Thyroid pathology Flashcards
in normal cases, the thyroid gland should weigh […], highly [vascularized] and appear […] in colour
20g, highly vascularized, and mahogany colored
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.
TSH
TSH receptor
GDP
T3 (triiodothyronine) and T4 (thyroxane)
TBG (thyroxane binding globulin)’
intracellular
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.
thyroglobulin chains
Iodide
Sodium
Na+/I- symporter channel (NIS)
pendrin
thyroid peroxidase
the colloid is filled with […] that stains […] upon H&E stain.
thyroglobulin
pink
In the thyroid gland, the thin fibrous […], surrounding […] of various sizes, is highly vascularized.
septa
follicles
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.
cuboidal
colloid
cuboidal to columnar.
scalloping (clear vacuoles in the colloid next to the epithelium where colloid has escaped out of the follicle.
hypothyroidism is characterized by inadequate levels of circulating [….}.
T3 and T4
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?
Hypothyroidism.
- bradycardia, angio, congestive heart failure (CHF), slow-relaxing reflexes
- constipation, decreased mood, reduced focus
- *Women may experience menorrhagia (and with progression eventually, amenorrhea)
what are some main Primary causes of hypothyroidism?
- *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
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?
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.
what are the primary causes of hyperthyroidism/thyrotoxicosis?
- 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.
true/false. a goiter may develop in an adult in states of hypothyroidism, hyperthyroidism, and euthyroidism.
TRUE.
a goiter is an enlarged thyroid gland, that may be diffuse or [….].
A goiter may extend into the […] space.
nodular
retrosternal
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 […].
normal, to slightly high
normal
–>will involute once TSH and fT4 levels balance out.
endemic goitres typically occur in areas …..
mountainous areas far from the sea–>greater than 10% prevalence required for endemic status (andes, himalayas, africa)
sporadic goiters may be caused by….
congenital biosynthetic defects, goitrogens (foods/environmental exposures)
histologically, a diffuse non toxic goiter (simple goiter) will appear?
cells are hyperplastic and hypertrophic.
follicles lined by crowded cells
–>with persistent high TSH, may rupture or hemorrhage
With cycles of hyperplasia and involution some simple goitres may become [….].
scarring and fatty deposits may be noted on histology.
multinodular
a multinodular goiter can develop autonomous nodules, a condition known as [….]
TMNG (toxic multinodular goitre)
—>patient will be hyperthyroid
describe “pemberton’s sign” as it relates to mass effect?
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
histological features of hashimoto’s thyroiditis?
mononuclear cell infiltrate (lymphocytes, plasma cells, AND germinal centres), thyroid cells with abundant eosinophilic granular cytoplasm, scar tissue (chronic inflammation)
histological features of graves disease?
follicular cells are tall and more crowded (hypertrophy and hyperplasia)
scalloping of colloid (and colloid often paler staining)
lymphocytic infiltrate
describe main pathogenesis behind graves disease?
-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.
describe main pathogenesis behind Hashimoto’s disease?
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.
