Endocrine Facts Flashcards
1
Q
Hashimoto thyroiditis - histologic findings
A
- Intense lymphocytic infiltrate with GERMINAL CENTERS
- Hurthle cells: large oxyphilic cells filled with granular cytoplasm
2
Q
Subacute thyroiditis (De Quervain) - histologic findings
A
- granulomatous inflammation
- mixed cellular infiltrate with multinuclear giant cells
3
Q
Riedel thyroiditis - histologic findings
A
- FIBROSIS of thyroid gland extending to surrounding structures
4
Q
Derivatives of neural crest cells: MOTEL PASS
A
M: melanocytes O: odontoblasts T: tracheal cartilage E: enterochromaffin cells L: laryngeal cartilage
P: parafollicular cells of thyroid
A: adrenal medulla
S: schwann cells
S: spiral membrane
5
Q
Inhibin is under the influence of which hormone?
A
FSH
- FSH causes increased production of inhibin to act negatively on PITUITARY only to inhibit FSH and LH release
- decrease FSH or response to FSH by FSH receptors causes low levels of inhibin
6
Q
Why do you want to check SERUM CREATININE before starting METFORMIN?
A
- Meformin inhibits hepatic gluconeogenesis —> increased peripheral glucose utilization
- decreased gluconeogenesis also increase LACTIC ACID because not being metabolized into glucose —> risk for LACTIC ACIDOSIS in patients with significant hepatic or renal deficiency
7
Q
Statins - side effects
A
- Myopathy
- hepatotoxicity
8
Q
Fibrates - side effects
A
- cholesterol gallstones
- myopathy
9
Q
Niacin - side effects
A
- hyperuricemia: GOUT
- hyperglycemia
- red, FLUSHED FACE: decreases if use NSAIDs before
10
Q
Bile acid sequestrates - side effects
A
- GI upset
- decreased absorption of other drugs and fat soluble vitamins
11
Q
Ezetamide - side effects
A
- increased LFTs
- diarrhea
- increase hepatotoxicity with statins
12
Q
Neurophysins
A
- are carrier proteins for oxytocin and ADH —> shuttle the hormones to the nerve terminal ends for release from posterior pituitary
- produced in the hypothalamus with the other two hormones
13
Q
Treatment of CAH
A
- low dose exogenous corticosteroids to suppress excess ACTH secretion and reduce stimulation of adrenal cortex —> decrease androgen production
14
Q
Role of beta-blockers in hyperthyroidism
A
- block beta-1 adrenergic receptors decreasing the stimulation from sympathetic impulses on target organs
- decrease PERIPHERAL CONVERSION of T3 to T4
15
Q
side effects of TZD (thiazolelidinediones)
A
Edema: increased Na retention in renal collecting tubes
Weight gain: from edema, also adipose weight gain
Excess fluid can exacerbate heart failure
16
Q
Clinical difference between Tay-Sachs and Niemann-Pick disease
A
Do not have HEPATOSPLENOMEGALY in Tay-Sachs
17
Q
What inhibits carnitine acyltransferase?
A
MALONYL-COA
- carnitine acyletransferase is involved in FATTY ACID OXIDATION —> transfers fatty acids from cytoplasm to mitochondria
- malonyl-CoA is involved in FATTY ACID SYNTHESIS
- do not want to break down newly made fatty acids so malonyl-CoA inhibits the transfer of FA into the mitochondria
18
Q
How are NE and EPI secretion activated in the adrenal medulla?
A
By ACh released from PREganglionic sympathetic neurons —> act on POSTganglionic sympathetic neurons to release EPI and NE
19
Q
What do you get from deficiency of dihydrobiopterin reductase?
A
Is enzyme needed to reduce BH2 to BH4, a cofactor for phenylalanine hydroxylase and tyrosine hydroxylase. Without it, get:
- hyperphenylalanemia (PKU)
- decreased dopamine, NE, Epi and serotonin
- increased prolactin from decreased dopamine inhibition
20
Q
Craniopharyngioma
A
- from remnant of Rathke’s pouch (gives rise to ant. pit.)
- three components: solid (tumor cells), cysts (“machinery oil” liquid) and calcified component —> THINK CRANIOPHARYNGIOMA WHEN SEE THESE THREE THINGS
- present in childhood
- Mass effect and visual deficits, increased prolactin from decreased dopamine inhibition
21
Q
Why do you get cataracts in galactosemia?
A
Excessive galactose gets converted to galactitol by ALDOSE REDUCTASE —> galactitol accumulates in lens and causes osmotic damage leading to cataract formation
22
Q
Test for hypothyroidism
A
TSH!
