Endocrine Function III: Adrenal Cortex and Adrenal Medulla Hormones Flashcards
1
Q
Basic anatomy of the adrenal cortex
A
- Capsule (outer)
- Adrenal cortex
- Adrenal medulla (inner)
2
Q
Three layers of the adrenal cortex
A
- Zona glomerulosa (outermost)
- Zona fasciculata (middle)
- Zona reticularis (innermost)
3
Q
Three major hormone classes of the adrenal cortex
A
- Estrane
- Andosane
- Pregnane
4
Q
Major hormone(s) produced by the zona glomerulosa layer
A
Mineralocorticoids
5
Q
Major hormone(s) produced by the zona fasciculata layer
A
Glucocorticoids
6
Q
Major hormone(s) produced by the zona reticularis layer
A
Sex hormones
7
Q
Number of carbons on estrogens, androgens, and adrenal steroids
A
- Estrogens: 18
- Androgens: 19
- Adrenal steroids: 21
8
Q
First biosynthetic pathway for adrenocorticosteroid formation
A
Acetate → Cholesterol → Pregnenolone → Adrenocorticoids
9
Q
Second biosynthetic pathway for adrenocorticosteroid formation (not preferred)
A
Pregnenolone → DHEA → Androstenedione → Testosterone → (Estradiol)
10
Q
Causes of adrenocorticosteroids utilizing alternate pathway instead of the preferred pathway
A
Enzyme deficiencies
11
Q
Importance of enzymes in steroid biogenesis
A
Takes enzymes to make conversions to final product
12
Q
Major site of steroid metabolism
A
Liver
13
Q
Form of adrenocorticosteroids excreted in the urine
A
- Liver is the site of catabolism
- Water-insoluble hormones must be conjugated w/ sulfates or glucuronic acid to be excreted in urine
14
Q
Which steroid has a negative feedback effect on adrenocorticotrophic hormone (ACTH)
A
Cortisol
15
Q
Name of the principle cortisol-binding protein
A
CBG
16
Q
Mineralocorticoids
- Metabolic effects
A
- Maintain sodium and potassium balance
- Aldosterone
17
Q
Four regulatory factors for aldosterone secretion (order of importance)
A
- Potassium concentration
- RAAS
- Total body sodium concentration
- ACTH (has minor effect unless ACTH is pathologically in excess or is deficient)
18
Q
Glucorticoids
- Metabolic effects
A
- Promotion of gluconeogenesis and lipolysis
- Promotion of liver glycogenesis
- Promotion of liver glycogenolysis
- Inhibition of protein synthesis and promotion of protein catabolism
- ↑ anti-inflammatory and immunosuppressive action
- ↓ intestinal absorption of Ca2+; ↑ loss of Ca2+ from bone matrix
- Miscellaneous: enzyme production, appetite promotion, regulation of blood pressure
19
Q
Most potent glucocorticoid
A
Cortisol
20
Q
Most potent mineralocorticoid
A
Aldosterone
21
Q
Most potent adrenocortical androgen
A
Testosterone
22
Q
What is the role of RAAS on the regulation of aldosterone?
A
Releases aldosterone and reabsorbs Na+ and releases K+
23
Q
Three regulatory factors for the release of glucocorticoids
A
- ACTH stimulation of hormone
- Normal diurnal variation
- Stress
24
Q
Feedback mechanism utilized in glucocorticoid hormonal regulation
A
Cortisol causes negative feedback on hypothalamus and anterior pituitary
25
Normal diurnal variation in cortisol
- While sleeping, cortisol is very low so negative feedback is removed
- ACTH is released and there is a sharp ↑ while waking up (BP and sugar ↑ so you don't pass out)
The cortisol levels ↓ over the day
- By 4pm it should be 1/3 the level it was at 8am
26
What androgen is produced in the greatest quantity by the adrenal cortex?
Testosterone
27
Six conditions associated w/ a hypofunctioning adrenal cortex
- Primary hypoaldosteronism
- Secondary hypoaldosteronism
- Addison's disease
- Acute adrenal insufficiency
- Secondary and tertiary adrenal insufficiency
28
Differentiate causes of primary hypoaldosteronism
Inability to adjust to stress, low Na+, high K+, high renin, low aldosterone
29
Differentiate causes of secondary hypoaldosteronism
Occurs in patient w/ renal disease,
| - Kidney is unable to produce and release renin and therefore cause low aldosterone
30
List the typical sodium, potassium, and renin levels observed in hypoaldosteronism
- Low Na+
- High K+
- High renin
31
Addison's disease
| - Clinical symptoms due to glucocorticoids deficiency
- Fatigue
- Weakness
- Weight loss
- GI disturbances
- Post-parandial hypoglycemia
32
Addison's disease
| - Clinical symptoms due to mineralacorticoid deficiency
- Dehydration
- Hypotension
- Hyperkalemia
- Metabolic acidosis (↓H+ secretion)
- Hyponatremia (↓Na+ reabsorption into blood)
33
Addison's disease
| - Reason for hyperpigmentation and infertility
No negative feedback on anterior pituitary (e.g., hyperpigmentation present b/c excess ACTH stimulates MSH production)
34
Addison's disease
- Na
- K
- Blood sugar
- Cortisol
- ACTH
- ↓ Na+
- ↑ K+
- ↓ Blood sugar
- ↓ Cortisol
- ↑ ACTH
35
What is the cause of the Addisonian crisis?
