Classification of thyroid disorders

Transcription

1 Hypothalamus TRH Hypophyse TSH Thyroïde T3 T4 Organes cibles T3 Foie Classification of thyroid disorders T3, T4 overt hyperthyroidism subclin. hyperthyroidism normal values sublin. hypothyroidism overt hypothyroidism TSH 1

2 Mrs. G.M., 1933 Past medical history - recurrent abortions Current history - fatigue, sleepy - weight gain (6 kg/ 6 mo) - muscle weakness Physical examination - slow reflexes - skin thickened and dry - no goiter clinical suspicion of hypothyroidism Mrs. G.M., which tests? blood tests: TSH free T4, total T4 free T3, total T3 TRAK (TSH-R Ab), anti-tpo, anti-tg others? 2

3 Mrs. G.M., which tests? blood tests: TSH = 56 mu/l (n: mu/l) additional tests? free T4, total T4 free T3, total T3 TRAK (TSH-R Ab), anti-tpo, anti-tg Mrs. G.M., which tests? blood tests: TSH = 56 mu/l free T4 = 6 pmol/l (n: 12-24) 3

4 Classification of thyroid disorders T3, T4 overt hyperthyroidism subclin. hyperthyroidism normal values sublin. hypothyroidism overt hypothyroidism TSH Mrs. G.M., further tests? blood tests: TSH = 56 mu/l free T4 = 6 pmol/l (n: 12-24) TRAK (TSH-R Ab), anti-tpo, anti-tg others? radiological exams thyroid ultrasound thyroid scintigraphy 4

5 Causes of hypothyroidism Hashimoto thyroiditis post thyroidectomy post I-131 post external irradiation drugs: antithyroid drugs, lithium, IFN, amiodarone chronic iodine excess other forms of thyroiditis (silent, post-partum, de Quervain) Subclinical Hypothyroidism risk of progression 4.3 % / year for TSH & Ab positive 2.1 % / year for TSH = & Ab positive 2.6 % / year for TSH & Ab negative NEJM 1996, 335: 99f (adapted) 5

6 Why has Hashimoto's thyroiditis (chronic lymphocytic thyroiditis) become so prevalent? 2. Hypothyroidism after I-131 or surgery NEJM 330: 1731f 6

7 3. Thyroiditis (silent, postpartum, de Quervain) Mrs. G.M., which dose of T4? blood tests: TSH = 56 mu/l free T4 = 6 pmol/l (n: 12-24) Dose of T mcg/d 25 mcg/d 50 mcg/d 75 mcg/d 100 mcg/d 7

8 Spectrum of hypothyroidism & treatment myxoedematous coma overt hypothyroidism subclinical hypothyroidism T4: µg/d iv T3: µg/d iv µg/d p.o µg/d p.o. (1.7 µg/kg/d) Thyroid hormone, digoxin & oral anticoagulants treatment with T4 - increases the clearance of digoxin - may dramatically increase the effect of oral anticoagulants 8

9 Follow-up of patients on T4 TSH measurements weeks after each dose change (target: TSH mu/l) - 1x / y (TSH only!) Δ absorption T4 sucralfate, iron, Al(OH) 2, resins, calcium Δ metabolism T4 carbamazepin, phenytoin, rifampicin, HRT pregnancy increase dose by % Classification of thyroid disorders T3, T4 overt hyperthyroidism inappropriate secretion of TSH subclin. hyperthyroidism normal values sublin. hypothyroidism central hypothyroidism overt hypothyroidism TSH 9

10 Traitement de l'hypothyroïdie infraclinique en focntion des symptômes! TSH <6 mu/l TSH à 3-6 mois, puis 1x/an TSH 6-10 mu/l si >3-6 mois (thyroïdite!), ad ttt TSH >10 mu/l substitution Traitement: commencer avec mg/j ( µg/kg/j), adaptation après 6 semaines (selon TSH) Contrôles: clinique et TSH 1x/an Prevalence of hypothyroidism 10

11 Subclinical hypo & cardiovasc. risk Ann Int Med 132: 270f Mr. A.F.,

12 Mr. A.F., 1928 what next? No symptoms or signs Thyroid nodule of 2 cm on routine PE blood tests? radiological exams? Mr. A.F., 1928 what next? No symptoms or signs Thyroid nodule of 2 cm on routine PE blood tests: TSH 0.1 mu/l (0.5 4 mu/l) free T4 16 pmol/l (11-24 pmol/l) total T3 normal 12

