Consists of Both Benign and malignant thyroid disorders

1. BENIGN & MALIGNANT
DISORDERS OF THYROID
& THEIR MANAGEMENT
PRESENTED BY- DR. ASHISH MISHRA
MODERATED BY - Dr DILIP KOTHARI

2. INTRODUCTION
• Word thyroid means shield.
• Located in the anterior triangle of neck.
• Lies against C5-T1 vertebra, extending from middle of thyroid cartilage to 6th tracheal ring.
• Weighs around 20-25 g.
• The functioning unit is the lobule supplied by single arteriole – consisting of 24-40 follicles
lined by cuboidal epithelium
• Follicles contain colloid in which thyroglobulin is stored.

3. ANATOMY
• ARTERIAL & VENOUS SUPPLY OF THYROID –

4. • RELATIONS –
• HISTOLOGY–

5. • LYMPHATIC DRAINAGE –

6. EMBRYLOGY
Median bud of pharynx –
thyroglossal duct
Starts from foramen caecum
(vestigial remnant of duct)
3rd Pouch – inferior parathyroid
gland & thymus 4th Pouch –
superior parathyroid gland &
ultimobranchial body
Amalgamation of 3rd & 4th
pharyngeal pouches with
descending thyroid lobes completes
the development.

7. ➢ CONGENITAL ANOMALIES –
• ECTOPIC THYROID
1. Ectopic lingual thyroid
2. Intralingual thyroid
3. Sublingual thyroid
4. Retrosternal thyroid
• AGENESIS
• DYSHORMOGENESIS

8. • THYROGLOSSAL CYST –
▪ Remnant of thyroglossal tract.
▪ Most commonly – sub-hyoid or infra-hyoid
▪ Clinical presentation –
Midline neck swelling.
Moves with deglutination.
Moves with protrusion of tongue.
▪ Diagnosis –
FNAC
USG neck – to rule out the presence or absence of normal thyroid tissue
▪ Management - Sistrunk procedure (Cyst + duct + central part of hyoid bone)
( Incision & drainage contraindicated)

9. PHYSIOLOGY

10. TESTS FOR THYROID FUNCTION
➢Blood investigations –
• T3, T4
• Sr. TSH
• Free T3, T4 – more sensitive
• Anti thyroid antibodies - >25 U/ml or titers >1:100 considered significant
• Corrected Sr. calcium & Sr. calcitonin
Thyroid function state
TSH
(0.3-3.3 mU/ml)
Free T4
(10-30 nmol/L)
Free T3
(3.5-7.5 umol/L)
Euthyroid Normal Normal Normal
Thyrotoxic Undetectable High High
Myxoedema High Low Low
Suppressive T4 therapy Undetectable High High (often normal)
T3 toxicity Low/ undetectable Normal High

11. ➢Chest & thoracic inlet X-ray –
• Detection of retrosternal goitre, tracheal
deviation.
• Calcifications & lung mets in few cases.
➢USG neck –
• Size
• Number
• Echogenicity
• solid or cystic
• Vascularity
• presence of significant lymphnode
• vascularity of gland by resistive index –
N=0.65 to 0.70, >0.7 indicates malignancy.
• Malignant nodule – anarchial angiogenesis

12. ➢CT, MRI and PET scan –
• Routinely not indicated but reserved for assessment of known malignancy.
• PET scan obscure role in management of patients with recurrent thyroid cancer.
➢Isotope scan –
• Indications – features of hyperthyroidism with low TSH
ectopic or aberrant thyroid tissue.
• 99mTc – there is only uptake of iodine by gland
• I123 – both uptake & organification of iodine by gland
• Cold nodule – 20% chances of malignancy, non- functioning nodule.
• Hot nodule – 4% turn into malignant, hyper-functioning nodule.
• Warm nodule – normal functioning nodule.

