Thyroid and Parathyroid

Question 1

Thyroid

Location and Structure

Answer 1

• Located in the anterior neck
• Left and right lobes joined by the isthmus
• Functional subunit of the thyroid gland is the follicle which produces thyroid hormone
• Also contains parafollicular cells (C-cells) responsible for calcitonin production
• A part of the developmental thyroglossal duct may persist to form a pyramidal lobe
• Highly vascularized with fenestrated capillaries

Question 2

Thyroid Development

Answer 2

• Begins as a ventral outgrowth of the floor of the oral cavity
• Initially connected to the tongue via the thyroglossal duct
  
  • Duct connection eventually lost and is marked by the foramen caecum on the surface of the tongue
  • Occasionally (40%), the proximal part of the duct persists producing a pyramidal lobe attached to the isthmus of the gland
  • Duct remnants may also produce thyroglossal duct cysts in tongue & anterior neck
• Thyroid migrates anteriorly to neck region
  
  • Ectopic thyroid tissue may be found anywhere along the migratory course of the gland
• Thyroid parenchyma (functional gland tissue) comes from 2 sources:
  
  • Endoderm of the floor of the oral cavity gives rise to the follicular cells
  • Neural crest via the ultimobranchial body gives rise to the parafollicular cells

Question 3

Thyroid Capsule

Answer 3

• Dense fibrous connective tissue envelops the gland
• CT also divides the gland into lobules

Question 4

Thyroid Follicle

Answer 4

• Functional subunit of the thyroid gland
• Consists of a single layer follicular cells surrounding a space filled with secretory product
  
  • Cell shape ranges depending on the functional activity of the gland from squamous (inactive) to cuboidal (active).
• Follicular space usually occupied with colloid

Question 5

Follicle cell structure

Answer 5

• Follicle cells form a squamous to cuboidal epithelium surrounding the follicle space
  
  • Tends to be squamous when gland is relatively inactive and colloid is being stored
  • Tends to be cuboidal when gland is active and releasing T3 and T4 into the circulation and colloid is being broken down
• Abundant RER in basal aspect making cell slightly basophilic
  
  • RER cisternae often distended and irregular
• Well-developed golgi
• Mitochondria with shelf-like cristae
• Many small lysosomes present to hydrolyze the absorbed colloid into thyroid hormones
• Junctional complexes present at apical end of lateral cell membranes

Question 6

Colloid

Answer 6

• Consists mainly of thyroglobulin (inactive storage form of thyroid hormone)
  
  • Follicles contain a 3-month supply
  • Thyroglobulin broken down into T3 and T4
• Acidophilic in H&E because of high carb content
• PAS positive due to carbs

Question 7

Thyroid Blood Supply

Answer 7

• Extensively supplied by fenestrated capillaries.
• Forms dense vascular plexuses that surround follicles
  
  • Uptake of amino acids and iodine from capillaries for production of thyroid hormones
  • Release of hormones upon stimulation into capillaries

Question 8

Classes of thyroid hormones

Answer 8

• Thyroid hormone produced in a T4 to T3 ratio of 20:1
  
  • T3 is the more potent form and most comes from peripheral conversion of T4 to T3 in the kidney, heart, and liver
• Calcitonin produced by parafollicular cells

Question 9

Thyroid Hormone Synthesis

Answer 9

1. Synthesis of thyroglobulin
   
   • Amino acids absorbed from blood to produce the protein portion of thyroglobulin
   • Assembly of protein portion occurs in RER
   • Protein glycosylated in RER and golgi
   • Completed thyroglobulin secreted constitutively into follicular space by exocytosis
2. Iodination of thyroglobulin
   
   • Uptake of iodide from blood by follicular cells
     
     • Able to concentrate 40x serum levels
   • Iodide oxidized to iodine in the follicular lumen by thyroid peroxidase in the apical membrane of follicular cells
   • Iodine released into follicular space
   • Iodination of tyrosine residues on thyroglobulin occurs near microvilli of apical cell surface
3. Release of active hormones
   
   • Stimulated by TSH from thyrotropes of anterior pituitary
   • Colloid taken up by follicular cells by endocytosis
   • Endosomes fuse with lysosomes
   • Within lysosomes, hydrolysis of thyroglobulin results in the release of active thyroid hormones
     
     • Production of T4 to T3 is 20:1
   • Active hormones released into fenestrated capillaries

Question 10

Regulation of thyroid function

Answer 10

Functions through a feedback mechanism involving the hypothalamo-hypophyseal axis.

