PATHOLOGY
Endocrine function is supervised by the nervous system, especially the hypothalamus. Several nuclei of the hypothalamus secrete hypothalamic hormones that stimulate peripheral endocrine tissues via the pituitary (hypophysis). These hormones include corti–cotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), luteinizing hormone-releasing hormone (LHRH), and growth hormone-releasing hormone (GHRH). In addition, there are several direct- and indirect-acting hypothalamic hormones, including arginine vasopressin (AVP), somatostatin, and dopamine. Hypothalamic function responds to extraneous physical and emotional stimuli as well as to internal feedback control.
Endocrine function
The pituitary gland controls the functional activity of peripheral endocrine tissues by secreting a large number of hormones, including thyroid-stimulating hormone (TSH), corticotropin (adrenocorticotropic hormone IACTH]), follicle-stimulating hormone (FSH), luteinizing hormone (LH), interstitial cell-stimulating hormone (ICSH), luteotropic hormone or prolactin (LTH), somatotropic hormone (STH), and melanocyte-stimulating hormone (MSH). Hypothalamic damage from viral or other infections, granulomatous diseases (e.g., sarcoidosis), degenerative disorders, or tumor metastases has pathologic effects on the function of other peripheral tissues and endocrine organs. Such relations exist in obesity or anorexia nervosa, hypogonadism (e.g., pubertas tarda, sterility, amenorrhea), and certain rare polysymptomatic syndromes (Prader–Labhart-Willi syndrome, Laurence-Moon-Bardet–Biedl syndrome).
Acidophil Adenoma
Acidophilic or chromophobe adenomas may secrete excessive somatotropin (growth hormone [GH]), which produces gigantism in prepubertal children or acromegaly in postpubertal individuals. Exposure to excessive GH before epiphyseal closure leads to symmetric giant growth. After symphyseal fusion, excessive GH causes asymmetrical growth affecting the nose, the chin, the hands, and the toes. Persons with acromegaly show hyperostosis, cardiomegaly and visceromegaly, thickened skin, and other endocrine abnormalities. Clinical features include arthralgia, muscle weakness, neuropathy, and hypertension in approximately one third of patients. Patients are at high risk for cardiovascular and respiratory failure and cerebrovascular death unless the adenoma is removed by surgery or radiation.
All peripheral endocrine glands (thyroid, adrenal, pancreas, sexual, parathyroid) are closely connected with each other as well as with the central endocrine glands (pituitary, epiphysis) and neuronal (hypothalamus). Besides, connection of the endocrine system with immune system, thymus in particular, has been proved, therefore, it is more correct to speak about neuro–immuno-endocrine regulation of the human organism homeostasis. It is necessary to remember about the systems of cells called APUD-system which produce biogenic monoamines.
It is known that when one endocrine gland is involved by a disease, dysfunction occurs in the other. [f several glands are damaged, the state is called polyglandular endocrinopathy. All diseases of the endocrine system are divided into 1) congenital, 2) developed.
They may be represented by 1) hypofunction, 2) hyperfunction, 3) dysfunction. In this case, dystrophy, atrophy, dysplasia, sclerosis and tumors may
develop.
A practical classification of endocrine pathology is based on the damage of the main (primary) gland. The most frequent are endocrinopathy of 1) pituitary body, 2) adrenal glands, 3) thyroid gland, 4) pancreas, 5) parathyroid gland, 6) sexual glands.
DISEASES OF THE PITUITARY BODY
Acromegaly, gigantism, Itsenko-Cushing disease, hypophyseal nanism, cerebro-hypophyseal cachexia, diabetes insipidus, tumors are the most frequent.
Acromegaly and gigantism usually develop in eosinophil-cell tumors, adenocarcinoma of pituitary anterior lobe. Excess of STH stimulates all mesenchymal derivatives (bones, cartilages, connective tissue). If the disease occurs at a young age, it is called gigantism; if at an older age it is called acromegaly (the bones does not grow but ears, nose, lower jaw, feet and hands enlarge). The other glands are also involved by the process (goiter, atrophy of insulin apparatus of pancreas, thymus and epiphysis hyperplasia, adrenal cortex hyperplasia, sexual glands atrophy occur).
Basophil Adenoma
Basophil adenomas are uncommon, usually small, and located within the normal-sized gland. They may secrete corticotropins (corticotropic adenoma) or related peptides, such as lipotropin and endorphins. Crooke hyaline, homogeneous hyaline globules consisting of densely packed, keratin-positive paranuclear intermediate filaments, is characteristic of basophil adenomas. Crooke hyaline is seen when Cushing disease is caused by primary adrenal tumors or in prolonged corticotropin therapy. Clinical features of functioning corticotropic adenomas are described as Cushing syndrome: truncal obesity with moon facies, systemic hypertension, muscle weakness (decreased muscle mass), hyperglycemia, and thirst. ()s–teoporosis, hirsutism (male-type hair distribution in females) and amenorrhea, mood swings, and depression are also charac teristk , The diagnosis is further confirmed by elevated free Cortisol in the 24-hour urine.
Itsenko-Cushing disease occurs in adenomas from basophilic cells of anterior lobe of the pituitary or adenocarcinoma in rare cases. Increased ACTH production causes cortex hyperplasia as well as increased production of glucocorticoids. It results in obesity of face and body, elevation of arterial pressure, diabetes mellitus, sexual gland dysfunction. Osteoporosis, nephrolithiasis and chronic pyelonephritis may also develop.
The disease should be differentiated from ItsenkoCushing syndrome. Its clinical manifestations are the same as in the disease (obesity of the upper part of the body), but the other signs are not clearly marked. The causes of these states are different. The syndrome is characterized by adrenals damage (tumor of zona fasciculata) which causes increased production of glucocorticoids. Cushingoid can be caused by administration of hormones (cortisole, prednisolone, hydrocortisone).
Pituitary nanism develops in congenital hypoplasia of the pituitary body or its necrosis in children. General underdevelopment of the organism with preserved proportions is observed.
Simmonds’ disease (cerebro-hypophyseal cachexia) is caused by necrosis of pituitary anterior lobe. It may occur after childbirth due to vascular embolism as well as due to syphilis, tuberculosis, tumor. It manifests by cachexia, inner organ atrophy, sexual dysfunction.
Diabetes insipidus is caused by tumors, inflammation, sclerosis, trauma of the posterior lobe of pituitary. It manifests by increased urine excretion due to deficiency of antidiuretic hormone.