13. ➢FNAC (fine needle aspiration cytology) –
• Investigation of choice in discrete thyroid swellings .
• 20G – 23G needle used.
• USG guided – yields better results & reduce results of unsatisfactory aspirates.
BETHESDA
CATEGORY
USUAL MANAGEMENT
Thy 1 Non diagnostic Repeat under USG guidance
Thy 1c Non diagnostic cystic Follow-up
Thy 2
Atypia of undetermined significance/
follicular lesion of undetermined
significance
Repeat FNAC or lobectomy
Thy 3
Suspicious of follicular neoplasm/
follicular neoplasm
Hemi-thyroidectomy
Thy 4 Suspicious of malignancy Hemi or total thyroidectomy
Thy 5 malignant Total thyroidectomy

14. CLASSIFICATION OF THYROID SWELLINGS
SIMPLE GOITRE
(EUTHYROID)
Diffuse hyperplastic Physiological
Pubertal
pregnancy
Multinodular goitre
TOXIC Diffuse (Grave’s disease)
Multinodular
Toxic adenoma
NEOPLASTIC Benign
Malignant
INFLAMMATORY Autoimmune Chronic lymphocytic thyroiditis
Hashimoto’s disease
Granulomatous De Quervain’s thyroiditis
Fibrosing Riedel’s thyroiditis
Infective Acute (Bacterial thyroiditis, viral
thyroiditis, ‘subacute thyroiditis’)
Chronic (tuberculous, syphilitic)
Others Amyloid

15. GOITRE
➢DIFFUSE HYPERPLASTIC GOITRE –
During iodine deficiency – physiological
primary iodine deficiency
secondary iodine deficiency

16. ➢MULTINODULAR GOITRE –
• Etiology –
Mainly fluctuation of TSH, iodine deficiency, goitrogens, hereditary,
dyshormonogenesis.

17. • Pathophysiology –
Diffuse goitre with variable stimulation TSH
Hyperfunctioning Non-functioning Normal
Mixed areas of active & inactive lobules
Active nodules with hyperplasia & increased vascularity
Hemorrhages with necrosis in centre
Nodule formation
Multiple nodules with necrotic centers & only internodular area functioning
Multinodular goitre

18. • Clinical features –
▪ females > males
▪ Slowly progressive disease
▪ Firm, nodular, non-tender & moves with deglutination.
▪ Positive Kocher's test
• Diagnosis –
▪ TSH, free T3, T4
▪ USG neck
▪ X-ray neck – coarse calcifications
▪ Indirect laryngoscopy
• Management –
Total, Sub-total or Partial thyroidectomy done depending upon diseased part of gland
Post-operative L-thyroxine supplementation

19. ➢DISCRETE THYROID SWELLING–
• Solitary or isolated thyroid nodule – discrete swelling in otherwise impalpable gland
• Dominant thyroid nodule – similar swelling with clinical evidence of generalized
abnormality in the form of a palpable contralateral lobe or generalized mild nodularity.
• Risk of malignancy –

20. • Clinical features –
▪ Most common thyroid surgical disease
▪ Single palpable nodule
▪ Commonest site at the junction of
isthmus with one of the lateral lobes.
• Diagnosis –
▪ USG neck, Power doppler
▪ FNAC – US guided being investigation
of choice
▪ Free T3-T4, TSH
▪ Radioisotope study (I123/ 99mT)

21. • Management –
▪ Non-toxic benign nodule – no role of hormone therapy, annual follow up,
hemithyroidectomy in cases with compressive symptoms or for cosmesis.
▪ Solitary toxic nodule – Anti-thyroid drugs, radioactive iodine therapy, occasionally
hemithyroidectomy.
▪ Colloid nodule – observed or hemithyroidectomy
▪ Follicular neoplasia of undetermined significance – total thyroidectomy is indicated.
▪ In malignant nodule – treatment is based on the type of carcinoma seen.

