Thyroid Evaluation, Thyroiditis and Hypothyroidism, Hyperthyroidism 😍

Thyroid gland secretes:

• T4: Primarily (93%)

• T3: Less (7%)
• T3 is the most active form.

Feature	T4	T3
Secretion Rate	Higher	Less
Plasma Concentration	Higher	Lower
Half-life	Longer (7 days)	Shorter (1 day)
Affinity for Nuclear Receptor	Lower	Higher
Potency	Lower	3-5 times more potent
Speed of Action	Slower	Faster action

Hormone Conversion:

• Most T4 → active T3
• Occurs in: Kidney, liver
• Mediated by: Type 1 Deiodinase.

• Some T4 → inactive Reverse T3 (rT3).

Transport

• T3 and T4 are lipophilic.

• In blood, thyroid hormones are mostly bound to plasma proteins.
• 99% bound to binding proteins.
• 1% Free (Responsible for actions).

• Major binding proteins:
1. Thyroxine binding globulin (TBG)
• Maximum T4
2. Thyroxine-binding pre-albumin (transthyretin)
3. Albumin
• Maximum T3

• Mnemonic:
• T3 → 3 → M →
• MCT
• MIT + DIT
• T4 → 4 → A
• oATP

Effect of Starvation

• Active T3 → ↑↑ BMR.

During starvation

• body conserves energy to ↓↓ BMR.

• T4 levels stable

• T4 → ↑↑ inactive Reverse T3 (rT3).
• T3 levels ↓↓ , rT3 levels ↑↑

Synthesis Mechanism

Raw Materials:

• Tyrosine: From thyroglobulin (Tg).

• Iodine: Present as iodide in diet.

1. Sodium Iodide Symporter (NIS)

• Basolateral end of follicular cells.

• Function: Iodide trapping 
• I from blood → cell
• Type: 2° active transport 
• uses Na+ gradient by Na+/K+ ATPase
• maintain low Na+ inside the cell.

• Other locations: Salivary gland, mammary gland, placenta.

2. Iodide Antiporter/Pendrin

• Location: Thyroid gland, inner ear.

• Transports Cl- into the cell and I- into the lumen

• Mutation
• Pendred syndrome.
• Symptoms: Goiter, Sensorineural hearing loss.
• Mnemonic: Pendrive → if Go (Goitre) → No song (SNHL)

3. Thyroid Peroxidase (TPO)

• Function:
• Oxidizes reduced iodide (I-) → oxidized I2.
• Organification:
• Catalyzes iodination of tyrosine residues on Tg
• form MIT (monoiodotyrosine) & DIT (diiodotyrosine)
• Coupling reactions:
• MIT + DIT → T3
• DIT + DIT → T4
• DIT + MIT → rT3 (inactive)

• Anti-thyroid drugs:
• Inhibit TPO activity.
• Examples: Propylthiouracil, Carbimazole, Methimazole.

4. Storage

• Thyroglobulin + attached MIT, DIT, T3, and T4
• stored in the colloid in lumen.

• reserve for 2-3 months.

5. Release

• Colloid breakdown → T3, T4 → Released into blood.

Thyroid Examination

• Pizzillo's method:
• Patient's hand on occiput & leans.

• Lahey's method:
• To feel margin of gland.
• Mnemonic: Lahey → touch Laterally

• Crile's method:
• Thumb → To palpate nodules.
• Mnemonic: Cry when using thumb

• Berry’s test → For common carotid artery
• CCA is berry important

Thyroid Function Tests (TFT)

• 1st investigation: 
• TSH & USG Neck.
• TSH abnormal:
• Check T3, T4.
• TSH normal / ↑
• FNAC (IOC):
• But Cannot differentiate b/w follicular adenoma vs carcinoma.
• TSH ↓
• Tc99 Thyroid scan.

• Additional: 
• Anti-thyroid antibodies.

Thyroid USG

Features of Malignant Nodule

• Hypoechoic.

• Microcalcifications.

• Border irregularity.

• Intranodular vascularity.

Gross features:

• Taller > Wider.

• Abnormal cervical lymph nodes:
• Round shape.
• Loss of fatty hilum.

TIRADS Score:

• TR3, TR4, TR5 lesions → FNAC.

• 2 → Benign

• 5 → Malignant

• DOPPLER → NOT CRITERIA

Fine-Needle Aspiration Cytology (FNAC)

Useful in:

• Thyroid

• Breast

• Lymph nodes (L.N.)

• Not useful in:
• Distinguishing between follicular adenoma and follicular carcinoma.

