endokrin - FK UWKS 2012 C

ENDOKRIN
dr. Jimmy H.W. , Sp.PA
ENDOKRIN
• Kelenjar mengeluarkan hormon
Figure 24-1 Hormones released by the anterior pituitary. The adenohypophysis (anterior pituitary) releases five hormones that are in turn
under the control of various stimulatory and inhibitory hypothalamic releasing factors. TSH, thyroid-stimulating hormone (thyrotropin); PRL,
prolactin; ACTH, adrenocorticotrophic hormone (corticotropin); GH, growth hormone (somatotropin); FSH, follicle-stimulating hormone; LH,
luteinizing hormone. The stimulatory releasing factors are TRH (thyrotropin-releasing factor), CRH (corticotropin-releasing factor), GHRH
(growth hormone-releasing factor), GnRH (gonadotropin-releasing factor). The inhibitory hypothalamic influences are comprised of PIF
(prolactin inhibitory factor or dopamine) and growth hormone inhibitory factor (GIH or somatostatin).
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Kelenjar Hipofise ( Pituitary )
• 1 cm, 0,5 gr, pada sella tursica
• Jenis hormon :
1. Adenohipofise - GH
- PRL
2. Neurohipofise
- ACTH
- TSH
- Oksitosin
- Vasopresin
- ADH
- FSH
- LH
Figure 24-7 Homeostasis in the hypothalamus-pituitary-thyroid axis and mechanism of action of thyroid hormones. Secretion of thyroid
hormones (T3 and T4) is controlled by trophic factors secreted by both the hypothalamus and the anterior pituitary. Decreased levels of
T3 and T4 stimulate the release of thyrotropin-releasing hormone (TRH) from the hypothalamus and thyroid-stimulating hormone (TSH)
from the anterior pituitary, causing T3 and T4 levels to rise. Elevated T3 and T4 levels, in turn, suppress the secretion of both TRH and
TSH. This relationship is termed a negative-feedback loop. TSH binds to the TSH receptor on the thyroid follicular epithelium, which
causes activation of G proteins, and cyclic AMP (cAMP)-mediated synthesis and release of thyroid hormones (T3 and T4). In the
periphery, T3 and T4 interact with the thyroid hormone receptor (TR) to form a hormone-receptor complex that translocates to the
nucleus and binds to so-called thyroid response elements (TREs) on target genes initiating transcription.
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Hiperpituitarism
Oleh karena :
 Adenoma
 Hiperplasia
 Carcinoma
 Kelainan Hipotalamus
ADENOMA HIPOFISE :
• 10 % tumor otak
• Usia 30 – 50 tahun
• Satu jenis tumor  1 jenis hormon
Makroskopis :
• Batas jelas, lunak
• Kecil (mm) – besar (cm)
• Lesi besar  invasive adenoma
• Perdarahan  apoplexi
Mikroskopis :
• Sel uniform, poligonal, jalur-
jalur/lembaran
• Jaringan ikat penyangga
• Inti uniform – pleomorfik
Klinik :
• Rö  bayangan pada sella tursica
 ekspansi sellar
 erosi tulang
 kerusakan diafragma
• Gangguan produksi  hipopituitarisme
• Penekanan tumor  gangguan chiasmo
opticum (bitemporal hemianopsi)
• Tekanan intracranial naik
 Pusing
 Mual/muntah
Figure 24-4 Pituitary adenoma. This massive, nonfunctional adenoma has grown far beyond the confines of the
sella turcica and has distorted the overlying brain. Nonfunctional adenomas tend to be larger at the time of
diagnosis than those that secrete a hormone.
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Figure 24-4 Pituitary adenoma. This massive, nonfunctional adenoma has grown far beyond the confines of the sella turcica and has distorted the overlying brain.
Nonfunctional adenomas tend to be larger at the time of diagnosis than those that secrete a hormone.
