Thyroid diseases

Benign and malignant disease of thyroid gland, surgical anatomy of thyroid, Hyperthyroidism, Thyrotoxicosis, Thyroid nodule, Hypothyroidism, Myxoedema, Thyroidectomy, Antithyroid drugs, carcinoma of thyroid, Papillary carcinoma, Follicular carcinoma, Medullary carcinoma, Anaplastic carcinoma, MEN-1, MEN-2a, MEN-2b, Thyroidectomy

1. Thyroid diseases By Dr. Abdul Qadeer MBBS; FCPS; FICS Assistant Professor in General Surgery King Faisal University College of Medicine Kingdom of Saudi Arabia

2. objectives Embryology & related diseases Anatomy of thyroid Physiology of thyroid hormones Benign thyroid disorders & their management Goiter & Solitary thyroid nodule & management Thyroid malignancy & management MEN 1 and MEN 2

3. 1. Embryology of thyroid Follicular cells: Thyroglossal duct as median bud in the pharynx Foramen cecum : at the base of tongue is its remnant Parafollicular (C) cells : from ultimobronchial body (neural crest) Inferior parathyroid: from 3 rd pharyngeal pouch Superior parathyroid: from 4 th pharyngeal pouch Thymus: from 3 rd pharyngeal pouch

4. Diseases of embryological maldevelopment Ectopic thyroid Ectopic parathyroid Thyroglossal cyst

5. 2. Surgical anatomy of thyroid Normal weight = 20-25 g Lobule: is the functional unit supplied by single arteriole Lobule is made up of 24-40 follicles with cuboidal epithelium Follicle contains colloid material in which thyroglobulin is stored Blood supply: rich supply by superior & inferior thyroid arteries + tracheal & esophageal arteries

6. Surgical anatomy of thyroid Extensive lymphatic drainage by different groups of lymph nodes i.e. Subcapsular lymph nodes Paratracheal nodes Nodes on superior & inferior thyroid veins (Level VI) Deep cervical nodes (Level II, III, IV, V) Mediastinal nodes (Level VII)

7. Relations of thyroid gland Recurrent laryngeal nerves Superior laryngeal nerves Thyroid arteries: superior & inferior Thyroid veins: superior, middle & inferior IJVs Carotid arteries Parathyroid glands Thymus Lymph nodes

8. 3. Physiology of thyroid hormones Tri- iodothyronine (T3) and Thyroxine (T4) are formed by: Iodide trapping Oxidation of iodide to iodine Binding of iodine to tyrosine = monoiodotyrosine MIT + MIT = DIT MIT + DIT = T3 DIT + DIT = T4 Calcitonin from parafollicular cells

9. Serum Transport proteins Albumin Thyroxine - binding globulin (TBG) Thyroxine - binding prealbumin (TBPA) Small amounts of free (unbound) hormones are biologically active Free T4 = 0.03% of total circulating hormone Free T3 = 0.3% of total circulating hormone T3 (& RT3) is quick acting (within few hours) T4 is slow acting (4-14 days)

10. Parathyroid hormone ( pth ) Secreted by parathyroid glands Released in response to low serum calcium or high serum magnesium level Functions include: Activates osteoclasts to reabsorb bone Increases Ca ++ reabsorption from urine Renal activation of vitamin D Increases gut absorption of Ca ++ Increases renal excretion of phosphate

11. The pituitary thyroid axis Thyrotrophin releasing hormone (TRH) is secreted by hypothalamus. It stimulates TSH Thyroid stimulating hormone (TSH) is secreted by anterior pituitary, depends upon the circulating level of thyroid hormones TSH is controlled by negative feedback mechanism

12. Treatment by thyroid hormones T4 replacement dose = 0.15 mg OD T4 suppressive dose = 0.2 mg OD T3 suppressive dose = 20µg TDS TSH (recombinant human) is used to maximize radioactive iodine uptake as an alternative to thyroid hormone withdrawal

13. 4. Benign thyroid disorders & their management Benign thyroid disorders include: Hypothyroidism: Infantile (cretinism) and adult ( myxedema and dyshormonogenesis ) Goitre (Thyroid enlargement) Hyperthyroidism

14. Fetal/infantile hypothyroidism (cretinism) Inadequate thyroid hormone production during fetal & neonatal development Endemic cretinism: due to dietary iodine deficiency Sporadic cretinism: may be due to ( i ). An inborn error of thyroid metabolism (ii). Complete or partial agenesis of the gland

