Disorders of the Thyroid

THE THYROID GLAND Thyroid cartilago Pyramidal lobe Left lobe Isthmus Right lobe Internal jugular vein External carored arteri

THYROID GLAND HISTOLOGY http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/anatomy.html

Thyroid hormone synthesis, storage and release ORGANIFICATION TRAPPING I I PEROXIDASE H2O2 OXIDIZED IODIDE MIT DIT T3 TGB TGB COUPLING STORAGE Tyr Tyr AA TGB Tyrosine Tyrosine? DIT DIT T4 TGB TGB Iodinase MIT DIT MIT DIT TGB DEIODINATION I RELEASE PROTEOLYSIS T3 T4 T3 --TGB T4 --TGB T3 Protease T4 CAPILLARY FOLLICULAR CELL COLLOID Cryer PE. Diagnostic endocrinology 1976:35

+ HYPOTHALAMUS Basic elements in regulation of thyroid function TRH T3 PORTAL SYSTEM I ANTERIOR PITUITARY T4 + “FREE” T3 _ TSH T4 T3 TISSUE THYROID + I T4

Usually Complain thyroid disease Thyroid enlargement which may be diffuse or nodular Symptom of thyroid deficiency or Hypothyroidism Symptoms of thyroid hormon excess, or Hyperthyroidism

Usually Complain thyroid disease Complications of a Spesific form hyperthyroidism : Graves’ disease which may present which prominence of the eyes or exophthalmos and thickening of the skin over the lower legs (rare) or thyroid dermopathy

Physical Examination Inspection : Good light coming from behind the examiner, The patient is instructed to swallow a sip of water, Observe the gland as it moves up and down. Enlargement and nodularity can often be noted.

Physical Examination Palpate the gland from behind the patient with the middle threes fingers on each lobe while the patients swallows. Nodules can be measured in a similar way.

Physical Examination On physical examination the normal thyroid gland about 2cm in vertical dimension and about 1cm in horizontal dimention above the isthmus Enlarged thyroid gland is called Goiter The generalized enlargement is termed diffuse goiter, irreguler or lumpy enlargement is called nodular goiter

Diffuse goiter Nodular goiter 3. Adenomatosa goiter Simple diffus goiter Hypertiroidism Hashimoto thyroiditis Nodular goiter 1. Thyroid nodul 2. Thyroid cyst 3. Adenomatosa goiter 4. Subacut /chronis thyroiditis 5. Plummer thyroiditis

HYPERTHYROIDISM HYPOTHYROIDISM THYROIDITIS THYROID NODUL THYROID DISEASES HYPERTHYROIDISM HYPOTHYROIDISM THYROIDITIS THYROID NODUL

Sublinical hypothyroidism 5-7 % Hyperthyroidism 0,2 % THYROID DYSFUNCTION PREVALENCE Hypothyroidism 2 % Sublinical hypothyroidism 5-7 % Hyperthyroidism 0,2 % Subclinical hyperthyroidism 0,1-6,0% Prevalensi disfungsi tiroid yang paling banyak ditemukan adalah: A. Hipotiroidisme Bhipotiroidi subklinis C.Hipertiroidisme D. Hipotiroidisme subklinis E. Nodul tiroid

Hyperthyroidism & Thyrotoxicosis Thyrotoxicosis is the clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormone. Thyroxicosis is due to hyperactivity of the thyroid gland or hyperthyroidism Occasionally, thyrotoxicosis may be due to other causes such us excessive ingestion of the thyroid hormone or excessive thyroid hormon from ectopis site Pasien wanita 27 tahun datang dgn keluhan utama berat badan menurun drastis, palpitasi, perasaan demam berkeringat, nafsu makan meningkat akan tetapi berat badan menurun. Pagi harti kedua kaki rasa lumpuh. Pemeriksaan fisis nadi 124 permenit, pulsus celer, tensi 160/70 mm Hg. Eksoftalmus mata kanan. Diagnosis yang paling mungkin pada pasien ini adalah: tirotoksikosis B.hipertiroidea C. penyakit Graves D. penyakit Addison E. penyakit Plummer Untuk menetapkan diagnosis maka pemeriksaan fisis yang dapat ditemukan adalah: tremor jari tangan B. vitilogo C. edema non pitting D. strabismus E. semua benar diatas Seandainya terbukti pasien menderita Penyakit Grasves maka pemeriksaan yang diperlukan untuk membuktikan diagnosis adalah: A. TSH receptor antibody B. tiroksin C Scanning tiroid D Tiroglobulin E. buikan salah satu diatas Pengobatan yang diberikan pada pasien ini adalah sebagai berikut KECUALI: PTU B. metrimazol C. beta bloker D. fenobarbital E. tirosin Bila pada pemeriksaan fisis ditemukan struma difus yang sangat besar maka pilihan pengobatan adalah: A. Radio terapi dgn yodium 131 B. PTU C Strumektomi D. solutio lugol E. kemoterapi Apabila pasien dilakukan strumektomi maka dapat terjadi komplikasi Dibawah ini ,KECUALI: A. Perdarahn pasca bedah B. hipoparatiroidisme C. parese n rekurens D. hipotiroid E tidak ada kecuali Pemeriksaan yang paling bermanfaat untuk diagnosis: A. TSH B. ACTH C. Aldosteron D. FT4 E. cortisol Bila hasil pemeriksaan PA menunjukkan karsinoma folikulare maka perlu dilakukan tindakan sebagai berikut: A.operasi ulang tiroidektomi total B. kemoterapi C, tiroksin D. Yodium 131 E. bukan salah satu doatas.