• FNNAC: Fine needle non - aspiration cytology.

Royal College of Pathologist Classification
(Similar to Bethesda classification):

Adequacy Criteria for Thyroid Fine Needle Aspiration Cytology (FNAC)

• Given by the Bethesda group.

• The 6/10 Rule:
• At least 6 follicular groups.
• Inside every group, at least 10 cells.

• Exceptions (CCI):
• Rule not followed in:
• Colloid goiter (more colloid).
• Cancer (diagnosis even if few cells).
• Inflammation (e.g., Hashimoto's thyroiditis).

Thyroid Scan

Isotopes

• Technetium 99.

• Iodine 123.

Indications

• Hyperthyroidism.

• ↓TSH.

• Ectopic or aberrant thyroid tissue.

Scan Types

Thyroiditis (Inflammatory Disorders)

 

 

Hypothyroidism (Low T3/T4):

Clinical Features

• Dull.

• Slow/lethargic.

• Cold intolerant.

• Bradycardia.

• Constipation.

• Weight gain.

Causes

• Iodine deficiency (m/c cause overall).

• Hashimoto's thyroiditis (m/c in western world).

• Wolf Chaikoff effect:
• I₂ induced hypothyroidism
• Excess iodide uptake through NIS 
• inhibits organification and synthesis of thyroid hormones
• Use: Pre-operative treatment for hyperthyroidism
• (e.g., Rx with lugols iodine prior to thyroidectomy).

• Non-functioning pituitary adenoma.

Signs

• Reliable sign:
• Hungup ankle jerk

• Note:
• Hungup reflex:
• Huntington's chorea
• Mnemonic: Hunt cheyyumbo pinne vilikkam enn prnj phone vakum

Hashimoto's Thyroiditis
(Lymphocytic Thyroiditis/ Struma Lymphamatosa)

• Autoimmune disorder.

• A/w: Down's Syndrome, Turner Syndrome.

• Antibodies Increased:
• Anti-TPO antibody, 
• Anti-thyroglobulin antibody.

Clinical: 

• Hypothyroidism.

• Painless neck swelling.

• Gross: Diffuse enlargement.

Course

• Hashitoxicosis (T3, T4 briefly ↑) → Hyperthyroidism → f/b → Prolonged hypothyroidism → Euthyroid.

Ix

• Autoantibodies (diagnostic):
• Thyroid receptor (Blocking).
• Thyroglobulin.
• Thyroid peroxidase.

• HPE:
• Lymphocytic infiltration.

Microscopy:

• Lymphoid aggregates with germinal centers.

Hallmark:

• Hurtle cells (Askanazy cells) → extremely pink

• Mnemonic: H for Hallmark, H for Hashimoto's, H for Hurtle cells

Increased Cancer Risk: 

• Papillary carcinoma thyroid, 

• Lymphoma (MALToma).

• Mnemonic:
• Hashime (Hashimotos) → Ask (Askanazy) malli (maltoma) aunty (Anti TPO) to hurry (Hurthle) before papi (papillary ca)
• Mnemonic: Malli () Elli Palli

Mx

• Thyroxine replacement.

• Surgery (Diffuse goitre).

Congenital Hypothyroidism

• MC preventable/ treatable cause of mental retraction/ intellectual disability in children

Thyroid dysgenesis

• MCC of congenital hypothyroidism.

• Thyroid dysgenesis > Thyroid dyshormonogenesis

Thyroid dyshormonogenesis

• Most common cause of congenital hypothyroidism in a child with goitre

Universal newborn screening for Cong. Hypothyroidism

• At birth, with umbilical cord blood

• Heel prick:
• dried blood spots,
• sample collected beyond 48 hrs or 48-72 hrs
• Should not be done in 1st 1-2 days,
• TSH surge in 1st 2 days

• Most sensitive approach
• check for T4 & TSH both

Investigations

• Thyroid scan: Radionucleotide uptake scan
• Isotopes: Iodine-123 (I-123) or Sodium Pertechnetate technetium 99m

• Thyroid ultrasound

• Serum thyroglobulin (TG)

Interpretation of Thyroid Scan

• 1. No Uptake
• Perform: USG + Serum Thyroglobulin
• TG absent → Thyroid aplasia
• TG present → Likely normal thyroid
• Measure TRAb
• If present → Maternal TRAb
• If negative → Iodine trapping defect

• 2. Ectopic Uptake
• Indicates Ectopic thyroid

• 3. Increased Uptake
• Suggests Dyshormonogenesis

Treatment

• Oral Levothyroxine (early morning with empty stomach)

• Dose is higher in the earlier age group
• as the babies grow → dose reduces.

