Paendocrine Hypo&Tiroid

8/13/2019 Paendocrine Hypo&Tiroid

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PATHOLOGY OFENDOCRINESYSTEMDepartment of Pathology GMUSM


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Hypophysis

A. Anterior pituitary (adenohyphophysis)

1. Anterior pituitary hyperfunction

a. Prolactinomawith hyperprolactinemia

- is most common/30% pituitary tumor- staining chromophobe

- in women amenorrhea &

galactorrhea

- caused by hypothalamic lesions or

mediations methyl dopa, reserpine

interfere with dopamine

(prolactin-inhibitory factors) secretion

- can also be associated with estrogen

therapy


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b. Somatotropic adenoma with hypersecretion of growthhormone

- 2ndmost common pituitary tumor

- staining acidophyl

- causes secondary hyperfunction of somatomedins by the

liver. End organ effects are caused by both growth

hormone and somatomedins, especially somatomedin C

(insulin-like growth factor 1/IGF-1)

- results gigantismif adenoma develops before epiphyseal

closure and acromegaly if adenoma develops after

epiphyseal closure- acromegalyovergrowth of jaws, face, hands and feet,

and general enlargement of viscera with hyperglycemia,

osteoporosis and hypertension

- can also result in local compression effects due to

expansion of the tumor within the sella tursica


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Anterior pituitaryhypofunctiona. Pituitary cachexia (Simmonds disease)

- is generelized panhypopituitarism

- characterized by marked wasting

- can result from any process that destroy the

pituitaryEtiology:

(1) Pituitary tumors

(2) Post partum pituitary necrosis (Sheehan

syndrome)

- is caused by ischemic necrosis of pituitarygland,

characteristically associated with hemorrhage

and shock during childbirth

- clinical manifestations are due at first to loss of

gonadotropins, then to subsequent loss of TSH

and ACTH


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b. Selective deficiency of one or more

pituitary hormones

(1) deficiency of growth hormone

- in children, result in growth retardation (pituitary dwarfism)

- in adults, may result in increased insulin sensitivity with

hypocalcemia, decreased muscle strength and anemia(2) deficiency of gonadotropins

- in preadolescent children, results in retarded sexual

maturation

- in adults, results in loss of libido, impotence, loss of muscular

mass, and decreased hair in men, and amenorrhea and vaginal

atrophy in women

(3) deficiency of TSH

- result in secondary hypothyroidism

(4) deficiency of ACTH

- results in secondary adrenal failure

- does not result in hyperpigmentation of the skin, probably

because of lack of both ACTH and -MSH; this is in contrast to

primary adrenal failure (Addison disease), in which ACTH isincreased and hyperpigmentation is the rule


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Growth hormone containing cell in adenoma ofadenohyphophysisImmunoperoxidase staining method


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POSTERIOR HYPOPHYSISNEUROHYPOPHYSIS) HORMONES

- are synthesized in the hypothalamus and

transported via axons to the posterior

pituitarya. Oxytocin: induces uterine contarction

during labor and ejection of milk from

mammary alveoli

b. Anti diuretic hormone(ADH, vasopressin)- promotes water retention through action

on the renal collecting ducts


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Syndrome of inappropriate ADH(SIADH)secretion is

most commonly caused by ectopic production of ADH

by various tumors, especially small cell carcinoma of

lung. Results in retention of water with consequentdilutional hyponatremia, reduced serum osmolality,

and inability to dilute urine

Deficiency of ADH: results in diabetes insipidus;

characterized by polyuria, with consequent

dehydration and insatiable thirst- can be caused by tumors, trauma, inflammatory

processes, lipid storage disorders, and other

conditions characterized by damage of the

neurohypophysis or hypothalamus


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C. NON FUNCTIONINGPITUITARY TUMORS Non secreting pituitary adenomas

