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54 Cards in this Set
- Front
- Back
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Principles of the pituitary function tests
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1. Measure basal pituitary hormone and target organ hormone levels.
2. Stimulation test if inadequacy suspected 3. Suppression test if excess suspected |
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What is the schematic for the H-P-Target Organ system?
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What is the H-P-Thyroid system? What are the specifics?
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TRH: thyrotropin releasing hormone
TSH: thyroid stimulating hormone |
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What is primary thyroid failure?
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Low free T4, high TSH
Ex: lymphocytic thyroiditis |
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What is 2ary thyroid failure?
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Low free T4, low or normal TSH
Ex: Pituitary tumor |
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What is the H-P-Ovarian Axis?
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Primary ovarian failure: low estradiol, high LH/FSH
Ex: menopause 2ary ovarian failure: low estradiol, low/normal LH and FSH Ex: Pituitary tumor |
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What is the H-P-Testes axis?
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How do pulsatile and constant GnRH affect LH and FSH levels?
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-Pulsatile: stimulates LH and FSH, used in pts w/ hypothalamic lack of GnRH (Kallman's Syndrome). LH and FSH in turn stimulate testes and increases testosterone and sperm production.
-Constant: suppresses LH and FSH after initial stimulation, which suppresses testes and decreases testosterone and sperm production. Occurs in idiopathic central precocious puberty and hormone-sensitive tumors (prostate/breast). |
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Describe the H-P-Adrenal Axis.
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Describe normal cortisol secretion.
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Highest right before we wake, lowest right before we go to bed.
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How do the various ACTH and cortisol diseases relate to each other?
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What does the Acute ACTH stimulation test cause? What does it show?
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-Primary adrenal insufficiency (addison's disease): no increase in cortisol
-2ary adrenal insufficiency: +/- cortisol increase |
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What does the dexamethasone suppression test show?
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Dexamethasone is an active synthetic steroid (ACTH) not picked up by cortisol assay. In normal people, Dexa causes decreased cortisol. In Cushing's, cortisol is not decreased.
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What is Cushing's Disease?
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Pituitary-tumor induced Cushing's Syndrome. Tumors may be too small/amorphous to be seen clearly on pituitary imaging. Lung carcinoid tumors may secrete ACTH and mimic Cushing's Disease.
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Describe the control of aldosterone
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Which hormones affect the gluco- and mineralo-corticoids?
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Gluco: ACTH. Replace glucocorticoids if pit def.
Mineralo: renin/angiotensin. Replace gluco and mineralo if adrenal def. |
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Describe the H-P-Growth hormone axis.
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-GH secretion is diurnal, w/ highest levels soon after sleep starts. Get a second peak soon after waking. Is pulsatile and changes w/ aging.
-Direct Effects: most metabolic effects, feedback -Indirect Effects: Most growth effects, mediated by IGF-1, feedback -Acute Effects: increase fat synthesis, increase glucose utilization -Chronic effects: decrease fat synthesis and glucose utilization, increase protein synthesis and gluconeogenesis. -GH secretion stimulation: Insulin-induced hypoglycemia, exercise, arginine, GHRH, glucagon. |
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Why/how is IGF-1 used as a screening test for growth hormone?
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-high in acromegaly, low in hypopituitarism.
-IGF-1 affected by age, sex, nutrition -Not affected by time of day, stress, etc. -not adequate as definitive test. |
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Describe the H-P-Prolactin axis.
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-Prolactin feeds back on own seretion via dopamine. If connection btwn hypothalamus and ant pit severed, all hormones decrease except prolactin.
-Get increase in hormone levels 30secs after suckling starts. -Direct Effects: lactation, immune effects (?), effects on fat and adipokines. -Indirect effects: mediation by IGF-1 |
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What is Whipple's Triad?
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To be hypoglycemic, must have all 3:
1. Plasma glucose < 45mg/dL 2. Concomitant sx 3. Relief of sx following carbs. |
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What is the hierarchy of response to hypoglycemia?
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Plasma glucose (mg/dL)
70: catecholamines, glucagon 60: cortisol, GH 50: Autonomic sx 40: Neuroglycopenic sx 30: Lethargy 20: seizures, coma |
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Differentiate between autonomic and neuroglycopenic sx.
