Disorders Of Adrenocortical Dysfunction Flashcards
Where is the adrenal gland?
→ On top of the kidney
What type of tissue is the adrenal cortex?
→ Glandular tissue
What are the 3 areas of the adrenal cortex, where are they and what do they produce?
→ Zona glomerulosa - outside - aldosterone
→ Zona fasciculata - middle - cortisol
→ Zona reticularis - inside - testosterone
What does the medulla produce?
→ Adrenaline
→ Noradrenaline
Where is noradrenaline also produced?
→ Sympathetic nervous system
Where is the 21 hydroxylase enzyme found?
→ Only in the adrenal
What is produced in the second half of the menstrual cycle?
→ 17 OH is decreased
→ Progesterone is increased
What is produced in the first half of the menstrual cycle?
→ Ovary produced testosterone
→ Aromatase is produced
→ Testosterone is converted to estradiol
What does testosterone become in men?
→ Testosterone is reduced
→ By 5 alpha reductase
→ Into dihydrotestosterone (main androgen in men)
What is congenital adrenal hyperplasia?
→ Genetically XX
→ Adrenal glands can’t make progesterone
How does cortisol increase plasma glucose levels?
→ Increases gluconeogenesis
→ Decreases glucose utilization
→ Increases glycogenolysis
→ Increases glycogen storage
What are the effects of cortisol?
→ Increases plasma glucose → Increases lipolysis → Proteins are catabolized - releases AA → Na+ and H2O retention maintains BP → Anti inflammatory → Decreases gastric acid production
What is the definition of Cushings syndrome?
→ Excessive levels of the steroid hormone cortisol
What is Cushings disease?
→ Excess cortisol
→ Due to an ACTH secreting pituitary tumor
What are the clinical features of Cushings syndrome?
→ Change in body shape → Central obesity → Moon face → Buffalo hump → Thin skin →Osteoporosis → Diabetes
What is the difference between a moon face and an obese face?
→ The obese face has indentation around the eyes
What are the changes in sex hormones in Cushings syndrome?
→ Excess hair growth
→ Irregular periods
→ Problems conceiving
→ Impotence
What are the 3 screening tests for Cushings?
→ Urinary free cortisol
→ Diurnal rhythm
→ Overnight dexamethasone suppression testing
What is the diurnal rhythm of cortisol?
→ Cortisol peaks in the morning
→ At night it is undetectable
When do you test for cortisol?
At midnight
→ There should be none
→ If there is cortisol at midnight then something is wrong
What is the renal threshold for cortisol?
→ 3-5% of cortisol appears in the urine
→ Freely filtered
How do you do a urine test?
→ 24h collection of urine
→ to check for abnormal cortisol levels
If you want to inhibit cortisol production from the pituitary what do you give?
→ Cortisol
→ Negative feedback
How do you clinically suppress cortisol and why?
→ Dexamethesone
→ Brain can’t tell the difference between cortisol and DMSone
What happens if a Dexamethesone tablet is given to a normal person?
→ negative feedback
→ ACTH production stops
→ Cortisol decreases
What are 3 possibilities if the dexamethesone test doesn’t work?
True Cushings
→ Pseudocushings
→ Exogenous steroids
Why does the dexamethesone test not work even if you don’t have Cushings?
→ Baseline cortisol levels may be high
What is the low dose dexamethesone test and what is the purpose of this?
→ 4 tablets for 2 days
→ Cortisol decreases below 50
→ Rules out people with pseudocushings
How do you know if a person has Cushings from a low dose dexamethesone test?
→ If after the test the cortisol levels are still high
What are 3 causes of Cushings?
→ Adenoma in pituitary - disease
→ Tumor in adrenal gland - Syndrome
→ Ectopic ACTH production - syndrome
What is the cortisol feedback loop?
→ CRH is released from the hypothalamus → goes to pituitary → Stimulates ACTH → ACTH stimulates adrenal gland to make cortisol → Cortisol inhibits hypothalamus
What does the pituitary gland do when there is high cortisol?
→ When it exposed to large amounts of cortisol
→ Downregulates ACTH
What is the higher dexamethesone test?
→ 4x higher dose of DMsone
→ Amount of cortisol should drop to 1/2
→ If it stays high
→ not pituitary
What are ACTH levels like in ectopic ACTH production?
