Bod: Endocrinology: Thyroid Disorders

Front 1

What is the first endocrine gland to develop?

Back 1

The thyroid gland.

Front 2

What forms the thyroid gland?

Back 2

The endodermal epithelial cells of the pharyngeal floor.

Front 3

Developmentally, the thyroid gland migrates along what structure?

Back 3

The thyroglossal duct.

Front 4

Developmentally, by what week has the thyroid finished descending?

Back 4

By week 7

Front 5

What are C cells (parafollicular cells) formed from?

Back 5

From neural crest cells.

Front 6

What is the normal weight of the thyroid?

Back 6

15-25 grams

Front 7

What is the blood supply of the thyroid?

Back 7

Superior thyroid artery (branch of the external carotid)

Inferior thyroid artery (branch of the thyrocervical trunk)

Front 8

What do parafollicular cells secrete?

Back 8

Calcitonin (they are also known as C cells)

Front 9

__ is the principal secretory product of the thyroid gland, comprising 90% of all secreted hormone.

Back 9

T4 is the principal secretory product of the thyroid gland, comprising 90% of all secreted hormone.

Front 10

What is the active thyroid hormone? Where is the inactive form metabolized to this active form?

Back 10

T3. T4 is metabolized to T3 in the peripheral tissues.

Front 11

What is the metabolic process that "activates" T4?

Back 11

Removal of the 5', outer ring iodine converts T4 into 3,5,3'-triiodothyronine (T3).

Front 12

What is the metabolic process that "inactivates" T4?

Back 12

Removal of the 5', inner ring iodine converts T4 into 3,3',5'-triiodothyronine, rT3 (reverse T3)

Front 13

What percentage of T4 is converted to T3?

Back 13

about 40%

Front 14

What is the half life of T4?

Back 14

1 week

Front 15

What is the half life of T3?

Back 15

2-3 days

Front 16

What percentage of T3 is sec by the thyroid gland?

Back 16

10%

Front 17

What is the enzyme that converts T4 to T3? Where is it found?

Back 17

Type I 5'-deiodinase, found in the liver

Front 18

List of things that decrease the activity of Type 1 5'-deiodinase (long)

Back 18

- Acute and chronic illness
- Caloric deprivation
- Malnutrition
- Glucocorticoids
- β-blockers
- Oral cholecytographic agents
- Amiodarone
- Propylthiouracil
- Fatty acids
- Fetal/Neonatal period

Front 19

What percentage of T3 and T4 are bound to serum binding proteins?

Back 19

99%

Front 20

Why does T4 have a longer half-life than T3?

Back 20

Thyronine-binding globulin (TBG) has a 10x more affinity for T4 than T3. This explains the longer half-life.

Front 21

What are the three main serum binding proteins for thyroid hormone?

Back 21

1. Thyronine-binding globulin (TBG)

2. Transthyretin (TTR), (mainly T4)

3. Albumin (Both T3 and T4)

Front 22

Where does T3 bind in the cell?

Back 22

In the nucleus. To DNA sequences called TRE (thyroid hormone response elements)

Front 23

What are the two genes that encode the thyroid receptor?

Back 23

c-erb A α (TR α)

c-erb A β (TR β)

Front 24

What are two thyroid antibodies that are routinely measured?

Back 24

Anti-thyroid peroxidase (anti-TPO)

Anti-thyroglobulin (anti-TG)

Front 25

What is the "gold standard" for evaluating T4 levels?

Back 25

Measurement by equilibrium dialysis.

Front 26

What are two methods by which you can estimate T4 levels?

Back 26

- Analog free T4
- Free T4 index (FTI)

Front 27

What is the calculation for FTI (free T4 index)?

Back 27

FTI = Total T4 x THBR

THBR = thyroid hormone binding ratio = the inverse estimate of the serum TBG concentrations.

Front 28

What are three major factors that increase TSH levels?

Back 28

1. Iodide
2. Lithium
3. X-ray contrast agents

Front 29

What is the list of factors that decrease TSH secretion?

Back 29

- Acute and chronic illness
- Adrenergic agonists
- Caloric restriction
- Dopamine
- Dopamine agonists
- Glucocorticoids
- Surgical stress
- Thyroid hormone metabolites

Front 30

Why is a thyroid scan done?

Back 30

To determine regional functionality of the thyroid gland.

Front 31

How is a thyroid scan done?

Back 31

Injest I123 --> taken up by thyroid --> imaging of gland.

Function of the gland can be measured by the percent uptake of I123

Front 32

What does a "cold nodule" look like on a thyroid scan?

Back 32

A white (not dark black) spot

Front 33

What does a "hot nodule" look like on a thyroid scan?

Back 33

A dark black spot.

Front 34

Explain Sick Euthyroid Syndrome

Back 34

The patient is clinically euthyroid, but thyroid function tests are abnormal.

