Endocrine Flashcards
1
Q
Thyroid development
- derived from
- connections to tongue and what it turns into
- thyroglossal duct cyst: sxs
- thyroid follicular and parafollicular cells derived from
A
- primitive pharynx
- thyroglossal duct -> normally disappears but can persist as pyramidal lobe
- anterior midline neck mass that moves w/ swallowing
- endoderm
2
Q
Adrenal Cortex
- derived from
- glomerulosa: primary reg, hormone produced, hormone class
- fasiculata
- reticularis
A
- mesoderm
- Angiotensin II, Aldosterone, mineralcorticoids
- ACTH, cortisol, glucocorticoids
- ACTH, DHEA, androgens
3
Q
Adrenal Medulla
- dervied from
A
- neural crest
4
Q
Ant pit
- secretes
- derived from
- basophila
A
- FSH, LH, ACTH, TSH, prolactin, GH,
- oral ectoderm
- FSH, LH, ACTH, TSH
5
Q
Post pit
- secretes
- created
- transported
- derived
A
- vasopressin and oxytocin
- hypothalamus
- post pit via neurophysins
- neuroectoderm
6
Q
Endocrine Pancreas
- alpha cell
- beta cell
- delta cell
- arise from
A
- glucagon
- insulin
- somatostatin
- pancreatic buds
7
Q
Insulin
- synthesis: 1st product, 2nd product, final product
- function: binds, next steps
- anabolic effects: muscle, adipose, glycogen, triglyceride, Na, proteins, K and AA, glucagon, lipolysis
- insulin dependent glucose transporters: location
- organs with non insulin dependent glucose transporters: BRICK LIPS
- regulation
- insulin binding pathway
- insulin release pathway
A
- preproinsulin -> cleavage of presignal -> proinsulin -> cleavage of proinsulin -> exocytosis of insulin and C peptide
- binds insulin receptor -> induce glucose uptake -> gene transcription
- increase glucose in muscle and adipose, glycogen synthesis and storage, triglyceride synthesis, Na retention, protein synthesis, cellular uptake of K and AA; decreased glucagon release, and lipolysis
- GLUT 4: adipose and muscles
- Brain, RBC, Intestine, Cornea, Kidney, Liver, Iselt cells, Placenta, Spermatocyte
- controlled by glucose concentration in blood, increase in glucose causes increase in insulin
- insuling binds receptor -> PIP 3 activated -> glut 4 to membrane -> glucose into cell
- glucose binds glut2 -> ATP/ADP ratio increased -> K channels close -> voltage gated Ca channel open -> increase in intracellular Ca -> exocytosis of insulin
8
Q
Glucagon
- made by
- function
- regulation
A
- alpha cells of pancrea
- glycogenolysis, gluconeogenesis, lipolysis, ketogenesis -> elevates blood sugar to maintain homeostasis
- secreted in response to hypoglycemia
9
Q
Hypothalamic - Ant Pit Hormones
- ADH: function,
- CRH: function
- Dopamine: function
- GHRH: function
- GnRH
- MSH
- Oxytocin
- Prolactin
- Somatostatin
- TRH
A
- ADH: increase in water permeability to DCT and collecting guct -> increase water reabsorption
- CRH: Increase ACTH and beta endorphin
- Dop: decrease in prolactin
- GHRH: increase GH
- GnRH: increase FSH, LH
- MSH: increase melanogenesis by melanocytes
- Oxy: causes uterine contraction during labor, responsible for milk letdown reflex
- Prolactin: decrease in GnRH
- Somato: decrease in GH, TSH
- TRH: Increase in TSH, prolactin
10
Q
Prolactin
- source
- function: breast milk, fertility
- reg: inhibition,
A
- ant pit
- stimulates milk production, inhibits ovulation and spermatogenesis by inhibiting GnRH synthesis and release
- inhibited by dopamine; prolactin inhibits own secretion by increasing dopamin synthesis
11
Q
Growth Hormone
- other name
- production
- function
