Adrenal Disorders Flashcards
1
Q
What percentage of cardiac output do the adrenal glands receive?
A
0.14% of the cardiac output for approximately 0.02% of total body weight
2
Q
What are the arterial supplies of the adrenal glands?
A
- superior suprarenal (adrenal) arteries
- middle suprarenal arteries
- inferior suprarenal arteries
3
Q
What is the venous drainage for the right adrenal gland?
A
right suprarenal vein
4
Q
What is the venous drainage for the left adrenal gland?
A
suprarenal vein
5
Q
What are the three zones of the adrenal cortex?
A
- zona glomerulosa
- zona fasciculata
- zona reticularis
6
Q
What hormones are produced by the zona glomerulosa?
A
Mineralocorticoids (aldosterone)
7
Q
What is the primary function of aldosterone?
A
Reabsorption of sodium
8
Q
What hormones are produced by the zona fasciculata?
A
Glucocorticoids (cortisol)
9
Q
What are the functions of cortisol?
A
- Glucose metabolism
- Inflammation
10
Q
What hormones are produced by the zona reticularis?
A
Androgens (DHEA, DHEAS)
11
Q
What is the primary product of the adrenal medulla?
A
Catecholamines (Epinephrine)
12
Q
What is the cellular organization of the adrenal cortex?
A
- Glomerulosa: clusters of small round cells
- Fasciculata: large polyhedral cells arranged in bundles
- Reticularis: smaller cells arranged in cords
13
Q
What provides blood directly to the adrenal medulla?
A
Medullary arterioles
14
Q
What drains steroid hormones from the adrenal cortex?
A
Cortical plexuses and sinusoids
15
Q
What are the effects of aldosterone?
A
- Na+ and water reabsorption
- K+ excretion
16
Q
What are the target organs for aldosterone?
A
- kidney
- colon
- salivary glands
- sweat glands
17
Q
What regulates aldosterone synthesis?
A
- Angiotensin II
- Extracellular K+
18
Q
What is the role of principal cells in aldosterone action?
A
Increase the activity of ENaC, ROMK, KCC, and Maxi-K
19
Q
What is the primary mechanism of Na+ reabsorption and K+ excretion?
A
Aldosterone increases Na+/K+ ATPase activity
20
Q
What regulates glucocorticoids in the body?
A
HPA axis
External stimuli: stress & circadian rhythm
21
Q
What is the precursor to adrenocorticotropic peptide?
A
Pro-opiomelanocortin (POMC)
22
Q
What essential enzymes are involved in cortisol synthesis?
A
- 17α-hydroxylase
- 21α-hydroxylase
- 11β-hydroxylase
- 3β-hydroxysteroid dehydrogenase
23
Q
What percentage of cortisol is transported bound to corticosteroid-binding globulin (CBG)?
A
~90% of the cortisol
24
Q
Fill in the blank: Only _______ of the circulating cortisol is free.
A
3% to 4%
25
What is the function of 11β-HSD I?
Catalyzes a reversible oxidation of cortisol to inactive cortisone and can reactivate cortisone to cortisol
## Footnote
11β-HSD I plays a dual role in cortisol metabolism, facilitating both inactivation and reactivation.
26
What does 11β-HSD II do?
Catalyzes only the oxidation reaction inactivating cortisol
## Footnote
11β-HSD II exclusively converts cortisol to cortisone, preventing cortisol's effects.
27
List the metabolic effects of cortisol.
* Increases plasma glucose
* Increases free fatty acid
* Increases protein catabolism
* Increased food intake
## Footnote
These effects contribute to cortisol's role in energy mobilization during stress.
28
What immune effects does cortisol have?
* Decreased production of interleukins 1 and 6 (IL-1 and IL-6)
* T-cell suppression
* Anti-inflammatory effects
* Decreases in capillary permeability
* Decreases prostaglandin and leukotriene synthesis
## Footnote
These actions help modulate the immune response and reduce inflammation.
29
How does cortisol affect the musculoskeletal system?
* Increases bone resorption
* Muscle loss
* Decreases collagen formation
* Weakness & fatigue
## Footnote
These changes can lead to osteoporosis and muscle wasting.
30
What renal and GI effects does cortisol have?
* Decreases Ca2+ reabsorption from the kidney
* Decreases Ca2+ absorption from the GI tract
## Footnote
These effects can lead to altered calcium metabolism.
31
What cardiovascular effects are associated with cortisol?