Chromophobe Adenoma
Chromophobe adenomas, the most common pituitary tumors, constitute approximately 15% of all intracranial tumors. They occur in both sexes, usually in later lite (sixth decade). Chromophobe adenomas, which may remain microscopic for long periods, most often compress the optic chiasm, causing subsequent bitemporal hemianopsia when they expand. Vision impairment is often the initial clinical sign. Functioning chromophobe adenomas produce a vari–
ety of hormones, including prolactin (lactotrophic adenomas i, somatotropin (somatotropic adenomas), LH and FSH (gonadotropic adenomas), and, rarely, TSH (thyrotropic adenomas). Clinical features differ according to adenoma type with signs of hypogonadism and virilization, acromegaly, hypothyroidism, and others. Some adenomas produce more than 1 hormone including corticotropins
The most wide-spread diseases of the hypophysis are hyperpituitarism and hipopituitarism. The hyperpituitarism often appears in the case of adenomas of adenohypophysis, which are almost always hormone-active and secrete one or another hormone. The somatotrophic adenoma or adenocarcinoma produces the progress of acromegalia for adults and giantism for children. Typical displays of tumours are eosinophilic cells: extra growth of the tissues of mesenchymal origin (connective, cartilaginous, bone, stroma of internal organs); evident growth of the size of ears, lips, tongues (macroglossia), noses, bones of extremities especially hands, feet, lower jaws, frontal bones. The dyschondrosteosis osteogenesis is restored in the bones. In the case of acromegalia of the goitre; the hyperplasia of the thymicis gland, the epiphysis, the cortex of the adrenals; atrophy of the sexual glands and pancreatic islets are discovered in the endocrine organs. The prolactinomic adenoma which develops on the basis of chromophoric cells is found very often and is displayed in the form of the giantism, the loss of libido, the sterility ((barrenness) among women), the galactorrhea, the amenorrhea. The corticotroph adenoma which develops on the basis of basophil cells is accompanied by hyper secretion of the adrenocorticotropic hormone (ACTH) which activates the cortex substance of the adrenals provokes the progress of the pituitary (Cushing’s) basophilism (Cushing’s syndrome). It is found more often among women. It is displayed by the progressive adiposity of the upper type, the arterial hypertension, the secondary steroid pancreatic (insular) diabetes, the dysfunction of ovaries, the hirsutism, the osteoporosis, the nephrolithiasis, the chronical pyelonephritis. The gonadotrop(h)ic adenoma if found very seldom, it is accompanied by the increase of the maintenance of the follicle-stimulating hormone (FSH) in the blood and displayed by the hypogonadism among men.
The hypopituitarism appears in the case of craniopharyngiomas and gliomas. The patients of prepubertal period have the pituitary nanism and the delay of pubescence. The disease appears in the case of the hypoplasia of the hypophysis or its destruction during the period of childhood by the inflammatory process or the necrotic one. It is displayed by the general hypoplasia of the organism. In this case adults have the hypogonadism, the absence of the secondary sexual characters. Women have amenorrhea, atrophy of the external genitals, sterility, decrease (degradation) of the activity of the thyroid glands and the adrenals.
The cerebrohypophysial cachexia is determined by the progress of the dystrophic and necrotic changes in the hypophysis, which is observed in the case of its tuberculous, atherosclerotic, thromboembolitic, syphilitic and tumorous affection of the hypophysis vessels. Sometimes young women have this disease after the child birth which is accompanied by the considerable uterine bleeding, the DIC syndrome or the embolism by the amniotic fluid. It is accompanied by the progressive cachexy.
The adiposogenital dystrophy appears after the neuroinfection, the tumourous affection of the hypophysis or the hypothalamus. It is displayed by the adiposity, the hypoplasia of the genitals and the decrease of sexual gland function, sometimes by the hypothyroidism, the decrease of the cortex adrenals function, the diabetes insipidus.
The syndrome of the empty ephippium is found very seldom, it is connected with the ephippium membrane defect. The constant pressure of the liquor provokes atrophy of the hypophysis. Such state can appear in the cases of the Shikhan syndrome, exposure to radiation, the hypophysis infarction and so on.
Suprasellar tumours of the hypothalamus are represented more often by gliomas and craniopharyngiomas. They can provoke hipo– and hyperfunction of the adenohypophysis. The craniopharyngioma appears on the basis of the Rathke’s pouch among children and teenagers. Its diameter can reach 3-
The syndrome of the back part of the hypophysis is displayed by the diabetes insipidus. The disease appears in the case of the decrease of the antidiuretic hormone secretion. It determines the disability of kidneys to concentrate urine, its great loss and profound violation of the water-electrolytic balance.
DISEASES OF THE ADRENALS
The diseases of the adrenals are divided into the affections of the cortex substances and the cerebral ones and accompanied by hyper- and hipofunctions of the proper hormones.
The hyperfunction of the cortex substance (hyperadrenalism) is often found on the basis of the pituitary (Cushing’s) basophilism (Cushing’s syndrome), the hyperaldosteronemia, the adrenogenital syndrome. The hyperadrenocorticism: the pituitary (Cushing’s) basophilism (Cushing’s syndrome) appears on the basis of increased secretion of the adrenocorticotropic hormone (ACTH) – adenoma of the hypophysis, adenoma or hyperplasia of the cortex substance of the adrenals because of the prolonged glucocorticoid therapy. The (hyper)aldosteronism appears on the basis of adenomas (the aldosteroma), the idiopathic hyperplasia of the adrenals. It can be primary (initial) and secondary. The disease is accompanied by the hypokaliemia, the hypernatremia, the arterial hypertensia. It is displayed by the muscle asthenia, the impaired cardial function (the cardiac decompensation, cardiac insufficiency) because of the hypokaliemia myopathy and the myocardiodystrophy, the paresthesia, the convulsions. The adrenogenital syndromes (congenital hyperplasia of the adrenals) is displayed by the malfunction of the steroid hormones synthesis and the accumulation of the androgenic hormones, which provoke the progress of the viricidism.
Hipofunction of the cortex substance (the hypo(adreno) corticism, the hypoadrenalism) can be primary (initial) or secondary (in the case of the adrenocorticotropic hormone (ACTH) shortage, acute (adrenal crisis) and chronic ((chronic) adrenocortical insufficiency, bronzed disease, bronzed skin, melasma, suprarenale, Addison’s disease). The primary acute hipofunction of the cortex substance develops on the basis of stresses, the chronic hypoadrenalism, the sudden (quick) stoppage taking steroidal agents, considerable extravasation (hemorrhage) into the adrenal during the period of the bacterial infection (the meningococcosis, the diphtheria, the septicaemia) accompanied by the progress of the Waterhouse-Friderichsen syndrome among little children.
The primary chronic cortex substance insufficiency ((chronic) adrenocortical insufficiency, bronzed disease, bronzed skin, melasma, suprarenale, Addison’s disease) develops in the case of the autoimmune adrenalitis, the tuberculous and metastatic affection of the adrenals. The patients have general asthenia, fatiguability, loss of weight, hypotonia, hyperpigmentation of skin (the melanoderma) and mucous tunics, the atrophy of the myocardium.
The secondary chronic cortex substance insufficiency develops in the case of the adrenocorticotropic hormone (ACTH) shortage. It is often found on the basis of tumours, the inflammation, the infarction, the extravasation (hemorrhage), exposure to radiation of the hypothalamus or the hypophysis, prolonged glucocorticoid therapy. The atrophy of the cortex (substance) takes place but the cerebral substance almost doesn’t change. The pheochromocytoma is found among the diseases of the cortex (substance) more often. It is accompanied by the increased synthesis of the catecholamines and high blood pressure. The tumour is found more often among women. It is one-side, its colour is red-grey or brown. It’s built of polymorphous cells with light cytoplasm. The malignant variant of the tumour might exist, it provides metastases into the lymph nodes, the liver, the lungs and bones.
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.
