PATHOLOGY

ENDOKRINOLOGY
T. Utoro
Department of Pathology
Gadjah Mada University School of Medicine

PATHOLOGY OF THE

THYROID

THYROID
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 (triiodothyronine) regulated by TSH
Serum T4 and T3 are bound to thyroid-binding
globulin (TBG)
3

Homeostasis in the
hypothalamuspituitary-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
4

Pathology of thyroid
A.
B.
C.
D.
E.
F.
G.

CONGENITAL ANOMALY
GOITER
HYPOTHYROIDISM
HYPERTHYROIDISM
THYROIDITIS
BENIGN TUMORS (ADENOMAS)
MALIGNANT TUMORS
5

Pathology of thyroid

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
6

Pathology of thyroid

B. GOITER
A chronic enlargement of thyroid gland
due to other than neoplasm
Synonim: STRUMA

Pathology of thyroid

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 iodine
c. Hashimoto thyroiditis
d. Goitrogens
- foods or drugs that suppress synthesis of thyroid hormone
e. Dyshormogenesis
- partial or complete failure of thyroid hormone synthesis; can
be caused by various enzyme deficiencies

Pathology of thyroid

B. GOITER

B.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)

Non-toxic goiter
Irregular nodules

Marked variation in the size of follicles

10

Nodular (non-toxic) Goiter

The gland is coarsely nodular and contains areas of fibrosis and cystic change.
11

Pathology of thyroid

C. HYPOTHYROIDISM
Diminished production of thyorid hormone, leading
to 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
12

Pathology of thyroid

C. HYPOTHYROIDISM

Dominant clinical
manifestation

13

Pathology of thyroid

C. HYPOTHYROIDISM
Laboratory abnormalities
1. Decrease serum free T4, increased serum TSH
2. Increase serum cholesterol
3. Classic thyroid test
-T3 resin uptake decreased
- Total T4 decreased

14

Pathology of thyroid

C. HYPOTHYROIDISM

Clinical syndromes
Hypothyroidism is manifest as Myxedema in
adults or as Cretinism in children

15

Pathology of thyroid: C. HYPOTHYROIDISM:

Myxedema

A. More common in women

B. Etiology:
1. Therapy for hyperthyroidism with surgery, irradiation, or drugs
2. Hashimoto thyroiditis
3. 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
16

Pathology of thyroid: C. HYPOTHYROIDISM:

Myxedema

C. Clinical charateristics
1. Incidious onset
2. Cold intolerance
3. Tendency to gain weight because of a low metabolic rate
4. Lowered pitch of voice
5. Mental and physical slowness
6. Menorrhagia
7. Constipation
8. 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.

17

Pathology of thyroid: C. HYPOTHYROIDISM:

CRETINISM

A. Etiology:
1. Iodine deficiency
2. Deficiency of enzymes necessary for the synthesis of
thyroid hormones
3. Maldevelopment of the thyroid gland
4. 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 retardation
2. Impairment of physical growth with retarded bone
development and dwarfism
3. Large tongue
18
4. Protuberant abdomen

Pathology of thyroid

HYPERTHYROIDISM

(THYROTOXICOSIS)

A. Clinical Features
1. Restlessness, irritability, fatigability
2. Tremor
3. Heat intolerance; sweating; warm, moist skin (especially palms)
4. Tachycardia, often with arrythmia and palpitation, sometimes
with high-output cardiac failure
5. Muscle wasting and weight loss despite increase appetite
6. Fine hair
7. Diarrhea
8. 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
19

Graves disease, hyperthyroidism

Exophthalmos

Thyroid mass
20

Major clinical
manifestations
of
Graves disease

21

Pathology of thyroid

HYPERTHYROIDISM

(THYROTOXICOSIS)

B. Graves Disease
General Charcteristics
1. Hyperthyroidism caused by diffuse toxic goiter
2. Associated with striking exophthalmos autoimmune?
3. More in women
4. incidence increased in HLA-DR3 and HLA-B8 positive individual
Mechanism
1. Thyroid-stimulating-immunoglobulin (TSI) reacts with TSH
receptors stimulates thyroid hormone production
2. Thyroid-growth-immunoglobulin (TGI) stimulates glandular
hyperplasia and enlargement
3. Antimicrosomal and other autoantibodies are characteristic
22

Pathology of thyroid

HYPERTHYROIDISM

(THYROTOXICOSIS)

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
23

Graves Disease

Diffusely hyperplastic thyroid with follicle are lined by tall,

columnar epithelium, and scalloped (moth eaten) appearance of
the edge of the colloid.
24

Graves disease, hyperthyroidism

The follicles are lined by hyperplastic, tall columnar cells

25

Immune mechanism of Graves Disease and

Hashimoto Thyroiditis

26

Pathology of thyroid

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. Riedels struma (Riedels disease)
27

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
28

Subacute/De Quervain/granulomatous
Thyroiditis

The release of colloid into the interstitial tissue has elicited a prominent
granulomatous reaction, with numerous foreign body giant cells
29

Subacute/De Quervain/granulomatous
Thyroiditis

The parenchyma contains chronic inflammatory infiltrate with a

multinucleate giant cells and colloid folicles

30

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
31

Chronic autoimmune (Hashimoto)

thyroiditis

The thyroid gland is symmetrically enlarged and coarsely nodular.

