Endocrine Flashcards
(88 cards)
1
Q
InsuIin-independent transporters - GLUT1
A
RBCs, brain, cornea, placenta
2
Q
InsuIin-independent transporters - GLUT2
A
(bidirectional): beta islet cells, liver, kidney, GI
3
Q
InsuIin-independent transporters - GLUT3
A
brain, placenta
4
Q
InsuIin-independent transporters - GLUT5
A
(Fructose): spermatocytes, GI tract
5
Q
InsuIin-independent transporters - SGLTl/SGLT2
A
(Na+-glucose cotransporters):
kidney, small intestine
6
Q
Anabolic effects of insulin: (7)
A
Anabolic effects of insulin:
• Inc. glucose transport in skeletal muscle and adipose tissue
• Inc. glycogen synthesis and storage
• Inc. triglyceride synthesis
• Inc. Na+ retention (kidneys)
• Inc. protein synthesis (muscles)
• Inc. cellular uptake of K+ and amino acids
• Dec. glucagon release
• Dec. lipolysis in adipose tissue
Unlike glucose, insulin does not cross the placenta.
7
Q
insulin receptors - tyrosine kinase - activate two pathways:
A
Phosphoinositide-3 kinase pathway ->glicogen/lipid\protien synthesis + vesicles (GLUT 4)
RAS/MAP kinase pathway -> Cell growth and DNA synthesis
8
Q
Insulin regulation:
A
alfa 2 dec.
beta 2 inc.
9
Q
GHRH Analog
A
Tesamorelin - used to treat HIV-associated lipodystrophy.
10
Q
Oxytocin Modulates
A
fear, anxiety, social bonding, mood, and depression
MD SAFe
11
Q
TRH increases…
A
TSH
Prolactin
12
Q
Dopamine decreases…
A
TSH
Prolactin
13
Q
Somatostatin decreases…
A
TSH
GH
14
Q
Prolactin increases____ and decreases____.
A
increases dopamine and decreases GnRH.
15
Q
____,____,____ increases Prolactin
A
TRH
Estrogen (pregnancy)
Renal failure
(“RET”)
16
Q
GHRH induced by
A
P- Puberty E - Exercise G - hypoGlycemia S - deep Sleep S - Stress
17
Q
GHRH inhibited by
A
AGO: Aging Obesity Glucose Somatostatin Somatomedin
18
Q
other names for GH and IGF-1
A
GH - somatotropin
IGF-1 - somatomedin C
19
Q
GH metabolic effects:
A
dec. glucose uptake and Inc. lipolysis in FAT CELLS
20
Q
IGF-1 metabolic effects in the BONE:
A
BONE: Inc. amino acid uptake Inc. Protein synthesis Inc. DNA and RNA synthesis Inc. Chondroitin sulfate Inc. Collagen Inc. Cell size and number
21
Q
IGF-1 metabolic effects in the Muscle
A
Inc. amino acid uptake
Inc. Protein synthesis
22
Q
Cortisol function in general:
A
Cortisol is A BIG FIB.
Appetite increased
Blood pressure
Insulin resistance (diabetogenic)
Gluconeogenesis, lipolysis, and proteolysis all increase (dec. glucose utilization)
Fibroblast activity decreased (poor wound healing, dec. collagen synthesis - striae)
Inflammatory and Immune responses decreased
Bone formation decreased (dec. osteoblast activity)
23
Q
Cortisol function - blood pressure mechanisms
A
- Upregulates alfa 1 - receptors on arterioles - inc. sensitivity to norepinephrine and epinephrine (permissive action)
- At high concentrations can bind to mineralocorticoid (aldosterone) receptors
24
Q
Cortisol function - Inflammatory and Immune responses mechanisms
A
just CHILL:
C - Cells: Eosinopenia, lymphopenia
H - Histamin: Blocks histamine release from mast cells
I - IL-2: Blocks IL-2 production
L - leukotrienes and prostaglandins: Inhibits production of leukotrienes and prostaglandins
L - Loose WBC: Inhibits WBC adhesion -> neutrophilia
25
Calcium homeostasis: Plasma Ca2+ exists in three forms:
Plasma Ca2+ exists in three forms:
• Ionized/free (45%, active form)
• Bound to albumin (40%)
• Bound to anions (15%)
26
Calcium homeostasis: Regulation of PTH (pH/albumin/Ca2+)
Ionized/free Ca2+ is 1° regulator of PTH
changes in pH alter PTH secretion
changes in albumin concentration do not.
