Pathoma- Chapter 15: Adrenal Cortex and Adrenal Medulla
Secondary/Tertiary Adrenal Insuffieciency What is the metyrapone stimulation test?
-Diagnosis involves measurement of serum electrolytes, morning/random serum cortisol and ACTH (low cortisol, high ACTH in 1° adrenal insufficiency; low cortisol, low ACTH in 2°/3° adrenal insufficiency due to pituitary/hypothalamic disease), and response to ACTH stimulation test. Alternatively, can use metyrapone stimulation test: metyrapone blocks last step of cortisol synthesis (11-deoxycortisol to cortisol). -Normal response is decrease cortisol and compensatory increase ACTH and 11-deoxycortisol. -In 1° adrenal insufficiency, ACTH is increased but 11-deoxycortisol remains decreased after test. -In 2°/3° adrenal insufficiency, both ACTH and 11-deoxycortisol remain decreased after test.
If surgery is not an option to remove the ACTH-secreting pituitary adenoma, what can be done?
-Drugs like ketoconazole or metyrapone can be useful if surgery is not an option
What is the underlying cause of the bilateral adrenal hyperplasia?
-Due to high ACTH levels (lack of negative feedback) acting on the adrenals
What is Chronic Adrenal Insufficiency due to?
-Due to the progressive destruction of the adrenal glands
Pheochromocytoma: Clinical Features
-Episodic HTN -Headaches -Palpitations -Tachycardia -Sweating
Cushing Syndrome: Causes What is the most common cause of Cushing Syndrome?
-Exogenous Corticosteroids
Cushing Syndrome: Causes Which cause is the only one that will result in atrophy of both adrenal glands (very high-yield)?
-Exogenous corticosteroid administration
What are the 4 main causes of Cushing Syndrome (very high-yield!!!)?
-Exogenous corticosteroids -Primary adrenal adenoma, hyperplasia, or carcinoma -ACTH-secreting pituitary adenoma -Paraneoplastic ACTH secretion
21-hydroxylase Deficiency How will the Classic form of the disease present in women?
-Females will have clitoral enlargement (genital ambiguity)
What is the treatment for 11-beta-hydroxylase deficiency?
-Glucocorticoids
What is the treatment for 21-hydroxylase deficiency?
-Glucocorticoids -Mineralocorticoids
What is the treatment for 17-alpha-hydroxylase deficiency?
-Glucocorticoids -Sex steroids
What are the treatments for adrenal insufficiency?
-Glucocorticoids and mineralocorticoids
What is the underlying problem in Cushing Syndrome?
-Have an excess of cortisol
Waterhouse-Friderichsen Syndrome What is it?
-Hemorrhagic necrosis of the adrenal glands
Waterhouse-Friderichsen Syndrome Pathophysiology (very high-yield!!!!)
-Hemorrhagic necrosis of the adrenal glands -This results in acute lack of cortisol- this would then exacerbate the pts. hypotension (that they already have from the N. meningitidis infection and DIC)- on top of that, they get this massive hypotension due to a lack of cortisol
What signs suggest primary adrenal deficiency?
-Hyperpigmentation (high ACTH) and hyperkalemia (low aldosterone)
Chronic Adrenal Insufficiency: Clinical Features
-Hypotension- due lack of cortisol which is necessary to maintain vascular tone -Hyponatremia, hypovalemia, and hyperkalemia- due to lack of aldosterone (so you will have salt- wasting) -Hyperpigmentation -Vomiting and diarrhea- due to a lack of cortisol
Chronic Adrenal Insufficiency: Clinical Features Why will pts. have hyperpigmentation?
-If you don't have any cortisol being produced, you are not going to be able to shut down the production of ACTH via negative-feedback on the anterior pituitary- this will result in excess production of ACTH -ACTH is derived from a molecule called POMC -One of the other derivatives of POMC is alpha-melanocyte stimulating hormone- which stimulate the melanocytes- resulting in hyperpigmentation -Excess ACTH production can also lead to an increase in alpha-MSH
Cushing Syndrome: Clinical Features (Based on Effects of Cortisol) Why will pts. have moon facies, a buffalo hump, and truncal obesity?
-If you have increased gluconeogenesis, you will have high glucose in the blood -The high glucose is going to result in excess insulin being produced by the pancreas -The excess insulin will then result in the storage of fat- in the face, on the back of the neck, and on the trunk
What are the mechanisms by which Secondary Hyperaldosteronism can occur?
