1. PTH and CALCIUM
HOMEOSTASIS
Parathyroid Gland
• 4 small glands located on the
dorsal side of the thyroid
gland
• The parathyroid glands are
usually embedded between
the posterior border of the
thyroid gland and its fibrous
capsule.
• At times, the parathyroids
may be intrathyroidal. They
measure 6 x4x2 mm in
maximum diameter and weigh
25-40 mg each.
• Number of glands can vary
from 4-6

2. History
 Sir Richard Owen, the curator of the British Museum of Natural
History, discovered the parathyroid glands in 1852 while
dissecting a rhinoceros that had died in the London Zoo.
 However, credit for discovery of the human parathyroid glands
usually is given to Sandstrom, a Swedish medical student who
published an anatomical report in 1890.
 In 1891, von Recklinghausen reported a new bone disease, which
he termed "osteitis fibrosa cystica," which Askanazy
subsequently described in a patient with a parathyroid tumor in
1904.
 The glands were rediscovered a decade later by Gley, who
determined the effects of their extirpation with the thyroid.
 Vassale and Generali then successfully removed only the
parathyroids and noted that tetany, convulsions, and death
quickly followed unless calcium was given postoperatively

3. Unique properties of PTH
PTH secretion responds to small alterations in plasma Ca2+
within seconds.
A unique calcium receptor within the parathyroid cell plasma
membrane senses changes in the extracellular fluid concentration
of Ca2+.
This is a typical G-protein coupled receptor that activates
phospholipase C and inhibits adenylate cyclase—result is
increase in intracellular Ca2+ via generation of inositol phosphates
and decrease in cAMP which prevents exocytosis of PTH from
secretory granules
PTH secretion also is stimulated by, low levels of 1,25-
dihydroxy vitamin D, catecholamines, and hypomagnesemia.
PTH is synthesized in the parathyroid gland as a precursor
hormone, preproparathyroid hormone, which is cleaved first to
proparathyroid hormone and then to the final 84-amino-acid PTH.
Secreted PTH has a half-life of 2 to 4 minutes

4. Role of PTH in Calcium Homeostasis

5. Parathyroid “C” Cells
PTH Calcitonin
Inhibit
Inhibit
Bone Bone
Kidney Kidney
Intestine
[Ca++] [Ca++]
In plasma In plasma

6. Control of bone formation and resorption
• Bone resorption of Ca++ by two mechanims:
osteocytic osteolysis is a rapid and transient effect and
osteoclasitc resorption which is slow and sustained.
• Both are stimulated by PTH.
• Does not merely extract calcium, it destroys entire
matrix of bone and diminishes bone mass.
• Cell responsible for resorption is the osteoclast.

7. Bone remodeling
• Endocrine signals to resting osteoblasts generate
paracrine signals to osteoclasts and precursors.
• Osteoclasts resorb an area of mineralized bone.
• Local macrophages clean up debris.
• Process reverses when osteoblasts and precursors
are recruited to site and generate new matrix.
• New matrix is minearilzed.
• New bone replaces previously resorbed bone.

8. Osteoclasts and Ca++ resorption

9. Calcium, bones and osteoporosis
• The total bone mass of humans peaks at 25-35 years of age.
• Men have more bone mass than women.
• A gradual decline occurs in both genders with aging, but
women undergo an accelerated loss of bone due to increased
resorption during perimenopause. Bone resorption exceeds
formation.
• Reduced bone density and mass: osteoporosis
• Susceptibility to fracture. Earlier in life for women than men but
eventually both genders succumb.
• How to reduce risk?
Inc in calcium in the diet
habitual exercise
avoidance of smoking and alcohol intake
avoid drinking carbonated soft drinks

10. Hormonal control of Ca2+
• Three principal hormones regulate Ca++ and three
organs that function in Ca++ homeostasis.
• Parathyroid hormone (PTH), 1,25-dihydroxy
Vitamin D3 (Vitamin D3), and Calcitonin,
regulate Ca++ resorption, reabsorption, absorption
and excretion from the bone, kidney and intestine.
In addition, many other hormones effect bone
formation and resorption.

11. Hyperparathyroidism
• Calcium homeostatic loss due to excessive PTH
secretion
• Due to excess PTH secreted from adenomatous or
hyperplastic parathyroid tissue
• Hypercalcemia results from combined effects of
PTH-induced bone resorption, intestinal calcium
absorption and renal tubular reabsorption
• Pathophysiology related to both PTH excess and
concomitant excessive production of 1,25-(OH)2-D.

12. Hypoparathyroidism
• Hypocalcemia occurs when there is inadequate response of
the Vitamin D-PTH axis to hypocalcemic stimuli
• Hypocalcemia is often multifactorial
• Hypocalcemia is invariably associated with
hypoparathyroidism
• PTH-deficient hypoparathyroidism
– Reduced or absent synthesis of PTH
– Often due to inadvertent removal of excessive
parathyroid tissue during thyroid or parathyroid surgery
• PTH-ineffective hypoparathyroidism
– Synthesis of biologically inactive PTH