13 Classification of thyroid disorders T3, T4 overt hyperthyroidism subclin. hyperthyroidism normal values sublin. hypothyroidism overt hypothyroidism TSH Mr. A.F., 1928 what next? No symptoms or signs Thyroid nodule of 2 cm on routine PE blood tests: TSH 0.1 mu/l (0.5 4 mu/l) free T4 16 pmol/l (11-24 pmol/l) total T3 normal and now? 13

14 n.s. after adj. for age & sex 14

15 Mr. A.F., 1928 what next? No symptoms or signs Thyroid nodule of 2 cm on routine PE blood tests: TSH 0.1 mu/l (0.5 4 mu/l) free T4 16 pmol/l (11-24 pmol/l) total T3 normal more labs? radiological exams thyroid ultrasound? thyroid scintigraphy? Treatment of hyperthyroidism Multinodular goitre / toxic adenoma Basedow (Graves') Thyroiditis 15

16 Radioiodine scan normal thyroïdite Basedow GMN thyroid scintigraphy ( 123 I ou 99m Tc) Treatment of hyperthyroidism Multinodular goitre / toxic adenoma radioiodine, thyroidectomy Basedow (Graves') drugs, radioiodine, operation Thyroiditis wait! (β-blockers, NSAR) rare causes 16

17 TSH TSH et T4L à l'hôpital T4L si maladie hypophysaire, psychiatrique aiguë ou non-steady state <0.3(-0.5) mu/l élevées si anamnèse nég. pour iode T4L, T3 hyperthyroïdie scintigraphie normales captation élevée captation basse mu/l stop hyperthyroïdie infraclinique non-thyroidal illness Basedow nodule(s) autonome(s) thyroïdite Summary thyroid dysfunction Hyperthyroidism consider treatment of subclinical hyperthyroidism in asymptomatic elderly patients (even if TSH mu/l) Hypothyroidism no screening! Measure TSH if Sx/signs. If TSH repeatedly > 7(-10) mu/l consider Rx with T4. Cave pregnant patients on T4! 17

18 Thyroid nodules Mme. T.N., 78 y old 18

19 Prevalence of thyroid nodules US, autopsy palpation Mazzaferri, NEJM 328: 553f (1993) What do you do next? 1. 19

20 What do you do next? 1. Function TSH, to exclude a toxic adenoma or Hashimoto s thyroiditis 2. Benign vs malignant Etiology of thyroid nodules 90-95% 5-10% 20

21 Prevalence of thyroid cancer In palpable nodules 5-10% nodules 8-10 mm 9% nodules mm 7% In nodules after XRT 15-25% Autopsy % Thyroid cancer: Incidence Prevalence at autopsy % Incidence of clinically significant thyroid cancers: Attributable mortality: <0.005% / y (ca. 1: / y) <5 / 1 mio Many (micro)papillary cancers are without any clinical relevance The estimated progression of microptc is <0.5% over a lifetime 21

22 Prognosis of thyroid cancer survival Struma maligna (Freiburg i. Br., 1833) What next? 1. Function? TSH, to exclude a toxic adenoma or Hashimoto s thyroiditis 2. Benign vs malignant? Ultrasound Scintigraphy? Fine-needle aspiration? 22

23 Meier C.A. Baillères Clinics in Endocrinology and Metabolism 14: p. 559f Fine-needle aspiration M. Bongiovanni JC Pache, HUG 23

24 75-80% 15% 5-10% Management of benign nodules - clinical follow-up 1x / y during the first (few) year(s) - US if? size - or high-risk patient (XRT, Cowden) - spontaneous regression in 50% surgery if >4 cm or significant progression no suppressive treatment 24

25 75-80% 15% 5-10% The problem of the over-use of thyroid ultrasound US: Nodules >8 mm in 40% of persons >50 y of age FNA: 15% microfollicular lesions (suspect for FTC) i.e. thyroidectomy in 0.4 * 0.15 = 6% of the population! Example for ZH (0.5 mio) persons / 0.5 million will die from thyroid cancer - when all nodules are detected, 30'000 persons (6%) will undergo a thyroidectomy 1 life safed for thyroids removed... 25

26 Tumor size & prognosis of differentiated thyroid carcinoma Mazzaferri EL et al, Am J Med 97: 418f (1994) Which nodules should be investigated? Nodules <1-1.5 cm (detection limit by palpation) in patients w/o FH, XRT: clinical follow-up at 6 & 12 mois, then 1x / an Nodules >1.5 cm should be biopsied Nodules cm: clinical context (age, appearance, palpation, LN, MNG...) Euthyroid nodules >4 cm generally ad OP 26