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)