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PATHOLOGY OF ENDOCRINE SYSTEM

Department of Pathology GMUSM

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Anterior pituitary (adenohyphophysis) 1.in women  amenorrhea & galactorrhea .Hypophysis  A.is most common/30% pituitary tumor . Anterior pituitary hyperfunction a. reserpine interfere with dopamine (prolactin-inhibitory factors) secretion .caused by hypothalamic lesions or mediations methyl dopa.staining  chromophobe . Prolactinoma with hyperprolactinemia .can also be associated with estrogen therapy .

staining  acidophyl . especially somatomedin C (insulin-like growth factor 1/IGF-1) . and general enlargement of viscera with hyperglycemia. face. End organ effects are caused by both growth hormone and somatomedins.causes secondary hyperfunction of somatomedins by the liver.acromegaly  overgrowth of jaws.2nd most common pituitary tumor . hands and feet. osteoporosis and hypertension .results gigantism if adenoma develops before epiphyseal closure and acromegaly if adenoma develops after epiphyseal closure . Somatotropic adenoma with hypersecretion of growth hormone . b.can also result in local compression effects due to expansion of the tumor within the sella tursica .

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Cushing syndrome  hypercorticism regardless of cause.results in increased production of ACTH / hypercorticism . Cushing disease  hypercorticism adenoma  most often a basophilic adenoma  basophilic microadenoma 2.is called Cushing syndrome or Cushing disease 1. Corticotropic adenoma and hypersecretion of ACTH . is most often of pituitary and less often of adrenal origin  may be due to ectopic ACTH production by various tumors especially small cell carcinoma of lung .

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can result from any process that destroy the pituitary Etiology: (1) Pituitary tumors (2) Post partum pituitary necrosis (Sheehan syndrome) . then to subsequent loss of TSH and ACTH .characterized by marked wasting .is caused by ischemic necrosis of pituitary gland. characteristically associated with hemorrhage and shock during childbirth .clinical manifestations are due at first to loss of gonadotropins.Anterior pituitary hypofunction a.is generelized panhypopituitarism . Pituitary cachexia (Simmonds disease) .

decreased muscle strength and anemia (2) deficiency of gonadotropins .does not result in hyperpigmentation of the skin.in preadolescent children. and decreased hair in men. may result in increased insulin sensitivity with hypocalcemia.results in secondary adrenal failure . results in retarded sexual maturation . this is in contrast to primary adrenal failure (Addison disease). in which ACTH is increased and hyperpigmentation is the rule . impotence. result in growth retardation (pituitary dwarfism) . probably because of lack of both ACTH and -MSH.in adults.in adults.b. Selective deficiency of one or more pituitary hormones (1) deficiency of growth hormone .result in secondary hypothyroidism (4) deficiency of ACTH . results in loss of libido.in children. and amenorrhea and vaginal atrophy in women (3) deficiency of TSH . loss of muscular mass.

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Growth hormone containing cell in adenoma of adenohyphophysis Immunoperoxidase staining method .

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Oxytocin : induces uterine contarction during labor and ejection of milk from mammary alveoli b.are synthesized in the hypothalamus and transported via axons to the posterior pituitary a. Anti diuretic hormone (ADH.promotes water retention through action on the renal collecting ducts .POSTERIOR HYPOPHYSIS (NEUROHYPOPHYSIS)  HORMONES . vasopressin) .

can be caused by tumors. and inability to dilute urine  Deficiency of ADH: results in diabetes insipidus. Syndrome of inappropriate ADH(SIADH) secretion  is most commonly caused by ectopic production of ADH by various tumors. inflammatory processes. lipid storage disorders. characterized by polyuria. Results in retention of water with consequent dilutional hyponatremia. with consequent dehydration and insatiable thirst . trauma. and other conditions characterized by damage of the neurohypophysis or hypothalamus . reduced serum osmolality. especially small cell carcinoma of lung.

NON FUNCTIONING PITUITARY TUMORS  Non secreting pituitary adenomas . and palsies caused by cranial nerve damage . headache.are most often chromophobe .are clinically variable .C.result in dysfunction because of local pressure phenomena .visual disturbance (bilateral hemianopsia / loss of peripheral visual fields due to pressure on optic chiasm).manifestations include hypopituitarism.

closely resembling the appearance of the embryonic tooth bud enamel organ . Craniopharyngioma .is often cystic.is benign childhood tumor derived from remnants of the Rathke pouch .is characterized by nests and cords of squamous or columnar cells in loose stroma.is not a true pituitary tumors . lining epithelium of flat or columnar cells often expands into papillary projections .is often detected radiographically because of calcification .similar to ameloblastoma of the jaw .