- regulation: released in response to, inhibited by
- excess secretion of GH causes -> TX
A
- somatotropin
- ant pit
- linear growth and muscle mass
- pulsatile, released in response to growth hormone releasing hormone, which is increased during exercise, deep sleep, puberty, hypoglycemia; inhibited by glucose and somatostatin
- acromegaly of gigantism; TX w/ somatostatin analogs
12
Q
Appetite Reg
- Ghrelin: function; produced by; sleep deprivation/ prader willi causes; location of effect
- Leptin: function; produced by; mutation causes; sleep deprivation or starvation causes
- Endocannabinoids: location; function; exogenous
A
- stimulates hunger and GH release; produced by stomach; sleep deprivation or prader willi causes increased ghrelin production; lateral area of hypothalamus
- satiety hormone; produced by adipose tissue; congenital obesity; decrease in leptin production
- act at cannabinoid receptor in hypothalamus to increase appetite; reason why exogenous cannabinoid causes the munchies
13
Q
Anti-diuretic Hormone
- other name
- production
- function
- regulation
- central diabetes insipidus vs nephrogenic
A
- vasopressin
- hypothalamus and stored and secreted in post pit
- reg serum osmolality and blood pressure via reg of aquaporin channel insertion in principal cells
- plasma osmolality/ hypovolemia
- ADH decreased vs ADH normal
14
Q
Cortisol
- source
- function: increases, decreases
- regulation
A
- adrenal zona fasiculata
- increase appetite, DP, insulin resistance, gluconeogenesis/lypolysis/proteolysis; decreases fibroblast activity, inflammatory and immune responses, bone formation
- CRH stimulates ACTH release causes cortisol
15
Q
Ca homeostasis
- forms
- increased pH
- decreased pH
A
- ionized, hound to albumin, bound to anions
- albumin binds more Ca -> decrease free Ca -> increase PTH
- albumin binds less Ca -> increase in free Ca -> decrease PTH
16
Q
PTH
- source
- function
- reg: increases PTH; decreases PTH
A
- chief cells of parathyroid
- increase bone resorption of Ca and PO4, kidney reabsorption of Ca in DCT, and D3 production; decrease reabsorption of PO4 in PCT
- decreased serum Ca, high PO4, low serum MG; very low MG
17
Q
Calcitonin
- source
- function
- reg
A
- parafollicular cells of thyroid
- decrease bone resorption of Ca
- increase serum Ca -> calcitonin secretion
18
Q
Thyroid Hormones
- source
- secreted form vs activated form
- function- 6 B’s
- reg
- TBG: what is it, function, increased by, decreased by
A
- follicles of thyroid
- T4 vs T3
- Brain maturation, bone growth, beta adrenergic effects, increase basal met rate, increase blood sugar, breaks down lipids
- TRH -> TSH -> T4 -> T3 -> w/ neg feeback from T3/T4
- thyroxine binding gobulin; binds T3 and T4 making it inactive in blood -> will increase w/ estrogen, heaptic failure, steroid use, nephrotic syndrome
19
Q
Signaling Pathways of endocrine hormones
- cAMP: pathway; FLAT ChAMP CGGH
- cGMP: BAD GraMPa
- IP3: GOAT HAG
- Intracellular receptor: PEE CAT TV
- Tyrosine Kinase: Get Found In the MAP
- Non TK: PIGGlET
A
- G-alpha-s -> AC -> cAMP -> PKA; FSH, LH, ACTH, TSH, CRH, hCG, ADH, MSH, PTH, calcitonin, GHRH, glucagon, histamine
- BNP, ANP, NO
- GnRH, Oxytocin, ADH, TRH, histamine, angiotensin II, Gastrin
- Progesterone, estrogen, tetosterone, cortisol, aldosterone, T3/T4, Vit D
- Insulin, IGF-1, PDGF
- Prolactin, Immunomodulators, GH,G-CSF, Erythropoeitin, Thrombopoeitin
20
Q
Adrenal Steroid Synthesis
- aldosterone
