📎
Hypothyroidism
Causes of Hypothyroidism – Mechanisms and Key
Features
1. Riedel’s Thyroiditis (Fibrous Thyroiditis)
Mechanism: IgG4-related autoimmune condition → progressive fibrosis of thyroid gland.
Hypothyroidism: Seen in ~30% of patients.
Associated conditions: Autoimmune pancreatitis, retroperitoneal fibrosis, other fibrosing
disorders.
Complications of fibrosis:
Compression of recurrent laryngeal nerve → hoarseness.
Compression of trachea → stridor.
Compression of esophagus → dysphagia.
2. Subacute (De Quervain’s) Thyroiditis – Infectious/Inflammatory
Trigger: Often post-viral (e.g., respiratory infections).
Pathology: Granulomatous inflammation of thyroid → painful goiter.
Clinical features:
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Painful, tender thyroid gland.
Transient hypothyroidism (may follow an initial thyrotoxic phase).
Systemic features: fever, malaise.
Lab: Elevated ESR.
Outcome: Usually self-limiting.
3. Iatrogenic Hypothyroidism
Causes:
Thyroidectomy (surgical removal).
Radioactive iodine therapy (I-131).
Drugs:
Amiodarone (contains iodine → can trigger hypo- or hyperthyroidism).
Lithium (inhibits thyroid hormone release).
Wolff–Chaikoff Effect:
Excess iodine → transient inhibition of thyroid hormone synthesis (negative feedback
on thyroid peroxidase/TPO activity).
Can lead to hypothyroidism, especially in susceptible patients.
4. Secondary Hypothyroidism (Central Causes)
Problem: Pituitary or hypothalamic dysfunction → low TSH → low T3/T4.
Examples:
Pituitary adenoma → compresses pituitary tissue or hypothalamic-pituitary tract → ↓
TSH.
Mass effect: headache, bitemporal hemianopia (optic chiasm compression).
Sheehan’s Syndrome: Postpartum hemorrhage → hypovolemic shock → ischemic
necrosis of pituitary → panhypopituitarism.
Traumatic brain injury → damage to pituitary/hypothalamus.
Hormone cascade:
TRH (hypothalamus) → TSH (pituitary) → T3/T4 (thyroid).
Defect in hypothalamus: ↓ TRH → ↓ TSH → ↓ T3/T4.
Defect in pituitary: ↓ TSH directly → ↓ T3/T4.
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✅ Summary Table
Cause
Pathology
Clinical Notes
Riedel’s Thyroiditis
Fibrosis (IgG4)
Hard thyroid, compressive symptoms, 30% hypo
De Quervain’s
Post-viral, granulomatous
Painful goiter, ↑ESR, transient hypo
Iatrogenic
Surgery, RAI, drugs
Wolff–Chaikoff, amiodarone, lithium
Secondary
Pituitary/Hypothalamic lesion
Low TSH + mass effect (adenoma, Sheehan, TBI
Classic Findings in Hypothyroidism – With
Mechanisms
1. Goiter
Mechanism: ↓ T3/T4 → loss of negative feedback → ↑ TSH → thyroid follicular
hyperplasia.
Clinical: Enlarged thyroid, palpable or visible goiter.
Types:
Painful goiter → De Quervain’s thyroiditis (post-viral).
Painless goiter → Hashimoto’s thyroiditis, postpartum thyroiditis.
Massive goiter → iodine deficiency.
2. Metabolic Dysfunction
Mechanism: ↓ T3/T4 → ↓ basal metabolic rate (BMR).
Consequences:
↓ Na⁺/K⁺ ATPase activity → ↓ cellular metabolism.
↓ Lipid and glycogen catabolism → weight gain.
↓ Heat production → hypothermia, cold intolerance.
3. Fluid & Electrolyte Balance
Mechanism: ↑ ADH secretion → water retention.
Clinical: Dilutional hyponatremia.
4. Neurological Dysfunction
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Mechanism: ↓ T3/T4 → ↓ neuronal activity and neurotransmitter regulation.
Clinical: Severe lethargy, fatigue, depression, slowed mentation.
Reflexes: Delayed relaxation phase of deep tendon reflexes (classical).
5. Cardiovascular Dysfunction
Mechanism:
↓ β₁-receptor sensitivity in myocardium → ↓ heart rate & contractility.
↓ T3 → ↑ systemic vascular resistance (vasoconstriction).
Clinical:
Bradycardia.
Diastolic hypertension.
↓ Cardiac output.
6. Lipid Metabolism
Mechanism: ↓ T3/T4 → ↓ LDL-receptor expression in liver.
Clinical: Hypercholesterolemia, hyperlipidemia.
7. Reproductive Dysfunction
Mechanism: Thyroid hormones regulate prolactin, estrogen, and progesterone.
↓ T3/T4 → ↑ TRH → ↑ prolactin → menstrual irregularities.
Clinical:
Amenorrhea, menorrhagia, infertility.
↓ Libido.
8. Gastrointestinal Dysfunction
Mechanism: ↓ T3/T4 → ↓ smooth muscle activity in GI tract.
Clinical: Constipation, reduced motility.
9. Integumentary Dysfunction
Mechanism:
↑ TRH → ↑ TSH.
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TSH stimulates fibroblasts → ↑ glycosaminoglycan (GAG) deposition in tissues → water
retention.
Clinical:
Non-pitting edema (myxedema).
Pretibial edema.
Orbital edema.
Carpal tunnel syndrome (median nerve compression by edema).
✅ Exam classic clues:
Goiter, cold intolerance, bradycardia, weight gain, constipation, delayed reflexes,
myxedema (non-pitting edema).
