endocrine-uii-2011.ppt

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T. UtoroDepartment of Pathology

Gadjah Mada University School of Medicine

PATHOLOGY ENDOKRINOLOGY

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PATHOLOGY OF THE

T H Y R O I D

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T H Y R O I D

• Normally weighs between 20 and 30 g.• Follicle is the functional unit of the thyroid

composed of an epithelium-lined sac filled with colloid stores thyroid hormones in the form of thyroglobulin T4 (thyroxine) and T3 (triiodo-thyronine) regulated by TSH

• Serum T4 and T3 are bound to thyroid-binding globulin (TBG)

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Homeostasis in the hypothalamus-

pituitary-thyroid axis, and mechanism of action of thyroid

hormones

Cellular effects of thyroid hormones-up-regulation of carbohydrate and

lipid catabolism-Stimulation of protein synthesis in

wide range of cells

Net result:Increased the basal metabolic rate

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Pathology of thyroid

A. CONGENITAL ANOMALYB. GOITERC. HYPOTHYROIDISMD. HYPERTHYROIDISME. THYROIDITISF. BENIGN TUMORS (ADENOMAS)G. MALIGNANT TUMORS

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A. CONGENITAL ANOMALY

1. Thyroglosal duct cyst- is a remnant of the thyroglossal duct- is the most common thyroid anomaly- does not lead to alterations in thyroid function

2. Ectopic thyroid tissue- may be found anywhere along the course of the thyroglossal duct

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B. GOITER

A chronic enlargement of thyroid gland

due to other than neoplasm

Synonim: STRUMA

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B. GOITER

A.CAUSES

a. Physiologic enlargement

- is not uncommon in puberty and pregnancy b. Iodine deficiency

- occurs in geographic areas where diet is deficient in iodinec. Hashimoto thyroiditis

d. Goitrogens

- foods or drugs that suppress synthesis of thyroid hormonee. Dyshormogenesis

- partial or complete failure of thyroid hormone synthesis; can be caused by various enzyme deficiencies

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B. GOITERB.TERMINOLOGY

a. Simple goiter (nontoxic goiter)- is goiter without thyroid hormone dysfunction

b. Toxic goiter- is goiter associated with hyperthyroidism

c. Endemic goiter- goiter occurring with high frequency in iodine-deficient geographic areas

d. Nodular goiter- irregular enlargement of the thyroid nodule formation- nodular colloid goiter: late stage simple goiter, in which goiter is most often nodular (most nodules are hypoplastic and do not take up radioactive iodine “cold” nodule)

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Non-toxic goiter

Irregular nodules

Marked variation in the size of follicles

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Nodular (non-toxic) Goiter

The gland is coarsely nodular and contains areas of fibrosis and cystic change.

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C. HYPOTHYROIDISMDiminished production of thyorid hormone, leadingto clinical manifestation of thyroid insufficiency.It can be the consequences of three general processes Defective synthesis of thyroid hormone, with

compensatory goitrogenesis (goitrous hypothyroidism)

Inadequate function of thyroid parenchyma (usually as a result of thyroiditis, surgical resection, or radioiodine therapy)

Inadequate secretion of TSH by the pituitary or TRH by the hypothalamus

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C. HYPOTHYROIDISM

Dominant clinical manifestation

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C. HYPOTHYROIDISM

Laboratory abnormalities1. Decrease serum free T4, increased serum TSH

2. Increase serum cholesterol

3. Classic thyroid test

-T3 resin uptake decreased

- Total T4 decreased

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C. HYPOTHYROIDISM

Clinical syndromesHypothyroidism is manifest as Myxedema in

adults or as Cretinism in children

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Pathology of thyroid: C. HYPOTHYROIDISM:

