LMP301 Lecture 9: Adrenal Disease Flashcards
Adrenal Diseases
Where are the adrenal glands?
On top of the kidneys
What happens to the adrenal gland during stressful situations?
enlarge
Adrenal gland is divided into…
- cortex
- medulla
The cortex of the adrenal gland is divided into…
- zona glomerulosa
- zona fasciculata
- zona reticularis
The adrenal medulla is a part of the…
SNS
Zona glomerulosa secretes….
aldosterone
zona fasciculata secretes…
- cortisol
- adrenal androgens & estrogens
zona reticularis secretes…
- cortisol
- adrenal androgens & estrogens
The adrenal medulla secretes…
- E
- NE
- Dopamine
What is the first enzyme to act on cholesterol during the biosynthesis of steroid hormones?
Cholesterol side chain cleavage hormone
What are the steroid hormones?
- aldosterone
- cortisol
- testosterone
ACTH
Signal needed for biosynthesis of steroid hormones
Enzyme cascade for aldosterone synthesis
- Cholesterol side chain cleavage hormone
- 3B-hydroxysteroid dehydrogenase
- 21 OH’ase
- 11 OH’ase
- 18 OH’ase
Enzyme cascade for cortisol synthesis
- Cholesterol side chain cleavage hormone
- 17 OH’ase
- 3B-hydroxysteroid dehydrogenase
- 21 OH’ase
- 11 OH’ase
Enzyme cascade for testosterone synthesis
- Cholesterol side chain cleavage hormone
- 17 OH’ase
- 17,20 OH’ase
- 3B-hydroxysteroid dehydrogenase
- 21 OH’ase
Which enzyme is unique to aldosterone synthesis?
18 OH’ase
Pathway of aldosterone synthesis
- Cholesterol
- Pregnenolone
- Progesterone
- Deoxycorticosterone
- Corticosterone
- Aldosterone
Pathway of cortisol synthesis
- Cholesterol
- Pregnenolone
- 17-OH pregnenolone
- 17-OH progesterone
- 11-deoxycortisol
- Cortisol
Pathway of testosterone synthesis
- Cholesterol
- Pregnenolone
- 17-OH pregnenolone
- DHEA
- Androstenedione
- Testosterone
Cortisol can affect…
metabolism of carbs, proteins, and fat
Effect of cortisol on carb metabolism
Raise blood glucose
- gluconeogenesis in liver
- reduce glucose used and stored
Effect of cortisol on protein metabolism
Break down muscle
Effect of cortisol on fat metabolism
Break down fat
What happens when glucocorticoids are present in excess?
cause central distribution of fat -> goes to face, neck, trunk
How do cortisol travel in the body?
90 - 98% is bound to proteins
- albumin
- cortisol binding globulin (CBG)
When can an increase of CBG be found?
- Pregnancy
- Estrogen treatment
How is cortisol metabolized in the body?
- Liver
2. Excreted in urine
Axis that controls cortisol secretion
Hypothalamic-pituitary-adrenaocortical axis
- Hypothalamus -> CRH
- a. pituitary -> ACTH
- adrenal cortex -> cortisol
Feedback of cortisol
Cortisol inhibits ACTH and CRH
What stimulates production of CRH?
Stress
Sleep/wake
What is too much cortisol called?
Cushing’s syndrome
Possible causes of Cushing’s syndrome
- tumour at pituitary (ACTH overproduction)
- ectopic ACTH
- adrenal gland tumour (excess cortisol)
- exogenous glucocorticoids
Ectopic ACTH
ACTH produced by cells other than the pituitary
What cells may produce ACTH, other than pituitary?
small cell carcinoma in the lung
some sources of exogenous glucocorticoids
- oral
- inhaled
- topical creams
Clinical features of Cushing’s Syndrome
- Acne
- Moon face
- Osteoporosis
- abdominal fat
- stripes on abdomen
- high BP
- buffalo hump
At what time during the day is cortisol levels the highest?
Morning
What is used to screen for Cushing’s?
24h urine test:
- High cortisol in the urine
- Can also be caused by stress & obesity
What tests are used to diagnose Cushing’s?
- plasma cortisol
- low dose dexamethasone test
- high dose dexamethasone test
- plasma ACTH
dexamethasone is…
a cortisol analogue
When is plasma cortisol measured?
8AM
10 PM
What is looked for in a plasma cortisol test?
Cortisol will not vary with time of day in patients with Cushing’s
What is looked for in a low dose dexamethasone test?
- normal: slow cortisol production by 50%
- Cushing’s: can’t slow cortisol production
What is looked for in a high dose dexamethasone test?
- Cushing’s disease: slow cortisol productivity by 50%
- Other causes: will not slow cortisol productivity
Why is high dose dexamethasone test used?