• Hypothalamus releases thyrotropin releasing hormone (TRH) in response to decreased blood levels of T3 and T4
• TRH stimulates thyrotropes in the anterior pituitary (adrenohypophysis) to produce and secrete thyroid stimulating hormone (TSH)
• TSH stimulates follicular resorption of colloid, hydrolysis of thyroglobulin, and release of thyroid hormones (T3 and T4)

Question 11

Parafollicular cells

Location & Function

Answer 11

• Derived from the neural crest cells of the ultimobranchial bodies
• Dispersed among the thyroid follicular cells
  
  • Located within the basement membrane of the follicles
  • Do not extend into the follicle lumen or contact colloid
• Produces calcitonin
  
  • Therefore also known as C-cells or calcitonin cells

Question 12

Parafollicular cells

Microscopic Anatomy

Answer 12

• Large, round, pale-staining cells by H&E
• Have many small electron dense grandules usually concentrated in the basal aspect
  
  • Contain stored calcitonin
• RER and golgi also abundant

Question 13

Calcitonin

Answer 13

• A non-essential calcium regulating hormone.
• Antagonist to parathyroid hormone
• High levels of Ca²⁺​ in the blood leads to increased calcitonin production
• Decreases blood calcium levels
  
  • by suppressing bone resorption
  • by increasing calcification of osteoid and inhibiting the action of osteoclasts
• Helps prevent excessive bone loss during lactation

Question 14

Iodine Deficiency

Answer 14

• Produces under-iodinated and inactive forms of T3 and T4
  
  • These forms do not exert negative feedback inhibition on the hypothalamic-hypophyseal axis
  • Results in abnormally high levels of TSH
  • Causes abnormal enlargement of the thyroid gland due to hypertrophy and hyperplasia of follicular cells and increase in stored colloid ⇒ goiter​

Question 15

Cretinism

Answer 15

• Insufficient production of thyroid hormone in an infant (hypothyroidism)
• Characterized by:
  
  • Lethargy
  • Mental retardation
  • Abnormal bone development

Question 16

Adult Hypothyroidism

Answer 16

• Results in myxedema
• Characterized by:
  
  • Edema
  • Low metabolic rate
  • Lethargy

Question 17

Hashimoto’s thyroiditis

Answer 17

• Autoimmune destruction of follicular cells
• Leads to hypothyroidism

Question 18

Graves Disease

Answer 18

• Hyperthyroidism associated with hypersecretion of thyroid hormone
• Characterized by:
  
  • Weight loss
  • Increased metabolic activity
  • Increased heart rate
  • In some cases bulging of the eyes (exophtalmos)

H&E of thyroid below shows pale staining area around the periphery of follicular space due to excess colloid use.

Question 19

Parathyroid Glands

Location and Function

Answer 19

• Generally 2 pairs of parathyroid glands: superior and inferior
• Located on posterior surface of the thyroid gland
• Essential for life and produces parathyroid hormone (PTH)
• Removal of all four parathyroid glands results in death due to tetany.

Question 20

Parathyroid glands

Development

Answer 20

• Parenchyma of the parathyroid glands forms from:
  
  • Endoderm of the third (inferior pair) and fourth (superior pair) pharyngeal pouches
    
    • Inferior pair pulled lower by the thymus during development
• Ectopic parathyroid tissue may be found in the neck or chest cavity

Question 21

Parathyroid glands

Microscopic Anatomy

Answer 21

• Each gland is surrounded by a thin connective tissue capsule
• Adipocytes increases in number with age
• Parenchymal cells arranged in clusters or cords
• Two cell types:
  
  1. Chief cells (principal cells)
     
     • Small, pale staining, slightly acidophilic cells
     • Contains granules at EM level
       
       • Granules contain a storage form of PTH
     • Can accumulate large amounts of glycogen
  2. Oxyphil cells
     
     • Larger than chief cells
     • Contains large numbers of mitochondria making them more acidophilic than chief cells by LM
     • Actual function unknown
     • Increases in number with age

Question 22

Parathyroid Hormone

(PTH)

Answer 22

• Raises blood calcium levels by:
  
  • Increasing the breakdown of bone tissue through the activity of osteoclasts
  • Stimulating the development of more osteoclasts
  • Promoting reuptake of Ca²⁺ from the glomerular filtrate by kidney tubules
  • Promoting uptake of Ca²⁺ from the GI tract
• Essential for life