LMP299Y1 Lecture Notes - Lecture 9: Dexamethasone Suppression Test, Adrenal Tumor, Acth Stimulation Test

10 views6 pages
Published on 12 Apr 2013
School
UTSG
Department
Laboratory Medicine and Pathobiology
Course
LMP299Y1
Professor
LECTURE NINE: ADRENAL DISEASES
ADRENAL GLANDS AND HORMONES
Adrenal Gland: Small triangular shaped glands situated just above the kidney. They enlarge in chronic stress.
The hormones of the adrenal glands are essential for survival (the adrenal gland also helps make the
reproductive hormone)
Adrenal consists of cortex (outside) and medulla (part of the sympathetic nervous system)
Adrenal cortex consists of: Zona Glomerulusa (this is the most outer layer; Aldosterone), Zona Fasciculate & Zona
Reticularis (cortisol and adrenal androgens and estrogens)
Adrenal medulla epinephrine, norepinephrine, dopamine
BIOSYNTHESIS OF STEROID HORMONES
CHOLESTEROL (this is the precursor for the steroid hormone)
17 OH’ ase (this is the important enzymes for these 2 (cortisol and testosterone) 17, 20 OH’ ase
PREGNENOLONE -----------------------------------------> 17-OH PREGNENOLONE -----------------------------
--> DHEA
PROGESTERONE 17-OH PROGESTERONE
ANDROSTENEDIONE
DEOXYCORTICOSTERONE 11-DEOXYCORTISOL
TESTOSTERONE
CORTICOSTERONE CORTISOL
ALDOSTERONE
CORTISOL (it is also a counter regulatory hormone) PHYSIOLOGY
Effects on metabolism:
- Carbohydrate promotion of gluconeogenesis (this is the making of new glucose in response to hypoglycemia)
in liver, reduction in glucose use and uptake by peripheral tissues (helps us save the glucose that we have)
- Protein increase of muscle proteolysis to release the proteins
- Fat activation of lipolysis and release of free fatty acids
* When present in excess, glucocorticoids cause central distribution of fat -- face, neck and trunk. (there is a
redistribution of fat in cases of excess cortisol production)
Circulating forms:
- 90% - 98% protein bound to cortisol-binding globulin (CBG) and albumin. CBG is increased in pregnancy and
estrogen treatment. (the free form is the biologically active form though most of its bound up)
Metabolic fate: after liver conjugation (this is under the normal physiology), excreted in urine (when there is
excessive free cortisol it can also be gotten rid of in the urine (i.e. it is too much and can’t be bound by the
binding proteins or albumin)
Hypothalamic pituitary adrenocortical axis
CUSHING’S SYNDROME (it is a group of diseases that have the cortisol excess)
Results from prolonged excessive exposure of body tissues to cortisol or other glucocorticoid
Causes:
- pituitary ACTH-producing tumor Cushing’s disease (ACTH will be stimulating the adrenal to male more
cortisol this specifically Cushing’s disease (due to the tumor))
- ectopic ACTH (it is made by other cancer cells not in the pituitary): ACTH produced by the cells other than
pituitary, e.g. small cell carcinoma in the lung may secrete ACTH
- adrenal cortisol-producing tumor (adenoma or carcinoma): this is independent of ACTH
- exogenous glucocorticoids (taken orally, inhaled or applied topically): cortisol-like compounds or medications
ACTH (this is there driver of the cortisol synthesis
21 OH’ ase
18 OH’ ase – this is
the important
enzyme for this one
3β-hydroxysteroid
Dehydrogenase /
Isomerase
11 OH’ ase
Cholesterol side-chain
cleavage enzyme
Unlock document

This preview shows pages 1-2 of the document.
Unlock all 6 pages and 3 million more documents.