27
Calcium homeostasis: Inc. pH?
Inc. pH (less H+) -> albumin binds more Ca2l+ -> dec. ionized Ca2+ (eg, cramps, pain, paresthesias, carpopedal spasm) -> Inc. PTH.
28
Calcium homeostasis: Dec. pH?
Dec. pH (more H+) -> albumin binds less Ca2+ -> Inc. ionized Ca2+ -> dec. PTH.
29
PTH secretion induced by:
Dec. Ca2+
Dec. Mg2+
Dec. 1,25(OH) D3
Inc. PO4-
CaMPeD
30
PTH secretion inhibited by:
Very low Mg2+
| Inc. 1,25(OH) D3
31
Dec. Mg2+ caused by:
```
Diarrhea
Aminoglycosides
Diuretics
Alcohol abuse.
DADA!
```
32
25 (OH) D3 -> 1,25 (OH) D3 conversion induced by?
High PTH
Low PO4-
"induced by a high and a low P"
33
Functions of thyroid peroxidase include:
Oxidation
Organification of iodide
Cupling of monoiodotyrosine (MIT) and diiodotyrosine (DIT).
34
Wolff-Chaikoff effect-
Excess iodine temporarily turns off thyroid peroxidase - dec. T3 & T4 production (protective autoregulatory effect).
35
T3 functions in general:
"Energy for work and growing"
36
T3 functions - Energy:
* Blood sugar (Inc glycogenolysis, gluconeogenesis)
| * Break down lipids (inc. lipolysis)
37
T3 functions - Work:
Beta-adrenergic effects. Inc. beta 1 receptors in the heart -> t CO, HR, SV, contractility
(beta-blockers alleviate adrenergic symptoms in thyrotoxicosis)
Basal metabolic rate Inc. (via Na+/K+ ATPase activity -> Inc. O2 consumption, RR, body temperature)
38
T3 functions - Growing:
* Brain maturation
| * Bone growth (synergism with GH)
39
Thyroid hormones negative feedback
Negative feedback primarily by free T3/4:
• Anterior pituitary -dec sensitivity to TRH
• Hypothalamus - dec TRH secretion
All about the TRH
40
Thyroxine-binding globulin (TBG) increased and decreased by:
Increased: TBG in pregnancy, OCP use (estrogen)
Decreased: hepatic failure, steroid use, nephrotic syndrome
41
Signaling pathways of endocrine hormones - cAMP
"5 CAMPS":
1. FLAT - FSH, LH, ACTH, TSH
2. "2" ADH (V2-receptor), histamine (H2-receptor).
3. "Ca2+" - PTH, calcitonin
4. "weird" - CRH, GHRH
5. Sweet Black Baby - glucagon, MSH, hCG
42
Signaling pathways of endocrine hormones - cGMP
BNP, ANP, EDRF (NO)
43
Signaling pathways of endocrine hormones - IP3
G - GnRH
O - Oxytocin
A - ADH (V1-receptor)
T - TRH
H - Histamine (H1-receptor)
A - Angiotensin ll
G - Gastrin
44
Signaling pathways of endocrine hormones -
| Intracellular receptor
Adrenals Progesterone, Estrogen, Testosterone, Cortisol, Aldosterone, Thyroid and vitamin D.
45
Signaling pathways of endocrine hormones - Receptor tyrosine kinase
Insulin, IGF-1, FGF, PDGF, EGF
MAP kinase pathway
46
Signaling pathways of endocrine hormones - Nonreceptor tyrosine kinase
JAK/STAT pathway
G - G-CSF
E - Erythropoietin
T - Thrombopoietin
a
P - Prolactin
I - immunomodulators (eg, cytokines IL-2, IL-6, IFN)
G - GH
47
Neuroendocrine tumors contain a special type of enzyme.
Cells contain amine precursor uptake decarboxylase (APUD).
