LECTURE № 4. “DISEASES OF ENDORINE SYSTEM”
I. DISEASES OF THYROID GLAND.
1.GOITER.
It is enlargement of the thyroid gland.
1)Diffuse nontoxic (simple) goiter.
Form of goiter that diffusely involves the entire gland without producing nodularity.
Because the enlarged follicles are filled with colloid, the term colloid goiter has been
applied to this condition.
2 types:
A.Endemic goiter occurs in geographical areas where the soil, water and food supply
contain only low levels of iodine. The term endemic is used when goiters are present in
more than 10% of the population in a given region.
B.Sporadic goiter occurs less frequently than does endemic goiter. It can be caused by a
number of conditions, including the ingestion of substances that interfere with thyroid
hormone synthesis.
2 stages:
a)Hyperplastic – thyroid gland is diffuse and symmetrically enlarged, although the
increase is modest, and the gland rarely exceeds 100 to 150 gm. The follicles are lined
by crowded columnar cell, which may pile up and form projections. The accumulation
is not uniform throughout the gland, and some follicles are hugely distended, whereas
others remain small.
b)Colloid involution – the stimulated follicular epithelium involutes to form an
enlarged, colloid-rich gland (colloid goiter). In these cases, the cut surface of thyroid is
usually brown, somewhat glassy and translucent. Histologically the follicular epithelium
is flattened and cuboidal, and colloid is abundant during periods of involution.
2)Multinodular goiter.
With time, recurrent episodes of hyperplasia and involution combine to produce a
more irregular enlargement of the thyroid, termed multinodular goiter. Virtually all
long-standing simple goiters convert into multinodular goiters. They may be nontoxic or
may induce thyrotoxicosis.
Multinodular goiters are multilobulated, asymmetrically enlarged glands,which
may achieve a weight of more than 2000 gm. The pattern of enlargement is quite
unpredictable and may involve one lobe far more than other. On cut section, irregular
nodules containing variable amounts of brown, gelatinous colloid are present.
Regressive changes occur frequently, particularly in old lesions and include areas of
hemorrhage, fibrosis, calcification and cystic change. The microscopic appearance
includes colloid-rich follicles lined by flattened, inactive epithelium and areas of
follicular epithelial hypertrophy and hyperplasia, accompanied by the degenerative
changes.
1
3)Graves disease.
It is the most common cause of endogenous hyperthyroidism. It is characterized by a
triad of clinical findings:
a)hyperthyroidism owing to hyperfunctional, diffuse enlargement of the thyroid,
b)infiltrative ophtalmopathy with resultant exophthalmos,
c)localized infiltravite dermopathy (local edema of skin).
Graves disease is an autoimmune disorder produced by autoantibodies. The thyroid
gland is usually symmetrically enlarged because of the presence of diffuse hypertrophy
and hyperplasia of thyroid follicular epithelial cells. Increases in weight to over 80 gm
are not uncommon. The gland is usually smooth and soft, and its capsule is intact. On
cut section, the parenchyma has a soft, meaty appearance resembling normal muscle.
Histologically the dominant feature is too many cells. The epithelial cells in untreated
cases are tall and more crowded than usual. This crowding often results in the formation
of small papillae, which project into the follicular lumen and encroach on the colloid.
The colloid within the follicular lumen is pale, with scalloped margins. Such
papillae lack fibrovascular cores. On occasion, the papillae are sufficiently large to
expand out and virtually fill the follicles. There is striking increase in the amount of
lymphoid tissue in the interfollicular stroma, and in some areas, large lymphoid
aggregates consisting of autoreactive B cells are present.
2.THYROIDITIS.
Thyreoiditis, or inflammation of the thyroid gland, encompasses a diverse group of
disorders characterized by some form of thyroid inflammation. These diseases include
conditions that result in acute illness with severe thyroid pain (e.g. infectious thyroiditis,
subacute granulomatous thyroiditis) and disorders in which there is relatively little
inflammation and the illness is manifested primarily by thyroid disfunction (subacute
lymphocytic thyroiditis and fibrous Reidel thyroiditis).