Already have an account? Log in
CLINICAL FEATURES OF CUSHING’S SYNDROME
- Not all of the patients have the same clinical picture but these are the common ones
Baldness and facial hirsuitism in females -Acne -Buffalo hump
Moon face -Plethoric cheeks - Hypertension
Osteoporosis (cortisol promotes bone lysis and inhibit the formation of the bone)
Skin thinning (the fat has gone somewhere else (abdominal)) - Increased abdominal fat (this is due to the
redistribution of the fat)
Abdominal striae (purple stripes of the blood vessels (the skin is thinned and the blood vessels are exposed)
Easy bruising - Poor wound healing -Avascular necrosis of
femoral head
Muscle weakness (due to the protein breakdown (lysis))
DIAGNOSIS OF CUSHING’S SYNDROME
Screening test: 24 hr urinary free cortisol (cortisol exceeds the plasma protein binding capacity, so unbound
cortisol is filtered into urine) elevated in Cushing’s; but stress and obesity can cause false positive results
Plasma cortisol: measured at 8:00am and 22:00pm. The normal ACTH DEPENDENT circadian rhythm (high peak
in the morning) is not apparent in the patient with Cushing’s.
Low dose (1 mg) dexamethasone (cortisol analogue) test: suppresses cortisol production (>50%) in normal
subject but not in patients with Cushing’s syndrome.
High dose dexamethasone test for differential the cause of Cushing’s: suppresses cortisol production (>50%)
in Cushing’s disease but not in other Cushing’s syndrome caused by adrenal adenoma or carcinoma, ectopic
production of ACTH
Plasma ACTH: suppressed in adrenal tumors and very high in ectopic ACTH secreting tumors
CASE 1, a 30-YEAR MAN WITH CUSHING’S
Clinical presentation: obese (fat redistribution), hypertensive (due to the cortisol production), glucose
intolerance (this is due to the cortisol counter to the insulin effect), wasting of proximal limb muscles (due to the
excessive cortisol), and abdominal striae
Laboratory findings:
1. Screening: Plasma cortisol concentrations measured at 8:00am was 400 nmol/L, and at 22:00pm 400 nmol/L.
(the levels of the cortisol don’t change with the time of the day (possibility of Cushing’s)
2. Confirmation of Cushing’s: Low dose dexamethasone test: baseline 420 nmol/L, post 410 nmol/L (there is no
suppression of the cortisol levels)
3. Differential diagnosis of cause of Cushing’s:
- High dose dexamethasone test: baseline 420 nmol/L, post 400 nmol/L (hence it is not Cushing’s disease)
- Plasma ACTH: at 8:00am, 150 ng/L (RI 7-51) (this is the high levels of ACTH from the pituitary (hence it
cannot be caused by an adrenal tumor (levels of ACTH would be low)))
Diagnosis? Ectopic ACTH secreting tumor
ALDOSTERONE PHYSIOLOGY
Produced exclusively by the Zona Glomerulosa (lacks (this tissue possesses the specific enzyme to make cortisol)
17-hydroxylase but has 18-hydroxylase and 18-hydroxysteroid dehydrogenase for aldosterone biosynthesis)
Regulation of synthesis and secretion: primarily by the renin-angiotensin system (not using the HPA axis). Other
factors, including ACTH, potassium are also involved.
Biological effect:
- Sodium and water retention
- Potassium and hydrogen ion secretion.
* Raises BP (this is due to the NA and water retention)
Unlock document

This preview shows pages 1-2 of the document.
Unlock all 6 pages and 3 million more documents.

Already have an account? Log in

Document Summary

Adrenal gland: small triangular shaped glands situated just above the kidney. The hormones of the adrenal glands are essential for survival (the adrenal gland also helps make the reproductive hormone) Adrenal consists of cortex (outside) and medulla (part of the sympathetic nervous system) Adrenal cortex consists of: zona glomerulusa (this is the most outer layer; aldosterone), zona fasciculate & zona. Acth (this is there driver of the cortisol synthesis. Cholesterol (this is the precursor for the steroid hormone) 17 oh" ase (this is the important enzymes for these 2 (cortisol and testosterone) Cortisol (it is also a counter regulatory hormone) physiology. 18 oh" ase this is the important enzyme for this one. Carbohydrate promotion of gluconeogenesis (this is the making of new glucose in response to hypoglycemia) in liver, reduction in glucose use and uptake by peripheral tissues (helps us save the glucose that we have) Protein increase of muscle proteolysis to release the proteins.

Get OneClass Grade+

Unlimited access to all notes and study guides.

YearlyMost Popular
75% OFF
$9.98/m
Monthly
$39.98/m
Single doc
$39.98

or

You will be charged $119.76 upfront and auto renewed at the end of each cycle. You may cancel anytime under Payment Settings. For more information, see our Terms and Privacy.
Payments are encrypted using 256-bit SSL. Powered by Stripe.