Endo 03: Adrenals

Front 1

Where are the adult adrenal glands located?

Back 1

- Retroperitoneum
- Above or medial to the upper poles of the kidneys

Front 2

What are the zones of the adrenal glands?

Back 2

Cortex (90% of mass)
- Glomerulosa
- Fasciculata
- Reticularis

Medulla (10% of mass)

Front 3

What is the blood supply to the adrenal glands? Significance?

Back 3

Main arterial supply from branches of:
- Inferior phrenic artery
- Renal arteries
- Aorta

*Prevents ischemic injury to adrenal gland during under perfusion

Front 4

What is the blood drainage to the adrenal glands? Significance?

Back 4

- R adrenal vein drains directly into the posterior aspect of the vena cava
- L adrenal vein drains into the L renal vein before entering the IVC

* Each vein is vulnerable to venous thrombosis and non-traumatic hemorrhage of adrenal glands is often d/t bilateral or unilateral venous thrombosis creating a vascular dam effect

Front 5

What controls steroid production in the zona fasciculata and reticularis?

Back 5

- CRH from the hypothalamus stimulates ACTH in a pulsatile manner
- ACTH stimulates the adrenal steroids

Front 6

What disease process has unregulated cortisol secretion?

Back 6

*Cushing's Disease - an ACTH-secreting pituitary tumor
- Manifested by deregulated cortisol secretion since the set point for negative feedback on ACTH is increased

*Stressors may also stimulate ACTH secretion overriding glucocorticoid negative feedback

Front 7

When is there peak cortisol secretion?

Back 7

Diurnal rhythm which causes a peak before awakening and a decline as the day progresses

Front 8

What is ACTH synthesized from?

Back 8

- Precursor molecule: Pro-opiomelanocortin (POMC) within the ACTH-secreting cells in the pituitary gland corticotroph
- Convertase enzymes direct synthesis and processing of POMC
- ACTH is one of the segments of POMC

Front 9

What causes increased skin pigmentation in primary adrenal insufficiency?

Back 9

Elevated ACTH; ACTH contains the amino acid sequence of alpha-melanocyte stimulating hormone (αMSH) is within the peptide hormone complex

Front 10

What does the cortisol synthetic pathway require?

Back 10

- ACTH-stimulated cholesterol import into the mitochondrion
- Action is initiated by Steroidogenic Acute Regulatory (StAR) protein, which shuttles cholesterol from outer to inner mitochondrial membrane

Front 11

What is the action of the Steroidogenic Acute Regulatory (StAR) protein)?

Back 11

Initiates the ACTH-stimulated cholesterol import from the outer to the inner mitochondrial membrane

Front 12

What stimulates the aldosterone synthesis pathway in the zona glomerulosa?

Back 12

- Angiotensin II
- Potassium
- Acutely, by ACTH

Front 13

What kind of enzymes are the steroidogenic enzymes? Location?

Back 13

Cytochrome P450 enzymes
- Located in the mitochondrion or in the ER membrane

Front 14

Which steroidogenic enzymes are located in the mitochondrion?

Back 14

- Side chain cleavage enzyme
- 11-hydroxylase
- Aldosterone synthase

Front 15

Which steroidogenic enzymes are located in the ER membrane?

Back 15

- 17-hydroxylase
- 21-hydroxylase

Front 16

What is the first precursor derived from cholesterol for steroid synthesis? What enzyme makes this conversion?

Back 16

Pregnenolone
- Generated by Cholesterol Side Chain Cleavage Enzyme (a CYP enzyme)

Front 17

How is Cholesterol converted to Glucocorticoids?

Back 17

1. Cholesterol → Pregnenolone by Side Chain Cleavage Enzyme
2. Pregnenolone → Progesterone by 3β-Hydroxysteroid Dehydrogenase (3-βHSD2)
3. Progesterone → 17-Hydroxyprogesterone by 17-Hydroxylase
4. 17-Hydroxyprogesterone → 11-Deoxycortisol by 21-Hydroxylase
5. 11-Deoxycortisol → Cortisol by 11-Hydroxylase

Front 18

What are the enzymes on the progression from Cholesterol to Cortisol?

