Thyroid Phys And Fxn, Hyperthyroid

Front 1

Normal function of the thyroid

Back 1

secretion of hormonally active iodinated amino acids, thyroxine (T4) and triiodothyronine (T3) into systemic circulation

Front 2

Na+/I- symporter (NIS): what is its role?

Back 2

Plasma membrane transport protein that couples Na+ and I- translocation into the follicular cell.

Front 3

Thyroid peroxidase: what is its role?

Back 3

enzyme expressed mainly in the thyroid that liberates iodine for addition onto tyrosine residues on thyroglobulin for the production of thyroxine (T4) or triiodothyronine (T3)

Front 4

MIT + DIT -->

Back 4

T3

Front 5

DIT + DIT -->

Back 5

T4

Front 6

What is the ratio of T4 to T3 within the thyroid gland?

Back 6

15:1

Front 7

How are T3 and T4 transported in plasma?

Back 7

almost completely bound to the plasma binding proteins TBG (thyroxine-binding protein), albumin, and transthyretin (TTR)

Front 8

How much of T3 is free? T4?

Back 8

0.3% of T3 is free; 0.03% of T4 is free.

Front 9

What is the significance of free hormone?

Back 9

The free hormone is the form available to tissues and is responsible for metabolic actions of thyroid hormone.

Front 10

What is the difference in the plasma half-lives between T3 and T3?

Back 10

T4 half life ~7 days; T3 half-life is ~1.5 days (36 hours)

Front 11

What is the major factor modulating thyroid hormone secretion?

Back 11

thyroid stimulating hormone (TSH aka thyrotropin) is regulated at the level of the pituitary thyrotroph by the antagonistic effects of TRH and circulating thyroid hormones

Front 12

T3 and T4 provide negative feedback for release of what?

Back 12

TRH and TSH

Front 13

Where is TSH Releasing Hormone (TRH) made?

Back 13

paraventricular nucleus of the hypothalamus

Front 14

What is the Wolff-Chaikoff effect?

Back 14

Reversible iodide-induced inhibition of organification reaction

aka <b>reduction in thyroid hormone levels caused by ingestion of a large amount of iodine</b>

Front 15

What are the actions of thryoid hormones?

Back 15

1) Stimulate calorigenesis - reflected by increased rates of O2 consumption

2) Growth and development stimulation

3) Intermediary metabolism effects

Front 16

What is clinically the most significant pharmacologic effect of iodide?

Back 16

Inhibition of Tg proteolysis , which inhibits TH release

Front 17

When does iodination of the tyrosine occur?

Back 17

After tyrosine is incorporated into thyroglobulin

Front 18

thyroxine is aka

Back 18

T4

Front 19

Through deiodination, thyroxine (t4) can become

Back 19

A) T3 (activation)
B) Reverse T3 (inactivation)

Front 20

Why is the production of T3 from T4 deiodination considered "activating" while production of rT3 is considered "inactivating?"

Back 20

The relative affinity of the thyroid hormone receptor for T3, T4, and reverse T3 is approximately 100:10:1.

tl;dr Reverse T3 is much less effective than T3

Front 21

MOA of TSH

Back 21

Its binding stimulates an activating G protein that activates adenylyl cyclase --> increased cAMP production

Front 22

How can The Wolff–Chaikoff effect can be used as a treatment principle against hyperthyroidism?

Back 22

Administering large amounts of iodine suppresses the thyroid gland

Front 23

What initiates most actions of TH?

Back 23

T3 binds to its nuclear receptor

Front 24

What are the steps in MOA of TH?

Back 24

1) T3 binds to its nuclear receptor (TR)

2) The nuclear T3 receptor (TR) forms heterodimer withthe Retinoid X Receptor (RXR)

3) The heterodimer RXR-TR binds to T3-responsive elements (TREs) in promoter region of thyroid hormone-responsive genes


Thus, when T3 binds its receptor, it causes a change in gene expression.

Front 25

What accounts for the significant differences in activity of the iodothyronines?

Back 25

The relative affinity for T3, T4, and reverse T3 is approximately 100:10:1

Front 26

What is the problem with measuring Total T4 Concentration?

Back 26

Only the free hormone is responsible for the metabolic effects of thyroid hormones at the cellular level.

Certain patients with thyroxine binding globulin (TBG) abnormalities will appear hyper or hypo thyroid.

Front 27

What effect does pregnancy and increased estrogen have on TBG?

Back 27

Increases TBG, therefore it increases the amount of Total T4 Concentration in plasma.

Front 28

What things cause decreased TBG, thus decreasing the amount of Total T4 Concentration in plasma?

Back 28

Severe nonthyroid illness

Nephrotic syndrome

Acromegaly

Androgens

Glucocorticoids

Front 29

What is the gold standard of Free T4 measurement?

