Adrenal Glands Flashcards
In order to sythesize cortisol in the adrenal cells, _ must be taken into the adrenal cells and processed
In order to sythesize cortisol in the adrenal cells, LDL must be taken into the adrenal cells and processed
Once LDL is transported into adrenal cells (for cortisol synthesis) the LDL is broken down into cholesterol esters within the _
Once LDL is transported into adrenal cells (for cortisol synthesis) the LDL is broken down into cholesterol esters within the lysosome
* Cholesterol esters are further hydrolyzed into cholesterol
_ is the protein which transfers cholesterol into the mitochondria (rate limiting step of steroid production)
Steroidogenic acute regulatory protein (StAR) is the protein which transfers cholesterol into the mitochondria (rate limiting step of steroid production)
Cholesterol is converted into _ inside the mitrochondria by the enzyme cholesterol desmolase
Cholesterol is converted into pregnenolone inside the mitrochondria by the enzyme cholesterol desmolase
* Pregnenolone –> progesterone (SER)
* Later 11 deoxycortisol –> cortisol (mitochondria)
Cortisol is (hydrophilic/lipophilic) and travels freely in the bloodstream
Cortisol is lipophilic and does not travels freely in the bloodstream
The vast majority of cortisol will be (free/bound)
The vast majority of cortisol will be bound
* 90% will be bound to corticosteroid-binding globulin/ transcortin
Only _ cortisol can enter cells and activate the receptor
Only free cortisol can enter cells and activate the receptor
Glucocorticoid receptors are found in the _
Glucocorticoid receptors are found in the cytosol of virtually every nucleated cell
The response to cortisol takes hours to days because cortisol acts by affecting _
The response to cortisol takes hours to days because cortisol acts by affecting gene expression, which in turn will affect protein synthesis
Cortisol (increases/decreases) GLUT4 transporter expression
Cortisol decreases GLUT4 transporter expression
* Glucocorticoids decrease glucose utilization to maintain availability
Cortisol acts on the pancreas to _ insulin and _ glucagon secretion
Cortisol acts on the pancreas to decrease insulin and increase glucagon secretion
* Cushing syndrome can cause a person to develop insulin resistant diabetes
Cortisol increases lipolysis to generate _ , which can be used for energy in times of stress
Cortisol increases lipolysis to generate glycerol, which can be used for energy in times of stress
Cortisol _ protein synthesis and _ peripheral amino acid uptake in muscles
Cortisol inhibits protein synthesis and decreases peripheral amino acid uptake in muscles
* Can cause muscle wasting in patients with excess
The way that cortisol maintains a normal blood pressure is by _
The way that cortisol maintains a normal blood pressure is by upregulating the number of alpha1 receptors on arterioles
* This increases the sensitivity to NE and E
Cortisol decreases inflammation by inhibiting the production of _
Cortisol decreases inflammation by inhibiting the production of proinflammatory mediators like leukotrienes, prostaglandins, IL-2, IFN-gamma, IFN-a, TNF-alpha
Cortisol can increase the total number of neutrophils on WBC via _
Cortisol can increase the total number of neutrophils on WBC via inhibiting the adhesion of WBCs to blood vessel walls, shifting the neutrophils from vessel wall to the circulation
Cortisol causes _ in fibroblast activity
Cortisol causes decreased fibroblast activity
* Leads to decreased collagen synthesis and diminished wound healing
Decreased fibroblast activity caused by cortisol can manifest as _
Decreased fibroblast activity caused by cortisol can manifest as striae
Cortisol _ osteoblast activity
Cortisol decreases osteoblast activity
* Patients on glucocorticoids are at risk of osteoporosis
Why are glucocorticoids given to mothers who go into labor prematurely?