X-ray Findings in Congenital Hypothyroidism

• Long bones
• Absent distal femoral and proximal tibial epiphyses at birth
• Punctate epiphyseal dysgenesis (multiple foci of ossification)

• Spine
• Deformity or breaking of T12 or L1/L2 vertebra

• Skull
• Large fontanels
• Wide sutures
• Enlarged, round sella turcica
• Wormian (intrasutural) bones → Also seen in Osteogenesis Imperfecta

De Quervain's Thyroiditis (Granulomatous Thyroiditis)

• Key Feature: 
• Only painful thyroiditis.

Microscopy: 

• Granulomas, 

• giant cells.

Etiology:

• Usually post-viral infection (e.g., mumps, adenovirus).

• Subacute.

• A/w HLA B35

C/F

• Painful neck swelling

Course

• Hyperthyroidism → Hypothyroidism → Spontaneous recovery → Euthyroid.

Mx

• Supportive care.

Subacute Lymphocytic Thyroiditis

• Associated with postpartum pregnancy history.

• Subacute, painless.

Riedel's Thyroiditis

• Extensive fibrosis.

• Mnemonic: Ridiculous (Riedel) → Stone (hard like stone) 4 God (Ig4)

Clinical:

• Thyroid gland very hard, like a stone → mimics cancer.

• Fibrous deposition in and around gland.

Reclassified: 

• IgG4-related disease (IgG4 causes fibrosis).

C/F

• Painless neck swelling.

• Woody hard gland.

• Hoarseness of voice (RLN involvement).

• Stridor (Tracheal compression).

Ix

• Trucut biopsy
• To rule out anaplastic thyroid cancer

Mx

• Steroids.

• Tamoxifen.

Hyperthyroidism

Clinical Features

• Thin & irritable.

• Weight loss despite good appetite.

• ↑ sleeping pulse/resting tachycardia

• Diarrhea.

• Tremors.

• Heat intolerance.

Causes

• Solitary toxic nodule.

• Factitious hyperthyroidism:
• Exogenous thyroxine intake.

• Jod Basedow phenomenon:
• I₂ induced hyperthyroidism.

• Struma ovarii:
• Thyroid tissue in ovary (usually malignant).

Management (Mx)

1. Drugs only:
• Propyl thiouracil (PTU):
• Safe in 1° pregnancy.
• Carbimazole.
• S/E: Agranulocytosis.

2. Drugs f/b radioactive iodine (I¹³¹).

3. Drugs f/b Sx
• inadequate preparation prior to Sx → causes Thyroid storm

Preparation for surgery

• Anti-thyroid meds
• for 6-8 weeks → 2 months
• Last dose → Evening before surgery.

• Long acting beta blockers: 
• Nadolol
• Beta blockers continued for 7 days post surgery.

Graves' Disease

• M/C → Endogenous hypothyroidism

• F>>M

• Type 2/5 hypersensitivity reaction

• 1° thyrotoxicosis.

• Autoimmune condition.

• Long acting thyroid stimulating antibodies.

• Associated with:
• Pernicious anemia, myasthenia gravis

• Thyroid hormone: OSTEOPENIA

Q. The most probable antibody detected in this condition is:

• A. Antithyroglobulin antibody.

• B. Anti gliadin antibody.

• C. Antitransglutaminase antibody.

• D. Long-acting thyroid stimulator antibody.

Clinical Triad:

1. Hyperthyroidism

2. Infiltrated Dermopathy → Pretibial Myxedema

3. Infiltrative Ophthalmopathy → Proptosis/Exolpthalmosis
• Both are due to accumulation of mucopolysaccharide/GAG (Hyaluronic acid)

Cause: 

• Anti TS1 (Thyroid stimulating immunoglobulins)

• Anti LATS (Long acting thyroid stimulator)

• Antibodies cross-react with TSH receptor analogs in preadipocyte fibroblasts
  → release cytokines → edema
• Retroorbital tissues → Exophthalmos.
• Pretibial dermatopathy
• Clubbing.

Eye Signs (Classical):

• Most Common Muscle Involved:
• Inferior Rectus (causing restriction in upgaze).
• Order of involvement (Mnemonic: I'M SLow):
• Inferior → Medial → Superior → Lateral.

ㅤ	ㅤ	ㅤ
True von Graefe sign	Graves’ disease	Lid lag on downgaze
Pseudo von Graefe sign	3rd nerve misdirection syndrome	• Aberrant regeneration of CN 3 • Wrongly innervate LPS Example: • Patient looks down → lid retraction

Gross:

• Thyroid gland becomes beefy red
• Mnemonic:
• Grave → We Reach grave when→ working too much and being on fire (Fire flares), becoming red(beefy red), and eating a lot (↑ colloid).