Coronal section irregular nodules and an intact capsule
32

Chronic autoimmune (Hashimoto)

thyroiditis

Atrophic thyroid follicles with conspicuous chronic inflammatory infiltrate

(the inflammatory cells form prominent lymphoid follicles with germinal centers)
33

Hashimoto Thyroiditis

Dense lymphocytic infiltrates with germinal centers

Residual thyroid follicle lined by Hurthle cells are also seen
34

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
35

Riedel thyroiditis

The thyroid parenchyma is largely replaced by dense, hyalinized fibrous tissue and a
chronic inflammatory infiltrate
36

Pathology of thyroid

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

37

FOLLICULAR ADENOMA

Embryonal adenoma
Fetal adenoma
Simple adenoma
Colloid adenoma
Hurthel cell adenoma
Atypical adenoma

38

Follicular adenoma

Embryonal adenoma

The tumor features a trabecular pattern with poorly formed follicles

that contain little if any colloid
39

Follicular Adenoma

COLLOID ADENOMA
The cut surface of an encapsulated mass reveals:

Hemorrhage

Fibrosis
Cystic change

40

Follicular Adenoma

Cystic

A solitary, well-circumscribed nodule is seen.

41

Follicular Adenoma

Well-differentiated follicles resembling

normal thyroid parenchyma.

42

Follicular adenoma

FETAL ADENOMA

Regular pattern of small follicles

43

Follicular adenoma

Hurthle cell Adenoma

Cells with abundant eosinophilic cytoplasm and small regular nuclei.

44

Pathology of thyroid

G. MALIGNANT TUMORS
Papillary Carcinoma
Follicular Carcinoma
Medullary Carcinoma
Anaplastic Carcinoma

45

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
46

G. MALIGNANT TUMORS

Papillary Thyroid Carcinoma (PTC)

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)

47

G. MALIGNANT TUMORS

Papillary Thyroid Carcinoma (PTC)

Macroscopic appearance with

grossly discernible papillary structure

FNAB - BAJAH

48

G. MALIGNANT TUMORS

Papillary
Thyroid
Carcinoma
(PTC)

Cut surface diplays a circumscribed

pale tan mass with foci of
cystic change

49

G. MALIGNANT TUMORS

Papillary Thyroid Carcinoma (PTC)

Well-formed papillae

Orphan Annie eye, or

ground-glass nuclei, or
empty appearing nuclei
50

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..

51

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
52

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

53

G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma (FTC)

Glandular lumen contains recognizable colloid

54

G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma (FTC)

ADENOMA

CARCINOMA

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)
55

G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma (FTC)

A microfollicular tumor has invaded veins in the thyroid parenchyma.

56

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)
57

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
58

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 catecholamines and phaeochromocytoma
Therapy: thyroidectomy local recurrencies 1/3
5-year survival rate is 75%
59

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.
60

G. MALIGNANT TUMORS:

Medullary Thyroid Carcinoma

Nest of polygonal cells embedded in a collagenous framework.

61

G. MALIGNANT TUMORS:

Medullary Thyroid Carcinoma

Amyloid: Congo red staining polarized light microscope

pale green birefringent
62

G. MALIGNANT TUMORS:

Medullary Carcinoma

Typically contain amyloid, visible here as homogenous

extracellular material, derived from calcitonin molecules
secreted by the neoplastic cells

63

G. MALIGNANT TUMORS:

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%
64

G. MALIGNANT TUMORS:

Anaplastic Carcinoma of the Thyroid

The tumor in traverse section partially surround the trachea

and extend into the adjecent soft tissue.
65

G. MALIGNANT TUMORS:

Anaplastic Carcinoma

The tumor is composed of bizarre spindle and giant cells with numerous mitoses
66

G. MALIGNANT TUMORS:

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
67

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

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

Delta
D

Somatostatin

1600

Delta
D1

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

Alpha

NORMAL PANCREAS

Staining of immunoperoxidase technique for

insulin insulin containing cells are darkly stained

DIABETES
Klasifikasi & gambaran umum
1. 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 1
Insulin-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 DM
1.Pulau-pulau Langerhans
a. 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 DM
4.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 hyperparathyroidism.
- is linked to different mutations in the ret
oncogene than is MEN IIa