1 / 29

GRAVES’ DISEASE IN ADOLESCENTS

GRAVES’ DISEASE IN ADOLESCENTS. Filippo De Luca Pediatric Unit Department of Pediatrics University of Messina , Italy. Graves’ Disease (GD) in pediatric age Epidemiology. GD accounts for more than 95% of hyperthyroidism cases in childhood

bethan
Download Presentation

GRAVES’ DISEASE IN ADOLESCENTS

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. GRAVES’ DISEASE IN ADOLESCENTS Filippo De Luca Pediatric Unit Department of Pediatrics University of Messina, Italy

  2. Graves’ Disease (GD) in pediatric age Epidemiology • GD accounts for more than 95% of hyperthyroidism cases in childhood • Prevalence of GD is approximately 0.02 in childhood, accounting for fewer than 5% of the total cases of GD • Female-to-male ratio of 3-6:1 • Incidence rate: 0.8/100.000/year • Peak Incidence in children aged 10-15 years • Monozygotic twins show 50% concordance for GD

  3. GD in pediatric age: Risk Factors • Positive family history • Association with HLA B8 and HLA DR3 haplotype • Association with other autoimmune diseases • Autoimmune polyglandular syndromes (APS) type 3 and type 2 • Down syndrome (relative prevalence 0.7%) • Turner syndrome (relative prevalence 1.7%)

  4. Pathogenetic Peculiarities of GD • In contrast to other autoimmune diseases (HT, celiac disease, type 1 diabetes), GD is traditionally considered an autoantibody-mediated T-helper (TH2) • Recent studies cast doubt on this traditional classification and the existence of a clear demarcation between HT and GD • In hyperthyroid patients with GD in the active phase, TH1 rather than TH2 cells predominate among peripheral blood lymphocytes • After initiation of methimazole, an ongoing transition from TH1 to TH2 occurs Inukaiet al Eur JEndocrinol 2007, 156:623

  5. Relationship between Hashimoto (HT) and Graves • In pairs of identical twins, one can develop HT and the other GD • GD and HT frequently aggregate in the same families • They can coexist in the same gland • They can occur in the same patient • They have the same predisposing HLA aplotype (DR3)

  6. HT antecedents in the clinical history of children and adolescents with GD • In a study population of 106 children and adolescents with GD, we report a frequency of HT antecedents in 4% of cases • The prevalence of this sequence of events is more frequent in Down syndrome (20%) • Our reports confirm the existence of a continuum between HT and GD within the spectrum of autoimmune thyroid diseases De Luca et al, Horm Res Paed 2010, 73:473 De Luca et al, EJE 2010,162:591

  7. GD in pediatric ageMajor Clinical Features (%) • Goiter 100% • Nervousness and Irritability 100% • Tachycardia 90% • Hyperreflexia and Hypertension 80% • Tremor 75% • Excessive sweating 70% • Weight loss without loss of appetite 65% • Hyperkinesia and behavioral disorders 60%

  8. GD in pediatric ageMinor Clinical Features (%) • Deteriorationofschoolperformances 45% • Intolerancetoheat 40% • Palpitations 40% • Disordersofdiuresis 25% • Diarrhea 20% • Headache 20%

  9. Basedow Ophthalmopathy in pediatric age • Frequencyvarieswidely in differentseries (35-70%) • Quite rare and rarely severe in children • Especially rare disordersofocularmotility and function • More common in countrieswithhigherincidenceofyouth smoking habit Krassaset al, Eur JEndocrinol 2004, 150:407

  10. Eye symptoms • Exophthalmos (sometimes unilateral) • Eye lid retraction and lid lag • Ophthalmoplegia • Fixed gaze • Conjunctival injection and chemosis • Periorbital edema • Optic atrophy • Diplopia Only some of these symptoms resolve with regression of hyperthyroidism!