Myxedema

A. More common in womenB. Etiology:

1. Therapy for hyperthyroidism with surgery, irradiation, or drugs 2. Hashimoto thyroiditis3. Unknown – primary idiopathic myxedema – is a poorly defined form of myxedema : TSH receptor blocking antibodies have been identified.4. Iodine deficiency is the most important cause in non-iodine deficient geographic regions

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MyxedemaC. Clinical charateristics

1. Incidious onset 2. Cold intolerance3. Tendency to gain weight because of a low metabolic rate4. Lowered pitch of voice5. Mental and physical slowness6. Menorrhagia7. Constipation8. Abnormal physical findings:

- puffiness of face, eyelids, and hands- dry skin- hair loss; coarse and brittle hair; scant axillary and pubic hair;

thinning of the lateral aspect of the eyebrows- increase in relaxation phase of deep tendon reflexes.

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CRETINISMA. Etiology:

1. Iodine deficiency 2. Deficiency of enzymes necessary for the synthesis of thyroid hormones3. Maldevelopment of the thyroid gland4. Failure of the fetal thyroid to descend from its origin at the base of the tongue 5. Trans placental transfer fo antithyroid antibodies from a mother with autoimmune thyroid disease

B. Characteristics:1. Severe mental retardation2. Impairment of physical growth with retarded bone development and dwarfism3. Large tongue4. Protuberant abdomen

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HYPERTHYROIDISM (THYROTOXICOSIS)

A. Clinical Features

1. Restlessness, irritability, fatigability2. Tremor3. Heat intolerance; sweating; warm, moist skin (especially palms)4. Tachycardia, often with arrythmia and palpitation, sometimes with high-output cardiac failure5. Muscle wasting and weight loss despite increase appetite6. Fine hair7. Diarrhea8. Menstrual abnormalities, commonly amenorrhoea or oligomen.9. Greatly increased free T4 and reduced TSH ------ and less commonly employed are increased total T4&T3, and resin uptake

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Graves disease, hyperthyroidism

Exophthalmos

Thyroid mass

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Major clinical manifestations

of Graves disease

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B. Graves DiseaseGeneral Charcteristics

1. Hyperthyroidism caused by diffuse toxic goiter2. Associated with striking exophthalmos autoimmune?3. More in women4. incidence increased in HLA-DR3 and HLA-B8 positive individual

Mechanism

1. Thyroid-stimulating-immunoglobulin (TSI) reacts with TSH receptors stimulates thyroid hormone production2. Thyroid-growth-immunoglobulin (TGI) stimulates glandular hyperplasia and enlargement 3. Antimicrosomal and other autoantibodies are characteristic

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B. Other causes of hyperthyroidism

1. Plummer Disease- the combination of hyperthyroidism, nodular goiter, and absence of

exophthalmos- the “hot” nodules can be adenomas or non-neoplastic areas of nodular hyperplasia

2. Pituitary hyperfunction- can cause excess production of TSH and secondary hyperthyroidism

3. Struma ovarii- ovarian teratoma made up of thyroid tissue, can be hyperfunctional

4. Exogenous administration of thyroid hormone

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Graves Disease

Diffusely hyperplastic thyroid with follicle are lined by tall, columnar epithelium, and scalloped (“moth eaten”) appearance of

the edge of the colloid.

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Graves disease, hyperthyroidism

The follicles are lined by hyperplastic, tall columnar cells

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Immune mechanism of Graves Disease and Hashimoto Thyroiditis

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E. THYROIDITIS

Inflammation of the thyroid gland(encompasses a heterogenous group of inflammatory disorders of the

thyroid gland, including those that are caused by autoimmune

mechanisms and infectious agents)

A. Acute suppurative thyroiditis: a bacterial infection,

usually occurs in young children or debilitated patients. It is rare

B. Subacute granulomatous thyroiditis (De Quervain thyroiditis)

C. Chronic thyroiditis (Hashimoto thyroiditis, Struma lymphomatosa, autoimmune thyroiditis)

D. Riedel’s struma (Riedel’s disease)

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Subacute/De Quervain/granulomatous Thyroiditis

