endocrinology Flashcards
1
Q
high dose dex test-when does it suppress?
A
- Suppresses ACTH/cortisol in a pituitary adenoma
- Does NOT suppress is ACTH caused by ectopic ACTH (small cell carcinoma)
- If adrenal secreting neoplasm, will have high cortisol, low ACTH and NO CHANGE with dexmethasone (ACTH already low and adrenal gland not responsive to it)
2
Q
PTHrP
A
Squamous cell lung cancer
Breast cancer
3
Q
branching papillae with a stalk and cuboidal epithelium. Ground glass appearance.
Psamomma bodies
A
papillary thyroid cancer
4
Q
Sheets of Hurthle cells(eosinophilic cytoplasm) OR follicular cells
A
follicular thyroid cancer
5
Q
large pleomorphic cells and multinucleated osteoclasts in thyroid histology. Also spindle cells
A
Anaplastic thyroid cancer
6
Q
Uniform polygonal/spindle cells positive for calcitonin and amyloid
A
MTC
7
Q
Carpal tunnel associated with:
A
hypothyroidism, diabetes
8
Q
What is the single best test for hypothyroidism? Why?
A
TSH. Will be high. Because T4 levels can be within normal limits early on. TsH more sensitive. Serum t3 is the last thing to decline, a late indicator.
BUT if a hypothalamic problem, (central) then will not detect….
9
Q
RANK-L is generated by
A
osteoblasts
10
Q
Differentiation of osteoclasts is done by
A
RANK-ligand and monocyte CSF
11
Q
OPG
A
secreted by osteoblasts, acts as a decoy receptor.
12
Q
Bone turnover increased when:
A
Ratio of RANK-L:OPG is high.
13
Q
How does PTH work on bone cells?
A
Stimulates secretion of Monocyte CSF and RANK-L BY osteoblasts to stimulate osteoclasts. Does not directly stimulate osteoclasts
14
Q
How does low estrogen cause breakdown of bone?
A
Overexpression of RANK receptors causes more osteoclastic activity
15
Q
Side effects of TZDs
A
Liver function–check LFTs.
Also, fluid retention
16
Q
Signs of hypercalcemia
A
Stones
Groans (GI)
Bones
and psychiatric overtones (mental status)
17
Q
rT3 made from
A
T4. Converted by hypothalamus and pituitary and also by peripheral tissues. If T4 is low, will have decreased rT3 too.
18
Q
How does glucocorticoid affect the HPA axis?
A
Suppresses all levels, hypothalamus, pituitary, and adrenal. Can have adrenal crisis.
19
Q
thyroid diverticulum arises from
A
floor of primitive pharynx
20
Q
connects thyroid to tongue
A
thyroglossal duct
21
Q
pyramidal lobe of thyroid=
A
persistence of thyroglossal duct
22
Q
normal remnant of thyroglossal duct
A
formaen cecum
23
Q
anterior midline neck mass that MOVES with swallowing
A
thyroglossal duct cyst
24
Q
lateral neck mass that does not move with swallowing
A
branchial left cyst –from PERSISTENT CERVICAL SINUS
25
when does fetal adrenal become active
secretes cortisol late in gestation
26
fetal cortisol secretion controlled by
ACTH and CRH from fetal pituitary and placenta
27
Neuroblastoma
tumor of adrenal medulla in children
28
cells in adrenal medulla
chromaffin cells
29
left adrenal drains to
left renal vein-->IVC
30
right adrenal vein drains to
IVC
31
posterior pituitary derived from
neuroectoderm
32
anterior pituitary derived from
oral ectoderm (Rathke's pouch)
33
Melanotropin secreted by
anterior pituitary
34
acidophils
GH and prolactin
35
Basophils
B-FLAT
| -FSH, LH, ACTH, TSH
36
alpha subunit of pituitary hormone
TSH, LH, FSH, hCG
37
B subunit of pituitary hormone determines
specificity
38
alpha cells of pancreas found where?
periphery
39
beta cells of pancreas found where?
inside
40
pathophys of insulin release
1. glucose enters
2. ATP increase
3. ATP gated K+ channels open
4. depolarization of beta cell
5. VG-Ca channel opens
6. insulin secretion
41
Does insulin cross the placenta?
No. Ok in pregnancy
42
which organs uptake glucose independently of insulin?
