Week 1 Day 4

Front 1

What does AVP do?

Back 1

activates passive reabsorption in the collecting duct

If there is no gradient, there is no waterflow

Front 2

What is the hallmark feature of SIADH?

Back 2

hyponatremia; d/t excessive dilution from excess water retention

Front 3

What are some causes of SIADH

Back 3

"inflammation or obstruction" of lungs or cerebral (sellar tumor, TB, aspergillosis)

Drugs:Antidepressives, anticonvulsants, opioids, chemo drugs

Front 4

What is the volume status in SIADH

Back 4

Euvolemic

Front 5

What is the serum osmolality in SIADH?

Back 5

Hypotonic (<275 mOsm/L)

Front 6

What are the required criteria for SIADH?

Back 6

Euvolemic (normal blood volume)
The serum sodium and serum osmolality are low
Urine Osmolality >100 (holding onto water since there is a low serum Osm!)
Urine sodium >20mEq/L
Hypothyroidism and adrenal insufficiency need to be ruled out (it is a diagnosis of exclusion)

Front 7

How do you treat SIADH?

Back 7

first treat the cause (sometimes it is idiopathic)
IV salt solution (has to be greater osmolarity than urine)
Vasopressin Receptor Antagonists (conivaptan and talvaptan)
Loop diuretics (furosemide and bumetanide; directly diminish concentration gradient)
Demeclocyline-->inhibits the collecting tubules response to AVP

Front 8

Deficient production/release of AVP

Back 8

Central Diabetes Insipidus

Front 9

Causes of Central DI

Back 9

Autoimmune injury to the hypothalamus/pituitary
Head trauma/surgery
Infiltrative disorders (sarcoidosis, histiocytosis)
Tumors

Front 10

Renal resistance to AVP

Back 10

Nephrogenic DI

Front 11

Causes of Nephrogenic DI

Back 11

X-linked recessive disorders
Hypokalemia
Hypercalcemia
Renal Diseases
Drugs (Lithium)

Front 12

Urine Osmolarity in DI

Back 12

Low (<300 mosm/kg); polyuria; perform a water restriction test

Front 13

Plasma osmolarity in DI

Back 13

higher (>300 mosm/kg); determined after water restriction test

Front 14

In Central DI how does the H20 Deprivation test work?

Back 14

With water deprivation, the urine osmolaity will slightly increase (not as much as normal) and with administration of AVP (desmopressin) you see a response

Front 15

In Nephrogenic DI how does the H20 depreivation test work

Back 15

There is NO change in urine osmolaity even with administration of desmopressin

Front 16

Treatment of central DI

Back 16

Replace the missing hormone with a synthetic form of ADH called DDAVP (Desmopressing, 1-deamino-8-D-arginine vasopressin)

Front 17

Treatment for Nephrogenic DI

Back 17

Recommend a low salt, low protein diet (limiting solute potentially lowers urine volume)
Start a THIAZIDE (Amiloride) diuretic
NSAIDs (inhibit renal prostaglandins; limits prostaglandin interference with AVP)
Some might even have a response to DDAVP

Front 18

Where does most of your dietary iodine go?

Back 18

To your kidneys/urine
Only a small amount goes to your thyroid

Front 19

If TBG increases

Back 19

Free T4 decreases, and TSH increases, and more T4 is released from thyroid-->leads to a greater amount of total T4 and a normal free T4 and TSH

In equilibrium

Front 20

Congenital hypothyroidism epidemiology

Back 20

More common ins Hispanics/asians/native americans
More common in girls

Front 21

What are the potential causes of Congenital hypothyroidism?

Back 21

Absent thyroid or small ectopic thyroid (dysgenesis; might not descent appropriately)

Iodine deficiency (most common worldwide but rare in US)

Central hypothyroidism (multiple pituitary hormone disease; or the hypothalamus not producing TRH)

Transient: Late maturation, Antibodies from mom (block TSH receptor), Drugs

Front 22

Presentation of congenital hypothyroidism?

Back 22

Most infants are ASYMPTOMATIC at birth (need to screen)

If untreated: lethargic, hoarse cry, feeding problems, constipation, hypotonia, chubby, developmental delay, hypothermia, large fontanels

Front 23

Newborn screening tests of congenital hypothyroidism

Back 23

Measure T4 and TSH; Mostly rely on the high values of TSH (it might be inappropriately normal)

Front 24

False positives for congenital hypothyroidism occur mainly because?