- glucocorticoids: 2 pathways; inhibited by
- androgens
- estrogen
A
- chol -> pregnenolone -> progesterone + 21- hydroxylase -> 11-deoxycorticosterone + 11 beta hydroxylase -> corticosterone -> aldosterone
- chol -> pregnenolone -> 17 hydroxy pregnenolone -> 17 hydroxy progesterone -> 11 deoxy cortisol -> cortisol –OR– Chol -> pregnenolone -> progeterone -> 17 hydroxy progesterone -> de oxy cortisol -> cortisol; metyrapone
- chol -> pregnenolone -> 17 hydroxy pregnenolone -> DHEA -> androstenidione -> testosterone -> DHT –OR – chol -> pregnenolone -> progesterone -> 17 hydroxy pregnenolone -> androstenidion -> testosterone
- aromatase, from androstenidione or testosterone
21
Q
Androgen Enzyme Deficiencies
- 17 alpha hydroxylase: amount of mineral corticoids, amount of cortisol, amount of sex hormone, BP, [K], labs, presentation
- 21 hydroxylase: amount of mineral corticoids, amount of cortisol, amount of sex hormone, BP, [K], labs, presentation
- 11 beta hydroxylase: amount of mineral corticoids, amount of cortisol, amount of sex hormone, BP, [K], labs, presentation
A
- used to make 17 hydroxy pregnenolone and progesterone -> will result in lots of mineral corticoids, low cortisol and androgens , high BP, low K; XY: ambiguous genitalia w/ undescended testes and XX lacks seconday sex development
- low mineral corticoids, low cortisol, high sex, low, BP, high K, high renin and 17-hydroxy progesterone; salt wastin or precocious puberty w/ virilization in women
- low aldosterone but high deoxycorticosterone, low cortisol, high sex, high BP (deoxycoritco), decreased K, decreased renin, virilization in women
22
Q
Cushing syndrome
- etiology
- causes (3 ish)
- findings
- DX
- Exogenous glucocorticoids or adrenal tumor
- Ectopic ACTH
- Cushing DX
A
- increased cortisol
- exogenous corticosteroids, adrenal adenoma/ hyperplasia/ carcinoma; ACTH secreting pit adenoma
- hypertension, weight gain, moon face, buffalo hump, skin changes, hirsutism, amenorrhea
- increased free cortisol on 24 hr UA, increased late night salivary cortisol, no suppression w/ low dose dexamethasone
- suppressed ACTH test
- elevated ACTH w/ no suppression on dexamethasone test and no increase in ACTH and cortisol w/ CRH
- elevated ACTH w/ adequate suppression on dexamethason test and an increase in ACTH and cortisol on CRH stim test
23
Q
Nelson Syndrome
- what is it
- sequalae
- sxs
- tx
A
- removal of cortisol feedback after bilateral adrenalectomy for refractory cushing dx
- enlargement of existing ACTH secreting pit adenoma
- hyperpigmentation, headache, bitemporal hemianopia
- pit radiation or resection
24
Q
Adrenal insufficiency
- what is it
- sxs
- tx
A
- inability of adrenal gland to generate enough glucocorticoids +/- mineralcorticoids
- weakness, fatigue, orthostatic hypotension,
- glucocorticoid and mineralcorticoid replacement
25
Primary Adrenal Insufficiency
- what is it// caused by
- acute
- addisons dx
- waterhouse- friedrichsen: what is it
- deficiency of aldosterone and cortisol production because of loss of gland function
- hypotension, hypekalemia, metabolic acidosis, skin/mucosal hyperpigmentation
- sudden, presents w/ shock in acute adrenal crisis
- caused by adrenal atrophy/destruction by DX (Autoimmune or TB)
- acute primary adrenal insuff bc of adrenal hemmorrhage associated w/ septicemia, DIC and endotoxin shock from N meningitidis
26
Secondary Adrenal insufficiency
- caused by
- sxs
- decreased in pit ACTH production
