Diseases of thyroid gland

Dr. Krishna Koirala

Goitre

Classification of goitre1. Simple (non-toxic) goitre

– Diffuse– Multi-nodular – Colloid (large size, soft consistency,

due to iodine deficiency)2. Toxic

– Diffuse (Graves’ disease)– Multi-nodular (Plummer’s disease)– Solitary nodule

3. Inflammatory : thyroiditis4. Thyroid neoplasm: benign (adenoma),

malignant

Multi-nodular goitre (MNG)

Etiology

1. Iodine excess

2. Iodine deficiency : Endemic, Sporadic, Familial

3. Goitrogens ( eg. Cabbage, drugs like

phenytoin)

4. Physiological: during puberty in females

Pathogenesis of goitreIodine deficiency Hypothyroidism

Increased TSH

Diffuse goitre

Follicles grow

heterogeneously

Nodular goitre

Follicles continue to secrete T4 despite

subsequent decrease in TSH levels

Toxic goitre

Diffuse hypertrophyof thyroid follicles

Increased TSH

Hypothyroidism

Etiology

A. Primary hypothyroid (99% cases) : defect in thyroid

• Iodine deficiency: common in developing countries

• Hashimoto’s : common in developed countries

• Subacute thyroiditis

• Thyroidectomy / iodine ablation / external RT to neck

• Drug-induced: Lithium, amiodarone, anti-thyroid drugs

B. Secondary hypothyroid: pituitary insufficiency 

C. Tertiary hypothyroid: hypothalamic disease

D. Euthyroid hypothyroidism: Low T4 binding proteins, sick euthyroid, peripheral resistance to T3 & T4

Common features of Hypothyroidism

Symptoms Signs

• Tiredness, weakness• Dry skin, hair loss• Feeling cold• Difficulty in

concentration• Constipation• Weight gain with poor

appetite• Dyspnea & hoarse

voice• Menorrhagia• Paresthesia • Impaired hearing

• Dry coarse skin • Cool peripheral

extremities• Puffy face &

extremities (myxedema)

• Diffuse alopecia• Bradycardia• Peripheral edema• Delayed reflex

relaxation• Carpal tunnel

syndrome• Serous cavity

effusions

Thyroiditis

Classification of Thyroiditis1. Acute: bacterial, fungal, post-radiation

2. Sub-acute

– Granulomatous / painful (De Quervain's)

– Lymphocytic / painless

– Silent / post-partum3. Chronic – Autoimmune: Hashimoto, atrophic– Invasive (Riedel) – Infective: TB, actinomycosis, parasitic

Hashimoto’s Thyroiditis

• Commonest cause of hypothyroidism in U.S.

• Associated with other autoimmune diseases

– Pernicious anemia, rheumatoid arthritis,

vitiligo, type 1 diabetes mellitus , Addison's

disease

• Common in elderly females

• Predisposing factor for thyroid lymphoma

Investigations• High TSH , Low T3 and T4

• Anti thyroid peroxidase antibodies (90%)

• Anti thyroglobulin antibodies (20 - 50%)

• Hyperthyroidism (5% )

• Histopathological exam

– Lymphocytic infiltration , atrophy of thyroid follicles, absence of colloid, fibrosis

Treatment• Oral Thyroxine: 25 g & increase gradually to 100

-150 g/day to get serum TSH in normal range

• Primary adrenal insufficiency should be ruled out

(with synthetic ACTH stimulation test) prior to

initiating thyroxine replacement in patients with

autoimmune hypothyroidism to avoid adrenal

crisis

Subacute Thyroiditis• Synonym: De Quervain’s or granulomatous thyroiditis

• Commonest cause of painful thyroiditis

• Etiology: inflammatory destruction of thyroid gland

often following upper respiratory tract infection

• Clinical course: painful thyrotoxicosis (3-6 wks)

painless euthyroidism hypothyroidism (1-3 months)

recovery (complete in 95% after 4-6 months)

Clinical phases

• Diagnosis : Elevated ESR , low or absent uptake of I 131

• Treatment

– NSAIDs for pain

– High doses of oral steroids in severe cases ( thyroid hormone binding proteins; peripheral conversion of T4 to T3; inflammation

– Propranolol for symptomatic hyperthyroidism

• Anti-thyroid drugs not indicated since hyperthyroidism results from release of T3 & T4 into circulation instead of thyroid hyper-function

Reidel’s Thyroiditis• Etiology: unknown (? auto-immune)

• C/F: woody-hard thyroid gland with pain, dysphagia or stridor (due to compression), hypothyroidism, retroperitoneal fibrosis & sclerosing cholangitis

