RE-VISITING EXAM 1 MATERIAL:

1. SCREENING TESTS FOR CUSHINGS: measure serum ACTH, low-dose dexamethasone sup
pression test, 24 hr urine free cortisol, midnight salivary cortisol, high-dose
dexameth supp test,
2.
3.
4.
5.
AL-TIKRITI: Thyroid & Parathyroid Histo [1 hr]
1. [COLLOID] within follicular cells of thyroid, rich in Thyroglobulin.
2. [PARAFOLLICULAR CELL] neural crest derivative. synthesize/secrete CALCITONIN.
3. [PARATHYROID] w Chief Cells (secrete PTH) & Oxyphil Cells (larger in size)
BI: Thyroid Phys [1 hr]
1. DEIODINASES: D1 (Liver/kidney. decreases in response to FASTING); D2 (thyroid
, pituitary, FEEDBACK); D3 (inactivation only! converts to rT3 @ brain, placenta
, fetus)
2. THYROID HORMONE EFFECTS: Heart-chronotropic/inotropic, Lypolysis, muscle prot
ein breakdown, bone growth, brain growth, inc rate carb absorb, LDL receptors, I
NCREASED metabolic rate
3. THYROPEROXIDASE (TPO): involved in (1) OXIDATION I- to I2. (2) ORGANIFICATION
I2+Tg=MIT or DIT (3) COUPLING=T3 or T4. note: Anti-TPO Ab found in Hashimoto's
hypothyroidism. Also, Rx: PTU and Methimazole inhibit TPO.
4. HIGH THYROID BINDING GLOBULIN (TBG) levels=DECREASED amount of free T3/T4 -->
INCREASES TSH (feedback mechanism)
5. WOLFF-CHAIKOFF EFFECT: excess iodine in bloodstream temporarily inhibits Thyr
operoxidase (TPO) --> DECREASED iodine organification --> DECREASED T3/T4 produc
tion.
ISSAR: Thyroid Pharm [1 hr]
1. LEVOTHYROXINE: take BEFORE meals bc absorption incr by FASTING. MOA: via nucl
ear receptors to alter gene expression/protein synthesis in target tissue. Metab
: Hepatic-->T3; T4 deiodination in kidney/periphery; glucuron/conjug w entero-he
patic recirculation.
2. PTU: (2 MOAs) inhibits TPO & inhibits PERIPHERAL deiodination. Use for 1st tr
imester of pregnancy. short half life, FASTER ONSET than methamizole. BBW=LIVER
FAILURE, must monitor LFTs.
3. METHIMAZOLE (more common) side effects-Rash, Agranulocytosis (sore throat/fev
er/mouthsores). Use @ 2nd/3rd trimester, poss teratogen=aplasia cutis/choanal at
resia.
4. Drugs contraindicated with Levothyroxine (narrow therapeautic index): Sodium
polystyrene sulfonate/cholestyramine (decrease T4 levels), Rifampin & Phenytoin
increase T4 excretion. Also Calcium and Iron sulfate decr T4 absorption.
5. SODIUM IODIDE-131: beta particles locally destroy thyroid cells from inside.
Oral. PREG CATEGORY X=fetal injury from emission of B particles. Also, precipita
tes Hypothyroidism bc difficult to know correct dose.
6. ADJUNCTS w hyperthyroidism: (1) B-blockers (Propranolol can also block periph
eral deiodinase); (2) Ca-Channel blocker (diltiazem/verapamil); (3) Glucocortico
ids (dexamethasone/prednisone)
GUO: Thyroid Path [2 hrs]
1. [GRAVES HYPERTHYROIDISM] "scalloping" clearing around cells lining follicles
2. FOLLICULAR CARCINOMA undergoes CAPSULAR/VASCULAR INVASION, gets encapsulated,
widely invasive. MUST BE SEEN FOR DIAGNOSIS (can't use frozen sections)