Craniopharyngioma : masses of keratin within tumour masses composed of loosely packed stellate epithelial cells surrounded by a pallisaded basal layer bordering an oedematous stroma .

PATHOLOGY OF THYROID AND PARATHYROID GLAND Harijadi Department of Pathology GMU SM .

NORMAL THYROID GLAND .

Autoimmune disease of thyroid gland .

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HYPERTHYROIDISM  GRAVE’S THYROIDITIS  FUNCTIONAL ADENOMA  TOXIC NODULAR GOITRE .

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GRAVE’S DISEASE .

Gross specimen of Grave’s disease .

MICROSCOPIC SPECIMEN OF GRAVE’S disease .

an autoimmune disease and endemic goitre .Hypothyroidism  Syndrome due to insufficient circulating T3 and T4  If congenital cause cretinism  Commonest case are Hashimoto’s thyroiditis.

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Papillary carcinoma thyroid .

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Follicular carcinoma of thyroid .

Anaplastic carcinoma of thyroid .

Medullary carcinoma of thyroid .

PARATHYROID GLAND .

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Parathyroid adenoma .

Parathyroid adenoma .

Pathology of adrenal glands Harijadi Department of Pathology GMUSM .

Normal adrenal gland

NORMAL CORTEX ADRENAL

Adrenal glands
 CORTEX - Hypercorticism / Cushing syndrome - Hyperaldosteronism - Adrenal virilsm - Hypocorticism  MEDULLA - Pheochromocytoma - Medulloblastoma

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thickened and multinodular .ADRENOCORTICAL HYPERPLASIA The adrenal cortex are yellow.

CIRCUMSCRIBED .ADRENOCORTICAL ADENOMA SOLITARY.

ADRENAL CORTICAL ADENOMA .

Cells in adrenocortical adenoma .

Compact adenoma .

Black cortex adenoma in Cushing syndrome .

Morphologic changes in adrenal glands
 Bilateral hyperplasia of adrenal zona fasciculata occurs when the syndrome results from ACTH stimulation  Adrenal cortical atrophy  is seen when exogenous glucocorticoid medication is cause  Adrenal cortical adenoma or carcinoma - Adenoma is more common - cannot be supressed by exogenous adrenal steroids in dexamethasone supression test, in contrast, hypercorticism of pituitary origin can usually be supressed  useful diagnosis measures in determining the cause of hypercorticism. - ACTH increased in pituitary hypercorticism and in ectopic ACTH production, and it is low when hypercorticism is adrenal origin

osteoporosis.Clinical characteristics of hypercorticism  Redistribution of body fat with round moon face. amenorrhea. often with relatively thin extremities caused by muscle wasting. and psychiatric dysfunction . hypertension. dorsal buffalo hump. skin atrophy with easy bruishing and purplish striae. hyperglycemia. and hirsutism  Muscle weakness. especially over abdomen .

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is caused by primary hyperfunction od adrenal mineralocorticoids .can results from hyperplasia of the zona glomerulosa .usually results from an aldosteron-producing adrenocortical adenoma (aldosteronoma) . sodium and water retention.is characterized clinically by hypertension.may rarely caused by adrenocortical carcinoma . often with hypokalemic alkalosis . and hypokalemia.demostrates decreased serum renin due to negative feedback of increased blood pressure on renin secretion .HYPERALDOSTERONISM  Primary aldosteronism ( Conn syndrome) .

cirrhosis.g. cardiac failure) .is secondary to renal ischemia. . and edema( e. renal tumors. which converted catalytically by angiotensin converting enzyme (mainly in lung) to AT II. nephrotic syndrome. The release of aldosterone is facilitated by AT II.demonstates increased serum renin. In contrast to primary aldosteronism. Secondary aldosteronism .is caused by stimulation of the renin-angiotensin system . Renin synthesized in the juxta glomerular apparatus of the kidney promotes the conversion of angiotensigen to angiotensin I.

hydroxylase deficiency most common result in salt loss and hypotension (2) 11.produces virilism in females and precocious puberty in males . with resultant adrenal hyperplasia with androgenic steroid production (1) 21.hydroxylase deficiency  less common  results in salt retention and hypertension b.Adrenal virilism (adrenogenital syndrome)  Causes a. Congenital enzyme defect  result in deminished corticol production and compensatory increased ACTH. Tumor of the adrenal cortex  Clinical characteristic: .