Hypopituitarism
Hypopituitarism refers to deficiencies in hormone production by the adenohypophysis (anterior lobe of pituitary) The lack of ho mone affects the function of peripheral endocrine tissues. Hypopituitarism is caused by destruction of the gland by tumor metastases, local tumors extending into the sella turcica, infiltrative processes such as infections (e.g., tuberculosis), metabolic disorders (e.g., hemochromatosis, Hand-Schiiller-Christian disease), ischemic postpartum necrosis (Sheehan syndrome), hemorrhagic infarction (pituitary apoplexy), or, rarely, hypophyseal atrophy secondary to subarachnoid space herniation (empty sella syndrome). Symptoms develop slowly and occur when approximately 75% of the adenohypophysis is lost. Hormone replacement is the therapy of choice. The underlying disease causing the hypopituitarism determines the prognosis.
Adrenal cortical adenoma is a wellcircutnscribed, 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 lumours 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.
DISEASES OF THE ENDOCRINE PART OF THE PANCREAS
The diseases can be displayed by the increase of decrease of the islet cells function. The decrease of the β-cells function is observed more often, that determines the progress of the pancreatic (insular) diabetes. When the tumour (adenoma) develops the antihyperglycemic syndrome appears in the case of the β- insulinoma. The Zollinger-Ellison syndrome (multiple endocrine neoplasms) with plural ulcers on the mucous tunic of the stomach in the case of insulinoma or gastrinoma.
The pancreatic (insular) diabetes is a cronical disease which appears because of insulin insufficiency and it is accompanied by the dysmetabolic dysfunction with the affection of vessels and internal organs. There are the following forms of the pancreatic (insular) diabetes: spontaneous, secondary, the diabetes of pregnant women, cryptic. Among the spontaneous forms there are the following ones:
– the pancreatic (insular) diabetes of the I type (insulin dependent) which appears because of the destruction of β-cells of autoimmune or idiopathic origin;
– the pancreatic (insular) diabetes of the II type (insulin independent) which is accompanied by the relative insulin insufficiency.
The secondary pancreatic (insular) diabetes develops in the cases of the pancreatitis, the diseases of endocrine system (the acromegalia, the Itsenko-Cushing syndrome, the pheochromocytoma), the genetic syndromes, in the case of the use of some kinds of medicaments – medical diabetes.
The spontaneous diabetes is observed as an independent (self-dependent) disease. The diabetes of the I and II type is mostly is genetically determined. The pancreatic (insular) diabetes of the I type often appears during the early years (juvenile diabetes) after the virus infections, the auto immunization to β-cells. In the process of disease progress the immune insulin with the presence in the inflammatory infiltratioumerous T and B – lymphocytes, macrophages. The pancreatic (insular) diabetes of the II type develops among the adults. The base of the disease is the insufficiency of the β-cells function and the insulin resistance of tissues. Insular insufficiency provokes dysfunction of the glycogen synthesis, the increase of sugar content in blood (the hyperglycemia), the advent of sugar in urine (the glycosuria), the progress of the hyperlipidemia, the acetonemia, the ketonemia, the acidosis. Macro- and microangiopathy develops in vessels, the insular apparatus of the pancreas, kidneys and the liver become damaged.
The morphological displays.
The pancreas: atrophy, lipomatosis, hyalinosis, sclerosis.
The liver: fatty atrophy, decrease of the glycogen content in hepatocytes.
The vessels: macro- and microangiopathies which are determined by the circulatory immune complexes and the products of disbalanced metabolism. The diabetic macroangiopathy is characterized by the affection of the elastic and muscular- elastic types arteries. It is displayed by the progressive atherosclerosis with the progress of the vessel necrosis and lower extremities gangrene. The diabetic microangiopathy is characterized by the system affection of the arterioles and capillaries of different organs and tissues: the plasmatic dripping and affection of the basal membrane, the lipohyalinosis, the dystrophic changes, the proliferation of the endothelium and perithelium, the atrophic changes of the cells, the inflammatory lymphohistiocytic seepage of the side (wall).
The retina of an eye: the seepage of the side (wall) develops because of the diabetic retinal microangiopathy. It is displayed by the hyaline degeneration and the capillaries silting, the vein microaneurism, the perivascular edema, the extravasation (hemorrhage), dystrophic and atrophic changes of the optic (II cranial) nerve. There are two types of the retinopathy: nonproliferative one (or simple diabetic) which provokes separate microaneurisms (and dotty extravasations) and proliferative one which provokes the capillaries neoplasm, considerable extravasations, the retina sclerosis, the sclerosis the optic (II cranial) nerve papilla with the progress of glaucoma, the retina exfoliation and loss of sight. Sudden extravasations into the vitreous body are possible with the following progress of one eye blindness.
The nervous system: the symmetric affection of the peripheral nerves especially in lower extremities with the following progress of the paresthesia, affection of temperature, vibratory and pain sensitivity. Sometimes the motor nerves are affected too. The progress of the segmental demyelinization, edema, axon dystrophy are observed too.
The kidneys: the diabetic intracapillary glomerulonephritis and glomerulosclerosis. There is the proliferation of the mesangium cells in the glomerules because of the soiling of the mesangium by the metabolic products and immune complexes, the hyaline degeneration of the mesangium develops gradually and death (destruction) of the glomerules. “The fibrin hats” appear on the capillary loops of the glomerules; glucogenic infiltration, fatty dystrophy and hydropic (vacuolar) degeneration are observed in the epithelium of the narrow segment of the nephron; epithelium becomes high with the light opaque cytoplasm. High proteinuria, edemata, arterial hypertension are found clinically. The kidneys decrease in their size symmetrically, the have the small-grained surface and hard consistence. The glomerulosclerosis can be nodular (follicular), diffusive and mixed diabetic.
Among the complications and causes of death one should mark out the gangrene of the upper extremities with the following progress of the septicopyemia, the myocardial (cardiac) infarction, the uremia and some infectious complications (the pyoderma, the furunculosis, the septicaemia).
The tumours of the endocrine part of the pancreas (insulinomas) can be benign (non-malignant) (the adenomas) and malignant (the adenocarcinomas, low-grade differentiated adenocarcinoma which provide metastasis into the regional glands and liver). The sclerosis, the hyaline degeneration, the amyloidosis of the stroma with the microcalcifications are often found in the tumours.
The insulinoma is a tumour (from 0,5 to
The alpha-cell tumour can reach the size of
The gastrinoma develops on the base of G-cells. It is displayed by the Zollinger-Ellison syndrome which appears as a result of gastrin hypersecretion. Numerous ulcers and erosions can appear on the mucous tunic of the stomach and duodenum. They can be followed by such complications as perforations, penetrations, bleedings (haemorrhages), stenosises, relapses. The tumour is found more often among young men, it reaches
The carcinoid (tumor) of the pancreas is displayed by the increased secretion biogenic amins: the serotonin and the histamine. Tachycardia, diarrhea, bronchial asthma fits are observed in this case clinically.
The vipoma is a tumour of a considerable size, it develops on the base of D-cells of the body or the tail of the gland, which produce vasoactive interstitial peptide. Clinically the disease is displayed by considerable water diarrhea, hypokaliemia, hypochlorhydria, acidosis, dehydration.
