Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
126 Cards in this Set
- Front
- Back
|
What is the result of untreated addison's disease?
|
Decrease production in hormones, importantly cortisol. Cortisol is improtant for life. No cortisol = no life
|
|
|
What tissue is the adrenal cortex embriologically derived from?
|
Mesoderm
|
|
|
What tissue is the adrenal medulla embriologically derived from?
|
Neural Crest
|
|
|
Name the zones of the adrenal cortex and what each zone produces in terms of hormones
|
From superfical to deep:
1. Glomerulosa -Aldosterone 2. Fasiculata -Cortisol 3. Reticularis -Androgen "Go Find Rex, Make Good Sex" Glomerulosa, Fasiculata, Reticulata, Mineralcorticoids, Glucocorticoids, Sex hormones |
|
|
What group of hormones are produced in the adrenal medulla?
|
Catecholamines
|
|
|
Why is the loss of the adrenal cortex's production of sex hormones more significant for women than men?
|
Men are able to produce sex hormones elsewhere, woman aren't
|
|
|
What is the rate limiting step for all steriod synthesis?
|
The converstion of cholesterol to pregnenolone
|
|
|
What are the actions of cortisol?
|
In general it affects glucose, protein and fat metabolism
Specifically 1. inhibits synthesis of protein in tissue 2. promotes the use of FAs as energy source 3. decrease the use of glucose 4. stimulates gluconeogensis 5. overall increase in blood glucose concentration 6. regulate immune function |
|
|
How is cortisol transported around the blood?
|
>95% are protein bound in plasma to cortisol-binding gobulin (CGB aka transcortin)
|
|
|
True of false
Cortisol is a steriod hormone thus regulates gene transcription |
True
|
|
|
True or false:
Since ACTH acts on the adrenals, ACTH deficiency (a hypothalamic/pituitary disease) causes the same clincal features as primary adrenal insufficiency |
False
ACTH deficiency will not cause shock, with severely depleted Na stores and K+ rentension as seen in primary adrenal insufficiency. This is because ACTH insufficiency spares the adrenals, therefore aldosterone (independent of the HPA axis) is still produced. Also in primary adrenal insufficiency, there is ACTH excess (no neg. feedback), thus pigmentation occurs. |
|
|
Finish the sentence:
Cortisol is both glucocorticoid and...... actions |
mineralcorticoid
|
|
|
What are the clinical features of primary adrenal insufficiency?
|
1. Glucocorticoid deficiency:
hypoglycaemia, weight loss, weakness, anorexia, N&V 2. Mineralocorticoid deficiency: hypotension, salt craving 3. ACTH excess pigmenetation |
|
|
How would you test the HPA axis for:
1. suspected deficiency in cortisol? 2. suspected excess in cortisol? |
1. Stimulation test: hypoglycaemia, CRH, synacthen
2. Suppression test: dexamethasone |
|
|
What is the criteria to exclude adrenal insufficiency?
|
1. Hyponatreaemia, hyperkalaemia (if not shows adrenals' production of aldosterone is present hence not adrenal insufficiency)
2. Low morning cortisol (personally not sure about this) 3. Lack of response to Synacthen 4. Lack of response to hypoglycaemia |
|
|
How low would cortisol have to be in the morning to be considered as "low"
|
<150nmol/L
|
|
|
What amount of cortisol would exclude the diagnosis of adrenal insufficiency?
|
>500nmol/L of cortisol in the morning
|
|
|
What is the most common therapy for adrenal insufficiency?
|
prednisone (glucocorticoid prodrug)
|
|
|
Why is dexamethasone not used to treat addison's disease?
|
Too high affinity for mineralcorticoid receptors = not a wide enough therapeutic range
|
|
|
What are some of the problems associated with steriod therapy?
|
Diabetes
Osteoporosis Peptic Ulcer HT Psychiatric disorders Weight gain Immunosuppression Activation of latent infections |
|
|
What is the main risk of stopping steriod therapy that has been going on for >2months?
|
HPA axis suppression
|
|
|
What time frame would it be considered safe to withdraw steriod therapy without major risk?
|
<4 weeks, no HPA axis suppression
|
|
|
What would the steps be to stop steriod therapy?
