Things I don't know: Path Flashcards
1
Q
PAX8 genetic defect
A
HYPOTHYROID
2
Q
FOXE1 genetic defect
A
HYPOTHYROID
3
Q
TSH receptor mutation
A
HYPOTHYROID
4
Q
THRB mutation
A
thyroid hormone resistance syndrome
HYPOTHYROID
5
Q
Drugs that can cause hypothyroid
A
lithium, iodides, p-aminosalicylic acid
6
Q
What causes the broad coarse facial features in hypothyroidism?
A
mucopolysaccharide-rich edematous fluid
7
Q
subacute lymphocytic thyroiditis (painless thyroiditis)
A
variant of Hashimotos goiter or hyperthyroidism most recover some progress to hypothyroidism anti-thyroid peroxidase Ab excludes women: one year after deliver, abortion or miscarriage
8
Q
thyroid stimulating immunoglobulin
A
Ab to TSH receptor
GRAVES
9
Q
thyroid growth stimulating immunoglobulin
A
Ab to TSH receptor
GRAVES
10
Q
Plummer syndrome
A
hyperthyroidism due to multinodular goiter
11
Q
goitrogens
A
interfere with thyroid hormone synthesis
Brassicaceae (Cruciferae) family: cabbage, turnips, cauliflower, brussel sprouts
12
Q
somatic mutations of TSH receptor signaling pathway
A
toxic adenomas
toxic multinodular goiter
13
Q
somatic mutation of TSHR
A
toxic adenoma
toxic multinodular goiter
14
Q
mutation of GNAS
A
alpha unit of Gs
- toxic adenoma
- toxic multinodular goiter
- anterior pituitary adenoma (40% of GH secreting, minority of ACTH secreting)
- macronodular ACTH independent adrenal hyperplasia
15
Q
RAS mutation
A
minority of follicular adenomas
shared with follicular carcinomas
16
Q
PIK3CA mutation
A
minority of follicular adenomas
shared with follicular carcinomas
17
Q
In what population is follicular carcinoma more prevalent?
A
area with iodine deficiency
18
Q
moans, groans, bones, stones
A
hyperparathyroidism
depression, muscle weakness, abdominal pain, kidney stones, osteitis fibrosa cystica, bone pain
19
Q
Sx of gonadotroph adenoma
A
FSH, LH
hypogonadism, mass effect, hypopituitarism
when deficient: more likely LH secretion is impaired
FSH predominant secreted hormone
20
Q
CDKN1B
A
gene associated with subset of MEN-like abnormalities
familial pituitary adenomas
21
Q
PRKAR1A
A
gene
familial pituitary adenomas
22
Q
AIP
A
gene associated with GH adenoma patients that are young
23
Q
atypical adenoma
A
p53 mutation
more aggressive
24
Q
GH excess Sx (besides acromegaly/ gigantism)
A
gonadal dysfunction, diabetes mellitus, generalized muscle weakness, HTN, arthritis, CHF, increased risk GI cancer
25
How does excess GH cause DM?
inhibits peripheral glucose uptake
increases hepatic glucose production
compensatory hyperinsulinism leads to insulin resistance
26
PAS stain
```
ACTH adenoma (may have hyper pigmentation)
DM: thickening of BM; hyaline sclerosis, Kimmelstiel-Wilson nodules
```
27
plurihormonal adenoma
pituitary
multiple hormones
more aggressive
28
pituitary carcinoma
most are functioning: PRL and ACTH most common
| recognized often by metastasis
29
empty sella syndrome: primary vs. secondary
any condition or treatment that destroys part or all of pituitary gland
Primary: anatomic defect: subarachnoid space herniates into the sella turcica and fills up with CSF; OBESE, HTN, MULTIPLE PREGNANCIES
Secondary: mass (ex: pituitary adenoma) enlarges the sella and is surgically removed or is infarcted
30
most common hypothalamic suprasellar tumors
gliomas
| craniopharyngiomas
31
WNT signaling pathway abnormalities
craniopharyngioma
32
B-catenin mutation
activating
| craniopharyngioma
33
wet keratin
craniopharyngioma
34
machine oil in cysts
looks like cholesterol cleft on histo
| craniopharyngioma
35
Diabetes is the leading cause of what three things
1. end stage renal disease
2. adult onset blindness
3. non-traumatic lower extremity amputation
36
what does excess glucose stick to in DM?