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PROLAKTINOMA
•
•
•
•
Tumor hipofise terbanyak ( 30 % )
Usia 20 – 40 th, pria > wanita
Mikro atau makro
Efek dari tumor  PRL naik - amenorrhea
- galactorrhea
- libido kurang
- infertil
PROLAKTINOMA
Prolaktin tinggi juga karena :
• Hamil
• Stress
• Hiperplasi sel laktotrof
PROLAKTINOMA
Hiperplasi sel laktotrof karena :
• Hipotalamus rusak  neuron dopaminergik
rusak
• Obat yang menekan reseptor dopamin pada
hipofise
- phenotiazin
- reserpin
- haloperidol
PROLAKTINOMA
Terapi :
• Bromocriptin  sebagai antagonist receptor
dopamin
Hipopituitarisme, karena :
Faktor Hipofise :
• Tumor non fungsionil / kista
• Operasi / radiasi
• Ischemic necrosis/post partum necrosis
(Sheehan syndrome)
• Empty sella syndrome
• Genetik
Faktor Hipotalamus :
• Tumor primer / sekunder
• Infeksi / degenerasi
Klinik hipopituitarisme :
1. Fungsi kelenjar perifer turun
• Adrenal
• Thyroid
• Gonad
2. Wajah pucat  MSH rendah
3. Atrofi genitalia
Hipofise posterior
• Hormon produksi
– ADH
– Oksitosin
• Diabetes insipidus
– ADH rendah
– Etiologi : trauma, infeksi, tumor
– Klinik : - haus
- urine banyak
- Na serum tinggi, osmositas 
• Syndrome of Inappropriate ADH
secretion :
– ADH tinggi
– Etiologi : Ca small cell paru-paru
– Klinik : - urine sedikit
- Na serum rendah
Tumor Hipotalamus
• Glioma
• Craniopharyngioma
Craniopharyngioma
• Dari : Vestigical Remnants Rathke Pouch
• Usia : anak – dewasa muda
• Morfologi :
– Umumnya jinak
– Soliter, kistik, multiloculated
– Mirip adamantinoma
Thyroid
•
•
•
Asal : evaginasi epitel pharyngeal
Normal : 15-20 gr
Hormon aktif : - T3,T4 bebas
- ikatan dengan
TBG
Thyroid
•
fungsi :
–
Katabolisme :
- karbohidrat
- lemak
–
Sintesa :
- protein
Hipertiroidisme
• lab : T3,T4 tinggi
• Gejala :
- nervous
- lemah otot
- palpitasi - kurus
- tremor
- diare
- kulit panas - tiroid besar
-
keringatan
emosionil
capek
gangguan
siklus M
Hipertiroidisme
Tirotoxicosis dapat karena :
Diffuse hiperplasi (85% Graves) 
hipertiroidisme
 Tx hormon tiroid berlebihan
 Multinodular goiter
 Neoplasma tiroid
 Tiroiditis

Hipertiroidisme
Terjadi :
1. Hipermetabolik
2. Overaktif simpatetik
Hipertiroidisme
Gejala Hipertiroid :
1. Cardiac : aritmi/palpitasi/cardiomegali
2. Otot : atrofi / fatty changes
3. Tulang : osteoporose, fraktur
4. Limfoid : hiperplasi
Hipertiroidisme
5. Ocular : Staring gaze, lid lag
6. Neuromuscular : tremor, cemas,
insomnia, emosional
7. Kulit : berkeringat, rasa panas,
kemerahan
8. GI : rasa haus, lapar
Hipertiroidisme
Dx :
Tanda klinik
o Lab :
- T4 bebas >>
- T S H <<
o
Tx :
-
 blocker  fungsi adrenergic 
propil tiouracil  sintesa T3T4 
jodium  pelepasan T3T4 
radioactive jodium
Hipotiroidi
Sebab :
1. Primer  gangguan tiroid
2. Sekunder
Hipotiroidi
Hipotiroidi karena parenchim tiroid  :
 Embrional
 Radiasi
 Operatif
 Hashimoto
Hipotiroidi
Hipotiroidi karena sintesa  :
 Idiopatik
 Cacat sintesa turunan
 Jodium intake kurang
 Bahan-bahan goitrogen
Hipotiroidi
Hipotiroidi karena supratiroidal :
• Lesi hipofise
• Lesi hipotalamus
Hashimoto Thyroiditis
• Penyakit autoimmune  hipotiroidi
• Umur 45-65, ♀ : ♂ = 10-20 : 1
• Ada unsur familiar  twin monozigote
= 30-60%
• Sering disertai Rh, arthritis, SLE
Morfologi
• Diffuse, berbatas jelas
• Pucat, abu-abu, kenyal, noduler
• Kapsul intak
Klinik
• Struma tidak nyeri, simetrik diffuse
• Kadang-kadang noduler
• Hipotiroidisme, kadang-kadang
hipertiroidisme transien
• Risk factor timbul limfoma
Figure 24-9 Pathogenesis of Hashimoto thyroiditis. Three proposed models for mechanism of thyrocyte destruction in Hashimoto disease. Sensitization of autoreactive
CD4+ T cells to thyroid antigens appears to be the initiating event for all three mechanisms of thyroid cell death. See the text for details.