-In a young woman, you can get something called fibromuscular dysplasia- which results in thickening of the wall of the renal artery- which would then decrease the blood flow to the kidney- this would activate the JGA -In elderly males, you could get atherosclerosis of the renal artery- which would then decrease the blood flow to the kidney- also activating the JGA
Where does aldosterone work in the nephron?
-In the late distal tubule and the collecting duct
What is hyperaldosteronism?
-Is when you have excess aldosterone
Cushing Syndrome: Clinical Features (Based on Effects of Cortisol) How does cortisol raise the blood sugar?
-It breaks down muscle to provides the AAs necessary for gluconeogenesis
What are the 3 pathways that pregnenolone can enter in the adrenal cortex?
-It can produce mineralocorticoids (aldosterone) (glomerulosa) -It can produce glucocorticoids (cortisol) (fasciculata) -It can also produce sex steroids (reticularis)
What does the high-dose dexamethasone do to ACTH production by an ectopic source?
-It fails to suppress ectopic ACTH production by a small cell lung carcinoma though -Since ACTH production has not changed- there will be no change in cortisol levels
What does the high-dose dexamethasone do to ACTH production by a pituitary adenoma?
-It has the ability to suppress ACTH production by a pituitary adenoma -This will decrease the amount of cortisol being produced
What is a Pheochromocytoma?
-It is a tumor of the chromaffin cells
What is the inheritance pattern of SAME?
-It is autosomal recessive
What is the inheritance pattern of congenital adrenal hyperplasia?
-It is autosomal recessive
What is cholesterol converted to in the adrenal cortex?
-It is converted into pregnenolone (via the enzyme desmolase)
Diagnosis of Cushing Syndrome How does the low-dose dexamethasone test diagnose Cushing syndrome?
-It suppresses cortisol in normal individuals but fails to suppress cortisol in all causes of Cushing syndrome
What does the alpha-intercalated cell do in response to aldosterone?
-It will dump H+ into the lumen of the nephron
Chronic Adrenal Insufficiency What type of cancer LOVES to metastasize to the adrenal glands (very high-yield!!!!)?
-Lung cancer LOVES to metastasize to the adrenal glands -This is very high-yield!!!!!!
What are the genetic syndromes that a pheochromocytoma are associated with?
-MEN 2A and 2B -von Hippel-Lindau disease -Neurofibromatosis type 1
What food can also result in SAME (high-yield!!!!)?
-May also arise with licorice (glycyrrhetinic acid)- which also blocks 11-Beta-HSD2
What is the key thing that kills pts. with MEN 2A and 2B?
-Medullary carcinoma of the thyroid is the key thing that ends up killing patients -One way to avoid the development of the medullary thyroid carcinoma is by removing the thyroid prophylactically
What will the epinephrine be broken down into?
-Metanephrine
Primary Hyperaldosteronism What is the treatment for bilateral adrenal hyperplasia?
-Mineralocorticoid receptor antagonist (e.g., spironolactone or eplerenone) -Adenoma and carcinoma are resected
Zona Glomerulosa What will this portion of the adrenal cortex secrete?
-Mineralocorticoids (such as aldosterone)
What enzyme breaks down metanephrine and normetanephrine into VMA?
-Monoamine oxidase
Cushing Syndrome: Clinical Features (Based on Effects of Cortisol)
-Muscle weakness with thin extremities -Moon facies, buffalo hump, and truncal obesity -Abdominal striae -HTN -Osteoporosis -Immune suppression
Cushing Syndrome: Clinical Features (Based on Effects of Cortisol) As a result of increasing gluconeogenesis by breaking down muscle, what symptoms will pts. have?
-Muscle weakness with thin extremities -This is because you are breaking down the muscle to provide the AAs necessary for gluconeogenesis
VHL Disease Pts. have an increased risk for what (high-yield)?
-Mutation of the VHL tumor suppressor gene -Pts. have an increased risk for hemangioblastoma of the cerebellum, an increased risk for renal cell carcinoma, and an increased risk for a pheochromacytoma
What will the Norepinephrine be broken down into?
-Normetanephrine
How will the adrenal glands appear if the underlying cause of the Cushing Syndrome is due to an adrenal adenoma, carcinoma, or hyperplasia?
