thyroid and parathyroid glands

1. THYROID AND PARATHYROID GLANDS
PHYSIOLOGY: ENDOCRINE

2. THE THYROID GLAND

3. THE THYROID GLAND
OVERVIEW
‣ The thyroid gland is an endocrine organ found in the neck,
‣ It is responsible for regulating the body’s metabolic rate
via hormones it produces
‣ Learning Goal
‣ To look at the anatomy, cellular structure, endocrine
physiology and clinical relevance of the thyroid gland

4. THE THYROID GLAND
ANATOMY
‣ The thyroid gland is a ductless alveolar gland found in the
anterior neck, just below the laryngeal prominence (Adam’s
apple)
‣ It is roughly butterfly-shaped, with two lobes wrapping around
the trachea and connected in the middle by an isthmus
‣ The thyroid gland is not usually palpable
‣ It is supplied by superior and inferior thyroid arteries, drained
via superior, middle and inferior thyroid veins and has a rich
lymphatic system

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6. THE THYROID GLAND
CELLULAR STRUCTURE
‣ The function of the thyroid gland is to produce and store thyroid
hormones
‣ Thyroid epithelia form follicles filled with colloid – a protein-rich
reservoir of the materials needed for thyroid hormone production
‣ These follicles range in size from 0.02-0.3mm and the epithelium
may be simple cuboidal or simple columnar
‣ In the spaces between the follicles, parafollicular cells can be found
‣ These cells secrete calcitonin, which is involved in the regulation of
calcium metabolism in the body

7. THE THYROID GLAND
FUNCTION
‣ The thyroid gland is one of the main regulators of metabolism
‣ T3 and T4 typically act via nuclear receptors in target tissues and initiate a
variety of metabolic pathways
‣ High levels of them typically cause these processes to occur faster or more
frequently
‣ This is achieved in a number of ways
‣ increasing the size and number of mitochondria within cells
‣ increasing Na-K pump activity
‣ increasing the presence of β-adrenergic receptors in tissues such as cardiac
muscle

8. THE THYROID GLAND
FUNCTION
‣ Metabolic processes increased by thyroid hormones include:
‣ Basal Metabolic Rate
‣ Gluconeogenesis
‣ Glycogenolysis
‣ Protein synthesis
‣ Lipogenesis
‣ Thermogenesis

9. THE THYROID GLAND
THYROID HORMONE SYNTHESIS
‣ There are six steps in the synthesis of thyroid hormone, and you can remember
them using the mnemonic ATE ICE:
‣ Active transport of Iodide into the follicular cell via the Sodium-Iodide
Symporter (NIS)
‣ This is actually secondary active transport, and the sodium gradient
driving it is maintained by a Sodium-Potassium ATPase
‣ Thyroglobulin (Tg), a large protein rich in Tyrosine, is formed in follicular
ribosomes and placed into secretory vesicles
‣ Exocytosis of Thyroglobulin into the follicle lumen, where it is stored as
colloid
‣ Thyroglobulin is the scaffold upon which thyroid hormone is synthesized

10. THE THYROID GLAND
THYROID HORMONE SYNTHESIS
‣ Iodination of the Thyroglobulin
‣ Iodide is made reactive by the enzyme thyroid peroxidase
‣ Iodide binds to the benzene ring on Tyrosine residues of Thyroglobulin,
forming monoiodotyrosine (MIT) then diiodotyrosine (DIT)
‣ Coupling of MIT and DIT gives the Triiodothyronine (T3) hormone and coupling of
DIT and DIT gives the Tetraiodothyronine (T4) hormone, also known as Thyroxine
‣ Endocytosis of iodinated thyroglobulin back into the follicular cell
‣ Thyroglobulin undergoes proteolysis in lysosomes to cleave the iodinated
tyrosine residues from the larger protein
‣ Free T3 or T4 is then released, and the Thyroglobulin scaffold is recycled

