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β–Ί Med 11 - USMLE 1 > Endo > Flashcards

Flashcards in Endo Deck (199):
1

Thyroid development
Where does it arise from?
Where does it descend to?
Connected to what by what?

Thyroid diverticulum arises from floor of primitive pharynx. Descends into neck. Connected to tongue by thyroglossal duct, which normally disappears but may persist as pyramidal lobe of thyroid

2

Foramen Cecum

Normal remnant of thyroglossal duct in tongue

3

Most common ectopic thyroid tissue site

Tongue

4

Presentation of thyroglossal duct cyst

Anterior midline neck mass that moves with swallowing

5

Presentation of persistent cervical sinus leading to branchial cleft cyst in lateral neck

Small mobile mass on side of neck that does not move with swallowing

6

What does the Fetal Adrenal Gland consist of?

Outer adult zone and inner active fetal zone

7

Adult zone of fetal adrenal gland
Activity?
Control of activity?

Dormant during early fetal life but begins to secrete cortisol late in gestation
Fetal pituitary and placenta make ACTH and CRH

8

What is fetal cortisol responsible for?

Fetal lung maturation and surfactant production

9

Embryological origin of adrenal cortex?

Mesoderm

10

Embryological origin of adrenal medulla?

Neural Crest Cells

11

Layers of Adrenal Gland w/ Secretory Products

"GFR --> Salt, Sugar, Sex
Deeper you go, the sweeter it gets"
Capsule
Zona Glomerulosa --> Aldosterone
Zona Fasciculata --> Cortisol, Sex Hormones
Zona Reticularis --> Sex Hormones (androgens)
Medulla --> Catecholamines (NE, Epi)

12

Zona Glomerulosa
Responsive to
Secretory Product

Renin-Angiotensin --> Aldosterone

13

Zona Fasciculata
Responsive to
Secretory Product

ACTH, Hypothalamic CRH --> Cortisol, Sex Hormones

14

Zona Reticularis
Responsive to
Secretory Product

ACTH, Hypothalamic CRH --> Sex Hormones (androgens)

15

Adrenal Medulla
Responsive to
Secretory Product

Preganglionic sympathetic fibers --> ACh --> Catecholamines (NE, Epi)

16

Most common tumor of adrenal medulla in adults?

Pheochromocytoma

17

Most common tumor of adrenal medulla in children?

Neuroblastoma

18

Pheochromocytoma vs Neuroblastoma in terms of clinical presentation

P --> episodic HTN

19

Adrenal gland venous drainage

L Adrenal --> L Adrenal Vein --> L Renal Vein --> IVC
R Adrenal --> R Adrenal Vein --> IVC

20

Posterior Pituitary Gland
AKA
Products
Source of products?
How are they transported?
Embryological origin

Neurohypophysis
Secretes ADH and Oxytocin made in hypothalamus and shipped to PP via neurophysins (carrier proteins)
Derived from neuroectoderm

21

Anterior Pituitary Gland
AKA
Secretory Products
Embryological origin

Adenohypophysis
"My FLAT PiG"
Melanotropin (MSH), FSH, LH, ACTH, TSH, Prolactin, GH
Derived from oral ectoderm (Rathke's Pouch)

22

Acidophils in the Anterior Pituitary gland secrete

GH and Prolactin

23

Basophils in the Anterior Pituitary gland secrete

"B FLAT"
Basophils --> FSH, LH, ACTH, TSH

24

Which hormones share the same Ξ± subunit?

FSH, LH, TSH, and hCG

25

Endocrine Pancreas
Name
Cell types: Products and Location
Embryological origin?

Islets of Langerhans
"INsulin is on the INside"
Ξ±: Glucagon, Peripheral
Ξ²: Insulin, Central
Ξ΄: Somatostatin, Interspersed
Pancreatic Buds

26

Mechanism of Insulin Release

↑ Glucose metabolism --> ↑ ATP --> closing of K channels --> depolarization --> V gated Ca channels open --> insulin secretion

27

Does insulin cross the placenta?

No

28

What organs take up glucose independently of insulin?

"BRICK L"
Brain, RBCs, Intestines, Cornea, Kidney, Liver

29

GLUT1

Insulin independent in Brain and RBCs

30

GLUT2

Bidirectional in Ξ² cells, liver, kidney, and small intestine

31

GLUT4

Insulin dependent in adipose tissue and skeletal muscle

32

Effects of Insulin

Anabolic
↑ G transport into skeletal muscles and adipose tissue
↑ Glycogen synthesis and storage
↑ Triglyceride synthesis and storage
↑ Na retention by kidneys
↑ Protein synthesis in muscles
↑ K uptake by cells
↑ AA uptake by cells
↓ Glucagon release

33

What triggers an ↑ in insulin release

Hyperglycemia
GH (via insulin resistance)
Ξ²2 agonists

34

What triggers a ↓ in insulin release

Hypoglycemia, Somatostatin, Ξ±2 agonists

35

Insulin Receptor Cellular Pathway

Insulin --> Tyrosine Phosphorylation --> IP3 and RAS/MAP
IP3 --> Glycogen, Lipid, + Protein synthesis and GLUT4 vesicle mobilization
MAP/RAS --> Cell Growth and DNA synthesis

36

What does the brain use for energy during starvation?