22. ➢RETROSTERNAL GOITRE –
• Types –
▪ Primary (10%)– ectopic thyroid tissue in the mediastinum
▪ Secondary (90%) – neck being the starting point which plunges into the mediastinum
• Clinical features
▪ Dyspnoea
▪ Stridor
▪ Dysphagia
▪ Swelling – where lower border not seen & not palpable.
▪ Pemberton’s sign - positive
• Investigations –
▪ Free T3, T4, TSH
▪ Radioactive iodine study
▪ CECT neck & thorax – investigation of choice

23. • Management –
▪ Surgical removal of thyroid – via neck or cervical incision.
▪ Sternotomy is only indicated in cases with –
i. Malignancy
ii. Primary mediastinal goitre
iii.Very large retrosternal part
iv. Recurrence in mediastinum

24. ➢GRAVES DISEASE –
• Autoimmune disease
• More common in females.
• Auto-antibodies against thyroid
receptors
▪ Stimulating antibody
▪ LATS (Long acting thyroid
stimulating antibody)
▪ TSH receptor antibody
• Present in association with diseases like
– pernicious anemia, myasthenia gravis,
Addison's disease.
• Histopathological examination –
▪ Scalloping of colloid
▪ Tall columnar cells

25. • Clinical features –
▪ Features of hyperthyroidism –
• Thin irritable patient
• Weight loss despite good appetite
• Tachycardia
• Diarrhea
• Oligomenorrhoea or amenorrhea
• Tremors
▪ Eye signs –
• Exopthalmos
• Stellwag sign – infrequent blinking
• Dalyrymple sign – lid retraction
• Von graffe’s sign – lid lag
• Joffroy sign – absence of forehead
wrinkling
• Moebius sign – loss of accommodation
reflex resulting in convulsions
▪ Pretibial myxoedema – dermopathy
▪ Thyroid achropachy –
• Dermopathy
• Clubbing
• Sub-periosteal bone formation.

27. • Diagnosis –
▪ Clinical features
▪ Free T3, T4 & TSH
▪ Presence of auto-antibodies
• Management –
▪ In children – by anti-thyroid drugs (carbimazole & propylthiouracil)
▪ In pregnant women – propylthiouracil is the drug of choice
▪ Adult without goitre – anti-thyroid drugs followed by radio-iodine ablation (RIA)
▪ Adult with goitre – anti-thyroid drugs followed by surgery
▪ Elderly with comorbid conditions – anti-thyroid drugs followed by RIA
▪ Eye signs – anti-thyroid drugs followed by surgery

28. • Surgical options in graves disease –
Total thyroidectomy
Sub-total
thyroidectomy
Thyroid failure
100%
(thyroxine
supplementation)
100% risk of thyroid
failure with in 30 yrs.
Control of toxicity Immediate Immediate
Risk of euthyroid Immediate Up to 12 months
Risk of permanent
hypoparathyroidism
5% 1%
Need for follow-up Minimal Lifelong

29. ➢HASHIMOTO THYROIDITIS –
• Lymphocytic thyroiditis, an auto-immune condition.
• Females > males
• Association with – HLA DR3/ B8, down’s syndrome & turner’s syndrome.
• Auto-antibody formation –
▪ Blocking antibody against thyroid receptors
▪ TPO enzymes
▪ Thyroglobulin

30. Auto-antibodies
stimulates
lymphocytic
infiltration
Destruction of
healthy follicles
Stored hormone
released
(transient
hyperthyroidism)
Repeated attacks
& no
regeneration –
destroys follicles
(hashi-toxicosis)
Prolonged
hypothyroidism
• Pathophysiology –
• Clinical features –
▪ Early stages – features of hyperthyroidism or patient presents with hashi-toxicosis

31. ▪ Prolonged cases – features of
hypothyroidism
• Dull & lethargic
• Alopecia
• Bradycardia
• Constipation
• Weight gain
• Cold intolerance
• Menorrhagia
▪ Diffuse enlargement of the gland
▪ In long standing cases – thyroid
lymphoma
• HPE –
▪ Lymphocytic infiltration
▪ Hurthle cells

32. • Diagnosis –
▪ Auto-antibody levels in blood
• Management –
• L-thyroxine supplementation
• If diffuse goitre present – surgery required.

