ENDOKRIN dr. Jimmy H.W. , Sp.PA.

Presentasi berjudul: "ENDOKRIN dr. Jimmy H.W. , Sp.PA."— Transcript presentasi:

1 ENDOKRIN dr. Jimmy H.W. , Sp.PA

2 ENDOKRIN Kelenjar mengeluarkan hormon

3 Figure 24-1 Hormones released by the anterior pituitary
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 :46 AM) © 2005 Elsevier

4 Kelenjar Hipofise ( Pituitary )
1 cm, 0,5 gr, pada sella tursica Jenis hormon : Adenohipofise - GH - ACTH - FSH - PRL - TSH - LH Neurohipofise - Oksitosin - Vasopresin - ADH

5 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. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :46 AM) © 2005 Elsevier

6 Hiperpituitarism Oleh karena : Adenoma Hiperplasia Carcinoma
Kelainan Hipotalamus

7 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

8 Mikroskopis : Sel uniform, poligonal, jalur-jalur/lembaran Jaringan ikat penyangga Inti uniform – pleomorfik

9 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

10 Figure 24-4 Pituitary adenoma
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. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :46 AM) © 2005 Elsevier

11 Figure 24-4 Pituitary adenoma
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. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :46 AM) © 2005 Elsevier

12 PROLAKTINOMA Tumor hipofise terbanyak ( 30 % )
Usia 20 – 40 th, pria > wanita Mikro atau makro Efek dari tumor  PRL naik - amenorrhea - galactorrhea - libido kurang - infertil

13 PROLAKTINOMA Prolaktin tinggi juga karena : Hamil Stress
Hiperplasi sel laktotrof

14 PROLAKTINOMA Hiperplasi sel laktotrof karena :
Hipotalamus rusak  neuron dopaminergik rusak Obat yang menekan reseptor dopamin pada hipofise - phenotiazin - reserpin - haloperidol

15 PROLAKTINOMA Terapi : Bromocriptin  sebagai antagonist receptor dopamin

16 Hipopituitarisme, karena :
Faktor Hipofise : Tumor non fungsionil / kista Operasi / radiasi Ischemic necrosis/post partum necrosis (Sheehan syndrome) Empty sella syndrome Genetik

17 Tumor primer / sekunder Infeksi / degenerasi Klinik hipopituitarisme :
Faktor Hipotalamus : Tumor primer / sekunder Infeksi / degenerasi Klinik hipopituitarisme : Fungsi kelenjar perifer turun Adrenal Thyroid Gonad Wajah pucat  MSH rendah Atrofi genitalia

18 Hipofise posterior Hormon produksi Diabetes insipidus ADH Oksitosin
ADH rendah Etiologi : trauma, infeksi, tumor Klinik : - haus - urine banyak - Na serum tinggi, osmositas 

19 Syndrome of Inappropriate ADH secretion :
ADH tinggi Etiologi : Ca small cell paru-paru Klinik : - urine sedikit - Na serum rendah

20 Tumor Hipotalamus Glioma Craniopharyngioma

21 Craniopharyngioma Dari : Vestigical Remnants Rathke Pouch
Usia : anak – dewasa muda Morfologi : Umumnya jinak Soliter, kistik, multiloculated Mirip adamantinoma

22 Thyroid Asal : evaginasi epitel pharyngeal Normal : 15-20 gr
Hormon aktif : - T3,T4 bebas - ikatan dengan TBG

23 Thyroid fungsi : - lemak Katabolisme : - karbohidrat
Sintesa : - protein

24 Hipertiroidisme lab : T3,T4 tinggi Gejala :
- nervous - lemah otot - keringatan - palpitasi - kurus - emosionil - tremor - diare - capek - kulit panas - tiroid besar - gangguan siklus M

25 Hipertiroidisme Tirotoxicosis dapat karena :
Diffuse hiperplasi (85% Graves)  hipertiroidisme Tx hormon tiroid berlebihan Multinodular goiter Neoplasma tiroid Tiroiditis

26 Hipertiroidisme Terjadi : Hipermetabolik Overaktif simpatetik

27 Hipertiroidisme Gejala Hipertiroid :
Cardiac : aritmi/palpitasi/cardiomegali Otot : atrofi / fatty changes Tulang : osteoporose, fraktur Limfoid : hiperplasi

28 Hipertiroidisme Ocular : Staring gaze, lid lag
Neuromuscular : tremor, cemas, insomnia, emosional Kulit : berkeringat, rasa panas, kemerahan GI : rasa haus, lapar

