2nd Endocrine exam Flashcards
Enzyme PTH acts on in kidneys
1alpha-hydroxylase
What prevents PTH secretion?
Ca2+ binds receptors
Gq inhibits exocytosis
Gi inhibits PTH secretion
Bone cells with PTH receptors
Osteoblasts
Osteophytes
Precursor of Vit D in skin
in lower dermis
7-dehydrocholesterol
Storage forms of Vit D
lumisterol
tachysterol
Calcitonin source and use for marker
C cells of thyroid
marker for medullary carcinoma of thyroid
Sx of hypercalcemia
renal stones/bone pain/abd pain/polyuria constipation
short QT interval
decreases neuronal excitability
Different b/t hypercalcemia with malignancy and primary hyperparathyroidism
malignancy-high PTHrp, low PTH
hyperparathryoid-low PTHrp, high PTH
Tx for severe hypercalcemia
saline
bisphosphonates
loop diuretics
mithramycin
Use of mithramycin
RNA inhibitor of osteoclasts
for hypercalcemia
do not use with liver/renal dysfxn or coagulopathy
MOA of gallium nitrate
decreases solubility of hydroxyapatite crystals
used for hypercalcemia
Use and risk with phosphate
rapid/profound hypercalcemia tx
risk with renal azotemia
Effects of PTH depending on administration
1-3hrs daily-builds bone
continuous-bone resorption
MOA of teriparatide
active PTH
for osteoporosis
Oral phosphate binders
Ca2+ carbonate/acetate- inhibit phosphate absorption
sevelamer-binds intestinal phosphate
used with CKD
MOA of cinacalet
calcimimetic
binds Ca2+ receptor on parathyroid
inhibits PTH release
Pro and con of bisphosphonates
long t1/2
poor GI absorption
Risk with etidronate long term use
osteomalacia
Use for calcitonin
osteoporosis
Paget’s disease
Pros and cons of estrogen/hormone replacement for osteoporosis
pro-decreased LDL, increased HDL and TG’s
con-increased endometrial hyperplasia/cancer
MOA of raloxifene
estrogen agonist
no endometrial stimulation
decreases LDL and cholesterol
Adverse effects of raloxifene
muscle cramps
DVT
peripheral edema
MOA of thyroid peroxidase
oxidizes I- to I
adds I to tyrosine
conjugates DIT/MIT
Transports of I in thryoid
basal-Na/I symport
apical-pendrin (I uniport)
Labs seen with iodine deficiency
decreaseds overall T3 and T4
increased T3/T4 ratio
Carriers of thyroid hormones
TBG-affected by heparin
transthyretin-affinity for T4
albumin
Types of deiodinase enzymes
type 1-provides T3 from T4
type 2-T3 levels in CNS
type 3-inactivates T3/T4 in placenta/glial cells
What extends the t1/2 of TSH?
glycosylation
T3 transport in cells
into via MCT8/10 or OATP1C1
binds Zn finger in DNA
Molecules decreasing T3/T4 release
dopamine
somatostatin
glucocorticoids
MOA of thyroid hormones
increase mitochondrial genes
use MAPK and STAT pathways
Actions of T3/T4
CNS-increase excitability/maturity
Bone growth
beta1 receptor upregulation
Impact of secondary hyperparathyroidism
renal osteodystrophy
calciphylaxis (vascular calcification)
Abs seen with Hashimoto’s thyroiditis
anti-microsomal Abs
anti-thyroid peroxidase Abs
anti-thyroglobulin Abs
What is seen with Hashimoto’s thyroiditis?
Huerthle cells
lymphocyte infiltrate
gradual failure
anti-microsomal/anti-TPO
What is seen with De Quervain’s thyroiditis?
aka subacute granulomatous thyroiditis
painful goiter
previous coxsackie/echovirus infection
hyper (1-3wks) followed by hypothyroidism
Post-partum thyroiditis
anti-TPO
2-10 post birth
Cause of proptosis in Grave’s disease
hyaluronic acid deposition around the eye
What is seen with Grave’s disease?
