Thyroid pathology

Question 1

in normal cases, the thyroid gland should weigh […], highly [vascularized] and appear […] in colour

Answer 1

20g, highly vascularized, and mahogany colored

Question 2

the pituitary releases [….] hormone onto the thyroid gland, which then binds to a g-protein coupled […] receptor. The G protein receptor up-regulates cAMP through a reaction converting GTP to [….]. The thyroid gland releases {…] and […] hormones that travel systemically, mostly bound to [….] blood protein], to target tissues. Once they reach the cell they bind to a [….intracellular/extracellular/membrane bound..] receptor in the nucleus on a target gene —–> turns on gene expression.

Answer 2

TSH

TSH receptor

GDP

T3 (triiodothyronine) and T4 (thyroxane)

TBG (thyroxane binding globulin)’

intracellular

Question 3

Thyroid hormone production in the thyroid gland:

Protein synthesis of enzymes and [….] occurs in the follicular cells. The thyrogolubulin chain is then released into the colloid to bind with [….].

Iodide is absorbed from the blood into the follicular cell along with [….] through a [……].

Iodine is shuttled accross the apical membrane of the follicular cell into the colloid via […].
On the outer apical membrane, the enyzme […..] converts iodide into the organic form iodine (I).

Organic iodine binds with the thyroglobulin chain in the colloid.

Answer 3

thyroglobulin chains

Iodide

Sodium

Na+/I- symporter channel (NIS)

pendrin

thyroid peroxidase

Question 4

the colloid is filled with […] that stains […] upon H&E stain.

Answer 4

thyroglobulin

pink

Question 5

In the thyroid gland, the thin fibrous […], surrounding […] of various sizes, is highly vascularized.

Answer 5

septa

follicles

Question 6

the active thyroid appears different histologically than the inactive thyroid.

• ->an inactive thyroid gland has low […] cells and follicle filled with […]
• ->an active thyroid gland has tall [….] cells and demonstrates [….] of the colloid.

Answer 6

cuboidal
colloid

cuboidal to columnar.
scalloping (clear vacuoles in the colloid next to the epithelium where colloid has escaped out of the follicle.

Question 7

hypothyroidism is characterized by inadequate levels of circulating [….}.

Answer 7

T3 and T4

Question 8

patient presents with cold intolerance, cold thickened skin, alopecia
weight gain AND decreased appetite, fatigue.
Blood test reveals High TSH and low fT4

Q1.What is the likely thyroid condition?
Q2. What other autonomic symptoms would they present with?

Answer 8

Hypothyroidism.

• bradycardia, angio, congestive heart failure (CHF), slow-relaxing reflexes
• constipation, decreased mood, reduced focus
• *Women may experience menorrhagia (and with progression eventually, amenorrhea)

Question 9

what are some main Primary causes of hypothyroidism?

Answer 9

• *autoimmune hypothyroidism (Hashimoto’s thyroiditis) presenting with goitrous hypothyroidism.
• iodine deficiency
• *postablative hypothyroidism
• most common in developed countries

–>it is rare for secondary cases involving pituitary or hypothalamic failure

Question 10

Patient presents with heat intolerance, warm flushed skin, fatigue, weight loss (despite increased appetite), and osteoporosis.

Blood test reveals Low TSH and high fT4

Q1.What is the likely thyroid condition?
Q2. What other autonomic symptoms would they present with?

Answer 10

Thyrotoxicosis (hyperthyroidism)

• palipitations, arrythmias, cardiomyopathy
• tremor, anxiety, insomnia, emotional lability
• diarrhea, MSK, eyelid lag,

*women may present with breast enlargement and amenorrhea.
men with gynecomastia.

Question 11

what are the primary causes of hyperthyroidism/thyrotoxicosis?

Answer 11

• diffuse hyperplasia of thyroid gland (Grave’s disease)
• hyperfunctioning “toxic” multinodular goiter

in rare cases: a secondary cause due to a TSH secreting pituitary adenoma.

Question 12

true/false. a goiter may develop in an adult in states of hypothyroidism, hyperthyroidism, and euthyroidism.

Answer 12

TRUE.

Question 13

a goiter is an enlarged thyroid gland, that may be diffuse or [….].

A goiter may extend into the […] space.

Answer 13

nodular

retrosternal

Question 14

Diffuse non-toxic (simple) goiter reflects impaired synthesis of thyroid hormone, but is usually euthyroid.
Patient may have TSH levels that are […] and fT4 levels that are […].

Answer 14

normal, to slightly high

normal

–>will involute once TSH and fT4 levels balance out.

Question 15

endemic goitres typically occur in areas …..

Answer 15

mountainous areas far from the sea–>greater than 10% prevalence required for endemic status (andes, himalayas, africa)

Question 16

sporadic goiters may be caused by….

Answer 16

congenital biosynthetic defects, goitrogens (foods/environmental exposures)

Question 17

histologically, a diffuse non toxic goiter (simple goiter) will appear?

Answer 17

cells are hyperplastic and hypertrophic.
follicles lined by crowded cells
–>with persistent high TSH, may rupture or hemorrhage

Question 18

With cycles of hyperplasia and involution some simple goitres may become [….].

scarring and fatty deposits may be noted on histology.

Answer 18

multinodular

Question 19

a multinodular goiter can develop autonomous nodules, a condition known as [….]

Answer 19

TMNG (toxic multinodular goitre)

—>patient will be hyperthyroid

Question 20

describe “pemberton’s sign” as it relates to mass effect?

Answer 20

This is used to determine whether a patient’s goiter is causing venous obstruction.

a positive pemberton’s sign is when bilateral arm elevation causes facial plethora.
–>caused by the thyroid obstructing the thoracic inlet, putting pressure on venous system

Question 21

histological features of hashimoto’s thyroiditis?

Answer 21

mononuclear cell infiltrate (lymphocytes, plasma cells, AND germinal centres), thyroid cells with abundant eosinophilic granular cytoplasm, scar tissue (chronic inflammation)

Question 22

histological features of graves disease?

Answer 22

follicular cells are tall and more crowded (hypertrophy and hyperplasia)

scalloping of colloid (and colloid often paler staining)

lymphocytic infiltrate

Question 23

describe main pathogenesis behind graves disease?

Answer 23

-autoimmune thyroid disease targetting the TSH receptor.
via thyroid stimulating immunoglobulins (TSI’s) or thyroid growth stimulating immunoglobulins.

The TSH binding inhibitor immunoglobulin may stimulate or inhibit the TSH receptor.
–>patient may at first present with HYPOthyroidism or even develop it during the course of the disease.

Question 24

describe main pathogenesis behind Hashimoto’s disease?

Answer 24

breakdown of tolerance to thyroid cells via CD8+ mediated cytotoxicity, cytokine-mediated cytotoxicity (IFN-gamma, Fas), antibody dependant cell mediated cytotoxicity

And TSH blocking Ab’s that further inhibit thyroid function.