- are most often chromophobe

- result in dysfunction because of local

pressure phenomena- are clinically variable ;manifestations

include hypopituitarism, headache,visual

disturbance (bilateral hemianopsia / loss of

peripheral visual fields due to pressure onoptic chiasm), and palsies caused by

cranial

nerve damage


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Craniopharyngioma- is benign childhood tumor derived from remnants of

the Rathke pouch

- is not a true pituitary tumors- similar to ameloblastoma of the jaw

- is characterized by nests and cords of squamous orcolumnar cells in loose stroma, closely resembling theappearance of the embryonic tooth bud enamel organ

- is often cystic; lining epithelium of flat or columnar cellsoften expands into papillary projections

- is often detected radiographically because of calcification


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Craniopharyngioma : masses of keratin within tumourmasses composed of loosely packed stellate epithelialcells surrounded by a pallisaded basal layer bordering anoedematous stroma


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PATHOLOGY OFTHYROID ANDPARATHYROID GLANDHarijadi

Department of Pathology GMU SM


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NORMAL THYROIDGLAND


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Autoimmune disease of thyroidgland


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HYPERTHYROIDISM GRAVES THYROIDITIS

FUNCTIONAL ADENOMA

TOXIC NODULAR GOITRE


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GR VES DISE SE


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Gross specimen of Graves disease


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MICROSCOPIC SPECIMEN OF GR VESdisease


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Papillary carcinomathyroid


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Follicular carcinoma ofthyroid


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Anaplastic carcinoma ofthyroid


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Medullary carcinoma ofthyroid


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Parathyroid adenoma


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Parathyroid adenoma


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Pathology ofadrenal glandsHarijadi

Department of Pathology GMUSM


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Normal adrenal gland


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NORMAL CORTEXADRENAL


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Adrenal glands CORTEX

- Hypercorticism / Cushing syndrome

- Hyperaldosteronism- Adrenal virilsm

- Hypocorticism

MEDULLA- Pheochromocytoma

- Medulloblastoma


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ADRENOCORTICAL HYPERPLASIA

The adrenal cortex are yellow, thickened and multinodular


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ADRENOCORTICAL ADENOMASOLITARY, CIRCUMSCRIBED


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ADRENAL CORTICALADENOMA


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Cells in adrenocorticaladenoma


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Compact adenoma


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Black cortex adenoma inCushing syndrome


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Morphologic changes inadrenal glands Bilateral hyperplasia of adrenal zona fasciculata occurs

when the syndrome results from ACTH stimulation

Adrenal cortical atrophy is seen when exogenousglucocorticoid 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, hypercorticismof

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 isadrenal

origin


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Clinical characteristics ofhypercorticism Redistribution of body fat with round

moon face, dorsal buffalo hump, oftenwith relatively thin extremities caused

by muscle wasting; skin atrophy witheasy bruishing and purplish striae,especially over abdomen , and

hirsutism Muscle weakness, osteoporosis,

amenorrhea, hypertension,hyperglycemia, and psychiatric

d sfunction


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HYPERALDOSTERONISM Primary aldosteronism ( Conn syndrome)

- is caused by primary hyperfunction od adrenal

mineralocorticoids

- usually results from an aldosteron-producing

adrenocortical adenoma (aldosteronoma)- can results from hyperplasia of the zonaglomerulosa

- may rarely caused by adrenocortical carcinoma

- is characterized clinically by hypertension, sodium

and water retention, and hypokalemia, often withhypokalemic alkalosis

- demostrates decreased serum renin due tonegative

feedback of increased blood pressure on renin

secretion


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Secondary aldosteronism

- is secondary to renal ischemia, renal tumors, and

edema( e.g. cirrhosis, nephrotic syndrome, cardiac

failure)

- is caused by stimulation of the renin-angiotensin

system

- demonstates increased serum renin. In contrast to

primary aldosteronism. Renin synthesized in the

juxta glomerular apparatus of the kidney promotes

the conversion of angiotensigen to angiotensin I,

which converted catalytically by angiotensin

converting enzyme (mainly in lung) to AT II. The

release of aldosterone is facilitated by AT II.