Microscopy:

• Scalloping of colloid.

• Fire flares on FNAC.

• Pseudopappilla - No fibrovascular core
• Associated with exophthalmos.

Eye Radiology

Management by Patient Status

• Preoperative administration of Potassium Iodide
• ↓ Thyroid synthesis
• ↓ Vascularity
• ↓ Bleeding during surgery

Goitre

Thyroid gland enlargement

Types

Retrosternal Goitre

• 1° Mediastinal:
• Ectopic thyroid tissue.
• Blood Supply: Mediastinal vessels.

• 2° Retrosteranal:
• Starts in neck → Goes behind sternum (Plunging goitres).
• Blood Supply: Neck vessels.
 

• Clinical Features:
• Dyspnoea, stridor, Pemberton Sign.

• IOC:
• 1st investigation → USG Neck
• CECT Neck/Thorax (IOC).

• Mx:
• Surgery → Neck only (Cervical only).

• Indications of median sternotomy:
• 2° Retrosternal is neck only surgery fails
• 1° mediastinal goitre.
• Large malignant retrosternal goitre.
• Recurrence in mediastinum.

Thyroidectomy

Types of Thyroidectomy

• Note: Difficult to redo surgery in case of recurrence.

• Complications:
• equal in all types of surgery
• Hypothyroidism.
• RLN injury.
• Hypoparathyroidism

Open Thyroidectomy Steps

1. Rose position:



• Neck extended.
• 30° head elevation (exposing incision site).

2. Collar incision:
• Just 2 finger breadths above suprasternal notch.

3. Subplatysmal tunnel.

4. Strap muscles retraction.

5. Cutting of strap muscles:





• To expand surgical field.
• Done high up to prevent ansa cervicalis injury.









 

6. Localization of parathyroid gland:



• Yellowish.
• D/t sentinel pad of fat.

7. Thyroid gland removal (observe RLN, Trachea).

8. Incision closure
1. Romovac suction drain

Minimally Invasive Video-Assisted Thyroid Surgery (MIVAT)

• Approaches:
• Transaxillary (m/c).
• Trans-oral.
• Retroauricular.
• Nipples.

• Indications:
• < 3 cm nodule.
• T1 papillary thyroid cancer.
• Parathyroid adenoma.

Complications of Thyroid Surgery

1. Hemorrhage

2. Nerve injury

• External laryngeal nerve
• M/c nerve injured during thyroidectomy
• Supplies Cricothyroid muscle
• Controls vocal cord tensor.
• Function: Tensor, adductor (intrinsic muscle)
• Injury → Hoarseness (due to inability to tense cords) → Low pitch
• Mnemonic: Ele (ELN) monu CT (cricothyrodi) edukkan poyapo tension (Tensor) ayi
• Preserved by ligating STA close to gland
• m/c goes unnoticed
• U/L or B/L: Hoarseness/inability to speak at high pitch.
• Not life threatening.

• Recurrent laryngeal nerve (Less common):
• Runs near Inferior Thyroid Artery
• Important for voice preservation
• Injured: Left > Right

3. Post-operative respiratory distress

• Laryngeal edema (m/c cause).

• Tension hematoma:
• Mx: Open sutures → Evacuate hematoma.

• Reactionary hemorrhage.

• Laryngomalacia.

• Bilateral RLN injury.

4. Hypoparathyroidism:

• Late cause (>48-72 hours after surgery).

• D/t vascular insult (ITA) to gland during surgery.

• Respiratory muscle paralysis (d/t hypocalcemia)
• m/c cause of death

• C/F: 
• Perioral numbness (initially)
• Trousseau sign (more specific).
• Sphygmomanometer → Carpopedal spasm
• Accoucheur’s hand position
• Chvostek sign.
• Tapping facial nerve infront of tragus
• Spasm of facial muscles
• NOTE: Troisier’s sign
• Left supraclavicular Lymphadenopathy
• In metastatic abdominal lymphadenopathy

• Mx:
• Monitoring symptoms, serum calcium & serum PTH levels.
• S. Ca²⁺ >8 mg/dL + minor symptoms:
• Oral Ca²⁺ + Oral vitamin D₃.
• S. Ca²⁺ <8 mg/dL (OR) major symptoms:
• IV Calcium Gluconate + Oral Ca²⁺ + Oral Vit D₃.