• Is characterized by focal destruction of thyroid tissue and granulomatous inflammation

• Etiology: variety of viral infections such as mumps or coxsackie virus

• Follows a limited course several weeks of duration consisting of flu-like illness along with pain and tenderness of the thyroid, sometimes with transient hyperthyroidism

• More common in women

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Subacute/De Quervain/granulomatousThyroiditis

The release of colloid into the interstitial tissue has elicited a prominent granulomatous reaction, with numerous foreign body giant cells

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Subacute/De Quervain/granulomatous Thyroiditis

The parenchyma contains chronic inflammatory infiltrate with a multinucleate giant cells and colloid folicles

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Chronic autoimmune (Hashimoto) thyroiditis

• Autoimmune disorder that occur more often in women• Common cause of hypothyroidism, may occasionaly

have an early transient hyperthyroid phase• Characterized histologically by massive infiltrates of

lymphocytes with germinal center formation, thyroid follicles are atrophic, and Hurthle cells are prominent

• Associated with various antibodies (antithyroglobulin, antithyroid peroxidase, anti TSH-receptor, anti-iodine receptor antobodies)

• May be associated with other autoimmune disorders: pernicious anemia, DM, Sjogren syndrome the incidence is increased in HLA-DR5 and HLA-B5 positive

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The thyroid gland is symmetrically enlarged and coarsely nodular.Coronal section irregular nodules and an intact capsule

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Atrophic thyroid follicles with conspicuous chronic inflammatory infiltrate(the inflammatory cells form prominent lymphoid follicles with germinal centers)

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Hashimoto Thyroiditis

Dense lymphocytic infiltrates with germinal centersResidual thyroid follicle lined by Hurthle cells are also seen

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Riedel thyroiditis

• Characterized by thyroid replacement of fibrous tissue

• Etiology is unknown, does not appear to be related to other thyroiditis

• Also involves extra thyroidal soft tissue of the neck, often associated with fibrosis in other location (retroperitoneum, mediastinum, orbit)

• May clinically mimick carcinoma

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Riedel thyroiditis

The thyroid parenchyma is largely replaced by dense, hyalinized fibrous tissue and a chronic inflammatory infiltrate

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F. BENIGN TUMORS (ADENOMAS)

• Are most often solitary• Present clinically as nodules• Can occur in a variety of histologic

pattern (follicular, Hurthle cell)• Are most often nonfunctional but can

occasionally cause hyperthyroidism• Female:male is 7:1

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FOLLICULAR ADENOMA

• Embryonal adenoma

• Fetal adenoma

• Simple adenoma

• Colloid adenoma

• Hurthel cell adenoma

• Atypical adenoma

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Follicular adenoma

Embryonal adenoma

The tumor features a trabecular pattern with poorly formed follicles that contain little if any colloid

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Follicular Adenoma

COLLOID ADENOMAThe cut surface of an encapsulated mass reveals:

Hemorrhage

Fibrosis

Cystic change

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Follicular Adenoma

A solitary, well-circumscribed nodule is seen.

Cystic

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Follicular Adenoma

Well-differentiated follicles resembling normal thyroid parenchyma.

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Follicular adenoma

FETAL ADENOMA

Regular pattern of small follicles

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Follicular adenoma

Hurthle cell Adenoma

Cells with abundant eosinophilic cytoplasm and small regular nuclei.