* Stimulates red blood cell production
* Potentiates vasoconstriction
* Increases catecholamine actions
## Footnote
These effects can influence blood pressure and overall cardiovascular health.
32
What is the role of zona reticularis in adrenal androgen synthesis?
* Produces DHEA
* Produces androstenedione
* Produces DHEA sulfate (DHEA-S)
## Footnote
The zona reticularis is crucial for the synthesis of adrenal androgens, especially during adrenarche.
33
What is adrenarche?
Pre-pubertal surge of adrenal androgens
## Footnote
Adrenarche marks the onset of increased adrenal androgen production, leading to physical changes.
34
What enzymes are involved in peripheral synthesis of sex steroids?
* Sulfatase
* 3β-hydroxysterol dehydrogenase
* 17β-hydroxysterol dehydrogenase
* P450 aromatase
## Footnote
These enzymes convert DHEAS into active sex steroids like testosterone and estradiol.
35
What is the major precursor for sex steroid synthesis?
DHEAS
## Footnote
DHEAS is stable and inactive in blood, serving as a reservoir for sex steroid synthesis.
36
What is the role of cholesterol in steroidogenesis?
* Obtained from LDL or HDL
* Synthesized de novo
## Footnote
Cholesterol is essential for the synthesis of all steroid hormones.
37
What does the steroid acute regulatory (StAR) protein do?
Transports cholesterol to the inner mitochondrial membrane
## Footnote
StAR is crucial for initiating steroid hormone synthesis.
38
What enzyme catalyzes the synthesis of pregnenolone?
Cholesterol side-chain cleavage enzyme (CYP11A1)
## Footnote
CYP11A1 is the first step in the steroidogenesis pathway.
39
What is the incidence of classic 21-hydroxylase deficiency?
1:15,000
40
What is the incidence of classic 11β-hydroxylase deficiency?
1:100,000
41
What is the incidence of 17α-hydroxylase deficiency?
1:50,000
42
Which gene is associated with 21-hydroxylase deficiency?
CYP21
43
Which gene is associated with 11β-hydroxylase deficiency?
CYP11B1
44
Which gene is associated with 17α-hydroxylase deficiency?
CYP17
45
What is the effect of 21-hydroxylase deficiency on cortisol levels?
↓
46
What is the effect of 11β-hydroxylase deficiency on mineralocorticoids?
↑
47
What is the effect of 17α-hydroxylase deficiency on sodium levels?
↑
48
What happens to potassium levels in 21-hydroxylase deficiency?
↑
49
Does 21-hydroxylase deficiency cause hypertension?
no; this CAH vairent causes hypoaldosteronism which exhibits hypotensive effects
50
Does 11β-hydroxylase deficiency cause hypertension?
yes
51
What is the effect of 17α-hydroxylase deficiency on androgens?
↓
52
What is the sexual development outcome in XX females with 21-hydroxylase deficiency?
Atypical
53
What is the sexual development outcome in XY males with 17α-hydroxylase deficiency?
Atypical; undescended testicles
54
What condition is associated with congenital adrenal hyperplasia (CAH)?
Steroidogenesis
55
What is the structure and histology of the adrenal medulla?
~10% of the mass of the adrenal gland
56
What type of cells are chromaffin cells?
Structural and functional equivalents of postganglionic neurons in the sympathetic nervous system
57
From which embryological layer do chromaffin cells arise?
Neuroectoderm
58
What stimulates chromaffin cells?
Acetylcholine
59
What is the primary hormone secreted by chromaffin cells?
Epinephrine (~80%)
60
What is the secondary hormone secreted by chromaffin cells?
Norepinephrine (~20%)
61
What enzyme is uniquely expressed in adrenal medulla epinephrine-secreting cells?
Phenylethanolamin-N-methyltransferase (PNMT)
62
What stimulates the expression of PNMT?
Cortisol draining from the adrenal cortex
63
What role does the adrenal medulla play in the sympathetic response to stress?
Amplifies the sympathetic response
64
Fill in the blank: Catecholamines are degraded by _______.
Catechol-O-methyltransferase (COMT)
65
Which organs are involved in the degradation of catecholamines?
* Endothelial cells
* Heart
* Liver
* Kidneys
66
What is the half-life of catecholamines?
Short (seconds)
67
What metabolites are excreted in the urine after catecholamine degradation?
