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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. - PowerPoint PPT Presentation
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Thyroid Diseases Thyroid Diseases
Steve OrmeSteve Orme
LeedsLeeds
IntroductionIntroduction
BackgroundBackground
Basic PrinciplesBasic Principles
Clinical SyndromesClinical Syndromes
SummarySummary
Hypothesis Testing?Hypothesis Testing?
Appreciate Limitation of Laboratory Appreciate Limitation of Laboratory Investigations Investigations
Treat ‘Normal Ranges’ with the Disdain Treat ‘Normal Ranges’ with the Disdain they Deserve they Deserve
Avoid Medicine by Proxy Avoid Medicine by Proxy
Do not Over InvestigateDo not Over Investigate
Basic PrinciplesBasic Principles
Too Much Hormone Too Much Hormone Measure at Nadir Try Measure at Nadir Try to Suppress Evaluate to Suppress Evaluate Their 24 Hour Secretion Measure the Their 24 Hour Secretion Measure the preceding Hormone preceding Hormone (Elevated (Elevated Free T4, Measure TSH)Free T4, Measure TSH)
Basic PrinciplesBasic Principles
Too Little Hormone Too Little Hormone Measure at Peak Measure at Peak Try to Stimulate Try to Stimulate Measure the preceding Hormone Measure the preceding Hormone (Low Free T4, Measure TSH)(Low Free T4, Measure TSH)
Basic PrinciplesBasic Principles
Try to Determine Aetiology Try to Determine Aetiology Supplementary Supplementary Hormone Tests Immunology Hormone Tests Immunology *Radiology/ Nuclear Medicine *Radiology/ Nuclear Medicine (* Use Sparingly)(* Use Sparingly)
Basic PrinciplesBasic Principles
Remember 1 in 20 Blood Investigations Will Remember 1 in 20 Blood Investigations Will be ‘Abnormal’ In An Average ‘Normal’ be ‘Abnormal’ In An Average ‘Normal’ PatientPatient Reference Range :- Mean (95 % Confidence Interval) Reference Range :- Mean (95 % Confidence Interval)
Small Sample SizeSmall Sample Size
Thyroid Disease Thyroid Disease
HypothyroidismHypothyroidism
ThyrotoxicosisThyrotoxicosis
Thyroid Nodules/ CancerThyroid Nodules/ Cancer
Amiodarone Induced Thyroid DiseaseAmiodarone Induced Thyroid Disease
Hypothyroidism Hypothyroidism
MyxoedemaMyxoedema
Hashimoto’s ThyroiditisHashimoto’s Thyroiditis
Post Surgery/Radioactive Iodine Post Surgery/Radioactive Iodine TherapyTherapy
Secondary/TertiarySecondary/Tertiary
Hypothyroidism Hypothyroidism
Free T4 & TSHFree T4 & TSH
TPO AntibodiesTPO Antibodies
Investigate possible co-existing Auto-Investigate possible co-existing Auto-immune Diseasesimmune Diseases
Thyroid Imaging Not IndicatedThyroid Imaging Not Indicated
Treatment Strategies Treatment Strategies Dictated by DiagnosisDictated by Diagnosis
Graves Disease Trial of Drugs
Toxic Nodule I131
Multinodular Goitre I131/Surgery
Graves DiseaseGraves DiseasePharmacology of CBZ/PTUPharmacology of CBZ/PTU
CBZ CBZ Plasma T Plasma T 1/21/2 6-8 6-8
Hrs Hrs Crosses Placenta & Crosses Placenta & Breast Epithelium Breast Epithelium >10 more Potent >10 more Potent than PTU than PTU Duration of Action >24 Duration of Action >24 HrsHrs
PTU PTU Plasma T Plasma T 1/2 1/2 1-2 Hrs 1-2 Hrs
Minimal Minimal Placental & Breast Placental & Breast TransferTransfer