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De Quervain Tiroiditis :
•
•
•
Jarang terjadi
Usia 30 – 50 tahun
Wanita : Pria = 3 – 5 : 1
Morfologi :
•
•
•
•
Unilateral / bilateral
Kenyal, kapsul intak
Kadang-kadang perlekatan jaringan
sekitar
Warna kuning pucat, kecoklatan
Klinik :
• Terjadi mendadak / bertahap
• Nyeri leher, panas, capek, malas, anorexi,
myalgin
• Terdapat struma
• Dapat sembuh spontan
• T3 T4  , TSH 
Figure 24-11 Subacute thyroiditis. The thyroid parenchyma contains a chronic inflammatory infiltrate with a
multinucleate giant cell (above left) and a colloid follicle (bottom right).
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Graves Disease
Triad yang harus ada :
1. Hipertiroidi, dengan goiter aktif
2. Ophthalmopathy  exophthalmos
3. Dermatopathy  pretibial myxedema
Klinik :
o Usia 20-40 tahun, wanita : pria = 7 : 1
o Ada faktor genetik
Figure 24-8 A patient with hyperthyroidism. A wide-eyed, staring gaze, caused by overactivity of the sympathetic nervous system, is one of the features of this disorder.
In Graves disease, one of the most important causes of hyperthyroidism, accumulation of loose connective tissue behind the eyeballs also adds to the protuberant
appearance of the eyes.
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Figure 24-12 Diffusely hyperplastic thyroid in a case of Graves disease. The follicles are lined by tall, columnar epithelium. The crowded,
enlarged epithelial cells project into the lumens of the follicles. These cells actively resorb the colloid in the centers of the follicles,
resulting in the scalloped appearance of the edges of the colloid.
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Ophthalmopathy graves
• Jaringan ikat orbita
• Otot extra ocular
 Mirip TSH receptor

Ab  B cell  T cell, CD4+ / CD8+
Morfologi :
• Struma, Sp 80 gr, simetri berkapsul
• Konsistensi lunak, halus, merah seperti daging
• Sel-sel silindris, papil-papil kecil
• Colloid sedikit, dengan ‘scalloped’ margin
• Infiltrasi limfosit ( B cell )
Terapi :
• Jodium
 involusi epitel
 sekresi tiroglobulin turun
• Propilthiouracil  sintesa kurang
• Radioaktif jodium
• pembedahan
Neoplasma Tiroid
•
•
•
•
Bentukan soliter, palpable
Wanita : pria = 4 : 1
Sebagian besar nodul soliter jinak
Nodul neoplastik  90% adenoma
Beberapa kriteria penyokong Dx
•
•
•
•
•
Nodul soliter  neoplasma
Usia muda  neoplasma
Jenis kelamin laki-laki  neoplasma
Pernah diterapi Rö  Ca
Hot nodule  jinak
Adenoma tiroid
• Soliter
• Folikel  follicular adenoma
• Beberapa jenis, tersering : simple
colloid adenoma
• Adenoma sangat jarang menjadi
Carcinoma
Figure 24-14 Follicular adenoma of the thyroid. A solitary, well-circumscribed nodule is seen.
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Figure 24-14 Follicular adenoma of the thyroid. A solitary, well-circumscribed nodule is seen.