48
Neuroblastoma lab findings:(4)
Bombesin positive.
NSE positive.
Homer-Wright rosettes.
HVA and VMA (catecholamine metabolites) in the urine.
49
Neuroblastoma clinical findings: (4)
Children, usually< 4 years old.
Abdominal distension and a firm, irregular mass that can cross the midline.
Normotensive.
Opsoclonus-myoclonus syndrome ("dancing eyes-dancing feet").
50
Neuroblastoma pathology findings:
Originates from Neural crest cells.
N-myc oncogene.
Classified as an APUD tumor.
51
Carcinoid syndrome rules of 1/3 and 3's:
Rule of 1/3 and 3's:
1/3 metastasize
1/3 present with 2nd malignancy
1/3 are multiple
Telotristat (telo-3-stat) and octreotide.
Dec. B3 (used for serotonin synthesis)
Tricuspid regurgitation, pulmonic stenosis
52
Pheochromocytoma Rule of 10's:
```
10% malignant
10% bilateral
10% extra-adrenal (eg, bladder wall, the organ of Zuckerkandl)
10% calcify
10% of kids
```
53
Pheochromocytoma (5 P's):
```
Episodic hyperadrenergic symptoms (5 P's):
Pressure (inc BP)
Pain (headache)
Perspiration
Palpitations (tachycardia)
Pallor
```
54
Pheochromocytoma May be associated with germline mutations eg:
NF-1
VHL
RET (MEN 2A, 2B)
55
insulinoma - Whipple triad:
Low blood glucose
Symptoms of hypoglycemia (eg, lethargy, syncope, diplopia)
Resolution of symptoms after normalization of glucose levels.
56
Glucagonoma 5D's:
```
Dermatitis (necrolytic migratory erythema)
Diabetes (hyperglycemia)
DVT
Declining weight
Depression
```
57
Somatostatinoma -> Dec. secretion of:
Dec. secretion of: SIC G's
S -secretin
I - insulin
C - cholecystokinin
G - glucagon
G - gastrin
G - gastric inhibitory peptide (GIP).
58
Somatostatinoma - May present with:
```
D (cell) - GAS
diabetes/glucose intolerance
steatorrhea
gallstones
achlorhydria.
```
59
Zollinger-Ellison syndrome - Positive secretin stimulation test:
Positive secretin stimulation test: gastrin levels remain elevated after administration of secretin, which normally inhibits gastrin release.
60
Hypothyroidism - electrolytic changes:
hyponatremia (dec. free water clearance)
61
Hypothyroidism vs hyperthyroidism - Both present:
Periorbital edema (Hypothyroidism- myoedema)
Myopathy (Hypothyroidis- inc CK and myoedema, hyperthyroidism -osteoporosis)
Sex - Abnormal uterine bleeding, dec libido, infertility (hyperthyroidism -gynecomastia)
Myxedema (hyperthyroidism -pretibial myxedema)
62
Congenital hypothyroidism (cretinism) 6 P's:
```
Pot-bellied
Pale
Puffy-faced child
Protruding umbilicus
Protuberant tongue
Poor brain development.
```
63
Hashimoto thyroiditis risk and histology?
Risk of non-Hodgkin lymphoma (typically of B-cell origin)
Hurthle cells, lymphoid aggregates with germinal centers.
64
Riedel thyroiditis findings
Fibrosis may extend to local structures (eg, trachea, esophagus - mimicking anaplastic carcinoma. 1/3 are hypothyroid.
65
Riedel thyroiditis considered a manifestation of
Considered a manifestation of lgG4 - related systemic disease (eg, autoimmune pancreatitis, retroperitoneal fibrosis, noninfectious aortitis).
66
Graves disease - activation of...
Activation of T-cells - lymphocytic infiltration of retroorbital space -> inc cytokines (eg, TNF-alfa, IFN-gamma ) -> inc fibroblast secretion of hydrophilic GAGs -> inc osmotic muscle swelling, muscle inflammation, and adipocyte count -> exophthalmos.
67
Jod-Basedow phenomenon
Iodine-induced hyperthyroidism. This occurs when a patient with iodine deficiency and partially autonomous thyroid tissue (eg, autonomous nodule) is made iodine replete. It can happen after iodine IV contrast or amiodarone use. Opposite to the Wolff-Chaikoff effect.
