10. Adrenal Glands Flashcards
What are chromogranins?
Chromogranins are proteins that complex with epinephrine and norepinephrine to decrease the osmotic burden of individual epinephrine molecules within the chromaffin granule.
What enzyme is responsible for the breakdown of catecholamines?
Catecholamine-O-methyltransferase (COMT).
Which adrenergic receptors are found on the α cells of the pancreas?
β2 receptors
What is the function of 17,20-lyase?
What do we see in its deficiency?
Allows cholesterol to move past the cortisol pathway and into the androgen pathway.
Underdeveloped genitalia.
How does cortisol cause striations and easier bruising?
Cortisol causes the breakdown of proteins – including elastin.
Which adrenergic receptor is found on the β cells of the pancreas?
α receptors
What three enzymes lead to congenital adrenal hyperplasia?
11β-hydroxylase
21β-hydroxylase
17α-hydroxylase
When is cortisol naturally higher vs. lower?
Cortisol is naturally higher just after waking, and lowest in the late evening.
What does the plasma renin activity to plasma aldosterone concentration ratio detect?
Primary hyperaldosteroneism.
If aldosterone is high without also having high renin, you know that something is producing aldosterone without being stimulated.
Would we expect ACTH to be elevated or depressed in patients with Cushing’s syndrome?
What about with Cushing’s disease?
In Cushing’s syndrome, ACTH would be low.
In Cushing’s disease ACTH will be unusually high.
Deficiency of which adrenocortical hormone synthesizing enzyme is likely to lead to high blood pressure?
11β-hydroxylase
17α-hydroxylase
What are the primary functions of cortisol on the immune system, liver, muscle tissue, and adipose tissue?
Immune system – Inhibition of T cells and immune suppression (anti-inflammatory effect).
Liver – ↑ Gluconeogenesis.
Muscle – ↑ Protein catabolism.
Adipose tissue – ↑ Lipolysis.
What is the negative feedback mechanism for the hypothalamus, pituitary, adrenal axis?
Cortisol feeds back and negatively inhibits the anterior pituitary’s production of ACTH, as well as the hypothalamus’s production of CRH.
How is norepinephrine in the chromaffin granule converted into epinephrine?
Norepinephrine in the chromaffin granule diffuses out into the cytoplasm by facilitated transport, and then is converted into epinephrine by the cytosolic enzyme phenylethanolamine-N-methyl transferase (PNMT).
Epinephrine is then transported back into the granule by vesicular monoamine transporters (VMATs)
What do we expect to see in 21β-hydroxylase deficiency?
Decreased function of aldosterone (no 11-deoxycorticosterone).
Salt wasting due to the above.
Decreased function of cortisol.
Virilization in females.
Increased renin activity to attempt to raise aldosterone.
Which of the named diseases discussed in this lecture leads to hyperpigmentation?
What is the mechanism for this symptom?
Addison’s disease leads to hyperpigmentation.
ACTH is elevated in a futile effort to increase cortisol levels from a malfunctioning adrenal cortex.
Cushing’s disease also causes increased ACTH, and therefore hyperpigmentation.
What adrenergic receptor is found in the liver?
β2
What test can we use to detect adrenal gland insufficiency?
How does this test work?
What is the next step?
The cosyntropin (synthetic ACTH) stimulation test.
Give a patient cosyntropin, if their cortisol fails to increase, adrenal insufficiency is confirmed.
The next step is to test their ACTH to see if it is low or elevated. This determines 1°, 2°, or 3° adrenal insufficiency.
If a patient is confirmed to have adrenal insufficiency, and their adrenocorticotropic hormone levels are high, what sort of adrenal insufficiency can we expect?
What about if ACTH is low?
Adrenal insufficiency with high ACTH indicates primary adrenal insufficiency (Addison’s disease).
Adrenal insufficiency with low ACTH indicates either 2° or 3° adrenal insufficiency.
What is the rate limiting step of catecholamine synthesis?
What stimulatory molecules regulate the step?
Tyrosine -> DOPA
(catalyzed by tyrosine hydroxylase)
Stimulated by ACh and ACTH.