Glucocorticoids are very important to the maturation of lungs and to the production of surfactant
The hypothalamus releases CRH in a _ fashion
The hypothalamus releases CRH in a pulsatile fashion
* We always have a basal level of cortisol, ACTH, CRH
* The HPA axis is responsible for cortisol regulation
The cell bodies that produce CRH are located in the _
The cell bodies that produce CRH are located in the paraventricular nucleus of the hypothalamus
Aldosterone is lipophilic and freely travels in the bloodstream; however the majority will be bound to _
Aldosterone is lipophilic and freely travels in the bloodstream; however the majority will be bound to albumin or transcortin, cortisol, progesterone
MR receptors have equal affinity for mineralocorticoids and cortisol; what is the consequence of this
High levels of cortisol can stimulate MR receptors and cause effects similar to hyperaldosteronism
The adrenal cortex originates from _ embryologic structure
The adrenal cortex originates from mesoderm
The adrenal medulla originates from _ embryologic structure
The adrenal medulla originates from neural crest
The superior adrenal artery branches off of the _
The superior adrenal artery branches off of the inferior phrenic artery
The middle adrenal artery branches off of the _
The middle adrenal artery branches off of the abdominal aorta
The inferior adrenal artery branches off of the _
The inferior adrenal artery branches off of the renal artery
The right suprarenal vein drains into the _
The right suprarenal vein drains into the IVC, directly
The left suprarenal vein drains into the _
The left suprarenal vein drains into the left renal vein –> IVC
The (right/left) renal vein crossses over the aorta
The left renal vein crosses over the aorta
The (right/left) renal vein is longer
The left renal vein is longer than the right
_ is a condition in which the SMA compresses the left renal vein and causes hematuria, flank pain, pelvic congestion
Nutcracker syndrome is a condition in which the SMA compresses the left renal vein and causes hematuria, flank pain, pelvic congestion
A patient with hematuria, flank pain, and pelvic congestion may have compression of the renal vein via the _
A patient with hematuria, flank pain, and pelvic congestion may have compression of the renal vein via the superior mesenteric artery (or sometimes the aorta)
Why might nutcracker syndrome cause pelvic congestion in a female?
The gonadal vein can’t drain
The adrenal cortex produces _ while the adrenal medulla produces _
The adrenal cortex produces steroid hormones (mineralocorticoids, glucocorticoids, androgens) while the adrenal medulla produces stress hormones (epi, norepi)
The zona glomerulosa produces _
The zona glomerulosa produces mineralocorticoids
The zona reticularis produces _
The zona reticularis produces androgens
The zona fasciculata produces _
The zona fasciculata produces glucocorticoids
_ cells secrete neurohormones epinephrine and norepinephrine; they are found in the adrenal medulla or celiac ganglion
Chromaffin cells secrete neurohormones epinephrine and norepinephrine; they are found in the adrenal medulla or celiac ganglion
Glucocorticoids (aka cortisol) have three important roles:
Glucocorticoids (aka cortisol) have three important roles:
1. Maintains BP (can inc RAAS and act on MR)
2. Increases glucose in the bloodstream
3. Anti-inflammatory effects
Clinical manifestations of glucocorticoid deficiency include:
Clinical manifestations of glucocorticoid deficiency include:
* Weakness, fatigue, muscle aches
* Orthostatic hypotension, hypoglycemia
* GI symptoms, weight loss
Mineralocorticoid (aka aldosterone) functions to _
Mineralocorticoid (aka aldosterone) functions to increase Na+ retention, excrete K+
Consequences of aldosterone deficiency:
Consequences of aldosterone deficiency:
* Hyperkalemia (palpitations, chest pain, N/V)
* Type IV RTA
* Normal Na+
Aldosterone deficiency can cause a hyperkalemic, hypercholeremic non-AG metabolic acidosis; explain
Aldosterone deficiency can cause a hyperkalemic, hypercholeremic non-AG metabolic acidosis due to hyperkalemia –> inhibits ammonium excretion
