Adrenal Flashcards
Regulation of cortisol
- StAR: transport proteins that moves cholesterol into the mitochondira
- stimulate CYP11a1: converts cholestrol into pregnenolone (controlled at ACTH)
- CYP17: converts pregnenolone into 17-OH-pregnenolone –(3bHSD2)–> 17-OH-progesterone –(CYP21)–> 11-deoxycortisone –(CYP11b)–> cortisol
Adrenal hormone functions: glucocorticoids
- intermediary metabolism - catabolism of protein, fat, carbs to get glucose and fatty acids
- cardiovascular - increase BP and HR
- immunity - lower inflammation (but if innappropriate can increase it)
- growth - decreases growth especially during development to reserve energy for body function if there is not enough
cortisol mechanism of action
- cortisol binds to binding protein
- interacts with intracellular glucocorticoid receptor (GR)
- a chaperone protein transports it into the nucleus
- cortisol+GR dimerize in nucleus and act as TF to alter cellular function
Effects of cortisol altering cellular function
- catabolic effect on muscle protein (muscle wasting)
- increased glycogen and BP –> anti insulin –> decreass uptake of glucose by insulin
- lymphocytes and eosinophils decreased in blood (neutrophilds onlu affect at high levels)
- decreased inflammatory responses
- increased CV contraction and vascular tone to increase output and BP
addison’s disease symptoms and reasons
- hyperpigmentation: less cortisol inhibition of ACTH –> so more aMSH –> aMSH stimulates melanin
- salt craving: less salt retention due to less aldosterone (less Na and Cl being retained)
- fatigue: due to lower BP
- dizziness upon standing: form of orthostatic hypotension
- nausea and vomiting: due to hyperkalemia, seen initially especially
- weightloss: due to vomiting and nausea - loss of appetit
clinical problems of of insufficient adrenal hormones
- primary: addison’s autoimmune disease - immune system attacks adrenal glands
- secondary adrenal insufficiency - congenital adrenal hyperplasia
- 21-hydroxyde insufficiency (more common)
- 11-hydroxyde insufficiency
examples of short and long acting glucocorticoids and mineralocorticoid drugs
short acting gluco.
- hydrocortisone (cortisol) - treats rashes to calm down immune system
long acting
- dexamethasone: high potency and is used for autoimmune diseases and to treat transplant patients
mineralo.
- fludrocortisone
therapeutic use of corticosteroids
- anti allergic and anti inflammatory
- contributing mechanisms: inhibition of proteolytic enzymes, inhibition of leukocyte response, inhibition FGF (fibroblast growth factor)
- common use: allergy, inflammatory, rheumatic, respiratory, dermatological conditions
cancer treatment with corticosteroids
lymphoma and leukemia
- used along antineoplastic
- anti lymphocytic properties
androgen dependent tumours
- use cortisol so suppress ACTH so that tumour can’t grow
hypercalcemia of malignancy
- anti vitamin DR and PTHR
- seen in breast and prostate cancer - excessive bone resorption
Cushing’s disease
- glucocorticoid excess due to innapropriate glucorticoid therapy or ACTH secreting pituitary adenoma
symptoms
- excess deposition of fat in back, face, stomach
- supraclavicular fat pad due to thinning of bones causing vertebral compression
- slow wound healing due to less immune response
- thin skin so easily injured
Pasireotide
indication
- treats cushing’s disease
MOA
- inhibits ACTH secretion from pituitary
- agonist of somatostatin receptor 5
adrenal related inhibitors
- ketoconazole
- inhibits CYP17 and 11A - mitotane
- targets adrenal proteins
- used for inoperable adenocarecinoma - mifepristone
- antagonist of GR - sprionolactone
- antagonist of MR
- used for hyperadrenosteronism
mechanism of action of thyroid hormone
- T3 and T4 can cross cell membrane and nucleus
- bind to TR and TXT complex, kick off CoR and recruit CoA
- trasncription occurs
effects of thyroid hormone on body
- regulates basal metabolic rate
- skeleton growth
- growth and development and function of CNS
- carb absorption
- lipid metabolism
- adrenal and gonadal function
- CV and renal function
- protein synthesis
Hypothyroidism
- infantile cretinism
- 1 in 4000 births
- mental retardation
- deaf and mute
- dwarfism
- CV issues
- mucosaccharides accumulation
- poor thermogenesis - adult hypothyroidism
- due to deficiency or hashimoto’s disease (autoimmune)
- dry skin
- cold intolerance
- constipation
- fatigue
- daytime somnolence
- weight gain
- hair loss