Why might we see low levels of serum cortisol in a patient who is taking oral prednisone?
Because exogenous glucocorticoids have the same negative feedback effect as cortisol.
What adrenergic receptors are found in adipose tissue?
β2, β3
Which receptor respond better to epinephrine then norepinephrine?
β2 receptors.
If a high dose dexamethasone suppression test fails to decrease cortisol levels, what should your differential be limited to?
Cushing’s syndrome (1° Cushing’s).
Ectopic ACTH secreting tumor.
What are the symptoms of cortisol excess?
(It’s a lot, just do your best.)
↑ Hepatic glycogen deposition.
↑ Peripheral insulin resistance – especially in adipose tissue.
↑ Gluconeogenesis.
↑ Free fatty acid production.
Adipose tissue distribution toward the abdomen and face.
↑ Salt and water retention.
↓ Bone formation – osteoporosis.
Protein catabolism and collagen breakdown of the skin, muscle, and connective tissue.
T cell inhibition and immunosuppression – anti-inflammatory actions.
↓ Linear growth.
If a low-dose of dexamethasone does not suppress cortisol levels, but a high dose of dexamethasone does – what might you suspect in your differential?
Adrenocorticotropic hormone releasing tumor – Cushing’s disease (2° Cushing’s).
Which adrenergic receptors found in the G.I. and urinary tracts?
β2
Where is DOPA converted into dopamine?
What enzyme catalyzes this step?
In the cytoplasm.
Catalyzed by aromatic amino acid decarboxylase (AADC).
What is the function of 11β-hydroxylase?
What will we see if this enzyme is deficient?
Allows the conversion of 11-deoxycorticosterone into aldosterone, as well as the final step of the conversion of cholesterol into cortisol.
Low aldosterone, high unregulated 11-deoxycorticosterone (net symptoms of high mineralcorticoids).
Low cortisol.
Increased presentation of androgens, leading to ambiguous genitalia in females.
The increase of what hormone should we associate with hyperpigmentation?
ACTH – the breakdown of which leads to α-melanocyte stimulating hormone.
How might you diagnose neck topic ACTH secreting tumor vs. Cushing’s disease?
In Cushing’s disease the pituitary tumor is derived from the same tissue of the anterior pituitary – and will respond to dexamethasone suppression at high doses.
An ectopic ACTH tumor will not have the ability to respond to negative feedback from cortisol or dexamethasone.
What adrenergic receptor is found both on the arterioles and cells of skeletal muscle?
β2
What is a pheochromocytoma?
A tumor of the adrenal medulla that secretes catecholamines.
Where is dopamine converted into norepinephrine?
What enzyme catalyzes the step?
Within the chromaffin granule.
Dopamine’s conversion into norepinephrine is catalyzed by dopamine β-hydroxylase.
What affect what elimination of ACTH have on aldosterone secretion?
Slight decrease, but essentially nothing, because aldosterone is primarily regulated by the RAAS system.
How do adrenocorticotropic hormone and cortisol influence the production of catecholamines?
ACTH stimulates synthesis of DOPA from tyrosine.
Cortisol stimulates the enzyme PNMT which converts norepinephrine into epinephrine.
What is Conn’s syndrome?
Hyperaldosteronism due to an adenoma in the adrenal cortex.
What are the signs and symptoms of Cushing’s syndrome?
(It’s a lot – do your best)
Truncal obesity.
Moon face.
Buffalo hump.
Easy bruising.
Purple striae.
Hypertension.
Edema.
Weakness.
Osteoporosis.
Hirsutism.
Acne.
Virilization.
Diabetes.
Immunosuppression.
Cognitive effects.
Why would we use a dexamethasone suppression test?
Dexamethasone suppression tests help us diagnose Cushing’s at low doses, and help us differentiate between primary and secondary Cushing’s (Cushing’s syndrome vs. Cushing’s disease) at high doses.
Which reaction is common for every pathway of adrenocortical hormone synthesis (towards aldosterone, cortisol, and androgens)?
Cholesterol -> pregnenolone.
(Catalyzed by cholesterol desmolase.)