|
1. Reduce to physiological dose (5-7.5 mg prednisone)
2. If tolerated, change to alternate day treatment 3. Slowly withdraw (2-4 week intervals) |
|
|
What is the basal need of hydrocortisone/day?
|
20-25
|
|
|
What would you need to consider when giving cortisol replacement therapy in terms of keeping the replacement as close to normal physiology as possible
|
Need to consider replicating the diurnal rhythm of cortisol release.
|
|
|
What is the standard therapy for physiological replacement therapy for primary adrenal insufficieny?
|
Hydrocortisone 10/5/5 plus fludrocortisone 100-150 mg daily
|
|
|
What would be the difference between the replacement therapy of a primary adrenal insufficieny, compared to a ACTH deficiency?
|
Don't give fludrocortisone in ACTH deficiency as aldosterone is still being made in the kidneys.
Only exception is CAH (congenital adrenal hyperplasia) |
|
|
What are the uses for tracers in imaging?
|
Permits the evaluation of:
1. regional BF of molecules 2. metabolism within tissues 3. organ function 4. intra- and intercellular communication |
|
|
Name the iodine isotope used for treatment of hyperthyrodism
|
131 Iodine
|
|
|
Name the iodine isotope used for the diagnosis of hyperthyrodisim
|
123 Iodine
|
|
|
True or false:
Radioactive imaging can diagnosis hyperthyrodism and hypothyrodism via imaging metabolic uptake of iodine tracers |
False
Not useful in hypothyrodism |
|
|
True or false:
Hyperparathyrodism is more common in woman |
True
|
|
|
Name three main biochemical features of Conn's syndrome
|
Conn's syndrome: aldosterone producing tumour
1. excess aldosterone 2. HT 3. hypokalaemia |
|
|
What is Cushing's syndrome due to?
|
Excess cortisol
|
|
|
Which part of the adrenals do phaeochromocytomas arise from?
|
Adrenal medulla
|
|
|
What are the clinical feature of phaeochromocytoma?
|
Hypertension -chronic or intermittent
Headache Palpitations Sweating Subclinical-incidental |
|
|
Toxic thyroiditis is usually a disease of what age popluation?
|
Older people
|
|
|
Subacute thyroditis is a disease of what age group?
|
Younger people
|
|
|
What clinical feature would point towards a subacute thyroiditis as oppose to grave's disease
|
Neck pain and a more diffused nuclear imaging result.
|
|
|
Once glucocorticoids bind to their receptor, where does this complex bind to and what happens?
|
Binds to target genes in the nucleus marked by nucleotide sequences known as glucocorticoid response elements (GRE). Once bound, the complex initates or repress transcription of mRNA
|
|
|
what are the mineralcorticoid activity of hydrocortisol?
|
Na+ retention
K+ and Ca2+ loss |
|
|
True or False
Mineralcortioid activity of hydrocortisol is normally suppressed |
True
Suppressed by 11(beta)H5D |
|
|
What are the mechanisms which glucocorticoids maybe mediating anti-inflammatory actions?
|
binding to GRE ->synthesis of anti-inflammatory proteins
reduces pro-inflammatory cytokines by the binding of hormone-receptor complex to transcription factors May facilitate ribonuclear degradation of pro-inflammatory cytokines by inhibiting protective proteins |
|
|
List some of the unwanted effects of glucocorticoids when used therapeutically
|
diabetes
muscle wasting (proximal) HT adrenal suppression psychiatric disturbances Cushings syndrome |
|
|
What would you expect a patient to look like if they present with Cushings syndrome?
|
Moon face
Striae Acne |
|
|
What are the improtant carbon sites for hydroxylation in cholesterol?
|
primarily C21
then C11 and C17 |
|
|
True or false:
Acetyl CoA is needed at the start of the Cholesterol synthesis chain |
True
|
|
|
What reaction does statin inhibit in the pathway of cholesterol synthesis?
|
Statins inhibit HMG CoA reductase which would normally convert HMG CoA to Mevalonate
|
|
|
What molecule do the carbons of cholesterol build themselves on?
|
Mevalonate
|
|
|
What suppresses the formation of C10 and C15 in the cholesterol synthesis pathway?