Vanillylmandelic acid (VMA) sulfates or glucuronides
68
T or F: Aldosterone regulates BP
False
it regulates extracellular volume which contributes to BP maintenance
69
T or F: DHEA-S is ;high during fetal development and diminishes after birth
True
70
DHEA-S gradual increase as it comes closer & closer to puberty. How does DHEA-S contribute to puberty
stimulates pubic & axillary hair growth
71
What are the adrenal glands?
Complex structures required for maintenance of life, triangular shaped organs located above each kidney.
72
What is the size and weight of the adrenal glands?
Measure between 2 and 5 cm and weigh 4-5 grams each.
73
What can happen without adrenal hormones?
Electrolyte abnormalities, circulatory collapse, and death.
74
What type of hormones are produced by the adrenal cortex?
Steroids.
75
What are the three major categories of adrenal steroid hormones?
* Mineralocorticoids
* Glucocorticoids
* Androgens
76
What is the main mineralocorticoid hormone?
Aldosterone.
77
What is the primary function of aldosterone?
Maintains the balance of sodium and potassium.
78
What is the main glucocorticoid hormone?
Cortisol.
79
What are the primary effects of cortisol?
* Helps the body with stress
* Increases blood sugar
* Suppresses the immune system
80
What is the main androgen hormone produced by the adrenal glands?
DHEAS.
81
What are the three zones of the adrenal cortex and their functions?
* Zona Glomerulosa: produces mineralocorticoids
* Zona Fasciculata: produces glucocorticoids
* Zona Reticularis: produces androgens
82
What regulates aldosterone production?
Angiotensin II as part of the renin-angiotensin-aldosterone system (RAAS).
83
What condition is characterized by excess aldosterone?
Primary aldosteronism or Conn's Syndrome.
84
What are the common causes of hyperaldosteronism?
* Unilateral Adrenal Adenoma: 60%
* Bilateral Adrenal Hyperplasia: 20-60%
* Unilateral adrenal hyperplasia: 2%
* Adrenocortical carcinoma: <1%
* Familial aldosteronism type I, II, III: <1%
85
What is a common symptom of elevated aldosterone levels?
High blood pressure.
86
What groups should be screened for hyperaldosteronism?
* Sustained BP above 150/100
* Elevated BP on 3 antihypertensive medications
* Controlled hypertension on 4 or more medications
* High BP and low potassium
* Hypertension with adrenal incidentaloma
* Hypertension and sleep apnea
* First degree relatives of patients with primary hyperaldosteronism
* Hypertension with early onset high BP or stroke before age 40
87
What does the diagnostic work-up for hyperaldosteronism include?
* Screening with plasma aldosterone and renin levels
* Confirmatory testing
* Determining the type of PA
88
What is the primary treatment for primary aldosteronism?
Curative surgical adrenalectomy.
89
What is a common medical therapy for hyperaldosteronism?
Mineralocorticoid receptor antagonists like Spironolactone.
90
What is Cushing's Syndrome?
A condition caused by excess cortisol.
91
What are the two main types of Cushing's Syndrome?
* ACTH dependent
* ACTH independent
92
What tests are used to screen for Cushing's Syndrome?
* 1 mg Dexamethasone Suppression Test
* 24 Hour Urine for Cortisol
* Midnight Salivary Cortisol Level
93
What is the treatment for Cushing's Syndrome?
Surgical removal of the growth producing excess cortisol or medication that blocks cortisol production.
94
What is adrenal insufficiency?
A rare but potentially life-threatening condition requiring steroid replacement.
95
How is adrenal insufficiency diagnosed?
Based on clinical and laboratory levels.
96
What are the two types of adrenal insufficiency?
* Primary disease
* Secondary disease
97
What is primary adrenal insufficiency also known as?
Addison’s disease
## Footnote
Addison's disease is characterized by a disorder affecting the adrenal gland.
98
What are the cortisol and ACTH levels in primary adrenal insufficiency?
Cortisol level is low and ACTH level is high
## Footnote
Both cortisol and aldosterone are deficient in primary adrenal insufficiency.
99
What are the most common causes of primary adrenal insufficiency?
* Autoimmune Addison’s disease
* Infections like Tuberculosis and AIDS
* Infiltrative disorders like Sarcoidosis, Lymphoma, and Metastases
* Bilateral adrenal hemorrhage
* Genetic disorders like congenital adrenal hyperplasia
## Footnote
These causes contribute to the dysfunction of the adrenal gland.
100
What is a notable symptom associated with primary adrenal insufficiency?
Hyperpigmentation
## Footnote
Caused by high levels of circulating ACTH and alpha melanocyte stimulating hormone.