33. ➢DE-QUERVAIN’S/ VIRAL/
GRANULOMATOUS THYROIDITIS –
• Type of sub-acute thyroiditis
• Has association with – HLA B35
• Pathophysiology – Self limiting condition
• Clinical presentation – painful neck
enlargement
• Diagnosis –
Raised ESR, association with HLA B35
• Managements –
▪ Steroids
▪ Symptomatic management till
euthyroid state is achieved

34. ➢RIEDEL’S THYROIDITIS –
• Fibrosing thyroiditis
• Pathogenesis – IgG4 mediated
• Clinical features –
▪ Diffuse & painless enlargement of neck
▪ Woody hard thyroid
(fibrosis in the gland as well as the tissues in the vicinity)
▪ Hoarseness (cases with tracheal or RLN involvement)
• Diagnosis –
▪ Tru-cut biopsy
• Management –
▪ Steroids
▪ Symptomatic management
▪ Tamoxifen (as association with Peyroni’s disease & dupytrene’s contracture )

35. MALIGNANT DISORDERS
➢Differentiated thyroid cancers –
• Papillary thyroid cancer (PTC)
• Follicular thyroid cancers (FTC)
• Hurthle cell cancer
➢Anaplastic thyroid cancer
➢Thyroid lymphoma
➢Medullary thyroid cancer (MTC)

36. ➢Syndromes associated with thyroid malignancies –
• Familial anenosis polyposis – APC gene (Chr. 5) mutation – Papillary thyroid carcinoma
(PTC) association.
• Gardners syndrome – Follicular thyroid carcinoma (FTC) association.
• Werner syndrome – WRN-1 gene – association with FTC/ PTC/ hurthle cell carcinoma
• MEN 2B mutation – RET oncogene – MTC association
• Cowden Syndrome – PTEN oncogene – GI polyps, breast ca, FTC/ PTC
• McCune Albright syndrome – fibrous dysplasia of gland
• Carney complex – PPARy gene mutation – BATMAN syndrome

37. TNM STAGING
(AJCC 8th edition)
TUMOR
Tx Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1
Tumor < or = 2 cm, greatest dimension limited to thyroid.
T1a - < or = 1 cm, greatest dimension limited to thyroid.
T2a - >1 cm or > or = 2 cm, greatest dimension limited to thyroid.
T2 >2 cm but < or = 4 cm, greatest dimension limited to thyroid.
T3
>4 cm, limited to thyroid or gross extra-thyroid extension invading only strap muscles.
T3a - >4 cm limited to thyroid
T3b – gross extra-thyroid extension invading only strap muscles
T4
Gross extra-thyroidal extensions into major neck structures
T4a – invading subcutaneous soft tissues, larynx, trachea, esophagus or RLN for any
tumor of any size
T4b – invading prevertebral fascia or encasing carotid artery or mediastinal vessels from
a tumor of any size.

38. NODES
N0
No nodal involvement
a – one or more confirmed benign lymph node
b – no evidence of locoregional lymph node metastasis
N1
N1a – mets to level VI or VII (U/L or B/L)
(pre-tracheal, para-trachea or pre-laryngeal/ delphian, upper mediastinal)
N1b – U/L, B/L or C/L lateral neck lymph nodes. (level I, II, III, IV or V) or retropharyngeal
lymph node.
METASTASIS
M0 No distant metastasis
M1 Distant metastasis

39. PAPILLARY CARCINOMA
• 80% relative incidence in primary malignant tumors of thyroid glands.
• Most common cancer of iodine sufficient areas.
• 3rd-4th decade of life.
• Females > males
• Risk factors –
▪ Past radiation exposure to neck – tend to be more aggressive.
▪ Long standing thyroglossal cyst.
• Genetics –
▪ BRAF gene – most common gene mutation
▪ RET/PTC mutation – RET/PTC-1 – less aggressive
RET/PTC-3 – more aggressive with less latency period

40. • Clinical features –
▪ Present as swelling.
▪ Rare presentation as micro-carcinoma or
occult carcinoma as well (<1cm in size)
or a cyst.
▪ Multifocal origin.
▪ Lymphatic spread more common than
hematogenous spread.
(delphian LN/ level VI nodes)
▪ Lateral aberrant thyroid – where there is
lymphnode enlargement due to
metastasis with an occult primary.
▪ Haematogenous spread – most common
to lungs.

