- There are 4 parathyroid glands located on the posterior surface of the thyroid gland that secrete parathyroid hormone (PTH), a polypeptide hormone. PTH increases calcium and decreases phosphate levels in the blood by acting on bone, kidney, and intestine. It mobilizes calcium from bone and increases calcium reabsorption in the kidney. PTH also increases vitamin D production, which further increases calcium absorption. Disorders of the parathyroid glands can lead to hypoparathyroidism or hyperparathyroidism and impact calcium and phosphate levels.

1. Parathyroid Hormone
Dr. Osama Mahmoud
MBChB, M.Sc., M.D.
Assist. Prof. of Physiology, Faculty of Medicine,
Taif University, KSA & Al-Azhar University, Egy.

2. Parathyroid Glands
• There are 4 parathyroid glands, located on the posterior surface of the
thyroid gland.
• Parathyroid secretes: Parathyroid hormone (PTH) by the chief cells

4. Parathyroid Hormone (Parathormone)
• Chemistry: it is a polypeptide hormone consisting
of 84 AAs.
• Secreted from the parathyroid glands in response
to a decrease in the plasma Ca2+ level
• PTH is the most important regulator of plasma
calcium and phosphorus concentration
• Its action is opposed by the hormone calcitonin.

5. Mechanism of Action of PTH
• PTH is released in
response to changes
in plasma Ca2+ levels.
• PTH binds to GPCRs
on the cell
membrane of target
cells → increases
cAMP and IP3-DAG

6. Actions of Parathyroid H.
Essential for Life
to maintain the solubility product constant.
Solubility product: Ca2+ x PO4
3- = Constant
So increase in Ca++ must be associated with
decrease in PO4
3- and vice versa.
PTH:  plasma Ca2+ and  plasma PO4
3-

7. Actions of parathyroid hormone
PTH Vs calcitonin?

8. Rapid Phase - Activation of Calcium Pump
 Bon matrix:
- 1% labile (exchangeable) calcium
- 99% calciumsalts
 In response to decreased
plasma Ca2+ level:
PTH within minutes activate
calcium pump located in the
osteocytic membrane thus
allowing labile calcium to
diffuse from bone fluid into
the ECF.
Effect of PTH on Bone

9. Slow phase- Activation of Osteoclasts
• Requires several days or even weeks to become fully developed
• PTH indirectly (via osteoblasts) stimulates osteoclasts
Activation of the osteoclastic system in 2 stages:
1. Immediate activation of the already formed osteoclasts.
2. Formation of new osteoclasts (proliferation).
The activated osteoclasts then secrete:
1. Proteolytic Enzymes from lysosomes that digest organic
matrix (osteoid).
2. Citric acid and lactic acid from mitochondria → solubilize
hydroxyapatite crystals → mobilizing both Ca2+ and PO4
3-
Effect of PTH on Bone

10. Parathyroid Hormone
secreted in hypocalcaemia
Intestine Bone Kidney
↑ Ca++ and
phosphate
absorption from
the intestine
indirectly by
increasing
formation of
1,25-dihydroxy
vitamin D
Rapid phase:
activates Ca-pump in
osteocytes  pumps Ca &
PO4 into the ECF
Slow phase:
1. Activates osteoclasts
(indirectly)
2. Synthesis of new osteoclasts
  Ca & PO4 resorption
- ↓ Phosphate reabsorption by
PCTs and increase its
urinary excretion →
Phosphaturia
- ↑ Ca++ reabsorption from LH
and late part of DCTs.
- ↑ Mg++ reabsorption
- ↑ activity of 1 α hydroxylase
→ ↑1,25-dihydroxy vitamin D

11. Calcium Homeostasis

12. Parathyroid H. Regulation
Plasma Ca++ level: PTH secretion is determined chiefly by serum
ionized calcium conc. through negative feedback (parathyroid cells
express calcium-sensing receptors on the cell surface)
 Ca++ →  PTH secretion and vice versa
Plasma phosphate level:
 Plasma phosphate level →  PTH secretion
Mg++:
 Mg++ →  PTH secretion and vice versa
1,25-dihydroxy vitamin D:
Its increase → increase Ca++ → decreased PTH

13. PTH related protein - (PTHrP)
• This is a protein member of the parathyroid hormone
family (with PTH activity).
• It is found that level of PTHrP in plasma is elevated in
patients with certain malignancies e.g. carcinomas of
lungs, esophagus and renal carcinoma.
• PTHrP can bind to PTH receptors and can mimic the
action of parathormone (PTH) produces hypercalcaemia
and hypophosphatemia like PTH.
Phosphate excretion
Resorption

14. Mechanism of Action of
PTH and PTHrP

15. Parathyroid disorders
 Hypoparathyroidism
 Hyperparathyroidism

16. Hypoparathyroidism
• A low level of PTH in the blood.
Causes:
• Accidental removal of glands during surgical
thyroidectomy (commonest)
• Autoimmune disease damaging the gland
• Pseudohypoparathyroidism: congenital receptor disorders
Manifestations:
• Hypocalcemia: numbness, tingling, intestinal and biliary
colic and cardiac arrhythmias “tetany” (main feature).
• Hyperphosphatemia.

17. Tetany
- Tetany is a state of increased neuromuscular excitability that
results from abnormally reduced plasma concentrations of
certain ions (Ca2+, Mg2+, or H+ [alkalosis]) → involuntary
spastic contraction of skeletal muscles.
- Manifest tetany: when plasma Ca2+ level is less 7 mg/dl
- Latent tetany: when plasma Ca2+ > 7mg % and < 9 mg%
- Pathophysiology: low Ca++ levels in ECF increase the
permeability of neuronal membranes to Na+ → progressive
depolarization

18. Hyperparathyroidism
• Hyperparathyroidism is an increase in PTH levels in the blood.
• This occurs from a disorder either within the parathyroid
glands (primary hyperparathyroidism) or outside the glands
(secondary hyperparathyroidism)
 Secondary hyperparathyroidism: excessive secretion of PTH
as a physiologic response to hypocalcemia (usually due to
decreased level of 1,25-dihydroxy-vitamin D3)

1. Thinning bones (osteoporosis)
2. Muscle weakness and hypotonia
3. Hypercalcuria-polyuria-renal stones
4. Cardiac arrhythmias
5. Metastatic calcification when plasma Ca2+ level ≥ 17 mg%

19. Thank you