Adrenal Pharm-Burkin Flashcards
What does somatostatin do?
What does dopamine inhibit?
inhibits GH
Prolactin
Hormones are released from the
anterior pituitary in a (blank) fashion. What is this regulated by?
pulsatile
fluctuations in neuronal activity
e.g. Growth hormone is release in a pulsatile
fashion with a diurnal rhythm.
Where does GH come from?
somatotroeps and somatommaotropes of anterior pituitary
What does GH do?
decreased insulin sensitivity increased lipolysis increased IGF-1 Increased protein synthesis increased epiphyseal (bone) growth
What stimulates GH?
GHRH, hypoglycemia, exercise, certain AAs, sleep
What inhibits GH?
somatostatin
IGF-1
Hyperglycemia
How do you treat a somatotrope tumor?
tumor removal
Somatostatin analogs
Octreotide
What can cause GH deficiency?
hypothalamic and pituitary lesions
What disease can you get if you have GH Deficiency early in life?
dwarfism
What will will GH deficiency cause in adults?
weakness, fine wrinkling and pale skin, loss of sex drive, genital atrophy, menstrual cycle cessation
What is Laron Dwarfs syndrome?
GH receptor defect in target tissues
What causes African Pygmies?
IGF-1 deficiency
How do you treat GH deficiency?
GH and IGF1 replacement
(blank) is a recombinant form of human GH and is used to treat patients with GH deficiency.
Somatrophin
Tx of Turners syndrome patients with (blank) leads to an increase in final adult height.
GH
What can GH treat in children?
What can it treat in adults?
failure to thrive due to chronic renal failure, HIV infections
AIDS associated wasting
(blank) is used to increase milk production in dairy cows.
Recombinant bovine GH
A synthetic version of GHRF called (blank or blank) is an alternative tx for idiopathic growth hormone deficiency
Sermoelin, or Geref
What is the source of prolactin?
What does it inhibit?
lactotropes and samatomammotropes of anterior pituitary
-gonadotropin actin in gonads (decreased steroidogenesis)
What stimulates prolactin?
oxytocin, TRH, VIP and estrogen
What is the tx for excess prolactin secretion?
dopamine agonist (bromocryptine/CB154/Parlodel) suppresses prolactin secretion and shrinks prolactinomas
What does oxytocin do?
stimulates release of milk during lactation and contributes to the initiation of uterine contraction during labor. IV oxytocin is used to induce or reinforce labor and as a nasal spray to induce postpartum lactation
(blank) is secreted in response to rising plasma tonicity or falling blood pressure. Deficiency in this causes (blank)
Vasopressin
Diabetes insipidous
(blank) is used to treat diabetes insipidus.
Desmopressin acetate
Bedtime administration of desmopressin is used to treat (blank)
nocturnal enuresis
what is this:
partial or complete loss of adrenocortical function
Addisons’ disease
What is this:
suppression in the ability of the adrenal cortex to produce corticosteroids
Adrenal suppression
What is this:
A metabolic disorder caused by excess secretion of adrenocorticoid steroids
Cushing’s disease
What is this:
a substance that activates glucocorticoid receptors
glucocorticoid
What is this:
a substance that activates mineralocorticoid receptors
mineralcorticoid
How many AAs make up ACTH?
What ones are for activation?
What ones are for binding?
6-10
15-18
What do you find in the glomerulosa?
angiotensin II
K+
-> causes aldosterone release
What is ACTH independent?
Zona glomerulosa
What is ACTH dependent?
Zona fasciculata
Zona Reticularis
Medulla
ACTH stimulates steroid synthesis via the action of (blank). What is the rate limiting step?
cAMP-PK
delivery of cholesterol to mitochondria via StAR
The steroid synthetic capacity of the adrenal gland is markedly enhanced by the action of (blank)
ACTH
What will ACTH do?
converts cholesterol to pregnenolone
What does angiotensin II do?
converts corticosterone to aldosterone
What will inhibit ACTH and CRH?
DHEA
Aldosterone
Cortisol
What is the main source of androgen in females?
DHEA
What affects kidney to regulate water and salt metabolism?
Aldosterone
What increases metabolic fuels: blood glucose, amino acids and fatty acids
Cortisol
ACTH synthesis is (blank) under the control of higher brain centers in response to (blank)
diurnal
light-dark cycles
App. (blank) mg of cortisol is released daily.
10
Cortisol circulates bound to (blank) and (blank)
transcortin (cortisol binding globulin) and albumin
Does aldosterone concentrations cahnge during the day?
no it is consistent
When are cortisol levels that highest?
during the day
ACTH can be administered parenterally as (blank or blank) with a T 1/2 of (blank)
Acthar or Cosyntropin
15 minutes
What is used as a diagnostic agent in adrenal insufficient? (i.e normal rise in cortisol rules out adrenal failure)
ACTH
What are the actions of ACTH?
