PARATHYROID GLANDS AND CALCIUM HOMEOSTASIS

Prof. Mark Ryan V. Domingo || March 09, 2023

Transcribers: Michael J. Natal, Marione C.A. Valdoz
CC2-LEC

OUTLINE
I. PARATHYROID GLANDS
A. Anatomy and Embryology
B. Normal Histology

II. HORMONES OF PARATHYROID GLANDS

C. Parathyroid Hormones (PTH)
a. Actions of PTH on Kidney
D. Calcitonin
a. Actions of Calcitonin on Bones

III. DISORDERS OF PARATHYROID GLANDS

E. Primary Hyperparathyroidism (PHPT)
F. Hypoparathyroidism
G. Differential Diagnosis
H. Familiar Hypocalciuric Hypercalcemia

PARATHYROID GLANDS
Anatomy
● Parathyroid Glands are usually oval, bean-shaped or oblong
● Weight: 40 – 50 mg each
● Size: 7mm (avg)
→ Smallest endocrine gland in the body (6 mm in diameter –
module)
● Appearance: light yellow to caramel color in adults
● Location: At the level of cricoid cartilages (Adam’s apple is the
thyroid cartilage)
→ Generally located posterior to the thyroid gland
→ The inferior parathyroid gland is located ventral to the nerve
→ On or near the thyroid capsule, sometimes within the thyroid
gland
● Types of Cells;
→ Principal cells/Chief cells – secretory cells secreting PTH
→ Oxyphil cells – non-secretory cells
Endocrine – Parathyroid
A. Anatomy and Embryology
Inferior Glands
o Origin: Derived from the third (3rd) branchial pouch
→ Gives rise also to the inferior PT gland and thymus
o Migration: Migrate caudally with the thymus
o Division: Separate at the level of the inferior thyroid pole
 The inferior glands vary more in their location than the superior
glands
Superior Glands
o Origin: Derived from the fourth (4th) branchial pouch and follow;
o Migration: The migration of the ultimobranchial bodies at the lateral
part of the thyroid anlage

 84% of adults have four (4) parathyroids
 Autopsy results reveal;
o 13% have greater than 4 parathyroids
o 3% have less than 4 parathyroids
 Normally, they are located on the posterior lateral surface of the
middle to superior thyroid lobe
o Location is variable (ectopic location) – they can be found
at locations where they are not usually found
 The superior glands are generally located (1) superior to the inferior
thyroid artery and (2) posterior to the recurrent laryngeal nerve
 Classically described as lying one (1) cm above the intersection of
the RLN (right laryngeal nerve) and inferior thyroid artery
 Truly ectopic superior PT glands are rare but they can be found in
middle or posterior mediastinum
Implications if the Location of the Parathyroid Gland Varies
 Has implications on surgeons if they will remove
o It will be difficult to know where is the parathyroid gland
o When they are performing neck surgery, chances are,
parathyroid gland are also surgically removed

 Can result in hypoparathyroidism

o Due to the accidental removal during thyroidectomy
o This will result in problems in calcium regulation

 The PT hormone is important in calcium regulation

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[CC2-LEC] PARATHYROID GLANDS AND CALCIUM HOMEOSTASIS – Prof. Mark Ryan V. Domingo
o Water-cleat cells are derived from chief cells and is rich in
glycogen

HORMONES OF PARATHYROID GLANDS

Hormones of Parathyroid Glands
● Parathyroid Hormones (PTH)
● Calcitonin

→ Remember that the main function of the parathyroid gland is

to maintain the calcium homeostasis

C. Parathyroid Hormones (PTH)

General
o Preproparathyroid Hormone is the precursor
o Blood supply to the superior and inferior glands is from the inferior
o Parathyroid Hormone (PTH) is an 84-amino acid peptide with the
thyroid artery in 86% of patients biologic activity residing at its amino terminal
→ Glands are usually surrounded by blood vessels so that the
→ From amino acid number 1 up to 34
hormones have means of transport to the target site
o Parathyroid Hormone (PTH) – hypercalcemic hormone
→ Released in low levels of calcium
o Primary Role: PTH regulates serum calcium concentration and bone
metabolism
→ Affects bone, kidney, and intestine particularly
→ With the actions/functions including;
▪ Preserves calcium and phosphate within normal range
▪ Promotes bone resorption – release calcium into the blood
stream
▪ Increase renal absorption of Calcium
▪ Stimulates conversion of inactive Vitamin D to activated
Vitamin D3
▪ Indirectly stimulates intestinal absorption of Calcium
B. Normal Histology of Parathyroid Gland
o Serum calcium concentration in turn regulates PTH secretion
Normal Histology → Calcium levels increase → PTH secretion suppressed
(decreases) → results: urinary loss of calcium, bone
maintenance (remain) of calcium