Myxedema Coma (Severe Hypothyroidism)
Definition
A rare, life-threatening emergency due to decompensated hypothyroidism.
Occurs in chronic untreated or poorly controlled hypothyroidism exposed to acute stress.
Precipitating Factors
Infections (esp. pneumonia, sepsis).
Surgery, trauma.
Cold exposure (hypothermia).
Drugs (sedatives, opioids, anesthetics).
Non-compliance with thyroid medication (levothyroxine).
Pathophysiology
Chronic hypothyroidism → low metabolic reserve.
Acute stress → ↑ metabolic demand.
Hypothyroid body cannot adapt → “metabolic shutdown.”
Clinical Features with Mechanisms
1. Thermoregulatory
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↓ Na⁺/K⁺ ATPase activity → ↓ heat production.
Hypothermia (<35°C) is a hallmark.
2. Cardiovascular
↓ β₁-adrenergic receptor sensitivity → bradycardia, ↓ contractility.
↑ Systemic vascular resistance → ↑ afterload.
↓ Cardiac output → acute heart failure.
Risk of AV node dysfunction & cardiogenic shock.
3. Neurological
↓ Cerebral metabolism → encephalopathy.
Clinical: confusion, lethargy, stupor → coma.
4. Respiratory
Hypoventilation → CO₂ retention, hypoxia.
Often worsened by sedative sensitivity.
5. Skin / Edema
Severe generalized myxedema (GAG deposition).
Non-pitting edema → pretibial, periorbital.
Summary Table
System
Effect
Mechanism
Thermoregulation
Hypothermia (<35°C)
↓ BMR, ↓ Na⁺/K⁺ ATPase
Cardiovascular
Bradycardia, ↓ CO, ↑ SVR, acute HF
↓ β₁ receptors, vasoconstriction
Neurological
Confusion → coma
↓ neuronal metabolism
Respiratory
Hypoventilation, CO₂ retention
↓ central drive
Skin/Edema
Pretibial myxedema, non-pitting edema
↑ GAG deposition
✅ Key Clinical Pearl: Myxedema coma has very high mortality unless promptly treated with
IV levothyroxine, IV hydrocortisone (rule out adrenal insufficiency), warming, and
supportive ICU care.
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🧪 Diagnostic Approach to Hypothyroidism
Step 1: Obtain TFTs (Thyroid Function Tests)
Measure TSH, free T4, and free T3.
Step 2: Interpret Results
🔹 Low TSH + Low T4
Suggests Secondary (Central) Hypothyroidism (pituitary or hypothalamic).
Next step:
Check T3 and rT3:
Secondary hypothyroidism → T3 ↓, T4 ↓, rT3 ↓.
Euthyroid Sick Syndrome (ESS) → T3 ↓, T4 normal/low, rT3 ↑.
Obtain pituitary MRI if central cause suspected.
🔹 High TSH + Low T4
Primary Hypothyroidism.
Next step:
Test Anti-TPO and Anti-thyroglobulin antibodies:
Positive → Hashimoto’s thyroiditis (most common), postpartum thyroiditis.
Negative → Consider other causes:
De Quervain’s (post-URTI, painful goiter).
Riedel’s thyroiditis (IgG4, fibrous hard goiter).
Drug-induced (amiodarone, lithium).
Iodine deficiency.
🔹 High TSH + Normal T4
Subclinical Hypothyroidism.
Often early Hashimoto’s or iodine deficiency.
Monitor progression.
🔹 Low TSH + High T4/T3
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Hyperthyroidism (not in this flow, but important differential).
✅ Summary Table
TSH
T4
T3
rT3
Likely Dx
Next Step
↑
↓
↓
↓
Primary
hypothyroidism
Anti-TPO, AntiTg Abs
↓
↓
↓
↓
Secondary
hypothyroidism
Pituitary MRI
↓
↓
↓
↑
Euthyroid Sick
Syndrome
↑
N
N
N
Subclinical
hypothyroidism
Treat
underlying
illness
Monitor, repeat
TFTs
🩺 Treatment of Hypothyroidism
1. Primary or Chronic Hypothyroidism
Goal: Normalize TSH and T4, relieve symptoms, prevent complications.
Drug of choice: Oral levothyroxine (T4).
Dosage: Start low in elderly or cardiac patients; titrate based on TSH every 6–8 weeks.
Mechanism: Replaces deficient T4 → restores metabolic activity, cardiovascular function,
CNS function, lipid metabolism.
Monitoring: TSH and free T4 levels; symptom improvement.
2. Myxedema Coma (Severe/Life-Threatening Hypothyroidism)
Goal: Rapid restoration of thyroid hormone, support vital functions, prevent multi-organ
failure.
A. Thyroid Hormone Replacement
IV levothyroxine (T4) ± IV liothyronine (T3).
Rationale: T4 is converted to T3 in peripheral tissues; T3 acts faster but higher risk of
arrhythmia.
B. Supportive Care
Hypothermia: Passive and active external warming.
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Cardiovascular support: Monitor for bradycardia, hypotension, heart failure.
Respiratory support: Oxygen, ventilatory support if hypoventilation occurs.
C. Treat Presumptive Adrenal Insufficiency
IV hydrocortisone (before or alongside thyroid hormone replacement).
Rationale: Chronic hypothyroidism can mask adrenal insufficiency; thyroid hormone
increases metabolic demand, which can precipitate adrenal crisis if untreated.
Key Principles
1. Start low, go slow in chronic hypothyroidism, especially in elderly or cardiac patients.
2. IV thyroid hormone for severe myxedema coma.
3. Supportive ICU care: temperature, blood pressure, respiratory support, treat
infections.Monitor electrolytes, cardiovascular function, and mental status.
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