Back 18

1. Side Chain Cleavage Enzyme
2. 3β-Hydroxysteroid Dehydrogenase (3-βHSD2)
3. 17-Hydroxylase (P450c17)
4. 21-Hydroxylase (P450c21)
5. 11-Hydroxylase (P450c11)

Front 19

What are the molecules on the progression from Cholesterol to Cortisol?

Back 19

Cholesterol →
1. Pregnenolone
2. Progesterone
3. 17-Hydroxyprogesterone
4. 11-Deoxycortisol
5. Cortisol

Front 20

How is Cholesterol converted to Mineralocorticoids?

Back 20

1. Cholesterol → Pregnenolone by Side Chain Cleavage Enzyme
2. Pregnenolone → Progesterone by 3β-Hydroxysteroid Dehydrogenase (3-βHSD2)
3. Progesterone → 11-Deoxycorticosterone by 21-Hydroxylase
4. 11-Deoxycorticosterone → Corticosterone by 11-Hydroxylase
5. Corticosterone → Aldosterone by Aldosterone Synthase

Front 21

What are the enzymes on the progression from Cholesterol to Aldosterone?

Back 21

1. Side Chain Cleavage Enzyme
2. 3β-Hydroxysteroid Dehydrogenase (3-βHSD2)
3. 21-Hydroxylase (P450c21)
4. 11-Hydroxylase (P450c11)
5. Aldosterone Synthase (P450c11AS)

Front 22

What are the molecules on the progression from Cholesterol to Aldosterone?

Back 22

1. Pregnenolone
2. Progesterone
3. 11-Deoxycorticosterone
4. Corticosterone
5. Aldosterone

Front 23

What happens to cortisol in the circulation?

Back 23

Binds to plasma proteins
- Mainly to Corticosteroid-Binding Globulin (CBG)
- A bit to Albumin

Front 24

How much of cortisol is free in the circulation? Implications?

Back 24

Only 5% is circulating free; bound steroids are biologically inactive

Front 25

How do you measure the free cortisol? Utility?

Back 25

- Can be done in saliva and is independent of the salivary flow rates
- Widely used for the assessment of the hypothalamic-pituitary-adrenal axis, particularly in states of suspected hypercortisolism

Front 26

How is cortisol metabolized and excreted?

Back 26

- Cortisol is metabolized in the liver and kidney
- Some metabolites are excreted in the urine

Front 27

What is the first step in the metabolism of cortisol? Where does it take place?

Back 27

- Cortisol is metabolized to Cortisone
- In kidney by 11β-Hydroxysteroid Dehydrogenase type 2 (11β-HSD2)
- Cortisol can bind mineralocorticoid receptor, but Cortisone can't

Front 28

What is the function of conversion of Cortisol to Cortisone in the liver?

Back 28

- Protects the mineralocorticoid receptor on the tubules of the distal nephron from the action of cortisol
- Cortisol has the same affinity for the mineralocorticoid receptor as aldosterone, but cortisol circulates at 1000x the total concentration

Front 29

How does cortisol affect the mineralocorticoid receptor?

Back 29

Cortisol has the same affinity for the mineralocorticoid receptor as aldosterone, but cortisol circulates at 1000x the total concentration

Front 30

What clinical circumstances may alter the protective effect of 11β-HSD2 on cortisol?

Back 30

- Large increases in cortisol secretion may overwhelm the intra-renal metabolism of cortisol
- This would cause significant mineralocorticoid effects such as HTN and hypokalemia
- Seen in Cushing Syndrome

Front 31

What is important about synthetic glucocorticoids (eg, dexamethasone)?

Back 31

Does not have a high affinity for the mineralocorticoid receptor

Front 32

What happens to the Cortisone produced in the kidney that is not excreted in the urine?