During infection or acute stress, Addison's patient cannot respond with ↑ aldosterone and cortisol and can go into shock with hypotension, fever, hypovolemia, and hyperkalemia (life threatening)
36
What is the cause of Waterhouse-Friderichsen?
Caused by meningococcal meningitis and septicemia; this causes acute adrenal insufficiency
37
What is the most common cause of tertiary adrenal insufficiency?
Chronic pharmacological administration of glucocorticoids
38
Four conditions associated w/ a hyperfunctioning adrenal cortex
- Primary aldosteronism (Conn's syndrome)
- Secondary aldosteronism
- Cushing's syndrome
- Congenital adrenal hyperplasia
39
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Primary aldosteronism (Conn's syndrome)
- Cause
```
Adenoma in outermost layer (tumors)
40
```
Primary aldosteronism (Conn's syndrome)
- Outstanding clinical symptom
```
Hypertension
41
Primary aldosteronism (Conn's syndrome)
- Na+ (blood)
- K+ (blood and urine)
- Aldosterone
- Renin
- ↑ Aldosterone
- Hypernatremia (b/c of ↑ aldosterone)
- Hypokalemia
- Hypokaluria
- ↓ Renin
- Metabolic alkalosis (↑H+ secretion in urine caused by ↑ Na+ reabsorption)
42
Secondary aldosteronism
| - Two causes
Characterized by elevated aldosterone in the absence of an adrenal tumor
- ↓ blood flow to kidney causing ↓ GFR
- Hyperactivity of RAAS causing ↑ renin production
43
Secondary aldosteronism
- Na+
- K+
- Aldosterone
- Renin
- Hypernatremia
- Hypokalemia
- Hypokaluria
- ↑ Aldosterone (b/c of ↑ Na+)
- ↑ Renin
- Metabolic alkalosis (↑H+ secretion in urine caused by ↑ Na+ reabsorption)
44
Why is renin increased in secondary aldosteronism?
RAAS is continuously being activated
45
Secondary aldosteronism
| - Clinical symptoms
↓ blood flow to kidney:
- Nephrosis
- CHF
- Obstructive renal disease
- Cirrhosis w/ Na+ depletion
- Pregnancy
- Diuretic use
46
Cushing's Syndrome
| - Five clinical symptoms
- Moon face
- Buffalo hump
- Truncal obesity
- Purple striae
- Hypertenion
47
Cushing's Syndrome
| - Three general causes
- Exogenous glucocorticoid therapy (prednisone)
- ACTH-dependent syndrome
- ACTH-independent
48
Cushing's Syndrome
| - Two specific causes of ACTH-dependent Cushing's
- Cushing's disease (ACTH-producing tumors)
| - Ectopic ACTH-secreting tumors
49
Cushing's Syndrome
| - Two specific causes of ACTH-independent Cushing's
- Adrenal adenoma (all 3 layers)
| - Nodular adrenal hyperplasia (out of control)
50
Cushing's Syndrome
| - Two recommended screening tests and typical results if patient has syndrome
- 24 hour free cortisol (>120 = Cushing's)
- Overnight dexamethasone suppression test
- AM/PM cortisol levels
51
Cushing's Syndrome
| - Expected morning and afternoon cortisol levels
↑ in AM, ↓ over the day normally
| - In Cushing's, it's increased all the time)
52
Cushing's Syndrome
- Na+
- K+
- Blood sugar
- Cortisol
- ACTH
- ↑ Na+
- ↓ K+
- ↑ Blood sugar
- ↑ Cortisol
- ↑ ACTH (due to adrenal cortex being continuously stimulated in Cushing's Disease, ectopic ACTH-secreting tumor, and Cushing's Syndrome)
53
CAH
| - Full name (as well as the name of the adult condition)
- Congenital adrenal hyperplasia
| - Aka adrenogenital syndrome
54
CAH/adrenogenital syndrome
| - Pathogenesis
- Caused by enzyme deficiencies in the pathways to produce the glucocorticoids and mineralocorticoids
- No negative feedback since cortisol is not produced and aldosterone is ↓
55
CAH/adrenogenital syndrome
| - Two common enzyme deficiencies
- 21-hydroxylase
| - 11-beta-hydroxylase
56
CAH/adrenogenital syndrome
- Cortisol
- ACTH
- Progesterone
- DHEA
- Sodium
- Potassium
- ↓ Cortisol
- ↑ ACTH
- ↑ Progesterone
- ↑ DHEA
- ↓ Sodium
- ↑Potassium
57
CAH/adrenogenital syndrome
| - Typical symptoms in boys and girls
```
Females
- Abnormalities of external genitalia at birth (cannot tell if male or female)
- Hirsutism
- Infertility
- Breast atrophy
Males
- Appear normal at birth but have sexual precocity (too much testosterone)
Both
- Acne
- Coarsening of voice
- Scalp recession early in life
```
58
CAH/adrenal hyperplasia
| - Lab test included in newborn screen to check for this condition