Back 24

Delayed TSH rise

Front 25

Treatment of Congenital Hypothyroidism

Back 25

Levothyroxine (T4); Serum free T4 should be kept in the upper range of normal during first year of life)

Especially important to treat in first 3 years of life d/t developmental implications

Front 26

Primary Hypothyroidism acts where?

Back 26

on the thyroid

Front 27

2ndary hypothyroidism acts where?

Back 27

On the anterior pituitary

Front 28

Sensitizatoin of the host's own lymphocytes to various thyroidal antigens including thyroglobulin, thyroid peroxidase, and the TSH receptor

Back 28

Hashimoto's Thyroiditis

Front 29

Hashimoto's Thyroiditis is d/t

Back 29

Viral/bacterial infection
High iodine intake
defects in suppressor T lymphocytes (genetic factors)

all can be responsible for the autoimmune process

Front 30

Create a differential diagnosis for primary hypothyroidism

Back 30

Iodine excess (Wolff-Chaikoff effect)
Antithyroid agents
Lithium
Hashimoto's
Thyroidectomy

Front 31

Create a differential diagnosis for 2ndary hypothyroidism

Back 31

Tumors
Dopamine
Glucocorticoids
Sarcoidosis

Front 32

What are the clinical features of hypothyroidism

Back 32

Hair loss
Fatigue
Weight Gain
Periorbital puffiness
Macroglossia
Hoarseness
Bradycardia
Non-pitting edema
Delayed relaxion of ankle jerks

Front 33

How to you diagnose adult hypothyroidism

Back 33

Serum TSH; much more sensitive

Front 34

TSH levels in Primary and 2ndary hypothyroidism

Back 34

Primary-->High (positive thyroglobulin antibodies)
Secondary-->low or inappropriately normal (negative thyroglobulin antibodies)

Front 35

Tx for Hashimoto's

Back 35

Levothyroxine (T4) or Liothyronine (T3)
You cant treat the actual cause of Hashimoto's

Front 36

Signs and Sx of Graves (Hyperthyoidism)

Back 36

Anxious, palpitations, voracious appetite, weight loss, Heat intolerance
Fine tremor, moist, thickened skin (usually over pretibial area-usually d/t mucopolysaccharide deposition), lid lag, stare, Propptosis, Tachycardia

Front 37

Radiotracer uptake

Back 37

Toxic multinodular goiter
multiple functioning thyroid nodules

Front 38

Radiotracer Uptake

Back 38

Nuclear Scan of Graves' disease

Front 39

131-Iodine

Back 39

thyroid destruction of an overactive or enlarged thyroid; deposited in colloid emitting both gamma rays and beta particles destroying parenchymal cells of thyroid (high incidence of delayed hypothyroidism)

Front 40

Methimazole

Back 40

Tx for hyperthyroidism; safer, less side effects; blocks the oxidation of iodine (one side effect is granulocytosis)

Front 41

Propylthiouracil

Back 41

Tx in Hyperthyroidism; Used in PREGNANT women/or intolerance of methimazole; blocks the oxidation of iodine and also inhibits deiodination of T4 to T3 (can cause hepatic failure)

Front 42

Iodine

Back 42

-->use in combo with other drugs and propranolol in the tx of thyrotixic crisis; can also protect the thyroid from radioactive iodine fallout; inhibits hormone release; also decreses the vascularity size and fragility of a hyperplastic gland

Front 43

Treatment in "thyroiditis"

Back 43

Beta, blockers and supportive care

Front 44

High iodine uptake? Graves or Thyroiditis?

Back 44

Graves disease

Front 45

If T4 and TSH are both high what is the next step in Tx?

Back 45

MRI sella, find pituitary adenoma, surgery

Front 46

Microscopic features of Hashimoto's thyroiditis

Back 46

Lymphocytic inflammation, Germinal centers, Hurthle cell change

Front 47

Back 47

Germinal centers in Hashimoto's Thyroiditis

Front 48

Back 48

Subacute Thyroiditis (de Quervain)

Front 49

Fibrous Riedel Thyroiditis

Back 49

Hard and fixed thyroid, painless, Microscopic appearance, Dense fibrosis (collagen fibers); Fibrosis can extend outside of thyroid

Front 50

Back 50

Graves Disease; Abnormal shaped follicles; Scalloped colloid

Front 51

Follicles lined by crowded columnar cells; variable sized follicles, abundant colloid, initial stages-->diffuse enlargement

Back 51

Goiter

Front 52

Back 52

Nodular Hyperplasia

Front 53

Majority are non-neoplastic (focal hyperplasia or simple cysts) or benign (adenomas)