Front 35

What are three factors that affect thyroid hormone levels in the Sick Euthyroid Syndrome?

Back 35

1. Alterations in peripheral metabolism of thyroid hormones (Type I 5'-deiodinase down --> T3 down, rT3 up, T4 normal)

2. Alterations in TSH regulation (acute illness phase: TSH normal, treatment phase: TSH low, recovery phase: TSH high)

3. Alterations in serum binding proteins (acute illness: transthyretin down, albumin down, TBG may go down)

Front 36

What is the bottom line message concerning Sick Euthyroid Syndrome?

Back 36

It is difficult to measure free thyroid hormone levels in patients with critical illness.

Front 37

If there was a T4, T3 receptor defect, what would the TSH and the T3, T4 level be?

Back 37

TSH would be normal, and T3, T4 would be high.

Front 38

What is the structure at the base of the tongue that the thyroid gland descends from during development?

Back 38

The foramen cecum

Front 39

What are the four most common sites of ectopic thyroid?

Back 39

- Lingual
- Sub-lingual
- Pre-laryngeal
- Substernal

Front 40

What are two types of non-toxic goiters?

Back 40

Diffuse (simple) goiter

Multi-nodular goiter

Front 41

What are two types of diffuse (simple) goiter?

Back 41

- Endemic goiter
- Sporadic simple goiter

Front 42

What causes an endemic goiter?

Back 42

Lack of iodine in the diet --> can't synthesize T3, T4 --> TSH not downregulated --> TSH up --> trophic effects on thyroid lead to goiter.

Front 43

(extra credit)

What are some other things that can contribute to goiter formation?

Back 43

- Cabbage
- Cassava
- Cauliflower
- Brussel sprouts
- Calcium, fluorides in water supply

Front 44

What are the characteristics of sporadic simple goiter? Causes?

Back 44

Unknown etiology.
Female > Male (8:1)
Peak incidence at puberty
Rare cases have defects in T3, T4 metabolic pathways, etc.

Front 45

What causes a multi-nodular goiter?

Back 45

Recurrent episodes of hyperplasia and involution create irregular enlargement of the gland.

- May be due to TSH receptor mutation or functional autonomy of follicles.

Front 46

What is the list of symptoms of hyperthyroidism?

Back 46

- Heat intolerance
- Hyperphagia
- Palpitations
- Weight loss
- Exopthalamos
- Diaphoresis
- Emotional liability
- Insomnia
- Muscle weakness
- Abdominal discomfort
- Diffuse scalp hair loss
- Hyperdefecation
- Hypomenorrhea (less periods and less blood)

Front 47

What is the list of signs of thyrotoxicosis?

Back 47

- Tremor
- Tachycardia
- Stare (can see upper white of the eye)
- Hyperactivity
- Emotional liability
- Irregular pulse
- Muscle weakness
- Diffuse hair loss
- Erosion under nail beds
- Fever (in thyroid storm)

Front 48

What is a toxic multinodular goiter?

Back 48

Long standing non-toxic multinodular goiters may become autonomous and produce thyroid hormone independent from TSH.

Front 49

What is a proposed etiology of toxic multinodular goiter?

Back 49

Mutation in TSH receptor gene --> TSH receptor is always on.

Front 50

What is the treatment for toxic multinodular goiter?

Back 50

Radioactive iodine ablation
Thyroidectomy

Front 51

In simple terms, what is the etio-pathogenesis of Grave's Disease?

Back 51

IgG auto-antibodies directed against the TSH receptor.

Front 52

What is the specific auto-antibody that causes Grave's disease?

Back 52

Thyroid Stimulating Immunoglobulin (TSI)

Binds to the TSH receptor and causes increased synthesis and release of thyroid hormone.

Front 53

People with long standing Grave's disease often have what kind of thyroid profile?

Back 53

HYPOthyroidism due to the presence of antibodies against thyroid peroxidase and thyroglobulin.

Front 54

What does a Grave's disease thyroid look like?

Back 54

- Uniform enlargement of the gland.
- Softer than normal thyroid.

Front 55

What is the microscopic attributes of a Grave's disease thyroid?

Back 55

- Lining cells are tall columnar
- Colloid is reduced and pale
- Stroma contains aggregates of lymphoid tissue.

Front 56

What is the most common caue of thyrotoxicosis?

Back 56

Grave's disease.

Front 57

What would a Grave's disease thyroid look like on radioactive iodine uptake scan?

Back 57

Very dense --> all aspects of thyroid function are elevated --> avidly concentrates iodine from circulation.

Front 58

Grave's disease: demographics

Back 58

Female > male (6:1)

Max incidence between 20-40 years of age.

Front 59

What are the three major signs/symptoms of Grave's disease?