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Figure 24-14 Follicular adenoma of the thyroid. A solitary, well-circumscribed nodule is seen.
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Morfologi adenoma
•
•
•
•
•
•
Tumor soliter
Bentuk speris
Berkapsul, tekanan jaringan sekitar
Ukuran sekitar 3 cm
Warna abu-abu putih, merah kecoklatan
Kadang2 perdarahan, fibrosis, kalsifikasi,
kistik
mikroskopis
• Folikel ukuran sama, isi folikel
• Jenis : - Simple colloid (macrofolicular)
- Fetal (microfolicular)
- Embryonal (trabecular)
- Hurthle cell (oxiphyl, oncocyte)
- Atypical
- Adenoma with papillae
(=Papillae adenoma)
(=Encapsuled Papillary Ca)
Tumor Tiroid Jinak yang lain
•
•
•
•
•
Kista tiroid : - deri adenoma folicular
- dari multinodular
goiter
Kista dermoid
Lipoma
Hemangioma
Terratoma
Carcinoma Thyroid
•
•
•
Umumnya usia dewasa
Wanita > pria, khususnya usia muda
Terdapat reseptor estrogen pada sel-sel
tumor
Jenis Carcinoma
•
•
•
•
Papillary Ca
Follicular Ca
Medullary Ca
Anaplastic Ca
75-85
10-30
5
5
%
%
%
%
Papillary Carcinoma
• Semua usia, terutama 20-40 tahun
• Erat hubungannya dengan fakta radiasi
Figure 24-17 Papillary carcinoma of the thyroid. A, The macroscopic appearance of a papillary carcinoma with grossly discernible papillary structures. This particular
example contains well-formed papillae (B), lined by cells with characteristic empty-appearing nuclei, sometimes termed "Orphan Annie eye" nuclei (C). D, Cells obtained
by fine-needle aspiration of a papillary carcinoma. Characteristic intranuclear inclusions are visible in some of the aspirated cells.
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Figure 24-17 Papillary carcinoma of the thyroid. A, The macroscopic appearance of a papillary carcinoma with grossly discernible papillary structures. This particular
example contains well-formed papillae (B), lined by cells with characteristic empty-appearing nuclei, sometimes termed "Orphan Annie eye" nuclei (C). D, Cells obtained
by fine-needle aspiration of a papillary carcinoma. Characteristic intranuclear inclusions are visible in some of the aspirated cells.
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Morfologi
•
•
•
•
Soliter atau multipel
Berbatas jelas / berkapsul / menyebar
diluarnya
Kadang2 fibrosis, kalsifikasi, kistik
Pada irisan  granula / papil-papil
kecil
Mikroskopis :
• Papil dengan fibrovasculer, dilapisi
epitel
 Inti dengan ground glass / orphan
annie
• Intra nuclear inclusion / groves
 Psammoma bodies
Klinik
•
•
•
•
Sering a symptomatic
Sering dengan metastasis kelenjar
leher
Radioactive jodium  cold nodule
FNA, cara Diagnosa yang tepat
Follicular Carcinoma
• Wanita > Pria
• Usia 40 – 50 tahun
• Sering sudah didapatkan colloid goiter
Morfologi :
• Single nodule
• Batas jelas / infiltratif
• Tumor besar  infiltrasi ke jaringan
sekitar
• Warna abu-abu – coklat – merah muda
• Kadang2 fibrosis, kalsifikasi
Figure 24-18 Follicular carcinoma. Cut surface of a follicular carcinoma with substantial replacement of the lobe of the thyroid. The tumor has a light-tan appearance and
contains small foci of hemorrhage.
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Figure 24-19 Follicular carcinoma of the thyroid. A few of the glandular lumens contain recognizable colloid.
