Endocrine Extra + Meds Flashcards
what is cushing’s syndrome?
symptoms and signs due to cortisol excess
- think of this as 4 main causes either due to exogenous or endogenous source of hormones
1) . exogenous: long term high dose glucocorticoid therapy (MC)
2) . endogenous: cushing’s disease, ectopic ACTH producing tumor, adrenal tumor
difference between cushing’s disease and syndrome
cushing’s disease can be a cause of cushing syndrome, disease is a pituitary gland tumor/hyperplasia that overproduces ACTH
CP of cushing’s syndrome
truncal/central obesity, moon facies, buffalo hump, supraclavicular fat pad, thin extremities, thin skin, striae, acanthosis nigricans, hirsutism, oily skin
what are the 3 screening tests often used for cushing’s syndrome?
1) . 24 hr free urinary cortisol (usually increased)
2) . nighttime salivary cortisol (increased)
3) . low dose (1 mg) overnight Dexamethasone suppression test (no suppression of cortisol level)
* any one of these with the results are suggestive of cushing’s
how do you differentiate between cushing’s disease and other causes of cushing’s syndrome based on testing?
cushing’s disease: cortisol suppression with high dose (8 mg) Dexamethasone test
- *plus increased ATCH
- both ectopic ACTH tumor and adrenal adenoma (dec ACTH) will NOT have cortisol suppression with high dose test
what are the classic Cushing syndrome labs?
hyperglycemia, hypokalemia, leukocytosis
how do you workup potential cushing syndrome causes after initial testing?
ACTH pituitary adenoma/hyperplasia = pituitary MRI
adrenal tumor = abdominal CT
ectopic ACTH producing tumor = chest imaging
how to treat causes of cushing’s syndrome?
1) . stop exogenous steroid use (WITH TAPER)
2) . cushing disease: transphenoidal resection
3) . adrenal tumor: tumor excision
4) . ectopic tumor: resect if possible
what is adrenocortical insufficiency?
adrenal gland does not produce enough hormones (cortisol, aldosterone or both) either in a chronic or acute situation (acute = addisonian crisis)
difference between primary and secondary chronic adrenocortical insufficiency
primary = Addison Disease, adrenal gland destruction (lack of cortisol and aldosterone)
*caused by AUTOIMMUNE (MC in US), infection (MC in developing), vascular, meds, trauma
secondary = pituitary failure of ACTH secretion (lack of cortisol ONLY)
*caused by history of exogenous corticosteroid use (MC)
sxs of chronic adrenocortical insufficiency
lack of cortisol = weakness, myalgias, fatigue, n/v, abd pain, anorexia/weight loss, ha, sweating, salt craving, hypotension
+ Primary (aldosterone loss) = hyperpigmentation, orthostatic hypotension
what baseline labs do you get in chronic adrenocortical insufficiency?
1) . 8am ACTH
* Primary = elevated, decreased in secondary
Hypoglycemia (addison’s also has HYPOnatremia and HYPERkalemia)
what is the screening test for chronic adrenocortical insufficiency?
high dose ACTH (cosyntropin) stimulation test (after administering ACTH, serum cortisol should rise)
* absence of cortisol rise at all or still under 18 means adrenal insufficiency
how do you treat chronic adrenocortical insufficiency
Glucocorticoid replacement: dexamethasone
Minerocorticoid replacement too in Addison’s: Fludrocortisone
what is important for patient education in a patient with chronic adrenal insufficiency?
cortisol is a stress hormone and people with this must be treated with IV glucocorticoids and isotonic fluids pre and post procedures
*normal daily dosing must be tripled during illness, surgery or high fever
what is adrenal crisis? what are common causes of this?
acute adrenocortical insufficiency
sudden worsening of sxs in a person with dx/un-dx chronic adrenal insufficiency due to a precipitated stressful event
*MC cause: abrupt stop of glucocorticoids
-others: undx addison pt subjected to stress, pt with addison who didn’t increase meds during illness, bilateral adrenal infarction
what additional sxs do you get with adrenal crisis?
SHOCK- hypotension, hypovolemia
how to tx adrenal crisis
isotonic fluids (normal saline or D5NS) + IV hydrocortisone (if known addison pt) OR IV Dexamethasone
what is hyperaldosteronism and what are the two main causes?