ADDISON DISEASE 2. often associated with mineralocorticoid deficiency 1. Waterhouse – Friderichsen syndrome .HYPOCORTICISM (adrenal hypofunction)  Can be primary adrenal cause or secondary to hypothalamic or pituitary hypofunction  Is characterized by deficiency of glucocorticoid (primary cortisol) .

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and increase of serum potasium . and bicarbonate. chloride. metastatic tumors and various infections. increased pigmentation of skin.ADDISON DISEASE  Is most commonly due to idiopathic adrenal atrophy ( autoimmune lymphocytic adrenalitis)  Can also be caused by tuberculosis. glucose. decreased serum sodium.  Is characterized by hypotension.

most often in association with meningococcal .Waterhouse – Friderichsen syndrome  Is catastrophic adrenal insufficiency and vascular collapse due to hemorrhagic necrosis of the adrenal cortex  Is often associated with disseminated intravascular coagulation  Is characteristically due to meningococcemia.

Adrenals in WaterhouseFriderichsen syndromedestroyed by hemorrhage .

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called paraganglioma      Most often benign. and vanillymandelic acid (VMA) Can also cause hyperglycemia Can be part of MEN IIa or MEN IIb(III) Can also be associated with bneurofibromatosis or with von Hippel-Lindau disease .Tumors of adrenal medulla 1. only 10% malignant Is characterized by increased urinary excretion of catecholamines (epinephrine or norepinephrine) and their metabolites ( metanephrine. normetanephrine. Pheochromocytoma  Is derived from chromaffin cells of adrenal medulla ( if derived from extra-adrenal chromaffin cells.

Pheochromocytoma the adrenal medulla is expanded by a darked-coloured tumour with areas of degeneration and hemorrhage .

Pheochromocytoma left adrenal right normal .

Chromaffin cells in pheochromocytoma .

Urinary catecholamine and cathecolamine metabolites are the same as in pheochromocytoma  Causes hypertension  Usually originates in the adrenal medulla and often presents as a large abdominal mass  Occasionally converts into a more differentiated form termed ganglioneuroma  Is characterized by amplification of the N-myc oncogene with thousands of gene copies per cell a. Neuroblastoma  Is highly malignant catecholamine producing tumor in early childhood. Amplification results in karyotypic changes  homogenous staining regions or double minutes chromosomes b. the number of N-myc gene copies is related to the aggressiveness of the tumor c. the malignant neuroblastoma sometimes differentiate into benign cells.2. and this changes is reflected by a marked reduction of gene amplification .

Microscopic appearance of neuroblastoma neurogenic primitive cells .

MULTIPLE ENDOCRINE NEOPLASIA (MEN) SYNDROMES  Are a group of autosomal dominant syndromes in which more than one endocrine organ are hyperfunctional  May be associated with hyperplasia or tumors  MEN I ( Werner syndrome) MEN IIa (Sipple syndrome) MEN IIb / III .

MEN I (WERMER SYNDROME)  Includes hyperplasia or tumors of the pituitary. or pancreatic cholera  Is linked to mutations in the MEN I gene . or pancreatic islets (3Ps)  Additionally may include hyperplasia or tumors of the thyroid or adrenal cortex  May manifest its pancreatic component by the Zollinger-Ellison syndrome. hyperinsulinism. parathyroid.

medullary carcinoma. and multiple mucocutaneous neuroma or ganglioneuroma. and hyperparathyroidism due to hyperplasia or tumor . MEN IIa (Sipple syndrome) . does not induce hyperparathyroidism. .is linked to different mutations in the ret oncogene than is MEN IIa .Includes pheochromocytoma.is linked to mutations in the ret oncogene  MEN IIb / III . medullary carcinoma of thyroid.includes pheochromocytoma. In contrast to MEN IIa.

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NORMAL PANCREAS

Staining of immunoperoxidase technique for insulin  insulin containing cells are darkly stained

TYPES OF DM .