Back 32

It can be converted back into cortisol by 11β-hydroxysteroid dehydrogenase type 1 in the liver and visceral fat

Front 33

Where are 11β-hydroxysteroid dehydrogenase type 1 and type 2 found? Effect?

Back 33

- Type 1: in liver converts cortisone to cortisol
- Type 2: in kidney converts cortisol to cortisone

Front 34

What does cortisol bind to and where to exert its effect?

Back 34

Cortisol interacts with the intracellular Glucocorticoid Receptor (GR)

Front 35

What is the mechanism of action for cortisol?

Back 35

- Cortisol binds in the cytosol of target cells to GR which results in dissociation of heat shock proteins (HSP)
- Cortisol bound GR dimerizes and translocates to the nucleus to activate glucocorticoid response elements (GRE)
- Enhances transcription of genes

Front 36

How does cortisol mediate an anti-inflammatory effect?

Back 36

- Cortisol-bound GR can form heterodimers with transcription factors such as AP-1 or NF-B
- This transrepresses pro-inflammatory genes\

Front 37

Which hormone besides cortisol can bind to the glucocorticoid receptors? Effect?

Back 37

- Corticosterone (precursor of aldosterone)
- It has much weaker binding activity

Front 38

How can patients with a 17-hydroxylase deficiency compensate for their lack of cortisol?

Back 38

They have higher concentrations of Corticosterone (precursor of Aldosterone) which has weak activity on the Glucocorticoid Receptor

Front 39

What is the specificity of the steroid receptors? Implications?

Back 39

- Steroid receptors may not always be specific and may occasionally bind other steroids causing unexpected clinical effects?
- Eg, high dose potent progesterone agents may occupy glucocorticoid receptor and cause cortisol-like effects

Front 40

What steroid compound can stimulate appetite in cancer patients? How?

Back 40

Progesterone compound, Megestrol Acetate - stimulates appetite and causes suppression of ACTH and cortisol

Front 41

What drug can be used for the treatment of endogenous hypercortisolism?

Back 41

Mifepristone - a glucocorticoid receptor antagonist

Front 42

What are the targets of glucocorticoids that impacts intermediary metabolism?

Back 42

- Liver
- Adipose tissue
- Skeletal muscle
- Plasma glucose

Front 43

How do glucocorticoids affect the metabolism in the liver? What are the effects of hypercortisolism and hypocortisolism?

Back 43

- Increases expression of gluconeogenic enzymes
- Hypercortisolism: increases hepatic glucose output, together w/ insulin, increases hepatic glycogen stores
- Hypocortisolism: decreases hepatic glucose output and glycogen stores

Front 44

How do glucocorticoids affect the metabolism in the adipose tissue? What are the effects of hypercortisolism and hypocortisolism?

Back 44

- Permissive for lipolytic signals leading to elevated plasma FFA to fuel gluconeogenesis
- Hypercortisolism: central / truncal obesity, moon facies, and buffalo hump
- Hypocortisolism: decreases adiposity and decreases lipolysis

Front 45

How do glucocorticoids affect the metabolism in skeletal muscle? What are the effects of hypercortisolism and hypocortisolism?

Back 45

- Degrades fibrillar muscle proteins by activating ubiquitin pathway, providing amino acids for gluconeogenesis
- Hyper-cortisolism: muscle weakness and wasting, mainly in proximal muscles; increased urinary nitrogen excretion (urea from amino acids)
- Hypo-cortisolism: muscle weakness, decreased muscle glycogen stores; decreased urinary nitrogen excretion

Front 46

How do glucocorticoids affect the metabolism in the plasma glucose? What are the effects of hypercortisolism and hypocortisolism?

Back 46

- Maintains plasma glucose during fasting (anti-hypoglycemic action); increases plasma glucose during stress
- Hyper-cortisolism: impairs glucose tolerance, insulin-resistant diabetes mellitus, increases plasma glucose d/t peripheral glucose utilization and increases hepatic glucose output
- Hypo-cortisolism: hypoglycemia, increases insulin sensitivity

Front 47

What are the targets of glucocorticoids that impact calcium homeostasis?

