Pathophysiology of Thyroid Diseases

Question 1

When might the thyroid have a whooshing sound or bruit?

Answer 1

Can occur in hyperthyroidism -> increased blood supply due to overactivity of the thyroid gland

Question 2

What transporter brings iodine into the follicular cell?

Answer 2

Sodium / iodide cotransporter

Question 3

What transporter is responsible for the transport of iodine into the colloid before it is oxidized via thyroperoxidase? What symptoms will these people have?

Answer 3

Pendrin - a Cl-/I- exchanger.

This exchange is also important in the ear and in the kidneys.

Pendred syndrome - mutation of this transporter:
Congenital deafness

Irregular acid/base balance in kidney (pendred is on luminal surface of kidney as HCO3-/Cl- exchanger)

Goiter - due to deficient uptake of iodine into thyroid.

Question 4

What are organification and coupling in the thyroid synthesis process?

Answer 4

Organification - conversion of iodide to an organic form via oxidation, mediated by TPO -> binds it to tyrosine residues on thyroglobulin as MIT or DIT

Coupling - combination of MIT / DIT to make T4>T3 in a 4:1 ratio

Question 5

How much of T3 / T4 is bound in circulation? To what proteins?

Answer 5

70% bound to thyroxine binding globulin (TBG)

Rest bound to albumin and transthyretin (negative acute phase proteins, explains thyrotoxicosis precipitated by infections)

Question 6

What things can increase and decresae the amount of TBG?

Answer 6

Increase - pregnancy and oral contraceptives (estrogen increases TBG)

Decrease - hepatic failure, androgens (decreased synthesis with testosterones or decreased protein synthesis. Think men getting super hyped up)

Question 7

How is T3 vs reverse T3 made?

Answer 7

T3: From Type 1 and Type 2 peripheral 5’ deiodinase

rT3: Inactive, from Type 3 peripheral 5’ deiodinase

Question 8

What thyroid condition may predipose to hyperprolactinemia and what is the mechanism?

Answer 8

Primary hypothyroidism

Because T3/T4 levels are low, TRH/TSH will be highly.

Remember, TRH is the only hormone which stimulates prolactin release. Increased TRH levels will lead to increased PRL levels.
-> return to euthyroid state will resolve the problem

Question 9

What are two common causes of iodine excess, and what physiologic effect do they cause?

Answer 9

1. Amiodarone (lots of iodine in structure)
2. Iodine in contrast agents

High levels of iodine temporarily inhibit thyroperoxidase, decreasing organification of iodine and thus its production
-> this is called the Wolff-Chaikoff effect

Question 10

What is it called if an iodine load induces hyperthyroidism and who can this happen in?

Answer 10

Jod-Basedow effect, can be viewed as the opposite of Wolff-Chaikoff effect.

This cannot happen to individuals with normal thyroids
-> usually occurs in patients who have had longterm iodine deficiency
or
-> can be seen in individuals with partially autonomous thyroid tissue (i.e. toxic goiter or Graves’ disease)

Question 11

How can amiodarone induce either hyperthyrodism or hypothyroidism?

Answer 11

Hyperthyroidism - via the Jod-Basedow effect

Hypothyroidism - some people fail to escape the Wolff-Chaikoff effect if they have underlying iodine autoregulation problems / disease

Question 12

How does the T3 resin uptake test work and what is it used for?

Answer 12

Used to assess between conditions of excess and deficiency of TBG

Radiolabeled T3 is added to a serum sample, and then a secondary resin binder of T3 is added to the sample.

If there is minimal excess TBG, as in hyperthyroidism, very little of the added T3 will bind the patient’s TBG, and most will be available to bind the resin. -> Hyperthyroidism = High resin uptake = Low excess TBG

If there is lots of excess TBG, as in hypothyroidism, most of the added T3 will bind the patient’s TBG, and very little will be available to bind the resin. -> Hypothyroidism = Low resin uptake = high excess TBG.

Question 13

When would Total T4/T3 be measured as high or low but the patient is actually euthyroid?

Answer 13

Euthyroid = appropriate levels of Free T4/T3, since this is hormonally active

When TBG is high (i.e. pregnancy), more T4 will be made in order to accommodate binding the increased TBG, but Free T4 will be normal (patient is euthyroid). However, total t4 would be measured as high.

When TBG is low (i.e. nephrotic syndrome, cirrhosis), less T4 is made in order to have the appropriate free T4 levels with less TBG. Patient is euthyroid, but total T4 is low.

Question 14

Give two situations in which measuring serum thyroglobulin might be useful.

Answer 14

1. Thyroiditis - indicates escape of thyroglobulin from damaged gland
2. Thyroid cancer - when gland is surgically removed, and rise in serum thyroglobulin will be a since of cancer recurrence.

Question 15

What antibodies should you test for in Graves’ disease and Hashimoto’s thyroiditis?

Answer 15

Graves - anti-TSH receptor antibodies (TSI)

Hashimoto’s - antithyroid peroxidase and antithyroglobulin antibodies

Question 16

Give two imaging tests / scans which can be used to diagnose nodules.

Answer 16

Ultrasound - to evaluate the character of a nodule and see if they are growing on follow-up

RadioActive Iodine Uptake scan (RAIU Scan) - increased uptake = hyperthyroidism i.e. Graves, decreased uptake = “cold” = suggestive of destroyed / damaged gland.

Question 17

What are the presenting symptoms of lingual thyroid, what will their thyroid function be, and what is the management?

Answer 17

Symptoms: Difficulty swallowing, foreign body sensation, dysphonia

Thyroid function: Hypothyroid (due to abnormal location) or euthyroid

Management: Give exogenous thyroid hormone -> decreased TSH will shrink the mass

Question 18

What is the normal thyroid levels of someone with thyroglossal duct cyst and what is the treatment?