| - no hyperpigmentation and no hyperkalemia bc aldosterone is intact
27
Tertiary Adrenal insufficiency
- caused by
- adlosterone
- chronic use of exogenous steroids w/ abrupt withdrawal
| - aldosterone unaffected so K and htn should be fine
28
Hyperaldosteronism
- what is it
- sxs
- primary: caused by; aldosterone vs renin levels; main sxs
- secondary:
- increased secretion of aldosterone from adrenal gland
- hypertension, decreased K, met alkalosis
- caused by adrenal adenoma or bilateral adrenal hyperplasia; increase in aldosterone with decrease in renin; treatment resistant HTN w/o edema
- pts w/ renovasc HTN, juxtaglomerular tumors and edema
29
Neuroendocrine tumors
- what is it
- GI, Pancreas, lungs, thyroid, adrenals
- heterogenous groups of neoplasms originating frm neuroendocrine cells
- GI tract (gastrinoma) , pancreas (insulinoma), lungs (small cell), thyroid (medullary carcinoma), adrenals (pheochromocytoma)
30
Neuroblastoma
- what is it
- derived from / location
- sxs
- most common tumor of adrenal medulla in children
- neural crest cells, anywhere along sympathetic chain
- abdominal distention and firm irregular mass that can cross midline, normotensive, opsoclonus-myoclonus syndrome (dancing eyes and feet)
31
Carcinoid Syndrome
- what is it
- sxs
- markers
- tx
- mets
- syndrome caused by neuroendocrine tumors secreting hormones such as serotonin, histamine, leukotriene
- recurrent diarrhea (serotonin on GI), cutaneous flushing (histamine dilating vessels), athmatic wheezing (serotonin causing broncho constriction) , right sided valvular heart dx (serotonin increasing fibrin deposition in heart)
- chromogranin A and synaptophysin
- surgical resection and somatostatin analog for sxs control (somatostatin binds to tumor and prevents release of hormones)
- liver
32
Pheochromocytoma
- etiology
- symptoms
- findings
- tx
- most common tumor of adrenal medulla in ADULTS
- chrommafin cells (come from neural crest cells)
- NF1, VHL, RET, MEN 2A and 2B
- epi, nor epi, dopamine -> HTN or EPO -> polycythemia; in spells
- increase in catecholamines and metabolites in urine
- Irreversible alpha antagonist (phenoxybenzamine) and beta blocker before resection
33
Insulinoma
- what is it
- whipple triad
- labs
- tx
- tumor of pancreatic beta cell -> over production of insulin -> hypoglycemia
- low blood glucose, sxs of hypoglycemia, and resolution of sxs after glucose normalization
- low glucose and high c peptide
- surgical resection
34
Glucagonoma
- what is it
- sxs (5 D's)
- tx
- tumor of pancreatic alpha cell -> over production of glucagon
- dermatitis, diabetes, DVT, declining weight, depression
- octreotide, surgery
35
Somatostatinoma
- what is it
- sequalae
- sxs
- tumor or pancreatic delta cells -> overproduction of somatostatin
- decrease in secretion of glucagon, insulin, gastrin
- diabetes, glucose intolerance, gallstones, steatorrhea
- surgical resection, somatostatin analogs
36
Zollinger Ellison Syndrome
- what is it
- sequelae
- sxs
- secretin stimulation test
- gastrin secreting tumor of pancreas or duodenum
- acid hyper secretion causes recurrent ulcers in duodenum and jejunum
- abdominal pain and diarrhea
- gastrin levels remain elevated after secretin administration
37
VIPoma
- what is it
- location
- syndrome
- sxs
- rare neuroendocrine tumor that secretes vasoactive peptide
- pancreas
- MEN 1
- Watery diarrhea, hypokalemia, achloryhydia
38
Hypothyroidism vs Hyperthyroidism
- metabolic findings
- skin/ hair findings
