AAW - Endo/Repro Flashcards
carcinoid syndrome
Rare syndrome caused by carcinoid tumors
(neuroendocrine cells), especially metastatic
small bowel tumors, which secrete high levels
of serotonin (5-HT). Not seen if tumor is
limited to GI tract (5-HT undergoes first-pass
metabolism in liver). Results in recurrent
diarrhea, cutaneous flushing, asthmatic
wheezing, and right-sided valvular disease.
increased 5-hydroxyindoleacetic acid (5-HIAA) in
urine, niacin deficiency (pellagra).
Treatment: resection, somatostatin analog (e.g.,
octreotide).
Every now and then, I get really flushed for about 5 minutes and then it goes away and I don’t know what it is!
think carcinoid syndrome
carcinoid tumors now called neuroendocrine tumors i guess
diagnostic test for carcinoid syndrome
5-hydroxyindolacetic acid in urine
salt and pepper chromatic pattern with oval nucleus
neuroendocrine tumor
Adrenal hemorrhage, hypotension, DIC
what syndrome
what bacteria
waterhouse-friederichsen syndrome
Acute 1° adrenal insufficiency due to adrenal hemorrhage associated with Neisseria meningitidis
septicemia, DIC, and endotoxic shock.
exophthalmos, weight loss, palpitations
what is it
how do you diagnose
graves disease - type II hypersensitivity
Most common cause of hyperthyroidism. Autoantibodies (IgG) stimulate TSH receptors on thyroid
(hyperthyroidism, diffuse goiter), retro-orbital fibroblasts (exophthalmos: proptosis, extraocular
muscle swelling B ), and dermal fibroblasts (pretibial myxedema). Often presents during stress
(e.g., childbirth).
ELIZA to look for those antibodies
cervical dysplasia and cacinoma in sity assc with what virus
what are the genetic effects of the virus
HPV 16 and 18, which produce both the E6 gene product
(inhibits p53 suppressor gene) and E7 gene
product (inhibits RB suppressor gene)
p53 normally recruits bax, which knocks out BCL-2 (the molecule that normally stabilizes the mitochondrial membrane) - if mit memb is bad, cytochrome C leaks out and the cell dies
destruction of Rb stops its inhibition of E2F, which moves cells into S phase
all hormones produced by the anterior pituitary (adenohypophysis)
FLAT PiG:
FSH LH ACTH TSH ProlactIn GH
bromocriptine
dopamine agonist
can be used to treat prolactinomas
octreotide
long acting somatostatin analog
treats acromegaly, glucagonoma, somatostatinoma (counter intuitive, but its for sx control), carcinoid syndrome, gastrinoma, esophageal varicies
pegvisomant
GH receptor antagonist
makes you short as a peg
main prolactin inhibitory factor
Tx for prolactinoma
Dopamine acting on D2 receptors
dopamine agonists (bromocriptine or cabergoline) are the Tx for prolactin secreting tumors
function of thyroid peroxidase what blocks it (used for what purpose? SE?)
oxidizes iodide to iodine in the thyroid, which eventually iodinates thyroglobulin tyrosine residues
propylthiouracil, methimazole block it (used for hyperthyroidism (PTU blocks Peripheral conversion (iodinase I), used in Pregnancy (otherwise methimazole is preferred))
SE skin rash, agranulocytosis (rare), aplastic anemia, hepatotox (PTU). Methimazole is a possible teratogen
HLA subtype for hashimoto
autoantibodies for it
increased risk of what cancer
histologic finding
btw, it is the most common cause of hypothyroidism in iodine-sufficient regions
DR5
“i got 5 on it” DR5 because self-medication
(on the hash)
Antimicrosomal, antithyroglobulin, anti-thyroid peroxidase
increased risk of non-hodgkin lymphoma
find Hurthle cells, lymphoid aggregates with germinal centers
Jod-Basedow phenomenon
thyrotoxicosis if a patient with iodine deficiency goiter is made iodine replete
propylthiouracil
antithyroid
used in thyrotoxicosis, graves disease
tx for thyroid storm
three Ps
beta-blockers (Propanolol), Propylthiouracil, corticosteroids (Prednisone)
methimazole
used to treat thyroid hormone hypersecretion due to Graves’ disease or thyroid storm
inhibit thyroid peroxidase
mifepristone
competitive inhibitor of progestins at progesterone receptors. “morning after pill”
Wolff-Chaikoff
excess iodine temporarily inhibits thyroid peroxidase, get decreased iodine organification, decreased T3/4 production
hashimotos antibodies
antithyroid peroxidase (antimicrosomal), antithyroglobulin antibodies
graves antibodies
anti-TSH receptor (it actually stimulates the receptors)
hurthle cells
hashimotos
lymphoid aggregate with germinal centers in the thyroid
HLA type in hashimotos
HLA-DR5
patient was sick NOS like a week ago, they have tender area around their adams apple and jaw pain
subacute thyroiditis (de quervain)
self-limited hypothyroidism
may be hyperthyroid early in course
granulomatous inflammation of the thyroid!