o The PTH has a very short half-life at around 2 to 4 mins (other

literatures: 5 minutes)
→ Easily cleared by the kidney probably because of its small
peptide nature

o Normal parathyroid histology showing chief cells interspersed with o The doctor may request to measure PTH or fragment of parathyroid
adipose cells peptide
o Oxyphil and water-clear cells are present → Intact Parathyroid Hormone – complete PTH is measured
→ Fragmented PTH – measures only N or C terminal

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[CC2-LEC] PARATHYROID GLANDS AND CALCIUM HOMEOSTASIS – Prof. Mark Ryan V. Domingo
o PT hormone also stimulates the activity of 1-alpha-hydroxylase
activity which is important in the activation of Vitamin D in the
kidneys
→ In turn, it promotes intestinal absorption of calcium →
increased blood calcium

PTH and Calcium – Regulation

PTH – Regulation

Osteoprotegrin Ligand (OPGL)

o Starts with the chief cells

o PTH and Vitamin D activates the osteoblasts
→ Cell membrane of the chief cells have receptors called calcium
→ Osteoblasts are the one acted upon the PTH
sensing receptors
→ Osteoblasts are not directly involved in bone resorption
→ Expressed on the surface of the parathyroid cells and senses
o It is targeted by the PTH so that osteoblasts can produce OPGL
fluctuation in extracellular calcium (ionized or non-ionized
calcium)
o OPGL is a growth factor (osteoclast differentiation factor)
→ These precursor osteoclasts are differentiated into mature and
→ The ionizing calcium is the one that has an effect on
active form
parathyroid hormone release

PTH Actions on the Kidney

o Activation of these receptors increase intracellular calcium levels
o Increased reabsorption of calcium, magnesium and hydrogen ions
→ If calcium levels are low in EC fluid, that activates the CSR to
o Decreased reabsorption of phosphate, sodium and potassium ions
increase the intracellular calcium levels
o Increased 1-alpha-hydrxylase activity
→ Which in turn inhibit PT hormone secretion if calcium is
increased
D. Calcitonin
→ Increase in PT hormone secretion leads to increased serum
calcium Calcitonin
o Polypeptide hormone
o PT hormone has an effect to the kidneys o Synthesized and secreted by the parafollicular C-cells of the thyroid
→ It stimulates the kidney to promote calcium reabsorption gland

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[CC2-LEC] PARATHYROID GLANDS AND CALCIUM HOMEOSTASIS – Prof. Mark Ryan V. Domingo
o Increased plasma calcium concentration stimulates Calcitonin
secretion ▪ Psychiatric Overtones = concerning with the central
o Calcitonin decreases plasma calcium concentration nervous system (lethargy, fatigue, depression, memory
loss, psychosis, ataxia, delirium)
Actions of Calcitonin – Bone
o Decreased osteoclastic activity
o Decreased osteoclastic number (decreased formation of osteoclasts) o Severe symptoms which are uncommon, including;
o The net result is reduced osteoblastic and osteoclastic activity → Osteitis fibrosis cystica, and nephrocalcinosis