11. THE THYROID GLAND
THYROID HORMONE SYNTHESIS
‣ T3 and T4 are the active thyroid hormones
‣ They are fat soluble and mostly carried by plasma proteins
‣ Thyronine Binding Globulin
‣ Albumin
‣ Less than 1% of T3 and T4 is in the unbound free hormone
‣ While T3 is the more potent form, it also has a shorter half-life due to its lower affinity for the binding
proteins
‣ As T4 has a longer half-life, it is used in the treatment of hypothyroidism over T3 as its plasma
concentrations are easier to manage
‣ At the peripheries, T4 is deiodinated to the more active T3
‣ T3 and T4 are deactivated by removing iodine
‣ This happens in the liver and kidney

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13. THE THYROID GLAND
THYROID HORMONE RELEASE
‣ Thyroid hormones are released as part of the hypothalamic-pituitary-
thyroid axis
‣ The Hypothalamus detects a low plasma concentration of thyroid
hormone and releases Thyrotropin-Releasing Hormone (TRH) into the
hypophyseal portal system
‣ TRH binds to receptors found on thyrotrophic cells of the anterior
pituitary gland, causing them to release Thyroid Stimulating
Hormone (TSH) into the systemic circulation
‣ TSH binds to TSH receptors on the basolateral membrane of thyroid
follicular cells and induces the synthesis and release of thyroid hormone

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19. THE THYROID GLAND
REVIEW QUESTIONS
‣ Which of the following best describes the ARTERIAL
supply to the Thyroid gland?
‣ Superior artery
‣ Inferior artery
‣ Superior, Middle and Inferior arteries
‣ Superior and Inferior arteries

20. THE THYROID GLAND
REVIEW QUESTIONS
‣ Which of the following best describes the ARTERIAL supply to
the Thyroid gland?
‣ Superior artery
‣ Inferior artery
‣ Superior, Middle and Inferior arteries
‣ Superior and Inferior arteries
(Superior, Middle and Inferior veins make up the VENOUS
DRAINAGE of the Thyroid, not the arterial supply.)

21. THE THYROID GLAND
REVIEW QUESTIONS
‣ Which ion in particular is key in the synthesis of thyroid
hormone (TH)?
‣ Bromide
‣ Magnesium
‣ Iodide
‣ Fluoride

22. THE THYROID GLAND
REVIEW QUESTIONS
‣ Which ion in particular is key in the synthesis of thyroid
hormone (TH)?
‣ Bromide
‣ Magnesium
‣ Iodide
‣ Fluoride
(The full name for T4 is tetraiodothyronine. It contains four iodide
ions.)

23. THE THYROID GLAND
REVIEW QUESTIONS
‣ Which of the following is considered a common symptom
of Hashimoto’s disease?
‣ Weight gain
‣ Intolerance to heat
‣ Palpitations
‣ Weight loss

24. THE THYROID GLAND
REVIEW QUESTIONS
‣ Which of the following is considered a common symptom
of Hashimoto’s disease?
‣ Weight gain
‣ Intolerance to heat
‣ Palpitations
‣ Weight loss

25. THE THYROID GLAND
REVIEW QUESTIONS
‣ Hashimoto's disease is an autoimmune condition that
brings about a hypothyroidism syndrome. Heat
intolerance, palpitations and weight loss are all common
symptoms of hyperthyroidism.

26. THE PARATHYROID
GLANDS

27. THE PARATHYROID GLANDS
OVERVIEW
‣ The parathyroid glands are small endocrine glands located in
the anterior neck
‣ They are responsible for the production of parathyroid
hormone (PTH)
‣ Learning Goal
‣ To consider the anatomical location, the different cells of the
parathyroid gland, the actions of parathyroid hormone and
the regulation of its secretion and to discuss clinical
applications