Ketone bodies

37

What do RBCs use for energy during starvation

RBCs can only use glucose b/c they cannot preform aerobic respiration

38

Functions of Glucagon

Catabolic
↑ Gluconeogenesis, Glycogenolysis, Lipolysis, Ketone production

39

What is glucagon secreted in response to?

Hypoglycemia

40

What inhibits glucagon production?

Insulin, Hyperglycemia, Somatostatin

41

What does TRH do?

TRH --> TSH and Prolactin

42

What does DA do in the Pituitary gland?

DA --/ prolactin

43

What does CRH do?

CRH --> ACTH, Melanocyte Stimulating Hormone (MSH), Ξ²-endorphin

44

What does GHRH do?

GHRH --> GH

45

What does somatostatin do in the Pituitary?

Somatostatin --/ GH and TSH

46

What does GnRH do?

GnRH --> FSH and LH

47

What does Prolactin do in the pituitary?

Prolactin --/ GnRH

48

Prolactin
Source
Function in Breast
Function in Pituitary

Anterior Pituitary Gland
Stimulates milk production in breasts
Prolactin --/ GnRH synthesis and release which leads to an inhibition of ovulation and spermatogenesis

49

Regulation of Prolactin Secretion

DA from Hypothalamus --/ Prolactin secretion from Anterior Pituitary
Prolactin in turn increases DA synthesis and secretion in the Hypothalamus thereby inhibiting its own secretion
TRH --> Prolactin secretion

50

Affects of DA agonists on prolactin?

DA agonists (bromocriptine) inhibit prolactin and can be used to treat prolactinoma

51

What stimulates prolactin secretion?

TRH, DA antagonists (antipsychotics) and Estrogens (OCP, pregnancy)

52

Growth Hormone
Name
Source
Function and MoA
Pattern of release
Regulation

Somatotropin
Anterior Pituitary Gland
Stimulates linear growth and muscle mass through IGF1/somatomedin secretion
↑ Insulin Resistance (Diabetogenic)
Pulsatile release in response to GHRH
Secretion ↑ during exercise and sleep
Secretion inhibited by glucose and somatostatin

53

Excess GH in adults vs children

Acromegaly in adults
Gigantism in children

54

Desmolase
Regulation
Action

ACTH --> Desmolase
Ketoconazole --/ Desmolase
D turns Cholesterol into Pregnenolone

55

Path of Aldosterone Synthesis

Pregnenolone --> [3Ξ² Hydroxysteroid dehydrogenase] --> Progesterone --> [21 hydroxylase] --> 11 deoxycorticosterone --> [11Ξ² hydroxylase] --> corticosterone --> [aldosterone synthase] --> Aldosterone

56

Path of Cortisol Synthesis

Pregnenolone --> [17Ξ± hydroxylase] --> 17 hydroxypregnenolone --> [3Ξ² Hydroxysteroid dehydrogenase] --> 17 hydroxyprogesterone --> [21 hydroxylase] --> 11 deoxycortisol --> [11Ξ² hydroxylase] --> Cortisol
or...
Pregnenolone --> [3Ξ² Hydroxysteroid dehydrogenase] --> Progesterone --> [17Ξ± hydroxylase] --> 17 hydroxyprogesterone -->

57

Path of Testosterone and DHT production

Pregnenolone --> [17Ξ± hydroxylase] --> 17 hydroxypregnenolone --> Dehydroepiandrosterone (DHEA) --> [3Ξ² Hydroxysteroid dehydrogenase] --> Androstenedione --> Testosterone --> [5Ξ± reductase] --> DHT
or...
17 hydroxyprogesterone --> Androstenedione

58

Synthesis of Peripheral Estrogens

Aromatase turns Androstenedione into Estrone
Aromatase turns Testosterone into Estradiol
Estrone can convert to Estradiol

59

Deficiencies in Bilateral Adrenal Hyperplasias

17Ξ± hydroxylase, 21 hydroxylase, 11Ξ² hydroxylase

60

Why do adrenal enzyme deficiencies lead to hyperplasia

↑ ACTH stimulation because of ↓ cortisol

61

17Ξ± hydroxylase deficiency
Mineralcorticoids
Cortisol
Sex Hormones
Presentation
Male vs Female