-One of the adrenal glands will be large (due to either the adenoma, carcinoma, or hyperplasia) -The large adrenal gland will be secreting excess cortisol -The excess cortisol will go into the blood- and hit the anterior pituitary and shut down the production of ACTH -When ACTH production is shut down, the opposite adrenal gland will actually become atrophied
Pheochromocytoma: Rules of 10s What is a high-yield location for an extra-medullary pheochromocytoma?
-Organ of Zuckerkandl at the inferior mesenteric artery root -Or the bladder wall (very high-yield!!!)
Pheochromocytoma: Adrenalectomy What drug must you give before you remove the tumor (very high-yield!!!!!!)?
-Phenoxybenzamine (irreversible alpha-blocker) followed by Beta-blocker is administered preoperatively to prevent a hypertensive crisis (very high-yield!!!!) -Catecholamines may leak into the bloodstream upon manipulation of the tumor!!!!!
Chronic Adrenal Insufficiency (Addison Disease) What are some other causes of Addison disease?
-Pituitary damage (secondary) -Hypothalamic damage (tertiary)
How does Liddle syndrome present?
-Presents as a child with HTN, hypokalemia, and metabolic alkalosis -With low renin and aldosterone levels (very high-yield!!!)
How will SAME present?
-Presents as a child with HTN, hypokalemia, and metabolic alkalosis -With low renin and aldosterone levels (very high-yield!!!)
21-hydroxylase Deficiency How will the Classic form of the disease present in neonates?
-Presents as hyponatremia and hyperkalemia with life-threatening hypotension (salt-wasting type)
21-hydroxylase Deficiency When does the Non-classic form present?
-Presents later in life with androgen excess (high-yield)
Cushing Syndrome: Causes Which cause is the only one that will result in atrophy of one of the adrenal glands and enlargement of the other (very high-yield)?
-Primary adrenal adenoma, hyperplasia, or carcinoma
What is Conn Syndrome?
-Primary hyperaldosteronism, also known as primary hyperaldosteronism or Conn's syndrome, is excess production of the hormone aldosterone by the adrenal glands resulting in low renin levels.
Primary vs. Secondary Hyperaldosteronism
-Primary is characterized by low renin and no edema (aldosterone escape) -Secondary is characterized by high renin; edema is often present
What is the key gene in MEN 2A and 2B before you remove the thyroid (very high-yield!!!!)?
-RET proto-oncogene
What is the treatment for Cushing Syndrome caused by a primary adrenal adenoma, hyperplasia, or carcinoma?
-Resection of the adenoma/carcinoma or bilateral resection of hyperplasia with hormone replacement
What is the treatment for Cushing Syndrome due to Ectopic ACTH secretion?
-Resection of the ectopic source
Glucocorticoid-remediable aldosteronism (GRA) How can it be treated (high-yield!!!!!)
-Responds to dexamethasone (high-yield???!) -He totally skipped this section in the videos....
So if there is a deficiency in 21-hydroxylase, pregnenolone will be shunted to what pathway?
-Result in the preferential production of sex steroids -So the levels of the sex steroids will increase
Why is spironolactone not effective at treating Liddle Syndrome?
-Spironolactone is a specific pharmacologic antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule -The underlying pathophysiology of Liddle syndrome is NOT mediated by the actions of aldosterone (in fact, aldosterone levels will be low in Liddle Syndrome); it is mediated by the aberrant expression of the ENaC channels -As a result of this, spironolactone will have no effect in regards to the treatment
What is the treatment for a Pheochromocytoma?
-Surgical Excision (adrenalectomy)
Chronic Adrenal Insufficiency What is the most common cause in the Developing World?
-TB destruction of the adrenal gland
What is the treatment for Cushing Syndrome caused by exogenous glucocorticoids?
-Tapering of steroids- if possible
Cushing Syndrome: Causes What will happen with an ACTH-secreting pituitary adenoma?
-The adenoma in the pituitary is secreting ACTH -This ACTH will hit both of the adrenal glands when it goes into the blood- this overstimulation via excess ACTH will result in both adrenals becoming large -Both of the adrenal glands will become large and produce excess cortisol- which will result in Cushing Syndrome
The Chromaffin cells of the adrenal medulla are the main physiologic source of what (very high-yield!!!)?
