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  1. Hyperthyroidism: Diagnosis, Management and Long-term ConsequencesKristien BoelaertSenior Lecturer in EndocrinologyConsultant EndocrinologistQueen Elizabeth Hospital Birmingham, UK Centre for Endocrinology, Diabetes & MetabolismUniversity of Birmingham, UK

  2. 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 131I – The Birmingham experience • Long-term consequences: • Association with mortality • Weight changes following Rx

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

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

  5. Age at diagnosis of Graves’ Disease * *** *** ** *** * Median age at presentation (y) T1DM RA PA CD Vitiligo IBD None N3188 39 25 40 25 2571 Boelaert et al. (2010) Am J Med 123, 183.e1

  6. Number of reported symptoms according to age P < 0.001 Number of patients (%) 0-2 symptoms 3-4 symptoms 5 or more symptoms Boelaert et al. (2010) JCEM 95, 2715

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

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

  9. 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

  10. SMR according to treatment modality Boelaert et al. (2012) JCEM resubmitted

  11. Multivariate within cohort analysis Boelaert et al. (2012) JCEM resubmitted

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

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

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

  15. Multi-level model to predict weight Boelaert et al. (2012) in preparation

  16. Parameters associated with weight gain Boelaert et al. (2012) in preparation

  17. Summary of weight gain study • Treatment of hyperthyroidism associated with significant weight gain • 131I 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 131I Boelaert et al. (2012) in preparation

  18. 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 131I may be required in certain patient groups • 131I-induced hypothyroidism is associated with reduced risk of mortality • 131I associated with small but definite increase in weight gain