Deficient hormone release by the neurohypophysis (posterior lobe of pituitary) results in inadequate ADH availability. Diabetes insipidus, characterized by uncontrolled water diuresis, polyuria, and polydipsia (excessive thirst), ensues. Although patients consume large amounts of water daily, they may experience life-threatening dehydration. Diabetes insipidus is caused by a variety of processes (head trauma, infection, neoplasm), but may cases develop without recognizable underlying disease. Craniopharyngioma, a dysontogenetic tumor derived from displaced epithelium of the Rathke pouch, is one of the more common tumors that compresses and destroys the neurohypophysis.
Jatrogenic 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 norepineph-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
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.
Addison ‘c disease
In 1849 Addison described the so-called bronze disease which develops in bilateral lesion of adrenal cortex with the develo5ment 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 I 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.
DISEASES OF THE THYROID GLAND
The diseases of the thyroid gland are divided into goitres, thyroiditises and tumours. They can be accompanied by the hyperthyroidism (the thyrotoxicosis) or the hypothyroidism (the myxedema). The goitre (the struma) is the growth of the thyroid gland. The base of this process is the hyperplasia. In this case the function of the gland can be increased, decreased or not changed at all. According to the morphological signs goitres are divided into diffusive, nodular, diffusive-nodular (mixed) ones. According to the histological structure they are divided into colloid goitres and parenchymatous ones.
The colloid goitre looks like a solid (dense) nodule which is built of the follicles of different sizes. Usually they are filled with the colloid. If the follicles are big, cyst-like with the flattened out epithelium it is the macrofollicular colloid goitre. If the follicles are small it is the microfollicular goitre. If the follicles have the growth of the epithelium in the shape of papillas it is the proliferative colloid goitre. If there are follicles of different size at the same time it is micro-macrofollicular goitre.
The parenchymatous goitre looks like a fleshy tissue. It’s colour is grey-pink. It is characterized by the proliferation of the follicles epithelium in the form of solid structures. The colloid in the follicles is almost absent.
The diffusive non-toxic (simple) goitre can be endemic and sporadic. During the first hyperplastic stage of the disease the hyperplasia of the gland develops. Its weight increases to 100-150 gr. During the histological analysis little follicles are found which are covered with the prismatic epithelium. They contain very little colloid. After the progress of the euthyroid state the proliferation of the follicles epithelium stops. After that the stage of the colloid involution develops. Gradually the follicles grow in their size and the epithelium atrophies. The weight of the gland grows rapidly. The gland becomes dense, gelatine-like in the incision. It is the colloid goitre which can compress (squeeze) internal organs and even provoke the asphyxia.
The endemic goitre is found in the regions, where there is lack of iodine that determines the decrease of the synthesis of thyroid gland hormones. Because of that the compensatory hypertrophy of the gland. Gradually the hypothyroidism develops. Adults have the myxedema, the children have the endemic cretinism which is displayed by the physical and mental gap.
The sporadic goitre is found very seldom. It appears among young women and is accompanied by the euthyroid state or the hypothyroidism. The fact that causes this disease is unknown.
The diffusive toxic goitre (Graves’ disease) appears among young women and is accompanied by the hyperthyroidism. One of the causes of the disease is autoimmunization: the appearance of the antibodies which stimulate the cellular receptors of the thyroticis. There is a genetic inclination for this disease. Among clinical displays of the disease there are the growth of the thyroid gland, tachycardia, loss of weight, increased nervous excitability. In the case of the Graves’ disease the typical visceral and local changes develop in the thyroid gland. The morphological changes in the gland are the following: the organ grows diffusively; it has the soft consistence; the prismatic epithelium of the follicles transforms into the cylindrical one; there is the proliferation of the epithelium; the pseudo papillas appear; there is the vacuolization and rarefaction of the colloid; there is the lymphoplasmocytic seepage of the stroma; the lymphatic follicles form. Among the visceral changes the most important is the affection of the liver, the heart, the brain (cerebrum). The thyrotoxic heart develops in the heart: the hypertrophy and fatty (adipose) degeneration of the cardiac hystiocytes; the serous oedema and the myocarditis which results in the diffusive focal localized myocardiosclerosis. The edema, the fatty (adipose) degeneration, the interstitial inflammation with the progress of the fibrosis and the cirrhosis in the end are found in the liver too. The dystrophic changes develop in the nerve cell of the brain, the perivascular infiltration develop in the medulla. The dystrophy of the cortex of the adrenals is observed too. Patients die because of the cardiovascular collapse, the acute adrenal gland insufficiency during operations.
THYROIDITIS
The hypothyroidism appears in the case of the thyroiditis which can be of the following types: the Hashimoto’s thyroiditis, the acute granulomatous one, the acute lymphocytic one, fibrous one, the purulent one.
The Hashimoto’s thyroiditis (autoimmune, lymphatic stroma) more often appears among women who have genetic tendency for this disease. In the pathogenesis the most important role is played by the autoimmune affection of the organ parenchyma. The diffusive lymphoplasmocytic seepage of the gland with the forming of the lymphoid follicles develops. Because of the influence of the immune cells parenchyma dies. It is replaced with the conjunctive tissue. The hypothyroidism develops afterwards.
The acute granulomatous thyroiditis appears among women after the viral infection. The gland grows asymmetrically; grey-yellow infiltrations are found in it. The leukocytic infiltrations with the gradual purulent fusion of the gland are observed too. The macrophage granulomas with the admixture of giant cells and fibrosis progress appear later.
The acute lymphocytic thyroiditis very often does not have symptoms. Usually it is found during histological examination of the operating materials. The lymphoplasmocytic infiltration are located subcapsularily. The cause of this disease is still unknown.
The fibrous thyroiditis (the struma) (ligneous (Riedel’s) thyroiditis)) is displayed by the hypothyroidism which appears because of the follicle atrophy and the growth of the fibrous tissue. The organ becomes very dense. The cause of this disease is still unknown.
The purulent (infectious) thyroiditis appears after the secondary hematogenic traumatic infection of the gland. The purulent inflammation and the insignificant decrease of the gland function are also found in this case.
TUMOURS OF THE THYROID GLAND
The tumours of the thyroid gland can be non-malignant and malignant.
Among the non-malignant tumours the follicular adenomas are found more often. They develop on the basis of A and B-cells. They are represented by the follicles of different size. The solid adenomas composed of C-cells which produce calcitonin are found too. The tumour is represented by the big light cells with the light cytoplasm. Also there are papillary adenomas. They have needle papillary accretions (excrescences) among the cystous neoplasms. The presence of the papillary accretions (excrescences) is a bad sign because the is possibility of the malignization. The secondary changes can be found in the tumours: little extravasations (hemorrhages); the areas of the necrosis, sclerosis and calcareous degeneration. There are atypical adenomas made of fusiform cells. There are also dermoid cysts, lipomas, hemangiomas, teratoblastomas.
The malignant tumours are often found among women. They are represented by the cancer which can be papillary, follicular, anaplastic or medullary carcinoma. The papillary carcinoma is found more often. Clinically it is displayed by the thyrotoxicosis. Macroscopically it is a dense tumour. Its of grey colour. It is the tumour with the petrifacts and cysts. Its diameter is 7-
DISEASES OF THE PRE-THYROID GLANDS
The diseases of the pre-thyroid glands are displayed by the hyper- and hypoparathyroidism.