Androgens have roles in _ physiology
Androgens have a role in regulating energy, concentration, mood, menses, libido
Decreased androgens can manifest as _
Decreased androgens can manifest as depressed mood, poor energy, decreased concentration, irregular menses, erectile dysfunction
Primary adrenal insufficiency causes ADH secretion to (increase/decrease)
Primary adrenal insufficiency causes ADH secretion to increase
Increased ADH secretion in primary AI is two-fold; explain
Increased ADH secretion in primary AI is two-fold:
1. CRH increases ADH and primary AI will increase CRH levels
2. Cortisol normally opposes ADH secretion so during AI, ADH is left unopposed
Causes of primary adrenal insufficiency:
Causes of primary adrenal insufficiency:
* Adrenalectomy
* Autoimmune conditions
* HIV
* Disseminated TB
* Fungal infections
* Waterhouse-Friderichsen
* Addison’s disease
* Drugs (azoles, rifampin)
Waterhouse-Friderichsen syndrome is caused by septicemia from _ infection that leads to adrenal hemorrhage
Waterhouse-Friderichsen syndrome is caused by septicemia from N. meningitidis infection that leads to adrenal hemorrhage
Chronic primary adrenal insufficiency is commonly caused by _ in developed countries and _ in developing countries
Chronic primary adrenal insufficiency is commonly caused by Addison’s disease in developed countries and TB in developing countries
Someone with a primary adrenal insufficiency will have
_ morning cortisol
_ morning ACTH
_ ACTH stimulation test
_ lab findings
Someone with a primary adrenal insufficiency will have
low morning cortisol
high morning ACTH
no response on ACTH stimulation test
low aldosterone, high K+ , low glucose, high eosinophils
New onset eosinophilia may be an indicator of _ due to the lack of cortisol and the high ACTH
New onset eosinophilia may be an indicator of adrenal insufficiency due to the lack of cortisol and the high ACTH
Only (primary/secondary) adrenal insufficiency will present with signs of mineralocorticoid deficiency
Only primary adrenal insufficiency will present with signs of mineralocorticoid deficiency
* Primary = problem with the adrenals themselves
* Secondary = problem with anterior pituitary (RAAS controls aldosterone not ACTH)
Explain the causes and pathophysiology of secondary adrenal insufficiency
Decreased anterior pituitary function –> low ACTH –> low adrenal cortex activity –> low cortisol
* Often involves damage to anterior pituitary from mechanical, infectious, infiltrative causes
* Mechanical: TBI, surgery, stroke, sheehan
* Infectious: TB, syphilis
* Infiltrative: hemochromatosis, sarcoidosis
Diagnostics expected with secondary AI:
Diagnostics expected with secondary AI:
* Low ACTH, low cortisol, normal aldosterone, normal K+
* Low morning cortisol
* Low morning ACTH
* ACTH stimulation test increases cortisol
A very common cause of “tertiary” adrenal insufficiency is _
A very common cause of “tertiary” adrenal insufficiency is abrupt cessation of exogenous steroid use
What happens if exogenous steroids (like prednisone) are suddenly stopped and not tappered?
Hypothalamic dysfunction –> low CRH –> low ACTH –> low cortisol
What are the next diagnostic steps after finding a low AM ACTH?
Low ACTH –> do a CRH stimulation test
* No response? secondary
* Increases ACTH? tertiary
If ACTH stimulation test increases cortisol, the adrenal insufficiency is either _ or _
If ACTH stimulation test increases cortisol, the adrenal insufficiency is either secondary or tertiary
Cushing syndrome is _ , cushing disease is _
Cushing syndrome is hypercortisolism , cushing disease is hypercortisolism from pituitary tumor
Things like adrenal adenoma or adrenal carcinoma cause increased cortisol from (unilateral/bilateral) adrenal atrophy
Things like adrenal adenoma or adrenal carcinoma cause increased cortisol from unilateral adrenal atrophy
Exogenous corticosteroid use (prednisone) can lead to decreased CRH, decreased ACTH and (bilateral/unilateral) adrenal hyperplasia