DISORDERS OF PARATHYROID GLANDS

Disorders of Parathyroid Glands
● Hyperparathyroidism
→ Primary Hyperparathyroidism (PHPT)
→ Secondary Hyperparathyroidism
→ Tertiary Hyperparathyroidism
● Hypoparathyroidism
→ Laboratory Diagnosis
F. Secondary Hyperparathyroidism
● Differential Diagnosis
Causes of Secondary Hyperparathyroidism
● Familiar Hypocalciuric Hypercalcemia
o Compensatory enlargement of the PTG due to chronic hypocalcemia
o Vitamin D-deficiency (Ricketts/osteomalacia)
E. Primary Hyperparathyroidism (PHPT)
o Chronic Renal Failure/Chronic Renal Disorders
PHPT
o Pregnancy and Lactation
o Syndrome of inappropriate secretion of PTH by one or more
abnormal glands
o Most cases are sporadic with female to male; 4:1 Laboratory Results
o Familial Syndrome are relatively rare, and include; o Increase PTH
→ MEN Types I and II o Decreased ionized Calcium
→ Multiple Endocrine Neoplasia = cluster of endocrine gland o High serum phosphates
neoplasia
▪ MEN Type I = involves pituitary gland, parathyroid gland G. Tertiary Hyperparathyroidism
and pancreas Tertiary Hyperparathyroidism
▪ MEN Type II – due to overactivity of PTG associated o Occurs with secondary hyperparathyroidism
with tumors in the adrenal and thyroid gland
H. Hypoparathyroidism
o 85 – 90% are caused by a ‘single adenoma’
o Multiple gland disease either as multiple adenomas or hyperplasia of Hypoparathyroidism
all four (4) glands 10 – 15% o PTH deficiency → lead to hypocalcemia
o < 1% parathyroid carcinoma o Most common is neck surgery
→ The most common cause of primary hyperparathyroidism is due → Cause: accidental injury to parathyroid glands (neck) during
to the PT gland becoming enlarged because of development of surgery
a benign, non-cancerous tumor (adenoma) ▪ Autoimmune parathyroid destruction
→ Diagnosed mainly in post-menopausal women o Effects depend on severity and rate of drop
o Neuromuscular features;
→ Paresthesia (perioral, fingertips)
▪ Characterized as abnormal sensation of the skin
▪ Tingling, prickling numbness with no apparent physical
cause
→ Muscle weakness and cramps, fasciculations (spontaneous
muscle twitching)

→ Tetany
Parathyroid Adenoma – Right Inferior
▪ Chvostek’s Signs
o Classical presentation;
→ ‘Stones, bones, abdominal groans, thrones, and psychiatric ▪ Trousseau’s Signs
overtones’
▪ Stones = refers to kidney stones, or nephrocalcinosis Chvostek’s Signs
▪ Bones = refer to bone-related complications (osteoporosis, o Elicited by tapping over facial nerve → result: twitching of
osteomalacia and osteoarthritis)
ipsilateral facial muscles
▪ Abdominal Groans = refers to GI symptoms → Cranial Nerve VII is affected (facial nerve)
(constipations, indigestions, nausea and vomiting) → Cheek is tapped and facial muscle on the same side of the face
▪ Thrones = refers to polyuria and constipation will detract sporadically and exhibit spasms
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[CC2-LEC] PARATHYROID GLANDS AND CALCIUM HOMEOSTASIS – Prof. Mark Ryan V. Domingo
→ Muscle hyperexcitability because of low blood calcium I. Differential Diagnosis
Differential Diagnosis
Condition Ca PO4 PTH 25-Vit D 1,25-Vit D
(Liver) (Kidney)
Hypoparathyroidism    N 
Pseudo-    N /N
hypoparathyroidism
Liver Disease     /N
Renal Disease    N /N

Trousseuae’s Signs J. Familiar Hypocalciuric Hypercalcemia

o Inflation of BP cuff to 20 mmHg above SBP for 3 minutes → Familiar Hypocalciuric Hypercalcemia
result: carpal spasm o Aberration in CSR’s
→ 140 mm pressure o Caused by mutation
→ If the patient has tetany, doctor will observe carpal spasm in o Upsets the PTG cells operating set point ranges
response to inflation of 20 mmHg above SBP o Laboratory Diagnosis;
→ Denotes muscle hyperexcitability due to decreased blood → Serum Calcium = mildly/moderately elevated
calcium → Serum Magnesium = mildly elevated
→ PTH = mildly elevated
→ Urine Calcium = low
→ No end-organ damage (bone/kidneys)

Sources;
- Lecture Video: https://www.youtube.com/watch?v=lXBciFmZSa4&t=5s
- Clinical Chemistry 2 (Fourth Edition) – Learning Module and
Laboratory Manual by Ma. Flordeliza Sy Gutierrez and Kathlene Joy
Labrador-Limcumpao
Laboratory Diagnosis
o Serum Calcium = decreased
o Serum Phosphorus = increased
o Serum i-PTH = decreased
o Differential diagnosis of the etiologies of hypocalcemia is necessary:
→ These laboratory works should be requested in order to
differentiate the causes of hypocalcemia
o Hypoparathyroidism, pseudohypoparathyroidism, liver disease,
kidney disease

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