3. [FOLLICULAR CARCINOMA] -densely packed follicules, little colloid seen, promi

nant nuclei
**4. [PAPILLARY CARCINOMA] - must see NUCLEAR INCLUSIONS, nuclear grooves papill
ary architechture psammoma bodies "MUST KNOW"
5. [HASHIMOTO'S] histo features: lymphocytic infiltrate & oncocytic change of
the follicular epithelium. High TSH; anti-TPO and anti-thyroglobulin Ab's in 90%
of cases.
6.
SATHANATHAN: Thryoid large group [3 hrs]
1. GRAVES (1' hyperthyroidism): exopthalmos/lid retract, palpitat/tachy, fine tr
emor, anxiety, goiter, proximal myopathy, diarrhea, incr appetite, osteoporosis,
heat intol, pretibial myxedema, hyperreflexia.
2. Causes of Thyrotoxicosis (high free T4): graves, destructive thyroiditis, thr
yotoxicosis factitia, struma ovarii, toxic multinodal goiter (HOT), toxic adenom
a, exogenous levothyroxine use.
3. TSH-Secreting Pituitary Adenoma: HIGH T4, Abnormally normal TSH (should be LO
W due to feedback, but the problem is its overproduction)
4. HYPOTHYROID & PREGNANT: increase dose of levothyrozine bc in preg, TBG increa
ses which decreases free T4 levels.
5.
6.
7. Subacute Thyroiditis (de quervain's, granulomatous, viral/fever- LOW Iodine u
ptake on scan. VERY TENDER THYROID) vs Graves Disease (normal or high diffuse io
dine uptake on scan, despite low TSH)
8. Evaluation of HYPOTHYROIDISM (see algorithm)
9. Approach to Pt w suspicious thyroid nodule (see algorithm)
*10. TUMOR MARKERS USED: Medullary Thyroid CA=CALCITONIN; Follicular carcinoma=T
hyroglobulin (Tg)
DAVIS: Thyroid Surgery
1. For Papillary Thyroid carcinoma: <1cm LOBECTOMY; >1cm TOTAL THYROIDECTOMY; if
+LNs add LN dissection. Post-Op Radioactive Iodine & T4 suppression.
2. For Medullary Thyroid carcinoma (sporadic-single tumor or familial-multiple t
umors on both sides: TOTAL THYROIDECTOMY+CENTRAL NECK DISSECTION regardless of t
umor size.
3. For Anaplastic Thyroid carcinoma (least common; most aggresive): TOTAL THYROI
DECTOMY + CHEMO + RADIATION. Dulbulking Surgery is indicated only for severe sym
ptoms.
4. DURING THYROIDECTOMY: locate MIDDLE THYROID VEIN 1st to allow thyroid to be m
obilized medially.
ANATOMY THYROID [see safaoui notes]
1.
2.
3.
______________________________________________________
SATHANANTHAN: LARGE GROUP-CALCIUM & BONE [3 hrs]
1.
**2. CORRECTED CALCIUM = measured total serum Calcium + [0.8*(4-current albumin)
] <--because we are concerned with IONIZED CALCIUM (not protein-bound Ca)
3. PRIMARY HYPERPARATHYROIDISM-PARATHYROID TUMOR (case 1) management algorithm
4. VIT D INTOXICATION-mediated HYPERCALCEMIA: Sarcoidosis, lymphoma, tuberculosi
s, fungal granulomatous diseases. (excess vit D synth by macrophages etc) Tx: Gl
ucocorticoids.
5. MEN 1 (Parathyroid tumors, pituitary tumors, pancreas tumors; MEN2A (Parathyr
oid tumors, medullary thyroid carcinoma, pheo)
6. FmHx of Hypercalcemia? MEN vs FHH on 24 hour urine Ca/Cr clearance ratio. <0.
01 in most Pts w FHH! tx for FHH: only observe!

7. HYPOcalcemia signs: CHVOSTEK SIGN=twitching face by tapping Facial N.; TROUSS

EAU SIGN=carpopedal spasm during BP cuff inflation
8.
9.
10.
DAVIS: PARATHYROID SURGERY
1. only need 0.5 parathyroid to keep functioning, can put gland in forearm of no
n-dominant side.
2. Indications _____________________________
3. PARATHYROID SURGERY: 4 total. have resected correct gland if PTH drops intrao
pertively.
BI: Calcium physiology
1. PTH INDIRECTLY influences GI Ca2+ reabsorption (NO direct effect). Indirect b
ecause it can increase active D3 which acts at gut
2. PTHrP can mimic PTH @ bind PTHR1 on bone and kidney cells, responsible for HU
MORAL HYPERCALCEMIA OF MALIGNANCY.
3. Vit D3 incr TRPV5 expresseion, then PTH incr TRPV5 Ca channel insertion @ api
cal membrane. Vit D3 incr Calbindin-D28/D9 for diffusion within;
BOTH PTH & D3 increase active tx of Ca at basolateral membrane
4. PTH @ Kidney. Increases Ca reabsorption & DECREASES Pi resorption via decreas
ing Na/PiIIa channel levels (increasing EXCRETION of Pi)
5.
GUO: Parathyroid Pathology
1. [PARATHYROID ADENOMA] NO adipose cells seen in portion of one parathyroid gla
nd, surrounded by thin capsule next to normal parathyroid tissue (w adipose)
2. PARATHYROID ADENOMA vs parathyroid HYPERPLASIA: Adenoma is seen in ONE GLAND,
hyperplasia is seen in all glands.
3. [BROWN TUMOR] interaosseous accumulation of CLASTs & Giant Cells, brown area=
old hemorrhage.
4. [PARATHYROID CARCINOMA]- increased vascularity seen

