L. Ionescu, C. Ungureanu, C. Radulescu, D. Guta, I. Trifescu, C. Vulpoi

University of Medicine and PharmacyIasi-2009

Thymo-Thyroid AssociationsClinical and Pathological Aspects

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

Thymic pathology

• Thymic lymphoid hyperplasia Clinical picture – MG

• ThymomaClinical picture: - MG till 50%

- SVC syndrome

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.

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.

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.

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

Thymic lesions - endocrinopathiesThe 3rd.Surgical Unit 1980-200985 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

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/dlCT scan- diffuse compressive goiter

Myasthenia gravis

EMG-D-30%, positive antiChE test, CT scan- ? Thymic Lymphoid Hyperplasia

Treatment: neostigmine, steroids

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

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

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

CT scan view of thymic hyperplasia

Thymic scintigraphyHeterogeneous captation

Myasthenia gravis and Grave’s diseaseCase 3

MM, 54-year-old woman9-year-history Grave’s disease 2005 - thyroid profile TSH-0,1 ui/ml, fT4 - 1,2ng/mlCT scan - diffuse goiter

MG and Grave’s disease

2005 MG EMG-D-18%, CT- heterogenous normal sized thymic region

Total thyroidectomy- 2005Thymectomy - 2006 Pathology report-thymolipoma

Postoperative outcome- myasthenic symptoms controlled with small doses of neostigmine

Myasthenia gravis and Hashimoto’s disease

2 cases

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

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.

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.

Surgical specimenPreop.thymic scintigraphy

Myasthenia gravis+ Hashimoto’s thyroiditisCase 2

• ML, 28-year-old woman• 6 months history of MG-Osserman IIB, and Hashimoto’s

thyroiditis.• 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

•

CT scan aspect

Nodular thymus- Thymic Lymphoid Hyperplasia Surgical specimen

Thymic hyperplasia and Hashimoto’s disease and

haemolitic anemia1 case

Thymic hyperplasia+Hashimoto’s thyroiditis+autoimmune hemolytic anemia

GE, 19-year- old man, Hashimoto’s thyroiditis, hemolytic anaemia, (Hb-2,6g/dl), CT- thymoma, op. dec 2005,

pathology report - thymic lymphoid hyperplasia

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

remitted

Thymoma with ACTH secretion

Cushing syndrome

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

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

Myasthenia gravis and toxic multinodular goitre

1 case

AM, 46-year-old woman, 2007 multinodular goitre and myasthenia gravis

Thyroid profile (TSH-0.1 µUI/ml, fT4-1.2ng/dl), Thyroid total volume of 65.9 ml. (Prof. dr. C. Vulpoi)

Compressive goiter Retrosternal goiter

Total thyroidectomy for MNG-2007,Myasthenia gravis aggravated

Normal Chest Normal thymus

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

Repeat CT scanAntero- inferior mediastinal mass

Thymectomy, 6 months following TT, june 2008

Paramedian low retrosternal mass Well-encapsulated mass

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).

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

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

Radiotherapy 44 Gy, chemotherapy, 1 year CP+PDNPericarditis at 1 year postRxT

Remission of MG 5 years, 2008- AChE

POSTOPERATIVE THYMIC SCINTIGRAPHYLACK OF RADIOTRACER FIXATION IN THE ANTERIOR MEDIASTINUM

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

2009Inflammatory pericarditis

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 investigations fail to confirm a clinical suspicion.