Mineralcorticoids ↑
Cortisol ↓
Sex Hormones ↓
HTN, HypoK
Male: ↓ DHT --> pseudohermaphroditism (variable, ambiguous genitalia with undescended testes)
Female: Externally phenotypic female with normal internal sex organs but lack secondary sex characteristics

62

21 hydroxylase deficiency
Mineralcorticoids
Cortisol
Sex Hormones
Presentation

Mineralcorticoids ↓
Cortisol ↓
Sex Hormones ↑
Hypotension, HyperK, ↑ Renin activity, Volume depletion
Masculinization leading to pseudohermaphroditism in females

63

11Ξ² hydroxylase deficiency
Mineralcorticoids
Cortisol
Sex Hormones
Presentation

Mineralcorticoids:
↓ Aldosterone, ↑ 11-deoxycorticosterone
Cortisol ↓
Sex Hormones ↑
HTN, Masculinization

64

Cortisol
Source
Function
Regulation

Adrenal Zona Fasciculata
"BBIIG"
Maintains BP
↓ Bone formation
↑ Insulin Resistance
AntiInflammatory/Immunosuppressive
↑ Gluconeogenesis, lipolysis, proteolysis
Inhibits Fibroblasts --> striae
CRH (hypothalamus) --> Anterior Pituitary --> ACTH --> Cortisol production in Zona Fasciculata

65

How is cortisol transported in the blood?

Corticosteroid binding globulin (CBG)

66

How does cortisol maintain BP?

Upregulates Ξ±1 receptors on arterioles --> ↑ sensitivity to NE and Epi

67

How is cortisol an anti-inflammatory/immunosuppressive?

--/ production of leukotrienes and prostaglandins
--/ leukocyte adhesion
--/ histamine release
Reduces eosinophils
--/ IL2 production

68

How does excess cortisol alter CRH, ACTH and Cortisol secretion

Decreases all of them

69

How does chronic stress affect cortisol secretion?

Stress induces prolonged secretion

70

PTH
Source
Function

Chief Cells of Parathyroid
↑ Bone resorption of Ca and PO4
↑ Kidney reabsorption of Ca in DCT
↑ Calcitriol production by stimulating kidney 1Ξ± Hydroxylase
↓ Reabsorption of PO4 in PCT

71

Regulation of PTH

↓ Serum Ca --> ↑ PTH
↓ Serum Mg --> ↑ PTH
↓↓ Serum Mg --> ↓ PTH
↑ Vit D --> ↓ PTH

72

Common causes of ↓ Mg

Diarrhea, Aminoglycosides, Diuretics, EtOH abuse

73

Number of Parathyroid glands

4 glands

74

How does PTH affect bone

Stimulate Ca release from bone mineral compartment
Stimulates osteoblastic cells
Stimulates bone resorption via indirect effect of osteoclasts
Enhances bone matrix degradation

75

Actions of Vit D

↑ Intestinal absorption of Ca and PO4
↑ Release of PO4 from bone matrix
↑ Bone resorption of Ca and PO4

76

Clinical manifestation of high PTH

↑ serum Ca, ↓ serum PO4, ↑ urine PO4

77

How does PTH affect osteoblasts and osteoclasts

PTH --> ↑ production of M-CSF and RANK-L in osteoblasts which stimulates osteoclasts

78

Source of Vit D

D3 from sun exposure in skin
D2 ingested from plants
Both converted to 25-OH in liver and 1,25-(OH)2 in the kidney

79

Regulation of Vit D

↑ PTH, ↓ [Ca], ↓ PO4 --> ↑ VitD
↑ Vit D inhibits its own production

80

24,25-(OH)2 D3

Inactive form of VitD

81

VitD deficiency in adults vs children

Children --> rickets
Adults --> osteomalacia

82

Calcitonin
Source
Function
Regulation

Parafollicular cells (C cells) of thyroid
↓ bone resorption of Ca
↑ serum Ca --> calcitonin secretion

83

Normal role of Calcitonin

"CalciTONin TONes down Ca levels"
Not important in normal Ca homeostasis but when active, opposes PTH

84

Which hormones use cAMP

"Go Go FLAT ChAMP"
GHRH, Glucagon, FSH, LH, ACTH, TSH, CRH, Calcitonin, ADH (V2 receptor), MSH, PTH

85

Which hormones use cGMP

"Vasodilators"
ANP, NO, EDRF (Endothelial Derived Relaxing Factor)

86

Which hormones use IP3

"HAG GGOAT"
Histamine (H1), Angiotensin II, Gastrin, GnRH, Oxytocin, ADH (V1 receptor), TRH