Back 47

- Kidney
- Bone, cartilage
- GI tract

Front 48

How do glucocorticoids affect calcium homeostasis in the kidney? What are the effects of hypercortisolism and hypocortisolism?

Back 48

- Decreases reabsorption of calcium
- Hyper-cortisolism: hypercalciuria without hypercalcemia leading to secondary hyper-PTH
- Hypo-cortisolism: retardation of bone growth mainly through decreased GH, hypercalcemia possible

Front 49

How do glucocorticoids affect calcium homeostasis in the bone/cartilage? What are the effects of hypercortisolism?

Back 49

- Inhibits collagen synthesis and bone deposition
- Hyper-cortisolism: retards bone growth and bone age by direct action and by decreasing GH; causes osteoporosis in adults

Front 50

How do glucocorticoids affect calcium homeostasis in the GI tract?

Back 50

Inhibits calcium, magnesium, and phosphate absorption

Front 51

What are the endocrine targets of glucocorticoids?

Back 51

- Hypothalamus and Pituitary
- Pancreas
- Adrenal Medulla

Front 52

How do glucocorticoids affect the hypothalamus and pituitary? What are the effects of hypercortisolism and hypocortisolism?

Back 52

- Decreases endogenous opioid production and depresses gonadotroph responsiveness to GnRH, stimulates GH expression by pituitary, inhibits GH secretion by hypothalamus

- Hyper-cortisolism: scanty menses d/t suppressed gonadotroph sensitivity go GnRH, also suppresses GH secretion by hypothalamic action, minimal suppression of TRH-TSH axis

- Hypo-cortisolism: scanty menses by upregulated CRH-endogenous opioid pathway-mediated suppression of GnRH, suppressed GH secretion, hypothyroidism (if present) is d/t autoimmune mechanism

Front 53

How do glucocorticoids affect the pancreas? What are the effects of hypercortisolism and hypocortisolism?

Back 53

- Inhibits insulin secretion by decreasing efficacy of cytoplasmic Ca2+ on exocytotic process
- Hyper-cortisolism: absolute hyperinsulinemia with relative hypoinsulinemia (lower plasma insulin than expected for the degree of hyperglycemia)
- Hypo-cortisolism: absolute hypoinsulinemia with relative hyperinsulinemia

Front 54

How do glucocorticoids affect the adrenal medulla? What are the effects of hypercortisolism and hypocortisolism?

Back 54

- Increases PNMT expression and activity (epinephrine synthesis)
- Hyper-cortisolism: increases response to sympathoadrenal activation
- Hypo-cortisolism: decreases response to sympathoadrenal activation

Front 55

What are the immune system targets of glucocorticoids?

Back 55

- Thymus / lymphocytes
- Granulocytes
- Erythrocytes

Front 56

How do glucocorticoids affect the thymus / lymphocytes? What are the effects of hypercortisolism and hypocortisolism?

Back 56

- Involution of the thymus
- Hyper-cortisolism: immunocompromised state, lymphocytopenia
- Hypo-cortisolism: relative lymphocytosis

Front 57

How do glucocorticoids affect granulocytes? What are the effects of hypercortisolism and hypocortisolism?

Back 57

- Demargination of neutrophils by suppressing the expression of adhesion molecules
- Hyper-cortisolism: granulocytosis and eosinopenia for peripheral blood
- Hypo-cortisolism: granulocytopenia and eosinophilia for peripheral blood

Front 58

How do glucocorticoids affect erythrocytes? What are the effects of hypercortisolism?

Back 58

- No significant effect
- Hyper-cortisolism: increased hemoglobin and hematocrit

Front 59

How do glucocorticoids affect skin and connective tissue? What are the effects of hypercortisolism and hypocortisolism?

