DISEASES OF ADRENAL GLANDS
Adrenal glands consist of cortex and medullar substance. There are 3 zones in the cortex: glomerular
zone which produces mineralocorticoids e.g. aldosterone, zona fasciculata which produces glucocorticoids, reticular zone which produces sexual hormones.
The adrenal medulla is derived embryologically from neural crest ectoderm and is a part of the sympathetic nervous system. It synthesizes and secretes vasoactive amines, adrenaline and noradrenaline, epinephrine and norepinephrine.
Excessive production of adrenal cortical hormones usually results from hyperplasia or a tumour. Production of adrenal cortical hydrocortisone and sex steroids is controlled by ACTH secreted by the pituitary gland; aldosterone secretion is controlled by renin production by the juxtaglomerular apparatus in the kidney.
Excessive ACTH production, for example by an ACTH-secreting adenoma of the pituitary, stimulates an increase in the number, size and secretory activity of the adrenal cortical cells, leading to adrenal cortical hyperplasia. The uncontrolled excessive production of adrenal cortical hormones may produce Cushing's syndrome. Excessive production of adrenal cortical hormones usually results from hyperplasia or a tumour. When a tumor develops in a definite zone of the cortex the following conditions develop respectively:
a) in glomerular zone — hyperaldosteronism syndrome;
b) in zona fasciculata — Cushing's syndrome;
c) in reticular zone — reduction in sexual function;
d) in medullar substance — pheochromocytoma.
Adrenal cortical adenoma is a well-circumscribed, yellow tumour in the adrenal cortex, which is usually 2—5 cm in diameter. The colour of the tumour, as with the adrenal cortex as a whole, is due to the stored lipid (mainly cholesterol), from which the cortical hormones are synthesized. These tumours are frequent incidental findings at post mortem examination, and appear to have produced no significant metabolic disorder; only a very small percentage produce Cushing's syndrome. Nevertheless, these apparently «non-functioning» adenomas are most often encountered in elderly obese people. There is some debate that they may really represent nodules in diffuse nodular cortical hyperplasia.
Very occasionally, a true adrenal cortical adenoma is associated with the clinical manifestations of Conn's syndrome, and can be shown to be excreting mineralocorticoids.
Adrenal cortical carcinoma is rare, and virtually every case is associated with excessive production of hormones, usually glucocorticoids and sex steroids. As a result the patients usually have features of Cushing's syndrome mixed with androgenic effects, which are particularly noticeable in women. The tumours are usually large and yellowish white, and local invasion and metastatic spread are common.
Acute adrenal cortical failure is usually due to hemorrhagic infarction, but may be iatrogenic.
Bilateral hemorrhagic necrosis of the adrenals is usually associated with disseminated intravascular coagulation. It is a feature of severe septicemia, particularly meningococcal septicemia, in which it is known as the «Waterhouse-Friderichsen syndrome». There is hypovolemic and hypotensive shock, with hypoglycemia, and high risk of sudden death.
Iatrogenic acute adrenal cortical failure may occur when prolonged high-dose therapeutic corticosteroid therapy is abruptly stopped. Prolonged corticosteroid therapy leads to suppression of normal endogenous steroid production by the adrenal cortex, which becomes markedly atrophied. Cessation of exogenous steroid therapy produces acute adrenal cortical failure (adrenal crisis), with hypovolemic and hypotensive shock, hypoglycemia, and risk of sudden death.
Tumours of the adrenal medulla may produce excess adrenaline/noradrenaline or their breakdown products.
The two principal types of tumour of the adrenal medulla are pheochromocytomas (occurring in adults) and neuroblastomas (occurring in children).
Pheochromocytoma is a tumour of the adrenaline- and noradrenaline- (epinephrine- and nore-pineph-rine) secreting cells of the adrenal medulla. It produces high levels of both hormones and their breakdown products, vanyl mandelic acid (VMA) and
homovanillic acid (HVA), both of which are excreted in the urine and can be estimated as a diagnostic test.
Macroscopically, the tumour is usually spherical and less than 5 cm in diameter. It has a pale, creamy cut surface that changes to dark brown almost instantly when exposed to air, due to oxygenation of tumour pigments. Despite the fact that the tumour is usually small and non-metastatic, it is a hazardous condition with high perioperative mortality.
The excessive amine production produces hypertension that is often initially paroxysmal and associated with severe headaches, but the hypertension eventually becomes constant. There may be intractable, and often unexplained, cardiac failure. Pheochro-mocytoma is one of the causes of surgically treatable systemic hypertension.
In 1849 Addison described the so-called bronze disease which develops in bilateral lesion of adrenal cortex with the development of acorticism (absence of hormones) or hypoadrenocorticosis.