15. Clinical features of cretinism Hoarse cry Macroglossia Umbilical hernia

16. Management of cretinism Immediate diagnosis & treatment with thyroxine is must to prevent physical & mental under-development Iodized salt in sporadic cases Biochemical screening of neonates using TSH & T4 assays on a heel-prick blood sample Monitoring of anti-thyroid drugs in women under treatment No radioactive iodine in pregnancy

17. Adult hypothyroidism SIGNS: Bradycardia Cold extremities Dry skin & hair Periorbital puffiness Hoarse voice Bradykinesis , slow movements Delayed relaxation phase of ankle jerk SYMPTOMS: Tiredness Mental lethargy Cold intolerance Weight gain Constipation Menstrual disturbance Carpal tunnel syndrome Myxoedema = Severe thyroid failure

18. Treatment of adult hypothyroidism Low T3 & T4 levels High TSH level High serum level of TPO antibodies: autoimmune disease Oral thyroxine 0.10 – 0.20 mg /day is curative 0.05 mg / day replacement dose T3 20 µg three times a day for rapid response

19. Myxoedema Severe hypothyroidism S/S: Typical facial appearance S upraclavicular puffiness M alar flush Y ellow tinge of the skin

20. Myxoedema coma Characterized by: Altered mental state Hypothermia Precipitating medical condition e.g. cardiac failure or infection High mortality Treatment: Bolus of 0.50 mg of T4 or 10 µg of T3 i /v or orally every 4-6 hours Slow warming of the patient Antibiotics Hydrocortisone

21. Primary or atrophic myxoedema An autoimmune disease like Hoshimoto’s thyroiditis , but without goitre formation

22. dyshormonogenesis Genetic deficiencies in the enzymes controlling the synthesis of the thyroid hormones e.g. TPO Usually autosomal recessive pattern Pendred syndrome: TPO deficiency leads to goitre associated with severe sensorineural hearing impairment and abnormality of bony labyrinth observed on the CT examination of the temporal bones

23. 5. Goiter & Solitary thyroid nodule & management Generalized enlargement of the thyroid gland Discrete swelling (nodule) in one lobe or Dominant swelling

24. Classification of thyroid swellings No Simple ( Euthyroid ) Toxic Neoplastic Inflammatory 1 Diffuse hyperplastic Physiological Pubertal Pregnancy Diffuse (Graves’ disease) Benign Autoimmune Chronic lymphocytic Hoshimoto’s disease 2 Multinodular Multinodular Malignant Granulomatous i.e. De Quervain’s thyroididtis 3 Toxic adenoma Fibrosing i.e. Riedel’s thyroididtis 4 Infective i.e. Acute (Bacterial, viral Subacute Chronic (TB, Syphilis) 5 Other i.e. amyloid

25. Simple goitre Simple goiter may develop by the stimulation of thyroid gland by TSH. This stimulation may be by: Microadenoma in the anterior pituitary Chronically low circulating thyroid hormones Dietary deficiency of iodine (endemic). Daily iodine requirement is 0.1–0.15 mg Defective hormone synthesis Other factors include growth factors and immunoglobulins

26. goitrogens Vegetables e.g. cabbage, kale, rape, which contain thiocyanate Drugs e.g. para- aminosalicylic acid (PAS), anti-thyroid drugs Large quantities of iodides

27. investigations Thyroid function tests X-ray thoracic inlet & chest USS CT scan FNAC

28. Complications Tracheal compression = acute respiratory obstruction Secondary thyrotoxicosis Carcinoma

29. Retrosternal goitre It may remain symptomless May lead to complications e.g. Dyspnea Dysphagia Engorgement of facial, neck and superficial chest wall veins RL nerve paralysis

30. Prevention & treatment of simple goitre Dietary iodized salt Thyroxine 0.15-2.0 mg daily for few months may regress the goiter Surgery due to: Cosmetic grounds Pressure symptoms Patient anxiety Retrostrenal goitre

31. Surgery of goitre The choice of surgical treatment in multinodular goiter may be: Total thyroidectomy Subtotal thyroidectomy leaving up to 8 g of normal tissue Near-total thyroidectomy leaving up to 2 g (Dunhill procedure) Lobectomy with isthmusectomy