The primary hyperparathyroidism appears in the case of the affection of the gland by the tumorous process (the adenoma, the the adenocarcinoma) or in the case of its hyperplasia or the autoimmune process. Commonly the adenomas are the same. They grow as the node on the basis of the acidophilic or transitional cells. They are accompanied by the extravasations (hemorrhages), the hemosiderosis, the necrosis, the fibrosis. The disease is also accompanied by the hypercalcinemia, the hypophosphatemia, the osteoporosis, the generalized fibrous-cystous osteit is, the parathyroid osteodystrophy with the overgrowth of the osteoid tissue, the metastatic tumor, the urolithiasis, the peptic stomach ulcers, the neurologic changes (the convulsions, the worsening of the memory) and the ophthalmologic ones (the cataract, the calcification of the cornea).
The secondary hyperparathyroidism appears at renal failure (uremic hyperparathyroidism), at vitamin D deficiency, osteomalation, at destruction of bone by metastasis of malignant tumors, multiple myeloma, rickets.
Hypoparathyroidism occurs after erroneous removal of the glands during operations, in the case of the innate absence of the glands (Di George syndrome), at hereditary and autoimmune diseases. The patients have the hypocalcemia, the increased neuromuscular excitability, the tetany, the laryngospasm, the increase of the calcium concentration in the bones, the cataract, the hypoplasia of the teeth
Hyperthyroidism is associated pathologically with diffuse or nodular goiter, Graves disease, thyroid adenoma and carcinomas, and certain forms of early thyroiditis. The etiology of Graves disease, the most common cause of hyperthyroidism, remains obscure. The diagnosis is confirmed by scintigraphic demonstration of increased T4, T3 uptake in the thyroid gland. Autoantibodies against follicular epithelial membranes, which may bind to the TSH receptor and thus contribute to thyroid stimulation, are frequently observed. The thyroid, which is grossly enlarged, firm, and red (struma parenchymatosa), shows histologically diffuse follicular activation and hyperplasia with resorption of colloid and eventual lymphocytic infiltration. The clinical course is variable, with exacerbations, remissions, and final hypothyroidism after secondary chronic nonspecific thyroiditis.
Congenital Hypothyroidism and Myxedema
Hypothyroidism is characterized by a reduction of the physiologic thyroid function with respectively reduced thyroid hormone excretion. Congenital hypothyroidism is related to developmental defects and may occur endemically. In addition, there exists a sporadic, intrauterine post-inflammatory or post-toxic hypothyroidism with unresponsiveness of the thyroid gland to TSH stimuli and deficient thyroid hormone synthesis. Patients are of short stature, with thick yellowish skin and a characteristic facial expression. Eyelids are puffy, the nose is flat and thick, and the tongue is enlarged and protruding. The neck is short and thick. Adult hypothyroidismmanifests as myxedema. Patients experience tiredness and lethargy. Their hair is dry and brittle, their skin is thickened (myxedema), and the face resembles to a certain extent that in cretinism. The heart rate is usually decreased, and some patients have psychotic < (myxedema madness). Laboratory tests show a decrease of T4 levels in the blood, whereas TSH is significantly increased.
Goiter
Goiter (struma) refers to an enlargement (usually nodular) of the thyroid related to either hyperthyroidism or hypothyroidism. Goiter in combination with hyperthyroidism, as is seen in Plummer syndrome (toxic goiter), is usually autonomous but not cancerous. Goiter can be caused by low dietary intake of iodine but is usually caused by increased levels of TSH in response to a defect in hormone synthesis in the thyroid gland. Patients with goiter usually remain asymptomatic except for progressive swelling of the neck with potential airway obstruction and dysphagia or compression of the recurrent nerve with hoarseness. Microscopically, there is diffuse or nodular crowding of enlarged follicles. In time, regressive changes with chronic reactive inflammation <\nc\ fibrosis develop. Focal intrafollicular hemorrhage and siderosis and follicle rupture with signs of colloid resorption and foreign body granulomatous reaction may occur
Thyroiditis
There are several forms of primary thyroiditis (Table 12-1). The thyroid gland is usually enlarged (except in Riedel thyroiditis, in which the gland is small to undetectable) and tender with radiating pain. Regional lymph nodes are enlarged, suggesting an inflammatory disease. Patients may be euthyroid with eventual hyperthyroidism related to follicle destruction (hashitoxicosis in Hashimoto disease) but eventually have hypothyroidism. Thyroid autoantibodies and cytotoxic T lymphocytes often can be shown. Some cases of autoimmune thyroiditis are part of systemic autoimmune disorders such as collagen-vascular diseases. Consequently, careful examination of the patient with primary thyroiditis is recommended. The nature of the autoimmune process usually determines the prognosis of the thyroiditis.
Main thyroid of the diseases are: 1) goiter (struma), 2) thyroiditis, 3) tumors. All these arei accompanied by either hyperthyroidism (thyrotoxicosis) or hypothy-roidism (mixedema).
Goiter is a pathologic enlargement of the thyroia gland. Goiters are classified according to thei9 morphology and epidemiology, course, functional and clinical peculiarities.
According to the morphology goiter may be:1 1) diffuse, 2) nodular, 3) diffuse nodular.
According to the histology there are 2 types 01 goiters — colloid and parenchymal.
According to the epidemiology goiter is classified into: 1) endemic, 2) sporadic, 3) diffuse toxic (also ermed thyrotoxic goiter, Basedowian disease, Graves disease).
Colloid goiter may be macrofollicular and microfollicular as well as mixed type. It consists of [ollicles. 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 puffr 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, pufl’ 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.
Hash imoto ‘s disease
Hashimoto’s disease is a destructive autoimmune thyroiditis leading to hypothyroidism. Hashimoto’s disease is most common in middle age, affecting women more ofien than men, a good example of organ- specific autoimmune disease. The most common auto- antibodies 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.
TUMORS
Solitary nodules in the thyroid usually require excision to confirm their nature. A solitary thyroid adenoina maybe 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.
Thyroid Adenomas and carcinoma
Autonomous proliferative diseases of the thyroid consist of adenomas (benign) and carcinomas (malignant), either of which may be hormone-producing tumors. Adenomas (usually autonomous nodules in a nodular goiter) show signs of hyperthyroidism, tachycardia, shortness of breath, nervousness, weight loss, and emotional instability, although they are usually less pronounced than in Graves disease. Iodine uptake is increased in the adenoma (scintigram), and blood iodine is moderately increased (protein-bound as well as butanol-extractable forms). Certain forms of adenoma are difficult to distinguish from well-differentiated follicular carcinoma (atypical adenoma with cellular atypia, mitoses, or even vascular invasion); therefore, adenomas should be removed and studied histologically
The 4 major types of thyroid carcinomas (Table 12-2) differ histologically, in their routes of metastasis, and in their prognosis. Papillary, follicular, and anaplastic carcinomas are derived from follicular epithelial cells. Medullary carcinoma is an endocrine tumor from calcitonin-producing interstitial C cells. This tumor may occur in combination with other related endocrine tumors forming familial MEN syndromes, such as MEN-2 with associated pheochromotoma. The clinical features of such tumors are determined by the combination of different neoplasms. Medullary carcinoma may show symptoms of carcinoids (flushing, watery diarrhea), Cushing syndrome, hyperparathyroidism (HPPT), and episodic hypertension. The life expectancy of patients with MEN is generally shorter than that of patients with solitary medullary carcinoma
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 oflen 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 Ifrom malignant lymphoma; the latter can also affect the thyroid in the elderly, but is more responsive to treatment.