The causes of Addison's disease are divided into two groups. One of them causes primary Addison's disease (genetic autoimmune disturbances). Secondary Addison's disease is caused by metastases in the adrenal glands, amyloidosis, hemorrhage, tuberculosis, necrosis due to vascular thrombosis, damage of the
pituitary body (decreases ACTH or corticotropin releasing factor).
Pathology: 1) hyperpigmentation of skin and mucous membrane due to excessive production of melanin stimulating hormone, 2) myocardial atrophy,
3) changes of the lumen in the aorta and large vessels,
4) hyperplasia of the cells of island of Langerhans in the pancreas (hypoglycemia), 5) gastric mucosa atrophy, 6) hyperplasia of thymus and lymphatic peripheral tissue.
The cause of death: 1) acute adrenal failure, 2) cachexia (suprarenal cachexia), 3) cardiovascular insufficiency.
Main thyroid of the diseases are: 1) goiter (struma), 2) thyroiditis, 3) tumors. All these are accompanied by either hyperthyroidism (thyrotoxicosis) or hypothy-roidism (mixedema).
Goiter is a pathologic enlargement of the thyroid gland. Goiters are classified according to their morphology and epidemiology, course, functional and clinical peculiarities.
According to the morphology goiter may be: 1) diffuse, 2) nodular, 3) diffuse nodular.
According to the histology there are 2 types of goiters — colloid and parenchymal.
According to the epidemiology goiter is classified into: 1) endemic, 2) sporadic, 3) diffuse toxic (also termed thyrotoxic goiter, Basedowian disease, Graves disease).
Colloid goiter may be macrofollicular and microfollicular as well as mixed type. It consists of follicles. In case of epithelial proliferation the disease is termed proliferating colloid goiter which is usually nodular.
Parenchymal goiter is characterized by epithelium proliferation with formation of small follicle-like structures without colloid. In the majority of cases the disease is diffuse.
Endemic goiter develops in the areas with iodine deficiency in the drinking water (the Urals, Siberia, Middle Asia, Switzerland). The thyroid gland has the structure of colloid or parenchymal goiter. The functional activity is decreased. In children, endemic cretinism may develop (physical and mental retardation).
Sporadic goiter manifests in young and old age. This may be either colloid, diffuse or colloid diffuse. It does not influence the organism as a whole, but it can cause compression of the esophagus, trachea, larynx, etc. with disturbance of their function. This goiter may be the cause of Basedowian disease.
Diffuse toxic goiter (Basedowian disease, Graves' disease) is caused by autoimmunization.
Morphology: prismatic epithelium turns into cylindrical, epithelium proliferation with formation of papillae, colloid vacuolization, lymphoid plasmocyte stroma infiltration, formation of lymphoid follicles with germ centers are observed.
In the other organs, hypertrophy of the left ventricle of the heart, serous edema and lymphatic infiltration myocardial interstitial spaces develop (thyrotoxic heart). The outcome is diffuse interstitial sclerosis. In the liver, there is serous edema causing thyrotoxic liver fibrosis. Thymus enlargement causes lymphoid tissue hyperplasia and adrenal hypertrophy.
The causes of death are cardiac insufficiency and cachexia.
Reduced output of thyroid hormone produces the symptoms and physical signs of hypothyroidism. In infants, hypothyroidism produces the clinical syndrome termed cretinism, which produces a puffy face and enlarged tongue (coarse features), a protu-berant abdomen, and delayed physical and mental developmental milestones. The main causes of cretinism are:
1. Untreated maternal hypothyroidism. This is now rare, due to better prevention, recognition and treatment of maternal hypothyroidism but it is still a problem in some areas of the world where endemic goiter due to dietary iodine deficiency is seen.
2. Inherited enzyme defect. This produces sporadic cretinism and is due to failure of normal T3 and T4 synthesis.
In adults, hypothyroidism manifests as the syndrome called myxedema, which is due to reduced metabolic rate. There is progressive slowing of physical and mental activity, increasing lethargy and sensitivity to cold, pufry face, coarse dry skin, thinning of hair (particularly of the eyebrows), hoarseness and deepening of voice, and various internal abnormalities, particularly heart failure and a predisposition to hyperlipidemia and hypothermic coma. The main causes of myxedema are:
1. Surgical ablation of the thyroid gland, which is usually as a result of total thyroidectomy for malignant disease, or aggressive subtotal thyroide-ctomy for hyperthyroid Graves' disease. 2. Hashi-moto's disease. 3. Some drug e.g. lithium.