68
Thyroid cancer - Complications of surgery include:
Hypocalcemia (due to the removal of parathyroid glands).
Transection of the recurrent laryngeal nerve - during ligation of the inferior thyroid artery.
Injury to the external branch of the superior laryngeal nerve - during ligation of superior thyroid vascular pedicle (noticeable in professional voice users).
69
Papillary carcinoma mutation(s):
RET/PTC rearrangements and BRAF mutations
70
Follicular carcinoma mutation(s):
RAS mutation and PAX8-PPAR-gamma translocations.
71
Medullary carcinoma mutation(s):
MEN 2A and 2B (RET mutations).
72
Anaplastic carcinoma mutation(s):
TP53 mutation.
73
Albright hereditary osteodystrophy:
shortened 4th/5th digits
short stature
obesity,
developmental delay.
74
Pseudohypoparathyroidism type 1A pathophysiology:
Autosomal dominant.
Due to inactive Gs protein alfa-subunit causing end-organ (kidney and bone) resistance to PTH.
hypocalcemia despite inc PTH levels.
Albright hereditary osteodystrophy
The defect must be inherited from the mother due to imprinting.
75
Pseudopseudohypoparathyroidism
Autosomal dominant.
Albright hereditary osteodystrophy
Without end-organ PTH resistance - PTH level normal and normal calcium levels.
Gs protein alfa-subunit inherited from the father - maternal a llele maintains responsiveness.
76
Familial hypocalciuric hypercalcemia
Excessive renal Ca2+ reabsorption -> mild hypercalcemia and hypocalciuria with normal to inc PTH levels.
Defective G-coupled Ca2+- sensing receptors in multiple tissues
Higher than normal Ca2+ levels required to suppress PTH.
77
Hypopituitarism (causes for) :
```
R - Radiation
A - apoplexy
I - injury to the brain
N - Nonsecreting pituitary adenoma, craniopharyngioma
E - Empty sella syndrome
S - Sheehan syndrome
```
78
pegvisomant
GH receptor antagonist
79
Laron syndrome
Autosomal recessive.
Defective GH receptors:
dec linear growth
inc GH,
dec IGF-1.
Clinical features: short stature (dwarfism), small head circumference, characteristic facies with saddle nose and prominent forehead, delayed skeletal maturation, small genitalia.
80
SIADH causes include:
```
L - Lung disease
A - ADH (Ectopic - small cell lung cancer)
C - CNS disorders/head trauma
e - empty.
D - Drugs (eg, cyclophosphamide)
```
81
Drugs affecting ADH:
Analog: Desmopressin
antagonist: conivaptan, tolvaptan, demeclocycline
82
MEN2B
Medullary thyroid carcinoma
Pheochromocytoma
MucosaI neuromas (oral/intestinal ganglioneuromatosis)
Associated with marfanoid habitus; mutation in RET gene
83
MEN syndromes
MEN1 = 3 P's: Pituitary, Parathyroid, and Pancreas
MEN2A = 2 P's: Parathyroid and Pheochromocytoma, Medullary thyroid carcinoma
MEN2B = 1 P: Pheochromocytoma, Medullary thyroid carcinoma, MucosaI neuromas
84
Demeclocycline USE AND ADVERSE EFFECTS
USE: SIADH
ADVERSE EFFECTS: Nephrogenic DI, photosensitivity, abnormalities of bone and teeth.
85
Fludrocortisone
MECHANISM
USE
ADVERSE EFFECTS
MECHANISM: Synthetic analog of aldosterone wi th little glucocorticoid effects.
USE: Mineralocorticoid replacement in primary adrenal insufficiency
ADVERSE EFFECTS: Similar to glucocorticoids; also edema, exacerbation of heart failure, hyperpigmentation. (black heart)
86
Somatostatin (octreotide) USE
A - Acromegaly
C - Carcinoid syndrome
E - Esophageal varices
Gs' - gastrinoma, glucagonoma
87
GH USE
GH deficiency, Turner syndrome.
88
Desmopressin USE
Central DI, von Willebrand disease, sleep enuresis, hemophilia A.