|
N-biosphosphonates
|
|
|
What is the first product synthesised from cholesterol in the steriod synthesis pathway?
|
Pregnenolone
|
|
|
True or false
Pregnenolone's product 17alpha-hydroxypregnenolone is the only precursor for Cortisol |
False
Progestrone can be made into cortisol too |
|
|
In Congential Adrenal Hyperplasia (CAH) why are the adrenals hyperplastic?
|
Due to the deficiency in cortisol production, there is no negative feedback to the pituitary thus there is elevated ACTH causing hyperplasia of the adrenals
|
|
|
In Congential Adrenal Hyperplasia (CAH) what would you expect the mineralcorticoid activity to be and what are the consqeuences?
|
Mineralcorticoid may/may not be deficient.
However, if it is deficient, salt-wasting can occur and the following consquences such as hypovolumic shock can occur. |
|
|
What are the two most common enzyme deficiencies in Congential Adrenal Hyperplasia?
|
1. 21-hydroxylase deficiency
2. 11beta-hydroxylase deficiency |
|
|
In Congenital Adrenal Hyperplasia (CAH), what would you expect the androgen production to be like? And what would the consquence of that be?
|
Enhanced adrenal androgens due to excess ACTH, which can cause virilization in girls
|
|
|
What is the inheritance pattern of Congenital Adrenal Hyperplasia?
|
Autosomal recessive
|
|
|
Which is the most common enzyme deficiency in CAH? And what is it's severity like?
|
21-hydroxylase deficiency
Variable serverity -depending on mutations |
|
|
List the features of CAH due to 21-hydroxylase deficiency
|
1. Cortisol and Aldosterone deficiencies
2. Salt wasting and hyperkalemia 3. Risk of Addisonian crisis after birth 4. Virilization in females |
|
|
How would CAH due to 21-hydroxylase deficiency be treated?
|
Typically: glucocorticoid (cortisone acetate) and mineralocorticoid (fludrocortisone) replacement orally
|
|
|
What is the prognosis of CAH due to 21-hydroxylase deficiency?
|
Severity falls with maturity and may be possible to withdraw fludrocortisone
|
|
|
What upstream intermediates would you expect to be elevated in CAH due to 21-hydroxylase deficiency?
|
17alpha- hydroxyprogesterone and 21deoxycortisol
|
|
|
What is the one key difference between CAH due to 21-hydroxylase deficiency vs. 11beta-hydroxylase?
And why? |
Salt retention (can present with HT)
Due to accumulation of upstream intermediate DOC (Deoxycorticosterone) |
|
|
True or false
Testosterone is dervived from pregnenolone |
True
Pregnenolone -> 17alpha-hydroxypregnenlone -> DHEA ->-> Testosterone |
|
|
What happens to testosterone once it's produced?
|
1. Conversion to active metabolite DHT
2. Conversion to estradiol (ovary) 3. Catabolism |
|
|
Name the enzyme that converts testosterone to estradiol as oppose to DHT
|
aromatase
|
|
|
ACTH provides a drive to which section(s) of the adrenal cortex?
|
Z. fasciculata
Z. reticularis |
|
|
What is the primary drive to Z. glomerulosa?
|
Angiotensin 2
|
|
|
How would you monitor the therapy for CAH?
|
Serum ACTH, 17-hydroxyprogesterone and DOC levels
|
|
|
List the promotors of cortisol secretion
|
1. Light/dark inputs to suprachiasmiatic nuclei
2. Physiological hypoglycaemia 3. Psychological chronic stress |
|
|
Cortisol provides negative feedback to it's secretion pathway. What does it inhibit?
|
Secretion of CRH in the hypothalamus and ACTH in the anterior pituitary
|
|
|
Why is cortisol so improtant for life?
|
Improtant for it's response to states of hypoglycaemia. It allows for blood glucose to be maintained and in prolonged hypoglycaemia, for ketones to be made by the liver. Glucose and ketones are the only products utilised by the brain.
|
|
|
How does cortisol inhibit glucose uptake by the periperhal tissues?
|
Inhibits the translocation of Glut4 and also it's expression by the cells.