28. THE PARATHYROID GLANDS
ANATOMICAL LOCATION
‣ The parathyroid glands are located on the posterior, medial aspect of each lobe of the
thyroid gland
‣ Anatomically, the glands can be divided into two pairs:
‣ Superior parathyroid glands
‣ Derived embryologically from the fourth pharyngeal pouch
‣ Usually located at the level of the inferior border of the cricoid cartilage
‣ Inferior parathyroid glands
‣ Derived embryologically from the third pharyngeal pouch
‣ Usually located near the inferior poles of the thyroid gland
‣ However in 1-5% of people they can be found deep in the superior mediastinum

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30. THE PARATHYROID GLANDS
PARATHYROID GLAND HISTOLOGY
‣ There are two types of cells within the parathyroid gland, the chief cells and the oxyphil cells
‣ Chief cells
‣ The role of this cell type is to secrete parathyroid hormone
‣ They contain prominent Golgi apparatus and endoplasmic reticulum to allow for the
synthesis and secretion of parathyroid hormone
‣ The chief cells are the smaller of the two cell types, however they are more abundant
‣ Oxyphil cells
‣ These cells are much larger but less abundant than chief cells
‣ Their purpose is unknown
‣ It is interesting to note however that the number of oxyphil cells increases with age and few
are seen before puberty
‣ Note that histologically fat cells (adipose cells) are also seen within the parathyroid gland

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32. THE PARATHYROID GLANDS
PARATHYROID HORMONE SYNTHESIS
‣ The synthesis of PTH begins within the rough endoplasmic reticulum,
where pre-pro-PTH is produced
‣ Pre-pro-PTH is 115 amino acids long and consists of a biologically
active sequence, a C terminal fragment sequence, a pro sequence and
a signal sequence
‣ The signal sequence is cleaved within the lumen of the endoplasmic
reticulum, leaving pro-PTH
‣ After transfer to the Golgi apparatus the pro sequence is also cleaved,
resulting in the production of mature PTH, which can then be stored in
secretory granules for release

33. THE PARATHYROID GLANDS
PARATHYROID HORMONE ACTIONS
‣ Parathyroid hormone (PTH) has three main actions, all of which act
to increase calcium levels in the body
‣ Increased bone resorption
‣ PTH acts directly on bone to increase bone resorption
‣ It induces cytokine secretion from osteoblasts that act on
osteoclast cells to increase their activity
‣ Osteoclasts are responsible for the breakdown of bone and thus
an increase in their activity leads to increased bone break down
‣ This leads to an increase in calcium in the extracellular fluid

34. THE PARATHYROID GLANDS
PARATHYROID HORMONE ACTIONS
‣ Increased reabsorption in the kidney
‣ PTH increases the amount of calcium absorbed from the Loop of Henle
and distal tubules, however the mechanism is not fully understood
‣ Additionally, PTH increases the rate of phosphate excretion which is
very important to prevent the formation of calcium phosphate kidney
stones
‣ Vitamin D synthesis
‣ Although PTH does not actively increase the absorption of calcium
from the gut it stimulates the formation of vitamin D, which
subsequently increases absorption from the gut

35. THE PARATHYROID GLANDS
PARATHYROID HORMONE REGULATION
‣ Like most endocrine organs, the parathyroid gland is controlled by a negative feedback loop
‣ Chief cells have a unique G-protein calcium receptor (CaR) on their surface, which regulates this
‣ When calcium levels in the blood are elevated…
‣ PTH production must be stopped in order to prevent further elevation of calcium which could
lead to hypercalcemia
‣ Calcium binds to the G protein CaR which subsequently leads to the production of a molecule
called phosphoinositide
‣ The activation of this molecule prevents PTH secretion thus calcium is deposited back into the
bones
‣ Remember that PTH stimulates vitamin D synthesis
‣ Vitamin D also acts directly on the parathyroid gland to decrease the transcription of the PTH
gene hence less PTH is synthesized

36. THE PARATHYROID GLANDS
PARATHYROID HORMONE REGULATION
‣ When Calcium is reduced, the reverse occurs
‣ Lowered calcium means reduced stimulation of CaR and
decreased phosphoinositide
‣ Subsequently, PTH secretion is not inhibited
‣ Decreased Vitamin D results in upregulation of PTH gene
transcription thus more PTH is synthesized
‣ Note: Elevated phosphate lowers free Calcium in the blood
and inhibits the formation of Vitamin D

