What is subclinical hypothyroidism?

Subclinical Hypothyroidism

Subclinical hypothyroidism is defined as an elevated thyroid-stimulating hormone (TSH) concentration with normal free thyroxine (FT4) levels, representing an early stage of thyroid dysfunction that may progress to overt hypothyroidism in 2-5% of cases annually. 1, 2

Definition and Diagnosis

• TSH reference range is typically 0.45 to 4.5 mIU/L 3
• Subclinical hypothyroidism diagnostic criteria:
  • Elevated TSH above the upper limit of normal (>4.5 mIU/L)
  • Normal free T4 levels
  • No overt symptoms of hypothyroidism 1, 4

Classification

Subclinical hypothyroidism is further classified based on TSH elevation:

• Mild subclinical hypothyroidism: TSH between 4.5 and 10 mIU/L
• Severe subclinical hypothyroidism: TSH >10 mIU/L 5

Epidemiology

• Prevalence: 4-8.5% of adults without known thyroid disease 3
• More common in women, especially those over 60 years (up to 20%)
• Less common in blacks (approximately one-third the prevalence seen in whites)
• Approximately 75% of cases have TSH values below 10 mIU/L 3
• Risk factors include:
  • Previous hyperthyroidism
  • Type 1 diabetes mellitus
  • Family history of thyroid disease
  • Previous head and neck radiation 3

Etiology

• Most commonly caused by autoimmune (Hashimoto's) thyroiditis 4
• Other causes include:
  • Iodine deficiency
  • Previous thyroid surgery or radioactive iodine treatment
  • Certain medications (amiodarone, lithium)
  • Recovery from thyroiditis 1

Natural History

• Annual progression to overt hypothyroidism: 2-5% of cases 2
• Risk factors for progression:
  • Higher baseline TSH (especially >10 mIU/L)
  • Presence of thyroid peroxidase (TPO) antibodies 3, 4
• Approximately 5% of cases normalize spontaneously within one year 3

Clinical Significance

Subclinical hypothyroidism may be associated with:

1. Cardiovascular effects:

   • Subtle decreases in myocardial contractility 3
   • Increased risk of heart failure and coronary artery disease events 4
   • Potential increased mortality from coronary heart disease 4

2. Metabolic effects:

   • Elevation in total and LDL cholesterol 3

3. Neuropsychiatric manifestations:

   • Fatigue and altered mood
   • Cognitive impairment in middle-aged patients 4

4. Pregnancy complications when untreated:

   • Increased risk of preeclampsia
   • Preterm delivery
   • Miscarriage 1
   • Impaired cognitive development of offspring 2

Clinical Considerations

• Age is an important factor - TSH levels naturally rise with age in people without thyroid disease, potentially leading to overdiagnosis in elderly patients 4
• The presence of TPO antibodies indicates higher risk of progression to overt hypothyroidism 4
• Symptoms may be subtle or absent, making laboratory diagnosis essential 6

Treatment Considerations

Treatment decisions should be based on:

1. TSH level:

   • TSH >10 mIU/L: Treatment generally recommended 2, 7
   • TSH 4.5-10 mIU/L: Treatment decisions more individualized 4, 7

2. Special populations where treatment is recommended regardless of TSH level:

   • Pregnant women or women planning pregnancy 2
   • Children and adolescents 7

3. Risk factors that may favor treatment in mild cases:

   • Presence of goiter
   • Positive TPO antibodies
   • Symptoms consistent with hypothyroidism
   • Fertility issues 7

4. Age considerations:

   • Treatment may be beneficial in young and middle-aged individuals with symptoms 4
   • Treatment should generally be avoided in those >85 years with mild elevation 2

Subclinical hypothyroidism represents an important clinical entity that requires careful consideration of patient factors, laboratory values, and potential progression to overt disease when making management decisions.