ISSAR: Calcium pharm

1. INTERMITTENT USE OF PTH (TERIPARATIDE) stimulate IGF-1 release, osteoblasts -> BONE FORMATION. BLACK BOX=OSTEOSARCOMA RISK!!!
2. PARICALCITOL-synthetic vit D3 for secondary hyperparathyroidism in CRF. DECR
PTH directly @ parathyroids w/o increasing Ca or P.
3. CALCIUM ACETATE (25%)-for secondary hyperparathyroidism w ESRD. keeps PTH und
er check.
4. CALCIUM CHLORIDE (IV only)-for hypocalcemic tetany/Mg intox/Hyperkalemia EKG
disturb. WARNING! may potentiate ACIDOSIS!
5.
____________________________
SAFAOUI: ANATOMY PANCREAS
1.
2.
3.
4.
5.
SQUIER: BIOCHEM OF DM [6 Q] -- see objectives/listen to final 15 mins.
1. INSULIN DEFICIENCY INCREASES Gluconeogenesis, Glycogenolysis, Lipolysis, Keto

genesis. deficiency in insulin --> decrease glucose transporters (GLUT4) --> les
s uptake of glucose in cells, more in blood--> mobilization of energy reserves (
because insulin isn't acting against glucagon)
2.
3. KETONE BODIES (made in LIVER, very soluble): (1) ACETONE; (2) ACETOACETATE; (
3) 3-OH-BUTYRATE. Glucagon stimulates Lipolysis --> incr free FAs --> incr ketog
enesis @ liver --> KETOACIDOSIS & decrease carbonate--> Bicarbonate lost thru HY
PERVENTILATION (compensatory effort to reduce CO2)
4. HbA1c=glycated hemoglobin (bc increased blood glucose results in glycation of
proteins) can be used to measure glycemic/glucose levels over past 3 months (12
0 days, life span of RBC). 6% A1c=120 mg/dL glucose--for every 1%, add 30 mg/dL
to glucose level.
5. POLYDIPSIA, POLYURIA: high blood glucose PREVENTS RESEQUESTRATION OF GLUCOSE
IN URINE bc downregulation of glucose transporter (SGLT) @ kidney, drives WATER
INTO URINE (osmotic), resulting in dehydration and thirst.
6. Obesity --> increase # adipocytes --> inflammatory response through cytokine
release --> blocks insulin sensing --> downregulation of insulin receptors in ta
rget tissues --> decreased glucose transporters --> decr glucose uptake! --> FA
oxidation downregulating insulin release
7. Insulin INCREASES AA uptake & protein synthesis (makes sense, because insulin
is secreted when you have abundant amounts of glucose, which supplies the energ
y needed for protein synthesis)
ISSAR: DM Drugs [6 Q]
1. METFORMIN (Biguinide)-1st tx for T2DM. Incr cAMP/PKA--> inhibit gluconeo/stim
glycolysis=maint normal glucose lvl. No wt gain, no hypoglycemia. FATAL LACTIC
ACIDOSIS in renal failure Pts.
2. SULFONYLUREAS (-ide)-close K channel, B-cell depol, increase endogenous insul
in secretion (T2DM ONLY!). hepatic/renal insuff=hypoglycemia, CROSSES PLACENTA,
oral absorbed.
*chlorpropamide adverse=Disulfiram Rxn/SIADH.
3. TZDs (-glitazones) T2DM. PPARy nuc transcription regulator @ Adipose; +GLUT4s
, Adiponectin secretion, decr TNFa, reg FA stores. !BLACK BOX=CHF+PULM EDEMA+MI
RISK!
4. GLARGINE: Long Acting Insulin, low pH formation (isolelectric point 6.7) so l
ess soluble @ neutral pH compared w normal insulin. lasts 24 hrs.
5. PRAMLINTIDE (Amylin Analog): SC T1DM&T2DM. slower gastric empty, inhibit gluc
agon release, stim satiety.!BLACK BOX=incr risk hypOglycemia if used w INSULIN.
DECR insulin dose 30-50%!
6. LIRAGLUTIDE (GLP-1 Analog): stim Insulin release, inhibit glucagon release, s
low gastric empty, decr appetite. !BLACK BOX=incr risk of C-CELL TUMORS! Contrai
nd in Medull Thyr CA/MEN2A,2B.
BI: PANCREAS PHYSIOLOGY [6 Q]
1. GLUT2 = glucose into B cell pancreas, GLUCOKINASE adds P, traps it inside cel
l (1st step in glucose metab), B cell glucose sensor in Pancreas.
2. STIMULATE INSULIN SECRETION: High blood glucose, B-keto acids, Ca2+, ACh, Arg
, Leu, Glucagon, GLP-1, secretin, CCK, gastrin, GIP, B-adrenergic agonist, PDE i
nhibitors.
INHIBITS INSULIN RELEASE=Somatostatin, K+ Depletion, Thiazides.
3. C-PEPTIDE: cleaved from PRO-INSULIN. Used as marker of ENDOGENOUS insulin pro
duction.
4.
5.
6.
DAVIS: SURGERY OF PANCREAS