-too much aldosterone (acts on principal cells to retain Na and water)
Primary (doesn’t depend on renin): idiopathic or bilateral adrenal hyperplasia most common, Conn syndrome (adrenal tumor in zona glomerulosa)
Secondary (due to increased renin): renal artery stenosis (MC), hypoperfusion to renal arteries (CHF, hypovolemia, nephrotic syndrome)
CP of hyperaldosteronism
USUALLY AS
but if sxs: HTN (HA, facial flushing) + HYPOkalemia (prox muscle weakness, polyuria, hypomag) + metabolic alkalosis
primary hyperaldosteronism is a cause of what?
secondary hypertension
*suspect pts who develop HTN at extremes of age (under 30 or over 60), not controlled on multiple BP meds
screening tests for primary vs secondary hyperaldosteronism
primary: aldosterone to renin ratio 20:1 (WAY higher aldosterone than renin)
Secondary: high renin levels
how to confirm primary hyperaldosteronism
1) . oral sodium loading test = get high aldosterone level in urine
2) . saline infusion test = no suppression of aldosterone levels (usually response is decrease)
3) . venous blood sample draining from adrenal = high aldosterone
tx of bilateral hyperplasia or conn syndrome (primary hyperaldosteronism)
BH: spironolactone, ACEI, or CCB + correct electrolyte probs
Conn syndrome: surgical excision + spironolactone
what are the five criteria of metabolic syndrome
1) . LOW HDL (under 40 M and under 50 W)
2) . HIGH fasting TGs ( at least 150)
3) . HIGH BP (at least 135 systolic or at least 85 diastolic)
4) . HIGH fasting BG (at least 100)
5) . increased abdominal obesity (waist circumference > 40in M and 35 in W)
* need at least 3 of the 5
what is the key component of metabolic syndrome?
insulin resistance
what is the most common type of pituitary adenoma?
prolactinoma
what hormone inhibits prolactin release?
dopamine
CP for prolactinoma in women and men
W: hypogonadism (oligomenorrhea, amenorrhea, infertility), galactorrhea (rare)
M: hypogonadism (erectile dysfunction, decreased libido, infertility)
*both could cause bitemporal hemianopsia if pressing on optic chiasm
how diagnose prolactinoma?
endocrine studies: increased prolactin, decreased LH/FSH
- also check for endocrine probs with other pituitary hormones (TSH, GH, ACTH)
- MRI to look for pituitary tumor
how to tx prolactinoma?
- dopamine agonists 1st line for sxs pts: bromocriptine, cabergoline
- may watch and wait if asxs
- transsphenoidial resection for those refractory to medical management
what is HTN, LDL, and A1c goals for a diabetic pt? what are the drugs we might use to tx over this goal?
HTN goal = under 140 systolic and under 90 diastolic
*use ACEI or ARB if BP is over OR microalbuminemia present
LDL < 100, A1c <7% (depends on pt)
what are the 4 types of diabetic neuropathy + MC?
1) . symmetric polyneuropathy (MC) = progressive sensory loss of distal extremities in “stocking-glove” distribution, usually LE first + may lead to foot ulcer formation
2) . autonomic: orthostatic hypotension, gastroparesis (occurs after many years)
3) . cranial mononeuropathy: often affects EOM (CN III: diplopia & ptosis with pupil sparing)
4) . peripheral mononeuropathy: carpal tunnel syndrome (median nerve), ulnar neuropathy
Tx of diabetic neuropathy
OPTIMAL GLUCOSE CONTROL = FIRST
- pregabalin and duloxetine FDA approved
- can also use amitriptyline or gabapentin
PP and CP of diabetic gastroparesis
PP: decreased GI motility and gastric emptying due to impaired neural control of gastric function
CP: N/V, EARLY SATIETY, upper abd pain, bloating + hx of longtime DM
how to diagnose and tx diabetic gastroparesis
dx: EGD usually done first to rule out other causes, nuclear gastric emptying scintigraphy shows delayed gastric emptying with NO obstruction
tx: 1st line is improved glycemic control and diet modifications, metoclopramide or erythromycin increase GI motility
what is the most common cause of end stage renal disease?
DM
what is diabetic nephropathy? how to diagnose this? what is seen on histology?
progressive kidney destruction leading to microalbuminuria (1st sign)
dx: urine dipstick positive for proteinuria (between 30-300), 24 hr urine protein
* histology = Kimmelstiel-wilson lesion (pink hyaline material around glomerular capillaries from protein leakage)
how to tx and screen for microalbuminemia?
tx: ACEI or ARB (reduces protein leakage and slows progression of damage)
*also low sodium diet and strict glucose control
screen annually for microalbuminuria, BUN, and Cr
what is the somogyi vs dawn phenomenon? how to tx each
1) . somogyi: nightly HYPOglycemia followed by rebound hyperglycemia (3 am LOW - sOmogyi)
- reduce nightly NPH, move PM NPH dose earlier, give a bedtime snack
2) . dawn: rise in serum glucose between 2-8am
- bedtime injection of NPH, increase NPH dose, avoid carb snack late at night
what level is considered hypoglycemia? how to tx mild-mod and severe types
<70 (sweating, tremors, palps, tachy, pale/clammy skin, HA, confused, blurred vision, nausea) mild-mod tx = fasta cting carb, juice, hard candies + recheck severe tx (under 40 usually) = IV bolus D50 or IV glucagon
C peptide is elevated with what?