Back 59

- Anti-proliferative for fibroblasts and keratinocytes

- Hyper-cortisolism: easy bruisability d/t dermal atrophy, striae or sites of increased tension, especially sites of adipose tissue accumulation; poor wound healing; hirsutism and acne are d/t ACTH-mediated increase of adrenal androgens; hyper-pigmentation is direct effect of ACTH on melanocortin 1 receptors

- Hypo-cortisolism: darkening of the skin is d/t ACTH-mediated stimulation of melanocortin 1 receptors; vitiligo may occur d/t direct auto-immune destruction of melanocytes in circumscribe areas

Front 60

How do glucocorticoids affect the heart? What are the effects of hypercortisolism and hypocortisolism?

Back 60

- Increased contractility
- Hyper-cortisolism: HTN
- Hypo-cortisolism: lower peripheral resistance, HTN w/ further postural decrease in blood pressure (orthostatic hypotension); low-voltage ECG

Front 61

How do glucocorticoids affect the vasculature?

Back 61

Increased vascular reactivity to vasoconstrictors (catecholamines and AngII)

Front 62

How do glucocorticoids affect Na+, K+, and the ECF volume? What are the effects of hypercortisolism and hypocortisolism?

Back 62

- Increase GFR and non-physiologic actions on mineralocorticoid receptors
- Hyper-cortisolism: hypokalemic alkalosis, increased ECF volume d/t MR activity
- Hypo-cortisolism: hyponatremia, hyperkalemic acidosis, and decreased ECF volume, mainly d/t loss of MR activity

Front 63

What psychiatric parameters of CNS function are affected by glucocorticoids?

Back 63

- Mood
- Appetite
- Sleep
- Memory
- Eye

Front 64

How do glucocorticoids affect the mood? What are the effects of hypercortisolism and hypocortisolism?

Back 64

- Eucortisolemia maintains emotional balance
- Hyper-cortisolism: initially euphoria, but later long-term depression and psychosis
- Hypo-cortisolism: depression

Front 65

How do glucocorticoids affect the appetite? What are the effects of hypercortisolism and hypocortisolism?

Back 65

- Increases appetite
- Hyper-cortisolism: hyperphagia
- Hypo-cortisolism: decreased appetite in spite of improved taste and smell

Front 66

How do glucocorticoids affect the sleep? What are the effects of hypercortisolism?

Back 66

- Suppression of REM sleep
- Hyper-cortisolism: sleep disturbances

Front 67

How do glucocorticoids affect the memory? What are the effects of hypercortisolism?

Back 67

- Sensitizes hippocampal glutamate receptors, induces atrophy of dendrites
- Hyper-cortisolism: impaired memory, bilateral hippocampal atrophy

Front 68

How do glucocorticoids affect the eye? What are the effects of hypercortisolism and hypocortisolism?

Back 68

- Increases intraocular pressure
- Hyper-cortisolism: cataracts and increased intraocular pressure
- Hypo-cortisolism: decreased intraocular pressure

Front 69

What is adrenal insufficiency? What can cause it?

Back 69

- Inadequate production of cortisol from the adrenal cortex

Causes:
- Primary - disease process in adrenal gland
- Secondary - disease process in pituitary gland
- Tertiary - disease process in hypothalamus

Front 70

What are the signs of untreated secondary or tertiary adrenal insufficiency?

Back 70

- Low cortisol
- Low or inappropriately normal ACTH levels (remember, ACTH should be high)

Front 71

What are the signs of untreated primary adrenal insufficiency?

Back 71

- Low cortisol
- Elevated ACTH

- Also, missing aldosterone (hypotension is more common and hyperkalemia may be present)
- Elevated Renin

Front 72

What are the signs and symptoms of adrenal insufficiency?

Back 72

- Fatigue, malaise, lack of energy
- GI: nausea, vomiting, anorexia → weight loss
- Hypotension → dizziness, orthostasis

Front 73

What are the signs and symptoms specific to PRIMARY adrenal insufficiency?

Back 73

- Increased skin pigmentation
- Salt craving

Front 74

What are the lab abnormalities in adrenal insufficiency?