Duration of Action 12-Duration of Action 12-24 Hrs24 Hrs
Graves DiseaseGraves DiseaseDrug Therapy (Adverse Effects)Drug Therapy (Adverse Effects)
Minor/Common (5-10%) Minor/Common (5-10%) Pruritis Pruritis Urticarial Rash Urticarial Rash Arthralgia Arthralgia FeverFever
Graves DiseaseGraves DiseaseDrug Therapy (Adverse Effects)Drug Therapy (Adverse Effects)
Uncommon Uncommon Abnormal Taste (CBZ) Abnormal Taste (CBZ) GI Upset GI Upset Hypoglycaemia (Anti-Insulin Antibodies) Hypoglycaemia (Anti-Insulin Antibodies)
Graves DiseaseGraves DiseaseDrug Therapy (Adverse Effects)Drug Therapy (Adverse Effects)
Major (Rare or *Very Rare) Major (Rare or *Very Rare) Agranulocytosis Agranulocytosis Aplastic Aplastic Anaemia* Anaemia* Thrombocytopenia* Thrombocytopenia* Hepatitis (PTU)* Hepatitis (PTU)* Cholestatic Jaundice (CBZ)* Cholestatic Jaundice (CBZ)* Lupus-like Syndrome* Lupus-like Syndrome*
Graves DiseaseGraves DiseaseDrug Therapy (Adverse Effects)Drug Therapy (Adverse Effects)
Minor Minor Usually TransientUsually Transient
Major (Agranulocytosis) Major (Agranulocytosis) Idiosyncratic. Idiosyncratic. Onset more Likely in the First 3 Months, Onset more Likely in the First 3 Months, High-Dose Therapy and the ElderlyHigh-Dose Therapy and the Elderly. .
Graves DiseaseGraves DiseaseDrug Therapy Drug Therapy
(Dose, Frequency and Duration) (Dose, Frequency and Duration)
TitrationTitration
Block and Replacement RegimenBlock and Replacement Regimen
Graves DiseaseGraves DiseaseManaging RelapseManaging Relapse
Relapse Rate 60% Relapse Rate 60% (10 Years Off Rx)(10 Years Off Rx)
No difference between 6 Months of Block No difference between 6 Months of Block and Replacement Regimen and 18 and Replacement Regimen and 18 Months of TitrationMonths of Titration
Further Relapses Further Relapses InevitableInevitable After First After First Failed Trial Of Medication. Failed Trial Of Medication.
Graves DiseaseGraves DiseasePredicting RelapsePredicting Relapse
Young PatientsYoung Patients
Large GoitreLarge Goitre
Presence of TAOPresence of TAO
High Levels of TSH-receptor Antibody at High Levels of TSH-receptor Antibody at Diagnosis. Diagnosis.
Graves DiseaseGraves DiseaseManaging Relapses Managing Relapses
II131131
Thyroid SurgeryThyroid Surgery
Long-term Low-dose Thionamide TherapyLong-term Low-dose Thionamide Therapy
Radioactive Iodine TherapyRadioactive Iodine Therapy
Counsel PatientsCounsel Patients
Avoid Pre-Treatment with PTUAvoid Pre-Treatment with PTU
Special Measures Special Measures
Carefully Monitor Thyroid Status for at Carefully Monitor Thyroid Status for at Least 6 MonthsLeast 6 Months
Thyroid SurgeryThyroid Surgery
Choose Your Surgeon CarefullyChoose Your Surgeon Carefully
Counsel PatientsCounsel Patients
Pre-Treatment MandatoryPre-Treatment Mandatory
Special Measures Special Measures
Carefully Monitor Thyroid and Calcium Carefully Monitor Thyroid and Calcium Status for at Least 6 Months Post OPStatus for at Least 6 Months Post OP
Long-term Data Base Follow UPLong-term Data Base Follow UP
Thyroid Nodules & CancerThyroid Nodules & Cancer