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Autonomic: tremors, nervousness, hunger, anxiety, palpitations, diaphoresis
Neuroglycopenic: visual disturbances, lethargy, confusion, impaired performance |
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Which glucose transporters are used in the CNS?
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GLUT1: to cross BBB
GLUT3: to enter neuron |
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How does the CNS react to hypoglycemia?
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-Acute: increases cerebral blood flow to get more glucose and alleviate sx. Increase in epinephrine release
-Chronic: 50% increase in GLUT-1, possible increase in GLUT-3. decrease in epinephrine release bc brain gets used to low glucose state. |
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If you do not have glycogen in your liver, can you respond to glucagon?
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No, glucagon triggers glycogenolysis in the liver.
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Describe the 2 types of reactive hypoglycemia.
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-Alimentary: people think they are hypoglycemic 2-3 hrs after a meal. Occurs after gastric surgery, may be related to islet proliferation (beta and ductal cells).
-Nesidioblastosis: hypoglycemia that occurs after bypass surgery. |
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How do you tx reactive hypoglycemia?
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1. alpha-glucosidase inhibitors work in most people
2. Diazoxide to decrease insulin secretion 3. avoid caffeine 4. rare - pancreatectomy |
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What are the 7 causes of spontaneous hypoglycemia?
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ONI HEAD: Organ failure, non-beta cell tumors, insulin secreting tumors, hormone deficiencies, enzyme deficiencies, autoimmune, drugs
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Describe insulin-induced hypoglycemia.
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-relatively common
-more frequent in DM1 who lack glucagon response to hypoglycemia. -more common in pts w/ hypoglycemia unawareness. |
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How does EtOH cause hypoglycemia?
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-EtOH inhibits gluconeogenesis. Alcoholics usually don't eat, are in starvation, and glycogen is depleted, so can't respond to glucagon. EtOH also impairs the cortisol and GH response to hypoglycemia.
-EtOH also actively inhibits gluconeogenesis. -To break down EtOH, pyruvate is not made, can't do gluconeogenesis, lactate builds up. Further can't release glucose from liver. |
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How do salicylates cause hypoglycemia?
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-Inhibit FFA oxidation, impairing gluconeogenesis.
-Also inhibits serine kinase IKK-beta -> increased insulin sensitivity -> hypoglycemia |
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How does caffeine affect cerebral blood flow?
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Caffeine decreases cerebal blood flow, so brain cant compensate as much to hypoglycemia. brain sees more hypoglycemia, get greater symptoms and release of epi.
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How do beta blockers cause hypoglycemia?
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Lowers the threshold for autonomic sx in poorly controlled pts w/ DM1, so sx used to start at 80 mg/dl, now start at 60. Have minimal decrease in adrenergic sx and increased cholinergic sx. Harder for them to recognize their hypoglycemic sx.
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What are the different enzyme deficiencies that can cause hypoglycemia?
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-defects in fatty acid oxidation
-G6P deficiency, glycogen storage disease -Galactosemia -Inborn errors of amino acid metabolism |
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How do non-beta cell tumors cause hypoglycemia?
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they are very large, and assoc w/ increased secretion of IGF-2, which circulates at lower molecular weight than IGF-1, permitting greater tissue accessibility.
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How do Insulinomas cause hypoglycemia?
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-very rare
-Do multiple tests -Insulin remains high even when fasting, have decreased glucose utilization. -Best way to find is via arteriography w/ Ca infusion |
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How do hypoglycemia and HbAlc levels relate?
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Higher HbA1c = more risk of hypoglycemic episodes, but have more severe hypoglycemic episodes with lower HbA1c.
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Describe hypoglycemia in diabetics.
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-Type 1 has more episodes with increased severity.
-Type 2 has fewer bc of greater preservation of counterregulatory response to early hypoglycemia, such as glucagon. -Tx: 15-25 gm carbs. -Sulfonylurea can prolong hypoglycemia, need to be hospitalized for 24 hrs, until drug is out of system. |
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Describe how glucose causes insulin secretion.
