficiency?
- Suppression from exogenous glucocorticoid Tx
A patient presents with symptoms that make you suspect adrenal insufficiency. Since you're a clever med student, what do you look for to differentiate betwixt the two?
Secondary Adrenal Insufficiency has:
- NO hyperpigmentation
- Near-normal aldosterone levels
What are precipitating causes of acute adrenal crises?
- Events such as trauma, sepsis, surgery (ie stress) in chronic adrenal insufficiency
- Hemorrhagic destruction of gland
- Rapid withdrawal of steroids
Describe the method used in order to diagnose adrenal insufficiency
- Administer Cosyntropin
- Normal: cortisol > 18 ug/dL, Abnormal: cortisol < 18 ug/dL
Describe the strategy for primary adrenal insufficiency treatment
Glucocorticoid: Highest dose Hydrocortisone in the morning and lower dose in the afternoon (mimic diurnal variation)
Mineralocorticoid: Fludrocortisone once a day. Liberal salt intake
How should primary adrenal insufficiency Tx be changed in a patient with minor febrile illness? Severe stress/trauma?
- Minor febrile: Increase glucocorticoid dose 2x-3x for a few days of illness. Do NOT increase mineralcorticoid
- Stress/trauma: Inject prefilled Dexamethasone IM
Describe the steroid coverage for those with primary AI going into surgery with moderate illness, major illness, those going into moderately stressful surgery and major surgery.
Moderate illness: Hydrocortisone (HC) 50 mg PO BID/IV
Severe Illness: HC 100 mg IV Q 8hr
Moderate Surgery: HC 100 mg IV just before procedure
Major Surgery: HC 100 mg IV before anesthesia and then Q8 hr for first 24hr
Describe the process of treating a patient with an acute adrenal crisis
Obtain blood for serum cortisol, renin, ACTH but do not delay Tx while waiting for definitive proof of Dx
Large amounts of IV fluid
High-dose IV glucocorticoids: Dexamethasone 4 mg IV every 12-24 hr if no previous Dx of adrenal insufficiency, Hydrocortisone 100 mg IV every 6 hrs until stable
Why should hypotonic solution not be used in acute renal crises?
It will worsen hyponatremia
- Two examples of ACTH-dependent glucocorticoid excess?
- Two examples of ACTH-independent glucocorticoid excess?
- Pituitary Adenoma (Cushing's disease), Ectopic ACTH production (SCLC)
- Adrenal adenoma or carcinoma
Describe the procedure used to diagnose Cushing's syndrome.
- Measure ACTH
- 24 hr cortisol excretion
- Low-dose overnight dexamethasone suppression test
- Midnight salivary cortisol level
Dx requires at least TWO of these tests to be positive
Describe the findings of a dexamethasone suppression test on a patient with Cushing's Syndrome
Normally, a patient would have suppressed ACTH and cortisol, but in a patient with CS, cortisol remains high
What will be the general lab findings of ACTH and Cortisol in a patient with:
- ACTH independent process?
- ACTH dependent process?
- Low ACTH, High Cortisol
- High ACTH, High Cortisol
What is a risk of surgical treatment of Cushing's Syndrome?
Patients are at risk for adrenal insufficiency due to abrupt drop in cortisol levels
What are the 5 medications to treat Cushing's Syndrome? Mechanisms?