Endo Exam 1: Citterio

The thyroid gland is a ______-shaped gland located around the trachea on the front of the neck, with its two lobes connected by an ______.

The ______ is the functional unit of the thyroid gland

Butterfly, isthmus, follicle

______ is the main component of colloid and serves as the precursor protein for thyroxine (T4) and tri-iodothyronine (T3)

______ cells (also called C cells), located around the follicles, secrete the hormone ______

Thyroglobulin, Parafollicular, calcitonin

______ is the most predominant form of thyroid hormone secreted by the gland, while ______ is considered the most active form

T4, T3

The hypothalamus releases ______ (abbreviation ______), which acts on receptors in anterior pituitary ______ to release thyrotropin, also called ______ (abbreviation ______).

Thyrotropin-releasing hormone, TRH, thyrotropes, thyroid stimulating hormone, TSH

TSH acts on TSH receptors in thyroid ______ cells to stimulate synthesis and release of T4 and T3; T4 and T3 then exert ______ feedback on TRH and TSH release

Follicle, negative

In T4, the 2 benzene rings are ______ to each other with restricted rotation due to ______ among iodine atoms

Perpendicular, repulsion

In T3, the 2nd aromatic ring is more ______ because it has only ______ iodine atom, giving T3 ______ (higher/lower) potency than T4

Flexible, one, higher

In reverse T3 (rT3), the 2nd aromatic ring has ______ bulky iodine atoms, which hinders ______ access, making rT3 ______ (active/inactive)

Two, receptor, inactive

The chiral carbon in thyroid hormones is in the ______ configuration, and only ______ and ______ forms are biologically active

Levo, levothyroxine, levoT3

Step 1 of thyroid hormone synthesis: uptake of iodine from blood by the ______ on the basolateral side, and transport of iodine into the follicle lumen by ______ on the apical side

Sodium iodine symporter, pendrin

Step 2 of thyroid hormone synthesis: oxidation of iodine by the enzyme ______ (abbreviation ______)

Thyroid peroxidase, TPO

Step 3 of thyroid hormone synthesis: incorporation of oxidized iodine into the tyrosine residue of thyroglobulin to form ______ and ______

Monoiodotyrosine, diiodotyrosine

Step 4 of thyroid hormone synthesis: coupling of mono- and diiodotyrosine by ______ to form ______ (T4) and ______ (T3)

TPO, thyroxine, triiodothyronine

Step 5 of thyroid hormone synthesis: uptake of iodinated thyroglobulin into the follicle cells, followed by ______ and release of T4 and T3 into plasma

Hydrolysis

In iodine deficiency, T4 and T3 synthesis and blood levels ______ (increase/decrease), TSH blood levels ______ (increase/decrease), and thyroid gland size becomes ______ (larger/smaller).

Decrease, increase, larger

In the absence of dietary iodine, TSH continues to stimulate thyroglobulin synthesis, resulting in enlarged glands — a condition called ______

Goitrogenesis

T4 has a daily production of ______ mcg, with ______% bound to thyroid binding globulin and only ______% free/unbound

100, 99.97, 0.03

T3 has a daily production of ______ mcg, with ______% bound to thyroid binding globulin and ______% free/unbound

29, 99.7, 0.3

Only the ______ (bound/unbound) hormone is available for crossing the blood vessel and plasma membrane to enter cells

Plasma protein binding increases the biological half-life of T4 to ______ day(s), compared to T3's half-life of ______ day(s)

unbound, 7, 1

The enzyme ______ converts T4 to T3 locally; type I of this enzyme is found in the ______ and ______, while type II is found in the ______ and ______.

5' deiodinase, liver, kidney, CNS, brown adipose tissue

T3 has ______ times higher affinity for thyroid receptors compared to T4

Four drug classes that inhibit 5' deiodinase are ______, ______, ______, and ______

10, Amiodarone, iodinated contrast media, BBs, corticosteroids

The classical genomic actions of thyroid hormones are mediated by high-affinity ______ receptors that directly regulate gene expression; non-genomic effects occur ______ (rapidly/slowly) and are unaffected by inhibitors of transcription and protein synthesis

Nuclear, rapidly

In the inactive phase of the genomic pathway, the unliganded receptor ______ bound to the thyroid hormone response element (abbreviation ______) along with corepressors acts as a suppressor of gene transcription

In the active phase, T3/T4 bind to the ligand-binding domain of the thyroid receptor (TR) ______, promoting disruption of the TR homodimer and heterodimerization with the ______ receptor (abbreviation ______) on the TRE, displacement of corepressors, and binding of coactivators — this activates gene transcription