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40. https://teachmephysiology.com/endocrine-system/thyroid-parathyroid-gland/parathyroid-gland/

41. THE PARATHYROID GLANDS
REVIEW QUESTIONS
‣ Which cell-type, found in the parathyroid gland, secretes
parathyroid hormone (PTH)?
‣ Oxyphil cells
‣ Chief cells
‣ Adipose cells
‣ Follicular cells

42. THE PARATHYROID GLANDS
REVIEW QUESTIONS
‣ Which cell-type, found in the parathyroid gland, secretes
parathyroid hormone (PTH)?
‣ Oxyphil cells
‣ Chief cells
‣ Adipose cells
‣ Follicular cells

43. THE PARATHYROID GLANDS
REVIEW QUESTIONS
‣ Chief cells are the cells in the parathyroid gland that
synthesise and secrete PTH. Oxyphil cells and adipose
cells are also in the parathyroid gland but do not secrete
PTH. Follicular cells are found in the Thyroid gland.

44. THE PARATHYROID GLANDS
REVIEW QUESTIONS
‣ Which of the following is NOT a primary function of
parathyroid hormone (PTH)?
‣ Increased calcium synthesis in the liver
‣ Increased Vitamin D formation
‣ Increased calcium resorption from bone
‣ Increased reabsorption of calcium in kidney

45. THE PARATHYROID GLANDS
REVIEW QUESTIONS
‣ Which of the following is NOT a primary function of
parathyroid hormone (PTH)?
‣ Increased calcium synthesis in the liver
‣ Increased Vitamin D formation
‣ Increased calcium resorption from bone
‣ Increased reabsorption of calcium in kidney

46. THE PARATHYROID GLANDS
REVIEW QUESTIONS
‣ Calcium is not synthesised in the liver. We receive calcium
from our diet, and absorb it into our body from our food.
PTH works to increase this absorption from food, as well as
decreasing its excretion.

47. THE PARATHYROID GLANDS
REVIEW QUESTIONS
‣ Which of the following types of hyperparathyroidism best
describes a high plasma PTH concentration secondary to
low plasma calcium concentrations?
‣ Primary hyperparathyroidism
‣ Secondary hyperparathyroidism
‣ Tertiary hyperparathyroidism
‣ Malignant hyperparathyroidism

48. THE PARATHYROID GLANDS
REVIEW QUESTIONS
‣ Which of the following types of hyperparathyroidism best
describes a high plasma PTH concentration secondary to
low plasma calcium concentrations?
‣ Primary hyperparathyroidism
‣ Secondary hyperparathyroidism
‣ Tertiary hyperparathyroidism
‣ Malignant hyperparathyroidism

49. THE PARATHYROID GLANDS
REVIEW QUESTIONS
‣ This is an example of secondary hyperparathyroidism,
where low calcium from other causes (eg renal) trigger an
increase in PTH secretion.

50. THE PARATHYROID GLANDS
REVIEW QUESTIONS
‣ Which of the following is most likely to cause
hypoparathyroidism?
‣ Post-menopausal osteoporosis
‣ Bowel surgery resulting in a left-sided colostomy
‣ Low-dairy diet due to allergy to milk
‣ Surgical removal of parathyroid tissue

51. THE PARATHYROID GLANDS
REVIEW QUESTIONS
‣ Which of the following is most likely to cause
hypoparathyroidism?
‣ Post-menopausal osteoporosis
‣ Bowel surgery resulting in a left-sided colostomy
‣ Low-dairy diet due to allergy to milk
‣ Surgical removal of parathyroid tissue

52. THE PARATHYROID GLANDS
REVIEW QUESTIONS
‣ Sometimes parathyroid gland tissue can removed with
thyroid tissue. This is will result in a reduction in the ability
of the body to produce and secrete PTH.

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