- ocular findings
- GI findings
- MS
- Reproductive
- Neuro
- CV
- Labs
- O: cold intolerance, sweating, weight gain-- ER: heat intolerance, sweating, weight loss
- O: dry/cool skin w/ brittle hair and diffuse allopecia, brittle nails, puffy face; ER: warm/moist skin, fine hair, pretibial myxedema
- O: peri-orbital edema; ER: exophthalmos and lid lag
- O: constipation; ER: diarrhea
- O: myopathy, carpal tunnel; ER: thyrotoxic myopathy w/ increased risk of fracture
- O: abnrml uterine bleeding and decreased libido; ER: abnrml uterine bleedin, gynecomastia
- O: lethargy, fatigue, weakness, depression; ER: restless, anxious, insomnia
- O: bradycardia, dyspnea on exertion; ER: tachcardia, palpations, arrythmias
- high TSH, low T3 and 4; low TSH, high T3 and 4
39
Hyperthyroidism Causes
- Graves Dx: epi, pathogenesis, triggers, HLA, histo
- Toxic multi nodular goiter: what is it, labs, prognosis
- Thyroid storm: what is it, triggers, labs, tx 4 ps
- Jod-Basedow phenomenon: what is it
- most common cause; Thyroid stimulating Ig stimulates TSH receptors, dermal fibroblasts, orbital fibroblasts; stress, HLA 3 and 8, tall crowded follicular epi cells w/ scalloped colloid
- focal patch of hyperfunctioning follicular cells w/ colloid working independently of TSH; increase release T3/4, non malignant
- complication when hyperthyroidism is untreated and significantly worsens w trigger, infection/ trauma/ surgery; agitation/ delirium/ fever/ diarrhea/ arrythmia; increase lfts; propanolol, propylthiouracil, prednisolone, potassium iodide
- Ionine induced hyperthyroidism, pt with iodine deficieny and autonomous thyroid tissue is given iodine
40
Hypothyroidism Causes
- Hashimotos Thyroiditis: epi, pathogenesis, HLA's, histo, increased risk of, sxs
- Post partum thyroiditis: what is it, sxs; tx; sxs; histo
- Congenital Hypothyroidism: what is it; caused by; sxs (6 Ps)
- Subacute Granulomatous thyroiditis: caused by; course; sxs; histo
- Riedel: what is it; mimics; thyroid feels
- Other causes
- most common cause of hypothryoidism; AI w/ anti-thyroid peroxidase and thithyroglobulin; HLA-DR3 and DR5; increase risk of non hodgkins lymphoma; huerthle cells; enlarged, non tender thyroid
- self limited thyroiditis; transient hyperthyroidism, hypothyroidism, or both; euthyroid following resolution; thyroid is painless and normal size; lymph infiltrate w/ occasional germinal centers
- severe fetal hypothyroidism bc of maternal anti-bodies; Pot bellied, Pale, Puffy face, protruding umbilicus, protuberat tongue, poor brain development
- self limited dx following flu like illness; can start as hyperthyroid and followed by hypothyroid; granulomatous inflammation; increased ESR, jaw pain, very tender thyroid
- thyroid replaced by fibrous tissue w/ inflamm infiltrate which can extend to local strx (trachea and esophagus); mimics anaplastic carcinoma; fixed, rockhard, painless goiter
- iodine deficiency
41
Radiation induced damage to thyroid gland
| - what is it
- exposure to radiation can increase risk of hypothyroidism
| - potassium iodide will saturate thyroid gland with stable iodine
42
Thyroid adenoma
- what is it
- hot vs cold
- histo
- benign solitary growth of thyroid
- most are cold and do not cause hyperthyroidism and others are hot
- follicular, absence of capsular or vascular invasion
43
Papillary Carcinoma
- epi
- prognosis
- histo
- mutation
- most common
- excellent
- empty appearing nuclei w/ central clearing, psammoma odies, nuclear grooves