→ ACTH will be high
What are the lab features of Cortisol excess?
→ Hypokalaemia
→ Metabolic alkalosis
→ Hyperglycaemia
Where does aldosterone bind in the kidney?
→ Mineralocorticoid receptor
What is the function of the mineralocorticoid receptor?
→ Retain sodium
How is the electrical balance retained at the mineralocorticoid receptor?
→ Na+ retained
→ K+ lost
What happens if there are no more K+ ions to exchange in the mineralocorticoid receptor?
→ Use H+
→ Metabolic alkalosis
Why does cortisol not usually bind to the mineralocorticoid receptor?
→ Cortisol can bind to the mineralocorticoid receptor
→ 11 beta hydroxysteroid dehydrogenase 2 is part of the mineralocorticoid receptor
→ Cortisol → cortisone by the enzyme (destroyed)
→ Only aldosterone can bind to the receptor
What happens during hypovolaemia to retain Na+ (mineralocorticoid receptor)?
→ The catalytic site of 11 beta hydroxysteroid dehydrogenase 2 has a saturation point which is set higher than normal cortisol
→ Saturation point is lower than extreme cortisol
→ In extreme cortisol the enzyme gets saturated and cortisol can access the receptor
→ so maximal sodium can be retained
What does the POMC gene provide?
→ Painkiller
→ Antibiotics
→ Hunger suppressor
What does the alpha MSH gene do?
→ Powerful appetite suppressor
→ Involved in pigmentation
What happens if you give CRH to a normal person?
→ ACTH double
What happens if you give CRH to an adrenal tumor person?
→ suppression of ACTH
→ Too much cortisol
→ cannot respond to CRH
What happens if you give CRH to an ectopic ACTH person?
→ ACTH are high
→ doesn’t rise
What happens if you give CRH to someone with Cushings?
→ ACTH rises a lot
→ Pituitary cells are still functional but there are more of them
What are 2 ways of localizing a pituitary tumor?
→ MRI
→ IPSS
What are 2 ways of finding an adrenal tumor?
→ CT
→ MRI
What are ways of finding ectopic cells?
→ Octreotide scan
→ ACTH sampling
What are 2 cortisol blockers?
→ Metyrapone
→ Ketoconazole
What are the clinical features of Addisons?
→ Hyponatremia
→ Hyperkalaemia
→ Salt craving
→ Nausea
What are some causes of Addisons?
→ Autoimmune
→ TB
→ Steroid withdrawal
→Enzyme defect
What happens if you give a person synthetic ACTH?
→Cortisol levels should rise
What is the insulin tolerance test?
→ Dose of insulin
→ Hypoglycaemic (stress)
How do you replace cortisol?
→ Hydrocortisone
→ mimic diurnal rhythm
What is the most common cause of congenital adrenal hyperplasia?
→ 21 hydroxylase deficiency
→ Yupik Eskimos
What do excess sex steroids cause?
→ Virilization
→ Hirsutism
→ Infertility
What is non classical adrenal hyperplasia?
→ 11 beta hydroxylase deficiency
What are symptoms of people who have non classical adrenal hyperplasia?
→ Cannot produce cortisol
→ Deoxycorticosterone is raised ( same effects as aldosterone)
→ Hypertension
What is phaeochromocytoma?
→ Tumor of enterochromaffin cells of the adrenal medullar
→ produce adrenaline
What is used to replace absent mineralocorticoid?
→ 21 hydroxylase deficiency
How is renin released?
→ Afferent arteriole brings blood in glomerulus and senses blood pressure
→ Macula densa in DCT senses salt
→ JG cells produce renin
What is primary excess of aldosterone?
→ Tumor producing aldosterone
→ Renin levels are low
What is secondary aldosterone syndrome?
→ Renin secreting tumor
→ renal artery stenosis
What is the treatment for Conns?
→ Spironolactone
→ Amiloride
What is phaeochromocytoma?
→ Tumor of enterochromaffin cells of the adrenal medullar
→ produce adrenaline
What are the symptoms of phaeochromocytoma?
→ high BP (paroxysmal)
→ Sweating
→ Anxiety
What do you look for in the urine of someone with phaeochromocytoma?
→ Metapnephrines
How do you manage phaeochromocytoma?
→ Alpha blockade
→ Beta blockade - propanolol
