Surgical management of benign multinodular goitre

According to the WHO about 200 million people are living with goitres worldwide. Of the benign cases, endemic goitres make up the bulk in iodine deficiency belts. Goitres may be simple or toxic. The aetiopathogenesis and surgical management of this condition is detailed in a practical sense in this presentation.

1. SURGICAL MANAGEMENT OF BENIGN MULTINODULAR GOITRE Dr. Alumona Christian

2. OUTLINE INTRODUCTION HISTORICAL PERSPECTIVE EPIDEMIOLOGY ANATOMY AND PHYSIOLOGY ETIOPATHOGENESIS AND CLASSIFICATION CLINICAL EVALUATION INVESTIGATIONS TREATMENT OPTIONS PRE OPERATIVE PREPARATION SURGICAL OPTIONS TECHNIQUES OF THYROIDECTOMY COMPLICATIONS EMERGING TRENDS CONCLUSION REFRENCES

3. INTRODUCTIONS Goitre refers to enlargement of the thyroid gland. Benign multinodular goitres arise from disorders of thyroid metabolism. Simple or Toxic

4. Historical perspective Goitres (L. gutter - throat): since 2700BC Hieronymus Fabricius ab Aqua- pendente (1537-1619): goitres arose from a gland Thomas Wharton (1656): thyroid gland Roger Frugardi (1170): 1 st thyroid surgery Emil Theodor Kocher (1841-1971): Nobel price C.A Theodor Billroth (1829-1894)

5. Epidemiology 200 million people have goitre (WHO) Prevalence : 21.4% (Jos, Nigeria), 23.4% (Oyo, Nigeria) Iodine deficiency commonest cause in Africa (endemic goitres: 1-90%) F:M ration- 4 :1 Simple goitres:58.9%, toxic goitres: 36.6%

6. Embryology Out-pouching of primitive foregut 3 rd week (Day 24) Medial thyroid anlage; endoderm, floor of pharyngeal anlage at base of tongue Paired lateral anlage; neuroectoderm, 4 th branchial pouch Thyroglossal duct; foramen ceacum, pyramidal lobe 5 th week: Anlages fuse Thyroid follicular cells, Parafollicular/C-cells Parathyroid glands: from 4 th and 3 rd branchial pouches

7. Gross Anatomy Bi-lobed anterior neck gland, ̴ 20g, C5-T1 Pyramidal lobe (50% of individuals) Capsules: True capsule, pre-tracheal fascia, strap muscles Relations: Anterior, posterior, post-lateral Nerves: RLNs, Sup. Laryngeal: ext. and internal Blood supply: Superior, Inferior thyroid arteries, thryroidea ima artery (10%) Venous drainage; sup., middle and inferior thyroid veins Lymph drainage: cervical LNs

8. Thyroid Histology Lobules: functional unit, containes 20-40 follicles Follicles: 3x10 6 , spherical, lined by cuboidal epithelial cells (thyrocytes) Thyroctes: secret colloids into follicular lumen under TSH influence Parafollicular/ C cells: located in the upper lobes, lie in the inter-follicular stroma and secret calcitonin

9. Thyroid Hormone Synthesis Iodine absorption: as iodides Iodide trapping: ATP dependent Na + /I - symporter Oxidation of iodides back to iodine Iodination of tyrosyl residues of thyroglobulin to form MIT & DIT under TPO Coupling to form T 4 &T 3 Secretion of Tg and its hydrolysis to release T 4 &T 3 Peripheral conversion of T4 to T3 by 5` mono-de- iodinase in pituitary, liver, kidneys % muscles

10. Control of thyroid hormone Hypothalamo -pituitary-thyroid axis Auto regulation Independent of TSH In iodine excess: uptake, synthesis and secretion are suppressed In iodine deficiency: preferential synthesis of T 3 Others: Adrenaline, bHCG , steroids

11. Functions of the thyroid hormone Fetal brain development Increases oxygen consumption and basal metabolic rate Ionotropic and chronotropic effects on the heart Maintains normal respiratory drives Bone and muscle turnover Increases glycogenolysis , gluconeogenesis , glucose absorption, cholesterol synthesis and degradation Calcitonin in response to hypercalceamia , stimulates movement of calcium to the bone

