Thymo-Thyroid Associations Clinical and Pathological Aspects

1. Thymo-Thyroid AssociationsClinical and Pathological Aspects L. Ionescu, C. Ungureanu, C. Radulescu, D. Guta, I. Trifescu, C. Vulpoi University of Medicine and Pharmacy Iasi-2009

2. Association of thyroid and thymic lesions • Hyperthyroidism - Myasthenia gravis, is sporadically reported in the literature • Both conditions can aggravate each other • Appropriate management is made by a multidisciplinary team judging on each individual case. • ? What condition must be treated surgically first or if both conditions require surgery at the same time is still a matter of debate

3. Thymic pathology • Thymic lymphoid hyperplasia Clinical picture – MG • Thymoma Clinical picture: - MG till 50% - SVC syndrome

4. Myasthenia gravis and hyperthyroidism • Present mainly in autoimmune thyropathy such as Grave’s disease. • Usually myasthenia gravis is secondary to hyperthyroidism due to thymus hyperplasia • An adequate anti-thyroid drug treatment or surgery result in remission of thymic hyperplasia.

5. Myasthenia gravis and hyperthyroidism • Murakami M. et al. demonstrated the presence of thymic hyperplasia in Grave’s disease patients. • Calculate on CT scan images the size and density of the thymus on untreated and treated Grave’s disease patients. • The conclusion was thymic hyperplasia regresses in patients treated either with anti-thyroid drugs or by total thyroidectomy.

6. Myasthenia gravis and hyperthyroidism • Yamanaka et al.- a case of Grave's disease associated with a mediastinal mass in which CT scan and MRI were suggestive for a thymoma. • The patient underwent total thyroidectomy and thymectomy at the same time. • Pathology report showed a thymic hyperplasia.

7. Myasthenia gravis and hyperthyroidism • Nakamura T. et al. demonstrated by mediastinal biopsy, the presence of thyrotropine receptors in the hyperplasic thymus of a young patient with hyperthyroidism. • The presence of these receptors raises the hypothesis that the thymus is also a target organ for the autoimmune aggression in Grave's disease

8. Thymic lesions - endocrinopathies The 3rd.Surgical Unit 1980-2009 85 thymopathies - 9 cases associated lesions • MG- Grave’s disease-3 cases • MG- Hashimoto’s disease-2 cases • Thymic HP-Hashimoto’s- hl. anaemia-1 case • Thymic carcinoma- Cushing sdr.- 1 case • MG (Thymoma) - Toxic MN goiter- 1 case • MG (Thymoma) - post rTh. Myxedema- 1case

9. Grave’s disease and Myasthenia gravis-case 1 JM, 33-year-old woman, The 3 rd Surgical Unit – 200410-year history of neglected Grave’s disease, anaphylactic shock to anti-thyroid drugs 2 weeks history of progressive myasthenia gravis Thyroid gland volume - 28.9 ml, TSH-0.2mU/l, Ft4-2.6nmol/dl CT scan- diffuse compressive goiter

10. Myasthenia gravis EMG-D-30%, positive antiChE test, CT scan- ? Thymic Lymphoid Hyperplasia Treatment: neostigmine, steroids

11. Therapeutic decision • Considering MG secondary to hyperthyroidism • Total thyroidectomy after 10 days Lugol preparation • Medical treatment of MG and reassessment after 6 months • Thymic hyperplasia might regress after adequate treatment of Grave’s disease

12. Postoperative outcome • Total thyroidectomy - august 2004 • Pathology report - bilateral micropapillary carcinoma on Basedow’s disease • Acute respiratory failure - prolonged mechanical ventilation • Intensive care of myasthenic severe status: anticholinesterase, steroids, plasmapheresis • Cardio-respiratory arrest on 28th post-op. day

13. Myasthenia gravis and Grave’s disease-case 2 • Avadanei M.Ileana, 42-year-old woman, • Grave’s disease- operated – oct. 2007 - total thyroidectomy • Associated MG Osserman IIB - EMG- D-20%, CT torace – thymic hyperplasia • Thymic scintigraphy – heterogenous captation • Neostigmine 3tb./day - good response

14. CT scan view of thymic hyperplasia

15. Thymic scintigraphyHeterogeneous captation

16. Myasthenia gravis and Grave’s diseaseCase 3 MM, 54-year-old woman 9-year-history Grave’s disease 2005 - thyroid profile TSH-0,1 ui/ml, fT4 - 1,2ng/ml CT scan - diffuse goiter

17. MG and Grave’s disease 2005 MG EMG-D-18%, CT- heterogenous normal sized thymic region Total thyroidectomy- 2005 Thymectomy - 2006 Pathology report-thymolipoma Postoperative outcome- myasthenic symptoms controlled with small doses of neostigmine

18. Myasthenia gravis and Hashimoto’s disease 2 cases

19. Myasthenia gravis+Hashimoto’s, case 1UD, 54-year-old woman • 4 years history of progressive MG- dg.2004 • EMG-D-20% , repeat EMG-D-25% • CT( 2005)- ant-sup. mediastinum with a fibrous - fatty tissues • Tretment-mestinon 60mg.de 3/zi, PDN-10mg every 2 days, some improvement • 2005- Hashimoto’s thyroiditis - ab. antiTPO-556UI/ml, compensated with 75ug/day Euthyrox: TSH-2uUI/ml., Ft4-1,2ng/dl • Myasthenia gravis got worse with increasing doses of AChE and CS. • CT 2008 – heterogenous thymic space. • Thymic scintigraphy - july 2008- discrete hyperfixation of 99mTc Tetrofosmin, heterogenous, with vertical trajectory in the left paramedian anterior mediastinum

20. Outcome • Op. july 2008- extended thymectomy through longitudinal sternotomy • Pathology report- atrophic thymus with areas of folicular hyperplasia . • Post-op.course- aggravating with ARF – prolonged mechanical ventilation. • Intensive care treatment: ACE, CS, PPH without result.