```
brain
RBC
intestine
Cornea
Kidney
Liver
```
43
GLUT 1 found in
RBC and brain (insulin independent)
44
GLUT 2 found in
beta cells, liver, kidney, small intestine
45
GLUT 4
adipose tissue, skeletal muscle
46
effect on insulin on kidneys
increased NA retention
47
Things that increase insulin
hyperglycemia
GH
B2 adrenergic ANTAGONIST
48
Things that decrease insulin
hypoglycemia
somatostatin
a-2 agonist
49
What type of receptor is insulin receptor?
tyrosine kinase
50
pathophys after insulin binds cell
Tyrosine kinase phosphorylates
- -IP3 causes GLUT-4 vesicles to fuse and glycogen, lipid, and protein synthesis
- -RAS/MAP kinase causes cell growth
51
Can RBCs use ketones for energy/
NO! they have no mitochondria
52
effects of glucagon
Glycogenolysis
gluconeogenesis
lipolysis
ketone
53
Glucagon inhibited by
somatostatin
| and obvi insulin and hyperglycemia
54
TRH stimulates
TSH and prolactin
55
Dopamine inhibits
prolactin
56
CRH stimulates
ACTH
MSH (melanocyte stimulating hormone)
beta endorphin
57
Somatostatin inhibits
GH
| TSH
58
which drugs would stimulate prolactin secretion?
Antipsychotics (dopamine antagonist)
| Also OCPs
59
prolactin negative feedback at
hypothalamus--increasees dopamine
60
what stimulates prolactin secretion
TRH
61
Describe how growth hormone works
GH stimulates liver to release IGF-1/somatomedin. Causese growth
62
when is secretion of GH high?
exercise and sleep (when glucose is low). Pulsatile secretion.
63
Gh inhibited by
glucose and somatostatin
64
bilateral adrenal hyperplasia
congential adrenal hyperplasia
65
Boy with ambiguous genitalia
| -->hypertension, hypokalemia
17a-OH deficiency ("boys are 17 when they hit puberty")
high aldo
low testosterone
66
Girl with normal sex organs
| --hypertension, hypokalemia
17alpha-OH deficiency
67
Girl with ambigulous genitalia
- -hypotension, hyperkalemia
- -High renin
21 OH deficiency
68
Boy with hypotension, hyperkalemia, and increased renin
21 OH deficiency
69
Girl with ambiguous genitalia
| --Hypertension
11B OH deficiency ("girls are 11 when they hit puberty")
| --will have high 11 deoxycorticosterone
70
Boy with normal genitalia
| --hypertension
11B OH deficiency
71
Cortisol effects
| BBIIG
```
blood pressure
decreased bone formation
Inflammatory (anti)
Insulin resistance
Gluconeogenesis
```
72
how does cortisol maintain blood pressure?
upregulates alpha 1 receptors on arterioles
73
how does cortisol effect anti-inflammatory response?
1. inhibit leukotriene and prostaglandin synthesis
2. inhibit leukocyte adhesion
3. block histamine release
4. reduce eosinophil count
5. block IL-2 production
74
PTH secreted by what cells
chief cells
75
effects of PTH
1. increased bone resorption Ca and Po4
2. Increased calcium resabsorption
3. Decreased phosphate in PCT
4. Stimulates kidney 1alpha-OH
76
Overall effect of PTH on serum levels
Ca increase
PO4 decrease
urine phosphate increase
PTH=Phosphate trashing hormone
77
What increases PTH secretion
decreased calcium
| slight decrease Mg2+
78
What decreases PTH secretion
HUGE decrease in Mg2+
79
Cause of MG2+ deficiency
diarrhea
Aminoglycosides
diuretics
alcohol
80
Effect of vitamin D?
Increases calcium reabsorption in GUT
Increases phosphate release from matrix
Increases intestinal phosphate reabsorption
-->Thus, INCREASES CALCIUM AND PO4
81
Vitamin D3 from
sun exposure
82
Vitamin D2 from
plants
83
what increases 1, 25 OH2 production
Increased PTh
decreased PO4
decreased ca
84
what cells make calcitonin
parafollicular cells
85
effect of calcitoning
decreases bone resorption
86
t3/T4 receptor
steroid
87
IGF-1, PDGF, EGF (growth factor) receptor
Intrinsic tyrosine kinase-->MAP kinase
88
acidophile and cytokine recptor
receptor tyrosine kinase
89
Nitric oxide, ANP receptor
cGMP
90
vitamin D receptor
steroid
91
GnRH, GHRH signaling pathway
IP3
92
Oxytonin and ADH signaling pathway
IP3
93
TRH signaling pathway
IP3
94
FSH, LH, ACTH, TSH, pathway
cAMP
95
hitamine and gastrin pathway
IP3
96
PTH and calcitonin signaling pathway
cAMP
97
glucagon signaling pathway
cAMP
98
SHBG and testosterone
Increase SHBG lowers testosterone.