12. Classification of thyroid swellings Simple goitre Diffuse hyperplastic Physiological: puberty, cyesis Multinodular goitre Toxic Diffuse (Graves disease) Multinodular Toxic Adenoma Inflammatory Autoimmune Chronic Lymphocytic thyroiditis, Hashimoto dis. Granulomatous De Quervain’s thyroiditis Fibrosing Riedel’s thyroiditis Infective Acute (bacterial, viral, subacute thyroiditis ) Chronic (tuberculous, syphilitic) others Amyloid Neoplastic Benign Malignant

13. Etiopathogensis of benign Multinodular Goitres Simple goitres Excessive stimulation by TSH Chronic iodine deficiency: endemic goitres, intestinal malabsorption Dyshormogenesis (defective hormone synthesis) familial Goitrogens: thyocyanate , anti thyroid drugs, perclorates Pituitary microadenoma Others: Growth factors, immunoglobulin

14. Natural history of simple goitres Diffuse hyperplasia Persistent growth stimulation All lobules are composed of active follicles Iodine uptake is uniform Reversible if stimulation ceases Corresponds diffuse hyperplastic goitre Mixed activity in the lobules Due to fluctuating stimulation Areas of active and areas of inactive lobules form

15. Necrosis in the active lobules Due to increasing vascularity and hyperplasia in the active lobules Heamorrhage occurs causing central necrosis A surrounding ring of active follicles remain Necrotic lobules coalesce to form iodine free colloids or a mass of new inactive follicles Continual repetition of above cycle results in nodular goitre Most nodules are inactive Active follicles present only in internodular tissues

16. Toxic nodular goitres Simple nodular goitre is present for several years Hyperthyroidism subsequently develops from Overactive internodular thyroid tissues or One or more thyroid nodules become autonomous and overactive Toxic nodule: Solitary autonomous overactive nodule Part of a generalized nodularity or True toxic adenoma: mutation in TSH-R gene

17. Clinical Evaluation: History Biodata Sex & age Commoner in females Endemic goitres appear early, toxic goitre commoner in middle age and above Pregnant women, pubertal girls: physiological goitre >60 years with nodule may likely be malignant Males: nodules more likely malignant Residence: Uzo-uwani (Enugu), Obudu (Cross river, Saki/Ifedapo (Oyo), Gwarzo (Kano) Occupation: Nuclear power facilities

18. Presentation Anterior neck swelling Onset Rate of growth Slow growing: likely simple goitre Rapidly growing: possibly anaplastic tumours, lymphoma Sudden increase in size: heamorrhage into a necrotic nodule or malignant change

19. Pain Heamorrhage into a benign nodule Inflammatory condition eg acute suppurative thyroiditis or malignancy (medullary ca) Pressure symptoms Dysphagia Dyspnoea and stridor Hoarseness/change in voice

20. Symptom category Thyrotoxicosis Hypothyroidism Metabolic weight loss despite increased intake, heat intolerance and preference for cold, sweating in cold weather Weight gain, cold intolerance and preference to heat Neuropsychiatric/ neuromuscular anxiety, emotional liability, confusion, coma lethargy, slow thought, depression, Muscle fatigue, pareasthesia in the hand Gastrointestinal inc. frequency of bowel movement, diarrhoea constipation Gyneacological oligomenorrhea menorrhagia Cardiorespiratory Palpitation, dyspnoea, chest pain Chest pain Dermatological Hair loss Dry skin, hair loss, outer 1/3 eye brow loss Eye Diplopia, protruding eyes, difficulty in closing the eyes, pain

21. History suggestive of malignancy/metastasis Cough, chest pain, dyspnoe Jaundice Bone pain Care received Previous hx of thyroid surgery, biopsies, exposure to ionizing radiation Dietary history: goitrogens, iodized vs local salt

22. Family History Hereditary enzyme defects Familial medullary ca Drug history: lithium carbonate, sulphonylureas, amiodarone can induce hypothyroidism

