Download - 21. diseases of thyroid gland kk
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