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G. MALIGNANT TUMORS

• Papillary Carcinoma• Follicular Carcinoma• Medullary Carcinoma• Anaplastic Carcinoma

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G. MALIGNANT TUMORS

Papillary Thyroid Carcinoma (PTC)

• Is the most common thyroid cancer (90%)• Most frequent between ages 20 – 50 years• Female:male is 3:1• Papillary growth pattern with ground glass nuclei• Better prognosis than other forms of thyroid cancer ,

even when adjacent lymph nodes is involved• Can be long-term consequence of prior radiotherapy to

the neck• Typically invades lymphatics and spreads to regional

lymph nodes

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G. MALIGNANT TUMORS


Pathogenesis:• Iodine excess

Animal exp., in endemic goiter region addition of iodine increase incidence

• Radiation

Radiation therapy, and radioactive ray• Genetic factors

First degree relatives of persons with tumor: 4-10 fold higher risk

• Somatic mutation

Somatic rearrangement of RET protooncogene in chromosome 10 (10q11.2)

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G. MALIGNANT TUMORS


Macroscopic appearance with grossly discernible papillary structure

FNAB - BAJAH

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G. MALIGNANT TUMORS

Papillary Thyroid

Carcinoma (PTC)

Cut surface diplays a circumscribed pale tan mass with foci of

cystic change

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G. MALIGNANT TUMORS


Well-formed papillae “Orphan Annie eye”, or ground-glass nuclei, or empty appearing nuclei

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G. MALIGNANT TUMORS

Papillary Thyroid Carcinoma (PTC) the most common thyroid cancer

Brancing papillae are lined by neoplastic columnar epithelium with clear nuclei. A calcospherite (psammoma body) is evident..

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G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma (FTC)

• FTC ia defined as a malignant neoplasm that is purely follicular and does not contain papillary or any other elements

• Mostly are detected as a palpable nodule or enlarged thyroid, or as advanced form as bone (pathological fracture), or lung metastasis

• Poorer prognosis than PTC• Differs from PTC in that metastses are blood

borne rather than lymphatic, directed principally to the bones of shoulder and pelvic girdles, sternum, and skull

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G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma FTC)

Cut surface of follicular carcinoma with the substantial replacement

of the lobe of the thyroid.

The tumor has a light-tan appearance and contains small foci

of hemorrage

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G. MALIGNANT TUMORS


Glandular lumen contains recognizable colloid

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G. MALIGNANT TUMORS


Capsular integrity in follicular neoplasm is critical in distinguishing follicular adenoma from carcinoma.Follicular adenoma: capsule is usually thin, occasionally more prominent; no capsular invasion is seen (arrows).Follicular carcinoma: capsular invasion (arrows)

ADENOMA CARCINOMA

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G. MALIGNANT TUMORS


A microfollicular tumor has invaded veins in the thyroid parenchyma.

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G. MALIGNANT TUMORS

Medullary Thyroid Carcinoma (MTC)

• MTC is distinguished by its secretion of the calcium-lowering hormone (calcitonin)

• Reprsents no more than 5% of all thyroid cancers• 80% are sporadic form: RET protooncogene

mutation are detected in 25-70% of cases• 20% are familial form: afflicted by MEN type 2

includes phaeochromocytoma and parathyroid hyparplasia, adenoma

• The mean age: 50 years (familial case 20 years)

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G. MALIGNANT TUMORS

Medullary Thyroid Carcinoma (MTC)

• Tends to arise in superior portion (the region that are richest in C cells--parafollicular)

• Often multicentric and bilateral (MEN setting)• Conspicuous feature: the presence of stromal

amyloid, representing the disposition of calcitonin• The preccursor of the familial form MTC is C cell

hyperplasia• Tumor markers: Calcitonin, CEA, Chromogranin

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G. MALIGNANT TUMORS: Medullary Thyroid Carcinoma (MTC)

Clinical Features

• Symptoms related to endocrine secretion: carcinoid syndrome (calcitonin), Cushing syndrome (ACTH)

• Watery diarhea in 1/3 cases, caused by secretion of vasoactive intestinal peptide, pros-taglandin, and several kinins

• Familial MTC: hypertension, episodic hypertension, symptoms attributable to the secretion of catechol-amines and phaeochromocytoma

• Therapy: thyroidectomy local recurrencies 1/3 • 5-year survival rate is 75%

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G. MALIGNANT TUMORS:

Medullary Carcinoma

Solid pattern of growth and do not have connective tissue capsule.

