Endocrine - Adrenal Gland (GFR, CAH)
*Adrenal Glands
- GFR zonas
Adrenal Gland Hormones
Adrenal Gland *Pathology
Pheochromocytoma
- adrenal medulla benign tumor
- chromaffin cells
--> chromocytoma - secretes atecholamines (Epi and NE)
Notes:
- Pheochromocytoma is a benign tumor of the adrenal medulla
- it is a catecholamine producing tumour
--> tachycardia
--> paroxysmal hypertensive episodes
Case Presentation:
Paraganglioma
- Differential to Pheochromocytoma
.
Clinical Case
Notes:
- note that the above, it doesn't matter that it is a paraganglioma or a pheochromocytoma
--> both produce excessive NE and Epi.
--> same clinical symptoms with high sympathetic NS: H/A, palpitations, acute HTN - NE and Epi. are both metabolised into normetanephrine and metanephrine
--> META nephrine - think of meta as being downstream of NE and Epi.
--> these would be raised in both the blood and in the urine
Adrenal Medulla = MIDDLE = "CAT in the MIDDLE of a BED curled up..."
Adrenal Cortex = OUTER = "OUTER part of kidney = GFR... and SEX"
--> In SEX, the DEEPER you go in GFR, the SWEETER IT GETS
GFR = think the RAAS system from kidney (GFR) to the adrenals for aldosterone production
G = glomerulus zona = salt = aldosterone
--> stimulated by Angiotensin 2
F = fascicularis zona = sugar = cortisol
--> stimulated by ACTH and CRH
R = reticularis zona = sex = androgens
--> stimulated by ACTH and CRH
--> note ACTH stims BOTH cortisol AND DHEA androgens
--> "CORTISOL is great in BED"
CAT in bed = adrenal medulla cat = c =atecholamines
--> Epi and norepi
--> stimulated by ACh from SNS
*Home
*CAH = congenital Adrenal Hyperplasia
- CAH are a cluster of disorders that ALL have 2 things in common
--> LOW cortisol
--> HIGH ACTH (in response to the low Cortisol) - 3 separate enzymes in order of
cholesterol --> GFR hierarchy of --> steroid hormone synthesis
CAH disorders:
- ⇩ 17 alpha A-H:
--> ⇩ 17 alpha A-H: ("17 = age you want to sexually develop and enter the Androstenedione pathway") - ⇩ 21 A-H:
--> ("21 age limit for entry to GF = GET FUCKED pathway") - ⇩ 11 Beta A-H:
--> ("11 = partial entry to 21 age limit for entry to GF = GET FUCKED pathway")
⇩ 17 alpha A-H
- ⇩ 17 alpha A-H: ("17 = age you want to sexually develop and enter the Androstenedione pathway")
- key is bigh BP and low adrostenedione
--> low adrostenedione = AMENORRHEA
⇩ 21 A-H:
- MOST COMMON of the Congenital CAH disorders
- ("21 age limit for entry to GF = GET FUCKED pathway")
⇩ 11 Beta A-H
- ("11 = partial entry to 21 age limit for entry to GF = GET FUCKED pathway")
CAH disorder Presentations
- CAH are a cluster of disorders that ALL have 2 things in common
--> LOW cortisol
--> HIGH ACTH - high ACTH acts on the melanocytes also and increases melatonin
--> High ACTH gives high skin pigmentation
decreased LH in 17 alpha hydroxylase
- you have less estrogen in 17 AH deficiency
--> no negative feedback to hypothal
--> keep producing high FSH and LH
Clinical Cases
Clinical Case
Clinical Case
Notes:
- note that
Clinical Case
Clinical Case
Notes:
- note that
Medulla = *Epi and NE
Catecholamine Synthesis
- Tyrosine --> DOPA --> dopamine --> NE --> Epi
- Tyrosine --> DOPA = rate limiting step
- TYRANTS are DOPE and they make PerMNT (permanent) Epi
Catecholamine Synthesis example
Case Presentation:
Notes:
- note PNMT = phenyl .. - N methyl transferase = last step to make Epi in the Tyrosine --> DOPA line
- note that ACTH also leaks from the cortex into the medulla to increase the PNMT and Epi synthesis
Catecholamine Release
- from the adrenal medulla --> cat in the bed
- stimulated by ACh release for Sympathetic NS
Notes:
- solution = adrenal medulla stimmed by ACH from SNS
- note that the adrenal medulla makes catechols
--> 80% mostly = epi, 20% norepi
Clinical Case
*GFR hormones
- "the deeper you go the sweeter it gets"
*Cortisol = Zona Fascicula
-
*Aldosterone = Zona Glomerulus
-
*DHEA Androgens = Zona Reticularis
-
*Metyrapone test for cortisol levels and HP-Adrenal axis
- blocks conversion of 11-hydrocortisone to cortisol in the adrenal gland
--> increases blood serum 11-hydrocortisol
--> increases urine 17- - stopping cortisol stops the negative inhibition of cortisol on the hypothal and pit
--> gives hyper ACTH release
*Adrenal crisis
- can't raise the cortisol levels int he body to respond to stress
- the most common cause of this is chronic glucocorticoid use
- nlong term prednisone causes atrophy of the CRH releasing cells of the hypothal
--> then that atrophies the ACTH cells of the anterior pit
--> then the FR of adrenal GFR atrophy and you lose the ability to make cortisol in response to stress - this is called adrenal crisis
- usually this can happen in surgeries
Clinical Cases
Clinical Case
Clinical Case
Notes:
- note that
*Addisons Disease
- "Addisons = Aldosterone Deficient"
*Conns Syndrome Disease
- "CONNs = TONS of aldosterone"
--> hyperaldosterone
Tx of Conns syndrome
- either surgery to remove primary tumors
- tx = spironolactone, epleronone
--> ONE = aldosterone blockers at the late DCT and CD
--> principle PT cells and alpha - IC cells with H+ pumps
*Cushing Disease
- Endogenous
--> either primary or
--> secondary = central - exogenous = steroid use
*dexamethasone test to diagnose Cushing Disease
-
P/C of Conns Syndrome
- recall that aldosterone acts ont he DCT and CD
- increases excretion of K+ and H+
- hypo H+ --> gives metabolic alkylosis
- hypo K+ --> gives muscle pains
*DIRTY USMAL
*CUSHINGS disease
BAE is FAT with cortisol
CUSHING 3 places you can get it
think of CUSHIN for the PUSHINin JAIL
look out in ALL 3 directions for SOAP DROPPPERS
--> 3 separate gangs in the showers
--> the DOMES and the SIDES
SYNDROME in the SIDE
DISEASE in the DOME
CUSHING SYNDROME
high cortisol
LOW ACTH
NO further workup
DEXAmethasone ACTH Supression test
Pituitary secreting
DEXA should lower ACTH
DOME goes DOWN
CENTRAL CUSHING DISEASE = "DOME DISEASE"
high cortisol
HIGH ACTH
need DEXAmethasone test
DEXAmethasone ACTH Supression test
Pituitary secreting
DEXA should lower ACTH
ECTOPIC ENDURES
ECTOPIC CUSHING
high cortisol
HIGH ACTH
need DEXAmethasone test
DEXAmethasone ACTH Supression test
ECTOPICsecreting
DEXA has NO EFFECT on ACTH
since it is ectopic SMALL cell lung CA
