Classification of thyroid disorders

Hypophyse Organes cibles Thyroïde Hypothalamus TRH TSH T3 Foie T4 T3

Classification of thyroid disorders

normal values subclin. hyper- thyroidism sublin. hypo- thyroidism overt hyper- thyroidism overt hypothyroidism T3, T4

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., 1933 - which tests?

• blood tests:

TSH

free T4, total T4 free T3, total T3

TRAK (TSH-R Ab), anti-TPO, anti-Tg others?

Mrs. G.M., 1933 - which tests?

• blood tests: TSH = 56 mU/L (n: 0.5 - 5 mU/L) additional tests? free T4, total T4 free T3, total T3

TRAK (TSH-R Ab), anti-TPO, anti-Tg

Mrs. G.M., 1933 - which tests?

• blood tests:

TSH = 56 mU/L

Classification of thyroid disorders

normal values subclin. hyper- thyroidism sublin. hypo- thyroidism overt hyper- thyroidism overt hypothyroidism TSH T3, T4

Mrs. G.M., 1933 - 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

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 2.6 % / year for TSH ↑ & Ab negative 2.1 % / year for TSH = & Ab positive 4.3 % / year for TSH ↑ & Ab positive

Why has Hashimoto's thyroiditis (chronic lymphocytic thyroiditis) become so

prevalent?

2. Hypothyroidism after I-131 or surgery

3. Thyroiditis

(silent, postpartum, de Quervain)

Mrs. G.M., 1933 - which dose of T4?

• blood tests: TSH = 56 mU/L free T4 = 6 pmol/L (n: 12-24) Dose of T4 12.5 mcg/d 25 mcg/d 50 mcg/d 75 mcg/d 100 mcg/d

Spectrum of hypothyroidism

& treatment

myxoedematous coma overt hypothyroidism subclinical hypothyroidism 12.5 - 50 µg/d p.o. T4: 200-300 µg/d iv T3: 10-30 µg/d iv 50-100 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

•  TSH measurements

- 4-6 weeks after each dose change (target: TSH 0.5 - 2 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 10-150%

Follow-up of patients on T4

Classification of thyroid disorders

normal values subclin. hyper- thyroidism sublin. hypo- thyroidism overt hyper- thyroidism overt hypothyroidism inappropriate secretion of TSH central hypothyroidism T3, T4

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 0.05 - 0.1 mg/j

(1.2-1.6 µg/kg/j), adaptation après 6 semaines (selon TSH)

• Contrôles:clinique et TSH 1x/an

Subclinical hypo & cardiovasc. risk

Ann Int Med 132: 270f

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

Classification of thyroid disorders

normal values subclin. hyper- thyroidism sublin. hypo- thyroidism overt hyper- thyroidism overt hypothyroidism TSH T3, T4

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

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 ?

• Multinodular goitre / toxic adenoma

• Basedow (Graves')

• Thyroiditis

Radioiodine scan

thyroid scintigraphy (123_{I ou} 99m_Tc) normal Basedow thyroïdite GMN

• Multinodular goitre / toxic adenoma

→radioiodine, thyroidectomy

• Basedow (Graves')

→drugs, radioiodine, operation

• Thyroiditis

→wait! (β-blockers, NSAR)

• rare causes

TSH

TSH et T4L à l'hôpital

T4L si maladie hypophysaire, psychiatrique aiguë ou non-steady state

stop 0.3-5 mU/l <0.3(-0.5) mU/l T4L, T3 hyperthyroïdie infraclinique non-thyroidal illness hyperthyroïdie normales élevées scintigraphie captation élevée captation basse Basedow nodule(s) autonome(s) thyroïdite si anamnèse nég. pour iode

Summary thyroid dysfunction

• Hyperthyroidism

consider treatment of subclinical hyperthyroidism in asymptomatic elderly patients (even if TSH 0.1 - 0.4 mU/L)

• Hypothyroidism

no screening! Measure TSH if Sx/signs. If TSH repeatedly > 7(-10) mU/L consider Rx with T4.

Thyroid nodules

Prevalence of thyroid nodules

Mazzaferri, NEJM 328: 553f (1993)

US, autopsy

palpation

What do you do next?

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%

Prevalence of thyroid cancer

• In palpable nodules 5 - 10% nodules 8-10 mm 9% nodules 11-15 mm 7% • In nodules after XRT 15 - 25% • Autopsy 6 - 25 - 50%

Thyroid cancer: Incidence

•  Prevalence at autopsy 6 - 25 - 50%

•  Incidence of clinically significant

thyroid cancers: <0.005% / y (ca. 1:40’000 / y) •  Attributable mortality: <5 / 1 mio

Many (micro)papillary cancers are without any clinical relevance

Prognosis of thyroid cancer Struma maligna (Freiburg i. Br., 1833) survival

What next?

1.  Function?

TSH, to exclude a toxic adenoma or Hashimoto’s thyroiditis

2.  Benign vs malignant?

Ultrasound Scintigraphy?

Meier C.A. Baillères Clinics in Endocrinology and Metabolism 14: p. 559f

15% 5-10%

75-80%

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

15% 5-10% 75-80%

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)

-  2.5 persons / 0.5 million will die from thyroid cancer

-  when all nodules are detected, 30'000 persons (6%) will

Mazzaferri EL et al, Am J Med 97: 418f (1994)

Tumor size & prognosis of differentiated thyroid carcinoma

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 1-1.5 cm: clinical context (age,

appearance, palpation, LN, MNG...)