Conditions associated with thyrotoxicosis Diffuse toxic goiter (Graves’ disease) Toxic adenoma (Plummer’s disease) Toxic multinodular goiter Subacute thyroiditis Hyperthyroid phase of Hashimoto’s thyroiditis Thyrotoxicosis factitia Rare: Ovarian struma, metastatic thyroid carcinoma, hydatiform mole Penyakit Graves disebut juga: A. Struma difusa toksik Bpenyakit Plummer C. Tirotoksikosis factitia D. Tiroiditis subakut E. Tiroiditis Hashimoto

GRAVES’ DISEASE (DIFFUSE TOXIC GOITER) GD is the most common form of thyrotoxicosis, may occur at any age, more commonly in females than in males (5X) The syndrome consist one or more of the following features: 1. THYROTOXICOSIS 2. GOITER 3.OPHTHALMOPATHY(Exophthalmos) 4. DERMOPATHY (Pretibial myxedema) Gejala penyakit Graves merupakan suatu sindrom yang terdiri 1. Struma 2. Tirotoksikosis 3. Eksoftalmus 4. miksedema pretibial Tirotoksiskosis yang paling banyak ditemukan adalah : 1. Penyakit Hashimoto 2. Mlahidatidosa 3. Penyakit Plummer 4.Penyakit Graves

ETIOLOGY & PATHOGENESIS GD is currently viewed as an autoimmun disease of unknown cause Ther is a strong familial predisposition in that about 15%. 50% GD have circulating thyroid autoantibodies Peak incidence 20-40-year T-lymphocytes sensitized to antigen within thyroid gland and stimulate B lymphocyte  antibodies Yang tersebut dibawah ini terkait dengan etiologi dan patogenesis Penyakit Graves A. Autoimun 2. predisposis familial 3. insidense paling tinggi 20-40ctahun 4. limposit B merangsang limposit T

Autoimmune thyroiditis Agonist Antibody TSHR-Ab Antagonist Antibody TSHR T. Hashimoto, miksedema primer ,Penyakit Graves ekspressinya berbeda pada proses autoimun yang sama mengakibatkan respons imun berspektrum dpt brp antibodi sitotoksik,antibodi stimulatori,antibodi bloking atau cell mediated immunity. Hashimoto disebabkan clinical expresssion predominan adalah sel mediated immunity yang menyebabkan destruksi sel tiroid yang pada bentuk severe menyebabkan failure tiroid dan miksedema idiopatik. CELL CELL STIMULATION BLOCKADE Davies TR. Graves’ disease in Werner & Ingbar’s : The thyroid ; 2000 ;520

Clinical features Graves’s disease Symptoms: in younger patients: palpitation, nervousness, easy fatigability, hyperkinesia, diarhhea, excessive sweating, intolerance to heat, weight loss, without loss appetite Signs: Thyroid enlargement, exophthalmos, tachycardia, muscle weakness, tremor Older patients cardiovascular & myopatic predominate clinical manifestation  palpitatation, dyspnea on exersice, tremor, nervousness, weight loss

Ophtamopathy Graves disease Infitratif  sympathetic overstimulation Lid retraction (Dalrymphe’s sign) Van Graves sign late palpebra sup Stellwat’s sign the wink eyes late Jefroy’s sign  fold of forehead not see Mobius’sign  convergention of the eyes late Infiltratif  autoimmune Exophthalmus, oculopathy congestif: cheimosis, conjunctivitis, periorbital edema Ulcerasi Cornea , neuritis optica, atrophi n opticus

The Eye signs of Graves’Disease (ATA ) Class Definition 0 No signs no symptoms 1 Only signs, no symptoms, (signs limited to upper lid retraction, stare,lid lag) 2 Soft tissue involvement (symptom & signs) 3 Proptosis (measured with Hertel exophthalmometer) 4 Extraocular muscle involvement 5 Corneal involvement 6 Sight loss (optic nerve involvement)

DISEASE SEVERITY Thyroid eye disease can be divided into MILD disease MODERATE disease SEVERE disease

MILD DISEASE Usually young patient Dry eyes---->lubricants Lid retraction Lid malposition-entropion Mild proptosis

MODERATE DISEASE Thyroid myopathy asymmetric involvement tends to involve vertical muscles in Asians

