Thyroid Basics

Question 1

thyroid - embryology

Answer 1

*arises from endoderm of the floor of the primitive pharynx
*descends and elongated but remains connected to the tongue by the thyroglossal duct
*duct then disappears leaving the foramen cecum at the base of the tongue
*rarely, duct persists or becomes a pyramidal thyroid lobe

Question 2

thyroglossal duct cyst

Answer 2

*thyroglossal duct remains patent and forms a midline cyst, which moves with tongue protrusion
*cyst is at risk for infection and possibly malignancy
*tx: surgery to prevent infection
*ddx: branchial cleft cyst (more lateral)

Question 3

ectopic thyroid

Answer 3

*thyroid fails to descent to its typical destination
*most common is a lingual thyroid at the base of the tongue
*about 70% experience hypothyroidism to some degree

Question 4

thyroid agenesis

Answer 4

*thyroid doesn’t develop
*all pts with thyroid agenesis are hypothyroid
*note - blood testing for congenital hypothyroidism is part of the newborn screening panel

Question 5

thyroid gland - anatomy

Answer 5

*R and L lobes; isthmus connects the 2 lobes
*lays over the top of trachea
*important structures near thyroid include: recurrent laryngeal nerves (vocals) & parathyroid glands

Question 6

thyroid gland - follicular cells

Answer 6

*majority of the cells in the thyroid
*responsible for making thyroid hormone
*arranged in round follicles, with central colloid
*derived from endoderm

Question 7

thyroid gland - parafollicular cells

Answer 7

*aka “c cells”; c stands for calcitonin
*responsible for secreting calcitonin, which helps with calcium homeostasis
*derived from 4th pharyngeal pouch

Question 8

hypothalamic-pituitary-thyroid axis

Answer 8

thyrotropin releasing hormone (TRH) from hypothalamus → thyroid stimulating hormone (TSH) from anterior pituitary → T3/T4 from thyroid gland

Question 9

key steps in thyroid hormone synthesis

Answer 9

1. iodine active transport through Na+/iodide symporter into thyroid follicular cell
2. iodine is shuttled out of the cell into the colloid within the follicle (lumen)
3. thyroid peroxidase enzyme facilitates iodine molecules (I-) combining with tyrosine residues on thyroglobulin to form MIT and DIT
4. coupling of MIT and DIT by thyroid peroxidase forms T3 and T4, the primary thyroid hormones
5. once T3/T4 are needed, there is thyroglobulin endocytosis and subsequent degradation of thyroglobulin to release T3/T4 into circulation

Question 10

regulation of thyroid hormone synthesis/release

Answer 10

TSH stimulates:
*Na+/iodide symporter
*pendrin (transports iodine across apical membrane)
*thyroid peroxidase (TPO)
*thyroglobulin proteolysis
*T3/T4 transporters
*increases the size, number, and activity of thyroid cells

Question 11

thyroid hormone transport

Answer 11

*majority of thyroid hormone is bound to protein, primarily thyroid-binding globulin (TBG), made mostly by liver
*only a small portion (<1%) is unbound (free thyroid hormone), and only the free thyroid hormone is able to enter cells and exert its effects
*things that alter these proteins will often alter the total levels of thyroid hormone in the serum, but not the free component:
-liver disease, nephrotic syndrome lowers TBG → lower total T4/T3
-estrogen (OCPs, pregnancy) increases TBG → higher total T4/T3
*half life of T4 = 1 week; half life of T3 = 1 day

Question 12

T4 vs. T3 physiology

Answer 12

*90% of what is made by the thyroid is T4; only 10% is T3
*T4 is “inactive form” (less affinity for thyroid hormone receptors); T3 is the “active form (greater affinity for thyroid hormone receptors(
*T4 gets converted to T3 by deiodinase type 2 (5’ deiodinase) in peripheral tissues on an as-needed basis
*T3 binds to thyroid hormone receptor alpha or beta within the nucleus of cell → transcription of various genes to upregulate metabolism/function of cells

Question 13

things that inhibit deiodinase type 2 (and therefore inhibit conversion of T4 to T3)

Answer 13

*amiodarone
*glucocorticoids
*propranolol
*critical illness

Question 14

non-thyroidal illness syndrome

Answer 14

*aka euthyroid sick; probably an adaptive response to illness
*mildly abnormal thyroid labs (low T3, normal to elevated T4) in the setting of acute illness due to downregulation of type 2 deiodinase
*TSH decreases early, then increases in the recovery phase

Question 15

functions of thyroid hormone

Answer 15

*affects the basal metabolic rate of every tissue
*brain maturation
*bone growth
*beta-adrenergic effects (increased CO, HR, SV, contractility)
*blood sugar
*break down lipids
*basal metabolic rate

Question 16

effect of iodine deficiency on thyroid & thyroid hormone

Answer 16

*iodine deficiency → decreased thyroid hormone levels → increased TSH (in response to low T3/T4) → increased number and size of thyroid follicular cells → GOITER (enlargement of the thyroid)

Question 17

sources of iodine

Answer 17

*seafood, kelp, milk, plants (as long as the soil and drinking water contain iodine)
*now, we iodize salt and fortify bread with iodine

Question 18

thyroid mechanism of prevention of iodine excess

Answer 18

*normally, the thyroid protects against excess iodine that might otherwise lead to hyperthyroidism:
-as iodine builds up within the cell, the increase in iodine concentration inhibits TPO
-Wolff-Chaikoff effect = a temporary effect as the thyroid cell adapts to the high levels of iodine

Question 19

iodine excess in pts with hyperthyroidism

Answer 19

*in cases of hyperthyroidism (Graves’ disease, toxic nodules), excess iodine can exacerbate the hyperthyroidism
*common sources of excess iodine: **radiographic dyes, amiodarone, povidone-iodine (an antiseptic)

Question 20

thyroid hormone resistance

Answer 20

*point mutation in the thyroid hormone receptor (usually THR-beta) that results in decreased sensitivity to thyroid hormone
*can cause an unusual lab pattern
*pts can often compensate by making extra thyroid hormone, but sometimes cannot and will have sx of hypothyroidism despite seemingly normal hormone levels

Question 21

lab evaluation of the thyroid: TSH level

Answer 21

*TSH = most commonly ordered test
-tells you whether the pituitary is content with the amount of thyroid hormone
-may not be reliable if you suspect the pituitary may not be working correctly
-long half-life

Question 22

lab evaluation of the thyroid: total T4

Answer 22

*free T4 + bound T4
*not accurate in patients with altered protein states

Question 23

lab evaluation of the thyroid: free T4

Answer 23

*better test compared to total T4
*commonly ordered alongside TSH level

Question 24

lab evaluation of the thyroid: free T3/total T3

Answer 24

*can be helpful in some situations, but in general less important than T4 levels