3/8 endo Flashcards
How does excess cortisol lead to HTN?
- up-regulates alpha-1 receptors on arterioles.
- has slight mineralocorticoid ability.
Dexamethasone suppression test
- low dose suppresses ACTH =
- high dose (8mg) suppresses ACTH =
- no suppression w/high dose (8mg) =
- low dose suppresses ACTH = normal
- high dose suppresses ACTH = pituitary adenoma
- no suppression w/high dose = ectopic ACTH prod.
How does excess cortisol lead to osteoporosis?
-cortisol dec. osteoblastic activity
CRH stimulation test
- differentiate btwn a pituitary adenoma and ectopic source.
- an ectopic source will not increase cortisol production in response to CRH b/c the pituitary is super suppressed by all the negative feedback of the ectopic ACTH.
- the pituitary adenoma will make even more ACTH and thus cortisol in response to CRH b/c its negative feedback mechanism is obviously fucked up which is a key property thats allowing it to pump out all of this ACTH in the first place.
Inoperable Cushings
-Tx:
Ketoconazole
Primary or secondary hyperaldo
-Tx:
-surgery (primary) or spironolactone
Which bug has been known to destroy the adrenals?
TB
Waterhouse-Friderichsen syndrome
-potential causes?
-Neisseria meningitidis septicemia, DIC, and endotoxic shock
Resting tone on vasculature?
- sympathetic
- hence neurogenic shock - you lose that sympathetic tone.
Neuroblastoma
- originates from what tissue?
- presentation?
- Neural crest cells
- abdominal distension and a firm, irregular mass B that can cross the midline (vs. Wilms tumor, which is smooth and unilateral).
- it does not cause HTN like pheo does.
Neuroblastoma
- what is increased in urine?
- associated w/which oncogene?
- Homovanillic acid (HVA) = breakdown product of dopamine.
- N-myc
Homovanillic acid (HVA)
- inc urinary levels in what disease?
- HVA is breakdown product of what?
- neuroblastoma
- breakdown product of dopamine.
*dopamine = precursor to catecholamines.
Neuroblastoma
- bombesin + or -
- what do you see on histology?
- bombesin + (tumor marker)
- rosettes & classic small, round, blue/purple nuclei.
pheochromocytoma
- arise from what cells?
- what color is it usually?
chromaffin cells
- neural crest cells
- brown - the adrenal medulla is usually brown.
pheochromocytoma
-rule of 10s
Rule of 10’s: 10% malignant 10% bilateral 10% extra-adrenal 10% calcify 10% kids
*More than 70% of cases of pheochromocytomas
are bilateral when familial.
pheochromocytoma
-associated w/which diseases?
-Associated with von Hippel-Lindau disease, MEN 2A and 2B.
pheochromocytoma
-Tx:
Irreversible α-antagonists (phenoxybenzamine) and β-blockers followed by tumor resection.
- α-blockade must be achieved before giving
- β-blockers to avoid a hypertensive crisis.
Hyperthyroidism
- diarrhea or constipation?
- inc or dec reflexes?
- diarrhea
- inc. reflexes
hyperthyroidism
- whats the skin & hair like?
- hypo or hypercholesterolemia?
- Warm, moist skin; fine hair
- Hypocholesterolemia (due to inc. LDL receptor expression). *you’re basically burning more fuel.
hyperthyroidism
- calcium level?
- blood glucose?
- hypercalcemia (inc. burn resorption).
- hyperglycemia (gluconeo & glycogenolysis going on).
dyspnea on exertion
-Sx of hypo or hyperthyroidism
hypothyroidism
large fontanels & macroglossia in children.
-hypo or hyperthyroidism?
hypothyroidism
Whats the most common cause of myopathy?
hypothyroidism
- myoedema will be present (edema of muscle s/p percussion), inc. creatine kinase, + other hypothyroid Sxs like weight gain, fatigue, etc.
- will present w/myalgia, proximal muscle weakness, & cramping.
Abs found in hashimotos thyroiditis
- anti-thyroid peroxidase
- antithyroglobulin antibodies
- anti-microsome
*they do not cause the disease, they are byproducts of the disease.
hashimotos
-HLA association?
HLA-DR5
*Pernicious anemia also associated w/HLA-DR5
hashimotos
-inc risk of what cancer?
non-Hodgkin lymphoma
-chronic inflammatory states like hashimotos (or sjogrens or h.pylori gastritis) inc. risk of developing a marginal zone lymphoma.
Hürthle cells
-which disease?
hashimotos thyroiditis
Which hypothyroid states can present w/initial transient hyperthyroid state?
- hashimotos
- Subacute thyroiditis (de Quervain)
Long standing hashimoto pt that suddenly has an progressively enlarging thyroid, think what?
