Thyroid and Parathyroid Histology

Question 1

formation of thyroid gland

Answer 1

i. The endodermal mass of cells invaginates into the underlying mesoderm—creates the thyroid diverticulum that is positioned b/w the anterior 2/3s and posterior 1/3 of the developing tongue
ii. The thyroid diverticulum grows inferiorly, often b/w the skeletal elements of the second and third pharyngeal arches
iii. Migrates to a position anterior to the upper portion of the developing trachea
iv. Thyroid gland responds to TSH at about week 22 in the fetus

Question 2

congenital hyperthyroidism*

Answer 2

1. Congential absence of the thyroid gland causes irreversible neurologic damage in the infants—cretinism/congenital hyperthyroidism

Question 3

anatomy of thyroid gland

Answer 3

i. Thyroid gland consists of 2 lobes connected by a narrow band of thyroid tissue called the isthmus
ii. Located b/w the larynx and the lobes rest on the sides of the trachea
iii. Thyroid gland is surrounded by a double CT capsule
iv. 2 pairs of parathyroid glands are located on the posterior surface of the thyroid gland, between or outside the two capsules
v. each lobe consists of follicles filled with colloid
1. colloid—suspension of thyroglobulin which is part of TH
2. follicle—single layer of epithelium
a. caries from cuboidal when inactive and columnar when active
b. surrounds central lumen of colloid

Question 4

regulation of thyroid

Answer 4

i. follicular epithelium has Rs for TSH from anterior pituitary
1. controls both synthesis (exocrine) and secretion (endocrine) of TH
a. thyroxine—tetraidodothyronine—T4
b. triiodothyronine–T3
2. long and short feedback loops
a. long—come from the peripheral gland and feedback onto the pituitary and hypothalamus
b. short—come from pituitary and feeds back to hypothalamus or from hypothalamus and feeds back to self

Question 5

synthesis of TH

Answer 5

i. exocrine b/c made and stored extracellularly
1. binding of TSH to its Rs in the follicle cells of the thyroid gland causes the cells to actively transport AAs and iodide ions across the cell membrane, from the bloodstream into the cytosol
a. as a result, the concentration of iodide ions “trapped” in the follicular cells is many times higher than the concentration in the bloodstream
2. iodide ions move to the lumen of the follicle cells that border the colloid, and the ions undergo oxidation
a. the oxidation of 2 iodide ions results in iodine (2I- to I2) which passes thru the follicle cell membrane into the colloid
3. addition of iodine to tyrosine residues of TGB by tyrosine peroxidase released into the lumen by exocytosiss
a. thyroid peroxidase activity and iodination process can be inhibited by propylthiouracil (PPI) and methyl mercaptoimidazole (MMI)
i. these drugs are used to inhibit the production of TH by hyperactive glands

Question 6

secretion of TH from thyroid

Answer 6

i. endocrine b/c goes into blood stream
1. endocytosis and digestion of colloid as a result of TSH stimulus
2. colloid droplets fuse with lysosomes
3. digestive enzymes breakdown TGB which releases T3, T4, and iodine
4. T3 and 4 diffuse thru membrane thru capillary
5. Capillary transport is facilitated by thyroxine binding protein
a. More T4 is secreted by thyroid, but T3 is more potent

Question 7

circulating T3 and T4

Answer 7

i. In the bloodstream, >1% of the circulating T3/4 remains unbound
1. Most is bound and held by thyroxine binding proteins
2. Free T3/4 can cross the lipid bilayer of cell membranes and be taken up by cells
a. Remaining 99% is bound to thyroxine binding proteins, albumin, and other proteinsprevents free diffusion into body cells
3. When blood levels of T3/4 begin to decline, bound T3/4 are released from these plasma proteins and readily cross the membrane of target cells
4. T3 has a shorter half life and is more potent, and is less abundant than T4
a. Half life of T4 is almost a week and represents about 90% of secreted TH

Question 8

function of TH

Answer 8

i. Stimulates basic metabolic rate
ii. Augments thermogenesis—body temp
iii. Augments glucose production
iv. Required for normal production of CNS