Back 74

* Hyponatremia
- Hyperkalemia (primary)
- Hypercalcemia, hypoglycemia (rare in adults)
- Lymphocytosis

Front 75

What are the potential imaging abnormalities in adrenal insufficiency?

Back 75

- Bilateral adrenal enlargement
- Pituitary mass

Front 76

What concurrent medical problems are associated with adrenal insufficiency?

Back 76

- Severe critical illness with hypotension
- Pituitary disease
- Traumatic brain injury
- Brain radiation

Front 77

What drugs are associated with adrenal insufficiency?

Back 77

- Withdrawal from corticosteroids (oral, inhaled, topical, parenteral)
- Narcotics (suppress CRH/ACTH - common cause of tertiary adrenal insufficiency)
- Adrenostatic / lytic: ketoconazole, etomidate, mitotane
- Glucocorticoid receptor antagonist: mifepristone

Front 78

What should you think if you see a patient with hyponatremia?

Back 78

Adrenal Insufficiency (both primary and secondary) - better check cortisol level

Front 79

What is a common cause of tertiary adrenal insufficiency?

Back 79

Narcotics - suppress CRH/ACTH

Front 80

What genetic abnormalities are associated with adrenal insufficiency?

Back 80

- Congenital Adrenal Hyperplasia
- Adrenoleukodystrophy (X-linked disorder w/ accumulation of very long chain fatty acids in adrenal glands and the brain)

Front 81

Your patient presents with weight loss, fatigue, postural hypotension, hyperpigmentation, and hyponatremia, what do you suspect?

Back 81

Adrenal Insufficiency

Front 82

You suspect your patient has adrenal insufficiency based on presentation (weight loss, fatigue, postural hypotension, hyperpigmentation, and hyponatremia), what do you test first?

Back 82

- Plasma cortisol 30-60 minutes after a 250 µg cosyntropin IM or IV (cortisol < 500 nmol/L)
- CBC, serum sodium, potassium, creatinine, urea, TSH

Front 83

What plasma cortisol result would indicate adrenal insufficiency 30-60 min after 250 µg cosyntropin IM or IV?

Back 83

< 500 nmol/L

Front 84

Once you've established your patient has adrenal insufficiency with a plasma cortisol 30-60 min after 250 µg cosyntropin test, how do you determine the cause?

Back 84

- Plasma ACTH
- Plasma Renin
- Serum Aldosterone

Front 85

What would indicate a diagnosis of Primary Adrenal Insufficiency?

Back 85

- High ACTH
- High PRA (plasma renin activity)
- Low Aldosterone

Front 86

How do you treat Primary Adrenal Insufficiency (high ACTH, high plasma renin activity, and low aldosterone)?

Back 86

Glucocorticoid and Mineralocorticoid replacement

Front 87

What should you first evaluate as a possible cause of primary adrenal insufficiency?

Back 87

Adrenal Auto-Antibodies
- If positive, auto-immune adrenalitis or auto-immune polyglandular syndrome (APS)

Front 88

What should you evaluate if your patient with primary adrenal insufficiency is negative for adrenal auto-antibodies?

Back 88

- Chest x-ray
- Serum 17OHP
- In men: plasma very long chain fatty acids (VLCFA)
- Adrenal CT

Front 89

What does it mean if your patient with primary adrenal insufficiency has a positive chest x-ray?

Back 89

- Adrenal infection (Tuberculosis)
- Infiltration (eg, Lymphoma)
OR
- Hemorrhage

Front 90

What does it mean if your patient with primary adrenal insufficiency has an elevated 17OHP?

Back 90

Congenital Adrenal Hyperplasia (17OHP ↑)

Front 91

What is likely the cause of adrenal insufficiency if they have a negative chest x-ray and normal serum 17OHP?

Back 91

- Auto-immune adrenalitis most likely diagnosis
- In men, consider adrenoleukodystrophy (VLCFA ↑)

Front 92

What would indicate a diagnosis of Secondary Adrenal Insufficiency?

Back 92

- Low or normal ACTH
- Normal Plasma Renin Activity
- Normal Aldosterone

Front 93

How do you treat Secondary Adrenal Insufficiency?