Back 59

1. Cardiac: tachycardia, atrial fibrillation
2. Eye changes: opthalmopathy
3. Skin changes: pretibial edema/myxedema (autoimmune etiology)

Other: sweating, weight loss, diarrhea, tremors.

Front 60

Describe the opthalmopathy associated with Grave's disease.

Back 60

Caused by a swelling of the extraocular muscles --> proptosis --> blindness if optic nerve is compressed.

Front 61

Treatment for Grave's associated proptosis?

Back 61

Steroids

Front 62

What are two strategies that can be used to guide medical treatment for Grave's disease?

Back 62

1. Decreasing the synthesis of thyroid hormone (methimazole [not of for preg], propylthiouracil [ok for preg])

2. Decreasing the uptake of iodine from the circulations (perchlorate, thiocyanate)

Front 63

What is the etiology of the thyrotoxicosis associated with thyroiditis?

Back 63

Extensive damage to the thyroid gland --> release of large amounts of stored thyroid hormone.

Front 64

What are two types of thyroiditis?

Back 64

1. Subacute thyroiditis
2. Silent thyroiditis

Front 65

What is used for the treatment of the cardiac symptoms of Grave's disease?

Back 65

Beta blockers

Front 66

What happens to a thyroid with thyroiditis?

Back 66

It swells rapidly and becomes painful to the touch.

Front 67

Subacute thyroiditis: findings on radioactive uptake scan?

Back 67

Thyroid stops taking up iodine --> very low density (white) on scan.

Front 68

Subacute thyroiditis: antibody level? Sed rate level?

Back 68

Thyroid antibodies are not present. Sed rate will be high.

Front 69

Subacute thyroiditis: treatment

Back 69

mild: aspirin
severe: steroids

Front 70

Subacute thyroiditis: prognosis and course?

Back 70

Good. Hyperthyroidism resolves over several weeks, gland back to normal in weeks/months.

Front 71

Subacute thyroiditis: complications once symptoms resolve

Back 71

Patients may become hypothyroid. May need thyroid replacement with L-thyroxine.

Front 72

Subacute thyroiditis: TSH levels?

Back 72

Low (because T4 is high)

Front 73

What is the most marked feature of silent thyroiditis?

Back 73

There is no neck pain!

Front 74

What are the characteristics of silent thyroiditis?

Back 74

T4 is high, TSH is low, radioactive uptake is low, but there is no neck pain.

Front 75

When is silent thyroiditis usually seen?

Back 75

In young women following pregnancy. (within first year postpartum = "Postpartum Thyroiditis")

Front 76

What are five rare causes of hyperthyroidism?

Back 76

1. Human chorionic gonadotropin (HCG) producing neoplasm (choriocarcinoma, hydatidiform mole --> HCG up --> thyroid up)

2. Struma ovarii (ovarian tumor that contains thyroid elements)

3. Factitious thyrotoxicosis (deliberate ingestion of thyroid hormone)

4. Accidental ingestion of thyroid hormone (Beef/pork contaminated with thyroid glands)

5. TSH secreting pituitary tumors.

Front 77

What is the most common cause of hypothyroidism in the US?

Back 77

Hashimoto's thyroiditis

Front 78

What is the most sensitive test for primary hypothyroidism?

Back 78

An elevated TSH!

Front 79

What is the list of the clinical features of hypothyroidism?

Back 79

- Sensitivity to cold
- Weight gain
- Hypermenorrhea
- Patchy hair loss
- Decreased fertility
- Constipation
- Low voltage on EKG
- Pericardial effusion
- Peritoneal effusion
- Entrapment neuropathies
- Carpel tunnel syndrome
- Delayed reflexes
- Bradycardia
- Fatigue
- Delayed relaxation
- Dry, coarse skin

Front 80

What is the etiology of Hashimoto's thyroiditis?

Back 80

Autoimmune: T cells help B cells make antibodies against:
- Thyroglobulin
- Thyroid peroxidase (TPO)
- TSH receptor
- Thyroid microsomal antigen

Also CD8 cells activate Fas-Fas ligand mediated apoptosis

Front 81

Hashimoto's thyroiditis: goiter? Hypo or hyperthyroid?

Back 81

Goiter present. Hypothyroid.

(In atrophic variant there is no goiter)

Front 82

What is the autoantibody most often present in Hashimoto's thyroiditis?

Back 82

Anti-thyroid peroxidase (TPO)

Front 83

Hashimoto's thyroiditis: patients have an increased risk of what?

Back 83

Lymphoma and carcinoma.

Front 84

Hashimoto's thyroiditis: gross pathology

Back 84

Diffuse enlargement, firm, no extension beyond outside of gland, cut surface is yellowish gray.

Front 85

Hashimoto's thyroiditis: microscopic pathology

Back 85

- Lymphocytic infiltrate in the stroma
- Oxiphil change of the follicular epithelium
- Small and atrophic follicles