- homeostatic hormone
- cant survive w/out it unless food, water and salt are always available and temp is consistent
Cortisol is a (Blank) hormone: low levels of catecholamine have little effect on (blank),
But in the presence of low levels of cortisol marked activation of lipolysis is seen.
Permissive
lipolysis
(blank) is the major form of glucocorticoid. It is bound to (blank) in circulation
Cortisol
transcortin
Cortisol is essential for life because of its important direct effects on intermediary metabolism of (blank X 3)
carbs, proteins, lipids
What does cortisol do?
- stimulates protein breakdown to AAs (especially muscles)
- facilitates lipid breakdown of adipose tissue to fatty acids and glycerol
- promotes hepatic gluconeogenesis from AAs, glycerol, and fatty acids (via oxaloacetate)
- make glucose available to brain by inhibiting utilization by other otissues
What is the permissive action of cortisol?
-small amount required for metabolisms, especially those promoted by catecholamines (e.g lipolysis, bronchodilation)
What is the major form of adrenal androgens but is weak (not important in males)?
DHEA
What is an important source (50%) of androgen in females? What is it important for?
DHEA
- enhancement of pubertal growth spurt
- maintains secondary sex characteristics-pubic and axillary hair
- libido
- some conversion by aromatase to estrogen (via testosterone) in peripheral tissues
What are the synthetic glucocorticoids that have mechanisms of actions identical to cortisol? What are their half lifes like and what do they do to sodium?
prednisone, prednisolone, dexamethasone, triamcinolone
-longer half lives, and reduced Na+ retention effects
(blank) is a glucocorticoid with a low degree of protein binding. Who is it given to?
Bethamethasone
Pregnant women in premature labor to hasten fetal lung maturation (increase surfactant)
(blank) has significant glucocorticoid activity, but because of its long duration of action compared to aldosterone it is favored in conditions requiring mineralocorticoid therapy (e.g. adrenalectomy)
fludrocortisone
What is primary hyperaldosteronism caused by? What are the clinical findings and lab findings?
Hypersecreting tumor of Z. glomerulosa causing excess aldosterone.
- hypernatremia
- hypokalemia
- HTN
What is secondary hyperaldosteronism caused by? What are the clinical and lab findings?
high renin-angiotensin
- hypernatremia
- hypokalemia
- HTN
What is cushings disease caused by?
What are the clinical findings and lab findings
excess CRH/ACTH
Hyperglycemia excess protein breakdown abnormal fat distribution insuling resistance -decreased immune response -decreased inflammatory response
What are all the causes of cortisol excess?
- excess CRH/ACTH
- Adrenal tumor
- ectopic ACTH (e.g lung cancer)
What are the conditions that cause androgen excess?
congenital adrenal hyperplasia (CAH, adrenogenital syndrome in females)
What causes congenital adrenal hyperplasia?
genetic deficiency in cortisol synthetic enzymes (21 and 11 OH)
What are the symptoms of androgen excess?
- inappropriate masculinization
- pseudohermaphroditism
- Virilization in females
- pseduopuberty in boys
What is the condition that has cortisol and aldosterone deficiency?
What is the cause?
Primary adrenal insufficiency (Addison’s disease)
Destruction or atrophy of adrenal cortex
What are symptoms of primar adrenal insufficiency (addison’s disease)?
related to cortisol deficiency
- poor response to stress
- hypoglycemia
- low metabolic activities
What is the condition associated with cortisol deficiency?
What is the cause?
secondary adrenal insufficiency
-Insufficient ACTH-hypoth/pituitary failure
What are the symptoms of cortisol deficiency?
Relating to aldosterone deficiency
- hyperkalemia
- hyponatremia
- hypotension
What are the signs and symptoms of Cushings syndrome?
- myopathy
- central obesity
- moon face
- Acne
- Hirsuitism
- Bruising and capillary fragility
- HTN
- Glucose intolerance
- hypokalemia
- arteriosclerosis
- infections
- osteoporosis
- hypogonadism
What percentage of cushings’ syndromes are ACTH dependent?
80%
- 60% are pituitary tumors
- 20% are due to lung cancers
What percentage of cushings syndromes are ACTH independent?
20%
- Benign adrenal tumors (adenomas)-25%
- Malignant adrenal tumors (adrenal cell carcinoma) 10%
How do you confirm Cushings disease?
dexamethasone suppression test.
NOTE: Tx w/ dexamethasone causes a reduction in cortisol in normal patiens. In Cushings patients cortisol will remain the same or even elevated
What are the effects of corticosteroids on carbohydrate and protein metabolism?