101
What are the cortisol and ACTH levels in secondary adrenal insufficiency?
Cortisol level is low and ACTH level is normal or low
## Footnote
Only cortisol is deficient in secondary adrenal insufficiency.
102
What are the most common causes of secondary adrenal insufficiency?
* Chronic use of glucocorticoids
* Pituitary adenoma
* Head trauma
* Infection
* Isolated ACTH deficiency
## Footnote
These causes affect the hypothalamus and/or pituitary gland.
103
What are signs and symptoms caused by glucocorticoid deficiency?
* Weakness
* Fatigue
* Loss of appetite
* Weight loss
* Myalgia
* Normochromic anemia
* Lymphocytosis
* Eosinophilia
* Hypoglycemia
* Hyponatremia
## Footnote
These symptoms can lead to chronic ill health.
104
What are signs and symptoms caused by mineralocorticoid deficiency?
* Dizziness and postural hypotension
* Abdominal pain
* Salt craving
* Hyponatremia
* Hyperkalemia
## Footnote
Symptoms can be vague leading to adrenal crisis.
105
What are the electrolyte abnormalities seen in primary adrenal insufficiency?
* Hyponatremia
* Hyperkalemia
## Footnote
These electrolyte imbalances are significant in diagnosing adrenal insufficiency.
106
When should cortisol be sampled for adrenal insufficiency diagnosis?
Between 8 and 9 am
## Footnote
A cortisol level of less than 3 ug/dL makes adrenal insufficiency likely.
107
What is the ACTH level typically in primary adrenal insufficiency?
Usually greater than 100 pg/mL
## Footnote
This helps differentiate primary from secondary adrenal insufficiency.
108
What is the treatment for primary adrenal insufficiency?
* Cortisol
* Aldosterone
## Footnote
DHEAS is also recommended for women experiencing low energy and libido after steroid replacement.
109
What is the usual dose of hydrocortisone for adrenal insufficiency?
20 mg divided into 1 to 3 times daily
## Footnote
Hydrocortisone is preferred due to its mineralocorticoid effect.
110
What is congenital adrenal hyperplasia (CAH)?
A group of autosomal recessive disorders caused by mutations in genes encoding enzymes for cortisol biosynthesis
## Footnote
The most common cause is a mutation in CYP21A2.
111
What is the most common cause of CAH?
Mutation in CYP21A2
## Footnote
This accounts for 95% of CAH cases.
112
What can overproduction of adrenal androgens in CAH lead to in females?
In utero virilization of external genitalia
## Footnote
This can range from mild labial fusion to complete masculinization.
113
What is the treatment for congenital adrenal hyperplasia?
* Hormone replacement with a steroid
* Fludrocortisone
## Footnote
These treatments address hormone deficiencies.
114
What is pheochromocytoma?
A neuroendocrine tumor originating predominantly in the adrenal medulla
## Footnote
It is functionally indistinguishable from paragangliomas.
115
What are common signs and symptoms of pheochromocytoma?
* Paroxysmal profuse sweating
* Pallor
* Tremor
* Tachycardia
* Episodic hypertension
## Footnote
Testing is recommended for individuals with these symptoms.
116
What catecholamines does the adrenal medulla produce?
* Epinephrine
* Norepinephrine
* Dopamine
## Footnote
The secretion is dependent on the phenotype of the tumor.
117
What is the best screening test for pheochromocytoma if there is low suspicion?
Measuring urinary fractionated metanephrines
## Footnote
This test has higher specificity.
118
What is the preferred test for pheochromocytoma if there is high suspicion?
Plasma metanephrines
## Footnote
This test has higher sensitivity.
119
What are catecholamine metabolites called?
Metanephrines
## Footnote
Metanephrines can be measured in plasma or urine.
120
Why are 24-hour urine collections recommended for quantitation of catecholamines and metanephrines?
Plasma catecholamines have short half-lives and their secretion may be episodic.
121
Which test is the best screening test if there is low suspicion of pheochromocytoma?
Measuring urinary fractionated metanephrines.
122
What is preferred if there is high suspicion of pheochromocytoma?
Plasma metanephrines.
123
What percentage of the general population has nonspecific anatomic adrenal abnormalities?
Approximately 3%–7%.
124
When is radiologic screening advisable for pheochromocytoma?
When biochemical screening tests reveal abnormal catecholamine release.
125
What is the best imaging test to localize a pheochromocytoma?
CT of the abdomen with and without contrast.
126
What Hounsfield Unit density is typically observed in pheochromocytoma?
