Endo/Histo: Thyroid and Parathyroid

Question 1

What are the function of bones?

Answer 1

• Serve as reservoir for calcium and phosphate
• Provide mechanical support to soft tissues
• Act as levers for muscle action
• House and protect the brain and spinal cord

Question 2

What cells are used for bone remodeling?

Answer 2

Osteoblasts - deposit bone

Osteocytes - maintain bone

Osteoclasts - digest bone by secreting acid into Howship’s lacunae (require lots of H pumps –> ATP –> and mitochondria)

Question 3

What embryonal layer does the thyroid develop from?

Answer 3

Oral endoderm

–> It originates in the foramen cecum and mirates down the thyroglossal duct system

–> can lead to ectopic thyroid hormone

Question 4

What is the histological structure of the thyroid gland?

Answer 4

It is an endocrine gland made up of follicles lined with follicular epithelium as the functional unit

• -> consists of parenchyma and stroma
• -> does NOT contain ducts
• -> Divided into lobes and lobules

Question 5

How is thyroid hormone synthesized?

Answer 5

• Thyroglobulin is synthesized and modified before being packaged into vesicles
• It is then secreted by exocytosis into the follicle lumen to wait until needed
• Iodide is transported into the cell and oxidized ito iodine, then also released into the follicle
• Thyroid peroxidase iodinates thyroglobulin into monoiodotyrosine (MIT) and diiodotyrosine (DIT) making T4 and T3
• Stimulation of thyroid cells by TSH leads to release of thyroid hormones

Question 6

What is the difference between Thyroxine (T4) and Triiodothyronine (T3)?

Answer 6

• *T₄ = DIT+DIT**
• less active
• *T₃ = MIT+DIT**
• more active

Question 7

What are C cells?

Answer 7

Thyroid parafollicular cells

• They secrete calcinotin
• Calcitonin reduces blood [Ca²⁺]

Question 8

What is the embryological development pattern of the parathyroid glands?

Answer 8

• *Early 5th week:**
• Inferior parathyroid glands form in dorsal portion of 3rd pharyngeal pouch
• Superior parathyroid glands form in the 4th pharyngeal pouch
• Detach and migrate inferiorly and medially
• *7th week:**
• Come to rest in final location

Question 9

What are the cells of the parathyroid?

Answer 9

• *Chief Cells:**
• Produce PTH and release it in response to low serum Ca levels
• *Oxyphils:**
• Eosinophilic due to large amounts of mitochondria
• Function unknown

Question 10

What are the hormones that regulate calcium homeostasis?

Answer 10

• Vitamin D: increases intestinal reabsorption
• PTH: Causes bone resorption
  Increases activation of Vit. D
  Increases renal Ca reabsorption

Question 11

How are serum Ca levels detected?

Answer 11

By Calcium-sensing Receptors (CaSR) on the chief cells of the parathyroid gland

Question 12

Where is PTH active?

Answer 12

Bone

Gut

Kidney

Question 13

How does the system of osteoclast activation/inhibition work?

Answer 13

Osteoclasts and osteoclast precurors express RANK (receptor activator of nuclear factor kappa-beta)

As PTH increases (along with growth factors, hormones, and cytokines), it activates osteoblast lineage cells to produce RANKL

In the absence of PTH, osteoprotegerin (OPG) is expressed by osteoblast lineage cells and inactivates RANKL, preventing it from binding to RANK and activating osteoclasts

Question 14

What is Denosumab?

Answer 14

Pharmalogical Antibody against RANKL

–> acts like OPG

–> Leads to increased bone mineral density in lumbar spine, total hip, distal third radius

Question 15

How does PTH and Estrogen expression affect RANKL and OPG?

Answer 15

RANKL
Expressed with:
Increaesd PTH
Decreased estrogen

OPG
Expressed with:
Decreased PTH
Increased estrogen

Question 16

Where does calcitonin come from and what is its MOA?

Answer 16

Produced in parafollicular cells of the thyroid

It inhibits absorptive activity of osteoclasts and decreases formation of new osteoclasts

Works to decrease serum [Ca²⁺]

Question 17

What stimulates bone formation?

Answer 17

- Increased blood Ca levels
(increased calcitonin levels)

- Increased mechanical loads

- Estrogen (decreases number of osteoclasts by reducing RANKL synthesis)

- Testosterone

Question 18

What are the target tissues of PTH?

Answer 18

Bone: osteoblasts
Increases expression of RANKL –> indirectly increases differentiation and activation of osteoclasts

Kidney: Late distal tubule
Decreases Ca²⁺ excretion
Increases phosphate excretion

Intestine:
Increases absorption of Ca²⁺ and Phosphate

Question 19

What stimulates bone resorption?

Answer 19

• Decreased serum Ca²⁺ levels
• Immobilization of bones
• -> bedrest, austronauts
• Estrogen deficiency