elevated ESR, de quervain is assc with pain
person comes in because they are having trouble breathing, and have a rockhard painless goiter
Reidel thyroiditis
thyroid replaced by fibrous tissue (they become hypothyroid)
fibrosis may extend to local structures, mimicking anaplastic carcinoma
related to IgG4 related systemic disease
thyroid biopsy shows empty-appearing nuclei
“orphan annie” eyes - seen in papillary carcinoma
most common thyroid cancer, excellent prognosis
also see psammoma bodies (little calcification lump - orphan annie’s dog is named sandy), nuclear grooves (looks like coffee beans),
increased risk with RET and BRAF mutations, childhood irradiation
Medullary carcinoma of the thyroid
Cells?
histo findings?
ass with what?
from parafollicular “C cells”; produces calcitonin, sheets of cells in an amyloid stroma. Associated with MEN 2A and 2B (RET mutations)
hypertension, hypokalemia, metabolic alkalosis
Conn syndrome (cortical adenoma, primary hyperaldosteronism)
hypokalemia - get weakness/fatigue/psycosis
secondary hyperaldosteronism vs primary - how can you tell the difference?
in secondary, your renin is up (kidneys are underperfused for example)
in primary, the renin is down (aldosterone secreting tumor, for example)
congenital adrenal hyperplasia - what enzyme is most commonly not working
21-hydroxylase -
hypotension, hyperkalemia, increased renin, increased 17-hydroxyprogenterone (can’t make aldosterone)
adrenal hemmorhage, hypotention, DIC
waterhouse-Friderichsed syndrome (meningococcemia)
caused by neisseria
Sx are from lack of mineralcorticoids
metanephrines in the urine
pheo
also see VMA
clusters of cells are called zellballen
diagnostic findings of neuroblastoma
oncogene?
homer-wright rosettes (circular grouping of dark tumor cells surrounding pale neurofibrils (aka neuropil))
homovanilic acid, a breakdown product of dopamine in urine.
Bombesin positive
(tumor of the adrenal medulla in kids)
N-myc gene copies all floatin around (a transcription factor)
MEN assc with medullary carcinoma
what do you do before they get it
MEN-2 A and B
take out the thyroid
MEN-1 mneumonic
three ps
parathyroid hyperplasia/tumors
pituitary adenoma - prolactin or GH
pancreatic endocrine tumors - ZE syndrome, insulinomas, VIPoma, glucagonoma
remember by drawing a diamond
commonly presents with kidneystones and stomach ulcers
AKA wermer syndrome
MEN-2A mnuemonic
2ps
Parathyroids (medullary thyroid carcinoma secreting calcitonin)
pheochromocytoma
remember by drawing a square
assc with ret gene mutations
MEN-2B mneumonic
1p
pheochromocytoma
(also this can lead to medullary thyroid carcinoma, marfanoid habitus)
remember by drawing a triangle (adrenals and mouth/thyroid)
assc with ret gene mutations
give 2 examples of a first gen sulfonylurea, SE too
give 3 examples of a second gen sulfonylurea, SE too
mech?
First gen: tolbutamide, chlorpropamide. SE: disulfiram-like effects
2nd gen: glipizide, glimepiride, glyburide (rarely used). SE: hypoglycemia
MECH:
binds to the SUR1 subunit of the K channel, closing it. Happens in the beta cell, depolarizes and triggers insulin release via Ca influx SO IT DOESN’T WORK IF THEY HAVE NO ISLETS LEFT
Pramlintide
not common
Amylin analog - makes people feel full - amy and LINT in her pocket - also the TIDE is the fullness feeling
used to decrease gastric emptying, decreases glucagon
used in type 1 and 2
can cause hypoglycemia, nausea, diarrhea
exanatide
GLP-1 analog - makes people feel full
increases insulin, decreases glucagon release, delays gastric emptying
used for type 2
SE: nausea, vom, pancreatitis
liraglutide
GLP-1 analog - makes people feel full
increases insulin, decreases glucagon release, delays gastric emptying
used for type 2
SE: nausea, vom, pancreatitis
acarbose
alpha-glucosidase inhibitor
inhibits intestinal brush-border alpha-glucosidases, causes delayed sugar hydrolysis and glucose absorption, leads to decreased postprandial hyperglycemia
SE: N/V/D
miglitol
alpha-glucosidase inhibitor
inhibits intestinal brush-border alpha-glucosidases, causes delayed sugar hydrolysis and glucose absorption, leads to decreased postprandial hyperglycemia
SE: N/V/D
pioglitazone, rosiglitazone
“glitazones”/thiazolidinediones (“TZDs”)
increase insulin sensitivity in peripheral tissue by binding to PPAR-gamma nuclear transcription regulator
SE: weight gain, edema, hepatotox, heart failure
not used often because of SE
You are in the zone if you are getting a lot of pars
what does activation of PPAR-gamma do
increases insulin sensitivity and levels of adiponectin
the glitazones do this
(also the fibrates activate PPAR-alpha to induce HDL synthesis!)