Coronal section total (bilateral) involvement by a firm, pale tumor.

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Medullary Thyroid Carcinoma

Nest of polygonal cells embedded in a collagenous framework.

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Medullary Thyroid Carcinoma

Amyloid: Congo red staining polarized light microscope pale green birefringent

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Medullary Carcinoma

Typically contain amyloid, visible here as homogenous extracellular material, derived from calcitonin molecules secreted by the neoplastic cells

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Anaplastic (Undifferentiated) Carcinoma of the Thyroid

• Usually fatal, principally afflict women (4:1) over the age of 60 years

• Constitutes 10% of thyroid cancers• It seems likely that the anaplastic carcinoma

represent the transformation of a benign or lower grade thyroid neoplasm into poorly differentiated and highly aggressive cancer

• Mutation of p53 is common• 5-year survival rate less than 10%

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Anaplastic Carcinoma of the Thyroid

The tumor in traverse section partially surround the trachea and extend into the adjecent soft tissue.

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Anaplastic Carcinoma

The tumor is composed of bizarre spindle and giant cells with numerous mitoses

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Lymphoma of the thyroid

• Are largely B-cell tumors• Accounts for 2% of all thyroid cancers• Most if not all cases arise in the setting of chronic

thyroiditis• More in women (4:1), the mean age is older than

man• Macros: large, soft, tannish masses of thyroid,

usually extending beyond the confines of gland• Micros: same spectrum as other sites, mostly

diffuse large cell pattern

PANKREAS ENDOKRIN

• Diabetes mellitus

• Tumor endokrin (islet cell tumors)

Secretory Products of Islet Cells and Their Physiologic Actions

Cell Secretory Product

Mol. Wt.

Physiological Action

Alpha Glucagon 3500 Catabolic, stimulates glycogenolysis & gluconeogenesis, raises blood glucose

Beta Insulin 6000 Anabolic, stimulates glycogenesis, lipogenesis, protein synthesis, lowers blood glucose. Inhibits secretion of alpha, beta, D1, acinar cells

DeltaD

Somatostatin 1600

DeltaD1

Vasoactive Intestinal Polypeptide (VIP)

3800 Same as glucagon, regulates tone & GE tract motility, activates cAMP of intestinal epithelium

PP Human pancreatic polypeptide (ppp)

4300 Stimulates gastric enzyme secretion, inhibits intestinal motility & bile secretion

EC Serotonin, substance P (motilin)

176 Induce vasodilatation, increases vascular permeability, stimulates motility of gastric muscle and tone of lower esophageal sphincter

NORMAL PANCREAS

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

DIABETESKlasifikasi & gambaran umum1. DM Tipe 1

2. DM Tipe 2

3. Maturity-onset DM of the young (MODY)

4. DM sekunder

a. Penyakit pankreas

(1) Hemokromatosis Herediter (bronze

diabetes)

(2) Pankreatitis

(3) Ca pankreas

b. Penyakit endokrin lain

c. Kehamilan

Patofisiologi

DIABETES Tipe 1Insulin-dependent DM (IDDM), juvenile or

ketosis-prone DM• Mulai lebih dini, biasanya sebelum umur 30 th• Lebih jarang dari pada tipe 2• Karena kegagalan sintesis insulin oleh sel beta pulau

Langerhans pankreas• Etiologi: predisposisi genetik dengan komplikasi proses

inflamasi autoimun dan dipicu oleh infeks virus atau faktor lingkungan

• Riwayat keluarga << tipe 2• Insiden sangat meningkat pada individu dengan mutasi

titik pada gena HLA-DQ, dan sangat tinggi pada individu dengan HLA-DR3 & HLA-DR4 positif