29 Hipertiroidisme Dx : Tx : -  blocker  fungsi adrenergic 
Tanda klinik Lab : - T4 bebas >> - T S H << Tx : -  blocker  fungsi adrenergic  - propil tiouracil  sintesa T3T4  - jodium  pelepasan T3T4  - radioactive jodium

30 Hipotiroidi Sebab : Primer  gangguan tiroid Sekunder

31 Hipotiroidi Hipotiroidi karena parenchim tiroid  : Embrional Radiasi
Operatif Hashimoto

32 Hipotiroidi Hipotiroidi karena sintesa  : Idiopatik
Cacat sintesa turunan Jodium intake kurang Bahan-bahan goitrogen

33 Hipotiroidi Hipotiroidi karena supratiroidal : Lesi hipofise
Lesi hipotalamus

34 Hashimoto Thyroiditis
Penyakit autoimmune  hipotiroidi Umur 45-65, ♀ : ♂ = : 1 Ada unsur familiar  twin monozigote = 30-60% Sering disertai Rh, arthritis, SLE

35 Morfologi Diffuse, berbatas jelas Pucat, abu-abu, kenyal, noduler
Kapsul intak

36 Klinik Struma tidak nyeri, simetrik diffuse Kadang-kadang noduler
Hipotiroidisme, kadang-kadang hipertiroidisme transien Risk factor timbul limfoma

37 Figure 24-9 Pathogenesis of Hashimoto thyroiditis
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. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :46 AM) © 2005 Elsevier

38 De Quervain Tiroiditis :
Jarang terjadi Usia 30 – 50 tahun Wanita : Pria = 3 – 5 : 1

39 Morfologi : Unilateral / bilateral Kenyal, kapsul intak
Kadang-kadang perlekatan jaringan sekitar Warna kuning pucat, kecoklatan

40 Klinik : Terjadi mendadak / bertahap
Nyeri leher, panas, capek, malas, anorexi, myalgin Terdapat struma Dapat sembuh spontan T3 T4  , TSH 

41 Figure 24-11 Subacute thyroiditis
Figure 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 :46 AM) © 2005 Elsevier

42 Graves Disease Triad yang harus ada :
Hipertiroidi, dengan goiter aktif Ophthalmopathy  exophthalmos Dermatopathy  pretibial myxedema

43 Klinik : Usia tahun, wanita : pria = 7 : 1 Ada faktor genetik

44 Figure 24-8 A patient with hyperthyroidism
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. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :46 AM) © 2005 Elsevier

45 Figure 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. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :36 AM) © 2005 Elsevier

46 Ophthalmopathy graves
Jaringan ikat orbita Otot extra ocular  Ab  B cell  T cell, CD4+ / CD8+  Mirip TSH receptor

47 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 )

48 Terapi : Jodium  involusi epitel  sekresi tiroglobulin turun Propilthiouracil  sintesa kurang Radioaktif jodium pembedahan

49 Neoplasma Tiroid Bentukan soliter, palpable Wanita : pria = 4 : 1
Sebagian besar nodul soliter jinak Nodul neoplastik  90% adenoma

50 Beberapa kriteria penyokong Dx
Nodul soliter  neoplasma Usia muda  neoplasma Jenis kelamin laki-laki  neoplasma Pernah diterapi Rö  Ca Hot nodule  jinak

51 Adenoma tiroid Soliter Folikel  follicular adenoma
Beberapa jenis, tersering : simple colloid adenoma Adenoma sangat jarang menjadi Carcinoma

52 Figure 24-14 Follicular adenoma of the thyroid
Figure Follicular adenoma of the thyroid. A solitary, well-circumscribed nodule is seen. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :36 AM) © 2005 Elsevier

53 Figure 24-14 Follicular adenoma of the thyroid
Figure Follicular adenoma of the thyroid. A solitary, well-circumscribed nodule is seen. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :36 AM) © 2005 Elsevier

54 Figure 24-14 Follicular adenoma of the thyroid
Figure Follicular adenoma of the thyroid. A solitary, well-circumscribed nodule is seen. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :36 AM) © 2005 Elsevier

55 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

56 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)

57 Tumor Tiroid Jinak yang lain
Kista tiroid : - deri adenoma folicular - dari multinodular goiter Kista dermoid Lipoma Hemangioma Terratoma

58 Carcinoma Thyroid Umumnya usia dewasa
Wanita > pria, khususnya usia muda Terdapat reseptor estrogen pada sel-sel tumor

59 Jenis Carcinoma Papillary Ca 75-85 % Follicular Ca 10-30 %
Medullary Ca 5 % Anaplastic Ca 5 %

60 Papillary Carcinoma Semua usia, terutama 20-40 tahun
Erat hubungannya dengan fakta radiasi

61 Figure 24-17 Papillary carcinoma of the thyroid
Figure 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. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :36 AM) © 2005 Elsevier