- RET/ PTC rearrangements and CRAF mutations
44
Follicular Carcinoma
- prognosis
- invades
- histo
- spread
- mutations
- good
- thyroid capsule and vasculature
- uniform follicles
- blood
- RAS and PAX8 - PPAR translocation
45
Medullary Carcinoma
- cells type
- secretes
- histo
- associated w
- parafollicular cells
- calcitonin
- sheets of amyloid stroma
- MEN 2A and B
46
Undiff anaplastic carcinoma
- epi
- sxs
- prognosis
- mutation
- older pts
- enlarging neck mass -> compressive sxs
- very poor
- TP53
47
Hypo-parathyroidism
- caused by
- sxs
- Chvosteck sign
- Trosseau sign
- pseudo 1A: genetics, pathogenesis, sxs, inherited from
- pseudo-pseudo: what is it, inherited from
- injury to parathyroid glands or their blood supply
- hypocalcemia, tetany, hyperphosphatemia
- tapping of facial n causing contraction of facial muscles
- occlusion of brachial a w/ BP cuff causing carpal spasm
- auto dom, inactive Gs protein causing kidney and bone resistance to PTH; hypocalcemia despite high PTH; shortened 4th and 5th digits, short, obese, developmental delay, inherited from mother and caused by imprinting
- auto dom, features of albright hereditary osteodystrophy (above findings) w/o PTH resistance and normal Ca levels; inherited from father but normal maternal allele maintain response to PTH
48
Hyperparathyroidism
- primary: caused by; labs; sxs
- secondary: caused by, labs
- tertiary: caused by, labs
- due to parathyroid adenoma or hyperplasia; hyper Ca, calciuria, hypophosphatemia, high PTH; asymptomatic
- secondary hyperplasia due to decrease in Ca absorption and/or increase in PO4 in CKD; hypo Ca w/ hyper PO4]
- Refractory hyperparathyroidism from CKD, high PTH and Ca
49
Familial hypocalciuric hypercalcemia
- what is it
- sequalae
- labs
- defective G coupled Ca sensing receptors in multiple tissues, specifically parathyroid and kidneys
- higher than normal Ca levels required to suppress PTH
- Excessive renal reabsorption causing hypercalcemia w/ normal PTH levels
50
Hypopituitarism
- what is it
- non secreting pituitary adenoma: what is it
- sheehan syndrome: what is it; pathogenesis; sxs
- empty sella syndrome: what is it; cause; associated with
- pit apoplexy: what is it; associated with; sxs
- TX
- undersecretion of pit hormone
- cancer in the pituitary gland that renders it unable to do its job
- ischemic infarct of pituitary following postpartum bleeding -> pituitary increases in size during pregnancy because of increase in hormones and since it is normally fed through a plexus it is already low in blood flow so when postpartum bleeding occurs it is one of first areas to become ischemic; failure to lactate, absent mensturation, cold intolerance
- atrophy or compression of pituitary; idiopathic; idiopathic intracranial hypertension
- sudden hemorrhage of pit; existing pit adenoma; sudden onset severe headache, visual impairment, diplopia
- hormone replacement therapy
51
Acromegaly
- what is it
- caused by
- sxs: tongue, voice, hands/feet, face, sweat
- DX
- tx
- excess GH in adults
- pit adenoma
- large tongue, deep voice, large hands and feet, coarsening of facial features w/ age, frontal bossing, diaphoresis
- increased serum IGF-1 and failure to suppress GH w/ oral glucose tolerance test; pit mass seen on MRI
- pit adenoma resection and octreotide
52
Laron Syndrome
- genetic
- caused by
- labs
- sxs
- AR
- defective GH receptors -> decreased linear growth,
- high GH, low IGF1