Greater than 10.
127
How do pheochromocytomas appear on MRI?
Very bright with high signal on T2 sequence.
128
What test may be used if a pheochromocytoma cannot be visualized?
MIBG Scintigraphy.
129
What is the optimal treatment for pheochromocytoma?
Removal of the tumor as soon as possible.
130
What team is usually involved in the treatment of pheochromocytoma?
Endocrinologist, anesthesiologist, and surgeon.
131
What is important to normalize before surgery for pheochromocytoma?
Blood pressure, heart rate, and restore volume.
132
What is the preferred first medication to start for pheochromocytoma?
Phenoxybenzamine.
133
Why should beta blockers not be used alone in pheochromocytoma treatment?
They can lead to unopposed alpha stimulation, causing hypertensive crisis.
134
When can a beta adrenoreceptor blocker be added to treatment?
After at least 7 days of alpha blockade if tachycardia is present.
135
What should be done if blood pressure remains high after initial treatment?
Add calcium channel blocker.
136
What is a treatment option for metastatic pheochromocytoma?
MIBG radiation or chemotherapy.
137
What symptoms did the 47-year-old man in the case study present with?
Episodic headaches, sweating, heart palpitations, and tremor.
138
What was the urinary metanephrines level in the case study patient?
1300 µg/24 hours (normal range: 45-290 µg/24 hours).
139
What did the CT of the abdomen reveal in the case study patient?
A 3 cm left adrenal adenoma.
140
What are the two main components of the adrenal gland?
Adrenal cortex and medulla.
141
What does the adrenal cortex produce?
Mineralocorticoids, glucocorticoids, and androgens.
142
What does the adrenal medulla produce?
Epinephrine and norepinephrine.
143
What condition is caused by overproduction of aldosterone?
Conn’s Syndrome.
144
What condition is caused by overproduction of cortisol?
Cushing’s Syndrome.
145
What leads to pheochromocytoma and paragangliomas?
Overproduction of epinephrine and norepinephrine.
146
aldosterone secretion is stimulated by what conditions?
low blood osmolality, low salt intake, and laying down
147
T or F: mineralocorticoids are regulated by the HPA axis.
False
aldosterone is regulated by the RAAS axis
148
List effects of glucocorticoids
stimulates gluconeogenesis to raise blood sugar
increases protein catabolism
fat redistribution
inhibits host response to infection
149
high levels of glucocorticoids and low levels of ACTH are indicative of what
primary ACTH-independent Hypercortisolism
150
How can cushing's disease be distinguished from cushing's syndrome?
Under normal physiological conditions, ACTH and cortisol levels share a positive correlation
If ACTH is low in the presence of elevated cortisol, this indicates cortisol is being secreted independently of ACTH; hence, the adrenal gland is what is dysfunctioning: Cushing's syndrome
Let's say ACTH and cortisol are both high. this indicates cortisol secretion is dependent on ACTH secretion; hence, the pituitary is what is dysfunctioning: cushing's disease
151
T or F: secondary AI affects all adrenal hormones? Explain your reasoning
False
only the zona fasciculata is affected b/c ACTH secretion from the anterior pituitary is what is impaired
152
For primary AI, all adrenal zonae are affected. List some of the main clinical presentations of each.
Glucocorticoid deficiency: hyponatremia, hyperkalemia induced myalgia w/ flaccid paralysis, salt cravings, hypoglycemia, heighted senses, hyperpigmentation
mineralocorticoid deficiency: dizziness w/ orthostatic hypotension, syncope, hypovolemia
sex hormone deficiency: decreased libido, impotences, ovarian failure
153
what are the most important complications of hyperaldosteronism
HTN, hypokalemia induced alkalosis, edema, cardiac arrhythmias, muscle wasting
154
what is the most common cause of secondary hyperaldosteronism
decreased renal blood flow and perfusion
155
CKD can lead to what long-term complication?
hypoaldosteronism
156
what are causes of adrenal hyperplasia?
decreased production of cortisol via enzymatic defects increases ACTH production
157
Compare and Contrast the presentational differences b/t congenital adrenal hyperplasia and adrenal insufficiency
Both:
increased ACTH secretion causing hyperpigmentation, myalgias & hypoglycemia
decreased cortisol production leads to salt-wasting, hyperkalemia, and hypotension
Different:
AI: sex hormone deficiency: amenorrhea, hypogonadism
CAH: sex hormone EXCESS: virilization, hirsutism, precocious pseudopuberty