-The catecholamines (epinephrine and norepinephrine)
Cushing Syndrome: Causes Exogenous Corticosteroids
-The doctors prescribed exogenous corticosteroids to the pt.- and as a result of those exogenous corticosteroids, the pt. will develop Cushing Syndrome
What is the underlying problem in primary hyperaldosteronism?
-The high aldosterone is due to a primary problem within the adrenal gland
Steroidogenesis in the Adrenal Cortex What happens if you are lacking 17-alpha-hydroxylase?
-The only thing that you are going to produce is excess mineralocorticoids -Need 17-alpha-hydroxylase to produce cortisol and sex steroids
What are the 2 main cell types in the late distal tubule and the collecting duct regions of the nephron?
-The principle cell -The alpha-intercalated cell
What does the principal cell do in response to aldosterone?
-The principle cell will reabsorb Na+ and secrete K+ into the lumen of the nephron
What will be seen in a pt. with hyperaldosteronism?
-The pt. will get hypernatremia- because they are increasing the reabsorption of sodium -They are going to get hypokalemia- because they are dumping potassium -They are going to get a metabolic alkalosis because they are dumping H+ ion
What is the function of renin?
-The renin converts angiotensinogen to angiotensin I
If on a Board exam they give you the classic history of someone who has 21-hydroxylase deficiency but they don't have salt-wasting or hyperkalemia and doesn't have hypovolemia, what should you be thinking about (very high-yield!!!!)?
-They have an 11-Beta-hydroxylase deficiency (very high-yield!!!!!)
On a Board exam, if you have a pt. who gets HTN when they urinate, what should you be thinking about (very high-yield!!!!!)?
-Think about a pheochromocytoma involving the wall of the bladder (very high-yield!!!!!!)
21-hydroxylase Deficiency What does the decrease in aldosterone result in?
-This loss of aldosterone will result in salt-wasting -The function of aldosterone is to reabsorb Na+ and dump K+ -So if you are lacking aldosterone, you are going to lose Na+ (salt-wasting), and you are going to hold onto K+ -So the patients will suffer from hyponatremia and hyperkalemia (due to the salt-wasting) -Furthermore, since water would follow the Na+ that was being reabsorbed, it will no longer come in due to the lack of Na+ reabsorption- this can result in hypovolemia
What are the manifestations of Nelson Syndrome?
-This will result in hyperpigmentation, headaches, and bitemporal hemianopsia
What is the treatment for Cushing Syndrome caused by an ACTH-secreting pituitary adenoma?
-Transsphenoidal resection of pituitary adenoma
Both metanephrine and normetanephrine be broken down into?
-VMA
How is the diagnosis of Cushing Syndrome made?
-Via increased 24-hour urine cortisol levels -Via late-night salivary cortisol level (increased) -Low-dose dexamethasone suppression test
Since both of the adrenal glands will enlarged in the case of an ACTH-secreting pituitary adenoma and Paraneoplastic ACTH secretion- how do you distinguish between the two?
-Via the High-dose dexamethasone suppression test
What is the classic high-yield example of acute adrenal insufficiency (very high-yield!!!!)
-Waterhouse-Friderichsen syndrome
Zona Reticularis What will this portion of the adrenal cortex secrete?
-Weak androgens (e.g., DHEA) (sex steroids)
What is the high-dose dexamethasone test?
-When you give a pt. high-dose dexamethasone (which is a cortisol analog) -It has the ability to suppress ACTH production by a pituitary adenoma -It fails to suppress ectopic ACTH production by a small cell lung carcinoma though
Why will pts. with hyperaldosteronism get HTN?
-When you grab Na+, water is going to follow- which will result in an increase in blood volume- leading to HTN
What is adrenal insufficiency?
-When you have a lack of adrenal hormones
Cushing Syndrome: Causes Why will the adrenal glands become atrophic as a result of exogenous corticosteroid administration?
-When you have exogenous cortisol in the blood- that cortisol will go to the anterior pituitary and shut down the production of ACTH -When you shut down the production of ACTH- this will then result in both adrenal glands becoming small (bilateral adrenal atrophy)
Primary Hyperaldosteronism Why will the renin levels be low (very high-yield!!!!)?
-When you have high aldosterone, you are going to grab sodium and H2O is going to follow- this will increase the blood volume -That high blood volume is then going to go to the kidney- so the kidney is going to see an increase in blood flow -This increased blood flow to the kidney will decrease the production of renin
What is congenital adrenal hyperplasia?