99
SHBG levels during pregnancy
Increase.
100
Excess iodide temporarily inhibits thyroid peroxidase
Wolff Chaikoff effect
101
what converts t4 to t3
5' deiodinase
102
thyroid binding globulin effect
binds hormone, preventing it from having any effects
103
When are TBG levels low? high?
low: hepatic failure
high: pregnancy
104
how does thyroid hormone increase basal metabolic rate?
Upregulates Na/K ATPase
105
peroxidase
coupling of MIT and DIT
| --oxidation of iodide
106
Methimazole effect
Inhibits peroxidase only
| 'A MONO EFFECT)
107
propylthiouracil effect
Inhibits peroxidase AND peripheral 5'deiodinase
| A POLY effect
108
Cushing's disease
INCREASED ACTH causing cushing's syndrome
109
Other causes of cushing's syndrome
ectopic ACTH
| Adrenal hyperplasia/adenoma
110
striae
hypercortisolism
111
low dose dex: cortisol elevated
| high dose dex: cortisol suppressed
cushing's disease
| -ACTH producing tumor
112
low dose dex: coritsol elevated
| high dose dex: cortisol elevated
Ectopic ACTH OR adrenal hyperplasia/adenoma/carcinoma
113
Conn's syndrome
aldosterone secreting adenoma
114
Treatment for Conn's or adrenal hyperplasia
surgery or spironolactone
115
Cause of secondary hyperaldosteronism
renal artery stenosis
CHF
nephrotic syndrome (perception of low intravascular volume)
116
Cause of addison's
Adrenal Atrophy
| Absence of hormone
117
hypotension
hyperkalemia
acidosis
signs of adrenal insufficiency
118
how to disginguish primary from secondary adrenal insufficiency
Primary
- -High ACTH: skin pigmentation
- -hyperkalemia (ALSO aldosterone is low!)
Secondary:
- -No hyperkalemia
- -ONLY cortisol is low
- -LOW ACTH
119
how to distinguish primary from secondary hyperaldosteronism?
renin levels
120
Pheos associated with:
NF-1
MEN2A
MEN2B
121
Treatment for pheo
1. alpha blockade
2. beta blockade
3. surgery
122
Rule of 10's
Pheos are 10%:
- malignant
- bilateral
- extra-adrenal
- calcify
- kids
123
describe pathway of phenylalanine breakdown
```
phenylalanine
tyrosine
L-dopa
Dopamine
norepinephrine
epinephrine
```
124
Breakdown product of dopamine
HVA, increased in pheos along with VMAs
125
Waterhouse friederichsen
acute primary adrenal insufficiency from adrenal hemorrhage
126
Waterhouse friederichsen is associated with
neisseria meningitidis
| DIC/Shock
127
dx: neuroblastoma
elevated homovanillic acid in the urine.
128
What's different about neuroblastoma vs a pheo?
Less likely to develop hypertension
129
oncogene associated with neuroblastoma
n-myc
130
how does a neuroblastoma classically present?
1. abdominal fullness
2. compression of sympathetic chain (horner's)
3. small blue round cells
131
facial/perorbital myxedema
sign of hypothyroidism
132
pretibial myxedema
| exopthalmos
Specific to graves. Not found in other causes of hyperthyroidism
133
dx: hypothyroidism
```
increased TSH (if primary)
Decreased T4
```
134
dx: hyperthyroidism
```
decreased TSH (if primary)
increased free or total T4/T3
```
135
What is the most sensitive test for primary hypothyroidism?
increased TSH
136
hashimotos association
HLA-DR5
137
Histology of hashimoto's
Hurthle cells
| lymphocytic infiltrate with germinal centers
138
enlarged nontender thyroid
hashimoto's
139
pathophys of hashimotos'
anti-thyroglobulin antibodies
140
cretinism caused by
severe fetal hypothyroidism
141
Cause of endemic cretinism
lack of dietary iodine
142
cause of sporadic cretinism
Defect in T4 formation
143
Pot bellied, pale, puffy faced kid with
| Protruding umbilicus and Protuberant tongue
5P's of hypocretinism
144
self-limited hypothyroidism after a flu like illness
subacute thyroiditis
145
Histology of subacute thyroiditis
granulomatous inflammation
146
hypothyroidism with increased ESR, jaw pain, early inflammation, and a tender thyroid
subacute thyroiditis
147
hypothyroidism where thyroid is replaced by fibrous tissue
riedel's thyroiditis
148
fixed, hard rock like and painless goiter
riedel's
149
Cause of Riedel's thyroiditis
IgG4 systemic disease
| --overproduction of IgG4, causing fibrosis
150
Jod basedow phenomenon
thyrotoxicosis if a patient with iodine deficiency goiter is made iodine replete
151
Toxic multinodular goiter etiology
mutation in TSH receptor
152
pathophys thyroid storm
stress causes a huge catecholamine surge and arrhythmia
153
serious complication of hyperthyroidism
thyroid storm.
