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Thyroid Diseases Steve Orme Leeds Introduction Background Basic Principles Clinical Syndromes Summary Hypothesis Testing? Appreciate Limitation of Laboratory Investigations Treat ‘Normal Ranges’ with the Disdain they Deserve Avoid Medicine by Proxy Do not Over Investigate Basic Principles Too Much Hormone Measure at Nadir Try to Suppress Evaluate Their 24 Hour Secretion Measure the preceding Hormone (Elevated Free T4, Measure TSH) Basic Principles Too Little Hormone Measure at Peak Try to Stimulate Measure the preceding Hormone (Low Free T4, Measure TSH) Basic Principles Try to Determine Aetiology Supplementary Hormone Tests Immunology *Radiology/ Nuclear Medicine (* Use Sparingly) Basic Principles Remember 1 in 20 Blood Investigations Will be ‘Abnormal’ In An Average ‘Normal’ Patient Reference Range :- Mean (95 % Confidence Interval) Small Sample Size Thyroid Disease Hypothyroidism Thyrotoxicosis Thyroid Nodules/ Cancer Amiodarone Induced Thyroid Disease Hypothyroidism Myxoedema Hashimoto’s Thyroiditis Post Surgery/Radioactive Iodine Therapy Secondary/Tertiary Hypothyroidism Free T4 & TSH TPO Antibodies Investigate possible co-existing Autoimmune Diseases Thyroid Imaging Not Indicated Treatment Strategies Dictated by Diagnosis Graves Disease Toxic Nodule Trial of Drugs I 131 131 Multinodular Goitre I /Surgery Graves Disease Pharmacology of CBZ/PTU CBZ Plasma T 1/2 6-8 Hrs Crosses Placenta & Breast Epithelium >10 more Potent than PTU Duration of Action >24 Hrs PTU Plasma T 1/2 1-2 Hrs Minimal Placental & Breast Transfer Duration of Action 1224 Hrs Graves Disease Drug Therapy (Adverse Effects) Minor/Common (5-10%) Pruritis Urticarial Rash Arthralgia Fever Graves Disease Drug Therapy (Adverse Effects) Uncommon Abnormal Taste (CBZ) GI Upset Hypoglycaemia (Anti-Insulin Antibodies) Graves Disease Drug Therapy (Adverse Effects) Major (Rare or *Very Rare) Agranulocytosis Aplastic Anaemia* Thrombocytopenia* Hepatitis (PTU)* Cholestatic Jaundice (CBZ)* Lupus-like Syndrome* Graves Disease Drug Therapy (Adverse Effects) Minor Usually Transient Major (Agranulocytosis) Idiosyncratic. Onset more Likely in the First 3 Months, High-Dose Therapy and the Elderly. Graves Disease Drug Therapy (Dose, Frequency and Duration) Titration Block and Replacement Regimen Graves Disease Managing Relapse Relapse Rate 60% (10 Years Off Rx) No difference between 6 Months of Block and Replacement Regimen and 18 Months of Titration Further Relapses Inevitable After First Failed Trial Of Medication. Graves Disease Predicting Relapse Young Patients Large Goitre Presence of TAO High Levels of TSH-receptor Antibody at Diagnosis. Graves Disease Managing Relapses I131 Thyroid Surgery Long-term Low-dose Thionamide Therapy Radioactive Iodine Therapy Counsel Patients Avoid Pre-Treatment with PTU Special Measures Carefully Monitor Thyroid Status for at Least 6 Months Thyroid Surgery Choose Your Surgeon Carefully Counsel Patients Pre-Treatment Mandatory Special Measures Carefully Monitor Thyroid and Calcium Status for at Least 6 Months Post OP Long-term Data Base Follow UP Thyroid Nodules & Cancer Nodules are Common Thyroid Cancer is not (80 Cases per year in West Yorkshire) Refer Palpable nodules Early Diagnosis Improves Prognosis Management Should be through an Endocrine Cancer MDT Thyroid Nodules & Cancer Prognosis for Most Cases of Well Differentiated Thyroid Carcinoma is Good Most Patients Require TotalThyroidectomy , I131 Radio-ablation and TSH Suppressive Doses of T4 Life Long Specialist Monitoring is Mandatory Amiodarone Benzofuranic Derivative Contains 37% Iodine 50-100 times RDI Amiodarone Inhibits Type I & II 5’- deiodinase Cytotoxic to Thyroid Cells Affects Thyroid Autoimmunity Acts on Thyroid Hormone Receptors Euthyroid Patients on Amiodarone Have Elevated Free T4 Low Normal Total T3 High Normal or Transiently Elevated TSH Amiodarone Pattern of Thyroid Disease is related to Population Iodine Intake In the UK 2 % AIT 15% AIH Amiodarone Induced Thyrotoxicosis Onset Explosive Median Duration of Therapy 3Yrs Unexplained Deterioration Weight Loss Overt Signs of Thyrotoxicosis Absent Amiodarone Induced Thyrotoxicosis Type I Goitre Present Iodine Uptake & Colour Flow Doppler Increased Type II No Small/Goitre Inflammatory Markers Increased Low Iodine uptake and Colour Flow Doppler Subsequent Hypothyroidism Amiodarone Induced Thyrotoxicosis Type I Carbimazole Potassium Perchlorate Radioactive Iodine Surgery Type II Prednisolone Surgery Amiodarone Induced Hypothyroidism Females Pre-existing Autoimmune Thyroid Disease Positive TPO Antibodies Treat as Primary Hypothyroidism Summary ‘Where Observation is Concerned, Chance Favours Only The Prepared Mind’ (Lois Pasteur 1822-95AD)
