Endocrine (Pathology) Flashcards
1
Q
Embryology of the parathyroid?
A
superior (4th pharyngeal pouch)
inferior (3rd pharyngeal pouch)
2
Q
Location of the parathyroid?
A
poles of the thyroid
weight= 30-40 mg/gland (adults)
3
Q
Most abundant cells in the parathyroid?
A
chief cells –> PTH
4
Q
Most important stimulus for PTH secretion?
A
Hypocalcemia (–ionized Ca) –> ++PTH
- bone (osteoclasts - Ca ++ mobilization)
- renal (++ca resorb, PO excretion), 1,25 Vit D3 synthesis (++intestinal Ca absorb)
5
Q
Age changes in PT?
A
it turns into fat by the age of 35
6
Q
Hyperparathyroidism causes?
A
primary (MCC adenoma)
secondary (MCC Renal fail)
7
Q
Features of Primary hyperparathyroidism
A
- adenoma (5g, solitary, capsulated, peripheral normal tissue (-fat, +cells)
- hyperplasia (1g, 4 glands, -fat, +cells, chief cell hyperplasia)
- carcinoma (10g, local invasion, metastasis)
8
Q
Most important criteria for diagnosis endocrine malignancy?
A
invasion and metastasis
9
Q
MC manifestation of primary hyperparathyroidism?
A
asymptomatic 90%
++ Serum Ionized Ca
10
Q
Primary hyperparathyroidism?
A
(MCC adenoma), >50s, F, cyclin D1, \++PTH-nephrolithiasis \++Ca blood(+Ca, +PTH, -PO4) TX: surgery
11
Q
10% pts with symptoms?
A
Adenoma:
- osteitis fibrosa cystica = brown tumors) (small bones)
- nephrolithiasis/nephrocalcinosis (renal)
- gallstone, acute pancreatitis, peptic ulcers
- seizures
12
Q
Secondary hyperparathyroidism?
A
(MCC Renal fail) old hyperplasia blood(+PO4 --> -- Ca or normal[established renal failure]) --> ++PTH Tx: treat RF
13
Q
MCC hypoparathyroidism?
A
surgery (thyroidectomy)
never preserve the parathyroid when removing the thyroid
14
Q
Clinical features of hypoPT?
A
Tetany (Trousseau sign, Chovstek's sign) CNS (seizures, basal ganglia calcification) EYE: cataracts CVS: long QT, heart stop in diastole DENTAL: enamel lost
15
Q
HypoPT: Surgery
A
- – PTH
- – Ca
- ++ PO4
16
Q
Pseudo-Pseudo HypoPT
A
Paternal Imprinting GNAS1 protein
All are normal
17
Q
Pseudo HypoPT
A
End organ resistance
Albright (maternal imprinting)
hypogonadism
++ PTH
– Ca
++ PO4
(like RF)
18
Q
Adrenal normal anatomy?
A
cortex (G F75% R)
Medulla
Weight: 4g/gland
19
Q
Adrenal gland changes with stress?
A
acute: – wt (loss of lipid)
chronic: ++wt (hypertrophy, hyperplasia)
20
Q
Adrenal Medulla cells?
A
chromaffin cells ==> catecholamines (epinephrine)
21
Q
Stressful states (ER)
A
infection
trauma
surgery
sudden withdrawal of steroid admin
22
Q
Hyperfunction (hyperAdre)
A
- Cushing’s syndrome (++ Cortisol)
- HyperAldosterone (++Aldos)
- Adrenogenital syndrome (++Androgenic steroid)
23
Q
Hypofunction (hypoAdre)
Acute
A
“Waterhouse-Friderichsen”
massive bilateral hemorrhage of adrenal glands
- pts with menigococcemia (death)
24
Q
Hypofunction (hypoAdre)
chronic
A
- adrenal defect - Addison’s dis
- pituitary defect
- hypothalamus defect
25
Exogenous cause of hypercortisol?
MCC - corticosteroid therapy excess
| bilateral cortical atrophy
26
Endogenous cause of hypercortisol?
