بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم

2. Management of toxic goiter Review Article By Dr. NABILYOUSEFF SALAH EL DIN ABOU EL DAHAB Lecturer of General Surgery Sohag Faculty of Medicine . South Valley University . 2003 - 1424

3. Introduction • Thyrotoxicosis is the clinical syndrome of increased systemic metabolism that results when the body is exposed to excessive amounts of thyroid hormone in the circulation . • Thyrotoxicosis has many adverse effects on different systems of the body . • It is usually not difficult to make the diagnosis, which has many recent investigations, but the problem is how to manage and cure the patient .

4. Although effective treatments for hyperthyroidism are available , non is perfect and no single treatment regularly results in permanent euthyroidism, but the options differ about the indications for them. • Particularly, with respect to Graves’ disease, what is needed is a therapy directed at modulating the disease process itself rather than reducing synthesis and secretion of thyroid hormones.

5. Historical Background • The first successful thyroidectomy was done by Moorish physician Aboucasis, أبوالقاسم الزهرائي in Zahra Arab city, of Spain about A.D. 952. • In the mid-nineteenth century, Kocher (1841 – 1917) advocated meticulous surgery that spared the parathyroid glands and the recurrent laryngeal nerve. So, the surgical mortality deceased from more than 50% to 0.2%. • Thyrotoxicocis has been known since its original descriptions by Parry in 1786. The disease is known as Graves’ disease after Robert Graves, a physician from Ireland, who described three patients in 1835 .

6. Surgical anatomy (Grant 2000)

7. Blood supply (Grant 2000)

8. Blood supply • Arterial supply: • four major arteries: • The paired superior thyroid arteries . • The paired inferior thyroid arteries. • Occasionally the thyroidea ima . • Venous Supply: • Two superior thyroid veins  to the internal jugular vein . • Two middle thyroid veins  to the internal jugular vein . • Two inferior thyroid veins  to the brachio-cephalic vein .

9. Histology of normal gland

10. Thyroglobulin Synthesis by thyroid follicle cells

11. This figure shows the normal feedback control loop that regulates thyroid hormonesecretion

12. Tests of thyroid functionLaboratorytests • Through Rodioimmuno Assay : Serum T.S.H. [ N. range : 0.15  5 m U / L ] Total serum thyroxin (TT4) [ 55  150 nmol /L ]  Free thyroxin (FT4) [ range 12  28 pmol / L] Total triiodothyronine.(TT3 ,1.5  3.5 nmol/L] Free triiodothyronine . [FT3 , 3  9 pmol / L ]

13. Specific thyroid function tests  Rodioactive iodine uptake test [N. = 33%] [range 15 to 45 % in 24 hours ] . Thyrotropin stimulation test . Thyroid suppression test.(T3 suppression test). Specific thyroid antibodies : Thyroid stimulating lmmunoglohulins [ TSIs ] (TsAb). T.S.H. binding inhibitor [ TB I ] . Current specific test: Immunometeric Assays , using monoclonal antibodies for detection of serum TSH. [ second and third generation ] to detect value < 0.005 mU/ml . Imaging studies: Technetium 99 Pertechnetate ( 99TcM)scintiscan .     

14. Thyrotoxicosis Hyperthyroidism: • Although the terms hyperthyroidism and thyrotoxicosis are frequently used interchangeably, in the strictest sense, hyperthyroidism refers to hyperfunction of the thyroid gland, whereas thyrotoxicosis refers to any state characterized by thyroid hormone excess, including ingestion of excess thyroid hormone and thyroiditis .

15. Common Causes of Hyperthyroidism ( Franklyn 1994)

16. Rare Causes of Hyperthyroidism ( Franklyn 1994)

17. Graves’ disease [Diffuse toxic goiter] Epidemiology: • In The U.S.A., Graves’ disease is the most frequent cause of thyrotoxicosis, accounting for 60 – 90 % of cases. For women, incidence ratio is 1 : 1000. Prevalence is estimated at about 1%. • Internationally : Worldwide, the highest incidence occurs in young, white females carrying the susceptible human leukocyte antigen (HLA) haplotype.

18. Pathophysiology and pathogenesis : (1) Graves’ disease : is an autoimmune disease caused by the presence of thyroid-stimulating immunoglobulins (TSIs) in the plasma. (2) Cloning theory : Graves' disease, resulted from cloning of the thyrotropin receptor ( T.S.H) and a genetically programmed presentation of a thyroid-specific antigen and the better knowledge of the interactions between these receptors, thyroid antigens and the immune system, may lead to optimal treatment. (3) Genetic factors: Risk for Graves’ disease is increased in Japanese families with haplotype HLA-BW36, and in Chinese families with haplotype HLA-BW46 .

19. Pathology • Macroscopically, the thyroid gland in patients with Graves’ disease is diffuse and smoothly enlarged, and the gland’s vascularity is also increased • Microscopically, the gland is hyperplastic, and the epithelium is columnar, with minimal colloid present. The nuclei exhibit mitosis, and papillary projections of hyperplastic epithelium are common. There may be aggregates of lymphoid tissue, and vascularity is markedly increased .

