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1.
Anatomy and function of parathyroid glands
Ever since the first description of parathyroid glands by the Swedish
medical student Ivar Sandström in 1889, the embryology, localization
and histo-logy of parathyroid glands have been investigated by numerous
researchers.
Parathyroid
glands are derived from the third and fourth branchial pouch.
These
are normally four, two upper glands and two lower glands, they have
a weight of about 40 mg each, and they are placed right against the
back surface of the thyroid lobes (picture1). The two upper glands are
generally situated next to the back surface of the thyroid capsule,
whereas the position of the lower glands, which are often located near
the lower thyroid margin, may vary, as they may be situated in the thymus,
in the anterior or superior mediastinum or in a intrathyroid or retroesophageal
position.
A distinctive feature of these endocrine organs is multiplicity, the
possibility of an ectopic localisation for each of them, and the existence
of supernumerary glands (picture 2). These factors influence both the
interpretation of instrumental diagnostic investigations and consequent
surgical therapeutic choices. Parathyroid glands are made up of epithelial
cells and stomal fat. Epithelial cells include chief cells, which are
more numerous, with a light cytoplasm and a slightly hypercromic nucleus,
oxyphil cells, which are slightly larger, with granular eosinophilic
cytoplasm and a smaller and strongly hypercromic nucleus, and clear
cells, represented by chief cells whose cytoplasm contains a great amount
of glycogen.
All
cellular types synthesise the parathyroid hormone (PTH). PTH is a single-chain
polypeptide made up of 84 aminoacids whose molecular weight is 9500
dalton. The biological activity of an intact hormone is asso-ciated
with aminoterminal aminoacids 1-34. PTH is produced by means of two
sequential enzymatic hydrolyses, starting from a larger precursory polypeptide,
also known as pre-hormone, which represents the product of the synthesis
coded by the gene of PTH and is named prepro-PTH (Picture 3).
The
prepro-PTH has a short half-life, as it is rapidly hydrolysed with the
formation of a smaller peptide, pro-PTH. Subsequently pro-PTH is also
hydro-lysed with the formation of the final product, PTH, which is stored
and secreted.
2. Physiology of the secretion of parathyroid glands Extracellular ionised
calcium regulates both the secretion and the synthesis of PTH. Parathyroid
cells behave differen-tly from the other tissues owing to their ability
to detect and react to the alterations of concentrated extracellular
calcium.
The
other endocrine cells require the presence of calcium for the stimulus-secretion
mechanism and are blocked when exposed to low calcium concen-trations.
On the other hand parathyroid glands secrete PTH in response to hypocalcemic
stimuli. Parathyroid glands are set up to respond to a decrease in extracellular
calcium, rather than to its increase. However, also hypocalcemia, when
persisting over a long period, can modify PTH levels, and thus inhibit
its production.
The
production of PTH is also inhibited by the synthesis of the active metabolite
of the Vitamin D3 hormone, 1,25(OH)2D3. In fact, in patients suffering
from renal insufficiency, hypocalcemia, the low levels of 1,25(OH)2D3
and probably the presence of toxins, prevent normal calcium homeostasis.
Irrespective
of whether 1,25(OH)2D3 has or has not a physiological role in the continuous
control of PTH secretion, treatment with 1,25(OH)2D3 and calcium generates
on one side an increase in the intestinal absorption of calcium and
on the other it inhibits the synthesis of PTH for its direct effect
on parathyroid glands, and it is therefore important in the treatment
of secondary hyperparathyroidism in chronic renal insufficiency.
It has also recently been demonstrated that hypophosphatemia causes
a decrease in the production of PTH.
The
spare hormonal contents of the parathyroid glands is sufficient to maintain
the normal PTH secretion rate for about 7 hours and the maximum secretion
rate for only 1.5 hours.
Therefore,
parathyroid glands do not store a great amount of hormone and therefore
a steady stimulus should also be accompanied by the sysnthesis of the
hormone.
Even
though there are various factors influencing the secretion of PTH, only
ionised calcium is a significant regulator of the moment-by-moment alterations
in the secretion of the hormone.
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ABSTRACT
BIBLIOGRAFIA