• Diagnosis: MRI of thyroid, open biopsy

• HPE: replacement of thyroid gland with dense fibrosis

• Rx: surgical debulking for compressive symptoms, chemotherapy (tamoxifen or methotrexate) to prevent recurrence & thyroxine for hypothyroidism

Silent Thyroiditis• Synonym : post-partum (within 1 year) thyroiditis

• Clinical course: Hyperthyroid at presentation

euthyroid hypothyroid (resolves within 1 year)

• Treatment

– Propranolol for symptomatic hyperthyroidism

– Thyroxine for 6 months in hypothyroid phase

T4 T3 TSH AntibodiesHashimoto

's thyroiditis

LowNormal or Low

HighAnti-TPO + ve in

90% Anti- Tg +ve in

50% Subacute thyroiditis Low

Normal or Low

High -

Secondary hypothyroi

dLow

Normal or Low

Low or

normal

-

Tertiary hypothyroi

dLow

Normal or Low

Low or

normal

-

Sick euthyroid syndrome• Low serum levels of T3 & T4 in clinically euthyroid

patients due to non-thyroidal systemic illness

• Etiology: starvation, protein-energy malnutrition,

major trauma, myocardial infarction, chronic renal

failure, diabetic ketoacidosis, anorexia nervosa,

liver cirrhosis, thermal injury & sepsis

• Pathogenesis: decreased peripheral

conversion of T4 to T3, decreased binding of

thyroid hormones to thyroxine-binding

globulin (TBG) caused by tumor necrosis

factor-α & Interleukin -1

• Diagnosis: decreased T3 & increased reverse

T3, T4 may be decreased, normal TSH

• Rx: of underlying illness; thyroxine not

indicated

Thyrotoxicosis

Etiology

1. Primary hyperthyroidism: low serum TSH– Graves' disease (commonest) – Toxic adenoma– Toxic multi-nodular goiter – Iodine excess

2. Secondary hyperthyroidism: normal serum TSH – TSH producing pituitary adenoma– Pituitary resistance to thyroid hormone

suppression

3. Thyrotoxicosis without hyperthyroidism:– Subacute thyroiditis– Thyrotoxicosis factitia – Thyroid cancer metastasis – Struma ovarii– Amiodarone thyroiditis – Radiation thyroiditis

Common symptoms & signs of thyrotoxicosis

Symptoms Hyperactivity, irritability Heat intolerance, sweating Palpitations Fatigue Weight loss with ed appetite Diarrhea Polyuria Oligomenorrhea Loss of libido

Signs Tachycardia Graves’ ophthalmopathy Atrial fibrillation in elderly Tremor Goitre (thyroid swelling) Warm, moist skin Proximal myopathy Lid retraction or lid lag Gynecomastia Graves’ dermopathy

Graves’ disease

• Commonest form of thyrotoxicosis (80-90%)

• Female : male = 5-10 : 1;

• Age: 30-50 years

• Etiology:

– Thyroid Stimulating Immunoglobulins (TSI)

• Antibodies against TSH receptor (TSHR- Ab) which act as TSH receptor agonists causing thyrotoxicosis

– Associated with other auto-immune diseases

Clinical features• Symmetric, firm, rubbery, pulsating, warm, goitre

• Thyrotoxicosis: palpitations, fine tremors,

diarrhea, excessive sweating, heat

intolerance, weight loss

• Eye signs and Graves’ ophthalmopathy

• Graves’ dermopathy

• Graves’ acropathy: clubbing

Eye signs• Von Graefe: upper eyelid lag when pt looks down• Griffith: lower eyelid lag when pt looks up• Joffroy: absence of forehead wrinkling on looking

up• Moebius: lack of medial convergence of eyeballs• Dalrymple: display of upper sclera• Stellwag: staring look due to absence of blinking• Enroth: edema of lower eyelid• Gifford: upper eyelid can’t be everted• Rosenbach: tremor of gently closed eyelids

Graves’ ophthalmopathy (seen in 3% cases)

• Infiltrative:

– Periorbital edema, proptosis, chemosis, extraocular muscle palsy (commonly inferior rectus), keratitis & loss of vision (optic nerve involvement)

– Unaffected by thyrotoxicosis treatment

• Non-infiltrative:

– Lid retraction, stare & lid lag. Due to hyperactivity of sympathetically innervated Mueller's fibers in upper palpebral muscle

– Resolves when thyrotoxicosis is treated

Graves’ ophthalmopathy

Graves’s dermopathyThickening of skin in

anterior tibial area

due to deposition of

glycos-aminoglycans

which cause local

fluid retention (seen

in 5 % cases)