Back 29

Equilibrium dialysis technique

Front 30

What is the T3 Resin Uptake test (T3RU)?

Back 30

It is a measure of available binding sites on Thyroid hormone binding proteins. Based ont he competition between available TBG binding sites and a synthetic resin for added radioactive T3.

Front 31

What will results of T3RU test be in hypothyroidism or increased TBG?

Back 31

There will be MORE available binding sites on TBG, so more radioactive T3 will fill them, less will be taken up by resin, and T3RU will be low.

Front 32

What will results of T3RU test be in hyperthyroidism or decreased TBG?

Back 32

There will be FEWER available binding sites on TBG, so less radioative T3 can bind to them, more radioactive T3 will be on the resin, and T3RU will be high.

Front 33

What does an
A) High
B) Low

T3RU mean?

Back 33

A) Hyperthyroidism (or decreased TBG)

B) Hypothyroidism (or increased TBG)

Front 34

What is the free thyroxine index (FTI?)

Back 34

Indirect estimate of the FT4 concentration provided by T3RU coupled with T4 tests

Front 35

What is the major clinical application of the T3 measurement?

Back 35

Dx of hyperthyroidism

Front 36

What do serum T3 concentrations discriminate well between?

Back 36

Normals and Hyperthyroid patients

Front 37

What do serum T3 concentrations discriminate poorly between?

Back 37

Normals and Hypothryoidism

Front 38

What is T3 thyrotoxicosis?

Back 38

Serum T4 remains normal, and the hypermetabolism sx are due entirely to high T3

Front 39

T/F There are patients with low T3 levels who are not hypothyroid, and there are patients with hypothyroidism who have normal T3 levels

Back 39

T. This is why serum T3 measurement is not helpful for hypothyroidism assessment.

Front 40

Why is TSH levels such a good test?

Back 40

A small change in T4 is reflected by a large change in TSH

Front 41

Most sensitive indicator of primary hypothyroidism (due to intrinsic thyroid disease)

Back 41

Serum TSH concentration

Front 42

What is subclinical hypothyroidism?

Back 42

Patients in whom serum T3 and T4 levels are normal and the only indication of failure is a high TSH.

They may still be symptomatic...

Front 43

When will TSH assay miss the appopriate dx?

Back 43

In patients with secondary (central) hypothyrodism.

Also, not all patients with low TSH are hyperthyroid.

Front 44

What is the radioactive iodine uptake (RAIU) test measuring?

Back 44

The percent of an orally administered dose of a radioactive isotopic of iodine taken up by thyroid over a fixed interval.

Front 45

What are the results of the RAIU in
A) hyperthyroid
B) hypothroid

Back 45

A) Elevated 24 hour uptakes
B) Depressed uptakes

Front 46

What is the RAIU rarely indicated in initial eval of a patient with suspected thyroid dysfunction?

Back 46

Because hypo and hyperthyroidism appear in all three categories - increased, decreased, and normal RAI uptake.

Front 47

6 main causes of hyperthyroidism

Back 47

1) Graves disease
2) Toxic multinodular goiter
3) Toxic uninodular goiter (adenoma)
4) Subacute thyroiditis
5) Exogenous thyroid hormone - iatrogenic or factitious
6) Drug-induced thyrotoxicosis (iodine, amiodarone, interferon)

Front 48

Hyperthyroidism is found more often in (men, women)

Back 48

WOMEN

Front 49

Symptoms of Hyperthyroidism

Back 49

Nervousness
Heat intolerance
Increased sweating
Palpitations
Fatigue
Weakness
Weight loss
Increase appetite
Hyperdefecation
Menstrual irregularities

Front 50

Signs of Hyperthyroidism

Back 50

Tachycardia
Atrial fibrillation
Widened pulse pressure
Warm, moist, smooth skin
Lid retraction
Lid lag
Exophthalmos
Goiter, thyroid bruit
Tremor
Hypekinesis
Muscle wasting

Front 51

In what diseases is diffuse vs. nodular thyroid enlargement seen?

Back 51

Diffuse: Graves, TSH producing tumor, trophoblastic tumor (since they're associated with a direct thyroid stimulator)

Nodular: benign thyroid neoplasms of toxic multi or uninodular goiters

Front 52

What is the difference between non-infiltrative vs. infiltrative eye disease of hyperthyroidism?

Back 52

Non-infiltrative: ocular manifestations associated with thyroid hormone excess of any cause

Infiltrative: specifically to Graves' disease

Front 53

What are sx of the infiltrative eye disease of Graves?

Back 53

eye irritation, excessive lacrimation, photophobia, diplopia.