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mikroskopis :
• Folikel2 seperti normal, atau dengan
diferensiasi yang rendah
• Kadang2 dengan sel Hurthle
• Invasi sel pada kapsul atau vascular
Klinik :
• Nodul kecil, lambat laun membesar
• Rö  cold nodule
• Metastasis hematogen  ke organorgan jauh
Medullary Carcinoma
• Dari para follicular cell
• Hormon yang dikeluarkan
-Calcitonin
- Serotonin
-CEA
- Somatostatin
-VIP (Vasoactive Intestinal
Peptide)
Figure 24-21 Medullary carcinoma of thyroid. These tumors typically show a solid pattern of growth and do not have connective tissue capsules. (Courtesy of Dr. Joseph
Corson, Brigham and Women's Hospital, Boston, MA.)
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Figure 24-21 Medullary carcinoma of thyroid. These tumors typically show a solid pattern of growth and do not have connective tissue capsules. (Courtesy of Dr. Joseph
Corson, Brigham and Women's Hospital, Boston, MA.)
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Morfologi
• Soliter  type sporadic
• Multipel  type familial
• Jaringan tumor halus, warna abu2coklat
• Kadang2 nekrosis, perdarahan
Klinis
• Nodul di thyroid
• Kadang2 disertai diare karena VIP
• Type sporadic / MEN  tumbuh
agresif
• Type familial  low grade
Mikroskopis
• Sel poligonal, spindle, dalam
sarang/trabekula/folikel
• Deposit amiloid ( dari molekul
calcitonin)
Anaplastic Carcinoma :
• Sangat agresif
• Usia tua, 65 tahun
• Sering didahului multinodular goiter
Morfologi :
• Large, pleomorfik giant cell
• Spindle cell
• Small anaplastic cell
Congenital anomali Tiroid
Ductus/cyst thyroglossus
• Sisa2 vestigial remnant
• Lesi kecil 2-3 cm
• Letak antara Glossus - Thyroid
Parathyroid
• Dari kantung pharyngeal, ada 4 kelenjar
• Berat 35-40 mg
• Terdiri dari - chief cell  germal parathormon
- oxyphil cell
• Kerja parathyroid dikendalikan oleh Ca ion darah
Figure 24-24 Parathyroid adenomas are almost always solitary lesions. Technetium-99m-sestamibi radionuclide scan demonstrates an area of increased uptake
corresponding to the left inferior parathyroid gland (arrow). This patient had a parathyroid adenoma. Preoperative scintigraphy is useful in localizing and distinguishing
adenomas from parathyroid hyperplasia, where more than one gland would demonstrate increased uptake.
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Figure 24-25 Parathyroid adenoma. A, Solitary chief cell parathyroid adenoma (low-power photomicrograph) revealing clear delineation from the residual gland below. B,
High-power detail of a chief cell parathyroid adenoma. There is some slight variation in nuclear size but no anaplasia and some slight tendency to follicular formation.
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Hormon PTH bekerja :
a. Pada tulang menambah aktivitas
osteoclast
b. Pada ginjal meningkatkan
- resorbsi calcium
- konversi vit D aktif
- ekskresi phosphat
c. Pada usus menambah absorbsi kalsium
Tumor2 ganas yang lain  calcium
darah tinggi
1. Metastasis tulang  osteolisis
2. PTH related protein ( PTH rP )
Hiperparatiroidisme primer
• Sebabnya :
• Adenoma
75-80
• Hiperplasia 10-15
• Carcinoma
5
%
%
%
• Usia tersering pada dewasa 50 th lebih
• Wanita lebih sering dp laki-laki
• Ada faktor radiasi sebelumnya
Figure 24-26 Cardinal features of hyperparathyroidism. With routine evaluation of calcium levels in most patients,
primary hyperparathyroidism is often detected at a clinically silent stage. Hypercalcemia from any other cause can
also give rise to the same symptoms.
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Morfologi
• Tumor soliter, kecil 0,5 – 5 gr
• Lunak, batas jelas, kecoklatan
• Mikroskopis :
• Sel2 poligonal, uniform
• Inti kecil, central
• Klinik, dapat berupa :
o A symptomatic hyperparathyroidism
o Symptomatic hyperparathyroidism
Pada symptomatic timbul :
• Tulang  osteoporosis
• Ginjal  nephrolithiasis
• Gastrointestinal  constipasi, ulcus dll
• CNS  depresi
• Neuromuscular  lemah
• Cardiac  kalsifikasi katup