23. Physical Examination General: anterior neck swelling Anxious, restless and lean with hasty gait, starring gaze Dull, obese pt with expressionless face, slow gait Chronically ill-looking, cachectic, Voice: Hoarse Husky Hearing: pendred syn- congenital goitre, deafness, mental retardation Trotters’s syndrome: deafness to high tones Features of Horner’s syndrome suggests malignancy

24. Vital signs PR: normal, tachycardia, arrhythmias Crile Grading: Grade I- < 90/min Grade ii- 90-110/min Grade iii- >110/min Bradycardia suggests hypothyroidism BP: may be elevated in thyrotoxicosis RR: respiratory distress Temp: may be elevated in thyrotoxicosis

25. Neck examination WHO grading of goitres Grade 0: goitre not palpable or visible Grade 1: Palpable goitre 1a: only palpable 1b: visible with neck in extension Grade 2: Visible with the neck in neutral position Grade 3: very large goitre Pizillo’s method for obese patients

26. Neck examination cont. Location: Right, left or middle, retrosternal Skin: shiny, puckered, hypereamic , dilated veins Movement with swallowing: up or – ve Tenderness and differential warmth: inflammatory Fixity of the skin and overlying muscles: adherent in advanced carcinoma Tracheal position

27. Surface Nodular or bosselted Smooth: grave’s, hyperplastic goitres Consistency: Soft: colloid goitres Firm: multinodular goitre, hashimoto thyroiditis Hard: carcinoma (irregular edges), Riedel’s thyroiditis Cystic: thyroid cyst (fluctuant)

28. Thrill: thyrotoxicosis Berry’s sign: absent in malignancy Cervical lymph nodes: enlarged and hard ca Dullness over superior mediastinum : retrosternal goitre (tenderness may be due to bony metastasis from follicular ca) Systolic bruit: thyrotoxicosis

29. Eye signs: lid lag, retraction, exophthalmos , naffziger’s , ophthalmoplegia , chemosis Gradding of exophthalmos Grade 0: No signs Grade 1: O nly sign is lid retraction Grade 2: S oft tissue involvement ( chemosis ) Grade 3: P roptosis Grade 4: E xtraocular muscle involvement Grade 5: C orneal involvement Grade 6: S ight loss

30. Hands: sweaty, erythematous , dry and pale skin, finger clubbing and onycholysis seen in hyperthyroidism, Tremors: fine(high frequency, low amplitude) Proximal myopathy , brisk ankle jerk are features of hyperthyroidism Skull swelling, spine and long bone tenderness and chest findings are suggestive of metastatic thyroid disease

31. Other Differential of Multinodular Goitres Thyroid neoplasia Graves disease Toxic adenoma Toxic phase of subacute thyroiditis

32. Laboratory evaluation Test of thyroid function Serum TSH T4 & T3(total, Free) Result of thyroid function test in different states TFT TSH (0.3-3.3mU/L) Free T4(10-30nmol/L) Free T3 (umol/L) Euthyroid Normal Normal Normal Thyrotoxic Undetectable High High Hypothyroidism High Low Low T3 toxicosis Low/undetectable Normal high Suppressive T4 therapy Undetectable High High/normal

33. Investigation cont. Ultrasound Cheap, fast, available, non invasive, non ionizing Differentiate cystic and solid masses Detect features of malignancy: micro calcifications, hypoechogenicity , irregular margins, increased intranodular vascularity, incomplete peripheral halo Evaluate other neck structures eg lymph nodes For guided biopsy Can not differentiate benign from malignant nodules

34. Thyroid Imaging Reporting and Data System (TIRADS) TI-RADS DESCRIPTION RISK OF MALIGNANCY TI-RADS 1 Normal thyroid gland TI-RADS 2 Benign condition 0% TI-RADS 3 Probably benign nodules <5% TI-RADS 4 4a 4b Suspicious nodule Undetermined suspicious 5-80% 5-10% 10-80% TI-RADS 5 Probably malignant >80% TI-RADS 6 Biopsy proven malignancy