Exogenous corticosteroid use (prednisone) can lead to decreased CRH, decreased ACTH and bilateral adrenal hyperplasia
Clinical presentation of hypercortisolism:
Clinical presentation of hypercortisolism:
* Moon facies
* Weight gain
* Hyperglycemia/insulin resistance
* Abdominal obesity
* Dorsocervical fat pad
* Purple striae/skin thinning
* Amenorrhea, hirsutism, osteoporosis
Hypercortisolism is associated with:
_ 24-hr urine free cortisol
_ late night salivary cortisol
_ ACTH
Hypercortisolism is associated with:
increased 24-hr urine free cortisol
increased late night salivary cortisol
? ACTH (increased from cushings or paraneoplastic, decreased if exogenous cause)
If a patient has cushing disease, high dose dexamethasone suppression test will show _
If a patient has cushing disease, high dose dexamethasone suppression test will show adequate suppression
If a high-dose dexamethasone test shows no suppression, the cause is likely _
If a high-dose dexamethasone test shows no suppression, the cause is likely exogenous
* If the source is pituitary, cortisol should decrease
If CRH stimulation test reveals increased ACTH and increased cortisol, the cause is (cushing/paraneoplastic)
If CRH stimulation test reveals increased ACTH and increased cortisol, the cause is Cushing disease
* Paraneoplastic will show no increase in ACTH or cortisol
Describe the pathway of normal aldosterone secretion
Low BP or low renal perfusion –> increase renin –> RAAS activation –> increases angiotensin II –> signals to the zona glomerulosa –> increase aldosterone
Primary hyperaldosteronism is caused by _
Primary hyperaldosteronism is caused by hyperplasia of zona glomerulosa
* Unilateral adrenal adenoma- Conn’s
* Bilateral adrenal hyperplasia
Secondary hyperaldosteronism is caused by _
Secondary hyperaldosteronism is caused by increased RAAS/renin release
* CHF, liver failure, renal artery stenosis
Low K+ levels can lead to ADH desensitization and _
Low K+ levels can lead to ADH desensitization and nephrogenic DI –> polyuria, polydipsia
Hyperaldosteronism may present with _ clinical signs
Hyperaldosteronism may present with secondary HTN, headache, muscle weakness, palpitations, cardiac arrhythmia
Na+ levels may be high or even normal in a patient with hyperaldosteronism, why?
Aldosterone escape –> adequate Na+ excretion in the urine (natriuresis) –> no edema
Hyperaldosteronism is associated with metabolic _
Hyperaldosteronism is associated with metabolic alkalosis
Primary hyperaldosteronism is associated with _ renin levels
Primary hyperaldosteronism is associated with low renin
_ is a drug that can be used in the treatment of hyperaldosteronism
Spironolactone is a drug that can be used in the treatment of hyperaldosteronism
The most common tumor of the adrenal medulla in children is _
The most common tumor of the adrenal medulla in children is neuroblastoma
The most common tumor of the adrenal medulla in adults is _
The most common tumor of the adrenal medulla in adults is pheochromocytoma
Pheochromocytoma involves abnormal proliferation of _ cells
Pheochromocytoma involves abnormal proliferation of chromaffin cells
* Increases production of epi, norepi, dopamine
Pheochromocytoma involves a proliferation of cells that are derived from _ embryologic structure
Pheochromocytoma involves a proliferation of cells that are derived from neural crest
Pheochromocytomas are associated with _ genetic markers
Pheochromocytomas are associated with:
* NF-1
* VHL
* MEN2a, 2b
Pheochromocytomas are associated with which MEN syndromes?
MEN2A, MEN2B
In addition to increased catecholamines, pheochromocytomas can be diagnosed by the presense of _ in the urine and plasma
In addition to increased catecholamines, pheochromocytomas can be diagnosed by the presense of metanephrines in the urine and plasma
Pheochromocytomas will have positive _ and _ neuroendocrine cell markers
Pheochromocytomas will have positive chromogranin and synaptophysin
How do we manage pheochromocytomas?
alpha antagonists –> beta blockers –> tumor resection
Why do alpha antagonists need to be given before beta blockers?