20. Clinical picture : • - Diffuse goiter is the major manifestation of Graves’ disease. Other features are ophthalmopathy, dermopathy, and acropachy. • - These manifestations do not necessarily occur simultaneously, and they can run an independent course .

21. Clinical picture : • Thyrotoxic symptoms include the following: • Nervousness (99%), Sweating (91%), Heat intolerance (89%), Palpitations (89%), Fatigue (88%), Weight loss (85%) andMenstrual irregularities. • Signs specific to Graves’ disease: These manifestations might occur together or independently. • Diffuse symmetrical thyroid enlargement. • An audible bruit can be heard over the gland in 50% of patients. • Infiltrative ophthalmopathy - Occurs in 20-40% of cases; often bilateral, but unilateral in 5-14% of cases. • Dermopathy and acropachy : Occurs in 5 – 10 % of cases.

22. Toxic goiter General Look of Patient

23. Bilateral exophthalmos Unilateral exophthalmos

24. Plummer’s disease(toxic nodular goiter ( • Toxic nodular goiter, also known as Plummer’s disease, is a consequence of one or more thyroid nodules trapping and organifying more iodine andsecreting more thyroid hormone in-dependently of TSH control. Toxic nodular goiter occurs most often in areas of endemic goiter . • It is not accompanied by the extrathyroidal manifestations . • History is of gradual onset and progressive course • Age of patients > 40 years .

25. Toxic nodule A solitary overactive nodule : It is autonomous and its hypertrophy and hyperplasia are not due to thyroid stimulating antibodies. Because T.S.H. secretion is suppressed by the high level of circulating thyroid hormones , the normal thyroid tissue surrounding the nodule is itself suppressed and inactive.  

26. The management of hyperthyroidism ( Franklyn 1994)

27. Investigations of Hyperthyroidism : • 1- Laboratory investigations . • 2- Specific thyroid antibodies . • 3- Radioactive iodine uptake . • 4- Radiography . • 5- Imaging studies .

28. (1) : Laboratory investigations 1- Thyrotropin (T.S.H.) - In cases of (Graves’ disease, toxic nodular goiter), TSH levels will be accordingly low < 0.1 and may be undetectable . - Immunometric assays , using monoclonal antibodies target two separate sites (increasing specificity) on the TSH molecule. One monoclonal antibody is labeled with a nonradioactive marker, allowing readings with an accuracy down to 0.005 mU/ml .

29. Laboratory investigations • 2- Total T4 > 15nmol /L . • 3- Free T4 > 28 pmol /L is more specific because of limitation of total T4 , and to avoid False high results (pregnancy , estrogen therapy ) and False low results (hypo proteinaemia , nephrotic syndrome). • 4- Total T3 > 3.5 nmol/L . • 5- Free T3 > 9 pmol /L . • Free T3 is most useful in cofirming the diagnosis of early hyper thyroidism, in which levels of free T4 and free T3 rise before total T4 and total T3 .

30. Investigations of Hyperthyroidism : • 2- Specific thyroid antibodies : Through receptor assay and in vitro slice assay, high titre of (TsAb) & (TBI) was found in 60-80 % of cases of Graves’ disease. • 3- Radioactive iodine 131I uptake : It is indicated if the T3 and the T4 are at the upper limit of normal. If it is increased  (45 - 90%), It is diagnostic. Radioactive iodine uptake is high in Graves disease, high or normal in toxic multinodular goiter, and low in thyroiditis. - Usually, it is performed to differentiate between Graves’ disease, toxic multinodular goiter, and thyroiditis and to calculate the dose of radioactive iodine for treatment.

31. Investigations of Hyperthyroidism : • 4- Radiography : chest X ray and radiographyof thoracic inlet views . • 5- Imaging studies : • A- Radioisotope 99TcM Scanning : diffuse in Graves’ disease , focal in toxic nodule , multi focal in toxic nodular goiter. • B- Ultrasonography : for detection of non palpable nodules and for differentiating solid from cystic nodule. • C- CT Scanning : for Assessment of invasion of surrounding structures in large nodular goiter. • E - Colored Doppler sonography : it is indicated in very small gland or graves’ disease without enlarged gland . • D - M . R . I .

32. C T scanning Tracheal deviation Toxic nodular goiter

33. Ultrasonography 99TcM isotope scanning Toxic nodular goiter

34. Rich diffuse vascularization Woman, 54 y.o. Colordoppler ultrasound scan of the left lobe of the thyroid: rich diffuse vascularization.High systolic peak speed ( 2.28 m/s') in the superior thyroid artery. (Weetman 2000)

35. Treatment of Hyperthyroidism • There are three principal treatment : • medical treatment, radioiodine and surgery - all of which are effective, but opinions differ about the indications for them because no single treatment regularly results in permanent euthyroidism. • medical treatment Includes: antithyroid drugs, ß-adrenergic – antagonist drugs, Iodine-contaning compounds and miscellaneous agents.