TSI
exophthalmos
pretibial myxedema
onycholysis of 4th/5th digit
Risk with antithyroid drugs
agranulocytosis
What helps with thyroid nodule dx?
MoAB 47 increases accuracy with needle aspiration
When are psammona bodies seen?
papillary carcinoma of thyroid
papillary renal cell carcinoma
papillary serous carcinoma
mesothelioma
Medullary thyroid carcinoma asscs
MEN 2A and 2B
Cause of subacute granulomatous thyroiditis
in summer
coxsackie/measles/mumps/adenovirus
triggered by URT infection
Microscopy of Grave’s disease
scalloped margins of colloid
Assc with papillary thyroid carcinoma
ionizing radiation
Orphan Anne’s eyes
psammona bodies
lymphatic spread
Spread of follicular thyroid carcinoma
hematogenous
Microscopy of Medullary thyroid carcinoma
amyloid deposits
secretes calcitonin
Risk with liothyronine
cardiotoxicity
Risk with thyroid agonists
induction by CYP450
cardio problems at higher doses
Con of antithyroid drugs
increased relapse
MOA of methimazole/propylthiouracil
inhibits TPO
Methimazole impact on fetus
fetal scalp defect
Adverse effect of methimazole
Adverse effect of propylthiouracil
change taste or smell
liver toxicity
Beta blockers used for sx of hyperthyroidism
propanolol
esmolol
Role of FOX01 gene
effects of fasting/decreasing beta cells
insulin inhibits it
Inhibitors of glucagon release
insulin
somatostatin
Zn2+
GABA
Insulin impact on K+
increased transport into cells
When is amylin increased?
obesity & HTN
packed with insulin in granules
Islet of Langerhans granule types
beta-rectangular matrix with halos
alpha-round with dense center
delta-pale granules (somatostatin)
PP-small dark granules
Defect with MODY
insulin-insulin recetpor signal
AD
Diabetes and microscopy of kidney
Kimmelstein-Wilson nodules (PAS (+))
sign of sclerosis
hyaline ateriolosclerosis (afferent only)
Gastrinoma assc
MEN 1
Zollinger-Ellison syndrome
Sx of VIPoma
watery diarrhea
hypokalemia
achlorhydria
Rapid acting insulins
aspart
lispro
glulisine
Long acting insulins
glargine
detemir
Metformin
biguanide
increases insulin sensitivity
decreases gluconeogenesis of liver
no hypoglycemia seen
Glipizide/glyburide/glimepiride
sulfonylureas
block K+ channels in beta cells
cause hypoglycemia
Rosiglitazone/pioglitazone
thiazolidinediones
same MOA as metformin
Acarbose/miglitol
alpha-glucosidase inhibitors
steady Glc uptake
work on brush border enzymes
Repaglinide/nateglinide
glinides/meglitinides
closes K+ channels in beta cells
less hypoglycemia
Sitagliptan/saxagliptan/linagliptan/alogliptan
dipeptidyl peptidase inhibitor-4
increase Glc mediated insulin production
allows incretins (GLP-1 & GIP) to act
DM type 1 asscs
HLA-DR3 and DR4
Honeymoon phase of DM1 tx
temporary regain of insulin secretion
goes away within weeks
Cause of acanthosis nigrans
ILGF stimulation from insulin
causes keratinocytes to proliferate
Risk with metformin
lactic acidosis
Exenatide/liraglutide
GLP-1 analogs
increase insuline release via Glc
Tx for autonomic impact of DM
midodrine for orthostatic hypotension
Tx for peripheral neuropathy of DM
amitryptiline
gabapentin
regabalin
duloxitine
Tx for GI neuropathy of DM
erythromycin
metocloperamide (cholinergic)
MODY mutation
glucokinase transcription factors
AD
Infection with diabetic ketoacidosis
mucor
klebsiella
Meds causing DKA
steroids
clozapine
pentamidine
Whipple’s triad
documented low BG
sx of hypoglycemia
reverasal of sx with Glc