-When you have hyperplasia of both adrenal glands due to a congenital defect in the enzymes necessary for steroidogenesis -Leading to excess sex steroids
What are the signs of 11-Beta-hydroxylase deficiency?
-Will see an androgen excess- leading to clitoral enlargement (genital ambiguity) in females -However, you will have increased levels of deoxycorticosterone
What signs suggest secondary/tertiary adrenal insufficiency?
-Will see no hyperpigmentation (low ACTH) and normal potassium (normal aldosterone)
What will the renin and aldosterone levels be in Liddle Syndrome?
-With low renin and aldosterone levels (very high-yield!!!)
What will the renin and aldosterone levels be in SAME?
-With low renin and aldosterone levels (very high-yield!!!)
Steroidogenesis in the Adrenal Cortex What would be seen with a 11-hydroxylase deficiency?
-Would not be able to produce cortisol -Would also get some shunting towards sex steroid synthesis -However, there would be a little bit of production of the weak mineralocorticoids (DOC)- so you wouldn't see any salt-wasting
What happens when the JGA is activated?
-You are going to then secrete renin
What is the cause of Secondary Hyperaldosteronism due to?
-You get high aldosterone secondary to the fact that you have activate the renin-angiotensin system
Cushing Syndrome: Causes What will happen in paraneoplastic ACTH secretion?
-You have a tumor (the most classic example is a small cell carcinoma of the lung)- the tumor secretes ACTH -That ACTH goes into the blood and acts on both adrenal glands -Both adrenal glands will become large and produce cortisol- which will result in Cushing Syndrome
Pheochromocytoma How will it appear on gross exam (very high-yield!!!!)?
-You will get a brown tumor!!!!!!! -This is because the adrenal medulla, itself, is brown- so a tumor of the adrenal medulla will also be brown
What will the renin levels be in Secondary hyperaldosteronism?
-You will have a high renin level
Primary Hyperaldosteronism What will the serum levels be of aldosterone and renin?
-You will have high aldosterone (hence the name) -Will have a low renin level
What are the 3 layers of the adrenal cortex (high-yield)?
-Zona glomerulosa -Zona fasciculata -Zona reticularis
What is the classic malignancy that results in paraneoplastic ACTh secretion?
-small cell carcinoma of the lung -Also seen in carcinoid tumors
Cushing Syndrome: Clinical Features (Based on Effects of Cortisol) Why will these pts. suffer from immune suppression (high-yield!!!)?
1.) Cortisol inhibits phospholipase A2- this results in the inability to generate arachidonic metabolites- which are essential for inflammation 2.) It inhibits IL-2- an important T-cell growth factor 3.) Inhibits the release of histamine from mast cells- histamine is essential for vasodilation and increased vascular permeability -These mechanisms are very high-yield!!!!!
Waterhouse-Friderichsen Syndrome Gross Example (very high-yield!!!)
-'Sack of blood' adrenal- that classically shows up on exams
Pheochromocytoma: Rules of 10s
-10% bilateral -10% familial (in kids) -10% malignant -10% located outside of the adrenal medulla -10% calcify
What happens in Syndrome of Apparent Mineralocorticoid Excess (SAME)?
-11-Beta hydroxysteroid dehydrogenase 2 (11-Beta-HSD2) deficiency allows cortisol to activate renal aldosterone receptors
What is the role of 11-Beta-HSD2?
-11-Beta-HSD2 converts cortisol to cortisone in mineralocorticoid-responsive cells (like the ones in the zona glomerulosa) -This prevents cortisol from acting on the Mineralocorticoid receptors- which it can do at high enough concentrations!!!!
Steroidogenesis in the Adrenal Cortex What do you need in order to produce the next level of mineralocorticoids (aldosterone)?
-11-hydroxylase
Steroidogenesis in the Adrenal Cortex What enzyme do you need in order for pregnenolone to enter into the pathway to develop cortisol and sex steroids?
-17-alpha-hydroxylase
Steroidogenesis in the Adrenal Cortex In which enzyme deficiencies will the levels of 17-hydroxyprogesterone be decreased?
-17-alpha-hydroxylase deficiency
Steroidogenesis in the Adrenal Cortex What enzyme do you need to produce weak mineralocorticoids (11-deoxycorticosterone (DOC))?
