Baseline serum thyroid stimulating hormone (TSH) normal suppressed - PowerPoint PPT Presentation

Johannes Gutenberg University Medical Center, Mainz, Germany GRAVES ‘ DISEASE George J Kahaly, MD, PhD

Hyperthyroidism – Causes / Types  Graves ’ disease > 60%  Toxic nodular goiter < 30%  Subacute thyroiditis (early) 5-10%  Other < 1-2% • Nutritional / Drugs / Intoxication • Transient neonatal • Inherited TSH receptor mutations • Thyroid hormone resistance (thyrotoxic variant) • TSH secreting pituitary adenoma

Baseline serum thyroid stimulating hormone (TSH) normal suppressed Thyroid stimulating immunoglobulins ( TSI ) Euthyroidism negative positive Other causes of thyrotoxicosis Graves´ hyperthyroidism (e. g. toxic nodules, thyroiditis) Earlier Differential Diagnosis for Thyrotoxicosis

THYROID AUTOANTIBODIES TSH - Receptor Graves ’ disease 90-99% Silent thyroiditis 0-10% Peroxidase Graves’ disease 70 -80% Silent thyroiditis 90-95% Thyroglobulin Graves ’ disease 20-40% Silent thyroiditis 30-50%

Vaidya & al., Clin Endocrinol 2008; 68: 814

Methimazole Propylthiouracil Cooper, N Engl J Med 2005

Pharmacology MMI PTU • Absorption rapid rapid • Bioavailability ~ 100% ~ 100% • Peak serum level 60-120 min 60 min • Serum half life 6-8h 90 min • Duration of action > 24h 8-12h • Thyroidal concentration 5x10 -5 mol/L unknown • Thyroidal turnover slow moderate Cooper, NEJM 2005; Brent, NEJM 2008

Pharmacokinetics MMI PTU Cooper, NEJM 2005; Brent, NEJM 2008  Serum protein binding nil 85 %  Crosses placenta ++ +  Levels in breast milk ++ +  Volume of distribution 40 L 20 L  Excretion renal renal  Metabolism during illness - renal nil nil - liver prolonged nil

Antithyroid Drugs DOSE (mg /day) Starting Maintenance  Methimazole 10-30 2.5-5  Propylthiouracil 100-300 25-50  Perchlorate 600-1200 100-400  Lithium 450-900 300

SIDE EFFECTS of ANTI - THYROID DRUGS Cooper, NEJM 2005

„ BLOCK and REPLACE “ McIver & al. NEJM 1996

Occurence of Relative Risk 4.1 Ophthalmopathy 95% CI 1.7 – 10.0 P = 0.002 after treatment for Graves ‘ hyperthyroidism Tallstedt & al., N Engl J Med 1992; 326: 1733

ß - Adrenergic Blocking Drugs Starting dose (mg/day) • Propranolol 80 - 160 • Atenolol / Metoprolol 50 - 200 • Nadolol 40 - 80 • Bisoprolol 2.5 - 5 ► Relief from palpitations, tremor, anxiety ! Caution: Asthma, bradyarrhythmia

Comparison between intravenous and oral glucocorticoids for Graves ’ orbitopathy % 80 IV 70 P < 0.001 Kahaly & al., 60 JCEM 2005 50 Oral 40 30 20 10 0 Response rate Side Effects