Back 93

Glucocorticoid replacement

Front 94

What should you first evaluate to determine a possible cause of secondary adrenal insufficiency?

Back 94

MRI of Pituitary:
- Positive: Hypothalamic-Pituitary mass lesion

Front 95

If a patient has secondary adrenal insufficiency (low/normal ACTH, normal plasma renin activity, and normal aldosterone), and their MRI of the pituitary is negative, what should you consider?

Back 95

- History of exogenous glucocorticoid treatment
- History of head trauma
- Consider isolated ACTH deficiency

Front 96

How should you first evaluate a suspected adrenal insufficiency? When? Why?

Back 96

Measure a morning level of cortisol (this is when it should be at its peak)
- Range of normal: 6 - 18 µg/dL
- Adrenal Insufficiency: < 5 µg/dL
- >14 µg/dL excludes adrenal insufficiency
- 5-14 µg/dL - need to have a stimulatory test of adrenal reserve w/ synthetic ACTH (Cosyntropin) followed by a cortisol sampling at 30 and/or 60 minutes (at any time of day)

Front 97

What constitutes a normal cortisol response to ACTH (Cosyntropin)?

Back 97

Peak response at 30-60 minutes > 18 µg/dL (500 nm/L)

Front 98

What constitutes an abnormal cortisol response to ACTH (Cosyntropin)? What should you do next?

Back 98

- Peak cortisol response to ACTH / Cosyntropin is < 18 µg/dL or < 500 nmol/L
AND
- Basal morning cortisol is < 5 µg/dL, then you should:

* Measure plasma ACTH to distinguish primary from secondary adrenal insufficiency

Front 99

If your patient has a low cortisol response to ACTH and has a basal morning cortisol < 5 µg/dL, then what should you do next? Implications?

Back 99

Measure Plasma ACTH:
- Elevated: primary adrenal insufficiency
- Low or Normal: secondary adrenal insufficiency

Front 100

When assessing someone for adrenal insufficiency in a critically ill or chronically ill patient, what do you need to consider during evaluation of their labs?

Back 100

- These patients may have low binding problems (ie, CBG)
- Total cortisol concentration may be low and the "free" or biologically active cortisol may be normal
- Assessment of "free" cortisol can be done in saliva, plasma, or by formula concentration med if conc. of CBG is known

Front 101

When assessing someone for adrenal insufficiency who is taking estrogen / oral contraceptives, what do you need to consider during evaluation of their labs?

Back 101

- These patients will have a significant increase in total cortisol levels that reflect an increase in CBG rather than any alteration of adrenal function
- Therefore even if they have a "normal" cortisol, this may be "low" for them given that the estrogen should be making their cortisol even higher

Front 102

What is a sensitive marker of adrenal reserve?

Back 102

Adrenal Androgen Production (DHEAS) - a normal level is very unusual in patients with any type of adrenal insufficiency

Front 103

What is the most common cause of Primary Adrenal Insufficiency?

Back 103

Auto-immune Polyglandular Syndromes

Front 104

Besides auto-immune polyglandular syndrome, what are some other causes of Primary Adrenal Insufficiency?

Back 104

- Metastases (from lung, breast, melanoma, GI)
- Primary adrenal lymphoma
- Bilateral adrenal hemorrhages (associated w/ coagulopathies such as anti-coagulation therapy, anti-phospholipid syndrome, heparin-induced thrombocytopenia) and usually d/t bilateral adrenal vein thrombosis
- Infection: TB, fungi (histoplasmosis, coccidiomycosis), HIV
- Genetic: congenital adrenal hyperplasia, familial glucocorticoid deficiency, adrenoleukodystrophy
- Infiltrative disorders: amyloidosis, hemochromatosis
- Drugs: Ketoconazole, Metyrapone, Mitotane, Etomidate

Front 105

What malignancies can cause Primary Adrenal Insufficiency?