Which of the Cushing’s syndrome causes it was
Difference between Cushing’s disease and syndrome
Disease: cause is specifically a pituitary tumour producing too much ACTH
Syndrome: tissues being exposed to too much cholesterol for too long
What is looked for in plasma ACTH?
- high ACTH = ectopic ACTH tumors
- low ACTH = adrenal tumours
What order are tests used to diagnose Cushing’s?
- Screening: plasma cortisol
- Confirmation: low dose dexamethasone
- Differential diagnosis of cause: high dose dexamethasone; plasma ACTH
Cortisol is the counter hormone of…
insulin
Aldosterone is only produced in the zona glomerulosa because…
- doesn’t have 17 OH’ase
- have 18 OH’ase
- have 18 hydroxysteroid dehydrogenase
What regulates aldosterone production and secretion?
- Renin-ANG II system (major)
- ACTH
- Potassium
Biological effect of aldosterone
Raise BP:
- Na and H2O retention
- K and H secretion
Why is hypertension seen in patients with Cushing’s?
all cortisol precursors and cortisol have some kind of mineralocorticoid effects (SAME EFFECT AS ALDOSTERONE)
Renin is released in response to…
- Low tubular Na+
- Low BP at renal arteries
- SNS stimulation
Increased K+ has what effect on aldosterone?
Stimulates secretion/production
ACTH has what effect on aldosterone?
Very little effect, especially in normal situations
Function of renin
angiotensinogen -> ANG I
Function of ACE
ANG I -> ANG II
Clinical features of excess aldosterone
- high BP
- neuromuscular weakness due to lack of K+
- polydipsia & polyuria
Why is a symptom of excess aldosterone polydipsia & polyuria?
- hypokalemia causes ADH resistance = more water secreted
nephrotic diabetes insipidus is caused by…
ADH resistance
High aldosterone is…
Conn’s syndrome
Low-renin hyperaldosteronism
High aldosterone is usually due to…
adrenal tumours
Conn’s syndrome is ___ hyperaldosteronism
primary
Secondary hyperaldosteronism = high ___
renin
Secondary hyperaldosteronism is usually associated with…
renal, heart, liver disease
Secondary hyperaldosteronism is also known as…
renal artery stenosis
Which type of hyperaldosteronism is more common?
secondary
Primary hyperaldosteronism: sequence of events
- adrenal gland secretes a lot of aldosterone
- aldosterone causes increased Na+ retention & increase K+ loss
- High Na+ causes decreased renin
- causes decreased ANG II
Secondary hyperaldosteronism: sequence of events
- Decreased blood flow at renal artery
- Increased renin
- Increased ANG II
- Increased aldosterone
- Increased Na+ retention
- Increased K+ loss (also caused by high aldosterone)
Diagnosis of hyperaldosteronism
- low K+ (a lot excreted)
- High aldosterone
- renin low (primary)
- renin high (secondary)
Acid-base status in patients with hyperaldosteronism?
Metabolic alkalosis (H+ secreted because Na+ is retained)
Low aldosterone is ___ disease
Addison’s
Addison’s disease (and what is it due to?)
Low aldosterone
- Due to autoimmune destruction of the cortex
Causes of hypoadrenalism
- Autoimmune destruction of cortex
- Gland destruction caused by tuberculosis, infections, cancer
- Secondary / tertiary hypoadrenalism caused by ACTH deficiency (pituitary / hypothalamus problem)
- Long-term corticosteroid therapy: breaks the HPA axis
Difference between primary and secondary and tertiary hypoadrenalism
- primary: problem at adrenal gland (ACTH high)
- secondary: problem at a. pituitary (ACTH low)
- tertiary: problem at hypothalamus (CRH low)
Clinical features of hypoadrenalism
- lethargy
- anorexia
- weight loss
- increased pigment in hand and mouth (Addison’s)
- abdominal pain
Why is there increased pigment for Addison’s?
melanocyte-stimulating hormone is secreted along with ACTH (which is secreted in high amounts)
Acute crisis for hypoadrenalism
- dehydration
- hypotension
- nausea
- vomiting
Biochemical features of hypoadrenalism
- low NA+
- high K+
- mild metabolic acidosis
- hyperuremia
- hypoglycemia
- high ACTH (primary)
Diagnosis of hypoadrenalism
Short Synacthen test
Problem with testing serum aldosterone
Have to have normal to compare to (the normal must be from the same person)
Synacthen is a ____ analogue
1-24 ACTH
Short Synacthen test is also called…
ACTH stimulation test
Short Synacthen test
- measure serum cortisol
- give synacthen
- measure cortisol 30 min later
Interpreting short Synacthen test
Normal: cortisol rise rapidly
Addison’s: no change
Adrenal atropy: slight rise
Anti-hypertensive agents used (RAAS)
- ACE inhibitor
- ANG II receptor blocker
- Block aldosterone receptor
- Block renin receptor