154
ALP during thyroid storm
Increased
155
Hashimoto's thyroiditis cancer
lymphoma
156
orphan annie's eyes, psamomma bodies, nuclear grooves. Excellent prognosis
papillary carcinoma
157
Calcitonin producing tumor with sheet of cells
medullary carcinoma
158
who gets anaplastic thyroid cnacer
older pts, poor prognosis
159
cystic bone spaces filled with brown fibrous tissue
osteitis fibrosa cystica
160
Cause of osteitis fibrosa cystica
High PTH
161
cause of primary hyper PTH
adenoma
162
lab findings in primary hyperPTH
hypercalcemia
hypercalciuria
hypophosphatemia
increased alkaline phosphatase
163
cause of secondary hyperparathyroidism
chronic renal disease
164
Labs in secondary hyperparathyroidism
hypOcalcemia
hypophosphatemia
increased alkaline phosphatase
165
renal osteodystrophy
bone lesions from 2ndary or tertiary hyperparathyroidism
166
Tertiary hyperparathyroidism
Autonomous hyperparathyroidism secretion from chronic renal disease.
- VERY high PTH
- hyPERcalcemia
167
Causes of hypoPTH
1. DiGeorge
2. Surgical excision accidnetal
3. autoimmune destruction
168
Findings of Hypoparathyroidism
hypocalcemia
tetany
Chvostek's sign
Trousseau's sign
169
Chvostek's sign
tapping of facial nerve=contraction of facial muscles
170
Trousseau's sign
Occlusion of brachial artery with BP cuff
171
Pseudohypoparathyroidism
Kidney unresponsive to PTH.
- -inherited.
- -hypocalcemia with shortened 4th/5th digits and short stature
172
Inheritance of pseudohypoparathyroidism
autosomal dominant
173
Dx of acromegaly
```
Increased serum IGF-1
OR
Glucose tolerance test-->failure to suppress serum GH
OR
MRI for pituitary mass
```
174
Treatment for prolactinoma
bromocriptine
cabergoline
--dopamine agonists
175
treatment of acromegaly
Pituitary adenoma resection
| somatostatin analog
176
causes of central DI
tumor
trauma/surgery
histiocytosis X
177
causes of nephrogenic DI
lithium
hypercalcemia
demeclocycline
178
lab findings of diabetes insipidus
Urine specific gravity < 1
| serum osmolality > 290
179
dx of diabetes insipidus
water deprivation test
180
how to distinguish central vs nephrogenic DI
Central: Will respond to Desmopressin
Nephrogenic: No response
181
Treatment for nephrogenic diabetes insipidus
hydrochlorothiazide
indomethacin
amiloride
182
Main problem in SIADH
hyponatremia from:
1. High ADH
2. Low aldosterone
183
treatment of SIADH
1. fluid restriction
conivaptan
demeclocycline
184
drugs that can cause SIADH
cyclophosphamide
| pulmonary dz too
185
Causes of hypopituitarism
1. Pituitary adenoma/craniopharyngioma
2. Sheehan
3. empty sella
radiation and brain injury
186
Cause of coma in type 2 diabetes
hyperosmolarity of blood
187
cause of dehydration in insulin deficiency
osmotic diuresis with glucose and ketones in the urine
188
Main BUZZWORD FOR DIABETES
nonenzymatic glycosylation
189
nonenzymatic glycosylation is responsible for
small vessel disease and large vessel disease
- -retinopathy, glaucoma, renal failure, nephropathy
- CAD
190
Ostmotic damage in diabetes causes
neuropathy and cataracts
191
Histology of T1D
islet leukocytic infiltrate
192
Histology of T2D
islet amyloid deposit
193
Serum labs in diabetic ketoacidosis
```
Hyperkalemia (but depleted intracellular K)
Acidosis
Decreased bicarb
(anion gap metabolic acidosis)
```
194
signs of carcinoid syndrome (labs)
Increased 5-HIAA
| Niacin deficiency
195
treatment of carcinoid syndrome
octreotide (somatostatin analog)
196
Rule of 1/3rds
applies to carcinoid syndrome
- -1/3 metastasize
- -1/3 present with a second malignancy
- -1/3 have multiple tumors
197
zollinger ellison associated with
MEN type I
198
Men 1 tumor
Pituitary, Pancreas, parathyroid (3P's)
199
Men 2A
Parathyroids and pheo(2P)
200
Men 2B
Pheo (1P)
201
MEN inheritance
autosomal dominant
202
gene mutation in MEN 2A and 2B
ret
203
pt with kidney stones and stomach ulcers
Men1
- -Hyperparathyroidism
- -Zollinger ellison (pancreas)
204
Medullary thyroid cancer seen in
MEN2
205
Oral ganglioneuromatosis
Men2B
| --Associated with marfanoid habitus
206
intermediate insulin
NPH
207
Effects of metformin
decreased gluconeogenesis
Increased glycolysis
Increased peripheral glucose uptake
208
Most serious adverse effect of metformin
1. lactic acidosis
209
Who is metformin contraindicated in?