everything, esp basement membranes
37
what happens to excess intracellular glucose in DM
sorbitol pathway to fructose (more potent glycosylator than glucose)
38
A1C, fasting glucose, oGTT
1. diabetic
2. prediabetic
1. A1C: 6.5 or above; fasting: 126 or above; oGTT: 200 or above
2. A1C: 5.7 to 6.4; fasting 100 to 125; oGTT: 140 to 199
39
Pitfalls in DM testing
```
hemoglobin variant (sickle cell)
anemia
hemolysis
heavy bleeding
recent blood transfusion
```
40
HLA-DR3
Hashimotos
Graves
T1DM
41
HLA-DR5
Hashimotos
42
HLA-B8
Graves
43
HLA-DR4
T1DM
44
anti-insulin
Ab against islets
| T1DM
45
anti-GAD
Ab against islets
| T1DM
46
anti-ICA512
Ab against islets
| T1DM
47
CTLA4 polymorphisms
inhibit T cell response
| T1DM
48
PTPN22 polymorphisms
inhibit T cell response
| T1DM
49
insulin gene VNTRs
T1DM
50
formation of advanced glycation end products
complication of DM
formed from glucose precursors and proteins
induce inflammatory cells on ENDOTHELIUM and SMOOTH MUSCLE
ROS, procoagulant, crosslinks and traps proteins in vessel walls (LDL, albumin)
51
complications of DM: activation of PKC
VEGF: neovascularization seen in retinopathy
52
disturbances in polyol pathways
complications of DM
in tissues that do NOT use insulin: so have HIGH intracellular glucose
glucose to sorbitol and eventually fructose: ALDOSE REDUCTASE
uses: NADPH (needed for glutathione reductase to generate GSH (an antioxidant)
sorbitol in lens: cataract formation
53
Most common cause of death in DM
1. MI
| 2. renal failure
54
types of diabetic nephropathy
1. glomerular lesions
2. renal vascular lesions (arteriolosclerosis)
3. pyelonephritis (inc. necrotizing papillitis)
55
glomerular lesions in diabetic nephropathy
1. BM thickens
2. diffuse mesangial sclerosis
3. nodular glomerulosclerosis (Kimmelstiel-Wilson disease)
56
Kimmelstiel-Wilson disease
nodules of hyaline in glomerular capillary loops in glomerulus due to non-enzymatic glycosylation of proteins
associated with RENAL FAILURE in DM
57
charcot joint (neuropathic arthropathy)
DM
| progressive, destructive: dead bone, subluxation, extreme deformity, fibrosis, reactive new bone
58
luxol fast blue
stains myelin blue
| if see pink: segmental demyelation
59
what is the first sign of diabetic neuropathy
segmental demyelination
| autonomic (ex: bladder) and peripheral
60
Why and where do diabetics get infection?
impaired innate immune system: (NEUTROPHILS) due to too much glucose
skin, feet, lungs, urinary tract
61
How does hyperglycemia impair neutrophils?
neutrophils: upregulate CD11b
endothelial cells: upregulate ICAM-1, VCAM-1, E-selectin
ADHESIVE phenotype impairs neutrophil exit from blood vessels to infection
62
pancreatic NETs (neuroendocrine tumors)
rare
most: middle age, sporadic, non-functioning
MALIGNANT
metastases: LIVER
CHROMOGRANIN A (not specific)
associations: MEN-1, von Hippel Lindau syndrome, neurofibromatosis-1, tuberous sclerosis
SALT and PEPPER; NESTs or CORDs
graded on: MITOTIC FIGURES, Ki-67
stains not helpful: stain does not correlate with secretion
63
What is the exception to a pancreatic NET being malignant?