87

Hormones that use steroid receptors

"VETTT CAP"
VitD, Estrogen, Testosterone, T3/T4, Cortisol, Aldosterone, Progesterone

88

Hormones that use Intrinsic Tyrosine Kinases

"MAP kinase pathway - Think growth factors"
Insulin, IGF1, FGF, PDGF, EGF

89

Hormones that use Receptor-Associated (Non-Receptor) Tyrosine Kinase

JAK/STAT pathway
Think Acidophiles and cytokines - "PIG"
Prolactin, Immunomodulators (cytokines IL2, IL6, IL8, IFN), GH

90

In men, what are the effects of ↑ sex hormone binding globulin

Lowers free testosterone --> gynecomastia

91

In women, what are the effects of ↓ sex hormone binding globulin

Raises free testosterone --> hirsutism

92

In a women, what happens to SHBG during pregnancy?

↑ SHBG

93

Thyroid Hormone
Formulations
Source

T3 and T4
Follicles of thyroid. Most T3 is formed in target tissues

94

Function of Thyroid Hormone

T3 --> 4 Bs
Brain maturation
Bone Growth (synergism with GH)
Ξ² adrenergic effects: ↑ Ξ²1 receptors in heart --> ↑ CO, HR, SV, and contractility
↑ Basal metabolic rate: ↑ Na/K ATPase activity --> ↑ O2 consumption, RR, body Temp
↑ glycogenolysis, gluconeogenesis, lipolysis

95

How is TH transported in the blood
When is it active?

Thyroxine binding globulin binds most T3/T4 in blood
Only free hormone is active

96

When does TBG levels change?

↓ TBG in hepatic failure
↑ TBG in pregnancy or OCP (estrogen ↑ TBG)

97

What is the major thyroid product?
What is it converted into?
Where is it converted?
What converts it?

T4
Converted to T3 in peripheral tissues by 5'-deiodinase

98

Which thyroid product binds with greater affinity?

T3

99

Peroxidase in Thyroid

Oxidation and organification of Iodide as well as coupling of MIT and DIT

100

Propylthiourcil
MoA
Use
Tox

Inhibits Peroxidase and 5'-deiodinase
Hyperthyroidism
Tox: skin rash, agranulocytosis, aplastic anemia, hepatotoxicity

101

Methimazole
MoA
Use
Tox

Inhibits Peroxidase
Hyperthyroidism
Tox: skin rash, agranulocytosis, aplastic anemia, teratogen

102

Thyroid Hormone Regulation

Hypothalamus --> TRH --> Pituitary --> TSH --> Follicular cells of thyroid gland --> TH
Negative feedback by T3 to anterior pituitary ↓ sensitivity to TRH

103

Wolff-Chaikoff Effect

Excess I temporarily inhibits thyroid peroxidase --> ↓ iodine organification --> ↓ T3/T4 production

104

Function of Follicular Cells in Thyroid Gland

Take up I- and oxidize it to I2 for excretion into lumen. In lumen TG and I2 form MIT and DIT.
Take up TG and proteolysis occurs to release T3/T4

105

Cushing's Syndrome
Primary Pathophysiology
Different kinds of causes

↑ cortisol
Exogenous vs Endogenous causes

106

#1 cause of Cushing's syndrome?

Exogenous steroids --> ↓ ACTH

107

Endogenous causes of Cushing's Syndrome

Cushing's Disease (70%): ACTH secretion from pituitary adenoma
Ectopic ACTH (15%): Non pituitary tissue makes ACTH (usually small cell lung cancer, bronchial carcinoids)
Adrenal (15%): adenoma, carcinoma, nodular adrenal hyperplasia. Low ACTH

108

Presentation of Cushing's Syndrome

HTN, Wt Gain, Moon facies, Truncal obesity, Buffalo hump, Hyperglycemia (insulin resistance), Skin changes (thinning, striae),peptic ulcers, osteoporosis, amenorrhea, immune suppression

109

Dexamethasone Suppression Test on Cortisol
Normal
ACTH pituitary tumor
Ectopic ACTH producing tumor
Cortisol producing tumor

Low dose High Dose
Suppressed Suppressed
Remains ↑ Suppressed
Remains ↑ Remains ↑
Remains ↑ Remains ↑

110

Primary Hyperaldosteronism
Causes
Presentation
Distribution
Treatment

Adrenal hyperplasia or aldosterone secreting adrenal adenoma (Conn's Syndrome)
HTN, HypoK, Metabolic alkalosis, low Renin
Maybe bilateral or unilateral
Surgery to remove tumor and/or spironolactone

111

Secondary Hyperaldosteronism
Pathophysiology
Underlying Causes
Associated with...
Treatment

