Hyperthyroidism: Diagnosis, Management and Long-term Consequences Hyperthyroidism: Diagnosis, Management and Long-term Consequences Kristien Boelaert Senior Lecturer in Endocrinology Consultant Endocrinologist Queen Elizabeth Hospital Birmingham, UK Centre for Endocrinology, Diabetes & Metabolism University of Birmingham, UK

Overview  Diagnosis of hyperthyroidism/thyrotoxicosis  Influence of endogenous/environmental factors on phenotype  Symptoms and signs of hyperthyroidism according to age  Co-existing autoimmune diseases  Management: Treatment with 131 I – The Birmingham experience  Long-term consequences:  Association with mortality  Weight changes following Rx

Family history  Family history: 47.7% females – 40.0% males  Inverse relationship between age at diagnosis – number of relatives with thyroid dysfunction  FH of hyperthyroidism more common than hypothyroidism (p<0.001) Manji, Boelaert et al. (2006) JCEM 91, 4873

Associated autoimmune diseases Boelaert et al. (2010) Am J Med 123, 183.e1  2791 subjects with Graves’ disease

Age at diagnosis of Graves’ Disease Median age at presentation (y) T1DM RA PA CD Vitiligo IBD None N *** * ** * Boelaert et al. (2010) Am J Med 123, 183.e1

Number of reported symptoms according to age Number of patients (%) 0-2 symptoms 3-4 symptoms 5 or more symptoms P < Boelaert et al. (2010) JCEM 95, 2715

Outcome according to dose regimen (%) Cure Hypothyroidism *** **  1278 patients treated with 131 I for hyperthyroidism  Single fixed dose of 131 I Outcome following 131 I therapy Boelaert et al. (2009) Clin End 70, 129

Factors predicting cure of hyperthyroidism Boelaert et al. (2009) Clin End 70, 129

Hyperthyroidism and mortality - Outstanding questions  Is mortality related to underlying aetiology - ? higher in toxic nodular hyperthyroidism (Metso et al. (2007) JCEM 92, 2190)  Is outcome affected by treatment modality?  What is the influence of biochemical control of hyperthyroidism on outcome?  How do pre-existing co-morbidities affect outcome? Brandt et al. (2011) Eur J Endo 165, 491

SMR according to treatment modality Cause of deathOverallWhilst on Thionamide Rx Following 131 I Not hypothyroid Following 131 I Hypothyroid SMR P P P All causes Males Females Comorbidity absent Comorbidity present < Sinus Rhythm Atrial fibrillation Circulatory deaths Boelaert et al. (2012) JCEM resubmitted

HR (95% CI)P- Value Gender Male Female ( )0.01 Cause of hyperthyroidism Graves’ disease TN hyperthyroidism Indeterminate ( ) 0.86 ( ) Cardiac rhythm at presentation Sinus rhythm Atrial fibrillation ( )0.02 Co-morbidities Absent Present ( )<0.001 Serial fT4 per 10 pmol/l increment1.21 ( )0.02 Treatment Whilst on antithyroid drugs After 131 I – not taking T4 After 131 I – on T ( ) 0.72 ( ) Multivariate within cohort analysis Boelaert et al. (2012) JCEM resubmitted

Control of hyperthyroidism Boelaert et al. (2012) JCEM resubmitted

Comparison with background population Proportion of females (%) Normal BMI Overweight Obese *** Normal BMI Overweight Obese Proportion of males (%) *** Normal BMI Overweight Obese * Proportion of males (%) Proportion of females (%) Boelaert et al. (2012) in preparation PRESENTATION DISCHARGE

Weight change during FU Boelaert et al. (2012) in preparation

VariableCoefficient95% CIP-value 131I treatment No Yes to1.04 <0.001 Levothyroxine RX No Yes to 0.61 <0.001 Serial fT4 (pmol/l) > to to <0.001 Serial TSH < > to to – to to 1.28 < <0.001 Multi-level model to predict weight

Parameters associated with weight gain Boelaert et al. (2012) in preparation Interaction with 131 IInteraction with levothyroxine InteractionCoefficient95% CIP-valueCoefficient95% CIP-value Gender Male Female < <0.001 Aetiology GD TN < <0.001 BMI category Normal Overweight Obese fT4 (pmol/l) > <

Summary of weight gain study Boelaert et al. (2012) in preparation  Treatment of hyperthyroidism associated with significant weight gain  131 I treatment and hypothyroidism associated with small amount of excess weight gain  Uncontrolled hyperthyroidism results in less weight gain  Males, GD subjects, higher BMI category and more severe hyperthyroidism associated with higher risk of weight gain from 131 I

Conclusions  Clinical presentation of hyperthyroidism widely varied – may be missed in elderly  Think of associated autoimmune diseases if response to treatment poor  Higher doses of 131 I may be required in certain patient groups  131 I-induced hypothyroidism is associated with reduced risk of mortality  131 I associated with small but definite increase in weight gain