  11. Clinical examination of thyroid • Goiter is mandatory for the diagnosis of GD! • It is rarely detectable from the beginning of clinical picture (this justifies any delay in diagnosis) • It is widely diffused and symmetrical • A murmur can be detected in cases of major thyromegaly (thyroid enlargement)

  12. Clinical picture onset • Often insidious , especially in children • Initially the most typical symptoms are rare (goiter and ophthalmopathy) • Atypical symptoms are more prevalent, especially behavioral disorders, deterioration of school performances and hyperactivity syndrome

  13. Growth and pubertal development in GD • Acceleration of growth and bone maturation is commonly found • Even in pre-pubertal-onset cases, final height is not significantly impaired despite initial bone age advancement • Target heights do not differ between males and females Segni et al, Thyroid 1999,9:871 Lazar et al, JCEM 2000, 85:3678 Cassio et al, Clin Endocrinol 2006,64:53

  14. GD peculiarities in Down syndrome • No typical female predominance • More prevalent than in the general population • HT may often precede GD • Prevalence of ophthalmopathy is low • Response to drug therapy is not poor Goday-Arno et al Clin Endocrinol 2009, 71:110 De Luca et al, EJE 2010,162:591

  15. The detection of autoantibodies to thyrotropin-receptor antibody (TRAb) • Commonly used: - in clinical practice for the diagnostic assessment of GD - in differential diagnosis between toxic multinodular goiter and autonomous adenoma. • New TRAB assays have specificity and sensitivity > 90% • It could have a prognostic value, either at the onset of GD or during treatment Cardia et al, Thyroid 2004, 14: 295 Cappelli et al, Endocrin J 2007, 54:713

  16. TrAb positivity Hashimoto’s Thyroiditis Graves’ Disease

  17. Otherdiagnostictests in GD (1) • Thyroid function tests are crucial for diagnosis confirmation and in d.d. between GD and other cases of hyperthyroidism • Evaluation of anti-peroxidase antibody is not very specific, and anti-thyroglobulin even less so

  18. Other diagnositic tests in GD (2) • Echographic picture is not different from that of HT • Scintigraphy has lost much of its traditional value but may be useful with suspected toxic adenoma

  19. Neonatal GD • Incidence of < 1% of all pediatric cases • No gender predominance • Caused by transplacental passage of TSI • Clinical signs: tachycardia, hypertension, tremors and hyperphagia without weight gain • Goiter and exophthalmos may be absent • Complications: craniosynostosis and mental retardation • Spontaneous resolution after 3-4 months

  20. Subclinical hyperthyroidism • More frequent in older patients • The only biochemical sign is the suppression of TSH with normal FT4 and FT3 values • Increased risk of osteopenia and atrial fibrillation • Spontaneous remission in 40% of cases • Antithyroid therapy is justified in only the patients aged > 65 yr and in those with cardiovascular and/or osteoporosis problems Ginsberg, Can Med Ass J 2003, 4:168

  21. Hashitoxicosis • Not a disease in itself but is the hyperthyroid phase of HT • Detectable in 10-15% of all cases at onset of HT • Short duration (usually< 6 months) • Concurrent with an increase in TPOA and TGA and only rarely in TRAB • Generally auto-resolution occurs, developing into euthyroidism or hypothyroidism • Responds to antithyroid therapy

  22. Toxic adenoma • Very rare in pediatric age • Mostly benign (not always!) • Hashitoxicosis can present in a biochemical fashion that is similar to Graves disease • Negative autoimmunity • Typical scintigraphic image

  23. Other rare causes of hyperthyroidism • Exogenous hyperthyroidism • Hyperthyroidism in McCune Albright syndrome (MAS) • Jod-Basedow thyrotoxicosis • HCG producing tumors • TSH-secreting pituitary tumor

  24. GD Therapy (1) • In our very recent multicenter experience methimazole treatment (initial and maintenance dosages 0.46±0.1 and 0.15±0.03 mg/kg/day, respectively) induced a significant remission rate even during the first therapeutical cycle • The prevalence of relapse rates after withdrawal of the 1° methimazole cycle was relatively high (31.2%) and further pharmacological cycles were needed in most cases De Luca et al, EJE 2010:162:591

  25. GD Therapy (2) • Persistent remission rates after prolonged methimazole withdrawal were 26.7% • Non-pharmacological therapies were needed in 11% of cases • Definitive remission rates after at least 2 years from withdrawal or after non-pharmacological therapies were obtained in 37.7% of cases De Luca et al, EJE 2010:162:591

  26. Conclusions • In young patients, methimazole therapy may be effective to induce transient GD remission but several and prolonged therapeutical cycles are often needed • The prevalence of side effects is very low (3.8%) De Luca et al, EJE 2010:162:591

More Related