week 10- hormones Flashcards
• Where are hormones made in adrenal cortex?
o mineralocorticoids: zona glomerulosa (outer cortex)
o glucocorticoids: zona fasciculate (middle)
o androgens: zona reticularis (inner)
o catecholamines: medulla
• what is adrenal steroidogenesis?
o cholesterol → pregnenolone, in mitochondria
o → (SER) mineralcorticoids, glucocorticoids, androgens ( 3 diff pathways)
• What is pregnenolone? What hormones does it make?
o The “mother” hormone o from cholesterol o Pregnenolone → progesterone OR DHEA o Progesterone → mineralocorticoids, glucocorticoids, OR T/E o DHEA → T/E
• What is DHEA?
o Produced in Adrenal Glands, Gonads, Brain
o DHEA → Androsterone →Testosterone & Estrone
o Peaks ~30
o Most abundant steroid hormone
• What can suppress DHEA? Low levels assoc w?
o Suppress: stress, excess corticol
o Assoc: Immune dysfunction, AI, DM II, CA, HTN, CVD, Depression, Cognitive dysfunction, Low libido, Osteoporosis
• What is the DHEA pathway?
o Pregnenolone → 17-OH-pregnenolone → DHEA
o → androsterone, etiocholanolone, androstenedione
o Androstenedione → T/E
• What is aldosterone?
o mineral and water balance
o ↑ Na re-absorption in distal tubules of kidney, + passive absorption of water by osmosis
o excretion of potassium (active and passive)
o ↑ Na re-absorption in sweat glands.
o ↓ BP, Na →JGCs → renin → angiotensinogen (liver) → angiotensin I → angiotensin II → adrenal → aldosterone → kidney tubules → ↑BP, Na
• What is cortisol?
o steroid hormone
o essential for life (long term); net effects are catabolic
o prevents hypoglycemia
o promotes gluconeogenesis, breakdown of skeletal muscle protein
o enhances fat breakdown (lipolysis)
o suppresses immune system
o breakdown of bone matrix (high doses)
• how is cortisol anti-inflammatory?
o ↓ capillary permeability (↓ entrance of cells to inflamed areas)
o Stabilize lysosomal membranes (↓ release lysozomes)
o ↓phagocytosis by WBCs, ↓ fever
o ↓T lymphocytes (↓ immunity), eosinophils (↓allergic rxns)
o ↓ synthesis interleukins
o inhibits synthesis collagenase
o → slow, but less painful healing
o Useful in transplant operations to reduce organ rejection
• What happens to cortisol in chronic stress?
o Prolonged ↑ cortisol → break down of muscle, excessive Epi release, hyperglycemia, weakening of bone, destruction of immune system, inhibition of reproductive function, other complications.
• How is cortisol release regulated?
o primarily neuroendocrine control
o ACTH stimulates adrenal gland to release cortisol
o (-) feedback on hypothalamus (CRH), pituitary (ACTH)
• What is the daily pattern of cortisol release?
o Changes ~30 mins after changes in ACTH
o ↑ few hours after sleep, then ↓ (diurnal rhythm)
o Lowest shortly before and shortly after sleep begins
o ↑ on waking in morning (peak), and sporadically throughout day
• How is cortisol transported?
o 95% bound to cortisol binding globulin (aka transcortin), 5% circulating is free
o not biologically available when bound to CBG
o CBG is made in liver (↑ by estradiol)
• How is cortisol metabolized?
o 90 min half-life
o in liver →conjugated to glucuronic acid
o = ↑solubility in water, excreted via kidneys
• What are the pahses of the general adaptation syndrome?
o Fight or flight
o Resistance
o exhaustion
• What is the “fight or flight” phase of the general adaptation syndrome?
o immediate short term response to crisis
o Sympathetic stim → adrenal medulla → Epi, NE
o Mobilize glucose reserves
o Changes in circulation
o ↑ HR and RR
o ↑ cell metabolism (energy)
• What is the resistance phase of the general adaptation syndrome?
o Long-term metabolic adjustmens
o GC/GH- mobilize remaining energy reserves: lipids, amino acids; conserve glucose
o GC/Glucagon: ↑ blood glucose, liver synthesis
o MC (RAAS): conserve salts, water; lose K, H
• What is the exhaustion phase of the general adaptation syndrome?
o Collapse of vital systems
o Dt exhaust lipid reserves, can’t make GCs, electrolyte imbalance, vital organ damage
• What are normal blood cortisol levels (mg/dL)? Interfering factors?
o Adult: 6-28 (8am); 2-12 (4pm) o Child: 3-21 (8am); 3-10 (4pm) o ↑ w Pregnancy o ↑ w Physical & emotional stress o Drugs
• What is Cushing’s syndrome? Dz?
o Syndrome= Supraphysiologic availability of glucocorticoid hormones (cause ↑ cortisol)
o Etio: Exogenous, Endogenous, Pseudo-Cushing’s (alcoholism)
o Dz: ACTH producing pituitary adenoma
• What are physiologic effects of Cushing’s?
o Hyperglycemia: stimulation of gluconeogenesis & glycogenolysis
o Negative nitrogen balance: osteoporosis, muscle wasting, reduced fibrogenesis, thin skin, easy bruising
o Salt and water retention: tendency to CHF with hypokalemia, HTN
o Reduced immune response: increased susceptibility to infection
• What are ssx of Cushing’s?
o Central obesity, Facial plethora, Striae o Glucose intolerance o Myopathy o Hypertension o Bruising o Hirsuitism, Acne o Oligo/amenorrhea, Impotence o Ankle edema o Fracture
• What are basic lab findings for Cushing’s?
o CBC: leukocytosis, lymphocytopenia, ↓eosinophils
o CMP: hyperglycemia, hypokalemia, hypernatremia
o Thyroid Function: ↓T3, TSH
• What are recommended test for Cushing’s?
o 1st line: UFC (urinary free cortisol), Low dose or overnight dexamethasone test, Night-time salivary cortisol
o test pts w multiple sxs
o if abn result: see endocrinologist for 2nd test (above) or serum midnight cortisol or dexamethasone-CRH test
• what is 24-hr UFC?
o Integration of plasma cortisol throughout day
o Assays (HPLC or MS) normal range 10-34 ug, M > F
o Pseudo-Cushings patients: mb have N values in newer assays, but ↑ in older assays
o Many Cushing’s patients N in new assay
o Most Cushing’s are periodic (need multiple days of collections)
o mb normal if high at night, low during day