micro adenoma or insulinoma
64
von Hippel Lindau syndrome
PANCREATIC NETs
PHEOCHROMOCYTOMA
cysts of kidney, liver, epididymis
renal cell carcinoma (clear cell type), angiomas, cerebellar hemangioblastoma
65
neurofibromatosis-1
pancreatic NETs
66
tuberous sclerosis
pancreatic NETs
67
How are carcinomas diagnosed?
based on LOCAL INVASION and DISTANT METASTASIS
68
glucagonoma (alpha cell tumor)
perimenopausal, postmenopausal women
| anemia, DM, NECROLYTIC MIGRATORY ERYTHEMA
69
somatostatinoma (delta cell tumor)
achlorhydria
CHOLELITHIASIS (inhibits CHOLECYSTOKININ release and therefore gallbladder emptying)
DM (inhibits insulin)
STEATORRHEA (inhibits pancreatic secretion and lipid absorption)
most don't have symptoms
70
insulinoma
MOST COMMON functioning pancreatic NET
EPISODIC HYPOGLYCEMIA, confusion, blurred vision, muscle weakness, sweating, palpitations
may have AMYLOID
71
VIPoma
vasoactive intestinal peptide
HYPOKALEMIA, acidosis, hypovolemia, ACHLORHYDRIA
SEVERE WATERY DIARRHEA
associations: neural crest tumors: neuroblastomas, ganglioneuroblastoma, ganglioneuromas, pheochromocytomas
72
gastrinoma
SECOND most common pancreatic NET
| parietal cell hyperplasia (increase acid): PEPTIC ULCERS, DIARRHEA
73
Zollinger-Ellison syndrome
gastrinoma
74
islet hyperplasia
hyperinsulinism
can happen in adults
most: CONGENITAL with hypoglycemia in neonates/infants
75
scenarios that may result in islet hyperplasia
1. maternal DM
2. Beckwith-Wiedemann syndrome
3. rare mutations in the B cell K channel protein or sulfonylurea receptor
76
How can maternal DM effect fetus/neonate?
maternal hyperglycemia results in increase in number and size of fetal islets
after birth: hyperactive islets cause serious episodes of hypoglycemia in neonate (transient phenomenon)
77
What pancreatic NET is associated with neural crest tumors?
| What are these neural crest tumors?
VIPoma
| includes: neuroblastoma, ganglioneuroblastoma, ganglioneuromas, pheochromocytomas
78
MEN1
1. What is the most common manifestation?
2. What is most likely to kill them?
3. What is the most frequent pituitary manifestation?
1. manifestation: primary hyperparathyroidism (hyperplasia or adenoma)
2. kill: pancreatic NET
3. pituitary: prolactin secreting
79
familial medullary thyroid cancer
variant of 2A medullary cancer without clinical manifestations
80
Wermer syndrome
MEN1
81
Sipple syndrome
MEN2A
82
Features of ACTH independent macro nodular adrenal hyperplasia (primary cortical hyperplasia)
```
greater than 3mm
sporadic
association: GNAS, McCune-Albright
prominent nodules of various sizes
mix of lipid poor and lipid rich cells between nodules have microscopic nodularity
```
83
Features of ACTH independent micro nodular adrenal hyperplasia (primary cortical hyperplasia)
1-3 mm
darkly pigemented: LIPOFUSCION
nodules with intervening atrophy
84
lipofusion
micronodular primary adrenal hyperplasia
85
primary adrenocortical neoplasia
malignant or benign
| more likely malignant in children: Li-Fraumeni, BeckwithWiedemann
86
Li-Fraumeni
primary adrenocortical neoplasia
87
Beckwith-Wiedemann
primary adrenocortical neoplasia
88
Are adrenal cortex carcinomas or adenomas more likely to be functional and virilizing?