metformin
exact mech unknown
decreases gluconeogenesis, increases glycolysis, increases peripheral glucose uptake (insulin sensitivity)
first like in T2DM
most serious SE is lactic acidosis (contraindicated in renal failure)
linagliptin
saxagliptin
sitagliptin
DPP-4 (dipeptidyl peptidase) inhibitors: blocks degradation of incretins (like GLP-1, which works by increasing cAMP in the beta cell, secreting insulin)
increase insulin, decrease glucagon release
used for type 2
can cause significant weight loss in certain patients
what diabetes medication has an increased risk of hypoglycemia in patients with renal failure
sulfonylureas (most common in glipizide)
Close K+ channel in β-cell
membrane cell depolarizes
insulin release via Ca2+
influx.
Signaling pathways of endocrine hormones:
cAMP
FLAT ChAMP
FSH, LH, ACTH, TSH, CRH, hCG, ADH
(V2-receptor), MSH, PTH
I don’t know why these aren’t in the mneumonic in FA, but these too:
calcitonin, GHRH,
glucagon
(i guess champs need to tone their bones, need to have a GROWTH HORMONE RELEASING HORMONE, and need to have sugar in their blood to perform like a champ)
Signaling pathways of endocrine hormones:
IP3
(Gq receptors)
GOAT HAG
GnRH, Oxytocin, ADH ((qinky) V1 receptor), TRH, Histamine (H1-receptor), Angiotensin II, Gastrin
Signaling pathways of endocrine hormones:
intrinsic tyrosine kinase
Insulin, IGF-1 (insulin like growth factor), FGF (fibroblast growth factor), PDGF (platelet derived growth factor - responsible for overgrowth of blood vessels in cancer), EGF
MAP kinase pathway
think growth factors
Signaling pathways of endocrine hormones:
Receptor-associated tyrosine kinase
Prolactin, Immunomodulators (e.g. cytokines, IL-2, IL-6, IL-8, IFN), GH
JAK/STAT pathway
think acidophiles and cytokines
P.I.G.
what drugs can be used in diabetes that decreases glucose absorption
SGLT2 inhibitors decrease reabsorption of glucose in the PCT
also the α-glucosidase inhibitors:
Acarbose
Miglitol
Propylthiouracil
Thyroglobulin peroxidase inhibitor - used in graves disease
(block tyrosine iodination (also known as organification)) and coupling
what cells secrete androgens that stimulate the development of mesonephric ducts and testosterone (in the presence of LH)
where are they found
leydig cells
testosterone production is unaffected by temp, btw
found in the interstitium between the seminiferous tubules
tunica albuginea
thick capsule around the testis that has septa that divide the different lobules
what cells secrete inhibit and what do they do
sertoli cells:
inhibin inhibits FSH directly at the pituitary (the sertoli cells themselves are stimulated by FSH, and increased spermatogenesis when bound by FSH)
also they secrete androgen-binding protein –> maintains local levels of testosterone
tight junctions between adjacent sertoli cells form the blood-testis barrier –> isolate gametes from autoimmune attack
temp sensitive, decrease sperm production and inhibin release when temps go up
main energy source for motile sperm
where is it made
fructose
made in the seminal vesicles (seminal fluid is rich in fructose, ascorbic acid, and prostaglandins)
finasteride
5-alpha reductase inhibitor, blocks the conversion of testosterone to DHT (the main stimulatory androgen of the prostate, external genitalia, and skin)
what is the difference between hypogonadotropic hypogonadism and primary hypogonadism
hypogonadotropic gonadism is a lack of LH and testosterone
primary hypogonadism is a lack of testosterone and an increase in LH
flutamide
a nonsteroidal competitive inhibitor of androgens at the testosterone receptor. Used in prostate carcinoma
person has failure to complete puberty, decreased GnRH, FSH, LH
also has anosmia (can’t smell)
Kallmann syndrome
defective migration of GnRH cells and formation of olfactory bulb.
what do modern pregnancy tests detect and what produces the thing that they detect
hCG
syncytiotrophoblasts