Dimer, TRE, Monomer, retinoid X, RXR

Primary hypothyroidism due to congenital thyroid hormone deficiency present at birth is called ______ (abbreviation ______), occurring in 1 in ______ live births

Congenital hypothyroidism, CH, 4000

The most common acquired cause of primary hypothyroidism is ______ disease, also known as chronic autoimmune thyroiditis, with a male-to-female ratio of ______

Hashimoto's, 1:10

Hashimoto's disease involves ______ and ______ cell-mediated destruction of the thyroid gland, resulting in decreased synthesis and secretion of thyroid hormones

B-cell, T-cell

The HLA types associated with high risk for Hashimoto's disease are ______, ______, ______, and the gene ______

HLA-DR3, DR4, DR5, CTLA4

Antibodies to ______ and thyroglobulin are present in Hashimoto's disease; antibodies to this enzyme are diagnostic of the condition

TPO (thyroid peroxidase)

The compensatory phase of Hashimoto's disease, where TSH rises to maintain normal T4 and T3, is called ______

Subclinical hypothyroidism

Iatrogenic causes of primary hypothyroidism include ______ or ______, as well as the drugs ______ and ______.

Surgery, radioactive iodine, lithium (Li), amiodarone

Dietary iodine deficiency causing primary hypothyroidism is endemic in populations in ______ and ______.
A: Southeast Asia; Central Africa

Four goiterogenic foods that can cause hypothyroidism are ______, ______, ______, and ______.
A: Cassava; cabbage; mustard; tapioca

KNOW

Secondary hypothyroidism is most often due to decreased secretion of ______ from the pituitary (from infection, surgery, radiation, or trauma), and rarely due to impaired ______ release from the hypothalamus

The most common cause of hyperthyroidism, accounting for 50-60% of cases and affecting ______ per 1000 people in the US, is ______ disease

TSH, TRH, 3, Graves

Graves' disease is an autoimmune disease in which B cells generate antibodies directed against ______ receptors, called ______ (abbreviation ______)

TSH, thyrotropin receptor abs, TRAbs

In Graves' disease, TRAbs bind to TSH receptors on thyroid follicles, activating receptor signaling and increasing synthesis and release of ______ and ______; excessive stimulation also causes enlargement of the thyroid, called a ______

T4, t3, goiter

In Graves' disease, TRAbs also bind to fibroblasts in the skin, causing ______, and to fibroblasts in orbital muscles around the eyes, causing ______ (bulging eyes) and ______ (proptosis)

Dermopathy, exophthalmos, lid retraction

In toxic adenoma, follicles in one region of the gland have TSH receptors that are constitutively active due to a mutation in the ______ protein, causing a single adenoma while the rest of the gland is ______

In toxic multinodular goiter, follicles in multiple regions have TSH receptors constitutively active due to a mutation in the ______ protein, giving the gland a ______ appearance

Gs, atrophied, Gs, nodular

Secondary hyperthyroidism can result from over-stimulation of the thyroid by increased pituitary TSH production or a TSH-secreting tumor, or from overproduction of ______ from the hypothalamus or a ______-secreting tumor

TRH, TRH

hCG-secreting tumors can cause secondary hyperthyroidism because TSH and hCG share ______ subunits, and hCG can activate TSH receptors at ______ the potency of TSH

alpha, 1/10,000

______ hyperthyroidism is caused by increased plasma hCG levels via the same mechanism as hCG-secreting tumors

Gestational

Thyroiditis causing hyperthyroidism can present as ______ thyroiditis (accompanied by severe pain in the thyroid region) or ______ thyroiditis; it is due to inflammation and damage of the thyroid from viral infection, generally accompanied by fever, malaise, and myalgia. It follows a ______ (triphasic/monophasic) T4 course: an initial ______, then a ______, and finally T4 returns to normal

Subacute, painless, triphasic, increase, fall

Thyrotoxicosis factitia is caused by abuse of ______ for indications such as obesity, baldness, or infertility, or by accidental ingestion of ______ (bovine/porcine) containing thyroid gland

Thyroxine, meat

A patient with elevated TSH, low free T4, low total T3, and elevated TPO antibodies has primary ______ due to ______ disease; the elevated TSH occurs because the damaged thyroid cannot synthesize enough T4/T3, removing negative feedback and causing the pituitary to compensate

Hypothyroidism, Hashimoto's

A patient with low/suppressed TSH, elevated free T4, elevated total T3, and elevated TRAbs has primary ______ due to ______ disease; the low TSH occurs because TRAbs continuously activate TSH receptors, driving excess T4/T3 production, which suppresses TSH via strong negative feedback.