Most common: <b>retraction of upper lid. </b>

Front 54

Lid lag: defn

Back 54

failure of upper lid to cover the upper margin of the iris as the globe traverses from upward to downward gaze

Front 55

What are signs of the infiltrative eye disease of Graves?

Back 55

Proptosis, conjunctival injection with chemosis, extraocular muscle dysfunction

Front 56

What does "apathetic" hyperthyroidism mean?

Back 56

Description of the atypical hyperthyroid patient, usually elderly, who present with unexplained weight loss, muscle weakness, atrial fib, and CHF.

Often overlooked bc patients lack the &beta; adrenergic symptoms

Front 57

What disease has a IgG that binds to the TSH receptor on thyroid plasma membranes?

Back 57

Graves

Front 58

How does Graves' disease cause hyperthyroidism?

Back 58

Autoimmune disease wherein IgG is directed against TSH receptor. It stimulates the receptor instead of inhibiting.

Front 59

3 extrathyroid manifestations of Graves' disease

Back 59

1) Ophthalmopathy - infiltrative
2) Dermopathy - raised lesions look like orange peel, generally on leg
3) Acropachy - clubbing of digits of hands and feet (rarest)

Front 60

3 approaches to hyperthyroid tx

Back 60

1) Ablative - sx or radioactive iodine
2) Non-ablative - antithyroid drugs
3) Symptomatic - &beta; blockers

Front 61

What causes of hyperthyroidism require ablation?

Back 61

The toxic multinodular goiter; Toxic adenoma

Front 62

What causes of hyperthyroidism don't necessarily require ablation?

Back 62

1) Graves
2) Subacute thyroiditis
3) Exogenous hyperthyroidism

Front 63

How do beta blockers work to tx hyperthyroidism?

Back 63

ONLY TX SYMPTOMS.

Should not be used alone bc they don't reverse the tissue effects, like negative nitrogen and calcium balance, weight loss, etc.

Front 64

What are the antithyroid drugs (2)?

Back 64

Thionamides: propylthiouracil, methimazole

Front 65

MOA of antithyroid drugs

Back 65

Inhibit thyroid hormone synthesis. (block organification and coupling)

PTU also inhibits the extrathyroidal T4 -> T3 conversion.

Front 66

Which antithyroid drug last longer?

Back 66

methimazole

Front 67

Side effects of the antithyroid drugs

Back 67

Minor : rash, transient leukopenia

Major: agranulocytosis, hepatitis (PTU has unacceptable risk and is almost never used now)

Front 68

What is propylthiouracil (PTU) almost never used now?

Back 68

has unacceptable risk of drug-induced hepatitis

Front 69

Pros of antithyroid drugs (as opposed to ablation)

Back 69

1) non-ablative
2) rapid acting
3) relatively safe

Front 70

Cons of antithyroid drugs (as opposed to ablation)

Back 70

1) prolonged therapy
2) dose adjustments
3) rare agranulocytosis

Front 71

In what patients are antithyroid drugs the tx of choice?

Back 71

1) Those under 40 (usually)
2) Pregnant women
3) Children
4) Patients with severe ophthalmopathy
5) Patients requiring rapid correction

Front 72

In what two very specific clinical situations should PTU be used over methimazole?

Back 72

1) First trimester of pregnancy

2) Tx of thyroid storm, because PTU but NOT methimazole inhibits T4->T3 conversion

Front 73

Which antithyroid drug inhibits T4->T3 conversion?

Back 73

PTU

Front 74

T/F Radioactive iodine (ablation) helps opthalmopathy

Back 74

F. It may exacerbate it.

Front 75

How long does it take for Radioactive iodine (ablation) to work?

Back 75

6-8 weeks for it to fully work.

Front 76

Pros of Radioactive iodine (ablation)

Back 76

1) Definitive
2) Convenient
3) Safe

Front 77

Cons of Radioactive iodine (ablation)

Back 77

1) Hypothyroidism - requires replacement for life

2) Acute thyroiditis (v rare)

3) Thyroid storm (v rare)

4) Exacerbates opthalmopathy

Front 78

Pregnant women and children should receive ___________ as initial therapy for hyperthyroidism

Back 78

antithyroid drugs

Front 79

Most patients >40 yo shouldl receive __________ as initial therapy for hyperthyroidism

Back 79

radioactive iodine (ablation)

Front 80

What happens in thyroid storm?

Back 80

Life threatening condition that usually occurs in patients with previously unrecognized hyperthyroidism who undergo some stressful medical illness (eg surgery, childbirth).

Fever, delirium, exaggerated signs of thyrotoxicosis. CV symptoms may include CHF, atrial fib.

Front 81

Tx of thyroid storm

Back 81

Aggressive combo of antithyroid drugs (PTU), iodides, beta blockers, glucocorticoids (presumably to protect adrenal glands)