1. INSULINOMA-Whipple Triad: Hypoglycemia, Neuro Sx, Relief w Glucose admin. 90%

benign/75% small & solitary <2 cm. CT SCAN THEN INTRAOPERATIVE U/S. (CANNOT use
somatost/ocreotide scan)
2. GASTRINOMA-(Zollinger-Ellison/MEN1) Excess Gastrin secretion from DUODENUM (m
ost commonly, Passaro's Triangle), pancreas or stomach.
3. GLUCAGONOMA-80% malig. Large 5-10cm @ tail pancreas. Necrolytic migratory ery
thema, mild DM, Cachexia, DVT, severe hypoaminoacidemia
4. SOMATOSTATINOMA-90% malig. @ HEAD pancreas (25% @ small bowel). T2DM, Choleli
thiasis, Steatorrhea, Hypochlorhydria
5. VIPoma (Watery diarrhea, Hypokalemia, Achlorhydria WDHA syndrome). EXCESS VIP
& Ca2+ levels. @ TAIL pancreas
6. PPoma-nonfunctional tumor, pancreatic mass=wt loss, SBA, bleeding. Incidental
CT finding.
SATHANANTHAN: LARGE GRP DIABETES
1. METFORMIN: Diarrhea, Lactic Acidosis. ACTIVATES cAMP-dependent PKA that inhib
its gluconeo & stimulates glycolysis. NOT dose-dependent, NO wt gain.
2. HbA1c measured 2x/yr in Diabetics. Glycemic Goal of tx is A1c < 7% (or blood
glucose < 154 mg/dL). A1c can be inaccurate in hemolytic anemia/hemoglobinopathi
es --> use Fructosamine Assay of Albumin instead, 2 week BG prediction.
4.
5.
6.
7.
8.
PARSA: PANCREAS PATHOLOGY
1.
2. long-term complications of DM: (1) Forms advanced glycation end products; (2)
Activation of protein kinase C, by Ca++ and DAG (due to intracellular hyperglyc
emia); promotes vascular injury
(3) Intracellular hyperglycemia and disturbances of polyol pathways
3. [AUTOIMMUNE INSULITIS] T2DM. Reduction in size & number of islets of Langerha
ns. Hyaline (amyloid-like/amylin) replacement of islet (a feature of long standi
ng NIDDM).
4. [DIABETIC VASCULOPATHY] Atherosclerosis of aorta and coronary vessels; Hyalin
ization of Renal Arteries
5. [KIMMELSTIEL-WILSON LESIONS] (diabetic glomerulosclerosis) Virtually diagnost
ic of DM (almost all also have retinal microaneuryms).
6. [INSULINOMA] amyloid deposition. whipple triad. Pt w episodic hypoglycemia.
7. Secretin Challenge Test-for GASTRINOMA.
8. T2DM: Islets at first, produce extra insulin, then will become deplete of ins
ulin --> AMYLOID in islets.
PARSA: PATH REVIEW
1. Hashimoto's=Hurthle Cells. Follicular cells' enlarged cytoplasm and accumulat
ion of lymphocytic infiltrate. anti-TPO, anti-Tg. generalized myxedema from accu
mulation of ground substance/fluids in soft tissues.
2. Papillary Carcinoma: ORPHAN ANNIE, Psammoma Bodies. "Cold Nodule"
3. Medullary Thryoid Carcinoma: AMYLOID. MEN2A/2B. Calcitonin Tumor Marker.
4.