Question 9

hyperthyroidism*

Answer 9

1. Excessive production of TSH
2. Symptoms: increased metabolic rate, weight loss, hyperactivity, and heat tolerance
3. Common causes:
   a. Excessive stimulation by adenohypophysis
   b. Loss of feedback control by thyroid gland—Graves’ Disease
   c. ingestion of T4 for weight loss

Question 10

Graves Disease*

Answer 10

a. Loss of feedback control by thyroid gland—Graves’ Disease
i. Caused by autoimmune disorder that produces antibodies to the Rs for TSH on the follicular epithelium
ii. Antibodies bind to the R and chronically stimulate it—b/c they outcomplete TSH, so keep thyroid turned on to secrete T3/4 as fast as it can
iii. Inflammatory response with cytokine production which reinforces the autoimmune response
1. Result is too much circulating TH
iv. Symptoms:
1. Enlargement of the thyroid gland—goiter
2. Bulging of the eyes—exophthalmos
a. Due to inflammatory response in CT and adipocytes behind eyes where we get infiltration of T cells and fibroblasts and the space is filled with Ct/adipocytes and pushing eyes forward
3. Tachycardia
4. Warm skin
5. Fine finger tremors
v. Tx: surgical removal, radioactive iodine
vi. Post tx regimen: requires supplementation of TH

Question 11

hypothyroidism*

Answer 11

1. Caused by insufficient production of TH
2. Symptoms:
   a. Low metabolic rate
   b. Feeling of being cold
   c. Weight gain in some pts
3. In the adult, hypothyroidism is manifested by coarse skin with a puffy appearance due to the accumulation of proteoglycans and retention of fluid in the dermis of the skin and muscle
4. Causes:
   a. Dec iodine intake
   b. Loss of pituitary stimulation
   c. Post therapeutic or destruction of the thyroid by the immune system

Question 12

Hashimoto’s Disease*

Answer 12

1. autoimmune dz associated with hypofunction of the thyroid gland
   a. Caused by autoantibodies to thyroid peroxidase and thyroglobulin so shut down ability of thyroid peroxidase to make TGB
   b. Tx: oral thyroid medication

Question 13

goiter

Answer 13

1. Vary considerably in size, and enlargement may be diffuse throughout the whole gland or irregular and affecting part of all of one lobe
2. Many nodules in the thyroid is called a multinodular goiter
3. Either endemic or sporadic
   a. Endemic—caused by iodine deficiency in diet
4. Pituitary releases more TSH but the gland cannot respond
5. Can be avoided by adding iodine to the diet—such as in iodized salt
6. Once goiter is formed, only tx is surgery
7. “goiter belt”—inland region of US where goiter was common as diet was based primarily food grown on iodine depleted soil

Question 14

congenital hypothyroidism*

Answer 14

1. condition of severely stunted physical and mental growth due to untreated congenital deficiency of TH
2. FKA: cretinism
3. Can be endemic (caused by mom’s abnormal thyroid), genetic, or sporadic
   a. Sporadic and genetic forms result from abnormal development or fcn of the fetal thyroid gland
   i. This type of cretinism mostly eliminated due to newborn screening followed by lifelong TH tx
4. Poor length growth is apparent as early as first eyar of life
   a. Dependent on severity, sex, and other genetic factors
5. Bone maturation and puberty are severely delayed
6. Ovulation is impeded and infertility common
7. Neurological impairment may be mild with reduced muscle tone and coordination, or so severe person can’t walk
8. Cognitive impairment may also range from mild to so severe that the person is nonverbal and dependent on others for basic care

Question 15

parafollicular/C cells

Answer 15

i. Derived from neural crest, contain small cytoplasmic granules, and secrete calcitonin

Question 16

calcitonin

Answer 16

1. Acts to decrease the Ca concentration by inhibiting bone resorption
2. Binds to R on osteoclast to inhibit osteoclasts to prevent the bone resorption/breakdown
3. Hypercalcemia—high blood levels of Ca stimulates calcitonin secretion

Question 17

formation of parathyroid glands

Answer 17

i. Originate from the interaction of the endoderm of the 3rd and 4th pouch
ii. Position of the glands reverses during development
1. Pair of glands which is ultimately inferior develops from the 3rd pouch and pair of glands which is ultimately superior from the 4th pouch
iii. Migration of the thymus—also pouch 3—repositions the parathyroid 3 glands to more inferior positions

Question 18

how are cells of parathyroid gland arranged?