Investigations• Increased total T4 and T3 levels

• Ratio of T3 (ng/dL) to T4 (mcg/dL) > 20

• Suppressed serum TSH

• Thyroid scan: diffuse, symmetric, increased uptake

• Thyroid antibodies: TSI (TSHR-Ab) specific for Graves’

disease, anti-TPO and anti-Tg may be present

• Orbital USG / CT / MRI: infiltrative ophthalmopathy

Medical treatment• Carbimazole: 5-15 mg TID for 12-18 months

• Propylthiouracil (PTU): 50-100 mg TID for 12-18 mth

– After 12-18 mths, positive TSHR-Ab = 90% risk of recurrence, negative TSHR-Ab = 20% risk

• Propranolol: 20 mg TID ( for tremor & tachycardia)

• Carbimazole & PTU : block thyroid peroxidase

• PTU & Propranolol: block deiodinase (peripheral T4 to T3)

Radioactive iodine (I-131)• Indications:

– Failed / refused / contraindicated medical therapy or surgery

• Contraindications:

– Pregnancy, age < 30 yr , ophthalmopathy, low RAIU (< 5%)

• 5 - 10 m Ci orally for 4 -12 wk

– Effective in 75% cases

• For thyrotoxicosis after 12 wks: double dose repeated

• Post-treatment hypothyroidism treated with thyroxine

Total Thyroidectomy• Indications:

– Age < 30 yr, pregnancy, compression of trachea by

goitre, suspected cancer, ophthalmopathy

• Pre-operative treatment:

– Propylthiouracil / Carbimazole: to make pt euthyroid

– Potassium iodide (prevents iodine trapping):

• 100-300 mg / day to decrease intra-operative blood loss in pts who don’t become euthyroid with anti-thyroid drugs

Toxic multi-nodular goitre• 2nd common cause of thyrotoxicosis after Graves’

• Emerges insidiously (over 10 years) from non-toxic multi-nodular goiter due to mutation in TSH receptor

• Serum TSH suppressed; T4 & T3 marginally elevated

• Thyroid scan shows areas of hot & cold nodules

• Rx:

– Carbimazole , Radioactive iodine ablation or subtotal thyroidectomy

Plummer’s toxic adenoma• Occurs in younger pt (unlike Graves’ or toxic

MNG)

• Hyper-functioning thyroid nodule secretes excess T3 & T4 inhibits pituitary TSH secretion remaining thyroid gland becomes quiescent

• I-123 thyroid scan shows hot nodule

• Rx: Carbimazole , Radioactive iodine ablation or thyroid lobectomy

DiagnosisDegree of

thyrotoxicosis

Radioactive iodine uptake

Thyroid scan

Grave’s disease + + + + + + + + Homogenou

s uptake

Toxic multinodula

r goitre+ / + + Normal or +

+ Multiple hot

& cold nodules

Toxic adenoma + / + + Normal or +

+Dominant hot nodule

Thyrotoxic subacute

thyroiditis + + + + < 1% Absent

uptake

Thyroid nodule

Risk factors for malignancy in thyroid nodule

• Age <20 or >45 years

• Male sex

• Size > 4 cm or rapid increase in size

• Hard nodule

• Fixed to adjacent structure

• Lymph node metastasis

• Vocal cord paralysis / hoarse voice

• H/o irradiation or family h/o thyroid cancer

Thyroid malignancy

Classification1. Follicular:

a. Differentiated: i. Papillary carcinoma (60 – 80% )

ii. Follicular carcinoma (10 – 20%)

b. Undifferentiated: Anaplastic carcinoma (05 – 10%)

2. Para-follicular: Medullary carcinoma (05 – 10%)

3. Non-thyroid origin: i. Lymphoma (02 – 05% )

ii. Metastasis (rare)

Clinical features of thyroid neoplasm

• Thyroid gland enlargement (diffuse / nodular)

• Compression & infiltration features

– Recurrent laryngeal nerve: stridor & hoarseness

– Superior mediastinal syndrome: engorged neck veins

– Esophagus: dysphagia

– Sympathetic chain: Horner’s syndrome

– Tethering of overlying skin & muscles

• Mostly euthyroid ; hyper / hypothyroidism is rare

• Regional metastasis: enlarged neck lymph nodes

• Distant metastasis to lung / bone

Papillary carcinoma• Etiology: previous external radiation to head & neck

• 40 % rule: mean age 40 years, multi-centric in 40 %

cases, neck node metastasis in 40% (to level 6)

• Female : male ratio - 3:1

• Non-encapsulated cancer

• Lung metastasis uncommon (diffuse miliary

lesions)

Follicular carcinoma• Mean age 50 years

• Female : male ratio is 3:1

• Well-encapsulated ( mistaken for follicular

adenoma)