35. Investigation cont. FNAC Safe, cost effective, 90% sensitivity, 70% specificity Can not differentiate between follicular adenoma from follicular carcinoma or Hurthle cell carcinoma Classification of FNAC reports Thy1 Non diagnostic Thy1c Non diagnostic cystic Thy2 Non neoplastic Thy3 Follicular Thy4 Suspicious of malignancy Thy5 Malignant

36. Radionuclide imaging: 123 I or 99 T Hot: functional, tracer uptake > surrounding thyroid tissue Warm: isofunctional , tracer uptake = surrounding thyroid tissue Cold: hypo functional, tracer uptake < surrounding thyroid tissue Limitations: low specificity, superimposition

37. Investigation cont Neck X-Ray (AP and Lt) Tracheal compression or displacement Retrosternal extension Chest x-rays, ECG Indirect laryngoscopy : assess vocal cord mvt . Others: FBC, EUCr , urinalysis, FBS, Ca 2+ , PO 4

38. Treatment Prevention: dietary supplementation; iodized salt Early stages: 0.15-0.2mg thyroxin Moltinodular stage Asymptomatic: may not require surgery Indication for surgery: Features of underlying malignancy Compressive symptoms Thyrotoxicosis Cosmetic reasons

39. Surgical options Extent of resection depends on Size of gland Age of the patient Surgeons experience Need to minimize recurrence of toxicity Wish to avoid postoperative thyroid replacement Thyroidectomy Total thyroidectomy Subtotal thyroidectomy Near-total thyroidectomy Lobectomy

40. Comparism of surgical options Total thyroidectomy Subtotal thyroidectomy Control of toxicity Immediate Immediate Return to euthyroid state Immediate Variable Risk of recurrence None lifelong Risk of thyroid failure (need for thyroid hormone replacement) 100% Lifelong Risk of permanent hypoparathyroidism 5% 1% Need for follow up Minimal lifelong Need for reoperation (for recurrence ) None Possible (with increased morbidity, RLN damage)

41. Preoperative Preparation D one on outpatient basis Admissions needed Severe symptoms at presentation Failure to control hyperthyroidism Non compliance with medication Multidisciplinary: ENT, Endocrinologists, surgeon,

42. Pre op. prep. cont Antithyroid drugs Carbimazol : 30-40mg/day for 8-12week, ( reduced to 5mg 8hourly when pt becomes euthyroid) Block and Replace: 30-40mg daily plus maintenance dose of thyroxin 0.1-0.15mg daily Last dose given on the evening before surgery

43. Β -adrenergic blocking drugs: propranolol 40mg tds or nadolol 160mg daily or higher Taken on the morning of surgery and for 7 days postoperatively Iodine with carbimazole or Β -adrenergic blocking drugs Iodine produces a transient remission Reduces vascularity

44. Documentation of pre op indirect video laryngoscopy Counseling and consent: ( risks of scar, RLN damage, bleeding, hypocalcaemia, hypothyroidism) General aneasthesia + Endotracheal intubation (reinforced) Prophylactic antibiotics Aneasthetic safety check list Positioning: supine with neck extended ( shoulder role, head rings) Cleaning (mandible to chest), draping and side packing Preparation for tracheostomy in large goitres

45. Surgical Technique of Thyroidectomy

46. Step 1: GA + ETT, Positioning, cleaning and draping

47. Step 2: Transverse skin crease incision At level of cricoid cartilage or 2 finger breath from the sternal notch Laterally to ant. Borders of sternocleidomastoids A suture may be use to indent the skin prior to incision

48. Step 3: Raising the Subplatysmal flaps Should be done with diathermy to avoid bloody fields Blunt dissection to thyroid notch superiorly and sternal notch inferiorly Flaps are help in position with Jolls retractors

49. Step 4: Incising the investing layer of deep cervical fascia & muscle retraction/division Step 5: Middle thyroid vein is divided Investing layer of deep cervical fascia is incised at the median raphe Strap muscles are retracted/divided