32. Management of clinically discrete swelling Clinically discrete swelling may be: Isolated or solitary (70%) Dominant (30%) 15% of isolated swellings prove to be malignant 30-40% are follicular adenomas Remaining are cysts, thyroididtis or colloid degeneration

33. investigations TSH & free T3, T4 Autoantibodies Isotope scan (if there is toxicity & nodularity). It may show hot (overactive), warm (active) or cold (inactive) areas USS: shows subclinical nodularity & cysts May show signs of neoplasia e.g. Microcalcification Increased vascularity Macroscopic capsular breach Nodal involvement

34. fnac Following conditions can be diagnosed by FNAC: Colloid nodules Thyroiditis Papillary carcinoma Medullary carcinoma Anaplastic carcinoma Lymphoma Note: FNAC cannot distinguish between a benign follicular adenoma & follicular carcinoma (i.e. by capsular & vascular invasion)

35. fnac

36. Classification of FNAC reports Non-diagnostic Thy 1 Non-diagnostic cystic Thy 1c Non-neoplastic Thy 2 Follicular Thy 3 Suspicious of malignancy Thy 4 Malignant Thy 5

37. Radiology & other Chest and thoracic inlet x-rays CTS MRI PET, to localize disease which does not take up radioiodine Laryngoscopy: vocal cords (medicolegal) Core biopsy: may cause pain, bleeding, tracheal damage, RL nerve damage Serum calcium estimation

38. Core biopsy needle

39. Hyperthyroidism / thyrotoxicosis Clinical types are: Diffuse toxic goiter (Graves’ disease) Toxic nodular goiter Toxic nodule Hyperthyroidism due to rare causes

40. Hyperthyroidism / thyrotoxicosis SYMPTOMS: Tiredness Emotional lability Heat intolerance Weight loss Excessive appetite Palpitations SIGNS: Tachycardia Hot, moist palms Exophthalmos Eyelid lag/retraction Agitation Goitre with bruit

41. Diffuse toxic goiter (Graves’ disease) Primary thyrotoxicosis The goiter is diffuse & vascular Affects younger women usually Family history in 50% cases Autoimmune disease Abnormal thyroid stimulating antibodies (TSH- RAb ) that bind to TSH receptor sites & produce a disproportionate and prolonged effect

42. Toxic nodular goiter & toxic adenoma Secondary thyrotoxicosis The goiter is nodular A simple nodular goiter is present for a long time before the hyperthyroidism The nodules are inactive & the internodular thyroid tissue is overactive If a nodule becomes overactive, it is toxic adenoma (autonomous) Toxic adenoma hypertrophy and hyperplasia is not due to TSH- Rab

43. Symptomatology of toxic goitre Primary thyrotoxicosis: Goitre diffuse & vascular Onset is abrupt Associated signs include orbital proptosis, ophthalmoplegia , pretibial myxedema Secondary thyrotoxicosis: Goitre is nodular Onset is insidious Cardiac signs are frequent e.g. cardiac failure or atrial fibrillations A fast heart rate, which persists during sleep is characteristic

44. Histology of normal gland & toxic goitre Normal gland: acini lined with flattened cuboidal epithelium and filled with homogeneous colloid Hyperthyroidism: hyperplasia of acini, lined by high columnar epithelium

45. Treatment of thyrotoxicosis Antithyroid drugs Surgery Radioiodine

46. Antithyroid drugs Carbimazole 10 mg TDS to QID Propylthiouracil β-adrenergic blockers e.g. propranolol (40 mg TDS), nadolol (160 mg OD) Iodides Advantages: No surgery, no radioactive material Disadvantages: prolonged treatment, 50% failure rate, dangerous drug reactions e.g. agranulocytosis or aplastic anemia

47. Thyroid surgery Advantages: G oiter is removed C ure is rapid and high Disadvantages: R ecurrent of thyrotoxicosis (5%) in subtotal thyroidectomy Hypoparathyroidism N erve injury Scar T hyroid failure

48. Radioiodine therapy Advantages: No surgery No prolonged drug therapy Disadvantages: Availability of isotope facility Avoid pregnancy (Absolute contraindication) Avoid close physical contact especially children (Relative contraindication) Eye signs may be aggravated

49. Posthyroidectomy complications Hemorrhage Tension hematoma Subcutaneous hematoma Respiratory obstruction ( Tracheomalacia ) RL nerve paralysis & voice change Thyroid insufficiency Parathyroid insufficiency Toxic crisis (storm) Wound infection Hypertrophic or keloid scar Stitch granuloma

