Endokrin Dr Jimmy-may2015

ENDOKRINdr. 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). Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 03:46 AM) © 2005 Elsevier Kelenjar Hipofise ( Pituitary ) • 1 cm, 0,5 gr, pada sella tursica • Jenis hormon : 1. Adenohipofise - GH - ACTH - FSH - PRL - TSH - LH 2. Neurohipofise - Oksitosin - Vasopresin - ADH which causes activation of G proteins. and cyclic AMP (cAMP)-mediated synthesis and release of thyroid hormones (T3 and T4). This relationship is termed a negative-feedback loop. TSH binds to the TSH receptor on the thyroid follicular epithelium. Elevated T3 and T4 levels. 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.Figure 24-7 Homeostasis in the hypothalamus-pituitary-thyroid axis and mechanism of action of thyroid hormones. in turn. 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. suppress the secretion of both TRH and TSH. In the periphery. Secretion of thyroid hormones (T3 and T4) is controlled by trophic factors secreted by both the hypothalamus and the anterior pituitary. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 03:46 AM) © 2005 Elsevier . causing T3 and T4 levels to rise. Hiperpituitarism Oleh karena :  Adenoma  Hiperplasia  Carcinoma  Kelainan Hipotalamus . lunak • Kecil (mm) – besar (cm) • Lesi besar  invasive adenoma • Perdarahan  apoplexi .ADENOMA HIPOFISE : • 10 % tumor otak • Usia 30 – 50 tahun • Satu jenis tumor  1 jenis hormon Makroskopis : • Batas jelas. poligonal. jalur- jalur/lembaran • Jaringan ikat penyangga • Inti uniform – pleomorfik .Mikroskopis : • Sel uniform. 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 . Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 03:46 AM) © 2005 Elsevier . This massive. Nonfunctional adenomas tend to be larger at the time of diagnosis than those that secrete a hormone.Figure 24-4 Pituitary adenoma. nonfunctional adenoma has grown far beyond the confines of the sella turcica and has distorted the overlying brain. libido kurang .infertil . pria > wanita • Mikro atau makro • Efek dari tumor  PRL naik .PROLAKTINOMA • Tumor hipofise terbanyak ( 30 % ) • Usia 20 – 40 th.galactorrhea .amenorrhea . PROLAKTINOMA Prolaktin tinggi juga karena : • Hamil • Stress • Hiperplasi sel laktotrof . phenotiazin .PROLAKTINOMA Hiperplasi sel laktotrof karena : • Hipotalamus rusak  neuron dopaminergik rusak • Obat yang menekan reseptor dopamin pada hipofise .haloperidol .reserpin . 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 . Wajah pucat  MSH rendah 3. Atrofi genitalia . Fungsi kelenjar perifer turun • Adrenal • Thyroid • Gonad 2.Faktor Hipotalamus : • Tumor primer / sekunder • Infeksi / degenerasi Klinik hipopituitarisme : 1. haus .urine banyak .Na serum tinggi.Hipofise posterior • Hormon produksi – ADH – Oksitosin • Diabetes insipidus – ADH rendah – Etiologi : trauma. infeksi. osmositas  . tumor – Klinik : . • 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 . ikatan dengan TBG .Thyroid • Asal : evaginasi epitel pharyngeal • Normal : 15-20 gr • Hormon aktif : .T4 bebas .T3. lemak – Sintesa : .Thyroid • fungsi : – Katabolisme : .protein .karbohidrat . emosionil .Hipertiroidisme • lab : T3.kulit panas .lemah otot .nervous . gangguan siklus M .tremor . capek .diare .palpitasi . keringatan .tiroid besar .kurus .T4 tinggi • Gejala : . Hipertiroidisme Tirotoxicosis dapat karena :  Diffuse hiperplasi (85% Graves)  hipertiroidisme  Tx hormon tiroid berlebihan  Multinodular goiter  Neoplasma tiroid  Tiroiditis . Hipermetabolik 2. Overaktif simpatetik .Hipertiroidisme Terjadi : 1. Cardiac : aritmi/palpitasi/cardiomegali 2. Limfoid : hiperplasi . fraktur 4. Otot : atrofi / fatty changes 3.Hipertiroidisme Gejala Hipertiroid : 1. Tulang : osteoporose. rasa panas. emosional 7. kemerahan 8. lapar .Hipertiroidisme 5. Ocular : Staring gaze. Kulit : berkeringat. lid lag 6. cemas. insomnia. GI : rasa haus. Neuromuscular : tremor. jodium  pelepasan T3T4  .T4 bebas >> . radioactive jodium . propil tiouracil  sintesa T3T4  .  blocker  fungsi adrenergic  .T S H << Tx : .Hipertiroidisme Dx : o Tanda klinik o Lab : . Hipotiroidi Sebab : 1. Sekunder . Primer  gangguan tiroid 2. 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 . arthritis. ♀ : ♂ = 10-20 : 1 • Ada unsur familiar  twin monozigote = 30-60% • Sering disertai Rh.Hashimoto Thyroiditis • Penyakit autoimmune  hipotiroidi • Umur 45-65. SLE . Morfologi • Diffuse. berbatas jelas • Pucat. kenyal. noduler • Kapsul intak . abu-abu. kadang-kadang hipertiroidisme transien • Risk factor timbul limfoma . simetrik diffuse • Kadang-kadang noduler • Hipotiroidisme.Klinik • Struma tidak nyeri. Sensitization of autoreactive CD4+ T cells to thyroid antigens appears to be the initiating event for all three mechanisms of thyroid cell death. Three proposed models for mechanism of thyrocyte destruction in Hashimoto disease. See the text for details. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 03:46 AM) © 2005 Elsevier .Figure 24-9 Pathogenesis of Hashimoto thyroiditis. 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). Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 03:46 AM) © 2005 Elsevier Dermatopathy  pretibial myxedema . Ophthalmopathy  exophthalmos 3. Hipertiroidi. dengan goiter aktif 2.Graves Disease Triad yang harus ada : 1. wanita : pria = 7 : 1 o Ada faktor genetik .Klinik : o Usia 20-40 tahun. is one of the features of this disorder.Figure 24-8 A patient with hyperthyroidism. staring gaze. A wide-eyed. In Graves disease. accumulation of loose connective tissue behind the eyeballs also adds to the protuberant appearance of the eyes. one of the most important causes of hyperthyroidism. caused by overactivity of the sympathetic nervous system. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 03:46 AM) © 2005 Elsevier . enlarged epithelial cells project into the lumens of the follicles. resulting in the scalloped appearance of the edges of the colloid. columnar epithelium. The crowded. These cells actively resorb the colloid in the centers of the follicles.Figure 24-12 Diffusely hyperplastic thyroid in a case of Graves disease. The follicles are lined by tall. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 09:36 AM) © 2005 Elsevier . Ophthalmopathy graves • Jaringan ikat orbita  Mirip TSH receptor • Otot extra ocular  Ab  B cell  T cell. CD4+ / CD8+ . halus.Morfologi : • Struma. dengan ‘scalloped’ margin • Infiltrasi limfosit ( B cell ) . papil-papil kecil • Colloid sedikit. simetri berkapsul • Konsistensi lunak. merah seperti daging • Sel-sel silindris. Sp 80 gr. Terapi : • Jodium  involusi epitel  sekresi tiroglobulin turun • Propilthiouracil  sintesa kurang • Radioaktif jodium • pembedahan . palpable • Wanita : pria = 4 : 1 • Sebagian besar nodul soliter jinak • Nodul neoplastik  90% adenoma .Neoplasma Tiroid • Bentukan soliter. 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. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 09:36 AM) © 2005 Elsevier . A solitary. well-circumscribed nodule is seen. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 09:36 AM) © 2005 Elsevier . A solitary.Figure 24-14 Follicular adenoma of the thyroid. well-circumscribed nodule is seen. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 09:36 AM) © 2005 Elsevier . well-circumscribed nodule is seen.Figure 24-14 Follicular adenoma of the thyroid. A solitary. merah kecoklatan • Kadang2 perdarahan. tekanan jaringan sekitar • Ukuran sekitar 3 cm • Warna abu-abu putih.Morfologi adenoma • Tumor soliter • Bentuk speris • Berkapsul. fibrosis. kalsifikasi. kistik . mikroskopis • Folikel ukuran sama.Hurthle cell (oxiphyl. oncocyte) . isi folikel • Jenis : .Simple colloid (macrofolicular) .Embryonal (trabecular) .Adenoma with papillae (=Papillae adenoma) (=Encapsuled Papillary Ca) .Fetal (microfolicular) .Atypical . deri adenoma folicular .Tumor Tiroid Jinak yang lain • Kista tiroid : .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 75-85 % • Follicular Ca 10-30 % • Medullary Ca 5 % • Anaplastic Ca 5 % . Papillary Carcinoma • Semua usia. terutama 20-40 tahun • Erat hubungannya dengan fakta radiasi . A. D. lined by cells with characteristic empty-appearing nuclei. sometimes termed "Orphan Annie eye" nuclei (C). Cells obtained by fine-needle aspiration of a papillary carcinoma. This particular example contains well-formed papillae (B). The macroscopic appearance of a papillary carcinoma with grossly discernible papillary structures. Characteristic intranuclear inclusions are visible in some of the aspirated cells. Figure 24-17 Papillary carcinoma of the thyroid. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 09:36 AM) © 2005 Elsevier . Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 09:36 AM) © 2005 Elsevier . The macroscopic appearance of a papillary carcinoma with grossly discernible papillary structures. sometimes termed "Orphan Annie eye" nuclei (C). Cells obtained by fine-needle aspiration of a papillary carcinoma. lined by cells with characteristic empty-appearing nuclei. A. D. Figure 24-17 Papillary carcinoma of the thyroid. This particular example contains well-formed papillae (B). Characteristic intranuclear inclusions are visible in some of the aspirated cells. kistik • Pada irisan  granula / papil-papil kecil . kalsifikasi.Morfologi • Soliter atau multipel • Berbatas jelas / berkapsul / menyebar diluarnya • Kadang2 fibrosis. dilapisi epitel  Inti dengan ground glass / orphan annie • Intra nuclear inclusion / groves  Psammoma bodies .Mikroskopis : • Papil dengan fibrovasculer. cara Diagnosa yang tepat .Klinik • Sering a symptomatic • Sering dengan metastasis kelenjar leher • Radioactive jodium  cold nodule • FNA. Follicular Carcinoma • Wanita > Pria • Usia 40 – 50 tahun • Sering sudah didapatkan colloid goiter . kalsifikasi .Morfologi : • Single nodule • Batas jelas / infiltratif • Tumor besar  infiltrasi ke jaringan sekitar • Warna abu-abu – coklat – merah muda • Kadang2 fibrosis. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 09:36 AM) © 2005 Elsevier . Cut surface of a follicular carcinoma with substantial replacement of the lobe of the thyroid.Figure 24-18 Follicular carcinoma. The tumor has a light-tan appearance and contains small foci of hemorrhage. A few of the glandular lumens contain recognizable colloid. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 02:32 PM) © 2005 Elsevier .Figure 24-19 Follicular carcinoma of the thyroid. atau dengan diferensiasi yang rendah • Kadang2 dengan sel Hurthle • Invasi sel pada kapsul atau vascular .mikroskopis : • Folikel2 seperti normal. Klinik : • Nodul kecil. lambat laun membesar • Rö  cold nodule • Metastasis hematogen  ke organ- organ jauh . Medullary Carcinoma • Dari para follicular cell • Hormon yang dikeluarkan -Calcitonin .Serotonin -CEA .Somatostatin -VIP (Vasoactive Intestinal Peptide) . Boston. (Courtesy of Dr.) Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 02:32 PM) © 2005 Elsevier . MA. These tumors typically show a solid pattern of growth and do not have connective tissue capsules. Joseph Corson.Figure 24-21 Medullary carcinoma of thyroid. Brigham and Women's Hospital. MA. These tumors typically show a solid pattern of growth and do not have connective tissue capsules.) Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 02:32 PM) © 2005 Elsevier . Joseph Corson.Figure 24-21 Medullary carcinoma of thyroid. Brigham and Women's Hospital. Boston. (Courtesy of Dr. Morfologi • Soliter  type sporadic • Multipel  type familial • Jaringan tumor halus. perdarahan . warna abu2- coklat • Kadang2 nekrosis. Klinis • Nodul di thyroid • Kadang2 disertai diare karena VIP • Type sporadic / MEN  tumbuh agresif • Type familial  low grade . dalam sarang/trabekula/folikel • Deposit amiloid ( dari molekul calcitonin) . spindle.Mikroskopis • Sel poligonal. Anaplastic Carcinoma : • Sangat agresif • Usia tua. 65 tahun • Sering didahului multinodular goiter . pleomorfik giant cell • Spindle cell • Small anaplastic cell .Morfologi : • Large. 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 .oxyphil cell • Kerja parathyroid dikendalikan oleh Ca ion darah .chief cell  germal parathormon . Figure 24-24 Parathyroid adenomas are almost always solitary lesions. This patient had a parathyroid adenoma. Preoperative scintigraphy is useful in localizing and distinguishing adenomas from parathyroid hyperplasia. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 02:32 PM) © 2005 Elsevier . Technetium-99m-sestamibi radionuclide scan demonstrates an area of increased uptake corresponding to the left inferior parathyroid gland (arrow). where more than one gland would demonstrate increased uptake. There is some slight variation in nuclear size but no anaplasia and some slight tendency to follicular formation.Figure 24-25 Parathyroid adenoma. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 02:32 PM) © 2005 Elsevier . 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. Hormon PTH bekerja : a.konversi vit D aktif . Pada ginjal meningkatkan . Pada usus menambah absorbsi kalsium . Pada tulang menambah aktivitas osteoclast b.resorbsi calcium .ekskresi phosphat c. PTH related protein ( PTH rP ) .Tumor2 ganas yang lain  calcium darah tinggi 1. Metastasis tulang  osteolisis 2. 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 . primary hyperparathyroidism is often detected at a clinically silent stage. Hypercalcemia from any other cause can also give rise to the same symptoms. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April 2005 02:32 PM) © 2005 Elsevier .Figure 24-26 Cardinal features of hyperparathyroidism. With routine evaluation of calcium levels in most patients. uniform • Inti kecil. dapat berupa : o A symptomatic hyperparathyroidism o Symptomatic hyperparathyroidism . batas jelas. central • Klinik. kecil 0. Morfologi • Tumor soliter. kecoklatan • Mikroskopis : • Sel2 poligonal.5 – 5 gr • Lunak. ulcus dll • CNS  depresi • Neuromuscular  lemah • Cardiac  kalsifikasi katup .Pada symptomatic timbul : • Tulang  osteoporosis • Ginjal  nephrolithiasis • Gastrointestinal  constipasi.