Parathyroid hormone

Recognising parathyroid hormone disorders is important and it is very much useful for both ug and pg students of medicine and other branches.

1. Dr.S.Sethupathy.M.D.,Ph.D.,
Professor of Biochemistry,
Rajah Muthiah Medical College,
Annamalai university.

2. Parathyroid hormone (PTH),
parathormone or parathyrin, is
secreted by chief cells of parathyroid
glands.
A polypeptide contains 84 amino
acids.
It increases the concentration of
calcium (Ca2+) in the blood.

4. The primary gene product is pre-proPTH (115
amino acids).
The N-terminal signal sequence(25 amino acids)
is cleaved and proPTH( 90 amino acids) is
released.
proPTH on further cleavage , releases PTH(84
amino acids).
PTH
1-34has full biologic activity. PTH
25-34is
responsible for receptor binding.

7. Serum PTH concentration is dependent upon the release
of PTH stored and the synthesis of new PTH.
Rapid PTH release from secretory granules in
hypocalcemic states is modulated by the binding of
Ca
2+
to CaSRs on chief cells
But long-term replenishment of PTH stores is dependent
on new PTH synthesis
Hypocalcemia also retards the rate of degradation of
PTH within the parathyroid gland
Phosphorus additionally alters PTH synthesis, but the
precise mechanisms are unknown

8. Secretion of parathyroid hormone is controlled
chiefly by serum [Ca2+] through negative
feedback.
Calcium-sensing receptors located on
parathyroid cells are activated when [Ca2+] is
low.
PTH is continuously produced and degraded.
When blood calcium is low, the degradation is
reduced and PTH is released.
When blood calcium is high, degradation is
increased and PTH is not released.

9. Secretion of parathyroid hormone is determined chiefly
byserumionized calciumconcentration thronegative
feedback.
Calcium bindscalcium-sensing receptorson the cell
surface.
It results in activation of the Gq G-protein coupled
cascade through the action ofphospholipase C
This hydrolyzesphosphatidylinositol 4,5-
bisphosphate(PIP2) to liberate intracellular
messengersIP3anddiacylglycerol(DAG).
It results in a release of calcium from intracellular stores
into the cytoplasmic space.
It inhibits release of PTH.
PTH is secreted when [Ca
2+
] is decreased

10. PTH increases blood calcium by acting
on parathyroid hormone 1 receptor (high
levels in bone and kidney)
The parathyroid hormone 2 receptor (high
levels in the central nervous system,
pancreas, testis, and placenta).
PTH half-life is approximately 4 minutes.
PTH uses G-protein mediated activation of
adenylyl cyclase and cAMP second
messenger for its actions.

12. Bone resorptionis done by osteoclasts which
are indirectly stimulated by PTH.
Osteoclasts do not have a receptor for PTH
PTH binds toosteoblasts.
Binding stimulates osteoblasts to increase their
expression of RANKL and inhibits their
expression ofOsteoprotegerin(OPG).
RANKL binds to the Receptor activator of
nuclear factor Kappa B(RANK) on the surface of
the osteoclasts.

13. Normally OPG blocks the binding of
RANKLwith RANK, a receptor for
RANKL.
Due to decreased OPG, the binding of
RANKL toRANK is increased
resulting in the fusion of these
osteoclast precursors
The new osteoclasts enhancesbone
resorption.

15. It enhances active reabsorption of calcium
and magnesium fromdistal tubulesand
the thick ascending limb.
It also decreases the reabsorption of
phosphate –Phosphaturic effect
Reduced plasma phosphate concentration
increase calcium:phosphate ratio
It results in more free calcium in blood.

17. PTH activates 1-alpha-hydroxylase enzyme
responsible for 1-alphahydroxylation of25-
hydroxy vitamin D3
Converts it to its active form ( calcitriol).
Calcitriol increases the absorption of calcium (as
Ca
2+
ions) by the intestine via calbindin protein.
Calbindin absorbs calcium in the intestine.

19. Intact (whole): 10-65 pg/mL or 10-
65 ng/L (SI units)
N terminal: 8-24 pg/mL
C terminal: 50-330 pg/mL

20. Primary hyperparathyroidism
-the unregulated overproduction
of parathyroid hormone (PTH)
resulting in abnormal calcium
homeostasis.

21. In approximately 85% of cases, primary
hyperparathyroidism is caused by a single adenoma.
In 15% of cases, multiple glands are involved (ie, either
multiple adenomas or hyperplasia).
Primary hyperparathyroidism is caused by parathyroid
carcinoma.
Familial cases can occur aseither part of the multiple
endocrine neoplasia syndromes (MEN 1 or MEN 2a),
hyperparathyroid-jaw tumor (HPT-JT) syndrome, or
familial isolated hyperparathyroidism (FIHPT).
Familial hypocalciuric hypercalcemia and neonatal
severe hyperparathyroidism
An increase in the cell numbers is probably the cause.

22. Bones, stones, abdominal groans, and
psychic moans
Bone and joint pain, pseudogout, and
chondrocalcinosis
Renal manifestations include polyuria, kidney
stones, hypercalciuria, and
rarelynephrocalcinosis.
GI manifestations -anorexia, nausea, vomiting,
abdominal pain, constipation, peptic ulcer disease,
and acute pancreatitis.

23. Neuromuscular and psychologic
manifestations -proximal myopathy,
weakness and easy fatigability,
depression, inability to concentrate, and
memory problems
75% of the patients -females ,usually
postmenopausal.

25. Serum ionized calcium –increased
Serum albumin
PTH –elevated
Vit D -< 20 ng/ml –secondary
hyperparathyroidsm
Hyperchloremic acidosis
Hypophosphatemia,
Mildto moderate increase in urinary
calcium excretion rate.
Renal function tests

26. It can be due to vitamin D deficiency or
renal failure.
It can also occur in Paget’s disease,
multiple myeloma, bone metastases.
Serum calcium is normal or low with high
PTH level.
Calcium and vitamin D supplements in
case of vitamin D deficiency
Calcitriol given in case of renal failure

27. A state of excessive secretion of
parathyroid hormone after longstanding
secondaryhyperparathyroidismand
resulting in hypercalcemia.
Or secondaryhyperparathyroidismthat
persists after successful renal
transplantation

28. It is commonly due to removal of the glands.
Wilson’s disease, hemochromatosis and
metastasis can also cause.
The clinical features are mainly the
neuromuscular effects of hypocalcemia.
The clinical features are numbness,
paraesthesia, muscle stiffness, cramps,
fasciculations and tetany.
Both serum calcium and PTH are low.
Treatment Calcium and vitamin D are given.
PTH is not used currently.

31. Serum calcium is low with normal PTH
level
It is due to end organ resistance.
The clinical features are short stature,
round facies, mental retardation, dental
abscesses.
vitamin D and calcium are given.

32. Calcitonin counteracts parathyroid
hormone (PTH).
It inhibits Ca2+ absorption by the
intestines.
It inhibits osteoclast activity in bones.
It inhibits renal tubular cell reabsorption of
Ca2+ and increases its excretion.
It inhibits phosphate reabsorption by the
kidney tubules.

33. The calcitonin receptor, found on
osteoclasts, and in kidney and regions of
the brain, is a Gs protein-coupled receptor
which activates adenylate cyclase and
increases cAMP in target cells.
Clinical applications
Calcitonin is used for the treatment of
Postmenopausal osteoporosis,
Hypercalcaemia, Paget's disease, Bone
metastases and Phantom limb pain.