50. 6. Thyroid malignancy & management Tumors of thyroid may be benign or malignant

51. Classification of thyroid neoplasms Benign Malignant Follicular adenoma Primary Follicular (20%) Papillary (60%) Anaplastic (10%) Medullary (5%) Lymphoma (5%) Secondary Metastatic Local infiltration

52. Papillary carcinoma Most common among the carcinomas of thyroid May be multifocal in one lobe or both Lymphatic spread is common Blood-borne spread unusual May infiltrate to esophagus, trachea or sternothyroid muscle Orphan Annie-eyed nuclei: characteristic pale, empty nuclei visible histologically as papillary projections Occult carcinoma ( microcarcinoma )

53. Histology of papillary carcinoma

54. Follicular carcinoma Macroscopically encapsulated but microscopically invades the capsule and the vascular spaces Rarely multifocal Lymph node involvement is less common Blood-borne metastasis is more common Mortality rate is twice as compared with the papillary carcinoma

55. Follicular carcinoma (Vascular invasion)

56. Hurthle cell tumor Variant of follicular carcinoma Contain Hurthle / Askanazy cells histologically Poor prognosis

57. Treatment of DTC Treatment of differentiated thyroid cancer (DTC) depends upon: Preoperative diagnosis or After diagnostic lobectomy Total thyroidectomy ±Node dissection Radioiodine to detect and ablate metastases Thyroglobulin monitoring Thyroxine 0.1-0.2 mg daily to suppress endogenous TSH

58. Thyroglobulin as tumor marker Very important in the follow-up and detection of metastatic disease after surgery of DTC Endogenous TSH production must be suppressed by T4 Surgery or therapeutic radioiodine is then indicated Presence of antithyroglobulin antibodies interferes with and invalidates thyroglobulin as serum marker for recurrence Careful clinical palpation of neck is important in such cases

59. Undifferentiated (Anaplastic) carcinoma Occurs mainly in elderly women Local infiltration is early feature Lymphatic & blood-borne spread is common Extremely lethal tumor & survival is calculated in months Usually needs palliative treatment by surgery or radiotherapy. Chemotherapy is ineffective Surgery for complications e.g. tracheal decompression

60. Medullary carcinoma Tumor of parafollicular (C cells) 10-20 % are familial, (affects children & young) Resembling carcinoid tumor Has characteristic amyloid stroma Levels of calcitonin & CEA are usually high

61. Medullary carcinoma Diarrhea occurs (30% cases) due to 5-HT and prostaglandins produced by the tumor cells May occur as part of MEN-2A or MEN-2B Calcitonin is its tumor marker Tumors are not TSH dependent, don’t take up radioiodine

62. Treatment of medullary carcinoma Total thyroidectomy Prophylactic or therapeutic resection of cervical lymph nodes Preoperatively, pheochromocytoma must be excluded by measuring urinary catecholamines

63. Lymphoma of thyroid May be isolated tumor of thyroid or part of widespread malignant lymphoma disease May cause tracheal compression, managed by isthmusectomy Very good response to radiotherapy in local disease Worse prognosis as part of generalized lymphoma disease

64. 7. Men-1 and men- 2 Multiple endocrine neoplasia are inherited syndromes Characterized by a combination of benign & malignant tumors in different endocrine glands Two types i.e. MEN-1 and MEN-2

65. Multiple endocrine neoplasia type 1 Also called Wermer’s syndrome Characterized by triad of tumors Tumor of anterior pituitary gland ( prolactinomas ) Hyperplasia of parathyroid causing primary hyperparathyroidism ( pHPT ) Pancreatico -duodenal endocrine tumors e.g. gastrinoma , insulinoma , VIPoma , glucagonoma , somatostatinoma

66. Multiple endocrine neoplasia type 2 Three subtypes Familial medullary thyroid carcinoma (FMTC) MEN-2a and MEN-2b

67. Multiple endocrine neoplasia type 2 MEN-2a ( Sipple’s syndrome): characterized by the combination of: MTC pHPT Pheochromocytoma (Bilateral) MEN-2b: characterized by MTC, pHPT , Pheochromocytoma Neuromas of lips, tongue, eyelids Marfanoid habitus

68. reference Bailey & Love’s short practice of surgery, 26 th edition, chapter 51 : pages 741-777

69. The end