Study guide: Hypothyroidism

📋 Course Outline

1. Definition and General Features
2. Epidemiology Across Ages
3. Pathophysiological Mechanisms
4. Typical Clinical Presentation
5. Clinical Forms and Complications
6. Etiological Classification
7. Paraclinical Assessment
8. Systemic Impact
9. Replacement Treatment and Monitoring

📖 1. Definition and General Features

🔑 Key Concepts & Definitions

• Hypothyroidism: reduced thyroid function causing a slowing of cellular activities, usually because thyroid hormone production is decreased

★ Must-know

📌 Primary hypothyroidism originates in the thyroid and is associated with elevated TSH, central hypothyroidism originates in the pituitary or hypothalamus and is associated with normal or decreased TSH, and peripheral hypothyroidism is extra-thyroidal and is associated with elevated TSH.

• Untreated hypothyroidism can cause:
  • cardiovascular complications
  • hematopoietic complications
  • metabolic complications
  • obstetric complications
  • fetal complications
  • neonatal and childhood complications
  • myxedematous coma

Further detail

• Hypothyroidism is the most frequent congenital endocrinopathy and the most frequent endocrine disease in adults.

💡 Memory Hook

Reduced thyroid function → slowed cellular activity

📖 2. Epidemiology Across Ages

★ Must-know

• In adults, the prevalence of hypothyroidism increases with age and is approximately 1–10% worldwide, while the prevalence of undiagnosed hypothyroidism in Europe is approximately 5%.

• Hashimoto thyroiditis is the most frequent cause of adult hypothyroidism, whereas iodine deficiency is the most frequent cause in iodine-deficient areas.

• Congenital hypothyroidism occurs in approximately 1 in 3,000–4,000 births, while central congenital hypothyroidism occurs in approximately 1 in 50,000 births.

Further detail

• The incidence of adult hypothyroidism is 0.5–1% per year and increases with age.

• In children, acquired hypothyroidism is most often Hashimoto thyroiditis, and congenital hypothyroidism is more frequent in premature infants weighing less than 1,500 g and in some Hispanic and Asian populations.

💡 Memory Hook

Adults: Hashimoto predominates; iodine-deficient areas: iodine deficiency predominates

📖 3. Pathophysiological Mechanisms

🔑 Key Concepts & Definitions

• Myxedema: results from infiltration of the skin and subcutaneous tissues by extracellular matrix rich in acidic polysaccharides

★ Must-know

• Hypothyroidism slows metabolism, reducing energy consumption and altering the availability of T4 and T3.

• In children, thyroid hormones are essential for bone growth and nervous-system development, especially brain growth; untreated hypothyroidism can cause disproportionate short stature, mental retardation, and cretinism.

Further detail

• Maternal thyroid hormones cross the placenta in sufficient quantity for early development, and the fetal thyroid takes over from the 18th week of amenorrhea.

💡 Memory Hook

Slowed metabolism + mucoid infiltration → myxedema

📖 4. Typical Clinical Presentation

★ Must-know

• Typical hypothyroidism causes fatigue, cold intolerance, constipation, weight gain despite reduced appetite, psychomotor slowing, delayed ideation, bradycardia, and delayed relaxation of deep tendon reflexes.

• Myxedematous infiltration causes dry skin, hoarseness, hearing loss, snoring, sleep apnea, myalgia, arthralgia, and carpal-tunnel paresthesia.

Further detail

• Typical signs include a puffy face, lateral eyebrow loss, macroglossia, periorbital edema, infiltrated pale-yellow skin, and erythrocyanotic cheekbones and lips.

• Other findings include: sparse hair, dry brittle hair, ridged fragile nails, diastolic hypertension from increased peripheral resistance, low blood pressure from reduced cardiac output, pleuropericardial effusion, cardiomegaly, galactorrhea

💡 Memory Hook

Hypometabolism slows function, whereas myxedema infiltrates tissues

📖 5. Clinical Forms and Complications

★ Must-know

📌 Subclinical hypothyroidism is asymptomatic or mildly symptomatic, with elevated TSH and normal peripheral thyroid hormone levels.

• Associated risks include:

  • coronary disease
  • heart failure
  • dyslipidemia
  • type 2 diabetes

• Maternal complications include:

  • early miscarriage
  • anemia
  • hypertension
  • placental abruption
  • premature rupture of membranes
  • postpartum hemorrhage

• Untreated congenital hypothyroidism threatens psychomotor and mental development, with irreversible neurological sequelae when treatment begins after 3 months.

Further detail

• Myxedematous coma is characterized by hypothermia, bradycardia, hypoxemia, arterial hypotension, and dilutional hyponatremia, with a risk of collapse.