- Stimulates formation of glucose
- Diminishes peripheral utilization of glucose
- Promotes the storage of glucose as glycogen.
What are the effects of corticosteroids on lipid metabolism?
-redistribution of body fat in the hypercorticoid state
-permissive effect on the actions of other agents that promotes lipolysis in adipocytes
NOTE: cushings patients have buffalo hump and moon face and thinning in the extremities
(Blank) patients are apathetic, depressed, and irritable, some displaying frank psychosis
Addison’s
Admin of corticosteroids to normal patients induces a feeling of (blank)
well being
What do glucocorticoids do to the blood?
- increase red cell hemoglobin and red cell content of blood
- increase neutrophils
- decreased lymphocytes, eosinophils, basophils and monocytes
What will your blood look like in Cushings?
polycythemia
What will your blood look like in Addisons?
normochromic normocytic anemia in Addisons
What are the anti-inflammatory and immunosuppressive actions of glucocorticoids?
- decrease circulating lymphocytes and suppress release of cytokines
- suppress inflammation to all stimuli
How do glucocorticoids prevent inflammation?
bind to transcription factors and inhibits them so that inflammatory cytokines cannot be created
Cortisol will block both (blank and blank) events in the inflammatory process and effect both (blank and blank) pathways
early and late
cellular and humoral
How do glucocorticoids effect macrophages and monocytes?
- inhibits arachidonic acid w/ lipocortin (blocks phospholipase A)
- inhibits cytokine synthesis
How do glucocorticoids effect basophils?
blocks IgE mediated release of Histamine and leukotriene C4 release
How does glucocorticoids effect fibroblasts?
inhibits arachidonic acid by lipocortin and suppresses growth factor-induced DNA synthesis and fibroblast proliferation
How does glucocorticoids effect lymphocytes?
blocks cytokine release
What are the 6 types of adrenocortical steroids and how do you use them?
- Becloethasone diproprionate (inhalation)
- Betamethason valerate (topical)
- Cortisol (topical, suppositories, rectal foam, injectable, oral)
Use of high dose steroid tx for weeks to months may result in (blank)
delayed return of adrenal function
How should you end corticosteroid tx?
A slow reduction in the dose over 1-2 weeks to end treatment is recommended
What can high dose chronic use of corticosteroids cause?
Hypokalemic alkalosis and edema Increased susceptibility to infection Peptic ulceration (H. pylori) Myopathy Behavioral disturbance Cataracts Osteoporosis & vertebral compression fractures Growth arrest in children
Mineralcorticoids work where in the kidney?
distal tubule to enhance reabsorption of Na+
In hypercorticism what happens?
hypernatremia hypokalemia alkalosis edema increase ECF
In cortical insufficiency there is a renal wasting of (bank)
sodium
What are the inhibitors of adrenal steroid biosynthesis?
Aminoglutethamide
Ketoconazole
Trilostane
Metyrapone
How does aminoglutethamide work?.
blocks the conversion of cholesterol into pregnenolone
How does ketoconazole work?.
blocks the 17-hydroxylase preventing creation of 17a-hydroxypregnenolone and 17 a-hydroxyprogresterone
How does trilostane work.
blocks 3HSD so you wont have conversion of prenenolone to progesterone or conversion of 17a hydroxyprenenolone to 17 a hydroxyprogesterone
How does metyrapone work?.
blocks 11-OHase so that you cannot convert 11-deoxycortisol to cortisol
(blank) inhibits the first step in biosynthesis (P450 scc) from cholesterol interrupting production of both cortisol and aldosterone.
Aminoglutethimide
What do you use aminoglutethimide for.?
- Cushngs disease (if too much suppression give cortisol and mineralcorticoids)
- adrenal tumors and overproduction of ACTH
What is ketoconazole and what does it do?
antifungal drug that blocks P450 17 a enzyme required for cortisol and inhibits P450 scc enzyme at high concentrations
What do you use ketoconzole in?
- adrenal carcinoma
- hirsuitism
- breast and prostate cancer
What does trilostane do?
inhibits 3b OH steroid dehydrogenase which blocks formation of cortisol and aldosterone and increases excretion of 17-keto steroids
What do you use trilostane for?
Cushing disease
NOTE: drug not realy used, would use aminoglutethemide more often)
What does metyrapone do?
blocks 11-b hydroxylation and increases 11-desoxycortisol and results in renal secretion of 17-OH steroids
Increases ACTH due to feedback (DOC is a very weak inhibitor of ACTH so ACTH is still increased)
What is 11-deoxyotisol (DOC)?
a weak inhibitor of ACTH production
Metyrapone results in an increase in ACTH production permitting assessment of the pituitary release of ACTH and adrenal response in the form of (blank) in the urine
17-OH steroid in the urine