DIABETES Tipe 1

• Kalau tidak diberikan insulin akan terjadi Intoleransi karbohidrat dengan hiperglikemia poliuri, polidipsi, penurunan berat badan / nafsu makan naik, ketoasidosis, koma kematian

• Ketoasidosis akibat dari meningkatnya katabolisme lemak keton bodies (yang tidak terbatas pada ketoasidosis tetapi juga pada kelaparan – jauh lebih ringan)

DIABETES Tipe 2

• Jauh lebih banyak dari pada tipe 1• Mulai pada umur pertengahan (paling sering)• Mekanisme:

1. peningkatan resistensi terhadap insulin akibat dari

penurunan reseptor insulin di membran atau

2. karena disfungsi pos-reseptor; atau

3. dapat berhubungan dengan terganggunya proses

perubahan proinsulin insulin

4. Penurunan sensing glukosa oleh sel beta

5. Gangguan fungsi protein pembawa intraselular

DIABETES Tipe 2

Faktor etiologik:• Riwayat keluarga positive lebih sering dari pada tipe 1• Paling sering dihubungkan dengan obesitas sedang

sampai berat

Gejala / karakteristik:• Kadar insulin plasma normal atau meningkat• Intoleransi karbohidrat ringan diet dan OAD, insulin

biasanya tidak diperlukan• Ketoasidosis tidak biasa kecuali pada keadaan stress

tertentu misalnya pada infeksi dan operasi

Maturity-onset diabetes mellitus of the young

MODY

• Sindroma autosom dominan ditandai dengan hiperglikemia ringan dan hiposekresi insulin, tanpa hilangnya sel beta

• Onset lebih dini dari pada tipe 2• Disebabkan karena keaneka-ragaman

kelompok dari defek gena tunggal pada

DM Sekunder

• Muncul sebagai manifestasi sekunder dari pankreas dan penyakit endokrin yang lain dan kehamilan

1. Penyakit pankreas

2. Penyakit endokrin lain

3. Kehamilan

DM Sekunder

1. Penyakit pankreas

1.Hemokromatosis herediter (bronze diabetes)• Ditandai oleh absorpsi besi berlebihan dan deposisi

hemosiderin parenkimal, dengan fibrosis reaktif pada berbagai organ terutama pankreas, hati, jantung

2.Pankreatitis• Radang akut ditandai hiperglikemi; radang kronis

berakibat destruksi pulau Langerhans DM sekunder

3.Ca pankreas• Diabetes bisa sebagai gejala

DM Sekunder

2. Penyakit endokrin lain

1.Cushing Syndrome• Berakibat hiperglikemia dan peningkatan

glukoneogenesis dan gangguan pemakaian glukosa perifer

2.Akromegali• Berakibat hiperglikemia karena efek laksana-anti insulin

dari GH (hormon pertumbuhan)3.Hipersekresi glukagon• Menyebabkan glikogenolisis – karena tumor sel alfa

(glukagonoma)4.Kelainan endokrin lain• Feokromositoma & hipertroidisme kadang dihubungkan

dengan hiperglikemia

Patofisiologi DM1.Pulau-pulau Langerhansa. DM tipe 1• Pulau-pulau kecil dan sel-sel beta sangat berkurang atau

hilang• Adanya radang dengan sebukan limfosit padat sangat

spesifik pada tingkat awal b. DM tipe 2• Fibrosis dan hialinisasi fokal pada pulau2 (karena

deposit amilin) cukup karakteristik tapi tidak spesifik• Depoisisi amylin (islet amyloid polypeptide, IAPP) dalam

pulau-pulau karakteristik untuk DM tipe 2 mengganggu perubahan proinsulin ke insulin atau sensing insulin oleh sel beta

Amyloid of a pancreatic islet

Patofisiologi DM

2.Ginjal• Manifestasi awal pada ginjal yang sering: penebalan

membrana basalis• Akibat umum: glomerulosklerosis difus, fokal (penyakit

Kimmelstiel-Wilson), lesi arteriolar, lesi eksudatif• Hiperglikemi lama tanpa terapi lesi Armani-Ebstein