36. Medical Treatment of Hyperthyroidism

37. Antithyroid Drugs  Indications: Mild and early hyperthyroidism . Young age < 40 years . Pregnancy . Active exophthalmos . Postoperative recurrence .

38. - Serious side effects occur in approximately 3 of every 1000patients . - Agranulocytosis is an absolute contraindication to further antithyroid-drug therapy, and treatment with radioiodine should be given.- Jaundice, hepatitis or vasculitis, and lupus-like syndromes are other rare but serious complications that make the discontinuation of therapy mandatory. * Side Effects of antithyroid drugs

39. * Side Effects of antithyroid drugs

40. Adrenergic-Antagonist Drugs Indications & Regimens : • 1- β Adrenergic-antagonist drugs are useful adjunctive agents in patients with Graves' hyperthyroidism. • 2- They block peripheral conversion of T4, relief of symptoms caused by thyroid storm, relief of some chronic thyrotoxic symptoms. • 3- Required dose : • Propranolol : 30 – 40 mg T.D.S / day Nadolol : 80 mg once / day

41. Iodine containing compounds Indications & Regimens : • Short-term iodine therapy is useful in the preparation of patients for surgery . • It is useful after radioiodine therapy to hasten the fall in serum thyroxine and triiodothyronine concentrations to normal . • It is used in the treatment of thyrotoxic crisis. • Usual dose: 0.1- 0.3 ml T.D.S [5% iodine in 10% potassiom iodide].

42. Radioiodine Therapy  Indications : - Graves’ hyperthyroidisim patient who relapse after long term anti thyroid drug therapy . - severe thyrocardiac old patients > 40 years . - Patients suffered from severe side effect of antithyroid drugs. - Recurrent hyperthyroidisim after antithyroid drugs therapy or subtotal thyroidectomy .

43. Radioiodine Therapy Contraindications : • Pregnancy and lactation . • young age < 20 years. • Malignant ophthalmopathy . • patients with cardiac failure or arrhythmias. • Thyrotoxic crisis .

44. Radioiodine Therapy Disadvantages and complications : • The high incidence of hypothyroidisim requiring lifelong thyroxine replacement therapy, So long term follow up is essential. • The slower correction of the hyperthyroidism, so antithyroid drugs or β–blockers are used as adjunctive treatment to suppress the symptoms. • Exacerbation of thyrotoxicosis with arrhythmias ; this usually becomes apparent within 10 days and may be a particular problem in the elderly, precipitating cardiac failure or death . • Radioiodine therapy has more adverse effect on ophthalmopathy than thyroidectomy . • It has carcinogenic and teratogenic effects . • A higher relapse rate .

45. Management of ophthalmopathy • Mild ophthalmopathy: It Is managed symptomatically with use of eye lubricants, steroid eye drops , or lateral tarsorrhaphy . • Progressive disease : It may need further management that includes systemic corticosteroids, immunosuppressive therapy, retrobulbar injection of steroids and orbital decompression. - Antithyroid drugs or subtotal thyroidectomy improve the degree ofophthalmopathy.

46. Exophthalmos in Graves’ disease Image of the left eye after tarsorrhaphy.

47. Surgical treatment of graves’disease Indications : - Failure of medical treatment due to drug resistence , side effects or relapse . - Large goiter with obstructive symptoms (esophagus, Trachea, Neck veins). - Compensated thyrocardiac patients. - Pregnancy . - Mild or severe ophthalmopathy . - Patients cannot tolerate long term antithyroid drugs . - Patients refuse radioiodine therapy . - Social and economic conditions.

48. Advantages of surgery - Immediate cure of disease and decreased long term incidence of hypothyroidism. - Cure symptoms of patients and ophthalmopathy. - Postoperative recurrence is very low (5-10 %). Preoperative Preparation Alternative methods of preoperative therapy include: 1- Methimazole combined with potassium iodide (60 mg three times a day for 10days). 2- Short-term therapy with propranolol alone or with a longer-acting β-adrenergic antagonist. 3- Potassium iodide (for 10 days) in combination with propranolol.

49. Surgical options • Whether subtotal, neartotal, or total thyroidectomy should be performed is controversial. • Total or near total thyroidectomy : Unilateral total lobectomy and contralateral near total lobectomy.(more than 90% of thecontralateral lobe). This procedure is characterized by less risk of recurrence, greater risk of injury to recurrent laryngeal nerve or parathyroid glands and requiring subsequent thyroid hormone therapy. • Bilateral subtotal thyroidectomy : This procedure is more safe and easier to be done. They are characterized by less risk of injury to R.L.N and parathyroid glands and minimal risk of recurrence.

50. Surgical options  The most commonlyprocedure, and perhaps the safest in terms of morbidity, is bilateral subtotal thyroidectomy, or a total lobectomy on one side and a subtotal lobectomy on the other side (Hartley – Dunhill procedure) , leaving about 4 to 5 gm of thyroid tissue.`