- more sensitive: shows marked changes to small changes in T3, T4
- is increased before a low thyroid hormone is seen
- cannot detect central hypothyroidism but this form is uncommon
23
Q
Primary adrenal insufficiency - labs
A
Decreased ADOLSTERONE
- hyponatremia, hyperkalemia, hyerchloremia (retain Cl- to maintain electrical neutrality of ECF), non anion gap metabolic acidosis (retain H+ with K+, and Na+ loss)
Do not see increased cortisol with ACTH stimulation
24
Q
Where is proinsuln cleaved?
A
In SECRETORY GRANULES —> get insulin and C-peptide
25
Which nerve is at risk of injury during a thyroidectomy?
External branch of the superior laryngeal nerve (due to proximity to the superior thyroid artery and vein) —> innervates the cricothyroid muscle
26
Osteitis fibrosa cystica
- most common characteristic skeletal manifestation of primary hyperparathyroidism
- affects cortical (compact bone) in appendicular skeleton
- bone pain
- subperiosteal erosions affecting the phalanges of the hand
- granular "salt and peper" skull
- BROWN TUMOR osteolytic cysts in long bones
27
Copper reduction test
Tests for presence of reducing sugars in the urine: unmetabolized fructose, glucose, galactose
28
Glucose oxidase dipstick test
Used to test for presence of urine glucose
29
Insulin-mediated glucose transporter
GLUT-4
| - in skeletal muscle and adipocytes
30
Insulin-independent glucose transporters
GLUT-1, 2, 3, 5
| - in liver, brain, kidney, RBC, intestine
31
GLUT-1 location
RBCs and at BBB
32
GLUT-2 location
hepatocytes, pancreatic beta cells, kidney, small intestine
33
GLUT-3 location
Placenta and neurons
34
GLUT-4 location
Spermatocytes and GI tract
35
Effects of HAART on fat redistribution
1. Lipoatrophy: loss of subcutaneous fat in face, extremities and buttocks
- NRTIs
- protease inhibitors
2. Central fat distribution: increased abdominal growth and buffalo hump
- can be seen with any HIV medication —> can be the result of treating HIV rather than the medication
36
Whipple's triad
- symptoms of hypoglycemia
- low blood glucose levels
- relief of hypoglycemic symptoms when blood glucose levels increase
37
Sheehan syndrome
ISCHEMIC NECROSIS of pituitary in case of systemic hypotension after peripartum hemorrhage
38
Adrenal crisis - treatment
Immediate stress-dose corticosteroids —> increases cortisol levels (cannot produce on own with adrenal crisis)
39
Diagnosis of 21-hydroxylase deficiency
High serum levels of 17-hydroxyprogesterone
40
Pioglitazone - class
TZD
41
Niacin - main effect
increase HDL
42
Fibrates - main effect
decrease Triglycerides
43
Bile acid sequestrants - main effect
decrease LDL
44
Ezitimide - main effect
decrease LDL
45
Statins - main effect
decrease LDL (LOTS)
46
Fish oil - main effect
decrease triglycerides but to a lesser degree
47
Ca sensing receptors
G-protein couple receptors
| - help regulate PTH
48
Familial hypocalciuric hypercalcemia - mutation
- defect CaSR in parathyroid glands and kidneys - can't sense Ca levels so higher levels of Ca are needed to suppress PTH
- AD
- have mildly elevated Ca, decreased urine Ca excretion and high normal or mildly elevated PTH
49
Meglitinides - MOA
- bind and close ATP-dependent K+ channels —> depolarize cell —> increase intracellular Ca —> increased insulin secretion (like sulfonylureas)
- shorter acting, have to be given more frequently but similar efficacy
- may have less risk of hypoglycemia
- still gain weight
50
Repaglinide, nateglinide - class
Meglitinides (for diabetes)
51
Molecules with intracellular receptors
- Steroid hormones
- thyroid hormone
- vit D
52
Molecules with tyrosine kinase receptors
- Insulin
| - IGF-1
53
Molecules that go through JAK/STAT pathway
- growth hormone
- prolactin
- erythropoietin
- cytokines
- colony stimulating factors
54
McArdle Disease - enzyme deficiency
- myophosphorylase (muscle form of glycogen phosphorylase): breaks alpha-1,4 glycosidic bonds in glycogen
55
How do free fatty acids contribute to insulin resistance?