62 Figure 24-17 Papillary carcinoma of the thyroid
Figure 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. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :36 AM) © 2005 Elsevier

63 Morfologi Soliter atau multipel
Berbatas jelas / berkapsul / menyebar diluarnya Kadang2 fibrosis, kalsifikasi, kistik Pada irisan  granula / papil-papil kecil

64 Mikroskopis : Papil dengan fibrovasculer, dilapisi epitel
Inti dengan ground glass / orphan annie Intra nuclear inclusion / groves Psammoma bodies

65 Klinik Sering a symptomatic Sering dengan metastasis kelenjar leher
Radioactive jodium  cold nodule FNA, cara Diagnosa yang tepat

66 Follicular Carcinoma Wanita > Pria Usia 40 – 50 tahun
Sering sudah didapatkan colloid goiter

67 Morfologi : Single nodule Batas jelas / infiltratif
Tumor besar  infiltrasi ke jaringan sekitar Warna abu-abu – coklat – merah muda Kadang2 fibrosis, kalsifikasi

68 Figure 24-18 Follicular carcinoma
Figure 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. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :36 AM) © 2005 Elsevier

69 Figure 24-19 Follicular carcinoma of the thyroid
Figure Follicular carcinoma of the thyroid. A few of the glandular lumens contain recognizable colloid. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :32 PM) © 2005 Elsevier

70 mikroskopis : Folikel2 seperti normal, atau dengan diferensiasi yang rendah Kadang2 dengan sel Hurthle Invasi sel pada kapsul atau vascular

71 Klinik : Nodul kecil, lambat laun membesar Rö  cold nodule
Metastasis hematogen  ke organ-organ jauh

72 Medullary Carcinoma Dari para follicular cell Hormon yang dikeluarkan
- Calcitonin - Serotonin - CEA - Somatostatin - VIP (Vasoactive Intestinal Peptide)

73 Figure 24-21 Medullary carcinoma of thyroid
Figure 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.) Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :32 PM) © 2005 Elsevier

74 Figure 24-21 Medullary carcinoma of thyroid
Figure 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.) Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :32 PM) © 2005 Elsevier

75 Morfologi Soliter  type sporadic Multipel  type familial
Jaringan tumor halus, warna abu2-coklat Kadang2 nekrosis, perdarahan

76 Klinis Nodul di thyroid Kadang2 disertai diare karena VIP
Type sporadic / MEN  tumbuh agresif Type familial  low grade

77 Mikroskopis Sel poligonal, spindle, dalam sarang/trabekula/folikel
Deposit amiloid ( dari molekul calcitonin)

78 Anaplastic Carcinoma :
Sangat agresif Usia tua, 65 tahun Sering didahului multinodular goiter

79 Morfologi : Large, pleomorfik giant cell Spindle cell Small anaplastic cell

80 Congenital anomali Tiroid
Ductus/cyst thyroglossus Sisa2 vestigial remnant Lesi kecil 2-3 cm Letak antara Glossus - Thyroid

81 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

82 Figure 24-24 Parathyroid adenomas are almost always solitary lesions
Figure 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. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :32 PM) © 2005 Elsevier

83 Figure 24-25 Parathyroid adenoma
Figure 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. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :32 PM) © 2005 Elsevier

84 Hormon PTH bekerja : Pada tulang menambah aktivitas osteoclast
Pada ginjal meningkatkan - resorbsi calcium - konversi vit D aktif - ekskresi phosphat Pada usus menambah absorbsi kalsium

85 Tumor2 ganas yang lain  calcium darah tinggi
Metastasis tulang  osteolisis PTH related protein ( PTH rP )

86 Hiperparatiroidisme primer
Sebabnya : Adenoma % Hiperplasia % Carcinoma 5 % Usia tersering pada dewasa 50 th lebih Wanita lebih sering dp laki-laki Ada faktor radiasi sebelumnya

87 Figure 24-26 Cardinal features of hyperparathyroidism
Figure 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. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 6 April :32 PM) © 2005 Elsevier

88 Morfologi Tumor soliter, kecil 0,5 – 5 gr
Lunak, batas jelas, kecoklatan Mikroskopis : Sel2 poligonal, uniform Inti kecil, central Klinik, dapat berupa : A symptomatic hyperparathyroidism Symptomatic hyperparathyroidism

89 Pada symptomatic timbul :
Tulang  osteoporosis Ginjal  nephrolithiasis Gastrointestinal  constipasi, ulcus dll CNS  depresi Neuromuscular  lemah Cardiac  kalsifikasi katup