Hyperparathyroidism
There are 2 major forms of hyperparathyroidism (HPPT), primary and secondary, as well as combinations of the two. Eighty-four percent of primary HPPT (autonomous HPPT) is caused by parathyroid adenomas, 12% is caused by hyperplasia, and 4% is caused by parathyroid carcinomas. Secondary HPPT follows chronic renal insufficiency (renal rickets, renal osteodystrophy) with hyperphosphatemia and decreased ionized serum calcium. Parathyroid glands show diffuse or nodular hyperplasia. Long-standing secondary HPPT may be complicated by development of autonomous adenomas, thus adding a form of primary HPPT. Clinical features of HPPT are variable combinations of serum hypercalcemia with calcium deposits (kidney stones, Gl mucosa, blood vessels, soft tissues, etc) and enhanced bone resorption (osteitis cystica fibrosa, dissecting fibroosteoclasia).
Adrenogenital Syndrome
Adrenogenital syndrome (congenital and adult forms) is caused by a form of adrenal cortical hyperplasia or tumors with excessive production of 17-ketosteroids (dehydro-epiandrosterone, etio-cholanolone, and androsterone). In addition to androgen abnormalities, the syndrome may be complicated by alterations in sodium metabolism, glucocorticoid deficiency, or both. Clinically, there are signs of masculinization in females (hirsutism, clitoral hypertrophy, oligomenorrhea) and precocious puberty and enlargement of genitalia in males. Some forms of congenital adrenal cortical hyperplasia occur with androgen deficiency and cause pseudohermaphroditism in males. Ninety-five percent of patients with congenital adrenal hyperplasia show defects in 21-hydroxylase, which results from mutations on chromosome 6.
DIABEYES MELLITUS
The disease is due to relative or absolute insulin rnsutliciency.
This is classified! into: 1) spontaneous, 2) Secondary, 3) diabetes ofpregnant, 4) latent (subclinical).
Spontaneous diabetes mellitus can be of 2 types:
1) type 1 (insulin-dependent), 2) type 2 (insulinindependent). Spontanceous diabetes is an independent disease.
Secondary diabetes may occur in pancreatic diseases, acromegaiy, Itsenko-Cushing disease,1 complicated genetic s’ndromes, at administration of1 some drugs.
Diabetes of pregnant occurs during pregnancy.
Latent (subclinicl) diabetes is not evident.
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Hyperinsulinism
The endocrine pancreas consists of the islets of Langerhans, which are composed of insulin-producing (} cells (60-70%), a cells (15-20%), which produce the “insulin-antagonist” glucagon, several clones of 8 cells (e.g., D cells, D1 cells), which secrete somatostatin or VIP, and other substances. Hyperinsulinism caused by (3-cell adenomas or carcinomas constitutes 75% of pancreatic endocrine neoplasms. Clinical features are spontaneous hypoglycemia with hunger, tremor, perspiration, confusion, anxiety, convulsions, and coma. In nesidioblastosis, which occurs in rare cases of reactive hypoglycemia, pancreatic P cells are hypertrophic and increased iumber. Islet cell carcinomas (10% of insulin-producing tumors) are less well demarcated, metastasize early, preferentially to the liver, and generally are associated with a poor prognosis.
Etiopathogenetic factors:
1) genetically determined disturbances of the number and structure øf beta-cells;
2) environmental factors which disturb beta-cell nutrition (bacteria, vijruses, autoimmune reactions),.I increase of activity of adrenergetic nervous system;
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, acetonand ketonemia.
Pathology: The pancreas is diminished with lipomatosis and sclerosis. Degeneration and hyalinosis 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. Macroangiopathy is represented by arterial atherosclerosis. Microangiopathy is characterized by plasmatic saturation, hyalinosis, sclerosis with lipohyalin. There s marked proliferation of epithelium and perithelium accompanied by lymphohistiocyte infiltration. The picture of vascuhtis is formed. There is generalized microangiopathy in the kidneys, retina, skeletal muscles, digestive tract mucosa, pancreas, brain, nerves.
Non-Insulin-Dependent Diabetes Mellitus
Non-insulin-dependent diabetes mellitus (NIDDM, type 2), the most common form of diabetes, is characterized by an initial decreased sensitivity of peripheral tissues to insulin (insulin resistance) followed by alterations in insulin secretion by p cells. Pancreatic islets show amyloid deposits, cell atrophy, and progressive fibrosis. The incidence of NIDDM increases with obesity and the consumption of glucose (in all nutritional forms). Metabolic disturbances, especially hyperglycemia, cause a number of complications and secondary diseases, including progressive microangiopathy with diabetic retinopathy, renal glomerular nephrosclerosis (Kimmelstiel-Wilson disease), peripheral neuropathy, ulcus cruris, and gangrene. Many patients have severe hypertensive cardiovascular disease, which is the leading cause of mortality in this population.
In the kidneys, diabetic glomerulonephritis and glomeruloscierosis 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.
Complications:
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 PARATIJYROID 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.
Parathyroidadenoma 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.
Hyperaldosteronism
Adrenal cortical adenomas that simulate structures of the zona glomerulosa cause primary hyperaldosteronism (Conn syndrome).
Excessive aldosterone secretion causes potassium depletion (increased potassium loss from kidneys and other exocrine glands), sodium retention, decreased plasma renin activity, and hypertension. Secondary hyperaldosteronisms in response to stimulation by the renin-angiotensin mechanisms show increased plasma renin activity. Adenomas in primary hyperaldosteronism usually remain small (less than
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 autoinmiune 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.
Acute Adrenal Cortical Insufficiency
Acute adrenal cortical insufficiency (adrenal crisis, Waterhouse-Friderichsen syndrome) follows the acute necrosis and hemorrhage of the adrenal cortex secondary to bacterial septicemia, usually meningococcal septicemia, and sometimes Pseudomonas, pneumococci, and Haemophilus influenzae. Bacterial toxins (endotoxins) are thought to cause diffuse vascular damage with intravascular coagulation and hemorrhage, which destroy large parts of the adrenal cortex. Other conditions that may be associated with similar adrenal hemorrhage and necrosis are birth trauma, treatment with anticoagulants, and almost all causes of disseminated intravascular coagulation (DIC). The resulting acute adrenal crisis is attributed primarily to the sudden loss of glucocorticoids.
Macroscopic changes
1. Atrophy and lipomatosis of pancreas at diabetes mellitus. An organ is withdrawn from the body of man who died of saccharine diabetes. A gland is diminished in sizes, thin, dense, anatomic structure is broken – scopes are not visible between a head and body. Her partiality is shallow, uneven. At simultaneous obesity there is a germination of fatty fabric in a gland.