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Adrenal virilismadrenogenital syndrome) Causes

a. Congenital enzyme defectresult in deminished

corticol production and compensatory increased

ACTH, with resultant adrenal hyperplasia with

androgenic steroid production(1) 21- hydroxylase deficiencymost common

result in salt loss and hypotension

(2) 11- hydroxylase deficiency less common

results in salt retention and hypertension

b. Tumor of the adrenal cortex

Clinical characteristic:

- produces virilism in females and precocious puberty

in males


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HYPOCORTICISMadrenal hypofunction) Can be primary adrenal cause or

secondary to hypothalamic or

pituitary hypofunction Is characterized by deficiency of

glucocorticoid (primary cortisol) ,

often associated with

mineralocorticoid deficiency

1. ADDISON DISEASE

2. Waterhouse Friderichsen

syndrome


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ADDISON DISEASE Is most commonly due to idiopathic adrenal

atrophy ( autoimmune lymphocyticadrenalitis)

Can also be caused by tuberculosis,metastatic tumors and various infections.

Is characterized by hypotension; increasedpigmentation of skin; decreased serumsodium, chloride, glucose, and bicarbonate;and increase of serum potasium


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Waterhouse Friderichsensyndrome Is catastrophic adrenal insufficiency

and vascular collapse due to

hemorrhagic necrosis of the adrenalcortex

Is often associated with disseminated

intravascular coagulation

Is characteristically due to

meningococcemia, most often in

association with meningococcal Adrenals in Waterhouse-


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Friderichsensyndromedestroyed by hemorrhage


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Tumors of adrenalmedulla1. Pheochromocytoma

Is derived from chromaffin cells of adrenal

medulla( if derived from extra-adrenal chromaffincells, called paraganglioma

Most often benign, only 10% malignant

Is characterized by increased urinary excretion of

catecholamines (epinephrine or norepinephrine)

and their metabolites ( metanephrine,

normetanephrine, 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


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Pheochromocytomathe adrenal medulla is expanded by a darked-coloured

tumour with areas of degeneration and hemorrhage

Pheochromocytoma


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left right normaladrenal


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Chromaffin cells inpheochromocytoma


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2. Neuroblastoma Is highly malignant catecholamine producing tumor in early

childhood. Urinary catecholamine and cathecolaminemetabolites 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 withthousands of gene copies per cell

a. 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, and this changes is reflected by a marked

reduction of gene amplification

Microscopic appearance of


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neuroblastoma neurogenic primitivecells

MULTIPLE ENDOCRINE


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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


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SYNDROME) Includes hyperplasia or tumors of the

pituitary, parathyroid, or pancreatic islets(3Ps)

Additionally may include hyperplasia ortumors of the thyroid or adrenal cortex

May manifest its pancreatic component bythe Zollinger-Ellison syndrome,

hyperinsulinism, or pancreatic cholera Is linked to mutations in the MEN I gene


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MEN IIa (Sipple syndrome)

- includes pheochromocytoma, medullary

carcinoma of thyroid, and hyperparathyroidismdue to hyperplasia or tumor

- is linked to mutations in the retoncogene MEN IIb / III

- Includes pheochromocytoma, medullarycarcinoma,

and multiple mucocutaneous neuroma organglioneuroma. In contrast to MEN IIa, does not

induce hyperparathyroidism.