Renal perception of low intravascular volume --> overactive Rennin-Angiotensin system
Due to Renal Artery Stenosis, Chronic Renal Failure, CHF, Cirrhosis, Nephrotic Syndrome
Associated with high Renin levels
Treat with Spironolactone

112

Addison's Disease
What is it?
Pathophysiology
Presentation
Diseases that can lead to it

"Adrenal Atrophy and Absence of hormones from All 3 cortical layers"
Chronic primary adrenal insufficiency due to adrenal atrophy or destruction.
Deficiency in aldosterone and cortisol leads to hypotension (hyponatremic volume contraction), hyperK, acidosis, skin hyper-pigmentation
Autoimmune, TB, Metastatic Cancer

113

Why is skin hyper-pigmented in Addison's disease?

MSH, a byproduct of ACTH production from POMC, is elevated

114

How is Primary adrenal insufficiency different from Secondary adrenal insufficiency

Secondary is from ↓ pituitary ACTH. No skin hyper-pigmentation and no hyperK

115

Waterhouse-Friderichsen Syndrome
What is it?
What is it due to?
What conditions is it associated with?

Acute Primary adrenal insufficiency
Due to adrenal hemorrhage
Associated with Neisseria meningitidis septicemia, DIC, and endotoxic shock

116

Pheochromocytoma
Arise from
Most tumors secrete
Findings
Associated with what other diseases?

Arise from chromaffin cells (neural crest cells)
Most secrete Epi, NE, and DA
Episodic HTN, Urinary vanillyl mandelic acid (VMA), ↑ plasma catecholamines
Associated with neurofibromatosis type 1, MEN Type 2A and 2B

117

Treatment of Pheochromocytoma

Tumor surgically removed only after effective Ξ± and Ξ² blockade is achieved
Irreversible Ξ± antagonists (phenoxybenzamine) must be given first to avoid hypertensive crisis. Ξ² blockers are then given to slow heart rate

118

Symptoms of episodic HTN

Pressure (elevated BP)
Pain (headache)
Perspiration
Palpitations (tachycardia)
Pallor

119

Rule of 10 with Pheochromocytoma

10% malignant
10% bilateral
10% extra-adrenal
10% calcify
10% kids

120

Path of DA, NE and Epi synthesis

Phenylalanine --> Tyrosine --> L DOPA --> DA --> NE --> Epi

121

Product of DA metabolism

HVA

122

Product of NE and Epi metabolism

VMA

123

Neuroblastoma
Frequency
Location
Findings
Presentation
Genetics

Most common tumor of adrenal medulla in children
Can occur anywhere along the sympathetic chain
HVA elevated in urine
HTN less likely to develop
Overexpression of N-myc oncogene associated with rapid tumor progression

124

Hypothyroidism
Temp
Wt
Activity
GI
Reflexes
Myxedema
Skin
Hair
Heart
TSH
TH

Cold intolerance
Wt Gain with ↓ appetite
Hypoactivity, lethargy, fatigue, weakness
Constipation
↓ reflexes
facial/periorbital myxedema
Dry cool skin
Coarse brittle hair
Bradycardia, SOBE
↑ TSH
↓ free T4

125

Hyperthyroidism
Temp
Wt
Activity
GI
Reflexes
Myxedema
Skin
Hair
Heart
TSH
TH

Heat intolerance
Wt loss with ↑ appetite
Hyperactivity
Diarrhea
↑ reflexes
Pretibial myxedema
Warm moist skin
Fine hair
Chest pain, palpitations, arrhythmias, ↑ Ξ² adrenergic receptors
↓ TSH (if primary)
↑ Free or total T3 and T4

126

Hashimoto's Thyroiditis
Kind of thyroidism
Frequency
Pathophysiology
Genetics
Risk
Histology
Physical exam
Course of disease

Hypothyroidism
Most common cause of hypothyroidism
Autoimmune disorder (thyroid peroxidase and anti thyroglobulin Abs)
Associated with HLA DR5
Increased risk of non-Hodgkin's lymphomas
Hurthle cells, lymphocytic infiltrate with germinal centers
Moderately enlarged nontender thyroid
May be hyperthyroid early in course (thyrotoxicosis during follicular rupture)

127

Cretinism
Kind of thyroidism
Pathophysiology with circumstances
Findings

Fetal Hypothyroidism
Endemic: Lack of dietary iodine
Sporadic: Defect in T4 formation or developmental failure in thyroid formation
Pot bellied, Pale, Puffy face, Protruding umbilicus and Protuberant tongue

128

Subacute Thyroiditis
Name
Kind of thyroidism
Description
Usually follows
Histology
Findings
Course

de Quervain's Hypothyroidism
Self limited
Often following flu like illness
Granulomatous inflammation
↑ ESR, Jaw pain, early inflammation, tender thyroid
May be hyperthyroidism early in course

129

Reidel's Thyroiditis
Kind of thyroidism
Pathophysiology
Findings

Hypothyroidism
Thyroid replaced by fibrous tissue (considered a manifestation of IgG4 related systemic disease)
Fixed, hard, painless goiter

130

Toxic multinodular goiter
Kind of thyroidism
PathoPhys
Malignant?