Don’t leave alpha unopposed –> could result in hypertensive crisis (drop HR with beta blockers can cause BP to shoot up)
Neuroblastoma is associated with the amplification of _ oncogene
Neuroblastoma is associated with the amplification of N-myc
Neuroblastomas result in a tumor along the _
Neuroblastomas result in a tumor along the sympathetic chain
The classic presentation of a neuroblastoma is a child with _
The classic presentation of a neuroblastoma is a child with abdominal distension and a firm mass that crosses the midline, may also have jerky movements of the eyes and feet (opsoclonus-myoclonus)
Neuroblastoma is associated with two markers, _ and _
Neuroblastoma is associated with two markers, +NSE and +Bombesin
Neuroblastoma will present with increased urine _
Neuroblastoma will present with increased urine VMA, HVA
Neuroblastoma has a characteristic _ on histology
Neuroblastoma has a characteristic homer-wright rosette on histology
Neuroblastomas are treated with _
Neuroblastomas are treated with resection, chemotherapy, and radiation
Adrenal carcinoma is _
Adrenal carcinoma is a tumor of the adrenal cortex
* May secrete glucocorticoids, mineralocorticoids, androgens, estrogens
Adrenal carcinoma will present clinically with _
Adrenal carcinoma will present clinically with abdominal/back pain, abdominal mass and sx of high cortisol, aldosterone, androgens, and estrogens
Adrenal carcinoma will have _ response to dexamethasone suppression test
Adrenal carcinoma will have no response to dexamethasone suppression test
Aromatase is present in _ tissue; it converts testosterone –> estrogen
Aromatase is present in adipose tissue; it converts testosterone –> estrogen
* Increased adipose = increased aromatase
_ is responsible for internal virilization in males
Testosterone is responsible for internal virilization in males
_ is responsible for external virilization in males
DHT is responsible for external virilization in males
If the enzyme (11,17,21) begins with 1, then its deficiency causes _
If the enzyme (11,17,21) begins with 1, then its deficiency causes HTN
If the enzyme (11,17,21) ends with 1, then its deficiency causes
If the enzyme (11,17,21) ends with 1, then its deficiency causes female virilization
The adrenal cortex is derived from the _
The adrenal cortex is derived from the mesoderm
The adrenal medulla is derived from the _
The adrenal medulla is derived from the neural crest (ectoderm)
The _ is composed of post-ganglionic sympathetic cells aka the chromaffin cells
The adrenal medulla is composed of post-ganglionic sympathetic cells aka the chromaffin cells
Pheochromocytoma and neuroblastoma are two neoplasms in the _ region
Pheochromocytoma and neuroblastoma are two neoplasms in the adrenal medulla
Neoplasms in the adrenal cortex are either _ or _
Neoplasms in the adrenal cortex are either carcinomas or adenomas
Presentation of pheochromocytoma:
Presentation of pheochromocytoma:
* Secondary HTN
* Episodes of sweating, headache, palpitations
* Paroxysmal hypertensive crisis
* Arrythmias, sudden death, heart failure
Pheochromocytomas are usually (benign/malignant) and (unilateral/bilateral)
Pheochromocytomas are usually benign and unilateral
Pheochromocytoma: well circumscribed, red-brown/dusty
Pheochromocytoma:
* Polygonal/spindle cells
* Nests with vascular network
* Round nuclei, nucleoli
* Red-purple cytoplasm
Pheochromocytoma may present with elevated urine/ plasma _
Pheochromocytoma may present with elevated urine/ plasma metanephrines (HVA, MVA)
Before pheochromocytoma surgery we pretreat with _ and _
Before pheochromocytoma surgery we pretreat with phenoxybenzamine (alpha antagonist) and metoprolol (beta blocker)
Pheochromocytoma and neuroblastomas are both neoplasms of the medulla but pheos are derived from _ cells and neuroblastomas are derived from _
Pheochromocytoma and neuroblastomas are both neoplasms of the medulla but pheos are derived from chromaffin cells and neuroblastomas are derived from neural crest cells (primitive cells)
Complications of neuroblastomas include:
Complications of neuroblastomas include:
* Metastasis
* Hypertension
* Opsoclonus-Myoclonus
* Constipation
* Spinal cord compression
Neuroblastoma: hereogeneous, necrosis, irregular border
Neuroblastoma
* Classic homer-wright rosettes
Of the adrenal hormones, _ and _ are regulated by ACTH
Of the adrenal hormones, cortisol and androgens are regulated by ACTH
* Aldosterone is regulated by renin and angiotensin
The one adrenal hormone that is not significantly affected in secondary AI is _
The one adrenal hormone that is not significantly affected in secondary AI is aldosterone
Hyperpigmentation is a sign of _ AI
Hyperpigmentation is a sign of primary AI (ACTH is high)
_ is an emergency that is triggered by a stressor and causes severe weakness, fatigue, weight loss, nausea, hypotension, hyponatremia, and hypoglycemia
Adrenal crisis is an emergency that is triggered by a stressor and causes severe weakness, fatigue, weight loss, nausea, hypotension, hyponatremia, and hypoglycemia
In primary AI, hyponatremia is two fold; _ and _
In primary AI, hyponatremia is two-fold
1. Low aldosterone
2. Low cortisol
Low cortisol causes hyponatremia through _
Low cortisol causes hyponatremia through excess secretion of ADH
In secondary AI, hyponatremia is caused by _ alone
In secondary AI, hyponatremia is caused by low cortisol –> high ADH alone (aldosterone is preserved by RAAS)
The most common cause of secondary AI is _
The most common cause of secondary AI is withdrawal of chronic glucocorticoids
Treatment for primary AI
Treatment for primary AI: glucocorticoids and mineralocorticoids
Treatment for secondary AI
Treatment for secondary AI: glucocorticoids (aldosterone will be normal bc of RAAS)
How do we treat adrenal crisis?