(deposisi glikogen tubular)• Pielonefritis: komplikasi yang sering, kadang bersama

nekrosis papilar renal

Hyaline arteriolosclerosis of afferent arteriolae of kidney

Nodular glomerulosclerosis

Nephrosclerosis in long standing diabetes

Patofisiologi DM

3. Sistem kardiovaskular• Insiden aterosklerosis sangat meningkat, pada usia

lebih muda, dan meningkat tinggi pada wanita pre & post menopausal

• Komplikasi: infark miokard dan insufisiensi vaskular perifer (sering dengan gangren tungkai bawah)

• Penebalan membrana basalis kapilar organ multipel dan diperkirakan karenaglikosilasi protein membran non-enzimatik

Patofisiologi DM4.Mata• Paling sering: katarak• Retinopati proliferatif (eksudat retina, edema,

hemoragi, mikroaneurisma vasa kecil)

5.Sistem syaraf• Perubahan: neuropati perifer, otak, dan medula

spinalis

6.Hati• Perlemakan hati

7.Kulit:• Xantoma• Furunkel dan abses, infeksi jamur

Diabetic retinopathy

TYPE I VERSUS TYPE II DM

TUMOR ENDOKRIN PANKREAS

1.Insulinoma (tumor sel beta)• Paling banyak, bisa jinak atau ganas• Sekresi insulin berlebihan (mengandung C-peptide)

harus dibedakan dengan insulin eksogen (terapi – tidak mengandung C-peptide)

• Trias Whipple:• Hiperinsinemia & hipoglikemia episodik• Disfungsi CNS sementara karena hipoglikemia (confuse,

anxiety, stupor, convulsion, coma)• Segera menjadi normal kembali dengan pemberian

glukose

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

TUMOR ENDOKRIN PANKREAS

2.Gastrinoma • Tumor ganas, bisa ekstra pankreas• Sekresi gastrin• Berhubungan dengan sindroma Zolinger-Ellison

3.Glukagonoma (tumor sel alfa)• Jarang, berakibat DM sekunder dan lesi kulit khas:

eritema migratori nekrolitik

4.Vipoma• Jarang, sekresi vasoactive intestinal peptide (VIP)• Berhubungan dengan sindroma WDHA (Watery

Diarrhea Hypokalemia and Achlorhydria) = sindroma Verner-Morrison = kolera pankreatik

Multiple Endocrine Neoplasia (MEN)

• Kelompok sindroma autosomal dominan dengan hiperfungsi lebih dari satu organ endokrin

• Kemungkinan berhubungan dengan hiperplasia atau tumor

• Jenis:

1. MEN I (sindroma Werner)

2. MEN IIa (sindroma Sipple)

3. MEN IIb (MEN III)

MEN I (WERMER SYNDROME)

• Termasuk hyperplasia tumor hipofisis, paratiroid, atau pankreas endokrin (3Ps)

• Bisa tambah hyperplasia atau tumor tiroid atau adrenal cortex

• Komponen pankreatiknya dapat bermanifestasi sebagai sindroma Zollinger-Ellison, hiperinsulinisme, atau cholera pankreatik

• Berhubungan dengan mutasio pada gena MEN I

MEN IIa (Sipple syndrome)

• Termasuk pheochromocytoma, medullary

carcinoma tiroid, dan hiperparatiroidisme karena hiperplasia atau tumor

• Berhubungan dengan mutasi onkogena ret

MEN IIb / III

• Includes pheochromocytoma, medullary carcinoma, and multiple mucocutaneous neuroma or ganglioneuroma. In contrast to MEN IIa, does not induce hyperparathy-roidism.

- is linked to different mutations in the ret

oncogene than is MEN IIa

endocrine-uii-2011.ppt

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