Nodules are Common Thyroid Cancer is Nodules are Common Thyroid Cancer is not (80 Cases per year in West Yorkshire)not (80 Cases per year in West Yorkshire)
Refer Palpable nodulesRefer Palpable nodules
Early Diagnosis Improves Prognosis Early Diagnosis Improves Prognosis
Management Should be through an Management Should be through an Endocrine Cancer MDTEndocrine Cancer MDT
Thyroid Nodules & CancerThyroid Nodules & Cancer
Prognosis for Most Cases of Well Prognosis for Most Cases of Well Differentiated Thyroid Carcinoma is GoodDifferentiated Thyroid Carcinoma is Good
Most Patients Require Total-Most Patients Require Total-Thyroidectomy , IThyroidectomy , I131131 Radio-ablation and Radio-ablation and TSH Suppressive Doses of T4TSH Suppressive Doses of T4
Life Long Specialist Monitoring is Life Long Specialist Monitoring is MandatoryMandatory
AmiodaroneAmiodarone
Benzofuranic DerivativeBenzofuranic Derivative
Contains 37% IodineContains 37% Iodine
50-100 times RDI50-100 times RDI
AmiodaroneAmiodarone
Inhibits Type I & II 5’- deiodinaseInhibits Type I & II 5’- deiodinase
Cytotoxic to Thyroid CellsCytotoxic to Thyroid Cells
Affects Thyroid AutoimmunityAffects Thyroid Autoimmunity
Acts on Thyroid Hormone ReceptorsActs on Thyroid Hormone Receptors
Euthyroid Patients on Euthyroid Patients on AmiodaroneAmiodarone
Have Elevated Free T4Have Elevated Free T4
Low Normal Total T3 Low Normal Total T3
High Normal or Transiently Elevated TSHHigh Normal or Transiently Elevated TSH
AmiodaroneAmiodarone
Pattern of Thyroid Disease is related to Pattern of Thyroid Disease is related to Population Iodine IntakePopulation Iodine Intake
In the UK 2 % AIT 15% AIHIn the UK 2 % AIT 15% AIH
Amiodarone Induced Amiodarone Induced ThyrotoxicosisThyrotoxicosis
Onset ExplosiveOnset Explosive
Median Duration of Therapy 3YrsMedian Duration of Therapy 3Yrs
Unexplained DeteriorationUnexplained Deterioration
Weight LossWeight Loss
Overt Signs of Thyrotoxicosis AbsentOvert Signs of Thyrotoxicosis Absent
Amiodarone Induced Amiodarone Induced ThyrotoxicosisThyrotoxicosis
Type I Type I Goitre Present Goitre Present Iodine Iodine Uptake & Colour Flow Uptake & Colour Flow Doppler Increased Doppler Increased
Type II Type II No Small/Goitre No Small/Goitre Inflammatory Markers Inflammatory Markers Increased Increased Low Low Iodine uptake and Iodine uptake and Colour Flow Doppler Colour Flow Doppler Subsequent Subsequent HypothyroidismHypothyroidism
Amiodarone Induced Amiodarone Induced ThyrotoxicosisThyrotoxicosis
Type I Type I Carbimazole Carbimazole Potassium Potassium Perchlorate Perchlorate Radioactive Iodine Radioactive Iodine SurgerySurgery
Type II Type II Prednisolone Prednisolone SurgerySurgery
Amiodarone Induced Amiodarone Induced HypothyroidismHypothyroidism
FemalesFemales
Pre-existing Autoimmune Thyroid DiseasePre-existing Autoimmune Thyroid Disease
Positive TPO AntibodiesPositive TPO Antibodies
Treat as Primary HypothyroidismTreat as Primary Hypothyroidism
SummarySummary
‘‘Where Observation is Concerned, Where Observation is Concerned, Chance Favours Only The Prepared Chance Favours Only The Prepared Mind’Mind’ (Lois Pasteur 1822-95AD)(Lois Pasteur 1822-95AD)