• Tendency to invade thyroid capsule & blood vessels

• Neck node metastasis seen only in 4% cases

• Metastasis to lung (cannon ball) & bone common

Medullary carcinoma• Malignancy of calcitonin -producing C-cells• Mutation of RET proto-oncogene present• Sporadic – 80% cases, no family history, other endocrine

tumors absent, normal physical appearance, unilateral, unifocal, poorer prognosis, peak in middle age to elderly

• Familial– 20% cases, autosomal dominant inheritance

within family, multiple endocrine tumors present, peak b/w 30-40 years

Anaplastic carcinoma• Non-encapsulated, rapidly growing, extra-thyroidal

spread with compression of trachea & esophagus

• Arise in pre-existing multi-nodular goiter or well-

differentiated thyroid cancers

• Node metastasis & pulmonary metastasis common

• Poorest prognosis (most die within 1 yr due to

airway obstruction, vascular invasion, distant

metastasis

TNM classification

Tumor:

T1: < 1 cm & limited to thyroid capsule

T2: > 1 to < 4 cm & limited to thyroid capsule

T3: > 4 cm limited to thyroid capsule

T4: any size extending beyond thyroid capsule

Neck lymph node enlargement:

NO: absent N1a: ipsilateral

N1b: midline / bilateral / contralateral

Distant metastasis: MO: absent M1: present

Treatment of thyroid

malignancy

Papillary & follicular cancer• Tumor size < 1 cm = Near total thyroidectomy  

• Tumor size >1 to < 4 cm = Total thyroidectomy

• Tumor size > 4 cm = Total thyroidectomy

• N0 = antero-lateral neck resection (levels 2,3,4 & 6)

• N1 = modified radical neck dissection + resection of

level 6 nodes + resection of level 7 nodes (if

involved)

Total thyroidectomy preferred in papillary cancer

1.Papillary carcinoma is multi-centric

2.Revision surgery more difficult than primary surgery

3.Limited surgery leads to:• Local recurrence & decreased survival rate

• Transformation into anaplastic carcinoma

• Inability to use thyroglobulin as tumor marker• Inability to use I131 for post-op imaging

• Inability to use I-131 for residual tumor ablation

Other Therapies1. Radioactive I 131: for recurrent / residual cancer

2. External radiotherapy:

• Inoperable cancer (invasion of trachea / esophagus): 3000 cGy debulking surgery 1500 cGy post-op

• Recurrent / residual cancer: 4500 – 5000 cGy

3. Chemotherapy: I.V. Doxorubicin 20 mg/week for inoperable cancer, recurrent or residual cancer

Medullary carcinoma• Total thyroidectomy + modified radical neck

resection + resection of level 6 & 7 nodes if involved

• Life long Thyroxine (250 g / day) aiming to keep serum TSH level < 0.5 mU/L

• Hypercalcemia present: remove 31/2 parathyroids

• Pheochromocytoma present: B/L total adrenalectomy

• Thyroid scan every 6 mth every yr every 3 yrs

Anaplastic carcinoma• External radiotherapy (3000 cGy) debulking

surgery post-op external radiotherapy (1500 c Gy) + I.V. Doxorubicin 20 mg / week

• Total thyroidectomy + radical neck dissection + post-op external RT (4500 – 6000 c Gy) + I.V. Doxorubicin 20 mg / week

• Emergency tracheostomy for airway obstruction

Thyroid lymphoma• 3-6 cycles of CHOP (cyclophosphamide,

doxorubicin, vincristine & prednisone) followed

by external radiotherapy to thyroid, bilateral

neck, supraclavicular regions & mediastinum

• Isthmusectomy for biopsy & relieving

compression

• Emergency tracheostomy for airway obstruction

Thyroid surgery

Why is right RLN commonly damaged in thyroid surgery?

• More superficial position

• Right nerve enters thyroid at 450 angle

whereas the left lies within tracheo-

esophageal groove

• Right nerve mostly passes superior to or b/w

branches of inferior thyroid artery; left nerve

mostly passes deep to inferior thyroid artery

• Lobectomy: removal of one thyroid lobe

• Isthmusectomy: removal of complete isthmus

• Hemi-thyroidectomy: lobectomy + isthmusectomy

• Subtotal thyroidectomy : preservation of some thyroid tissue in same and opposite tracheo-esophageal groove (8 g) + 2 parathyroid glands on opposite side

• Near-total thyroidectomy: preservation of thyroid tissue in opposite tracheo-esophageal groove (8 g) + 1 parathyroid gland on opposite side

• Total thyroidectomy : removal of total thyroid gland

Types of Thyroid surgeries