PARATHYROID GLANDS

The parathyroid glands

lie in close proximity to the upper and lower poles
of each thyroid lobe,
1. . Most of the gland is composed of chief cells.
contain secretory granules of parathyroid
hormone (PTH).
2. Oxyphil cells slightly larger than the chief
cells, have acidophilic cytoplasm,.

The activity of the parathyroids is controlled by

the level of free (ionized) calcium in the
bloodstream rather than by trophic hormones
secreted by the hypothalamus and pituitary.
The net result of these activities is an increase in
the level of free calcium, which inhibits further
PTH secretion.

HYPERPARATHYROIDISM

1. primary
2. secondary
3. less commonly, astertiaryhyperparathyroidism
. The first condition represents an autonomous, spontaneous
overproduction of PTH, while the latter two conditions typically
occur as secondary phenomena in individuals with chronic renal
insufficiency.

Primary Hyperparathyroidism
Primary hyperparathyroidism is one of the most common endocrine
disorders, and it is an important cause ofhypercalcemia.

4. Adenoma-75% to 80%
5. Primary hyperplasia (diffuse or nodular)-10% to 15%
6. Parathyroid carcinoma-less than 5%

1. In more than (95% )sporadic parathyroid

adenomas or sporadic hyperplasia.
2. The genetic defects identified in
I. familial primary hyperparathyroidism
include multiple endocrine neoplasia
syndromes, specifically MEN-1 and MEN2A
II. Familial hypocalciuric hypercalcemia is a
rare cause of hyperparathyroidism,
caused by inactivating mutations in the
calcium-sensing receptor(CASR)gene on
parathyroid cells, leading to constitutive
PTH secretion.

Morphology

1. almost invariably confined to single glands )(75%

-80% ) solitary adenoma,
2. ( either in it is place or in etopic regions),
3. a well-circumscribed, soft, tan nodule, invested by a
delicate capsule.
4. Wt.(0.5- 5 gm).
5. the remaining glands are normal in size or somewhat
shrunken, as a result of feedback inhibition by
elevations in serum calcium.

Microscopically,
1) composed predominantly of chief cells
2) larger oxyphil cells are also present.
3) A rim of compressed, non-neoplastic parathyroid
tissue, generally separated by a fibrous capsule, is
often visible at the edge of the adenoma.

Parathyroid hyperplasia is characteristically a

multiglandular process.
Microscopically,
the most common pattern seen is that of chief-cell
hyperplasia, which may involve the glands in a
diffuse or multinodular pattern.

Solitary chief-cell parathyroid adenoma(low-power

view)revealing clear delineation from the residual gland
below.B,High-power detail of chief-cell parathyroid adenoma.

Parathyroid carcinomas

1. are usually firm or hard tumors,

2. adhering to the surrounding tissue
3. Parathyroid carcinomas are larger
than adenomas(5 gm -10 gm) or
more.
4. typically single-gland disorders, and
chief cells tend to predominate in
most cases.
5. The only two valid criteria for
malignancy are
(1) invasion of surrounding tissues and
(2) metastatic dissemination.

Clinical Features

Primary hyperparathyroidism
is usually a disease of adults
and is more common in women than in men by a ratio of nearly 3 :
1.
. Hypercalcemia causes:
"painful bones, Skeletal manifestations of hyperparathyroidism
include
bone resorption,osteitis fibrosa cystica,and "brown tumors.
renal stones, Renal changes include ,nephrolithiasis (stones) ,and
nephrocalcinosis.
abdominal groans,
and psychic moans
Gastrointestinal disturbances,including constipation, nausea,
peptic ulcers, pancreatitis, and gallstones
Central nervous system alterations,including depression,
lethargy, and seizures
Neuromuscular abnormalities,including weakness and hypotonia
Polyuriaand secondary polydipsia

Causes of Hypercalcemia
A-Raised PTH
1.
2.
3.
4.
5.

Hyperparathyroidism
Primary (adenoma >hyperplasia)*
Secondary
Tertiary
Familial hypocalciuric hypercalcemia

B-Decreased PTH
6. Hypercalcemia of malignancy
7. Osteolytic metastases(PTH-rP mediated)
8. Vitamin D toxicity
9. Immobilization
10.Drugs (thiazide diuretics) Granulomatous diseases
(sarcoidosis)

Hyperparathyroidism)
(Secondary

is most often caused by renal failure, Chronic renal insufficiency is

associated with decreased phosphate excretion directly depress serum
calcium levels &stimulates (PTH)
Malignancies are the most important cause of symptomatic
hypercalcemia.
Morphology
The parathyroid glands in secondary hyperparathyroidism are
hyperplastic.not necessarily symmetric.
Microscopically, the hyperplastic glands contain
1. an increased number of chief cells,
2. or cells with more abundant, clear cytoplasm(water-clear cells),
.in a diffuse or multinodular distribution. Fat cells are decreased in
number.
.Bone changessimilar to those seen in primary hyperparathyroidism
may also be present.
.Metastatic calcificationmay be seen in many tissues, including lungs,

Clinical Features of 2ndry hyperparathyrodism

usually dominated by those related to chronic renal failure.

other changes associated with PTH excess are, in general, less
severe than those seen in primary hyperparathyroidism.
Serum calcium remains near normal because the compensatory
increase in PTH levels sustains serum calcium.
The metastatic calcification of blood vessels (secondary to
hyperphosphatemia) may occasionally result in significant
ischemic damage to skin and other organs, a process
sometimes referred to ascalciphylaxis.

In a minority of patients, parathyroid activity may become

autonomous and excessive, with resultant hypercalcemia, a

process sometimes termedtertiary
hyperparathyroidism.Parathyroidectomy may be necessary
to control the hyperparathyroidism in such patients.

HYPOPARATHYROIDISM

The major causes include the following:

1. Surgical ablation:inadvertent removal of parathyroids during
thyroidectomy.
2. Congenital absence:usually occurs in conjunction with thymic
aplasia and cardiac defects in DiGeorge syndrome
3. Autoimmune hypoparathyroidism:a hereditary polyglandular
deficiency syndrome arising from autoantibodies to multiple
endocrine organs (parathyroid, thyroid, adrenals, and pancreas).
4. Chronic fungal infections involving the skin and mucous membranes
(mucocutaneous candidiasis) are sometimes encountered in these
individuals, suggesting an underlying defect in T-cell function.

The major clinical manifestations of hypoparathyroidism are referable to

hypocalcemia and includeincreased neuromuscular irritability (tingling,
muscle spasms, facial grimacing, and sustained carpopedal spasm or
tetany),cardiac arrhythmias, and, on occasion, increased intracranial
pressuresandseizures.Morphologic changes are generally inconspicuous but
may include cataracts, calcification of the cerebral basal ganglia, and dental
abnormalities.

clinical manifestations
The major clinical manifestations of hypoparathyroidism are
referable to hypocalcemia and include
increased neuromuscular irritability
1. tingling,
2. muscle spasms,
3. facial grimacing,
4. and sustained carpopedal spasm
5. or tetany
.cardiac arrhythmias,
.Increased intracranial pressures
.andseizures.

Morphologic changes are generally inconspicuous but may include

.cataracts,
.calcification of the cerebral basal ganglia,
.and dental abnormalities.

thank
you