17-hydroxyprogesterone
59
This is an enzyme kinetic assay used to measure angiotensin I produced from angiotensinogen by renin
Plasma renin activity test (PRA)
60
Stimulation tests are used to assess ____ hormonal states (hypofunctioning vs. hyperfunctioning)
Hypofunctioning
61
Suppression tests are used to assess ____ hormonal states (hypofunctioning vs. hyperfunctioning)
Hyperfunctioning
62
ACTH stimulation test
| - Diagnostic use
Differentiate primary adrenal insufficiency (Addison's) from secondary (hypopituitarism)
63
ACTH stimulation test
| - Analyte measured
Cortisol
64
ACTH stimulation test
| - Expected normal response
Serum cortisol should double in 30 minutes
65
ACTH stimulation test
| - Results in Addison's disease
Little or no change in cortisol levels
66
ACTH stimulation test
| - Results in hypopituitarism
Increased levels of cortisol on successive days (2-3) of ACTH stimulation (delayed or "staircase" response)
67
Metyrapone test
| - Principle
Selectively inhibits 11-beta-hydroxylase, so the conversion of 11-deoxycortisol to cortisol is inhibited, allowing unrestricted release of ACTH
68
Metyrapone test
| - Diagnostic use
Differentiation of normal patients from secondary adrenal insufficiency (hypopituitarism);
- Assesses pituitary ACTH reserve basically to see how much ACTH the patient can produce
69
Metyrapone test
| - Expected normal response
- ↓ cortisol
- ↑ 11-deoxycortisol
- ↑ ACTH
70
Metyrapone test
| - Results in hypopituitarism
Unchanged cortisol, 11-deoxycortisol, and ACTH levels
71
Clinical use of the corticotropin releasing hormone (CRH) test
Differentiates secondary (pituitary) and tertiary (hypothalamic) adrenal sufficiency
72
Overnight Dexamethasone Suppression Test (screening test)
| - Principle
Feedback mechanism of hypersecretion can be tested by administering a potent glucocorticoid and judging suppression of ACTH secretion
73
Overnight Dexamethasone Suppression Test (screening test)
| - Analytes measured
Serum or urine cortisol levels
74
Overnight Dexamethasone Suppression Test (screening test)
| - Diagnostic use
Differentiate normal patient from Cushing's syndrome (either due to Cushing's disease, adrenal tumor, or ectopic ACTH syndrome)
75
Overnight Dexamethasone Suppression Test (screening test)
| - Expected normal response
↓ cortisol (<3 ug/dL)
76
Overnight Dexamethasone Suppression Test (screening test)
| - Cause of abnormal results
↑ cortisol (>10 ug/dL) = Cushing's Syndrome
77
Which causes of Cushing's syndrome may be differentiated using the high-dose test?
- Adrenal tumors
- Nonendocrine ACTH-secreting tumors
- Pituitary Cushing's disease
78
What do normal results look like in high dose dexamethasone suppression test look like?
50% suppression of cortisol production
79
How do abnormal results differ in Cushing's and adrenal/ectopic tumors during the high dose test?
- Cushing's = mostly suppressed cortisol production
| - Adrenal/ectopic tumors = no change in cortisol levels
80
Three principle hormones classified as catecholamines and their sites of synthesis.
- Epinephrine (80-90% medulla production)
- Norepinephrine (10-20% medulla production)
- Dopamine (small amt produced in adrenal medulla)
81
These catecholamines have a marked influence on the vascular system
Dopamine and norepinephrine
82
This catacholamine influences metabolic processes, especially carbohydrate metabolism
Epinephrine
83
This catecholamine inhibits phenylethanolamine-N-methyltransferase
Epinephrine
84
This catecholamine inhibits tyrosine hydroxylase
Norepinephrine
85
Pheochromocytomas
| - Cause
- Tumor in adrenal medulla
| - Too much catecholamines
86
Pheochromocytomas
| - Principle clinical symptom
Hypertension
87
Pheochromocytomas
| - Best specific urine screening test
Urinary metanephrines
88
Pheochromocytomas
| - Best diagnostic test
Urinary VMA
89
Neuroblastomas
| - Commonly affected age group
Pediatric
90
Neuroblastomas
| - Clinical symptoms
Tumor in or near adrenal gland producing a lot of dopamine, causing transient hypertension and tachycardia
91
Neuroblastomas
| - Best specific urine screening test
Urinary HVA (diagnostic0