Hyperthyroidism
Focal patches of hyperfunctioning follicular cells working independently of TSH due to mutation of TSH receptor
Rarely malignant

131

Jod-Basedow Phenomenon

Thyrotoxicosis if a pt with iodine deficiency goiter is made iodine replete

132

Graves' Disease
Kind of thyroidism
PathoPhys
Presentation
Often presents during

Hyperthyroidism
Autimmune with thyroid stimulating immunoglobulins
Ophthalmopathy (proptosis, EOM swelling), pretibial myxedema, ↑ connective tissue deposition, diffuse goiter
Often presents during stress (childbirth)

133

Thyroid Storm
Kind of thyroidism
What is it?
What does it cause?
What causes it?
Findings

Hyperthyroidism
Stress-induced catecholamine surge leading to death by arrhythmia
Seen as a complication of Graves' and other hyperthyroid disorders
↑ ALP due to increased bone turnover

134

Papillary Thyroid Carcinoma
Frequency
Prognosis
Histology
Predisposing factors

Most common thyroid cancer
Excellent prognosis
empty-appearing nuclei (Orphan Annie's Eyes), Psammoma bodies, Nuclear grooves,
↑ risk with childhood radiation

135

Follicular Thyroid Carcinoma
Prognosis
Histology

Good prognosis
Uniform follicles

136

Medullary Thyroid Carcinoma
Source
What molecules does it produce?
Histology
Associated with what other diseases

Parafollicular C cells
Produces calcitonin
Sheets of cells in amyloid stroma
Associated with MEN types 2A and 2B

137

Undifferentiated/anaplastic thyroid cancer
Kind of pt?
Prognosis

Older pt with very poor prognosis

138

What is thyroid lymphoma associated with?

Hashimoto's Thyroiditis

139

Primary Hyperparathyroidism
Usually caused by...
Findings
Symptoms

Usually an adenoma
HyperCa, Hypercalciuria (renal stones), ↑PTH, ↑ALP, ↑cAMP in urine
Often asymptomatic but can present with weakness and constipation

140

Osteitis Fibrosa Cystica

↑ PTH --> Cystic bone spaces filled with brown fibrous tissue --> bone pain

141

Secondary Hyperparathyroidism
What causes it?
Most often seen in what disease?
Findings

↓ Gut Ca absorption and ↑ Phosphate
Most often in chronic renal disease (low VitD)
HypoCa, HyperPO4 (in chronic renal disease), HypoPO4 (with other causes), ↑ALP, ↑PTH

142

Renal Osteodystrophy

Bone lesion due to secondary or tertiary hyperparathyroidism due to renal disease

143

Tertiary Hyperparathyroidism
What causes it?
Findings

Refractory (autonomous) hyperparathyroidism resulting from chronic renal disease. ↑↑PTH and ↑ Ca

144

Hypoparathyroidism
Causes
Findings

Surgical excision, autoimmune, DiGeorge Syndrome
HypoCa, Tetany, Chvostek's Sign, Trousseau's Sign.

145

Chvostek's Sign

Tapping of facial nerve --> contraction of facial muscles

146

Trousseau's Sign in Hypoparathyroidism

Occlusion of brachial artery w/ BP cuff --> carpal spasm

147

PseudoHypoparathyroidism
Name
Genetics
PathoPhys
Findings

Albright's Hereditary Osteodystrophy
Autosomal dominant
Kidney unresponsive to PTH
HypoCa, Shortened 4th/5th digit, short stature

148

Low Ca, High PTH

Secondary Hyperparathyroidism

149

Low Ca, Low PTH

Hypoparathyroidism

150

High Ca, High PTH

Primary Hyperparathyroidism

151

High Ca, Low PTH

PTH independent HyperCalcemia

152

Most common pituitary adenoma

Prolactinoma

153

Prolactinoma
Findings
Treatment

Amenorrhea, Galactorrhea, Low Libido, Infertility
DA agonist (bromocriptine or cabergoline)

154

Common presentation of pituitary adenoma

Bitemporal hemianopia from impingement on optic chiasm

155

Acromegaly
What is it?
What causes it?
Findings

Excess GH in adults
Typically caused by pituitary adenoma
Large tongue with deep furrows, Course facial hair, Insulin resistance

