Disorders Of Adrenocortical Dysfunction Flashcards by Kisspeptin GnRH

Where is the adrenal gland?

→ On top of the kidney

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What type of tissue is the adrenal cortex?

→ Glandular tissue

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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

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What does the medulla produce?

→ Adrenaline

→ Noradrenaline

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Where is noradrenaline also produced?

→ Sympathetic nervous system

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Where is the 21 hydroxylase enzyme found?

→ Only in the adrenal

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What is produced in the second half of the menstrual cycle?

→ 17 OH is decreased

→ Progesterone is increased

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What is produced in the first half of the menstrual cycle?

→ Ovary produced testosterone
→ Aromatase is produced
→ Testosterone is converted to estradiol

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What does testosterone become in men?

→ Testosterone is reduced
→ By 5 alpha reductase
→ Into dihydrotestosterone (main androgen in men)

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What is congenital adrenal hyperplasia?

→ Genetically XX

→ Adrenal glands can’t make progesterone

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How does cortisol increase plasma glucose levels?

→ Increases gluconeogenesis
→ Decreases glucose utilization
→ Increases glycogenolysis
→ Increases glycogen storage

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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

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What is the definition of Cushings syndrome?

→ Excessive levels of the steroid hormone cortisol

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What is Cushings disease?

→ Excess cortisol

→ Due to an ACTH secreting pituitary tumor

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What are the clinical features of Cushings syndrome?

→ Change in body shape
→ Central obesity
→ Moon face
→ Buffalo hump
→ Thin skin
→Osteoporosis
→ Diabetes

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What is the difference between a moon face and an obese face?

→ The obese face has indentation around the eyes

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What are the changes in sex hormones in Cushings syndrome?

→ Excess hair growth
→ Irregular periods
→ Problems conceiving
→ Impotence

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What are the 3 screening tests for Cushings?

→ Urinary free cortisol
→ Diurnal rhythm
→ Overnight dexamethasone suppression testing

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What is the diurnal rhythm of cortisol?

→ Cortisol peaks in the morning

→ At night it is undetectable

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When do you test for cortisol?

At midnight
→ There should be none
→ If there is cortisol at midnight then something is wrong

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What is the renal threshold for cortisol?

→ 3-5% of cortisol appears in the urine

→ Freely filtered

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How do you do a urine test?

→ 24h collection of urine

→ to check for abnormal cortisol levels

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If you want to inhibit cortisol production from the pituitary what do you give?

→ Cortisol

→ Negative feedback

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How do you clinically suppress cortisol and why?

→ Dexamethesone

→ Brain can’t tell the difference between cortisol and DMSone

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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