Hyperthyroidism, Graves

The four thyroid hormone preparations used to manage hypothyroidism are synthetic ______ (T4), ______ (T3), ______ (a 4:1 mixture of synthetic T4 and T3), and ______ (made from pig thyroids).

Levothyroxine, liothyronine, liotrix, desiccated thyroid gland

Levothyroxine (T4) is well absorbed orally, bound to ______, has a long half-life of ______ days, and is converted to ______ in peripheral tissues for biological activity.

Thyroxine-binding globulin (TBG), 7, T3

Advantages of levothyroxine include low cost, content uniformity, and ______ (dosing frequency); switching between commercial brands is ______ (recommended/not recommended) due to variable effects; ______ preparations are available for myxedema coma

Once-daily administration, not recommended, IV

Liothyronine (T3) is well absorbed orally and is more potent than levothyroxine, but its major disadvantage is a short half-life of ______ day(s), and its higher potency predisposes patients to increased risk of ______

Liotrix uses a ______ ratio of T4:T3 to mimic natural thyroid secretion but is ______ (cheap/expensive).

1, cardiotoxicity, 4:1, expensive

Disadvantages of desiccated thyroid extract include variation in hormone content, ______, and the fact that its T3 portion does ______ (cross/not cross) the placenta

Antigenicity, not cross

The four classes of anti-thyroid drugs for hyperthyroidism are ______, ______, ______, and ______.

Thionamides, iodides, radioactive iodine, BBs

The three thionamide drugs are ______, ______, and ______ (a pro-drug)

Propylthiouracil, methimazole, carbimazole

SAR of thionamides: a ______ group at C2 plus an unsubstituted nitrogen at position 1 is essential for ______ enzyme inhibition, because the sulfur moiety may interact directly with the iron atom in TPO's heme molecule

Thioketone, TPO (thyroid peroxidase)

In carbimazole, the ______ group is removed by CYP metabolism to form ______

Carbethoxy, methimazole

Thionamides work by inhibiting the enzyme ______, thereby inhibiting T4 and T3 synthesis; because release of preformed T4/T3 is not prevented, these drugs have a lag of ______ weeks before clinical effect

Methimazole has a half-life of ______ hours with ______ (no/high) protein binding and is ______ potent than PTU, while PTU has a half-life of ______ minutes with ______% protein binding

TPO, 3-4, 4-6, no, more, 75, 75

During the first trimester of pregnancy, ______ (methimazole/PTU) may be preferred for hyperthyroidism because less amount crosses the placenta due to high protein binding; however, in the second trimester, ______ (methimazole/PTU) carries higher risk due to hepatotoxic effects

PTU, PTU

Methimazole does ______ (effectively/not effectively) block deiodinase, whereas PTU ______ (does/does not) inhibit deiodinase, thus blocking peripheral conversion of T4 to T3

Not effectively, does

Two examples of iodide preparations are ______ (abbreviation SSKI) and ______'s solution

Saturated solution of potassium iodide, Lugol's

The MOA of iodides includes: iodine inhibits its own ______; inhibits synthesis of iodotyrosines and iodothyronines via the ______ effect; and inhibits T4/T3 release, possibly by preventing ______ proteolysis

Transport, Wolff-Chaikoff, thyroglobulin

Radioactive iodine (I¹³¹) is well absorbed orally, efficiently taken up by the thyroid, and emits ______ rays that cause necrosis of thyroid follicle cells, decreasing T4/T3 synthesis; it has a half-life of ______ days, and ______ to ______ is required to achieve a euthyroid state in most patients

Beta, 8, 6 months, 1 year

Iodides have a ______ (rapid/slow) onset of action and are used in ______; "escape" from their effect happens in about ______ weeks, and they are contraindicated before or along with ______

Rapid, thyroid storm, 2 weeks, radioactive iodine

Radioactive iodine should not be given to pregnant or nursing women because it crosses the ______ to destroy the fetal thyroid gland and is excreted in ______

Placenta, breast milk

Beta blockers ameliorate symptoms of hyperthyroidism caused by increased ______ tone, effectively controlling anxiety, tremors, and cardiac symptoms; they do ______ (typically/not typically) alter thyroid hormone levels

Beta-adrenergic, not typically

______ has been the beta blocker most widely studied and used in the therapy of thyrotoxicosis; at doses greater than ______ mg/day, it may also reduce T3 levels by approximately ______% by inhibiting the peripheral conversion of T4 to T3

Propranolol, 160, 20