carcinomas
89
Histo: adrenal cortical adenomas
LIPID rich
90
Histo: adrenal carcinoma adenoma
anaplastic (can't tell it's carcinoma without this until it metastasizes)
poor prognosis
larger than adenoma
91
Causes of hypercortisolism in order from most common to least
1. exogenous
2. pituitary adenoma
3. primary adrenal neoplasm
4. paraneoplastic ACTH tumor
92
Conn's syndrome
```
SECOND most common hyperaldosteronism
adrenal adenoma producing aldosterone
Tx: Sx
Sx: HTN, hypokalemia, low renin
SPIRONOLACTONE BODIES after spironolactone Tx
```
93
bilateral adrenal hyperplasia
MOST COMMON primary hyperaldosteronism
idiopathic
Tx: spironolactone (K sparing)
Sx: HTN, hypokalemia, low renin
94
secondary hyper-aldosteronism
due to activation of renin-aldosterone system (decreased renal perfusion, arterial hypovolemia, pregnancy)
95
21-hydroxylase deficiency
MOST common adrenogenital syndrome
low cortisol: more production of precursors leading to excess androgens
wastes Na
96
11-B-hydroxylase deficiency
second most common adrenogenital syndrome
low cortisol: more production of precursors leading to excess androgens
DOC maintains Na levels
97
congenital adrenal hyperplasia
suspect in neonate with AMBIGUOUS GENITALS
huge adrenals with cerebriform appearance
BROWN on cut surface rather than yellow (lipid depleted)
may have hyperplasia of corticotrophs in the pituitary
may have tumors in TESTES HILUS (due to increased ACTH)
98
causes of primary adrenocortical insufficiency
acute?
chronic?
acute: adrenal crisis, acute hemorrhagic necrosis
| chronic/Addison's: autoimmune, infection (TB, fungal, HIV), amyloid, sarcoid, metastatic carcinoma
99
APS1/APS2
```
Ab to steroidogenic enzymes
AUTOIMMUNE ADRENALITIS (one form of chronic adrenalitis)
```
100
Addison's labs
low Na, glucose
high K
all due to lack of cortisol
HYPERPIGENTATION: ACTH increased
101
Tumors that metastasize to adrenal
```
lung
breast
kidney
suspect if: bilateral and multifocal
metastases: MOST COMMON adrenal malignancy
```
102
Zellballen
cluster of cells
| PHEOCHROMOCYTOMA
103
Familial causes of pheochromocytoma
MEN2A/B
Sturge-Weber
von Hippel Lindau
von Recklinghausen
104
Sturge-Weber
hemangioma of trigeminal nerve
| PHEOCHROMOCYTOMA
105
von Recklinghausen
aka: neurofibormatosis type 1
neurofibromatosis, schwannoma, meningioma; composite tumors with neuroblastoma, ganglioneuroma, ganglioneuroblastoma
PHEOCHROMOCYTOMA
106
paragangliomas
extra-adrenal pheochromocytomas
| sites: branchiomeric, intravagal, aortico-sympathetic
107
neuroblastoma
neoplasm of POSTGANGLIONIC SYMPATHETIC neurons
ADRENAL MEDULLA (other sites: sympathetic chain, neck, thorax, retroperitoneum, pelvis)
N-MYC, DNA ploidy
metastasize to (lymphatics or blood): SKIN, BONES (SKULL or ORBIT), liver
Sx: PALPABLE ABDOMINAL MASS, diastolic HTN
Dx: increased urine VMA and HVA; bone scan, 131I-MIBG
HOMER-WRIGHT ROSETTES
108
N-MYC amplification
poor prognosis in neuroblastoma
109
good prognosis for neuroblastoma
metastasize to skin, liver, bone
| stage 4S
110
VMA in urine
neuroblastoma (very sensitive)
111
HVA
neuroblastoma (very sensitive)
112
BRAF point mutations
part of MAP kinase signaling
poor prognosis factors: metastasis and invasion
papillary cancer
113
RET/PTC rearrangements
part of MAP kinase signaling
papillary carcinoma
medullary carcinoma
114
manifestations of pheochromocytoma
palpitations, headache, episodic sweating (PHE)
HTN
cardiac arrhythmias, myocarditis, MI, dilated cardiomyopathy, pulmonary edema
hypertensive crisis: leading to encephalopathy (confusion, neuro probs, seizure, stroke)
115
chromogranin stain
pancreatic NET
| Neuroblastoma
116
synaptophysin
neuroblastoma
117
Hutchinson's syndrome
neuroblastoma metastasis to SKELETAL system (skull and orbit common)
118
Pepper's syndrome
neuroblastoma metastasis to LIVER