50. Step 6: Superior pole management A plane btw the larynx and superior pole is developed to reveal the superior vascular pedicle The superior thyroid artery and vein are dissected and ligated individually and close to the gland External laryngeal nerve must be protected The superior pole is gradually mobilised

51. Step 7: Identification of the Recurrent Laryngeal nerve and Parathyroid gland identification The thyroid lobe is elevated and rotated medially The strap muscles are retracted laterally Recurrent laryngeal nerve and parathyroid glands are identified

52. Step 8: Inferior thyroid vessel management The inferior thyroid artery is ligated and divided near the capsule of the gland RLN and inf. Parathyroid are protected Step 9: Thyroid dissection from bed Having dissected both poles, the gland remains attached by the berry’s ligament The RLN is most commonly damaged at this point Pre-emptive diathermy is applied on the ligament and layer by layer dissection done to free the lobe The same steps are repeated on the contra lateral side for total thyroidectomy

53. Step 11: Achieving hemostasis Hemostasis is carefully secured Wound is irrigated with saline Valsava maneuver is done to ensure adequate hemostasis

54. Step 12: Drain placement and wound closure Closed suction silastic drain left insitu Strap muscle closed in midline with interrupted suture Platysma is closed Skin closed using absorbable subcuticular suture Dressing is applied

55. Complication Intraoperative Difficult intubation Primary heamorrhage Injury to external laryngeal nerve Injury to cervical sympathetic trunk Injury to the recurrent laryngeal nerve Devascularization of the parathyroid gland

56. Complications cont Early postop complication Airway obstruction Tension hematoma Laryngeal edema from trauma and surgical manipulation Tracheomalacia Thyrotoxic crisis (thyroid storm): restless, hyperpyrexia, severe tachycardia, heart failure, dehydration. Trx : fluid resuscitation, hydrocortisone, antithyroid drug, digoxin , ICU CARE

57. Complications cont Late complication Hypothyroidism Hypoparathyroidism Recurrent thyrotoxicosis Hypertrophic scar or keloid Stitch granuloma Wound infection

58. Post op monitoring Vigilance for hematoma Serial calcium monitoring TFT Thyroxin replacement Follow up

59. Emerging trends Intermittent nerve monitoring Continuous nerve monitoring Ultrasonic shear Enhanced bipolar diathermy Minimally invasive video assiste d techniques Robotic techniques via axillary incisions

60. Conclusion Benign multinodular goitres are relatively common in our environment. Effort must be made to rule out malignant disease in evaluating these patients. Adequate preoperative preparation is essential to success of surgery. The surgeon must have a good understanding of the anatomy of the thyroid and the neck to ensure safety.

61. References Bailey, H., Love, R. J. M. N., Mann, C. V., & Russell, R. C. G. Bailey and Love short practice of surgery . 27 th Edition. London: Chapman & Hall medical. (2018) Archampong E. Q., Naaeder S. B., Ugwu B. Baja’s Principle and practice of Surgery. 5 th Edition. Ghana Publishing Corporation. (2015) M.A.R Alfallouji . Post-graduate surgery, candidates guide ,2nd edition Townsend, Beauchamp, Evers, Mattox. Sabiston Textbook of Surgery. 20 th Edition. Elsevier. (2017) Brunicardi F., Anderson D. K,. Billiar T. R., Dunn D. L., Hunter J. G., Mattews J. B., Pollock R. E. Schwartz’s Principles of Surgery. 10 th Edition. McGraw-Hill Education. (2015) Ogbera , Anthonia & Kuku, Sonny. (2011). Epidemiology of thyroid disease in Africa. Indian journal of Endocrinology and metabolism. 15. S82-8. 10.4103/2230-8210.83331. Chuhwak E, Ohwovoriole AE. Clinical features of goitres on the Nigerian plateau. Nigerian Postgraduate medical Journal. 2005 Dec: 12 (4): 245-9. PMID: 16380732 Vikas J. Safe and Optimum Steps for Total/Hemi Thyroidectomy. Otolaryngology Open Access Journal. 2016 Aug: 22. 2476-2490