2. Colloid goitre. A thyroid gland is considerably megascopic in sizes, the surface of gland is hilly, on a cut evidently there are semilucent, yellow brown, sometimes chocolate brown the masses which come forward and parted the layers of connecting fabric. What are the forms of colloid goitre?
3. Papilar cancer of thyroid gland. Tumouris evidently of oval form, is homogeneous on a cut, yellow white color, with numerous shallow hemorrhages. In what organs are there metastasis the cancer of thyroid gland?
4. Pancreonekrosis. Pancreas, considerably diminished in sizes, are presented. Well evidently particular structure due to, that interparticular connecting and fatty tissue necrotic, white color. What morfogenesis of pancreonekrosis?
5. Adenoma of adrenal gland. An organ is megascopic in sizes. On a cut a tumour of rose brown color, is obviousadenomatous structure is with clear bordered from healthy tissue. What layer of adrenal gland do the tumours of such structure and color develop from more frequently?
6. Corticosteroma. On the serial cuts of adrenal gland evidently expressly marked off yellow color tumour. In color a tumour is similar to the cork layer of adrenal gland. Tumour of high quality, though sometimes can acquire malignant motion and give metastases. A tumour can reach10-12sm in diameter.
7. “Bull heart” (cardiomegaly). On preparation a heart which is sharply megascopic in sizes is presented. An organ is withdrawn from a dying woman which suffered from a thyreotoxic goitre. What are the changes due to it in a heart?
9. Goitre of Hashimoto. A thyroid gland is megascopic almost in 3 times, has a hilly surface, on a cut there is evidently excrescence of connecting tissue of yellow-grey color which gives the gland considerable closeness. A gland has a large grainy structure
Macroscopic changes
1. Atrophy and lipomatosis of pancreas at diabetes mellitus. An organ is withdrawn from the body of man who died of saccharine diabetes. A gland is diminished in sizes, thin, dense, anatomic structure is broken – scopes are not visible between a head and body. Her partiality is shallow, uneven. At simultaneous obesity there is a germination of fatty fabric in a gland.
2. Colloid goitre. A thyroid gland is considerably megascopic in sizes, the surface of gland is hilly, on a cut evidently there are semilucent, yellow brown, sometimes chocolate brown the masses which come forward and parted the layers of connecting fabric. What are the forms of colloid goitre?
3. Papilar cancer of thyroid gland. Tumouris evidently of oval form, is homogeneous on a cut, yellow white color, with numerous shallow hemorrhages. In what organs are there metastasis the cancer of thyroid gland?
4. Pancreonekrosis. Pancreas, considerably diminished in sizes, are presented. Well evidently particular structure due to, that interparticular connecting and fatty tissue necrotic, white color. What morfogenesis of pancreonekrosis?
5. Adenoma of adrenal gland. An organ is megascopic in sizes. On a cut a tumour of rose brown color, is obviousadenomatous structure is with clear bordered from healthy tissue. What layer of adrenal gland do the tumours of such structure and color develop from more frequently?
6. Corticosteroma. On the serial cuts of adrenal gland evidently expressly marked off yellow color tumour. In color a tumour is similar to the cork layer of adrenal gland. Tumour of high quality, though sometimes can acquire malignant motion and give metastases. A tumour can reach10-12sm in diameter.
7. “Bull heart” (cardiomegaly). On preparation a heart which is sharply megascopic in sizes is presented. An organ is withdrawn from a dying woman which suffered from a thyreotoxic goitre. What are the changes due to it in a heart?
9. Goitre of Hashimoto. A thyroid gland is megascopic almost in 3 times, has a hilly surface, on a cut there is evidently excrescence of connecting tissue of yellow-grey color which gives the gland considerable closeness. A gland has a large grainy structure
Illustrations to theme
DISEASES OF THE ENDOCRINE SYSTEM
Diabetic glomerulosclerosis.
Different variant of goitres.
Adenoma of adrenal gland.
Thyrotoxicosis cirrhosis and cardiosclerosis.
Hemorrhage into the adrenal.
Hemorrhage into the cerebrum
Numerous ulcer by the Zollinger-Ellison syndrome.
Microscopic changes
1. Atrophy of pancreas is obvious at the time of diabetes mellitus. Colouring of tissue by hematoxilyn-eosin and method of Van-Gizon. Surplus excrescence of interparticular connecting tissue among which evidently fatty tissue as connecting variety is marked in a gland. Also surplus excrescence of connecting tissue round the muffs of conclusions are evident. Insular of little body, that the glands presented in parenchyma by the nests of round mews with hyperchrome kernels, sclerosed, mews for them little, that devastation of insular little bodies was. Fully substituted for some little bodies – by connecting tissue as round scars.
2. Intracapillar diabetic glomerulosclerosis. Preparation is painted in hematoxilin and eosin. The hearth of piling up in mesangium of eosinophil masses and diffuse bulge of basal membranes of capillaries of balls is marked. Placed fully substituted for separate balls of connecting tissue. Hyalinosis is marked in some balls, bulge of walls of capillaries.
3. Colloid macrofolicular goitre. Preparation is painted hematoxilin and eosin. The follicles of thyroid are megascopic, the walls of follicles are refined, an epithelium is cube. In blooming of follicles thick colloid, intensively colored by eosin in a rose color. Follicles are of different form, often irregular-shaped as a result of their increase and compression. Stroma of gland is expressed poorly, vessels are little.
4. Thyreotoxic (based’s) goitre. Preparation is painted by hematoxilin and eosin. Follicles are of different forms, often wrong, different in sizes. For Thyreotoxical goitre the following histological signs are typical: -changes of prismatic epithelium of follicles in high cylinder; to the –proliferation of epithelium with formation of papillae which grow at follicles; –vacuolysation and change of tinktorial properties of colloid (he is poorly painted in a rose color) in connection with dilution of him and diminishing in the colloid of iodine; –lymphoplasmocytary infiltration of stromi, forming of lymphoid follicles. In preparation all four signs of Thyreotoxical goitre are evident, except for lymphatic follicles.
5. Parenchymatous goitre. Preparation is painted by hematoxilin and eosin. Proliferation of epithelium of follicles which overgrow as solid follicles are evident , that as tension bar with formation of follicular of shallow structures without a colloid or with very his two-bit. Stroma is developed well and presented mainly magnificent connecting fabric. Placed stroma prevails above follicles. Macroscopically a thyroid has the appearance of homogeneous rose tissue. In some preparations combination of parenchymatous and colloid goitre are evident.
6. Cancer of thyroid gland. Colouring of gematoxilin and eosin. Tissue of thyroid gland is largely transferable connecting tissue of a fibrosis goitre. In the aits of the stored tissue of thyroid gland numerous infiltrate large, by mainly round mews with hyperchrome kernels, in which calculation of mitosis take place. In infiltrates areas of blooming are evident in which at the large increase of microscope large oval mews of epitheliums are evident with a poorly contrasting kernel – chromatin as shallow granules, located on all cytoplasm – pathological mitosis. Infiltration of mews with hyperchrome kernels is also evident in connecting tissue. The contours of infiltration are washed out. Evidently area, presented the disfigured mews of epitheliums of different form and size with hyperchrome kernels on the different stages of mitosis. Mews are located densely is trabecular adenocarcinoma – and form no structures, that follicles, peculiar for a thyroid gland. Stroma is expressed poorly. Consequently, adenocarcinoma of thyroid gland is developed on the basis of fibrose goitre.
