What is the management of subclinical hypothyroidism?

Subclinical Hypothyroidism: Clinical Presentation and Management

Definition and Laboratory Findings

Subclinical hypothyroidism is defined as an elevated TSH (typically >4.5 mIU/L) with normal free T4 and T3 levels 1, 2. This represents a compensated state where the thyroid gland maintains adequate hormone production but requires increased pituitary stimulation 2.

The diagnosis requires:

• Elevated TSH above the reference range (typically 0.45-4.5 mIU/L) 1
• Normal free T4 levels (within laboratory reference range) 1, 2
• Normal T3 levels 2

Confirm the diagnosis with repeat testing after 3-6 weeks, as 30-60% of elevated TSH levels normalize spontaneously 1, 3. This is critical to avoid unnecessary lifelong treatment 1.

Clinical Presentation

Most patients with subclinical hypothyroidism are asymptomatic or have minimal symptoms 3, 4. When symptoms occur, they may include:

• Fatigue and decreased energy 5, 6
• Cold intolerance 5
• Weight gain 5, 3
• Constipation 5, 3
• Dry skin 5
• Voice changes or hoarseness 5, 3

However, these symptoms are nonspecific and overlap with many other conditions 5.

Treatment Algorithm Based on TSH Levels

TSH >10 mIU/L

Initiate levothyroxine therapy regardless of symptoms for all patients with confirmed TSH >10 mIU/L 1, 2. This threshold carries:

• Approximately 5% annual risk of progression to overt hypothyroidism 1, 4
• Increased cardiovascular risk, particularly heart failure and coronary heart disease 4
• Potential for symptom improvement and LDL cholesterol reduction 1, 6

TSH 4.5-10 mIU/L

Routine levothyroxine treatment is NOT recommended for most patients with TSH 4.5-10 mIU/L 1. Instead, monitor thyroid function tests at 6-12 month intervals 1.

Consider treatment in specific situations:

• Symptomatic patients with fatigue, weight gain, cold intolerance, or constipation 1, 2
• Positive anti-TPO antibodies (4.3% vs 2.6% annual progression risk) 1, 2, 4
• Pregnant women or those planning pregnancy 1, 2, 5
• Presence of goiter 1, 2
• Infertility 2
• Elevated LDL cholesterol 6

Avoid treatment in patients >85 years with TSH 4.5-10 mIU/L, as limited evidence suggests potential harm 2.

Levothyroxine Dosing

Initial Dosing

For patients <70 years without cardiac disease:

• Start with full replacement dose of 1.6 mcg/kg/day 1, 5
• Take on an empty stomach 3

For patients >70 years or with cardiac disease:

• Start with lower dose of 25-50 mcg/day 1, 5, 3
• Titrate gradually to avoid cardiac complications 1, 3

Monitoring and Adjustment

Monitor TSH every 6-8 weeks while titrating hormone replacement 1. Target TSH within the reference range (0.5-4.5 mIU/L) 1, 2.

Once adequately treated, repeat testing every 6-12 months or if symptoms change 1.

Adjust dose by 12.5-25 mcg increments based on current dose 1. Larger adjustments risk overtreatment 1.

Special Populations

Pregnancy

Women with hypothyroidism who become pregnant should increase their weekly levothyroxine dosage by 30% 5. TSH should be monitored and dosage adjusted during pregnancy 7. Untreated maternal hypothyroidism is associated with:

• Spontaneous abortion 7
• Gestational hypertension and pre-eclampsia 7
• Stillbirth and premature delivery 7
• Adverse effects on fetal neurocognitive development 7, 5

Elderly Patients

For patients >70 years, start with 25-50 mcg/day and monitor closely for cardiac complications 1. Atrial fibrillation is the most common arrhythmia observed with levothyroxine overtreatment in the elderly 7.

Children

Initiate levothyroxine therapy in children with TSH persistently >10 mIU/L, regardless of symptoms 8. Children with TSH 4.5-10 mIU/L should be treated if they have Hashimoto's thyroiditis, goiter, hypothyroid symptoms, or conditions like Turner or Down syndrome 8.

Critical Pitfalls to Avoid

Never treat based on a single elevated TSH value—30-60% normalize on repeat testing 1, 3. This represents transient thyroiditis in many cases 1.

Overtreatment occurs in 14-21% of treated patients and increases risk for:

• Atrial fibrillation, especially in elderly patients 1, 2
• Osteoporosis and fractures 1, 2
• Abnormal cardiac output and ventricular hypertrophy 1

Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH 1, 2.

In patients with suspected central hypothyroidism or concurrent adrenal insufficiency, start corticosteroids before levothyroxine to avoid precipitating adrenal crisis 1, 2.

Drug Interactions

Iron and calcium reduce gastrointestinal absorption of levothyroxine 3. Enzyme inducers reduce its efficacy 3. Separate administration by at least 4 hours 3.