- is linked to different mutations in the retoncogene

than is MEN IIa


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NORMAL PANCREAS

Staining of immunoperoxidase technique


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for insulin insulin containing cells aredarkly stained


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TYPES OF DM

TYPE I VERSUS TYPE II


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DM


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DIABETES MELLITUS Classification and general features

A. Type 1 (insulin-dependent diabetes mellitus / IDDM),

juvenile or ketosis-prone diabetes mellitus

- often begins early in life, before age 30

- is less common than type 2

- is due to failure insulin synthesis by beta cells of the pancreas

islets- a genetic predisposition complicated by

autoimmune inflammation / insulinitis triggered by a viral

infection or environmental factors. Family history lessfrequently

than type 2 DM

- Increased incidence with specific point mutation of HLA- DQ

gene, and incidence markedly increased in HLA-DR3- and

HLA-DR4-positive individuals

- marked carbohydrate intolerance with hyperglycemia, leading

polyuria, polydipsia, weight loss despite increased appetite,

ketoacidosis, coma and death

- ketoacidosisketon bodiesincreased catabolism of fat


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B. Type 2 (non-insulin dependent diabetesmellitus / NIDDM, adult onset, ketosis-

resistent DM

- More common than type 1 DM

- Most often in middle age

- due to increased insulin resistance

mediated by decreased cell membrane

insulin receptors or post receptordysfunction, impaired processing of pro-

insulin to insulin, decreased sensing of

glucose by beta cells, or impaired

function of intracellular carrier proteins


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(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, often increased, plasma insulin

concentration

(b) mild carbohydrate intolerance, most often

managed by oral antidiabetic agents; insulin

therapy is not usually required

(c) ketoacidosis is unsual but does occur,characteristically precipitated by unusual stress

such as infection or surgery


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C. Maturity-onset diabetes mellitus of the young (MODY)

- an autosomal dominant syndrome characterized by

mild hyperglycemia and hyposecretion of insulin, but

without loss of beta cells

- onset earlier than type 2 DM

- is caused by a diverse group of single gene defects

D. Secondary DM occurs as a secondary phenomenon in pancreaticand other endocrine disease and pregnancy

(a) pancreatic disease

- hereditary hemochromatosis (bronze diabetes)

excess iron absorption and parenchymal deposition of

hemosiderin, with reactive fibrosis in various organs,

especially pancreas, liver and heart

(b) pancreatitisacute pancreatitis hyperglycemia,

chronic pancreatitis islet cell destruction and secondary DM

(c) carcinoma of pancreas DM may be the presenting sign


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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- 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


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Pregnancy May associated with transient DM

(gestational diabetes)

Is characteristically associated with

increased fetal birth weight and increasedfetal 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


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Pathologic changes in DM Pancreas islets

(1) Type 1 DM islets are small and beta cells are

greatly decreased in number or absent; insulinitis

marked by lymphocytic infiltration is highlyspecific

early change

(2) Type 2 DM focal islet fibrosis and

hyalinization due to deposit amylin are

characteristic but not specific. Amylin (islet

amyloid polypeptide/IAPP) deposition inpancreatic islet is characteristic of type 2 DM and

thought to interfere either with conversion of

proinsulin to insulin or with the sensing of insulinby

beta cells

Amyloid of a pancreatic


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islet


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Hyaline arteriolosclerosis of


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afferent arteriole of kidney

Nodular


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glomerulosclerosis

Nephrosclerosis in long


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standing diabetes


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Diabetic retinopathy


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ISLET CELL TUMOR Insulinoma (beta cell tumor)

- is most common islet cell tumor

- benign / malignant

- characterized by greatly increased of

insulin- clinically Whipple triad

1. episodic hyperinsulinemia and

hypoglycemia

2. CNS dysfunction temporally related tohypoglycemia (confusion, anxiety,

stupor, convulsion, coma)

3. Dramatic reversal of CNS abnormalities

by glucose administration

Insulinoma : ribbon or brown stained cells


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resembling those of the normal islet ofLangerhans


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Gastrinoma

- is often a malignant tumor, sometimes

occuring in extrapancreatic sites

- results in gastrin hypersecretion andhyper-

gastrinemia

- is associated with Zollinger-Ellison

syndrome ( marked gastric hypersecretion

of HCl, recurrent peptic ulcer disease and

hypergastrinemia

Paendocrine Hypo&Tiroid

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