Classification:
1.Acute thyroiditis:
1)Infectious (bacterial infections, fungal infections).
2)Radiation.
2.Subacute thyroiditis:
1)Subacute granulomatous thyroiditis,
2)Subacute lymphocytic thyroiditis.
3)Tuberculous thyroiditis.
3.Chronic thyroiditis:
1)Hashimoto thyroiditis.
2)Reidel’s thyroiditis
2
1)Subacute (granulomatous) thyroiditis, which also refered to as granulomatous
thyroiditis or DeQuervain thyroiditis, occurs much less frequently than does Hashimoto
disease. The gland may be unilaterally or bilaterally enlarged and firm, with an intact
capsule. It may be slightly adherent to surrounding structures. On cut section, the
involved areas are firm and yellow-white and stand out from the more rubbery, normal
brown thyroid substance. Histologically the changes are patchy and depend on the stage
of the disease. Early in the active inflammatory phase, scattered follicles may be
entirely disrupted and replaced by neutrophils forming microabscesses. Later the more
characteristic features appear in the form of aggregations of lymphocytes, histiocytes,
and plasma cell about collapsed and damaged thyroid follicles. Multinucleate giant cells
enclose naked pools or fragments of colloid, hence the designation granulomatous
thyroiditis. In later stages of the disease, a chronic inflammatory infiltrate and fibrosis
may replace the foci of injury.
2)Subacute lymphocytic thyroiditis, which also is referred to as painless thyroiditis,
silent thyroiditis is uncommon cause of hyperthyroidism. Except for possible mild
symmetric enlargement, the thyroid appears normal on gross inspection. Microscopic
examination of the gland reveals a multifocular inflammatory infiltrate composed
predominantly of small lymphocytes and patchy disruption and collapse of thyroid
follicles. Plasma cells and germinals are not conspicuous and when present, suggest the
possibility of Hashimoto disease.
3)Hashimoto thyroiditis is the most common cause of hypothyroidism in areas of the
world where iodine levels are sufficient. It is characterized by gradual thyroid failure
because of autoimmune destruction of thyroid gland. The thyroid is diffusely enlarged,
although more localized enlargement may be seen in some cases. The capsule is intact,
and the gland is well demarcated from adjacent structures. The cut surface is pale, graytan, firm and somewhat nodular. Microscopic examination reveals extensive infiltration
of the parenchyma by a mononuclear inflammatory infiltrate containing small
lymphocytes, plasma cells, and well-developing germinal centers. The thyroid follicules
are small and are lined in many areas by epithelial cells with abundant eosinophilic,
granular cytoplasm, termed Hurthle cells.
4)Riedel’s thyroiditis, also called Riedel’s struma or invasive fibrous thyroiditis, is a
rare chronic disease characterized by stony-hard thyroid that is densely adherent to the
adjacent structures in the neck. The condition is clinically significant due to
compressive clinical features (dysphagia, dyspnoea, recurrent laryngeal paralysis and
stridor and resemblance with thyroid cancer. Riedel’s struma is seen more commonly in
females in 4th to 7th decades of life. The thyroid gland is usually contracted, sony-hard,
asymmetric and firmly adherent to the adjacent structures. Cut section is hard and
devoid of lobulations. Microscopically, there is intensive fibrocollagenous replacement,
marked atrophy of the thyroid parenchyma, focally scattered lymphocytic infiltration
and invasion of the adjacent muscle tissue by the process.
3
3.NEOPLASMS OF THYROID GLAND.
1)Benign tumors – adenomas.
2)Malignant tumors – carcinomas.