Answer 18

• supplied by sinusoidal capillaries

- arranged in cordlike/follicular like clusters

Question 19

chief cells or principal cells

Answer 19

a. secrete parathyroid H
i. Ca sensing R (CaSR) is associated with G protein in the plasma membrane of chief cells
ii. Serum Ca binding to the extracellular region of the CaSR triggers the release of intracellular signals suppressing the secretion of PTH with the consequential decrease in the Ca concentration
iii. When serum Ca conc dec, the secretion of PTH is stimulated, resulting in an increase in serum Ca

Question 20

oxyphil/acidophilic cell

Answer 20

a. function unknown

b. possibly transitional chief cells

Question 21

parathyroid H

Answer 21

i. PTH acts on osteoblasts to promote osteoclast activityinc in circulating Ca levels
ii. Acts on renal tubules to stimulate resorption of Ca
iii. Controls rate of Ca uptake in GI tract by regulating production of vitamin D (kidneys)
iv. Vitamin D stimulates cells of intestinal mucosa to absorb Ca and synthesize calbindin—carrier protein

Question 22

low Ca and vitamin D

Answer 22

i. Low Castimulates 1 alpha hydroxylase to produce biologically active calcitriol (1,25-hydroxycholecalciferol)

Question 23

high Ca and vitamin D

Answer 23

i. High Castimulates 24 hydroxylase to produce biologically inactive 24, 25-hydroxycholecalciferol

Question 24

calbindin

Answer 24

i. In the duodenum, calcitriol binds to cytosol and nuclear Rs in enterocytes and induces the synthesis of a Ca binding protein calbindin by inc expression of mRNA
1. Calbindin—transports Ca across the enterocyte thru a Ca insensitive ATPase dependent channel and into the blood stream—active transport

Question 25

Ca in the jejunum and ileum

Answer 25

i. In the jejunum and ileum, Ca is transported across the intercellular space into the blood

Question 26

RANK

Answer 26

i. A monocyte reaches an area of bone formation and remodeling and has a receptor for M-CSF on its surface
ii. Monocyte becomes a macrophage.
1. M-CSF ligand bind to the M-CSF R and induces the expression of RACK and its ligand RANKL expressed on the surface of osteoblasts
iii. Osteoblast expressed RANKL binds to the osteoclast RANK and commits the cell to osteoclastogenesis
1. The monocyte becomes an osteoclast precursor which still cannot resorb bone
iv. RANKL stimulated osteoclastgenesis is inhibited by the osteoblast derived RANKL decoy protein osteoprotegrin which blocks RANKL from binding to RANK
1. Osteoblast/osteoprotegrin regulates the population of functional osteoclasts
v. A resting nonfunctional osteoclast uncouple form the osteoblast
vi. The maturation of osteoclasts is completed when the sealing zone and ruffled border appear which required alphav beta3 integrin

Question 27

Hypo/Hyperparathyroidism

*

Answer 27

i. Deficiency in PTH secretion
ii. Blood Ca is low but bone Ca is not released
iii. Ca deficiency results in spontaneous depolarization of neurons and muscle fibers resulting in tetany
iv. High blood Ca levels—hypercalcemia
1. Results in bone loss and can result in osteomalacia and osteitis fibrosa cystica
2. Causes abnormal Ca deposition in arteries and kidneys

Question 28

Rickets/Osteomalacia

Answer 28

1. In children, a deficiency of vitamin D causes rickets.
   a. Bone remodeling is defective
   b. Ends of bones bulge—rachitic rosary at the costochondral junctions
   c. Poor calcification of the long bones causes bending–bowlegs
2. In adults, a deficiency in vitamin D causes osteomalacia
   a. Calcification of the bone matrix osteoid is deficient in both
   b. Pain, partial bone fractures, and muscular weakness is typical in adults
3. Chronic renal failure or a congenital disorder—resulting in the lack of 1 alpha hydroxylase—can also cause rickets or osteomalacia