Hashimoto's disease is a destructive autoimmune thyroiditis leading to hypothyroidism. Hashimoto's disease is most common in middle age, affecting women more often than men, a good example of organ-specific autoimmune disease. The most common autoantibodies are an anti-microsomal antibody and antibody to thyroglobulin. Hashimoto's disease is particularly observed in patients with the HLA antigen, HLA-DR5.
The initial clinical manifestations include diffuse enlargement of the thyroid, occasionally with a
preliminary phase of hyperthyroidism, but by the time most patients seek medical attention, they have passed through hyperthyroid and euthyroid phases and are becoming progressively hypothyroid.
On clinical examination, the thyroid is usually symmetrically enlarged and firm, with a bosselated surface. As a result of the disappearance of brown (iodine-rich) colloid, and its replacement by lymphocytes, the cut surface is white rather than the normal brown colour. It may be that some Hashimoto thyroids proceed to primary atrophic thyroiditis. Laboratory demonstration of the anti-thyroid antibodies forms the basis of the diagnosis of Hashimoto's disease, rendering biopsy unnecessary.
Macroscopically, the thyroid is diffusely enlarged and slightly bosselated with a fleshy, white cut surface due to the lymphocytic infiltrate and the replacement of brown colloid. Microscopically, it shows follicular and diffuse lymphocytic infiltration, with replacement of thyroid follicles.
Solitary nodules in the thyroid usually require excision to confirm their nature. A solitary thyroid adenoma may be full of colloid or have a more cellular follicular pattern. The latter may appear fleshy on cut surface.
Macroscopically, a single, well-circumscribed, ovoid nodule, partly brown but with flecks of white calcification, occupies one pole of the thyroid. Microscopically, from the edge of the nodule shows at least part of the adenoma to be composed of large colloid-filled acini (colloid adenoma). Other variants may be more cellular.
There are three main types of malignant tumour derived from thyroid follicle cell. The most common type is papillary carcinoma, a well-differentiated tumour that arises most frequently in young adults. It is often multifocal within the thyroid, and tends to metastasize via lymphatics to nodes in the neck. It is slow-growing and has an excellent prognosis; even metastatic tumours grow slowly and can be cured by surgical resection. Follicular carcinoma most commonly affects middle-aged people. Metastasizing via the bloodstream, it is one of the tumours that characteristically spreads to bone. Patients may occasionally present with a spontaneous fracture due to metastatic disease, before the primary tumour is detected. It has a good prognosis. Entirely confined to the elderly, anaplastic carcinoma grows very rapidly, extensively invading tissues near the thyroid, such as the trachea and soft tissues of the neck. It may present with a rapidly enlarging thyroid mass causing tracheal compression or jugular vein invasion. The prognosis is very poor. The cells of the tumour, which are usually small, undifferentiated and round, must be distin-
guished histologically from malignant lymphoma; the latter can also affect the thyroid in the elderly, but is more responsive to treatment.
The disease is due to relative or absolute insulin insufficiency.
This is classified into: 1) spontaneous, 2) secondary, 3) diabetes of pregnant, 4) latent (subclinical).
Spontaneous diabetes mellitus can be of 2 types: 1) type 1 (insulin-dependent), 2) type 2 (insulin-independent). Spontaneous diabetes is an independent disease.
Secondary diabetes may occur in pancreatic diseases, acromegaly, Itsenko-Cushing disease, complicated genetic syndromes, at administration of some drugs.
Diabetes of pregnant occurs during pregnancy.
Latent (subclinical) diabetes is not evident.
1) genetically determined disturbances of the number and structure of beta-cells;
2) environmental factors which disturb beta-cell nutrition (bacteria, viruses, autoimmune reactions), increase of activity of adrenergetic nervous system;
Risk factors I Type 1 I Type 2
_______Age_____________until 30____________after 40
Virus infection high antibody titres antibodies to virus
to a number of are absent
Genetic factors association with association with
definite HLA-D histocompatibility
__________________antigens___________antigens is absent
Autoimmunization presence of none
antibodies to beta-
3) risk factors of different kinds of spontaneous diabetes are different:
Pathogenesis: insulin insufficiency increases blood glucose amount because cellular membranes are closed for glucose thus hyperglycemia and glucosuria develop. Considerable amount of sugar is formed from the fats and proteins causing hyperlipidemia, aceton-and ketonemia.