156

Acromegaly
Diagnosis
Treatment

↑ serum IGF1; Failure to suppress serum GH following oral glucose tolerance test; Pituitary mass on MRI
Resection followed by somatostatin analog (Octreotide)

157

Diabetes Insipidus
PathoPhys
Presentation

Central: Lack of ADH (pituitary tumor, trauma, surgery, histiocytosis x)
Nephrogenic: Lack of renal response to ADH (hereditary, hyperCa, Li, demeclocycline)
Thirst and Polyuria

158

Diabetes Insipidus
Findings
Diagnosis
Treatment

Urine specific gravity 290
Water deprivation test (urine osmolality doesn't ↑)
Response to desmopressin distinguishes central vs nephrogenic
Fluid intake. For central: intranasal desmopressin. For Nephrogenic: hydrochlorothiazide, indomethacin, or amiloride

159

SIADH
Characteristics
Normal body response
Dangerous complication
Possible causes
Treatment

Excess water retention, Low Na, Urine osmolarity > serum osmolarity
Body responds with ↓ aldosterone
Low Na can lead to seizures
Ectopic ADH (small cell lung cancer), CNS disorder, Head trauma, Pulmonary disease, Drugs (cyclophosphamide)
Fluid restriction, IV saline, Conivaptan, Tolvaptan, Demeclocycline

160

Hypopituitarism
What causes it?
Treatment

Nonsecreting pituitary adenoma, craniopharyngioma
Sheehan's Syndrome
Empty Sella Syndrome
Brain injury, hemorrhage
Radiation
Treat with substitution therapy

161

Sheehan's Syndrome

Postpartum ischemic infarct of pituitary. Usually presents with failure to lactate

162

Empty Sella Syndrome

Atrophy or compression of the pituitary. Often idiopathic. Common in obese women

163

Acute manifestations of Diabetes Mellitus

Polydipsia, Polyuria, Polyphagia, Wt loss, DKA (type1), HHS (type2), Unopposed secretion of GH and Epi (exacerbate hyperglycemia)

164

Reason for coma and death in DM?

Dehydration and Acidosis

165

Chronic manifestations of DM?

Nonenzymatic glycosylation and Osmotic damage

166

Nonenzymatic Glycosylation in DM

Small Vessels: diffuse thickening of basement membrane --> retinopathy (hemorrhage, exudates, microaneurysm, vessel proliferation), glaucoma, nephropathy (nodular sclerosis, progressive proteinuria, chronic renal failure, arteriosclerosis leading to HTN, Kimmelstiel Wilson nodules)
Large Vessels: Atherosclerosis, CAD, Peripheral vascular occlusive disease, gangrene --> limb loss cerebrovascular disease

167

Osmotic Damage in DM

Sorbitol accumulation in organs with aldose reductase
Neuropathy (motor, sensory, autonomic)
Cataracts

168

Tests for DM

Fasting serum glucose
Oral GTT
HbA1C (3 months)

169

DM1
Defect
Insulin in treatment
Age
Obesity
Genetics
HLA
Glucose intolerance
Insulin sensitivity
Ketoacidosis
Ξ² cell #
Serum insulin level
Classic symptoms
Histology

Autoimmune destruction of Ξ² cells
Insulin always used
Pt

170

DM2
Defect
Insulin in treatment
Age
Obesity
Genetics
HLA
Glucose intolerance
Insulin sensitivity
Ketoacidosis
Ξ² cell #
Serum insulin level
Classic symptoms
Histology

Insulin resistance with progressive Ξ² cell failure
Insulin sometimes used
Pt >40
Obese
Strong genetic connections
No HLA
Mild to moderate glucose intolerance
Low insulin sensitivity
Rare ketoacidosis
Ξ² cell # variable w/ amyloid deposits
Variable insulin levels
Classic symptoms occur sometimes
Islet amyloid deposits

171

Diabetic Ketoacidosis
Which DM
What precipitates it?
PathoPhys

DM1
Usually due to ↑insulin requirement from ↑ stress (infection)
Excess fat breakdown and ↑ ketogenesis from ↑ free fatty acids which are then made into ketone bodies (Ξ² hydroxybutyrate > acetoacetate)

172

DKA
Signs and Symptoms
Labs

Kussmaul Respirations, nausea, vomiting, abdominal pain psychosis/delirium, dehydration, fruity breath odor (acetone)
Hyperglycemia, ↑H+, ↓Bicarb (aniongap metabolic acidosis), ↑ blood ketone levels, leukocytosis, HyperK (but depleted intracellular K)

173

DKA
Complications
Treatment

Mucormycosis, Rhizopus infection, cerebral edema, cardiac arrhythmias, heart failure
IV fluids, IV insulin, K, Glucose