The typical thyroid adenoma is a solitary, spherical, encapsulated lesion that is well
demarcated from the surrounding thyroid parenchyma. Follicular adenomas average
about 3 sm in diameter, but some are smaller and other are much larger (up to 10 cm in
diameter). In freshly resected specimens, the adenoma bulges from the cut surface and
compresses the adjacent thyroid. The color ranges from grey-white to red-brown,
depending on the cellularity of the adenoma and its colloid content. Areas of
hemorrhage, fibrosis, calcification and cystic change similar to those encountered in
multinodular goiters are common, particularly within larger lesions. The neoplastic cells
are demarcated from the adjacent parenchyma by a well-defined intact capsule. Careful
evaluation of the integrity of the capsule is important in the distinction of follicular
adenomas from well-differentiated follicular carcinomas. Microscopically the
constituent cells often form uniform-appearing follicles that contain colloid Various
histologic subtypes of adenomas are recognized, based on the degree of follicle
formation and the colloid content of the follicles: macrofollicular (simple colloid),
microfollicular (fetal), embrional (trabecular), Hurthle cell adenomas, atypical
adenomas and adenomas with papillae.
Carcinomas are solitary or multifocal lesions within the thyroid. Some tumors may
be well circumscribed and even encapsulated, whereas others may infiltrate the adjacent
parenchyma with ill-defined margins. Larger lesions may penetrate the capsule and
infiltrate well beyond the thyroid capsule into the adjacent neck. The lesions may
contain areas of fibrosis and calcification and are often cystic. The major subtypes of
thyroid carcinoma and their relative frequencies include: papillary carcinoma (75 to
85% of cases), follicular carcinoma (10 to 20% of cases), medullary carcinoma (5% of
cases), anaplastic carcinoma (less than 5% of cases).
II.DIABETES MELLITUS.
Diabetes mellitus is a chronic disorder of carbohydrate, fat, and protein metabolism.
A defective or deficient insulin secretory response, which translates into impaired
carbohydrate (glucose) use, is a characteristic feature of diabetes mellitus, as is the
resultant hyperglycemia.
Classification:
1)Type 1 diabetes, also called insulin-dependent diabetes mellitus and previously
referred to as juvenile-onset diabetes.
2)Type 2 diabetes, also called non-insulin-dependent diabetes mellitus and previously
referred to as adult-onset diabetes.
3)Maturity-onset diabetes of the young, results from genetic defects of β-cells function.
4
Morphology.
Pancreas. Lesions in the pancreas are inconstant and rarely of diagnostic value.
Distinctive changes are more commonly associated with type 1 than with type 2
diabetes. One or more of the following alterations may be present.
1)Reduction in the number and size of islets. Most of the islets are small, inconspicuous,
and not easily detected.
2)Leukocytic infiltration of the islets (insulitis) principally composed of T lymphocytes.
This may be seen in type 1 diabetes.
3)Amyloid replacement of islets in type 2 diabetes appears as deposition of pink,
amorphous material.
Vascular system. The aorta and large- and medium-sized arteries suffer from
accelerated severe atherosclerosis. Myocardial infarction, caused by atherosclerosis of
the coronary arteries, is the most common cause of the death in diabetics. Gangrene of
the lower extremities, as a result of advanced vascular disease, is about 100 times more
common in diabetics than in the general population. Hyaline arteriolosclerosis, the
vascular lesion associated with hypertension.
Diabetic microangiopathy. One of the most consistent morphologic features of
diabetes is diffuse thickening of basement membranes. The thickening is most evident
in the capillaries of the skin, skeletal muscle, retina, renal glomeruli, and renal medulla.
Despite the increase in the thickness of basement membranes, diabetic capillaries are
more leaky than normal to plasma proteins. The microangiopathy underlies the
development of diabetic nephropathy and some forms of neuropathy.
Diabetic nephropathy. Three lesions are encountered:
1)glomerular lesions (nodular or diffuse glomerulosclerosis),
2)renal vascular lesions, principally arteriolosclerosis,
3)pyelonephritis.
Diabetic ocular complications. The ocular involvement may take the form of
retinopathy, cataract formation, or glaucoma. Visual impairment, sometimes even total
blindness, is one of the more feared consequences of long-standing diabetes.
Diabetic neuropathy. The most frequent pattern of involvement is a peripheral,
symmetric neuropathy of the lower extremities that affect both motor and sensory
function but particularly the latter. In the brain may be cerebral vascular infarcts and
hemorrhages.
5
6