LID RETRACTION

HERTEL EXOPHTHALMOMETER EXOPHTHALMOS : >18 MM

Computerised Axial Tomography

Thyroid Dermopathy Thickening of the skin,over the lower tibia due to accumulation glycosaminglicans , rare (2-3%) TSH-R Ab high titer Osteopathy in the metacarpal bones

Non Pitting oedema

Suspected hyperthyroidism TSH &FT4 Normal FT4 &TSH Hyperthyroidism excluded Low TSH & Normal FT4 Measure FT3 Normal FT3 High FT3 Subclinical hyperthyroidism Evolving Graves’ disease Or toxic nodular goiter Excess thyroxine replacement Non thyroidal illness Repeat tests in 2-3 months: annual follow-up if no progression T3 Hyperthyroidism Low TSH & high FT4 Normal / high TSH & high FT4 TSH- secreting pituitary adenoma. Thyroid hormone-resistance syndrome Hyperthyroidism Graves’disease Toxic nodular goiter Thyroiditis Gestational Hyperthyroidism Factitious or iatrogenic hyperthyroidism Thyroid Carcinoma Struma Ovarii Tumor secreting Chorionic gonadotropin Familial nonautoimmun hyperthyroidism Laboratoy tests useful in DD of hyperthyroidism

Atypical fashion Graves’ Disease Thyrotoxic periodic paralysis: usually Asian males, sudden attack flacid paralysis, hypokalemia, usualy subsides spontaneously. Prevention: K+ supplement & Betablockers Thyrocardiac disease: primarily with symptoms of heart involvement: refrsctory AF insensitif digoxin or high output heart failure, no evidence underlying heart disease (50%). Treatment of thyrotoxicosis  cure Kerluahn kedua tungkai sering mengalami lumpuh terutam pada pagi hari pada pasien ini adalah akibat: krisis tiroid B. kadar hormon FT4 teralu tinggi C. hipokalemia D. anti tiroglobulin meningkat E. tpenyakit jantung tiroid Penyebab hal ini adalah : hipokalemia B. hiperkalemia C. stroke D. gagal jantung E. krisis tiroid Pengobatan yang dapat diberikan adalah : A. Digoxin B. kortikosteroid C. kalium D. kalsium E. antagonis kalsium

Atypical fashion Graves’ Disease Apethetic hyperthyroidism: Older patients: weight loss, small goiter, slow AF, severe depression with none clinical features Penyakit graves pada orang tua sering bermanifeastasi sebagai hipertiroid apetetik SEBAB pada orang tua gejala menonjol s tidak klasik dan kadang tanpa gejala Krisis tirotoksik timbul pada : 1 operasi yang tidak dipersiapkan 2. Persalinan 4. RAI 131

Treatment modalities Anti-thyroid Surgery I131 radioactive

Treatment of Graves’ Disease 1. Antithyroid drug therapy: Young pts, small glands, mild disease Propylthiouracil, methimazole (6m-15 mo), relaps 50-60%. PTU inhibits the conversion T4T3, effect more quickly compare to methimazole Methimazole - longer duration, single dose Therapy 3-6 months  tapering dose and combination levothyroxin 0.1 mg/d 12-24 months Allergic reaction (rash), agranulocytosis, jaundice, liver failure PTU vmenekan

Treatment of Graves’ diseae Surgical treatment Subtotal thyroidectomy  treatment of choice for very large glands, or multinodular goiter, prepared wth anti thyroid drug (about 6 months) Complication : Hypothyroidism,recurent laryngeal nerve injury

Treatment of Graves’ disease Radioactive iodine therapy USA  NaI 131I  euthyroid over 6-12 weeks Complication: hypothyroidism

Treatment of Graves’ disease Other medical measures: Beta-adrenergic blocking agents Propranolol 10-40 mg every 6 hours, multivitamin supplements, phenobarbital as sedative + to lower T4 levels Cholestyramine, 4 gr orally 3X daily lower T4

Complication of Graves’ Disease Thyrotoxic crisis (thyroid storm) Acute exacerbation symptoms thyrotoxicosis. May be mild & febrile until life threatning. Etiology : after thyroid surgery in patients who has been inadequatlely prepared, RAI131, parturition in adequately controlled thyrotoxicosis or stressfull illnes.

Thyrotoxic crisis(thyroid “storm”): Clinical manifestation: Fever, Sweating, flushing, tachycardia / AF, heart failure, agitation, delirium, coma, jaundice, nausea, vomiting and diarrhea. 75% death………….

Treatment of Thyrotoxic crisis (“thyroid storm”) Prophiltriourasil (PTU): 4 x 300 mg atau Neomercazole 6 x 20 mg. Yodium : Sodium yodida IV 1 mg/12 jam, atau lugol 5% 3x10 tts /hr Propranolol (Inderal): IV 1-5 mg/6jam, atau tab 4x60-80 mg/hr via sonde lambung Kortikosteroid: Dexamethason 2 mg/6 jam Antibiotik dianjurkan jika infeksi sebagai pencetus.

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