- increase lipolysis and free fatty acids in INSULIN RESISTANCE
- increased FFA contribute to insulin resistance even more by: impairing insulin dependent glucose uptake in liver and muscle and increasing hepatic gluconeogenesis
56
Long acting sulfonylureas - name of drugs
- Glyburide
- glimepuride
longer acting so increased risk of HYPOGLYCEMIA
57
Short acting sulfonylureas - name of drug
- Glipizide
| shorter acting so DECREASED risk of HYPOGLYCEMIA
58
MEN1 - associated cancers
3 Ps
- parathyroid tumors
- pituitary tumors: prolactin or GH
- pancreatic endocrine tumors: zollinger-ellison syndrome, insulinomas, VIPomas, glucagonomas
59
MEN 2A - associated cancers
2 Ps
- parathyroid hormone
- pheochromocytoma
- MEDULLARY thyroid carcinoma
- mutation in RET gene
60
MEN 2B - associated cancers
1 P
- pheochromocytoma
- MEDULLARY thyroid carcinoma
- oral/intestinal MUCOSAL NEUROMAS
- mutation in RET gene, associated with marfanoid habits
61
Anastrozole, letrozole, exemestane - class
AROMATASE inhibitors
62
Effects of ethanol on gluconeogenesis
INHIBITS gluconeogenesis
- ethanal reduces NAD+ to NADH so increases the NADH/NAD+ ratio —> less NAD+ —> cannot drive reactions that need NAD+
- HYPOGLYCEMIA (after glycogen stores are used)
63
Metyrapone stimulation test
- Metyrapone blocks cortisol synthesis by inhibiting 11-beta-hydryoxylase which converts 11-deoxycortisol to CORTISOL
- reduction in cortisol levels causes increase in ACTH
- increased ACTH causes increased 11-doxycortisol which is converted to 17-hydroxycorticosteroids —> both of these hormones should rise if HPA axis is intact
- if HPA axis is not intact due to primary or secondary adrenal insufficiency, then these two steroids will NOT INCREASE
64
Causes of hypoglycemia in type 1 diabetes:
- excessive insulin dose
- inadequate food intake
- physical activity, exercise
65
Histology of Type 2 diabetes
islet amyloid polypeptide (IAPP) deposits
66
Histology of Type 1 diabetes
islet leukocyte infiltrate
67
Medullary thyroid cancer - histology
- neuroendocrine tumor that arises from parafollicular calcitonin-secreting C CELLS
- nests or sheets of polygonal or spindle-shaped cells with extracellular amyloid deposits derived from calcitonin (amyloid stains with CONGO RED)
68
Glargine and Detemir - insulin type
Long acting - once a day
69
NPH - insulin type
long acting - twice a day
70
Regular insulin
short acting
| best for IV use
71
Lispro, Aspart, Glulisine - insulin type
short acting - best for post-meal hyperglycemia
72
Sympathetic stimulation on insulin release
overall DECREASE insulin
- beta 2 is coupled to Gs and stimulates insulin secretion
- alpha 2 is coupled to Gi and inhibits insulin secretion —> PREDOMINATES
73
Parasympathetic stimulation of insulin release
overall INCREASE insulin
| - M3 receptors coupled to Gq and stimulates insulin secretion induced by smell and/or sight of food
74
Pathyphys of exophthalmos and pretibial myxedema
Response to AB in Grave's disease, not due to thyroid hormone
- caused by lymphocytic infiltration, enlargement of the extra ocular muscles by myositis, fibroblast proliferation and overproduction of mucopolysaccharides in response to anti-thyroid antibody
75
Immediate treatment of SEVERE hypoglycemia
- IM glucagon in non medical setting
| - IV glucose in medical setting
76
Flutamide - class, MOA
Nonsteroid anti-androgen
- acts as competitive inhibitor of testosterone receptors
- blocks stimulatory effect of androgens on the primary tumor and the metastases and leads to DECREASE IN SIZE
77
Role of tamoxifen in MEN with prostate cancer
Can help prevent gynecomastia in men receiving anti androgen deprivation therapy by modulating estrogen receptors in the breast
78
Enzymes dependent on THIAMINE as cofactor
- pyruvate dehydrogenase: pyruvate to Acetyl-CoA
- alpha-ketoglutarate dehydrogenase complex: alpha-ketoglutarate to Succinyl CoA
- transketolase: pentose phosphate pathway
79
Finasteride - MOA, uses
Anti-androgen drug
- inhibits 5-alpha reductase: decreases conversion of testosterone to DHT
- treatment for BPH and androgenetic alopecia
80
Enzymes that require biotin as a cofactor
Carboxylase enzymes
- Biotin acts as a CO2 carrier on the surface of carboxylase enzymes
- acetyl Co-A carboxylase: acetyl CoA to malonlyl CoA
- pyruvate carboxylase: pyruvate to OAA in gluconeogenesis
- propionyl carboxylase
- beta-methylcrontonyl CoA carboxylase
Biotin deficiencies are seen in excessive ingestion of avidin (raw egg whites)
81
Molecules that signal through G-protein
TSH, glucagon and PTH
82
Human insulins without any amino acid modifications
- Regular insulin
| - NPH
83
Smooth ER
- contains enzymes for steroid and phospholipid synthesis -
| - all STEROID PRODUCING cells have highly developed smooth ER
84
Rough ER:
- site of synthesis for secretory, lysosomal and integral membrane proteins