1. ACTH secreting pituitary micro adenoma
2. Primary adrenal (adenoma, hyperplasia, carcinoma)
3. Ectopic ACTH secretions (Small CC Lung)
27
ACTH secreting pituitary micro adenoma
```
Cushing's disease
25, F
POMC (skin pigmnt.)
nodular cortical bilateral hyperplasia
++ACTH
++Cortisol
```
28
1* Adrenal causes?
ACTH indpt. Cushing's syndrome
Adrenal syndrome
Female
Carcinoma (MC Children)
wt of gland: 300 (Carinoma)
++Cortisol
-- ACTH
Atrophy of uninvolved gland
29
Ectopic ACTH secretions = Paraneoplastic syndrome
```
Males, 50
smokers
bilateral hyperplasia
++ACTH
++Cortisol
```
Crooke hyaline change (Keratin intermediate)
30
Clinical course for Cushing's syndrome?
Early: HTN, ++weight, (trunk), moon face, buffalo hump, type 2 atrophy, --muscle mass
Metabolism: ++gluconeogenesis -> 2 DM
Bone: loss of collagen -> resorb -> osteoporosis
Skin: bruise, fragile (striae)
Other: --imune, altered mental status, hirsutism
31
Lab values for Cushing's syndrome?
1. 24 hr urine free cortisol levels
| 2. dexamethasone suppression test (PT)
32
What is hyperaldosteronism?
++ adosterone
| surgical treatable cause of HTN
33
Causes of hyperaldosteronism?
1. primary (adenoma = Conn's syndrome)
| 2. secondary (--renal blood flow -->RAS, HTN, DM, Pregnancy)
34
Pregnancy in relation with ++Aldos?
estrogen --> ++Renin
35
Genetic markers for primary (Conn's)?
```
CYP11B2 (hyperplasia)
Chrimeric gene (fusion of CYP11B2 + CYP11B1)
```
36
Lab values for primary v.s secondary HyperALD?
both ++Aldos
1. low renin
2. high renin
37
Etiology for adrenogenital syndrome?
1. part of Cushing's dis (++ACTH)
2. primary adrenocortical neaoplasm (MC: carcinoma)
3. congenital adrenal hyperplasia (enz deficiency)
38
MCC enzyme def in adrenogenital syndrome?
21-hydroxylase
39
Genetic marker for adrenogenital syndrome?
CYP21A
40
Clinical types of adrenogenital syndrome?
1. Classic
2. Simple
3. Non-Classic
41
Classic type syndrome
def?
clinical?
def: --glucocorticoid, ++androgen
clinic: salt wasting, acidosis, --BP, CVS collapse --> death
F- phalloid organ
M- normal at birth, salt wasting 1 wk later
42
Simple type syndrome
def?
clinical?
```
no salt wasting
adrenal hyperplasia
def: -- glucocorticoid, ++ACTH (adrenal hyperplasia)
F- ambiguous genitalia
M- enlarged genitalia
```
43
Non-Classic type syndrome
| clinical?
MC
| Asymptomatic (hirsutism)
44
Adrenogenital syndrome treatment?
glucocorticoids --> --ACTH, --Androgen activity
45
MCC adrenocortical insufficiency?
secondary (withdrawal from corticosteroids)
46
Adrenocortical inssuficiency types?
Primary (acute, chronic)
| Secondary
47
Clinical features of Adrenocortical insufficiency?
until 90% of cortical damage
early - weakness, fatigue, anemia, vomit, wt. loss, diarrhea
ACTH-pigmentation (not in secondary)
48
-- glucocorticoids?
```
hypoglycemia
intractable vomiting
abdominal pain
--BP
coma
death
```
49
Diagnose adrenocortical insufficiency? Exogeneous ACTH?