TYPE I VERSUS TYPE II DM .

and HLA-DR4-positive individuals . polydipsia. leading polyuria. Family history less frequently than type 2 DM .marked carbohydrate intolerance with hyperglycemia.a genetic predisposition complicated by autoimmune inflammation / insulinitis triggered by a viral infection or environmental factors. and incidence markedly increased in HLA-DR3. before age 30 .DIABETES MELLITUS  Classification and general features A.is due to failure insulin synthesis by beta cells of the pancreas islets . ketoacidosis.ketoacidosis keton bodies increased catabolism of fat . coma and death .DQ gene.Increased incidence with specific point mutation of HLA.is less common than type 2 . Type 1 (insulin-dependent diabetes mellitus / IDDM). weight loss despite increased appetite.often begins early in life. juvenile or ketosis-prone diabetes mellitus .

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impaired processing of proinsulin to insulin.due to increased insulin resistance mediated by decreased cell membrane insulin receptors or post receptor dysfunction. Type 2 (non-insulin dependent diabetes mellitus / NIDDM. or impaired function of intracellular carrier proteins . B. decreased sensing of glucose by beta cells.Most often in middle age . adult onset.More common than type 1 DM . ketosisresistent DM .

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insulin therapy is not usually required (c) ketoacidosis is unsual but does occur. plasma insulin concentration (b) mild carbohydrate intolerance. often increased. most often managed by oral antidiabetic agents. characteristically precipitated by unusual stress such as infection or surgery .(1) Etiologic factors (a) positive family history more frequent than type 1 (b) most often associated with mild to moderate obesity (2) Characteristics (a) normal.

is caused by a diverse group of single gene defects D.an autosomal dominant syndrome characterized by mild hyperglycemia and hyposecretion of insulin. liver and heart (b) pancreatitis acute pancreatitis  hyperglycemia. but without loss of beta cells .hereditary hemochromatosis (bronze diabetes)  excess iron absorption and parenchymal deposition of hemosiderin. Secondary DM  occurs as a secondary phenomenon in pancreatic and other endocrine disease and pregnancy (a) pancreatic disease . with reactive fibrosis in various organs. especially pancreas. Maturity-onset diabetes mellitus of the young (MODY) . chronic pancreatitis  islet cell destruction and secondary DM (c) carcinoma of pancreas  DM may be the presenting sign .C.onset earlier than type 2 DM .

insulin like effect of GH  Glucagon hypersecretion  promotes glycogenolysis is characteristically caused by an islet alpha cell tumor (glucagonoma)  Phaeochromocytoma and hyperthyroidism are sometimes associated with hyperglycemia .Other endocrine diseases  Cushing syndrome  produces hyperglycemia a s a result of increased gluconeogenesis and impaired peripheral utilization of glucose  Acromegaly  produces hyperglycemia due to the anti.

Pregnancy  May associated with transient DM (gestational diabetes)  Is characteristically associated with increased fetal birth weight and increased fetal mortality. notably from neonatal respiratory distress syndrome (hyaline membrane disease)  When the mother has hyperglycemia can result in an infant born with hyperplasia of the pancreatic islets and hypoglycemia .

Pathologic changes in DM  Pancreas islets (1) Type 1 DM  islets are small and beta cells are greatly decreased in number or absent. Amylin (islet amyloid polypeptide/IAPP) deposition in pancreatic islet is characteristic of type 2 DM and thought to interfere either with conversion of proinsulin to insulin or with the sensing of insulin by beta cells . insulinitis marked by lymphocytic infiltration is highly specific early change (2) Type 2 DM  focal islet fibrosis and hyalinization due to deposit amylin are characteristic but not specific.

Amyloid of a pancreatic islet .

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Hyaline arteriolosclerosis of afferent arteriole of kidney .

Nodular glomerulosclerosis .

Nephrosclerosis in long standing diabetes .

Diabetic retinopathy .

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is most common islet cell tumor . CNS dysfunction temporally related to hypoglycemia (confusion.benign / malignant . anxiety. coma) 3. episodic hyperinsulinemia and hypoglycemia 2. Dramatic reversal of CNS abnormalities by glucose administration . convulsion.characterized by greatly increased of insulin . stupor.clinically  Whipple triad 1.ISLET CELL TUMOR  Insulinoma (beta cell tumor) .

Insulinoma : ribbon or brown stained cells resembling those of the normal islet of Langerhans .

is often a malignant tumor.is associated with Zollinger-Ellison syndrome ( marked gastric hypersecretion of HCl. recurrent peptic ulcer disease and hypergastrinemia . Gastrinoma . sometimes occuring in extrapancreatic sites .results in gastrin hypersecretion and hypergastrinemia .