ENDOGENOUS insulin production (body’s insulin)
8 classes of DM 2 medications
1) . biguanides
2) . sulfonylureas
3) . meglitinides
4) . thiazolidinediones (TZDs)
5) . alpha-glucosidase inhibitors
6) . GLP-1 agonists
7) . DPP4 inhibitors
8) . SGLT2-inhibitors
what is the process of managing type 2 DM?
1) . Initial management: diet, exercise, lifestyle changes
2) . if unable to control glucose with lifestyle changes then initiate oral medications (Metformin usually initial therapy)
3) . maximize metformin before adding new medication
4) . add insulin if glucose control still not good after multiple oral meds (also consider HA1c)
MOA of metformin
decreases hepatic glucose metabolism and increases peripheral glucose utilization
metformin has no effect on what?
pancreatic beta cells = no risk of hypoglycemia
4 benefits to metformin
NO hypoglycemia, weight loss, decreased triglycerides, decreased CV risk
3 AtDRs of metformin and two contraindications
ADRs: GI complaints (MC), vitamin b12 deficiency (dec b12 absorption), lactic acidosis in pts predisposed to hypoperfusion
Contraindications: Severe renal or hepatic impairment
can you give iodinated IV contrast to a patient on metformin?
NO- must hold metformin 24 hrs prior to IV contrast and resumed 48 hrs after with creatinine monitoring
what are the sulfonylurea medications?
2nd gen (MC used) = "ides" *Glipizide, glyburide, glimepiride 1st gen less commonly used due to ADRs = tolbutamide, chlorpropamide
MOA of sulfonylurea and therefore biggest ADR
stimulates beta cell insulin release (non glucose dependent) = risk of HYPOGLYCEMIA
indication for sulfonylurea medications
in addition to metformin or initial therapy in pts with contraindications to metformin
5 ADRs of sulfonylurea meds
HYPOGLYCEMIA, weight gain, GI upset, dermatitis, disulfuram rxn (chlorpropamide only)
what are the two meglitinide meds and their MOA
“glinides” = repaglinide, nateglinide
stimulates beta cell insulin release (more glucose dependent, postprandial) = LESS HYPOglycemia than sulfonylureas
2 ADRs for meglitinide meds and what is special about repaglinide
Hypoglycemia (less than sulfas tho) and weight gain
*R = safer to use in pts with chronic renal dz
meglitinide indications for use
in combination with metformin or initial therapy in pts with contraindications to metformin
2 TZD meds and MOA
"glitazones" = Pioglitazone, Rosiglitazone MOA = increases insulin sensitivity at peripheral receptor sites, muscle and adipose (no effect on beta cells)
2 big ADRs of TZD meds
1) . CARDIO- peripheral edema, fluid retention, CHF
2) . Monitor LFTs (hepatotoxicity)
* NO pts with heart failure, active liver dz, bladder ca hx
two alpha-g meds and MOA
acarbose, miglitol
MOA = delays intestinal glucose absorption
big ADR for alpha-g meds
GI = flatulence, diarrhea, hepatitis
3 meds for GLP1 agonists and MOA
LIRAGLUTIDE*, exenatide, dulaglutide
MOA = increases insulin secretion (glucose dependent) and delays gastric emptying
indications for Liraglutide and other GLP1 agonists
weight loss and reduction of CV events
ADRs and contraindications for GLP1 agonists
ADRs: hypoglycemia (less than sulfas bc glucose dependent), GI, Pancreatitis
Contras: hx of pancreatitis or gastroparesis, medullary thyroid cancer
2 DPP4 inhibitor meds and MOA
"gliptins" = sitagliptin, linagliptin MOA = increases GLP1 levels (increased insulin release, decreased glucagon, dec hepatic glucose production)
ADRs for DPP4 inhibitors
acute pancreatitis, renal failure, GI
*not associated with hypoglycemia unless combined with insulin secretagogues
3 SLGT-2 inhibitor meds and MOA
"flozin" = empagliflozin, canagliflozin, dapagliflozin MOA = inhibits sodium-glucose transport leading to increased urinary glucose excretion
3 good things about SLGT-2 inhibitors
1) . improves CV outcomes and decreases HF risk (esp E)
2) . reduces BP
3) . weight reduction
2 main ADRs of SLGT-2 inhibitors
transient N/V, UTIs/yeast infections