Give exogeneous ACTH
1. no ++ in cortisol (primary)
2. ++ cortisol (secondary)
50
Causes of Primary Adrenocortical insufficiency (acute)
```
Sudden steroid withdrawal
Hemorrhage
New born –hypoxia, prolonged delivery)
DIC
Bacteremia (Waterhouse- Frideiricsen’s)
```
Life threatening (coma --> death)
51
Causes of Primary Adrenocortical insufficiency (chronic)
Autoimmune (MCC- 70% pts) – Addison's
Infections- TB, Fungus
Adrenal metastasis
Genetic (AHC)
granuloma (infection)
52
Waterhouse-Friderichsen syndrome
MC = children with meningococcemia
Adrenal hemorrhage = uncertain
Histology =hemorrhage starts within medulla later into cortex
53
Adrenocortical Neoplasms
Functional / nonfunctional
Adenomas/ carcinoma
How to know functional or not = lab tests only (not by biopsy)
54
Adrenocortical adenoma
silent
incidental
small 2.5cm
yellow on cut section (lipid)
55
Adrenocortical carcinoma
Functional
Large >20cm
Death in 2 yrs
56
Normal Adrenal Medulla
1. Specialized neural crest (neuroendocrine) cells
2. Chromaffin cells= brown-black color after exposure to potassium dichromate
Paraganglion system= extra-adrenal Neuroendocrine cells
Synthesize/secrete catecholamines (mainly -Epinephrine or adrenaline)
57
Adrenal Medulla Neoplasms
1. Pheochromocytomas (chromaffin cells)
| 2. Neuronal (neuroblastoma, ganglioneuromas)
58
Pheochromocytoma
Synthesize and release catecholamines (more norepinephrine unlike normal gland)
59
Pheochromocytoma
| "rule of 10s"
```
10% - association with familial syndromes
10% - extra-adrenal
10% - bilateral
10% - biologically malignant
10% - arise in childhood
```
60
Average weight of pheochromocytoma?
100g
61
Light microscopy of pheochromocytoma?
Zellballon pattern = Cells in small nests or alveoli surrounded by a rich vascular network, "salt and pepper" chromatin
62
Electron microscopy of pheochromocytoma?
membrane-bound
| electron dense granules
63
Immunoreactivity of pheochromocytoma
1. neuronal markers (chromogranin and synaptophysin, NSE) in the chief cells
2. Sustentacular cells = S-100 protein (marker for schwann cells)
64
Criteria for determining malignancy of pheochromocytoma?
1. No single histologic feature = can predict clinical behavior
2. Definitive diagnosis of malignancy = metastases
65
Clinical course of pheochromocytoma?
1. dominant deature (HTN)
| 2. catecholamine cardiomyopathy
66
Laboratory diagnosis (pheochromocytoma)
1. ↑ urinary free catecholamines
| 2. metabolites = metanephrines, (VMA)
67
Multiple Endocrine Neoplasia Syndromes?
Proliferative lesions (hyperplasia, adenomas, and carcinomas) of multiple endocrine organs
68
Distinct features of MEN?
```
more aggressive and recur
multiple endocrine organs
multifocal
asymptomatic stage of endocrine hyperplasia
younger age
```
69
Treatment for MEN 2?
prophylactic thyroidectomy
70
```
MEN- TYPE 1
MC organ involved?
MC cause of morbidity and mortality?
MC site of gastrinoma?
Other associated lesions?
```
MC organ involved = Primary hyperparathyroidism
MC cause of morbidity/mortality =tumors of the pancreas
MC site of gastrinoma = duodenum
Other associated lesions = carcinoid tumors, thyroid and adrenocortical adenomas, and Lipoma
71
Familial Medullary thyroid cancer
In 20% of familial pts. (older age)
72
MEN-1
Wermer's
Pituitary
Parathyroid
Pancreas
Gene: MEN1-TSG (ch11)
73
MEN-2A
```
Sipple's
Parathyroid
Adrenal (pheochromocytoma)
Thyroid (C-cell hyperplasia, ***Medulalry carcinoma)***
RET gene (gain of function)
```
74
MEN-2B
```
no parathyroid
Adrenal (pheochromocytoma)
Thyroid (C-cell hyperplasia, Medulalry carcinoma)
Mucocutaneous ganglioneuromas
**Marfanoid**
```
RET (ch10)