- short stature, small head circumference, saddle nose and prominent forehead, small genitals
53
Syndrome of inappropriate ADH
- what is it
- causes
- labs
- pathogenesis of labs
- tx
- ADH being secreted when its not supposed to be
- ectopic ADH, CNS disorder, pulm dx, drugs (cyclophosphamide)
- hyponatremia with continued urinary excretion of Na and urine osmolality > serum osmolality
- increase in water causes decrease in ADH and increase ANP -> increases Na excretion
- cerebral edema and seizures
- fluid restriction, salt tablets, IV hypertonic saline, diuretics, ADH antagonist; must be corrected slowly to avoid osmotic demyelination syndrome
54
Diabetes Insipidus
- what is it
- central: what is it, causes
- nephrogenic: what is it, causes
- labs
- water deprivation test: central vs nephrogenic
- TX: central, nephrogenic
- inability to concentrate urine caused by problems with ADH
- central: unable to produce ADH; pit tumor, AI, trauma, surgery
- nephrogenic: ADH unable to bind on CT of kidney; hereditary, secondary to hyper Ca, hypo K, lithium
- urine gravity and urine osmolality are low, serum osmolality is high
- C: > 50% increase in urine osmolality after ADH analog given; N: minimal change in urine osmolality
- C: Desmopressin and hydration; HCTZ, indomethacin, hydration, salt restriction
55
Diabetes mellitus
- sxs
- small vessel complications
- large vessel complications
- dx
- polydipsia, polyuria, polyphagia, weight loss, DKA (I)
- diffuse thickening of basement membrane -> retinopathy, glaucoma, nephropathy
- atherosclerosis, CAD, peripheral vascular occlusive dx -> gangrene and high incidence of MI
- HgbA1C greter than 6.5, fasting glucose over 126, 2 hr oral glucose tolerance over 200
56
Type I vs Type II DM
- primary defect
- insulin in tx
- age
- obesity
- genetic
- glucose intolerance
- insulin sensitivity
- ketoacidosis
- beta cell number in islets
- serum insulin levels
- histo
- primary cause - 1: AI destruction of beta cells; 2: increased resistance to insulin w/ progressive pancreatic beta cell failure
- insulin tx - 1: always; 2: sometime
- age - 1: < 30 yrs, 2: > 40 yrs
- obesity - 1: no; 2: yes
- genetic - 1: relatively weak; 2: relatively strong
- gluc intol - 1: severe, 2: mild to moderate
- insulin sen - 1: high, 2: low
- DKA - 1: common, 2: rare
- B cell - 1: low, 2: variable
- serum - 1: low, 2: variable
- hist - 1: islet leukocyte infiltration, 2: Islet amyloid deposits
57
DKA
- caused by
- occurs in
- sxs
- labs
- sequlae of labs
- complications
- TX
- excess fat break down causing increase in ketoacids made
- type I DM
- Delirium/ psychosis, kussmaul respirations, abd pain, dehydration, fruity breath
- hyperglycemia, high H, low HCO3, high ketones in blood and urine
- K starts being switched out for H intracellularly to help with acidosis -> increase in K levels causes increase in excretion of K -> causes decreased overall K levels
- cardiac arrythmias, heart failure
- IV fluids, IV insulin, and K+, glucose to prevent hypoglycemia
58
Hyperosmolar hyperglycemic state
- what is it
- epi
- pathogenesis
- sxs
- w/o tx
- labs
- tx
- state of profound hyperglycemia induced dehydration and high serum osmolality
- elderly Type 2 DM, unable to drink much
- hyperglycemia -> excessive osmotic diuresis -> dehydration
- thirst, polyuria, lethargy, focal neuro deficits
- coma/death
- hyperglycemia and high serum osmolality w/o acidosis
- aggressive IV fluids and insulin therapy
59
MEN 1