-21-hydroxylase
What enzyme do you need to produce mineralocorticoids and cortisol from pregnenolone?
-21-hydroxylase
Steroidogenesis in the Adrenal Cortex What enzymes do you need in order to produce Cortisol?
-21-hydroxylase -11-hydroxylase
Congenital Adrenal Hyperplasia What is the most common deficiency seen?
-21-hydroxylase deficiency
Steroidogenesis in the Adrenal Cortex In which enzyme deficiencies will the levels of 17-hydroxyprogesterone be increased?
-21-hydroxylase deficiency -11-alpha-hydroxylase deficiency
What is the most common cause of primary hyperaldosteronism?
-A benign tumor (adenoma) of the adrenal gland
What test is used to distinguish between secondary and tertiary adrenal insufficiency?
-ACTH response with CRH stimulation test suggests hypothalamic (tertiary) disease
What happens in Glucocorticoid-remediable aldosteronism (GRA) and what is its inheritance pattern?
-Aberrant expression of aldosterone synthase in the zona fasciculata due to an autosomal dominant genetic mutation- leading to familial hyperaldosteronism -This makes the aldosterone synthase fall under the control of ACTH instead of angiotensin II -So with release of ACTH- aldosterone synthase now goes to work- producing more aldosterone -It is autosomal dominant -Read the attached image!!!
Other causes of Acute Adrenal Insufficiency
-Abrupt withdrawal of glucocorticoids -Treatment of Cushing Syndrome
What are the 2 forms of adrenal insufficiency?
-Acute and Chronic forms
Cushing Syndrome: Causes What kind of adrenal problem can lead to Cushing Syndrome?
-Adrenal adenoma -Adrenal hyperplasia -Adrenal carcinoma -All 3 of these things can produce cortisol
What are the two portions of the adrenal gland?
-Adrenal cortex -Adrenal medulla
What hormones will be decreased with 21-hydroxylase deficiency?
-Aldosterone -Cortisol
Zona Glomerulosa What is the function of aldosterone?
-Aldosterone is important for salt maintenance within the body
Glucocorticoid-remediable aldosteronism (GRA) What will the aldosterone and renin levels be?
-Aldosterone will be high, and renin will be low
Steroidogenesis in the Adrenal Cortex 17-alpha-hydroxylase Deficiency What are the signs seen in males?
-Ambiguous genitalia with undescended testes (males)
What is the treatment for Liddle Syndrome?
-Amiloride and triamterene- two K+-sparing diuretics that block the tubular Na+-channels
21-hydroxylase Deficiency How will the Non-classic form present in females?
-Androgen excess leads to hirsutism with menstrual irregularities in females
21-hydroxylase Deficiency How will the Non-classic form present in males?
-Androgen excess leads to precocious puberty in males
What is the function of Angiotensin II?
-Angiotensin II goes to the adrenal gland and causes the release of aldosterone -So you will have high aldosterone levels because of the fact that you have activated the RAAS
What enzyme converts Angiotensin I to Angiotensin II?
-Angiotensin-Converting Enzyme
Glucocorticoid-remediable aldosteronism (GRA) How will it classically present?
-As a child with HTN and hypokalemia -Aldosterone will be high, and renin will be low
Neurofibromatosis Type 1
-Associated with an increased risk for Pheochromocytoma
Chronic Adrenal Insufficiency What is the most common cause in the West?
-Autoimmune destruction of the adrenal gland
What are the 3 major causes of Chronic Adrenal Insufficiency (very high-yield!!!)?
-Autoimmune destruction of the adrenal gland -TB destruction of the adrenal gland -Metastatic carcinoma from the lung to the adrenal gland
What is the underlying cause of the adrenal hyperplasia in all 3 of the enzyme deficiencies?
-Because in all 3 of the enzyme deficiencies- cortisol levels will be low- leading to an increase inACTH stimulation- resulting in adrenal hyperplasia
Why is cortisol necessary for life (very high-yield!!!!)?
-Because it helps to maintain vascular tone- via upregulation of Alpha-1 receptors on arterioles -Excess cortisol will result in an increase in Alpha-1 receptors- which will then increase the effect of norepinephrine of the arterioles- giving the patients HTN
What is Nelson Syndrome?