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In basal state, ATP dep K channel is open, K runs out, makes cell negative. Ca channels are closed. When we eat, glucose is metabolized, makes ATP, ATP binds to K channel, closes it, cell becomes depolarized/positive bc K not leaving. Ca channel then opens after depolarization. Ca entering cell causes release of insulin.
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How does GLP-1 cause insulin secretion?
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GLP-1 bings to receptor, AC turns ATP into cAMP, which binds to K channel, closing it. Depolarization of cell causes Ca channel to open and Ca to enter cell. cAMP and Ca both act to release insulin.
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How does insulin lead to glucose uptake?
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Insulin binds to extracellular alpha subunit of receptor. Transmembrane portion is a kinase, and phosphorylates self by making ATP -> ADP. This starts a kinase cascade, which includes IRS. Phosphorylation of GLUT4 leads to its translocation to the plasma membrane.
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What happens when there is no insulin or insulin resistance?
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No glucose can be taken up by muscles, so think you are hypoglycemic. Get glycogen breakdown and protein degradation. Leads to increased lactate, aa's, and alanine in blood.
-Fat: LPL is insulin sensitive and in bloodstream, so not able to move triglycerides into adipose cells. HSL is sensitive to cortisol, catecholamine, glucagon, -> causes release of TAGs into blood. LIPOLYSIS. -Overall: glycogenolysis, gluconeogenesis, ketogenesis (from FFAs), increased hepatic glucose output. |
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How is glucagon secreted by the alpha cells?
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Glucose enters cell, made into pyruvate to make ATP. ATP closes K channel, cell depolarizes, Ca enters, glucagon leaves.
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How does insulin influence glucagon secretion?
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If present, insulin + Zn will bind to separate receptor and keep K channel open, so cell cannot depolarize.
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How does epinephrine affect glucagon secretion?
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Epi binds to receptor, makes cAMP, cAMP binds to K channel, cell depolarizes, Ca enters, glucagon leaves.
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What scenarios cause glucagon release?
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1. Hypoglycemia - islet interstitial conc of insulin low, or release of catecholamines.
2. Diabetes induced hyperglycemia - insulin conc too low or alpha cell is insulin resistant |
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How does glucagon increase ketogenesis?
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1. Stimulates hormone sensitive lipase (HSL) to make more FFAs
2. Inhibits acetyl coA carboxylase to decrease malonyl coA resulting in more fatty acid oxidation 3. Stimulates ketogenic enzymes (HMG-CoA synthase and lyase). |
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What are the consequences of hyperglycemia?
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1. osmotic diuresis: pee out glucose, fluids, electrolytes
2. Urinary loss of water, electrolytes leave w/ glucose, get dehydrated 3. Weakness, weight loss, shock b/c can't maintain BP. |
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What are the consequences of ketosis?
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-Acidosis
-impaired cardiovascular fxn. |
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What are the differences between DKA and non-ketotic comas?
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in DKA - usually sick for some other reason, not as severe as ketotic, but comes on much quicker, w/in hrs. Osm higher in non-ketotic bc of higher glucose. Also have much more renal insufficiency in non-ketotic coma.
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What are the diagnostic criteria for diabetes?
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1. Presence of classic sx plus a casual plasma glucose > 200mg/dL
2. Fasting plasma glucose > 126mg/dL 3. 2 hr plasma glucose >200 mg/dL during OGTT 4. HbA1c > 6.5% |
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What is the diagnostic criteria for gestational diabetes? Why is is stricter?
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Stricter bc of risk of fetal loss and/or malformations.
1. Initial screen >140mg/dl one hr after 50g glucose load 2. Diagnosis: fasting greater than 95, 1 hr greater than 180, 2 hr greater than 155, 3 hr greater than 140 during a 100g glucose challenge. |
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What is the criteria for impaired glucose tolerance?
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1. Fasting plasma glucose btwn 100 and 126.
2. 2hr post glucose load btwn 140 and 200. 3. Not assoc w/ microvascular complications of DM but at risk for developing DM. 4. Assoc risks of insulin resistance syndrome. |
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What is the best clinical parameter for differentiating btwn type 1 and type 2?
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Type 1 is ketoacidosis prone.
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