📖 6. Etiological Classification

★ Must-know

• Adult primary hypothyroidism may be iatrogenic, autoimmune, subacute, infiltrative, genetic, nutritional, or medication-related, including thyroidectomy, cervical irradiation, Hashimoto thyroiditis, postpartum thyroiditis, iodine deficiency, and goitrogen exposure.

📌 Central hypothyroidism results from acquired causes such as tumors, irradiation, surgery, trauma, infiltrative disease, or infection, or from rare congenital and genetic defects affecting TRH, TSH, or combined pituitary function.

• Thyroid dysgenesis includes:
  • ectopia in 70%
  • athyreosis in 25%
  • hypoplasia or hemiagenesis in 5%

Further detail

• Transient congenital hypothyroidism may result from maternal dysthyroidism or antibodies, iodine intoxication or deficiency, or maternal medications such as antithyroid drugs and iodides.

• Acquired childhood hypothyroidism is mainly autoimmune, iodine-deficient, surgical, irradiation-related, medication-related, tumoral, traumatic, infiltrative, or infectious.

💡 Memory Hook

Primary, central, peripheral: thyroid, pituitary-hypothalamus, or extra-thyroidal

📖 7. Paraclinical Assessment

★ Must-know

📌 TSH is the first-line test for suspected primary hypothyroidism: it is elevated in overt and subclinical primary hypothyroidism but often inappropriately normal in central hypothyroidism.

📌 Free T4 confirms central hypothyroidism, confirms subclinical primary hypothyroidism when interpreted with TSH, and assesses the depth of hormone deficiency; free T3 is unnecessary.

Further detail

• Positive anti-thyroid peroxidase antibodies support the diagnosis of autoimmune thyroiditis, while urinary iodine helps identify iodine overload or deficiency.

• Thyroglobulin is a marker of thyroid tissue and is particularly useful in congenital hypothyroidism; ultrasound assesses thyroid location, goiter, and signs of autoimmunity, while scintigraphy identifies ectopia and hormone-synthesis disorders.

💡 Memory Hook

TSH → free T4 → antibodies and imaging

📖 8. Systemic Impact

★ Must-know

• Hypothyroidism can cause myxedematous pericarditis, non-anginal chest pain, reversible systolic and diastolic dysfunction, and silent irreversible coronary atherosclerosis.

• Potential triggers include:

  • cold
  • infection
  • overhydration
  • medical or surgical stress
  • diuretics
  • opioids
  • sedatives

• Myxedematous coma causes death in 20% of cases.

Further detail

• Metabolic and hematopoietic consequences include: dyscalcemia, increased bilirubin, increased muscle enzymes, hyperlipidemia, dysglycemia, anemia, low protein S and C, acquired von Willebrand disease with hemorrhage

💡 Memory Hook

Deep neglected hypothyroidism + trigger → myxedematous coma

📖 9. Replacement Treatment and Monitoring

★ Must-know

📌 Levothyroxine replacement is usually lifelong and should be taken fasting 30–60 minutes before breakfast or at bedtime 2 hours after the last meal, under consistent daily conditions.

• Adult levothyroxine dosage is usually 1.5–1.8 μg/kg/day, is lower in older adults at 1.1–1.3 μg/kg/day, and increases by 30–50% during pregnancy.

📌 In fragile or elderly patients and in deep or longstanding hypothyroidism, treatment is initiated with 12.5–25 μg and increased gradually with clinical, hormonal, and electrocardiographic monitoring.

📌 TSH is reassessed every 6–8 weeks during dose adjustment and then every 6–12 months when normal; in central hypothyroidism, free T4 is measured fasting before levothyroxine.

• In children, levothyroxine dosage is age-dependent, ranging from 10–15 μg/kg/day before 3 months to 1.6 μg/kg/day after 16 years, and monitoring includes growth and puberty.

📌 In congenital hypothyroidism, earlier treatment is associated with a better IQ, and treatment targets are normal TSH and free T4 in primary disease and free T4 and free T3 in the upper half of normal in central disease.

Further detail

• Factors reducing absorption include:
  • meals
  • iron salts
  • calcium salts
  • magnesium salts
  • cholestyramine
  • aluminum hydroxide
  • sucralfate
  • proton-pump inhibitors

💡 Memory Hook

Dose, administer, monitor, adjust

📊 Synthesis Tables

Biological distinction of hypothyroidism

Type	TSH	Peripheral hormones
Primary overt	Elevated	Free T4 decreased
Primary subclinical	Elevated	Normal
Central	Often normal or low/inappropriate	Free T4 decreased
Peripheral or tissue resistance	Often elevated	Tissue response impaired