-Bilateral adrenalectomy in refractory cases of Cushing disease can lead to enlargement of pituitary adenoma -This will result in hyperpigmentation, headaches, and bitemporal hemianopsia
Cushing Syndrome: Causes What will happen to the adrenal glands as a result of exogenous corticosteroid administration (high-yield!!!)?
-Both adrenal glands will actually become atrophic
How do we screen for Congenital Adrenal Hyperplasia (high-yield)?
-By checking the serum for levels of 17-hydroxyprogesterone
Primary Hyperaldosteronism What imaging modality is useful for determining the etiology?
-CT
What does the adrenal medulla secrete?
-Catecholamines- such as epinephrine and norepinephrine
The adrenal cortex secretes hormones derived from what precursor molecule?
-Cholesterol
What molecule is the starting point for steroidogenesis in the adrenal cortex?
-Cholesterol
All of the hormones produced by the adrenal cortex are derived from what precursor molecule (high-yield)?
-Cholesterol -The adrenal gland has a very distinct yellow color- which is due to the fact that it is loaded with cholesterol- which will go on to make all of the hormones secreted by the adrenal cortex
The adrenal medulla is composed of what kind of cells (very high-yield)?
-Chromaffin cells
Chronic Adrenal Insufficiency: Clinical Features Where will the hyperpigmentation classically be seen?
-Classically arises in the oral mucosa but also be present on the skin
Waterhouse-Friderichsen Syndrome Is due to what pathogen?
-Classically due to sepsis and DIC in young children with a Neisseria meningitidis infection
Glucocorticoid-remediable aldosteronism (GRA) How can the diagnosis be confirmed?
-Confirmed with genetic testing
Zona Fasciculata What will this portion of the adrenal cortex secrete?
-Cortisol
Cushing Syndrome: Clinical Features (Based on Effects of Cortisol) What is the cause of the abdominal striae?
-Cortisol impairs the synthesis of collagen -So when you have weak collage, the blood vessels can rupture very easily- so you will get these striae on the abdomen which basically represent ruptured blood vessels
21-hydroxylase Deficiency What does the decrease in cortisol result in?
-Cortisol is necessary for life because it maintains vascular tone- so lack of cortisol can lead to life-threatening hypotension -Also, decreased cortisol levels will result in decreased inhibitory feedback on the anterior pituitary- leading to an excess production of ACTH -The excess ACTH will get into the blood- acting on both adrenal glands and causing them to becoming large (why we call it congenital adrenal hyperplasia)
Cushing Syndrome: Clinical Features (Based on Effects of Cortisol) Why can the pts. develop HTN (very high-yield!!!)?
-Cortisol upregulates alpha-1 receptors on the arterioles- which then increases the effect of norepinephrine on the arterioles -At very high levels, cortisol cross-reacts with mineralocorticoid receptors (aldosterone is not increased)
Other causes of Primary Hyperaldosteronism
-Could also be due to sporadic hyperplasia or a carcinoma of the adrenal gland- which are less common causes
Steroidogenesis in the Adrenal Cortex 17-alpha-hydroxylase Deficiency What are the signs seen in females?
-Decreased androgens lead to primary amenorrhea and lack of pubic hair (females)
What are the signs of 17-alpha-hydroxylase deficiency?
-Decreased cortisol and androgen levels -Weak mineralocorticoids (DOC) are increased leading to HTN- with mild hypokalemia -Renin and aldosterone are low (?????)
What is Liddle Syndrome and what is its inheritance pattern?
-Decreased degradation of sodium channels in collecting tubules due to a genetic mutation -It is autosomal dominant
What are the signs of 11-Beta-hydroxylase deficiency?
-Deoxycorticosterone (DOC) leads to HTN (sodium retention) with mild hypokalemia -Renin and aldosterone are low -Clitoral enlargement is seen in females (genital ambiguity)- due to shunting towards androgen production
The Chromaffin cells are derived from what (very high-yield!!!)?
-Derived from the neural crest!!!!!
Pheochromocytoma How is it diagnosed (very high-yield!!!!)?
-Diagnosed by increased serum metanephrines and increased 24-hour urine metanephrines and VMA
How is SAME diagnosed?
-Diagnosed by low urinary free cortisone (high-yield- due to deficiency in the activity of 11-Beta-HSD2) and genetic testing!!!
How is Liddle syndrome diagnosed?
-Diagnosed via genetic testing