B-cell lymphoma
Congenital hypothyroidism (cretinism) -Sxs:
The 6 P’s Pot-bellied Pale Puffy-faced child Protruding umbilicus Protuberant tongue Poor brain development
Subacute thyroiditis (de Quervain)
- What type of inflammation?
- Tx?
- granulomatous inflammation (released colloid acts as a foreign body)
- aspirin for pain.
Reidel thyroiditis
-manifestation of what?
-Considered a manifestation of IgG4 -related
systemic disease.
Wolff-Chaikoff:
-Reduction in thyroid hormone levels caused by
ingestion of a large amount of iodine.
Histo look of goiter:
enlarged follicles and flattened epithelial cells
Toxic multinodular goiter
- Focal patches of hyperfunctioning follicular cells working independently of TSH due to mutation in TSH receptor.
- inc. T4 & T3
*Hot nodules are rarely malignant.
Jod-Basedow phenomenon
-Thyrotoxicosis if a patient with iodine deficiency goiter is made iodine replete.
Thyroid storm
- most common cause of death?
- ALP level? why?
- tachyarrythmia
- Inc. ALP due to bone turnover.
“scalloping” of the colloid
-which disease?
Graves
Are thyroid cancers usually functional?
- no
- and remember, “hot” (functional) nodules are rarely malignant.
Thyroid adenomas & carcinomas
-inc or dec iodine uptake?
-dec.
“Orphan Annie” eyes & psammoma bodies
-which disease?
papillary carcinoma of thyroid.
-Orphan annie eyes = white clearing in the center of the nucleus
-also see “nuclear grooves” which are dark lines in middle of nucleus.
Papillary carcinoma of thyroid
- inc. risk w/mutations in which genes?
- inc. risk w/exposure to what?
- RET and BRAF mutations.
- childhood exposure to radiation.
*-RET - receptor tyrosine kinase encoding gene.
Orphan Annie eyes
-aka?
ground glass nuclei
Follicular carcinoma vs follicular adenoma
Follicular carcinoma invades thru the capsule.
Medullary carcinoma
- which cells?
- produce what?
- histo appearance?
- From parafollicular “C cells”; produces calcitonin.
- sheets of cells in an amyloid stroma.
Medullary carcinoma
-associated w/which mutations/diseases?
-Associated with MEN 2A and 2B (RET mutations).
osteoclast-like multinucleated giant cells found
-which thyroid cancer?
anaplastic
hyperparathyroidism
- urinary cAMP levels?
- ALP levels?
- high urinary cAMP = PTH works through Gs pathway
- inc ALP
hyperparathyroidism & acute pancreatitis
-connection?
- hypercalcemia due to PTH can cause acute pancreatitis.
* high calcium always = chance of metastatic calcification. ie. nephrocalcinosis.
hyperparathyroidism
-mnemonic for Sxs
“Stones, bones, groans, and psychiatric overtones.”
- stones = calcium oxalate renal stones
- bones = osteitis fibrosa cystica
- groans = constipation
- depression
Tertiary hyperparathyroidism
- Refractory (autonomous) hyperparathyroidism resulting from chronic renal disease.
- very high PTH, high calcium
Chvostek sign:
- what is it?
- sign of what?
- Tapping of facial nerve (tap the Cheek) => contraction of facial muscles.
- hypocalcemia
Pseudohypoparathyroidism (Albright hereditary osteodystrophy):
- inheritance pattern:
- what is it?
- Sxs:
-autosomal dominant
-unresponsiveness of kidney to PTH.
-Hypocalcemia, shortened 4th/5th digits, short
stature.
*defective Gs receptors, b/c PTH acts via Gs receptors.
Pseudohypoparathyroidism (Albright hereditary osteodystrophy):
- inheritance pattern:
- what is it?
- Sxs:
-autosomal dominant
-unresponsiveness of kidney to PTH.
-Hypocalcemia, shortened 4th/5th digits, short
stature.
cabergoline
dopamine agonist
-like bromocriptine
Link btwn GH secreting tumor & DM2
GH causes insulin resistance and hyperglycemia.
pegvisomant
-growth hormone receptor antagonist
demeclocycline
-ADH antagonist
Nephrogenic DI
-Tx:
-HCTZ, indomethacin, amiloride, Hydration
complete central DI vs partial central DI
- follow water deprivation & subsequent DDAVP admin.
- In pts w/complete central DI, urine osmolarity should rise >50%! So less than 50 would be partial central DI.
Does cortisol inc or dec glycogen synthesis in the liver?
- inc. glycogen synthesis!
- seems counter intuitive!
Why do glucocorticoids cause muscle weakness?
Proteolysis
Which organ actually has increased protein synthesis in response to glucocorticoids?