Pathology: The pancreas is diminished with lipomatosis and sclerosis. Degeneration andhyalinosis are observed in the islets, some of them are hypertrophic. The liver is enlarged, glycogen is absent, fat degeneration is observed. Diabetic macro- and microangiopathy is seen in the vessels. Macro-angiopathy is represented by arterial atherosclerosis. Microangiopathy is characterized by plasmatic saturation, hyalinosis, sclerosis with lipohyalin. There is marked proliferation of epithelium and perithelium accompanied by lymphohistiocyte infiltration. The
picture of vasculitis is formed. There is generalized microangiopathy in the kidneys, retina, skeletal muscles, digestive tract mucosa, pancreas, brain, nerves.
In the kidneys, diabetic glomerulonephritis and glomerulosclerosis develop. Microscopically proliferation of mesangial cells in response to mesangium clogging with «ballast» metabolic products and immune complexes are observed. Mesangium hyalinosis and glomeruli death cause sclerosis. Diabetic glomerulosclerosis may be diffuse and nodular as well as mixed type. Its clinical manifestations are Kimmelstiel-Wilson syndrome (proteinuria, edema, increased arterial pressure).
In the lungs, lipogranulomas consisting of macrophages and gigantic cell of foreign bodies are present in the walls of the arteries.
In the spleen, liver, lymphatic glands: infiltration of histiomacrophagal system and skin with cell lipids (xantomatosis) develop.
1) diabetic coma,
2) those connected with angiopathy (gangrene of extremities, myocardial infarction, blindness),
3) diabetic nephropathy (acute and chronic renal failure),
4) infectious sepsis.
The death is caused by coma, diabetic glomerulosclerosis, gangrene.
PATHOLOGY OF PARATHYROID GLANDS
The parathyroid glands are small endocrine glands whose sole function is the secretion of parathormone. There are usually four, and sometimes up to eight, parathyroid glands, which are usually located close to the thyroid gland.
Parathormone (PTH), the parathyroid hormone, is important in calcium balance, acting at two sites:
1. The bone surface, where it stimulates the resorption of bone by osteoclasts, with the release of calcium.
2. The renal tubules, where it stimulates the resorption of calcium from the urine, minimizing phosphate resorption.
Parathyroid adenoma is usually a solitary tumour that affects only one of the parathyroid, the other parathyroids often showing atrophy. The tumours are usually small and are very rarely palpable in the neck, the main presenting symptoms being due to excessive secretion of parathyroid hormone (primary hyperparathyroidism), which produces the symptoms and signs of hypercalcemia.
Malignant parathyroid tumours, with invasion and metastatic spread, are very rare, although some parathyroid adenoma may show considerable pleomorphism and nuclear and cytoplasmic atypia.
Primary parathyroid adenoma is only one of the possible causes of hypercalcemia. Rarely, primary hyperparathyroidism is the result of diffuse hyperplasia of the parathyroids rather than a solitary tumour.
Diffuse hyperplasia of all parathyroid glands is usually a compensatory response to persistently low serum calcium levels. The most common cause of compensatory parathyroid hyperplasia is in renal failure, in which excessive urinary loss of calcium leads to a persistent serum hypocalcemia.
The parathyroid glands may be removed inadvertently or deliberately during surgery on the thyroid gland. If not surgically excised, they may be severely damaged by operative trauma or by interference with their blood supply. Much less commonly, the parathyroid glands may be damaged by an autoimmune disease process (autoimmune parathyroid disease) associated with the presence of an auto-antibody; this usually occurs in patients who have another autoimmune endocrine disease, e.g. Hashimoto's disease or Addison's disease. Reduced PTH secretion leads to a reduction in the serum calcium, with a corresponding increase in serum phosphate levels. Hypoparathyroidism is only one of the causes of hypocalcemia.
Stages of individual work in classStudy and describe macrospecimens
Atrophy of the pancreas in diabetes mellitus. Note the changes of the size, consistency, colour of the pancreas, appearance of the organ on incision. Define the changes which develop in the organism in diabetes mellitus.
Gangrene of the foot. Pay attention to the colour of the skin, presence of the border between necrosis and healthy tissue. Name pathological process being the causes of gangrene.
Skeleton in acromegaly. Describe the body height, proportionality of the development of all body parts. Specify the causes of the disease, complications and causes of death.
Colloid goiter. Pay attention to the change in the size and surface of the gland, its consistency, kind of the tissue on incision. Functional activity of the thyroid gland in goiter; the basic causes of death in Basedowian disease.
Adenoma of the adrenal gland. Characterize the size of the adrenal gland, the kind of the tumour, its colour, presence of the capsule. Name hormone-active adenomas of the cortical layer of the adrenal glands.
Bone in parathyroid osteodystrophy. Describe the character of the bone, its colour on cut surface, condition of the spongiosa. Specify the cause of the disease, changes of calcium content in the blood, kidneys; the causes of death.
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