renal failure
210
can you use metformin in type 1?
YES--does not require islet function to work! It enhances glucose uptake without insulin
211
Mechanism of sulfonylureas
Increases insulin release
212
tox: sulfonylureas
first generation: disulfiram
| 2nd generation: hypoglycemia
213
Tobultamide
| chlorpropamide
first generation sulfonylurea
214
glyburide
glimepiride
glipizide
second generation sulfonylureas
215
pioglitazone
| rosiglitazone
TZDs
216
mechanism of TZDs
increase insulin sensitivity in peripheral tissue
| --Binds PPAR-y nuclear transcription factor
217
Indication of TZDs
Type 2 diabetes
218
Side effect of TZD
weight gain, edema
hepatotoxicity
heart failure
219
acarbose
| miglitol
alpha glucosidase inhibitors
220
mech: alpha glucosidase inhibitor acarbose miglitol
Inhibit intestinal brush border a-glucosidases
- -decreased sugar absorption
- -reuces postprandial hyperglycemia
221
tox: a-glucosidase inhibitors
GI disturbances
222
pramlintide
amylin analog
223
mechanism pramlintide
decreases glucagon
224
Mechanism: exenatide/liraglutide
increase insulin
| decrease glucagon
225
linagliptin
saxagliptin
sitagliptin
DPP-4 inhibitors
226
-gliptin mechanism
Increase insulin
| decrease glucagon
227
Which oral anti-diabetic agents can be used in type 1?
metformin
| pramlintide
228
side effect of acarbose/miglitol
GI disturbance
229
Side effect of GLP-1
GLP-1
230
Side effect of DPP4 gliptins
urinary/respiratory infections
231
Side effects of propylthiouracil/methimazole
agranulocytosis
aplastic anemia
skin rash
232
side effect of propylthiouracil
hepatotoxicity
233
side effect of methimazole
teratogen
234
demecoglycline use
SIADH
235
octreotide use
Somatostatin analog
```
acromegaly
carcinoid (somatostatin inhibits gastric neuroendocrine cells, gastrin, CCK,
gastrinoma
glucaonoma
esophageal varices
```
236
oxytocin use
```
stimulates labor
milk let down
uterine hemorrhage (contracts spiral arteries?)
```
237
tox of demeclocycline
nephrogenic DI (if too much)
photosensitivity
bone/teeth abnormalities
238
Mechanism glucocorticoids
Inhibits phospholipase A2 and Cox2
| --decreases leukotrienes and prostaglandins
239
How do you treat addison's disease
Give glucocorticoids
240
What happens if you stop giving glucocorticoids suddenly?
Can have adrenal insufficiency (takes time for adrenal to take over, HPA has been suppressed for such a long time)
241
Side effect of glucocorticoids
peptic ulcers
| diabetes
242
origin of thyroid parafollicular cells
neural crest cells
243
classic addison's presentation
```
Hyperpigmentation!
Less insulin requirement if diabetic
Orthostatic hypotension
GI symptoms
Fatigue, weight loss
--TYPICALLY LOSS OF CORTISOL AND ALDOSTERONE
```
244
Leuprolide mechanism
```
GnRH agonist:
--Increase testo/DHT
--then DECREASE
a form of androgen deprivation therapy
--abolishes pulsatile secretion
```
245
Finasteride
5a-reductase
- -increase in testosterone
- -decrease in DHT
246
flushing
diarrhea
bronchospasm
carcinoid syndrome
247
Sarcoidosis results in hypercalcemia from
Excess vitamin D (calcitriol)