Liver
-upregulated proteins (enzymes) involved w/gluconeo & glycogenesis (glycogen synthesis!)
*cortisol increases glycogen synthesis, NOT breakdown!
Why does BUN increase w/glucocorticoid administration?
Proteolysis!
Miglitol
alpha glucosidase inhibitors
canagliflozin, dapagliflozin
- mechanism
- side effects
SGLT-2 inhibitors: oral DM drugs.
- prevent glucose resorption at PCT.
- causes urinary excretion of glucose.
- may cause urinary tract & genital mycotic infections due to glucosuria.
- assess renal fcn before starting this drug.
Age range for DM1?
Fasting blood sugar of _____ of ____ separate occasions is diagnostic of DM.
> 126mg/dl, two.
PTH level & magnesium
-Hypoparathyroidism may be caused by severe hypomagnesemia which can be seen in prolonged diarrhea.
Serum chemistry in pseudohypoparathyroidism
- Ca
- phosphate
- PTH
- low Ca
- high phosphate
- high PTH
Suprasellar mass w/3 components (solid, liquid, calcification) is suggestive of what?
craniopharyngioma
Renal failure - serum levels of:
- Ca
- PTH
- Ca = low
- PTH = high
Why is hypernatremia rarely observed in mineralocorticoid excess?
Aldosterone escape w/ANP.
- also, inc. Na and water retention will increase renal blood flow and GFR => inc rate of sodium excretion.
- ADH also kicks in to keep Na conc. in check.
Why do you get profound muscle weakness w/too much Aldo?
-how about parasthesias?
- Hypokalemia leads to muscle weakness.
- hypokalemia & met. alkalosis can cause parasthesias.
Stimulation tests are used in times of hormone excess or insufficiency?
insufficiency
Whats the most common cell type in the ant. pituitary?
Somatotrophs
- make GH
- 50% of normal pituitary
Oxytocin
-made in which nucleus?
paraventricular nucleus of hypothalamus
SIADH
- serum Na?
- volume status?
Euvolemic hyponatremia.
- ADH leads to excess water.
- Body responds w/dec. aldo.
- Dec. aldo = losing sodium and water.
What happens if you correct SIADH pt’s sodium too quickly?
Central pontine myelinolysis
- neuron dysfunction due to destruction myelin covering neurons in the middle of the brainstem (pons).
- AKA osmotic demyelination syndrome.
Which drugs can cause SIADH?
-mnemonic?
Can’t Concentrate Serum Sodium
- Carbamazepine
- Cyclophosphamide
- SSRIs
SIADH
- first step in management?
- tx:
- 1st step = water restriction
- demeclocycline = ADH antagonist
- lithium
- conivaptan, tolvaptan = ADH antagonists
conivaptan, tolvaptan =
- ADH antagonists
- Tx for SIADH
Losing pubic hair after pregnancy
Sheehan
-need LH for pubic hair.
Empty sella syndrome
- what is it?
- common in who?
- atrophy or compression of pituitary, often idiopathic, common in obese women.
- could be due to trauma/congenital reasons.
Severe hypoglycemia
-Tx?
glucagon injection
Most common cause of death in DM?
MI
DM1
-HSR, which type?
-type 4 HSR
DM1
-HLA association? if so, which ones?
- HLA-DR3 and 4
- Sxs may be preceded by a viral infection.
What does glucose intolerance mean?
Unable to take up insulin into cells.
-no insulin.
Maturity-onset diabetes of the young (MODY)
associated w/mutation in what?
-Glucokinase mutation.
Genetic predisposition in DM1 or 2?
DM2
- 90% concordance in idential twins
- (DM1 has 50% concordance in identical twins).
What triggers DKA?
- inc. insulin req due to inc. stress (ie. infection).
- stress triggers symp. nervous system = catecholamines & glucagon.
Name some Sxs of DKA.
- Abdominal pain
- delirium
- kussmaul respiration
- fruity breath
- N/V
- dehydration
DKA
- total body K?
- serum K?
- depleted intracellular K = low total body K
- normal/high serum K
Why do you get dehydrated in DKA?
- glucosuria causes osmotic diuresis.
- can lead to pre-renal azotemia & elevated BUN.
Whipple triad of episodic CNS symptoms:
- what is it?
- whats it seen in?
- lethargy, syncope, and diplopia
- insulinoma
Episodic hypoglycemia w/mental status changes that
are relieved by glucose.
insulinoma
Neuroendocrine tumors are positive for what?
chromagranin
carcinoid tumor can lead to what vitamin deficiency?
niacin deficiency
-tryptophan required to make niacin, but your bodys stores are being used to make serotonin instead.
carcinoid heart disease
-mnemonic:
TIPS: tricuspid insufficiency, pulmonary stenosis.