41. • Diagnosis by
▪ FNAC –
• Orphan annie-eyed nuclei
• Nuclear grooving
• Psammoma bodies (foci of
dystrophic calcification)
▪ Raised TSH.
▪ Cold nodule in radio-isotope scan.
▪ Plain X-ray neck – fine calcifications
▪ USG neck – non-palpable node & lymph
nodes
▪ MRI in some cases.

42. • Management –
▪ Surgery is the mainstay –
if there is T3-T4 disease – prophylactic
level VI clearance is done.
▪ After surgery if there is presence of residual
disease or metastasis
Whole body iodine scan is done

43. • Further management –
▪ Requirements – omit thyroxine for 4-6 weeks after surgery
recombinant TSH injection can be used – 2 injections for 2 days.
▪ If residual disease present – radioiodine ablation (RIA) with I131
▪ No residual disease or metastasis –
1. Regular follow-up advised – 6 monthly - USG neck & Serum Thyroglobulin levels
2. TSH suppression is continued – L-thyroxine
(So TSH reaches to the lower limit of normal)
▪ If Sr. Tg - >2 gm/mL – suspect recurrence & repeat whole body scan.
• Patients with LN & extracapsular metastasis – Single dose of RIA required.
• If tumor resistant to RIA – EBRT (external beam radiotherapy) is the next best option.

44. • Prognosis –
▪ Best prognosis of all thyroid malignancies.
▪ Indolent cancer.
▪ One can say patient will attend the onco-surgeons funeral.
• LINDSEY TUMOR –
Follicular variant of papillary thyroid carcinoma

45. FOLLICULAR CARCINOMA
• 10% relative incidence in primary malignant tumors of thyroid glands.
• Most commonly seen in iodine deficient areas.
• Risk factor –
▪ long standing multi-nodular goitre
• Genetics –
▪ Upregulation of miRNA – 197, 346
▪ PTEN gene
▪ BAX gene

46. • Clinical features –
▪ Presents as thyroid swelling.
▪ Tracheal compression, infiltration & stridor.
▪ Hematogenous spread more common than lymphatic spread.
▪ Hematogenous spread mostly to bones – pulsatile bony metastasis
Skull, long bones & ribs.
▪ Lymphatic spread to level VI nodes only observed in 10% of cases.
• Diagnosis –
▪ FNAC – inconclusive as capsular angioinvasion of follicular carcinoma cannot be
visualized - reported as follicular neoplasm – hemithyroidectomy is done & then frozen
section is used for final diagnosis.
▪ USG neck, Chest X-ray, X-ray skull are the other investigations.

47. • Management –
Surgical principles, post-op period &
follow-up is same as PTC.
• Prognosis –
Slightly bad as compared to PTC.

48. HURTHLE CELL CANCER
• Earlier it was thought to be a variant of FTC.
• More aggressive than follicular carcinoma.
• In association with hematogenous spread, lymphnode involvement is more common as
compared to follicular carcinoma.
• Resistant to RIA, thyroglobulin secreting tumor.
• Diagnosis – FNAC – abundant oxyphill cells (Askanazy) are specific.
• Management – same as PTC & FTC.
• Poorer prognosis than FTC.