- organs involved
- mutation
- pituitary (prolactin or GH), pancreas (zollinger-ellison syndrome, insulinoma, VIPoma), parathyroid adenoma
- MEN1 (menin on chrom 11)
60
MEN 2A
| - organs involved
- parathyroid hyperplasia, medullary thyroid (parafollicular C cells -> secrete calcitonin), pheochromocytoma (catecholamines)
- mutation in RET
61
MEN 2B
- organs involved
- associated w
- mutation
- thyroid, pheochromocytoma, mucousal neuroma
- marfanoid habitus
- RET gene
62
Diabetic Injectables
- Insulin preparation: MOA (liver, muscle, fat); side effect
- Amylin Analog: MOA
- GLP-1 analog: MOA
- bind insulin receptor -> liver and muscle stores glucose, fat stores TG; hypoglycemia, lipodystrophy, hypersensitivity
- decrease glucagon release, decrease gastric emptying, increase satiety; hypoglycemia
- decrease glucagon release, decrease gastric emptying, increase glucose dependent insulin release; nausea, vomiting, pancreatitis, weight loss
63
Insulin preparation
- rapid acting: name and peak
- short acting: name and peak
- intermediate acting: name and peak
- long acting: name and peak
- Lispro, aspart, glulisine; 1 hr peak
- regular; 2-3 hr peak
- NPH: 4-10 hr peak
- detemir, glargine; no real peak
64
Diabetic oral drugs
- biguanides
- sulfonylureas
- meglitinides
- DPP4 inhibitors
- glitazone
- Na- gluc cotransporter inhibitor
- alpha glucosidase inhibitors
- inhibit hepatic gluconeogenesis and action of glucagon
- close K channel in pancreatic beta cell membrane -> cell depolarizes -> insulin release via increase in Ca influx; 1 - chlorpropamide, tolbutamide; 2 - glimepiride, glipizide, glyburide
- same as sulfonylureas; nateglinide, repaglinide
- inhibit DPP-4 enzyme that deactivates GLP-1 -> decrease glucagon release and gastric emptying while increasing glucose dependent insulin release; linagliptin, saxagliptin, sitagliptin
- activate PPAR - gamma -> increase insulin sensitivity and levels of adiponectin -> regulates glucose metabolism and fatty acid storage; pioglitazone, rosiglitazone
- block reabsorption of glucose in PCT; canagliflozin, dapagliflozin, empagliflozin
- inhibit intestinal brush border alpha glucosidases -> delayed carb hydrolysis and glucose absorption -> decreased postprandial hyperglycemia; acarbose, miglitol
65
Thionamide
- MOA
- indication
- med first tri-mester vs 2nd and 3rd
- block thyroid peroxidase -> inhibit oxidation of iodide -> inhibit thyroid hormone synthesis
- hyperthyroidism
- propylthiouracil and then methimazole
66
Levothyroxine
- MOA
- indication
- abused
- thyroid hormone replacement
- hypothyroid, myxedema
- can be abused for weight loss
67
Hypothalamic/pit drugs
- ADH antagonist
- desmopressin
- GH
- oxytocin
- somatostatin analog
- block activation of ADH at V2 receptor; SIADH; conivaptan, tolvaptan
- Central DI
- GH deficiency, turners syndrome
- labor induction
- acromegaly
68
Demeclocycline
- MOA
- indication
- adverse effects
- ADH antagonist
- SIADH
- Nephrogenic DI
69
Fludrocortisone
- MOA
- indication
- synthetic analog of aldosterone w/ little glucocoticoid effects
- mineralcorticoid replacement in primary adrenal insuff
70
Cincacalcet
- MOA
- indication
- sensitizes Ca sensing receptor in parathyroid gland to circulating Ca -> decrease PTH
- secondary hyperparathyroidism in CKD, hyper CA in primary hyperparaythyroidism
71
Sevelamer
- MOA
- indication
- nonabsorbable phosphate binder that prevents phosphate absoprtion from the GI tract
- hyperphosphatemia in CKD