Thus causing insulin resistance |
|
|
List 3 ways of getting hypercortisolism (Cushing's syndrome)
|
1. Latrogenic
2. Adrenal tumour (excess cortisol) 3. Pituitary tumor (excess ACTH) |
|
|
List the 5 main groups of steroids
exception vitamin D |
1. Glucocorticoids
2. Mineralcorticoids 3. Androgens 4. Estogens 5. Progesterone |
|
|
Where are the 5 main groups of steroids synthesised and what are some examples of steroids produce at those sites?
|
Adrenal cortex: aldosterone, cortisol and adrenal androgens (androstenedione and DHEA)
Gonads: testosterone, estradiol and progesterone Placenta: estradiol and progesterone Fat: peripheral conversion of testosterone to estradiol |
|
|
What hormone does the leydig cells of the testis synthesise? and what stimulates these cells to produce hormones?
|
leydig cells produce testosterone
They are stimulated by LH |
|
|
What enzyme turns testosterone to estradiol and where are these enzymes found?
|
Enzymes in fat cells called aromatase
|
|
|
What is the major site of estradiol production in non-pregnant and pre-menapausal women? And what hormone promotes the production of estradiol?
|
Ovarian follicular cells under the influence of FSH
|
|
|
After ovulation, what hormone does the corpus luteum secrete and what hormone influences it's secretion?
|
Secrets progesterone
Under the influence of LH |
|
|
What hormones does the placenta secrete and what controls the secretion?
|
Secretes progesterone and estradiol under the control of HCG
|
|
|
What hormones can progesterone be converted into?
|
cortisol
aldosterone or sex steroid |
|
|
What is the secretion of aldosterone mainly dependent on?
|
renin-angiotensin system
|
|
|
Where is renin secreted from?
|
renal juxtaglomerular apparatus
|
|
|
Where is angiotensin converted into angiotensin-1 by renin?
|
Liver
|
|
|
What converts Angiotensin-1 to angiotensin-2?
|
peptidase angiotensin converting enzyme (ACE)
|
|
|
What does ACTH cause the increase of intracellularly for the synthesis of cortisol and adrenal androgens?
|
increase in cAMP
|
|
|
What is Cushing's Disease?
|
Elevated ACTH
Likely due to a secreting pituitary tumour |
|
|
What does increase in ACTH do?
|
Increase in cortisol
Adrenal hyperplasia Skin hyperpigmentation |
|
|
What is addison's disease?
|
Auto-immune mediated atrophy of adrenal cortex leading to adrenal insufficiency
|
|
|
What does addison's disease result in?
|
reduced cortisol, aldosterone and adrenal androgens
Life-threatening esp with stress |
|
|
Why do you get hyper pigmentation with addison's disease?
|
reduced cortisol = reduced inhibition of ACTH = overproduction of ACTH = hyperpigmentation
|
|
|
What is congenital adrenal hyperplasia?
|
Reduction of cortisol levels due to enzyme deficiency (commonly: 21 hydroxylase or 11 beta hydroxylase)
|
|
|
True or false:
Aldosterone remains unaffected in congenital adrenal hyperplasia, as the production of aldosterone is mainly dependent on renin-angiotensin system |
False
Though true that aldosterone production is mainly dependent on RAS. In the case of CRH, aldosterone production is reduced if 21 hydroylase is affected as it's also required to make aldosterone |
|
|
If aldosterone production is impaired, what would you expect to happen?
|
Salt wasting
Life-threathening hypotension |
|
|
In congenital adrenal hyperplasia, what causes adrenal hyperplasia?
|
unopposed ACTH production
|
|
|
in CAH, why does masculinization in female infants occur?