7. Pancreonekrosis. Preparation is painted by hematoxilin and eosin. In the areas of the stored tissue structure of pancreas is evident. On a considerable draught a gland is necrosed homogeneous non-structural mass of pale grey color is evident. On the verge of necrosis line of demarcation is evident, more intensively colored in dark blue due to multiplying the amount of mews: neutrophil leucocytes, macrophags, histiocytes. Vessels are sharply extended, in blooming are blood clots.
8. Glykogen is in a kidney. Preparation is painted in after the method of Shabadash. In the epithelium of channels piling up of small granules of glykogen of raspberry red color are evident. At the time of diabetes mellitus glucose from blood as a result of hyperglicemia hatches from urine is glucosuria. Thus there is glikogenes infiltration of channels, mainly narrow and distal segments. Epithelium becomes high, cytoplasm light, foamy. It is predefined by the synthesis of glykogen (polymerization is from glucose) in the epithelium of channels at resorbtion of rich in glucose ultrafiltrate of plasma, that primary or pharmacist urine. The balls of kidney suffer at the time of diabetes mellitus, the basal membranes of capillaries of balls also littered glucose and squirrel of plasma, that is why in preparation they are more intensive painted in red. These changes end with the development of intercapillar (diabetic) glomerulosclerosis.
9. Goitre of Hashimoto. Preparation is painted by hematoxilin and eosin. In the areas of the stored tissue of thyroid gland diffuse limpho-plasmocytary infiltration are evident with forming of numerous centers of reproduction, atrophy of thyroid follicles is simultaneously marked, proliferation of connecting tissue and considerable oxiphil metaplasy. Substituted for more greater part of parenchima of gland lymphoid follicles and connecting fabric.
Microscopic changes
1. Atrophy of pancreas is obvious at the time of diabetes mellitus. Colouring of tissue by hematoxilyn-eosin and method of Van-Gizon. Surplus excrescence of interparticular connecting tissue among which evidently fatty tissue as connecting variety is marked in a gland. Also surplus excrescence of connecting tissue round the muffs of conclusions are evident. Insular of little body, that the glands presented in parenchyma by the nests of round mews with hyperchrome kernels, sclerosed, mews for them little, that devastation of insular little bodies was. Fully substituted for some little bodies – by connecting tissue as round scars.
2. Intracapillar diabetic glomerulosclerosis. Preparation is painted in hematoxilin and eosin. The hearth of piling up in mesangium of eosinophil masses and diffuse bulge of basal membranes of capillaries of balls is marked. Placed fully substituted for separate balls of connecting tissue. Hyalinosis is marked in some balls, bulge of walls of capillaries.
3. Colloid macrofolicular goitre. Preparation is painted hematoxilin and eosin. The follicles of thyroid are megascopic, the walls of follicles are refined, an epithelium is cube. In blooming of follicles thick colloid, intensively colored by eosin in a rose color. Follicles are of different form, often irregular-shaped as a result of their increase and compression. Stroma of gland is expressed poorly, vessels are little.
4. Thyreotoxic (based’s) goitre. Preparation is painted by hematoxilin and eosin. Follicles are of different forms, often wrong, different in sizes. For Thyreotoxical goitre the following histological signs are typical: -changes of prismatic epithelium of follicles in high cylinder; to the –proliferation of epithelium with formation of papillae which grow at follicles; –vacuolysation and change of tinktorial properties of colloid (he is poorly painted in a rose color) in connection with dilution of him and diminishing in the colloid of iodine; –lymphoplasmocytary infiltration of stromi, forming of lymphoid follicles. In preparation all four signs of Thyreotoxical goitre are evident, except for lymphatic follicles.
5. Parenchymatous goitre. Preparation is painted by hematoxilin and eosin. Proliferation of epithelium of follicles which overgrow as solid follicles are evident , that as tension bar with formation of follicular of shallow structures without a colloid or with very his two-bit. Stroma is developed well and presented mainly magnificent connecting fabric. Placed stroma prevails above follicles. Macroscopically a thyroid has the appearance of homogeneous rose tissue. In some preparations combination of parenchymatous and colloid goitre are evident.
6. Cancer of thyroid gland. Colouring of gematoxilin and eosin. Tissue of thyroid gland is largely transferable connecting tissue of a fibrosis goitre. In the aits of the stored tissue of thyroid gland numerous infiltrate large, by mainly round mews with hyperchrome kernels, in which calculation of mitosis take place. In infiltrates areas of blooming are evident in which at the large increase of microscope large oval mews of epitheliums are evident with a poorly contrasting kernel – chromatin as shallow granules, located on all cytoplasm – pathological mitosis. Infiltration of mews with hyperchrome kernels is also evident in connecting tissue. The contours of infiltration are washed out. Evidently area, presented the disfigured mews of epitheliums of different form and size with hyperchrome kernels on the different stages of mitosis. Mews are located densely is trabecular adenocarcinoma – and form no structures, that follicles, peculiar for a thyroid gland. Stroma is expressed poorly. Consequently, adenocarcinoma of thyroid gland is developed on the basis of fibrose goitre.
7. Pancreonekrosis. Preparation is painted by hematoxilin and eosin. In the areas of the stored tissue structure of pancreas is evident. On a considerable draught a gland is necrosed homogeneous non-structural mass of pale grey color is evident. On the verge of necrosis line of demarcation is evident, more intensively colored in dark blue due to multiplying the amount of mews: neutrophil leucocytes, macrophags, histiocytes. Vessels are sharply extended, in blooming are blood clots.
8. Glykogen is in a kidney. Preparation is painted in after the method of Shabadash. In the epithelium of channels piling up of small granules of glykogen of raspberry red color are evident. At the time of diabetes mellitus glucose from blood as a result of hyperglicemia hatches from urine is glucosuria. Thus there is glikogenes infiltration of channels, mainly narrow and distal segments. Epithelium becomes high, cytoplasm light, foamy. It is predefined by the synthesis of glykogen (polymerization is from glucose) in the epithelium of channels at resorbtion of rich in glucose ultrafiltrate of plasma, that primary or pharmacist urine. The balls of kidney suffer at the time of diabetes mellitus, the basal membranes of capillaries of balls also littered glucose and squirrel of plasma, that is why in preparation they are more intensive painted in red. These changes end with the development of intercapillar (diabetic) glomerulosclerosis.
9. Goitre of Hashimoto. Preparation is painted by hematoxilin and eosin. In the areas of the stored tissue of thyroid gland diffuse limpho-plasmocytary infiltration are evident with forming of numerous centers of reproduction, atrophy of thyroid follicles is simultaneously marked, proliferation of connecting tissue and considerable oxiphil metaplasy. Substituted for more greater part of parenchima of gland lymphoid follicles and connecting fabric.
Diabetic intracapillary glomerulosclerosis.
Adenoma of the adrenal.
Figure 10 – Sclerosis and atrophy of the pancreas.
Figure 11 – Goitre of Hashimoto.
Figure 12 – Thyreotoxic (Based`s) goiter.