Isotonic fluids, glucocorticoids, dextrose
Congenital adrenal hyperplasia are disorders caused by _
Congenital adrenal hyperplasia are disorders caused by enzyme deficiencies in adrenal steroid synthesis pathway
All congenital adrenal hyperplasia conditions are _ inheritence pattern
All congenital adrenal hyperplasia conditions are autosomal recessive
Females with androgen excess may present with _
Females with androgen excess may present with ambiguous genitalia, clitoromegaly, irregular infertility, hirsuitism
The gene mutation associated with 21-hydroxylase deficiency is _
The gene mutation associated with 21-hydroxylase deficiency is CYP21A
The gene mutation associated with 11B-hydroxylase deficiency is
The gene mutation associated with 11B-hydroxylase deficiency is CYP11B1
The gene mutation associated with 17a-hydroxylase deficiency is
The gene mutation associated with 17a-hydroxylase deficiency is CYP17A1
21-hydroxylase deficiency is associated with:
_ cortisol
_ aldosterone
_ androgens
21-hydroxylase deficiency is associated with:
Low cortisol (deficient)
Low aldosterone (deficient)
High androgens
21-hydroxylase deficiency can be diagnosed with _ 17-OH-progesterone and _ DHEA
21-hydroxylase deficiency can be diagnosed with high 17-OH-progesterone and high DHEA, along with low cortisol and high ACTH
What are the hormone deficiencies/excesses seen in 11B-hydroxylase deficiency?
Cortisol and aldosterone = deficient
Androgen and 11-deoxycorticosterone = excess
17a-hydroxylase is associated with which hormone def/excesses?
Mineralocorticoid excess
Androgen deficiency
The hallmark of CAH is excess _ which causes adrenal hyperplasia
The hallmark of CAH is excess ACTH which causes adrenal hyperplasia
All CAH have low _
All CAH have low cortisol
Severe hypokalemia can cause muscle weakness or _ changes on EKG
Severe hypokalemia can cause muscle weakness or T wave inversions on EKG
Adrenal adenoma
Renal artery stenosis
_ or _ can be used for an aldosterone suppression test
IV saline or oral salt loading can be used for an aldosterone suppression test
Ald/Renin > 30 indicates _
Ald/Renin < 30 indicates _
Ald/Renin > 30 indicates primary hyperaldosteronism
Ald/Renin < 30 indicates secondary hyperaldosteronism
What are the complications associated with cushings?
- Diabetes
- Hypertension
- Osteoporosis
- DVT
- Infections
- Cataracts
- Glaucoma
Why does cushing syndrome have signs and sx of mineralocorticoid and adrenal androgen excess?
High levels of cortisol can have effects on MR and androgen receptors
High dose dexamethasone suppression test will only suppress (cushing disease/ectopic ACTH secretion)
High dose dexamethasone suppression test will only suppress cushing disease, not ectopic ACTH
The 6 P’s of pheochromocytomas:
The 6 P’s of pheochromocytomas:
1. Pain (headaches)
2. Pressure (BP)
3. Palpitations
4. Perspiration
5. Pallor
6. Panic attacks
The most common inherited syndrome in a patient with pheochromocytoma is _ and this is associated with a _ gene mutation
The most common inherited syndrome in a patient with pheochromocytoma is MEN2 and this is associated with a RET gene mutation
* NF-1 and VHL are less common
We can use a _ suppression test to confirm a pheochromocytoma
We can use a clonidine suppression test to confirm a pheochromocytoma
Ingestion of licorice mimics which hormone excess?
Aldosterone
The classic triad of pheochromocytoma is _
The classic triad of pheochromocytoma is
1. Headache
2. Hypertension
3. Palpitations
