Endo Flashcards
1
Q
Thyroid development
Where does it arise from?
Where does it descend to?
Connected to what by what?
A
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
Q
Foramen Cecum
A
Normal remnant of thyroglossal duct in tongue
3
Q
Most common ectopic thyroid tissue site
A
Tongue
4
Q
Presentation of thyroglossal duct cyst
A
Anterior midline neck mass that moves with swallowing
5
Q
Presentation of persistent cervical sinus leading to branchial cleft cyst in lateral neck
A
Small mobile mass on side of neck that does not move with swallowing
6
Q
What does the Fetal Adrenal Gland consist of?
A
Outer adult zone and inner active fetal zone
7
Q
Adult zone of fetal adrenal gland
Activity?
Control of activity?
A
Dormant during early fetal life but begins to secrete cortisol late in gestation
Fetal pituitary and placenta make ACTH and CRH
8
Q
What is fetal cortisol responsible for?
A
Fetal lung maturation and surfactant production
9
Q
Embryological origin of adrenal cortex?
A
Mesoderm
10
Q
Embryological origin of adrenal medulla?
A
Neural Crest Cells
11
Q
Layers of Adrenal Gland w/ Secretory Products
A
“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
Q
Zona Glomerulosa
Responsive to
Secretory Product
A
Renin-Angiotensin –> Aldosterone
13
Q
Zona Fasciculata
Responsive to
Secretory Product
A
ACTH, Hypothalamic CRH –> Cortisol, Sex Hormones
14
Q
Zona Reticularis
Responsive to
Secretory Product
A
ACTH, Hypothalamic CRH –> Sex Hormones (androgens)
15
Q
Adrenal Medulla
Responsive to
Secretory Product
A
Preganglionic sympathetic fibers –> ACh –> Catecholamines (NE, Epi)
16
Q
Most common tumor of adrenal medulla in adults?
A
Pheochromocytoma
17
Q
Most common tumor of adrenal medulla in children?
A
Neuroblastoma
18
Q
Pheochromocytoma vs Neuroblastoma in terms of clinical presentation
A
P –> episodic HTN
19
Q
Adrenal gland venous drainage
A
L Adrenal –> L Adrenal Vein –> L Renal Vein –> IVC
R Adrenal –> R Adrenal Vein –> IVC
20
Q
Posterior Pituitary Gland AKA Products Source of products? How are they transported? Embryological origin
A
Neurohypophysis
Secretes ADH and Oxytocin made in hypothalamus and shipped to PP via neurophysins (carrier proteins)
Derived from neuroectoderm
21
Q
Anterior Pituitary Gland
AKA
Secretory Products
Embryological origin
A
Adenohypophysis
“My FLAT PiG”
Melanotropin (MSH), FSH, LH, ACTH, TSH, Prolactin, GH
Derived from oral ectoderm (Rathke’s Pouch)
22
Q
Acidophils in the Anterior Pituitary gland secrete
A
GH and Prolactin
23
Q
Basophils in the Anterior Pituitary gland secrete
A
“B FLAT”
Basophils –> FSH, LH, ACTH, TSH
24
Q
Which hormones share the same α subunit?
A
FSH, LH, TSH, and hCG
25
Endocrine Pancreas
Name
Cell types: Products and Location
Embryological origin?
```
Islets of Langerhans
"INsulin is on the INside"
α: Glucagon, Peripheral
β: Insulin, Central
δ: 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 β 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)
β2 agonists
34
What triggers a ↓ in insulin release
Hypoglycemia, Somatostatin, α2 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), β-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 --> [3β Hydroxysteroid dehydrogenase] --> Progesterone --> [21 hydroxylase] --> 11 deoxycorticosterone --> [11β hydroxylase] --> corticosterone --> [aldosterone synthase] --> Aldosterone
56
Path of Cortisol Synthesis
Pregnenolone --> [17α hydroxylase] --> 17 hydroxypregnenolone --> [3β Hydroxysteroid dehydrogenase] --> 17 hydroxyprogesterone --> [21 hydroxylase] --> 11 deoxycortisol --> [11β hydroxylase] --> Cortisol
or...
Pregnenolone --> [3β Hydroxysteroid dehydrogenase] --> Progesterone --> [17α hydroxylase] --> 17 hydroxyprogesterone -->
57
Path of Testosterone and DHT production
Pregnenolone --> [17α hydroxylase] --> 17 hydroxypregnenolone --> Dehydroepiandrosterone (DHEA) --> [3β Hydroxysteroid dehydrogenase] --> Androstenedione --> Testosterone --> [5α 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
17α hydroxylase, 21 hydroxylase, 11β hydroxylase
60
Why do adrenal enzyme deficiencies lead to hyperplasia
↑ ACTH stimulation because of ↓ cortisol
61
```
17α 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
```
11β 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 α1 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 1α 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)
β adrenergic effects: ↑ β1 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 α and β blockade is achieved
Irreversible α antagonists (phenoxybenzamine) must be given first to avoid hypertensive crisis. β 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, ↑ β 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 < 1.006; Serum osmolality > 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
β cell #
Serum insulin level
Classic symptoms
Histology
```
```
Autoimmune destruction of β cells
Insulin always used
Pt <30
Not obese
Weak genetic connection
HLA DR3 and DR4
Severe glucose intolerance
High insulin sensitivity
Ketoacidosis common
β cell # ↓
Serum insulin ↓
Classic symptoms common
Islet leukocytic infiltration
```
170
```
DM2
Defect
Insulin in treatment
Age
Obesity
Genetics
HLA
Glucose intolerance
Insulin sensitivity
Ketoacidosis
β cell #
Serum insulin level
Classic symptoms
Histology
```
```
Insulin resistance with progressive β cell failure
Insulin sometimes used
Pt >40
Obese
Strong genetic connections
No HLA
Mild to moderate glucose intolerance
Low insulin sensitivity
Rare ketoacidosis
β 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 (β 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 β 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 PPARγ nuclear receptor
DM2
Wt gain, edema, Hepatotoxic, heart failure
189
```
α glucosidase inhibitors
Names
MoA
Use
Tox
```
Acarbose, Miglitol
Inhibits intestinal brush border α 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