Answer 18

Typically euthyroid

Treatment is surgery (has potential for malignant transformation)

Question 19

What drugs are considered “goitrogens” and thus induce hypothyroidism?

Answer 19

1. Lithium
2. Iodine-containing drugs -> i.e. amiodarone
3. Tyrosine kinase inhibitors / immune therapies in oncology

Question 20

What is the most common cause of hypothyroidism in iodine-sufficient areas of the world? What precipitates it?

Answer 20

Hashimoto thyroiditis

Precipitated by infection, stress, and genetic susceptibility (can run in families and show anticipation)

Question 21

What two genetic conditions have an association with Hashimoto thyroiditis?

Answer 21

1. Turner syndrome

2. Down syndrome

Question 22

How can hypothyroidism predipose to anemia, especially in women?

Answer 22

1. Impaired hemoglobin synthesis as a result of thyroxine deficiency
2. Iron deficiency from increased iron loss with very heavy menstrual bleeding (menorrhagia)

Question 23

What is myxedema coma? What are the symptoms?

Answer 23

An extremely rare condition which is endstage untreated hypothyroidism

Symptoms:
Decreased mental status
Hypothermia, hypotension
Bradycardia
High TSH with low T3/T4

Question 24

Why can pregnancy cause hyperthyroidism and when is this most likely?

Answer 24

Pregnancy, during the first trimester, leads to increased levels of hCG

alpha chains of HCG can mimic TSH -> cause hyperthyroidism

Question 25

What is factitious hyperthyroidism?

Answer 25

Hyperthyroidism caused by someone taking too much levothyroxine in order to try to lose weight.

Question 26

What test is useful in differentiating between Graves’ disease causing hyperthyroidism vs subacute thyroiditis causing hyperthyroidism?

Answer 26

24 hour radioiodine uptake test

• > uptake will be increased in Graves’ disease and TSH producing tumors
• > uptake will be decreased in thyroiditis causes of hyperthyroidism since TSH levels will be low.

Question 27

What is acropachy and what condition is it associated with?

Answer 27

Finger clubbing - perostitis of the fingers

Soft tissue swelling of the hands

Acropachy = “distal thickness” like pachymeninges = dura,

Associated with Graves disease -> one of the distinctive findings due to overstimulation of TSH receptors by TSI antibodies

Question 28

What is seen on histology in the dermopathy of Graves’ disease?

Answer 28

Lymphocytic infiltration of the dermis
-> stimulating fibroblasts to make GAGs

Dermopathy = pretibial myxedema

Question 29

Is toxic nodular goiter usually as bad as Graves’ disease? Will ophthalmopathy be seen?

Answer 29

No. They have just lost their autoregulatory mechanism, but is usually a mild presentation of Graves’ disease

Ophthalmopathy will NOT be seen (none of the distinctive TSH-stimulating features of Graves’ will be seen)

Question 30

What is subacute lymphocytic thyroiditis also called and when does it typically occur? What’s the clinical course?

Answer 30

Also called PAINLESS thyroiditis, since de Quervain’s is similar but is painful.

Typically occurs 3-6 months post-partum.

Clinical course = hyperthyroidism (transient, due to cell lysis) -> hypothyroid -> recovery of euthyroid

Question 31

What are the two forms of thyroiditis that are marked by progressive failure of the thyroid and often do not recover thyroid function to normal?

Answer 31

1. Hashimoto’s thyroiditis

2. Riedel’s thyroditis

Question 32

What are the usual causes of Thyroid storm?

Answer 32

1. Untreated / undertreated hyperthyroidism
   +
2. Infection (lowers transthyretin levels), trauma (breaks cells open), or surgery (breaks cells open)

Question 33

What are the symptoms of thyroid storm?

Answer 33

Mental status, fever, palpitations, diarrhea, weight loss, nervousness, heat intolerance, tachyarrhythmias which can cause death, sweating

Question 34

What is the treatment for thyroid storm?

Answer 34

1. Hydroxycortisone - steroids block peripheral conversion of T4 to T3
2. Propylthiouracil - Blocks TPO and peripheral conversion of T4 to T3
3. Beta blockers - treats SANS (stops cardiac issues)
4. Iodine - stuns the thyroid from releasing more T3/T4
5. Antipyretics - bring down th e fever
6. Cooling blanked / supportive care

Question 35

What is Sick Euthyroid Syndrome also called and what is the pathogenesis?

Answer 35

“Nonthyroidal illness”

During a serious illness, there is decreased peripheral conversion of T4 to t3, and rT3 is favored.

Body does this to conserve energy during illness -> no true underlying thyroid issue which needs to be treated

Question 36

What are a couple causes of diffuse true goiter?

Answer 36

1. Inborn errors of thyroid hormone synthesis -> TSH is increased to try to pump out more thyroid hormone
2. Iodine deficiency

Question 37

Who tends to get multinodular goiter and when is it treated? How is this done?

Answer 37

Tends to be in elderly women who lived in iodine deficient areas during their life (low iodine sets the process in motion of diffuse goiter -> nodular goiter (See Bosch))

Treatment when goiter becomes toxic, or masses become so large they cause dyspnea / dysphagia (press on trachea / esophagus), or dysarthria
-> Treat via thyroidectomy

Question 38

What is the mainstay of treatment in Papillary and Follicular thyroid carcinoma?

Answer 38

Surgical removal of thyroid gland

Radioactive iodine therapy -> ablate thyroid areas

Question 39

What tumor markers can be used for papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma to monitor recurrence?

Answer 39

Papillary - Thyroglobulin levels
Follicular - Thyroglobulin levels
Medullary - calcitonin, CEA (same as colorectal cancer)