Back 53

Solitary Palpable thyroid nodules

Front 54

Can be diagnostic in papillary carcinoma, madullary carcinoma, lymphoma and metastatic tumors but CANNOT differentiate follicular adenoma from follicular carcinoma or from hyperplastic nodules

Back 54

Fine needle Aspiration

Front 55

Characteristics of Follicular adenomas

Back 55

Solitary
Completely surrounded by a FIBROUS CAPSULE
Different growth pattern from adjacent normal gland
Variable appearances

Front 56

Most significant proven risk factor for development of thyroid cancer

Back 56

Ionizing radiation

Front 57

Most common type of thyroid cancer

Back 57

Papillary CA-->85%-95%

Front 58

Mutations/chromosomal abnormalities in Thyroid papillary carcinoma

Back 58

BRAF oncogene
RAS
Inv(10)
t(10;17)

Front 59

Mutation in follicular thyroid carcinoma

Back 59

RAS oncogene

Front 60

Mutation in Anaplastic Thyroid Cancer

Back 60

p53 tumor suppressor

Front 61

Epidemiology of Papillary thyroid cancer

Back 61

Most occur in younger age group (20s-40s)
Metastasize by way of lymphatics to regional lymph nodes
Excellent prognosis

Front 62

Histology of Papillary Carcinoma

Back 62

NUCLEAR FEATURES!
Clear nuclei-->Orphan Annie Eyes
Intranuclear cytoplasmic inclusions
Intranuclear grooves

Front 63

Back 63

Orphan annie nuclei (papilary carcinoma)

Front 64

Back 64

Longitudinal nuclear grooves (papillary carcinoma)

Front 65

Back 65

Intranuclear Pseudoinclusions (papillary carcinoma)

Front 66

Second most common thyroid cancer

Back 66

Follicular Thyroid Carcinoma

Front 67

Features of thyroid carcinoma

Back 67

Older age than papillary (40s to 50s)
Slowly enlarging painless nodule
Vascular spread to bone, lungs, liver
Generally worse prognosis than papillary carcinoma

Front 68

Criteria for Malignancy of follicular carcinoma

Back 68

Capsular invasion
Vascular invasion
Need extensive sampling of the capsule

Front 69

Back 69

Follicular Carcinoma-Capsular invasion

Front 70

Back 70

Follicular Carcinoma-Vascular invasion

Front 71

What is the main cause of follicular carcinoma?

Back 71

Nodular Goiter

Front 72

Metastatic Spread of Follucular Carcinoma

Back 72

Hematogenous to lung, liver, and bone

(papillary goes to lymph nodes)

Front 73

Neuroendocrine tumors derived from the parafollicular (C-cells) of the thyroid

Secrete Calcitonin

Back 73

Medullary Carcinoma

Front 74

Causes of Medullary Carcinoma

Back 74

80% are sporadic
20% occur within families (MEN-2 syndrome)

Front 75

Histologic features of Medullary carcinoma

Back 75

Nests of neuroendocrine cells
Amyloid Stroma (picture)

Front 76

Back 76

Nest of neuroendocrine cells; Medullary carcinoma

Front 77

What main antibody is stained against in Medullary carcinoma

Back 77

Calcintonin

Front 78

Ugly, unifferentiated tumor of the follicular epithelium

Back 78

Anaplastic Carcinoma

Front 79

Epidemiology/prognosis of Anaplasic carcinoma

Back 79

65 yo
May have a history of long-standing goiter, differentiated thyroid carcinoma or concurrent papillary carcinoma
Most have extrathyroidal spread or distant metastiasis pat presentation
Mortality rate is 100%!!! 6 month survival

Spindle cell and epitheloid type

Front 80

What is the primary determinant of free water excretion in humans

Back 80

ADH circulating levels

Front 81

What is the major factor controlling AVP release?

Back 81

Plasma osmolality; a small 1% rise in plasma osmolality stimulates AVP release by a detectable amount

The change in volume or pressure is less sensitive (need 10-15% drop), but once it reaches a threshold, the stimulated response is exponential

Front 82

Where is the nephron is the primary site of AVP response?

Back 82

The collecting duct

Front 83

In SIADH, what determines the symptoms?

Back 83

depend on the rate of onset and degree of hyponatremia

Front 84

Primary polydopsia

Back 84

Psychiatric disorder: persistent consumption of oral fluids results in appropriate diuresis that resembles high urine volumes