Back 105

- Metastatic spread from lung, breast, melanoma, or GI
- Primary adrenal lymphoma
- Fairly unusual because it is rarely bilateral

Front 106

What can cause adrenal hemorrhage bilaterally? What would this cause?

Back 106

- Primary Adrenal Insufficiency
- Associated with coagulopathies (anti-coagulation therapy, anti-phospholipid syndrome, heparin-induced thrombocytopenia) and usually d/t bilateral adrenal vein thrombosis

Front 107

What infections can cause Primary Adrenal Insufficiency?

Back 107

- Tuberculosis
- Fungi (Histoplasmosis and Coccidiomycosis)
- HIV

Front 108

What genetic abnormalities can cause Primary Adrenal Insufficiency?

Back 108

- Congenital Adrenal Hyperplasia
- Familial Glucocorticoid Deficiency
- Adrenoleukodystrophy

Front 109

What infiltrative disorders can cause Primary Adrenal Insufficiency?

Back 109

- Amyloidosis
- Hemochromatosis

Front 110

What drugs can cause Primary Adrenal Insufficiency?

Back 110

- Ketoconazole
- Metyrapone
- Mitotane
- Etomidate

Front 111

What are the causes of secondary adrenal insufficiency?

Back 111

- Withdrawal from exogenous corticosteroid therapy
- Pituitary / hypothalamic disease

Front 112

What pituitary / hypothalamic disease can cause Secondary Adrenal Insufficiency?

Back 112

Hypophysitis may cause isolated ACTH deficiency
- Auto-immune
- Granulomatosis
- Drug-induced (Ipilimumab)

Front 113

How do you treat Primary Adrenal Insufficiency?

Back 113

- Hydrocortisone: morning (bigger dose) and afternoon (smaller dose); should have injectable version available for emergency use
- Fludrocortisone: given daily (given for mineralocorticoid replacement)

Front 114

What do you need to monitor in a patient taking Hydrocortisone?

Back 114

- Monitor sense of well-being
- Plasma ACTH should remain elevated even w/ adequate hydrocortisone
- Low/normal ACTH levels may reflect over-replacement

Front 115

What do you need to monitor in a patient taking Fludrocortisone?

Back 115

- Monitor electrolyte composition
- Monitor plasma renin activity (<5 ng/mL/min)

Front 116

What patient education should you do for a patient with Primary Adrenal Insufficiency?

Back 116

- Identification card / medical alert bracelet
- Sick day management: 3x3 → triple the dose for three days or until illness resolves

Front 117

How should you treat a patient with Primary Adrenal Insufficiency in an acute adrenal crisis?

Back 117

- Administer hydrocortisone 100 mg IV every 6 hours for 24 hours
- When stable decrease to 50 mg every 6 hours and then taper to maintenance as clinically warranted
- Support w/ isotonic, glucose containing IV fluids to replace volume

Front 118

How should you treat a patient with Primary Adrenal Insufficiency undergoing surgery?

Back 118

- Correct electrolytes, BP, and hydration status if necessary
- Give hydrocortisone 100 mg IM or IV on call to OR
- Hydrocortisone 50 mg every 6-8 hours and then taper judiciously to maintenance

Front 119

How do you treat a patient with Secondary Adrenal Insufficiency?

Back 119

- Hydrocortisone: lower doses needed than in primary AI

Front 120

Do patients with primary or secondary adrenal insufficiency need less hydrocortisone therapy? Why?

Back 120

- Secondary Adrenal Insufficiency requires lower doses
- These patients usually still have some cortisol secretion from adrenals

Front 121

Does Primary or Secondary Adrenal insufficiency require Fludrocortisone? Why?

Back 121

- Primary Adrenal Insufficiency requires Fludrocortisone
- This has mineralocorticod activity
- Secondary AI does not need MR replacement since renin-angiotensin-aldosterone system and zona glomerulosa remain intact

Front 122

How do you treat a patient with Primary vs Secondary Adrenal Insufficiency for sick days, adrenal crises, and surgical steroid coverage?

Back 122

Same therapies