49. • PROGNOSTIC FACTORS FOR DTC –
MAYO – AGES CRITERIA
A Age (young – good; >50yr – bad prog.)
G Grade (pathologic)
E Extent of tumor
S Size (<4 cm better prog.)
LAHEY – AMES CRITERIA
A Age
M Metastasis
E Extent of tumor
S Size
MAYO – MACIS CRITERIA
(Post-op score)
M Metastasis
A Age
C Completeness of resection
I Invasion
S Size

50. ANAPLASTIC CARCINOMA THYROID
• Least common thyroid carcinoma.
• 5th-7th decade of life.
• Genetics –
▪ p53 mutation
▪ miRNA – 17-92 upregulated
▪ Beta-catenin mutation.

51. • Clinical features –
▪ Rapidly progressive thyroid swelling.
▪ Local invasion is there
• To RLN – hoarseness
• To trachea – stridor, dyspnoea
▪ Very hard swelling.
▪ Distant metastasis – most commonly to lungs.
• Diagnosis – FNAC is diagnostic, if inconclusive Tru-cut biopsy is done.
• Staging is same for all thyroid carcinomas.

52. • Management –
▪ If tumor restricted to thyroid – aggressive surgery – TT + CND +/- MRND
▪ If beyond thyroid only palliative management to relive respiratory symptoms –
tracheostomy & isthumectomy.
▪ External beam radiotherapy is used.
▪ In metastasis – chemotherapy is used.
i. Dabrafenib – tyrosine kinase inhibitor (metastatic anaplastic cancers)
ii. Doxyrubicin (Adriamycin) – topo isomerase-2 inhibitor.
• Prognosis –
Worst prognosis of all thyroid cancers.

53. THYROID LYMPHOMA
• 5th-7th decade of life
• Non-hodgkins B-cell type
▪ Diffuse large B-cell
▪ Small blue cell.
• Clinical features –
▪ Thyroid swelling
▪ B-cell symptoms – fever, night sweats, weight loss.
• Diagnosis –
▪ FNAC – cannot characterize a lymphoma.
▪ Tru-cut biopsy preferred.

54. • Management –
▪ Chemotherapy –
a. R – Rituximab (monoclonal antibody for CD20)
b. C – Cyclophosphamide
c. H – Hydroxydaunorubicin
d. O – Oncovin/ Vincristine
e. P – Prednisolone
▪ Followed by radiotherapy.
▪ In cases with residual disease after chemotherapy & radiotherapy or in recurrence –
surgery is done.

55. MEDULLARY CARCINOMA
• Tumor of parafollicular-C cells.
• Calcitonin as its tumor marker.
• Types –
▪ Sporadic (more common)
▪ Familial – MEN-2 syndrome
most aggressive in MEN-2B syndrome
younger age
multicentric
penta-gastrin stimulation – to see calcitonin rises or not.

56. • Clinical features –
▪ Thyroid swelling
▪ Diarrhea (due to serotonin)
▪ Flushing (due to histamine)
▪ Cushing’s features (due to ACTH)
▪ Multifocal
▪ Both lymphatic spread & hematogenous
spread – to level VI & most commonly
to liver respectively.
▪ Aggressive tumor.
• Diagnosis –
▪ USG neck
▪ FNAC – amyloid rich stroma with
dispersed malignant cells & C-cell
hyperplasia.
▪ Sr. Calcitonin level - >100pg/mL
unstimulated suggests MCT.
▪ Raised carcinoembryonic antigen
(CEA).

57. • Management –
▪ Surgery is the main therapeutic modality.
▪ If lesion restricted to thyroid – TT + CND
▪ Lesion in thyroid with level VI lymphnode involvement – TT + CND + MRND
▪ Lesion in thyroid with lateral LN spread – TT + CNC + MRND
▪ No role of an iodine scan or RIA in medullary carcinoma.
▪ For metastatic MTC - vandetanib, carbozantinib (tyrosine kinase inhibitors),
palliative surgery is required in these case.
▪ Always better to rule out phaeochromocytoma before operating for MTC – as there is
very high mortality rate of this patients.

58. THANK YOU!