Thyroid Flashcards
What is the primary constituent of the colloid of the thyriod gland?
Thryroglobulin (TG)
What do parafollicular cells (C cells) secrete?
Calcitonin
Which is considered the “thyroid hormone:” T3 or T4?
T3
Which is considered the “prohormone:” T3 or T4?
T4
What are the two ingredients for thyroid hormone (TH)?
Iodide and tyrosine
What anion acts as a competitive inhibitor or iodide uptake?
Perchlorate (ClO4)
Where does organification of iodide occur?
At the follicular cell-colloid interface
Which enzyme catalyzes iodination of thyroglobulin?
Thyroperoxidase
Where is thyroglobulin produced?
In the follicular cell
What is the source of the tyrosine used to make thyroid hormone?
Thyroglobulin
Where do all of the iodination and coupling reactions of TH synthesis occur?
On tyrosyl residues of TG
Is most TH carried in bloodstream bound or unbound? To what is it bound?
99% exists bound to TBG
Which inhibitory compound leads to goiter?
Thiourea drugs
Why is T3 considered to be the active form of TH?
Because its affinity for the Th receptor is 10 fold greater for T3 than for T4
What is the main action of TH?
Maintain basal metabolic rate
What can congenital hypothyroidism lead to in a neonate?
Severe and irreversible mental retardation
Define cretinism
Severely stunted physical and mental growth due to congenital hypothyroidism
What are the CV effects of TH?
Upregulates beta adrenergic activity
How does T3 provide negative feedback?
Free T3 and T4 can influence the response of the anterior pituitary to TRH (high levels reduce response, low levels sensitize response)
Describe the Wolff-Chaikoff effect
Iodine deficient diets will lead to a decrease in TH synthesis, but paradoxically, a short term effect of high doses of iodine will also lead to a decrease in TH release. This is the Wolff-Chaikoff effect. This happens because high iodide will diminish the response to TSH.
Is high iodide intake used for chronic management of hyperthyroidism?
No, because the Wolff-Chaikoff effect is only transient
What is the pathophysiology of Graves’ Disease?
Autoantibodies mimic actions of TSH leading to hyperthyroidism
Does the thyroid produce more T4 or T3?
Much more T4, but then T4 is later converted to T3
In cases of severe illness, stress, or starvation, is more or less T3 produced?
Much less; advantageous to have a lower BMR
What is the half-life of T4?
7 days
What is the half-life of T3?
1 day
What is the main cause of increased TOTAL (not free) T4 and T3?
Increased binding proteins
What is the main cause of increased FREE T4 and T3?
Hyperthyroidism/Thyrotoxicosis
What is the main cause of decreased TOTAL T4 and T3?
Hypothyroidism
How can liver disease cause low total or free T3/T4?
Liver produces the binding proteins. Less binding proteins means less hormone.
How can kidney disease cause low total or free T3/T4?
Proteins can leak out in urine. Less binding proteins means less hormone.
The level of what is the primary indicator of someone’s thyroid status (aka what do you check)?
TSH
Is TSH elevated or reduced in primary hypothyroidism?
Elevated
Is TSH elevated or reduced in primary hyperthyroidism?
Reduced
When can we not rely on the TSH?
Anytime there is an abnormal pituitary gland
Define thyrotoxicosis
High circulating levels of TH (does not always mean it’s hyperthyroidism)
What is true hyperthyroidism/
OVERPRODUCTION of T4 and T3
How can radioactive iodine uptake and scan help us distinguish between true hyperthyroidism and thyrotoxicosis?
When TSH is low, there should be no uptake of iodine. A normal or elevated uptake of iodine in the setting of a low TSH indicated true hyperthyroidism.
What is the most common cause of thyrotoxicosis?
Hashimoto’s thyroiditis
What are the most common causes of true hyperthyroidism?
Graves’ disease and toxic nodules
What is the pathophysiology of Graves’ ophthalmopathy?
There are fibroblasts behind the eye that express TSH receptors. Binding of auto-antibodies to these receptors can cause the fibroblasts to differentiate into adipocytes.
What is the skin finding of Graves’ disease?
Pretibial myxedema
What are the two medications used to treat Graves’ disease? What is their mechanism?
Methimazole adn propylthiouracil; inhibit synthesis of thyroid hormone. Beta blockers to counteract systemic effects.
What are other ways to treat Graves’ disease?
Radioactive iodine and surgery
What is the pathophysiology of Hashimoto’s?
Autoantibodies against thyroid peroxidase and thyroglobulin
What is the treatment for hypothyroidism?
Levothyroxine (synthetic T4)
What is myxedema coma?
An extreme form of hypothyroidism. Life-threatening. High mortality rate.
What is the most common type of malignant tumor of the thyroid?
Papillary
What percentage of nodules are cancer?
10-15%
What kind of spread does papillary thyroid cancer have?
Lymph node spread
Define central hypothyroidism
A reduction in TH as a result of inadequate stimulation of a normal thyroid gland by TSH and may be secondary, due to pituitary disease, or tertiary, due to hypothalamic dysfunction.
What is the prognosis of a papillary carcinoma of the thyroid?
Excellent
Optically clear nuclei is indicative of which type of thyroid cancer?
Papillary carcinoma
What is the prognosis of a anaplastic carcinoma of the thyroid?
Poor
What are the three patterns of anaplastic carcinoma of the thyroid?
Spindle cell, giant cells, and squamoid cells
What are the two types of follicular/hurthle cell carcinoma of the thyroid?
Minimally invasive and widely invasive
What is the most common pathway that is messed up in thyroid cancer?
MAP kinase pathway
What is the most common mutation in all thyroid cancer?
BRAF - leads to papillary carcinoma
The thyroid gland arises from what?
Originates as a proliferation of endodermal epithelial cells on median surface of pharyngeal floor between 1st and 2nd arches
85% of cases of congenital hypothyroidism are caused by what?
Abnormal development of the thyroid gland (dysgenesis)
Those with congenital hypothyroidism due to mutation in PAX8 may also present with what abnormality?
Renal agenesis
Those with congenital hypothyroidism due to mutation in TITF2 may also present with what abnormality?
Bamforth-Lazarus syndrome (very rare)
Those with congenital hypothyroidism due to mutation in TITF2 may also present with what abnormality?
Respiratory distress and neurologic disorders
Those with congenital hypothyroidism due to mutation in SCL26A4 also present with what?
Pendred syndrome - Aut rec disorder characterized by sensorineural congenital deafness and goiter
What do THOX1 and THOX2 encode?
NADPH oxidases which are involved in H2O2 generation in the thyroid; H2O2 is an essential cofactor for iodination and coupling reactions
