Hypothalamic Pituitary Relationships and Feedback Part 2 Dr.LH Flashcards
What does the adrenal cortex secrete? (Specifically each layer)
- Zona Reticularis and Zona Fasciculata secrete Glucocorticoids and Androgens
- Zona Glomerulosa secretes Aldosterone (Mineralocorticoids)
Epinephrine and Norepinephrine fall into what class of hormones?
Catecholamines
Cortisol falls under what hormone class, and what is the action?
- Steroids (Glucocorticoid)
- Longer acting stress response
- Regulates glucose use, immune and inflammatory homeostasis
What class does Aldosterone fall under? Fxn?
- Mineralocorticoids a steroid hormone
- Regulates salt and ECF homeostasis
What is DHEAS? Fxn?
- Steroid hormone
- Androgen precursor
Where does CRH and ACTH come from, what regulates them, what do they target?
- CRH hypothalamus
- stimulated by stress physically, emotionally, or metabolic
- ACTH anterior pituitary
- stimulated by CRH
- Cortisol has negative feedback on both CRH and ACTH
Actions of cortisol?
- Immune suppression
- Gluconeogenesis
- Protein catabolism
- Lipolysis
Circadian rhythm of cortisol?
- Highest in the morning but low in late evening
Describe step by step what causes aldosterone secretion and how it fixes the issue starting with decreased BP and ending with raising the BP
- BP is decreased
- Kidney produces renin
- Liver makes Angiotensinogen
- Renin works on Angiotensinogen converting it to Angiotensin I
- ACE converts Angiotensin I to Angiotensin II
- Angiotensin II travels to Adrenal cortex and gets taken in wherer it stimulates release of Aldosterone from the cortex
- Aldosterone causes an increase in Water and Na reabsorption
- BP is increasaed
What are sx of Cushings syndrome?
- Truncal obesity
- Moon face
- Easy bruising
- Htn
- Edema
- Purple Striae
- Weakness
- Osteoporosis
- Buffalo Hump
- Acne
- Diabetes
- Immunosuppressioin
What does the Dexamethasone Suppression test do at low and high doses?
Low
- Differentiates patiess with CS of any cause from patients who don’t have CS
- No ACTH suppression indicates CS, but doesn’t tell you where this overproduction comes from
High
- Distinguishes patients with CS caused by pituitary adenoma from a non pituitary AT+CTH secreting tumor
- used after CS diagnosis
Describe the negative feedback seen in the high dose dexamethasone test.
- If ACTH decreases there is a pituitary tumor, seen by -FB on pituitary
- If ACTH doesn’t change there is an ectopic tumor as there was no -FB to decrease ACTH
How do exogenous glucocorticoids effect adrenal cells?
They c an atrophy them, they have the same negative FB effect as cortisol does
Etiology of Cushings?
- Exogenous glucocortiocoids excess
- Psuedo cushings- major depression, anxiety, acutre or chronic infections, alcoholism (rare)
- ACTH depdndent- ectopic ACTH secreting tumors, CRH secreting tumors
- ACTH independent- Adrenal adenoma/carcinoma
A patient with CS has hihgh cortisol levels, but low ACTH. Where is the tumor causing this located?
Adrenal tumor because the cortisol is exerting a -FB on the pituitary keeping ACTH low, but adrenal gland is secreting cortisol despite no signal
Cushing syndrome patient has high low CRH but high levels of ACTH and Cortisol, where is the tumor?
Pituitary tumor as it is secreting ACTH despite no signal from CRH
CS patient has high cortisol, but low ACTH release from pituitary, (High levels of ACTH in lab) and low CRH. What is happening?
Ectopic ACTH secreting tumor
Low CRH, low ACTH and low Cortisol, what caused this?
Decreased cortisol but the exogenous glucocorticoids can mimin cortisol actions so it caused -FB to occur decreasing everything.
Exogenous glucocorticoids can cause symptoms of excess cortisol
How does aldosertone work at a cellular level?
- Combines with cytoplasmic receptor and then ccomplex travels to nucleus
- Initiates transcription in the nucleus, translation & protein synthesis occur making new protein channels and pumps
- Aldosterone induced proteins mudulate existing channnels and pumps
- Results in increased Na reabsorption and K secretion
Where is ACTH derived from?
POMC, its a peptide hm also
How does increased ACTH cause hyperpigmentation?
- Formed from Pro-opiomelanocortin (POMC) in anterior pituitary
- the POMC has many peptides and some are alpha-MSH which stimulates Melanocytes
- High levels of ACTH competes with a-MSH it can be a source of producing melanin as well resulting in an increase in pigmentation
- Normally UV exposure results in a-MSH producing melanin, elevated ACTH increases this
How does the Cosyntropin stimulation test work what is it for?
- Determining primary Adrenal gland insufficiency
- Measure cortisol at 8 am where it should be high >15
- If it is less than 3 you measure ACTH
- if its btw 3-15 use Cosyntropin stimulation test
- test cortisol levels 30 min later and if levels are >18 rule out AI
- If levels are <18 after 30 min meausre ACTH comfirm AI
- ACTH low or normal you have tertiary or secondary AI
- If ACTH elevated you have primary AI
Cortisol and aldosterone secretion is decreased. What disorder primary secondary tertiary is it?
Primary adrenal deficiency it is at adrenal cortex
Cortisol decreased but renin angiotensin aldosterone axis exists. What kind of deficiency is this? 1 2 or 3
- 2 or 3 adrenal insufficiency anterior pituitary is not secreting ACTH and cortisol is not made
Causes of 1 adrenal insufficiency? (Addisons)
- Autoimmune
- Adrenal hemorrhage
- Infections
- TB
- N. Meningitidis
- Tumor metastases to adrenal gland
How do you treat Adrenal Insufficiency?
- Replacing hormones that adrenal glad isn’t making
- cortisol replaced with corticosteroid
- Aldosertone replaced with fludrocortisone a mineralocorticoid hormone
- Usually maintain aldosterone production with 2 adrenal insufficiency
Hyperaldosteronism
- Primary Hyperaldosteronism: excesssive release of aldosterone from aderenal cortex
- Secondary Hyperaldostetronism: excessive renin secretion by juxtaglomerular cells in kidney
Hypoaldosteronism
- Destruction of adrenal cortex
- Defects in aldosterone synthesis
- Inadwquate stimuation of aldosterone stimulation
What does 11B-hydroxylase do?
Pheochromocytoma presentation?
Htn
Headaches
Palpitations
Sweating
What is a pheochromocytoma?
- Benign unilateral adrenal tumor
- Catecholamines secreted by this tumor stimulate alpha and beta adrenergic receptors
Pathway to make epinephrine?
- Tyrosine to DOPA via tyrosine hydroxylase
- DOPA to Domapine via AADC and transport into vesicle called chromaffin granule
- Inside chromaffin granule dopamine converted to NE by DBH
- NEpi diffuses out and is methylated by PMNT to make Epi
- EPi transported back into Chromaffin cell via VMAT
How are catecholamines degraded?
- COMT takes Epi to Metanephrine and NEpi to Normetanephrine
- Dihydryxymandelic acid COMT to Vanillylmandelic acid
- MAO converts Normetanephrine and Metanephrine to Vanillylmandelic acid in urine
How can you confirm pheochromocytoma in a lab?
- Measure catecholamines and their byproducts such as metanephrines and VMA to see if they are elevated
Describe how B1 B2 B3 & alpha receptors respond to NE and Epi
- alpha and B3 receptors respond better to NE than Epi
- B1 responds equally
- Epi is more potent than NE for B2 receptor