I.E. what does insufficient cortisol got to do with adrenal androgens? |
deficiency in cortisol = unopposed ACTH = adrenal androgen production is still normal in these cases, therefore increase in ACTH causes increase in androgen production
|
|
|
Where are glucocorticoid receptors present?
|
Just about every tissue in the body
|
|
|
What is the inactive form of cortisol?
|
Cortisone
|
|
|
What is the precursor for ALL steroid hormones?
|
Pregnenlone
|
|
|
What are the downstream reactions in the cell after the binding of ACTH to it's receptor?
|
activation of adenylate cyclase ->
increase second messenger cAMP -> activates protein kinase A -> cholesterol -> pregnenolone |
|
|
What is the percentage of cortisol that remains unbound to CBG?
|
5%
|
|
|
What is cortisol's affect on muscles?
|
1. decrease sensitivity to insulin = decrease glucose uptake
2. suppressed glucose oxidation = production and release of lactate 3. elevate proteolysis = release of a.a (can lead to muscle wasting) |
|
|
What is core cycle?
|
gluconeogenesis from the redistribution of carbon atoms from muscles to liver from a.a. and glucose.
|
|
|
What is the effect of cortisol on the liver?
|
gluconeogenesis
|
|
|
What is cortisol's affect on carbohydrate metabolism?
|
counteract insulin = elevates plasma glucose level
|
|
|
How are glucagon, adrenalin and cortisol similar?
|
They all counter act insulin and elevate plasma glucose
|
|
|
How are glucagon, adrenalin and cortisol different?
|
Cortisol promotes hepatic glycogen stores
Adrenalin and glucagon inhibits hepatic glycogen stores |
|
|
How does cortisol promote protein metabolism?
|
Increase ubiquitin -> ubiquitin attaches to protein -> tags protein ->increase degradation of protein by proteosomes
|
|
|
What hormones counteracts cortisol's protein metabolism actions in muscle?
|
Testosterone
Insulin IGF-1 |
|
|
How does cortisol cause central fat redistribution giving the moon face, buffalo hump and central obesity?
|
promotes peripheral fat cells' hormone-sensitive lipase (enzyme) which increase FAA. FAA is taken up by the liver and made into VLDL and this promotes the incorporation of FAs into tryglcerides in fat cells centrally
|
|
|
what enzyme does glucocorticoids upregulate the activity of in the glycogen synthesis pathway?
|
Glycogen synthase
|
|
|
True or false:
Adrenal insufficiency is always life threatening? |
False
Adrenal insufficiency which results in insufficient cortisol and aldosterone is potentially life-threathing. But loss of adrenal androgens is not life threatening. Adrenal insufficiency refers to the adrenals being unable to produce these hormones, so it's not ALWAYS life threathening |
|
|
True or false:
In secondary and tertiary adrenal insufficiency mineralcorticoid lack is only partial |
True
Adrenals are intact and functioning therefore able to be influenced by RAAS |
|
|
Which of the following steroid deficiency may improve with age in CAH?
mineralcorticoid or glucocorticoid? |
Mineralcorticoid
|
|
|
What is the most common cause of adrenal insufficiency?
|
suppression by exogenous steroids
|
|
|
How long would you expect for a suppressed HPA axis to recover when patient has been treated with long term exogenous steroids?
|
12 months
|
|
|
What is the common causes of PRIMARY adrenal insufficieny?
|
1. Autoimmune disease
2. Granulomatous disease |
|
|
True or false
First presentation of primary adrenal insufficiency may be life-threatening? |
True
Most likely precipitated by intercurrent infection |
|
|
In primary adrenal insufficiency, would you expect pigmentation?
|
Yes
|
|
|
Is life-long treatment of glucocorticoid and mineralcorticoid treatment needed in primary adrenal insufficiency?
|
Yes
|
|
|
Is exogenous suppression of steroid production temporary or permanent?
|
Temporary
|
|
|
When (primary/secondary/tertiary) would a patient present as being pale as one of the clinical features of adrenal insufficiency?
|
Secondary and tertiary
Loss of ACTH production |
|
|
Why would electrolyte disturbance be less prominent in secondary and tertiary adrenal insufficiency?
|
RAAS able to maintain mineralcorticoid secretion
|
|
|
How would diagnosis secondary adrenal insufficiency?
|
stimulation of HPA axis by insulin induced hypoglycaemia
or very low dose synacthen or CRH stimulation (not available in Australia) |
|
|
True or false:
Once patient has been diagnosed with adrenal insufficiency, they are not required to carry identifying tags of their conditions because that would lead to discrimination. |
False
Patients need bracelet or neck tag identifying diagnosis and treatment *LT 5 As for discrimination...I made that up...it might happen, but I suppose patient's life is more important... |