Zollinger Ellison
-mechanism behind steattorhea / malabsorption
-too much acid = pancreatic enzymes wont work. They need alkaline environment to operate!
Rapid acting insulin
- mnemonic?
- use?
There is no LAG w/rapid acting insulin. Lispro Aspart Glulisine -postprandial glucose control.
Long acting insulin
Glargine
Detemir
Biguanides
- aka?
- mech:
- major side effects?
- Metformin
- dec. gluconeo, inc. glycolysis, inc. glucose sensitivty.
- GI upset, lactic acidosis.
- contraindicated in renal failure
Sulfonylureas
- 1st gen:
- 2nd gen:
First generation:
Tolbutamide
Chlorpropamide
Second generation:
Glyburide
Glimepiride
Glipizide
OSUs (sulfonylureas)
-used in DM1 or DM2?
DM2
- requires some islet function, so useless in DM1.
- closes the K channel (so it mimics normal action of ATP)
sulfonylureas
- side effects
- 1st gen:
- 2nd gen:
Risk of hypoglycemia inc. in renal failure.
- First generation: disulfiram-like effects.
- Second generation: hypoglycemia.
*-can cause weight gain b/c anything that inc. insulin inc. TG storage in adipocytes.
Diazoxide and minoxidil mechanism
-opposite of which drugs?
- exactly the opposite as sulfonylureas, which is how they can cause drug induced diabetes (prevent insulin release from beta-cells).
- potassium channel openers, causing hyperpolarization of cell membranes.
Glitazones
- aka?
- mech?
- inc levels of what?
- thiazolidinediones (TZDs)
- inc. insulin sensitivity in peripheral tissue. Binds to PPAR-γ nuclear transcription regulator.
- increase levels of adiponectin (inc. insulin sensitivity).
Glitazones/TZDs
-side effects?
-Weight gain, edema, Hepatotoxicity, heart failure (CHF).
Amylin analogs
- name?
- mech?
- Pramlintide
- dec. gastric emptying, dec. glucagon.
- amylin deposits in islets seen in DM2.
GLP-1 analogs
- name them:
- mech:
- notable tox:
- Exenatide, Liraglutide
- inc. insulin release
- pancreatitis
*An incretin. Its a small peptide released from small intestine whenever you eat.
Which DM drug can lead to pancreatitis?
GLP-1 analogs (incretins)
-exenatide, liraglutide.
DPP-4 inhibitors (“liptins”)
- name them
- mech
- tox
- Linagliptin, Saxagliptin, Sitagliptin
- DPP-4 = enzyme that breaks down GLP-1. So by inhibiting DPP-4 you inc. GLP-1.
- indirectly inc. insulin release.
-tox: Mild urinary or respiratory infections.
Propanolol
-addition effect thats useful in thyrotoxicosis besides bocking beta receptors?
-also inhibits 5′-deiodinase
Propylthiouracil, methimazole
- which one used in pregnancy?
- toxicities?
- PTU used in pregnancy, highly protein bound.
- Skin rash, agranulocytosis (rare), aplastic anemia, hepatotoxicity (propylthiouracil).
- Methimazole is a possible teratogen (can cause aplasia cutis).
Demeclocycline
-side effects
- Nephrogenic DI, photosensitivity, abnormalities of bone and teeth.
- member of the tetracycline family. hence the s/e profile.
Do glucocorticoids inhibit or stimulate txn factors like
NF-κB?
-Inhibit transcription factors such as NF-κB.
- NF-kB: transcription factor that stimulates cytokine production in the immune response to infectious pathogens.
- needed for inflammation.
Glucocorticoids & peptic ulcers
-how?
- phospholipase A2 inhibitor
- so same mech as NSAID ulcer.
Spondyloarthropathies
- HLA association?
- HLA association of RA?
- spondylos = HLA-B27
- RA = HLA-DR4
Crest Abs =
Systemic sclerosis Abs =
- CREST=anti-centromere
- SS=anti-DNA topoisomerase 1
Anti-histone Abs
Drug induced lupus
-no renal or CNS involvement
Antiphospholipid ab syndrome
- Sxs
- PTT time
- hypercoag state, frequent miscarriages
- PTT increased (paradoxically)
chronic anemia affect on cardiac output.
-chronic anemia inc. CO.
Sup. gluteal nerve.
-if you give an injection in which quadrant will you likely damage this nerve?
Supero-medial quadrant.
PTH
-which pathway
inc. cAMP.
ankylosing spondylitis
-which murmur can it lead to?
-aortic regurg.
Probenacid
- inhibits resorption of uric acid in PCT
- also inhibits secretion of penicillin.
*dont give if possible uric acid stones.
febuxostat
xanthine oxidase inhibitor
-like allopurinol