21. Post operative complications • Tracheostomy at 5 weeks postop. • Ventilator dependent infection, • Multiple eschars, • Axillary vein thrombosis. • Eso-tracheal fistula • Perforated corneal ulcer LE • MSOF - death - septembre 2008.

22. Surgical specimenPreop.thymic scintigraphy

23. Myasthenia gravis+ Hashimoto’s thyroiditisCase 2 • ML, 28-year-old woman • 6 months history of MG-Osserman IIB, and Hashimoto’sthyroiditis. • MG-EMG-D-62%, + anticholinesterase test, CT- nodular thymus (14/11 mm, 14/18 mm) • Hashimoto’s - AAT-TPO-76,7 (N<50) • Thymectomy - april 2008 • Pathology- TLH, complete remision

24. CT scan aspect

25. Nodular thymus- Thymic Lymphoid Hyperplasia Surgical specimen

26. Thymic hyperplasia and Hashimoto’s disease and haemolitic anemia 1 case

27. Thymic hyperplasia+Hashimoto’s thyroiditis+autoimmune hemolytic anemiaGE, 19-year- old man, Hashimoto’s thyroiditis, hemolytic anaemia, (Hb-2,6g/dl), CT- thymoma, op. dec 2005, pathology report - thymic lymphoid hyperplasia

28. GE-Hashimoto’s thyroiditisPost operative course- hl.anaemia remitted

29. Thymoma with ACTH secretion Cushing syndrome

30. Thymoma+ Cushing sdr. • G. M. C., 32-year-old woman , • Diagnosed- Cushing sdr.- july 2008 (dr. C. Ungureanu) • ACTH, plasmatic and urinary cortizol – high levels (ACTH-292pg/ml. basal plasmatic cortizol -582ng/ml and 590ng/ml at 23.00 PM, free urinary cortizol -532 mg/24 h.) • DZ tip II • hipoKemie, metabolic alcalosis • Abdominal CT scan, pituitary gland MRI, thyroid USS – WNL • Calcitonin, normal, CXR-normal

31. GM, 32-year-old woman, Cushing sdr. , ACTH -292pg/ml.(n<46). CT- anterior mediastinal mass, pericardial adhesion,Op. sept. 2008-thymectomy+pericardectomy+mediastinal pleurectomy. Histology: well-differentiated thymic neuroendocrine carcinoma, transcapsular invasion, pT2NxMx, Immunhistochemistry: NSE, chromogranin, synaptophizin- intense positive, MNF116-moderate positive, Ki 67-10%, post.op. ACTH-37pg/ml. Chushing clinical aspect remitted

32. Myasthenia gravis and toxic multinodular goitre 1 case

33. Retrosternalgoiter AM, 46-year-old woman, 2007 multinodular goitre and myasthenia gravisThyroid profile (TSH-0.1 µUI/ml, fT4-1.2ng/dl), Thyroid total volume of 65.9 ml. (Prof. dr. C. Vulpoi) Compressive goiter

34. Normal thymus Total thyroidectomy for MNG-2007,Myasthenia gravis aggravated Normal Chest

35. Thymic scintigraphyHypercaptation of 99mTc-tf. consistent with a thymoma

36. Well-encapsulated mass Repeat CT scanAntero- inferior mediastinal massThymectomy, 6 months following TT, june 2008 Paramedian low retrosternal mass

37. Discussions • In this case the thyroid lesion was more evident, and thus first treated while MG was erroneously considered secondary to hyperthyroidism and consequently likely to remit following total thyroidectomy. • On thymic scintigraphy, the hyperfixation in lower anterior mediastinum raised the suspicion of thymoma, • Pathology report of the surgical specimen (mixt thymoma - Muller-Hermelink classification or AB type - WHO classification, with capsular microscopic invasion, Masaoka II stage).

38. Myasthenia gravis, thymomaInflammatory pericarditis • C T, 64-year-old woman • 8 year-history of MG, CT- evident tumour • op. 2002-thymectomy+pleurectomy • Pathology report- Invasive thymoma-Masaoka III • Post-operative radiotherapy 44 Gy, • Chemotherapy 1 year- CPh+PDN • 2003- post-radiotherapy myxedema

39. CT, 60 years old, thymoma+MG, Oss.IV, op. 2002, Lymphocitic thymoma (type I malignant thymoma)-Masaoka II ( well encapsulated but microscopic capsular invasion), adhesions to left M. pleura which was resected

40. Radiotherapy 44 Gy, chemotherapy, 1 year CP+PDNPericarditis at 1 year postRxTRemission of MG 5 years, 2008- AChE

43. POSTOPERATIVE THYMIC SCINTIGRAPHYLACK OF RADIOTRACER FIXATION IN THE ANTERIOR MEDIASTINUM

44. CT aspects-2009The absence of the tumour recurrence, pericarditis

45. 2009Inflammatory pericarditis

46. Conclusions • Hyperthyroidism may be associated with: • thymic hyperplasia, in which no surgical action should be taken regarding the thymus, • thymoma, in which surgical treatment is essential. • The thymic 99mTc tetrofosmin scintigraphy can be efficient in diagnosing the thymic lesions when conventional imaging investigationsfail to confirm a clinical suspicion.