174

Carcinoid Syndrome
Most common tumor of which organ?
Rule of 1/3
Lab findings

Appendix
1/3 metastasize, 1/3 malignant, 1/3 multiple
5-HIAA in urine and niacin deficiency

175

MEN1
Name
Location of tumors
Common presentation

Wermer's Syndrome
"Diamond"
Pituitary (Prolactin, GH)
Parathyroid
Pancreas (Zollinger Ellison, Insulinomas, VIPomas, Glucagonomas)
Commonly presents with kidney stones and stomach ulcers

176

MEN2A
Name
Location of tumors

Sipple's Syndrome
"Square"
Parathyroid and Pheochromocytomas
Medullary thyroid carcinomas (calcitonin)

177

MEN2B

"Triangle"
Oral/intestinal ganglioneuromatosis (associated with marfanoid habitus)
Pheochromocytoma
Medullary thyroid carcinomas (calcitonin)

178

Genetics of MEN syndromes

Autosomal dominant
2A and 2B associated with ret gene mutation

179

Treatment for DM1

Low sugar diet + insulin replacement

180

Treatment for DM2

dietary modification, exercise for wt loss, oral hypoglycemics, insulin replacement

181

Insulin Replacement Drugs

Lispro (rapid)
Aspart (rapid)
Glulisine (rapid)
Regular (short)
NPH (intermediate)
Glargine (long)
Detemir (long)

182

Uses of insulin replacement drugs

DM1 and DM2, gestational diabetes, hyperK, stress-induced hyperglycemia

183

Toxicity of insulin replacement drugs?

Hypoglycemia, Hypersensitivity rxn

184

Biguanides
Names
MoA
Uses
Tox
Contraindications

Metformin
↓ gluconeogensis, ↑ glycolysis, ↑ peripheral glucose uptake (insulin sensitivity)
First line DM2. Can be used in pts without islet function
GI upset, lactic acidosis
Contraindicated in renal failure

185

First generation sulfonylureas

Tolbutamide, Chlorpropamide

186

Second generation sulfonylureas

Glyburide, Glimepiride, Glipizide

187

Sulfonylureas
MoA
Use
Tox

Close K channels in Ξ² cells --> insulin release
DM2. Requires some islet function (useless in DM1)
1st gen: disulfiram-like effects
2nd gen: hypoglycemia

188

Glitazones/Thiazolidinediones
Names
MoA
Use
Tox

Pioglitazone, Rosiglitazone
↑ insulin sensitivity in peripheral tissue. Binds PPARΞ³ nuclear receptor
DM2
Wt gain, edema, Hepatotoxic, heart failure

189

Ξ± glucosidase inhibitors
Names
MoA
Use
Tox

Acarbose, Miglitol
Inhibits intestinal brush border Ξ± glucosidase
Delayed sugar hydrolysis and glucose absorption
DM2
GI disturbances

190

Amylin analogs
Names
MoA
Use
Tox

Pramlintide
↓ glucagon
DM 1 and 2
Hypoglycemia, nausea, diarrhea

191

GLP1 analog
Names
MoA
Use
Tox

Exenatide, Liraglutide
↑ insulin, ↓ glucagon
DM2
Nausea, vomiting, diarrhea

192

DPP4 inhibitors
Names
MoA
Use
Tox

Linagliptin, Saxagliptin, Sitagliptin
↑ insulin, ↓ glucagon
DM2
Mild urinary and respiratory infections

193

Levothyroxine, Triiodothyronine
MoA
Use
Tox

Thyroxine replacement
Hypothyroidism, myxedema
Tachycardia, heat intolerance, tremors, arrhythmias

194

Use of GH as a medicine

GH deficiency and Turners Syndrome

195

Uses of octreotide

Acromegaly, Carcinoid, Gastrinoma, Glucagonoma, Esophageal varices

196

Uses of Oxytocin

Stimulates labor, uterine contraction, milk let-down. Controls uterine hemorrhage

197

Uses of Desmopressin

Central DI

198

Demeclocycline
Class of drugs
MoA
Use
Tox

Tetracycline
ADH antagonist
SIADH
Nephrogenic DI, Photosensitivity, abnormalities or bone and teeth

199

Glucocorticoids
Names
MoA
Use
Tox

Hydrocortisone, Prednisone, Triamcinolone, Dexamethasone, Beclomethasone
↓ production of leukotrienes and prostaglandins by inhibiting PLA2 and expression of COX2
Addison's disease, Inflammation, Immune suppression, Asthma
Cushing's syndrome, Peptic ulcers, Adrenocortical atrophy.
Adrenal insufficiency if stopped abruptly