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PARATHYROID GLANDS

The parathyroid glands lie in close proximity to the upper and lower poles of each thyroid lobe, . Most of the gland is composed ofchief cells. contain secretory granules ofparathyroid hormone (PTH). 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

primarysecondaryless 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 HyperparathyroidismPrimary hyperparathyroidism is one of the most common endocrine disorders, and it is an important cause ofhypercalcemia.Adenoma-75% to 80%Primary hyperplasia (diffuse or nodular)-10% to 15%Parathyroid carcinoma-less than 5%

In more than (95% )sporadic parathyroid adenomas or sporadic hyperplasia. The genetic defects identified in familial primary hyperparathyroidism include multiple endocrine neoplasia syndromes, specifically MEN-1 and MEN-2AFamilial 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

almost invariably confined to single glands )(75% -80% ) solitary adenoma,( either in it is place or in etopic regions), a well-circumscribed, soft, tan nodule, invested by a delicate capsule. Wt.(0.5- 5 gm). the remaining glands are normal in size or somewhat shrunken, as a result of feedback inhibition by elevations in serum calcium.

Microscopically, composed predominantly of chief cellslarger oxyphil cells are also present. 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. There is slight variation in nuclear size and tendency to follicular formation but no anaplasia.

Parathyroid carcinomas

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

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 gallstonesCentral nervous system alterations,including depression, lethargy, and seizuresNeuromuscular abnormalities,including weakness and hypotoniaPolyuriaand secondary polydipsia

Clinical Features

Causes of HypercalcemiaA-Raised PTH HyperparathyroidismPrimary (adenoma >hyperplasia)*SecondaryTertiaryFamilial hypocalciuric hypercalcemia

B-Decreased PTHHypercalcemia of malignancyOsteolytic metastases(PTH-rP mediated)Vitamin D toxicityImmobilizationDrugs (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.

MorphologyThe parathyroid glands in secondary hyperparathyroidism are hyperplastic.not necessarily symmetric.

Microscopically, the hyperplastic glands contain an increased number of chief cells, 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, heart, stomach, and blood vessels.

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:Surgical ablation:inadvertent removal of parathyroids during thyroidectomy.Congenital absence:usually occurs in conjunction with thymic aplasia and cardiac defects in DiGeorge syndromeAutoimmune hypoparathyroidism:a hereditary polyglandular deficiency syndrome arising from autoantibodies to multiple endocrine organs (parathyroid, thyroid, adrenals, and pancreas). 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 includeincreased neuromuscular irritabilitytingling, muscle spasms, facial grimacing, and sustained carpopedal spasm or tetanycardiac arrhythmias,Increased intracranial pressuresandseizures.

Morphologic changes are generally inconspicuous but may include cataracts, calcification of the cerebral basal ganglia, and dental abnormalities.

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