What is Cushing Syndrome?
Excess cortisol
Truncal obesity
Buffalo hump
Moon facies
What do you think…?
Cushing syndrome
Gluconeogenesis High blood sugar Excess insulin produced Fat storage in: Face = moon facies Back = buffalo hump Trunk = truncal obesity
Why is hypertension seen in Cushing syndrome?
Cortisol upregulates alpha 1 receptor on arterioles, amplifying effects of NE
Why is abdominal striae seen in Cushing syndrome?
Cortisol impairs synthesis of collagen
Weaken of blood vessels/rupture = abdominal striae
What 3 ways does cortisol cause immune suppression?
- Inhibits phospholipase A2 - can’t make AA metabolites for inflammation
- Inhibits IL-2 (an important T-cell growth factor)
- Inhibits histamine release from mast cells (essential for vasodilation and increased permeability)
What are the 4 main causes of Cushing syndrome?
- Exogenous corticosteroids
- Primary adrenal adenoma, hyperplasia, or carcinoma
- ACTH-secreting pituitary adenoma
- Paraneoplastic ACTH secretion (small cell lung cancer)
What cancer commonly produces paraneoplastic ACTH causing Cushing Syndrome?
Small Cell Lung Cancer
What is Cushing “DISEASE”
Pituitary Adenoma
What is the most common cause of cushing syndrome?
Exogenous corticosteroids
**bilateral adrenal atrophy
What is the only cause of Cushing syndrome that will give you bilateral adrenal atrophy?
Exogenous corticosteroids
What is the point of doing the high-dose dexamethasone test?
To distinguish a pituitary adenoma from ectopic ACTH production….
Dex suppresses ACTH production in pituitary adenoma
Dex does NOT suppress ACTH is ectopic production
Will dexamethasone shut down ACTH production from a small cell carcinoma of the lung?
NOPE! That is a cancer and it ain’t going to listen to nobody…..
What part of the adrenal gland secretes aldosterone?
Adrenal cortex- glomerulosa
Describe the renal/aldosterone axis
Low BP/flow
JGA secretes renin
Renin converts angiotensinogen to angiotensin I
ACE converts ATN 1 to ANT2
Angiotensin II stimulates aldosterone secretion from adrenal
What are the functions of aldosterone?
Increased Na+ resorption in kidney
Increased K+ excretion
H+ is excreted from alpha-intercalated cells
RAISES BLOOD PRESSURE
What is the usual cause of primary hyperaldosteronism?
Adrenal Adenoma:
High aldosterone
LOW RENIN!!!!
What are some causes of secondary hyperaldosteronism?
Activation of RAS system leading to increased Renin/Aldosterone
CHF
Decreased renal blood flow (renal artery stenosis, or fibromuscular dysplasia)
Renin-producing tumors
What is the pathology for congenital adrenal hyperplasia?
Congenital adrenal enzyme deficiency
Characterized by an enlargement of both adrenal glands due to increased ACTH stimulation (due to low cortisol)
What is the most common deficient enzyme in congenital adrenal hyperplasia?
21 hydroxylase
Which congenital adrenal hyperplasia….
Hyponatremia
Hyperkalemia
Hypovolemia & hypotension
Females have clitoral enlargement (genital ambiguity)
21-hydroxylase
Which congenital adrenal hyperplasia….
HTN w/ mild hypokalemia
Renin and aldosterone are low
11-hydroxylase
*get HTN because some 11-deoxycorticosterone is a weak mineralcorticoid thus raising blood pressure
(But still can’t make aldosterone and cortisol)
Which congenital adrenal hyperplasia….
Females = amenorrhea, lack of pubic heair Males = pseudohermaphroditism
HTN
17-hydroxylase
What infection is commonly associated with Waterhouse-friderichsen syndrome?
N. Meningititidis
DIC causes hemorrhagic necrosis of the adrenal glands
Abrupt withdrawal of glucocorticoids
Lack of cortisol exacerbates hypotension , often leading to death
What are the 3 things that can cause chronic adrenal insufficeincy?
Autoimmune destruction
TB
Metastatic Carcinoma
What type of cancer LOVES to metastasize to the adrenal glands?
LUNG CANCER!
Hypotension Hyponatremia Hypovolemia Hyperkalemia Hypoglycemia Hyperpigmentaiton Vomiting and diarrhea
What do you think?
Addison’s Disease!
Chronic Adrenal Insufficiency
What is the adrenal cortex composed of? Where is it derived from?
What is it’s main function?
Chromaffin cells
Neural crest-derived
Main physiologic source of catecholamines (Epi and NE)
Episodic HTN Headaches Palpitaitons Tachycardia Sweathing
Increased serum metanephrines and increased VMA
What do you think…?
Pheochromocytoma!
Why do you need to give phenoxybenzamine before surgical removal of a pheochromocytoma?
It is an irreversible alpha antagonist
Need to give before surgery because whey surgeons grab the tumor, may squeeze out NE and epi causing a surge…. can lead to massive HTN and death
What lesions are present in MEN-1?
Three P’s!
Pituitary Adenoma
Parathyroid Tumors
Pancreatic Tumors
What is the genetic abnormality in MEN-1?
MEN-1 gene
Tumor suppressor gene (like the breaks on the cell cycle)
What lesions are present in MEN2a?
Two P’s!
Medullary thyroid Carcinoma
Pheochromocytoma
Parathyroid Hyperplasia
What is the genetic abnormality in MEN2a?
RET gene
Protooncogene
Encodes tyrosine kinase receptor that binds to neurotrophic ligands
What lesions are present in MEN2b?
1 P!
Pheochromocytoma
Medullary thryoid carcinoma
What is the genetic abnormality in MEN2b?
RET gene
Protooncogene
Encodes tyrosine kinase receptor that binds to neurotrophic ligands
What type of inheritance for MEN syndromes?
Autosomal Dominant