What is the management of hypothyroidism?

Management of Hypothyroidism

The principal treatment for hypothyroidism is oral T4 monotherapy (levothyroxine sodium), which should be titrated to normalize TSH levels and improve clinical manifestations. 1

Diagnosis and Initial Evaluation

• Hypothyroidism is diagnosed based on biochemical testing; a high thyrotropin (TSH) level and a low free thyroxine (T4) level indicate overt primary hypothyroidism 2
• The serum TSH test is the primary screening test for thyroid dysfunction; multiple tests should be done over a 3-6 month interval to confirm abnormal findings 1
• Follow-up testing of serum T4 levels in persons with persistently abnormal TSH levels can differentiate between subclinical (normal T4 levels) and overt (abnormal T4 levels) thyroid dysfunction 1
• Common symptoms include fatigue (68%-83%), weight gain (24%-59%), cognitive issues (45%-48%), cold intolerance, constipation, dry skin, and menstrual irregularities (approximately 23%) 2, 3

Treatment Algorithm

Overt Hypothyroidism

• All patients with overt hypothyroidism (elevated TSH with low free T4) should be treated with levothyroxine 4
• Initial dosing should be tailored to patient-specific factors 2:
  • Young, otherwise healthy patients can start with full calculated dose 4
  • Lower starting doses should be used for elderly patients or those with atrial fibrillation and coronary artery disease 5, 2
  • For patients with severe or long-standing hypothyroidism, start with lower doses to avoid cardiac complications 5, 4

Subclinical Hypothyroidism

• For subclinical hypothyroidism with TSH >10 mIU/L, levothyroxine therapy is recommended 1, 4
• For subclinical hypothyroidism with TSH between 4.5-10 mIU/L:
  • Routine treatment is not recommended 1
  • Thyroid function tests should be repeated at 6-12 month intervals to monitor for improvement or worsening in TSH level 1
  • Consider treatment in symptomatic patients, patients with infertility, and patients with goiter or positive anti-thyroid peroxidase (TPO) antibodies 4
  • Treatment should probably be avoided in those aged >85 years 4

Special Populations

Pregnancy

• Women who are pregnant or planning pregnancy with subclinical hypothyroidism should receive levothyroxine therapy 1, 5
• TSH should be monitored every 6-8 weeks during pregnancy and the levothyroxine dose modified as needed 1, 5
• The requirement for levothyroxine in treated hypothyroid women frequently increases during pregnancy 5
• After delivery, the levothyroxine dosage should return to the pre-pregnancy dose 5

Central Hypothyroidism

• In central hypothyroidism (pituitary or hypothalamic cause), treatment is tailored according to free or total T4 levels, which should be maintained in the upper half of the normal range for age 4
• If hypopituitarism is present, adrenal deficiency must be corrected prior to starting thyroid hormone replacement to avoid precipitating adrenocortical insufficiency 6

Monitoring and Dose Adjustment

• TSH monitoring should be performed 6-8 weeks after initiating levothyroxine treatment or when changing the dose 2
• Once the TSH level is at goal, annual monitoring is recommended 2
• For primary hypothyroidism, target TSH is typically 0.5-2.0 mIU/L 4
• Overtreatment is common in clinical practice and should be avoided as it is associated with increased risk of atrial fibrillation and osteoporosis 4
• In patients with persistently elevated TSH despite an apparently adequate replacement dose, check for poor compliance, malabsorption, and drug interactions 4

Alternative Treatment Considerations

• While levothyroxine monotherapy remains the standard of care, some patients report residual symptoms despite normalized TSH levels 7
• Combination therapy with levothyroxine plus liothyronine (T3) has been evaluated in multiple clinical trials with mixed results 7, 8
• Until clear advantages of levothyroxine plus liothyronine are demonstrated, levothyroxine alone should remain the treatment of choice 8

Common Pitfalls and Caveats

• Overdiagnosis of thyroid dysfunction is common, as many persons labeled with hypothyroidism spontaneously revert to a euthyroid state over time 1
• Overtreatment can lead to iatrogenic hyperthyroidism with risks of osteoporosis, fractures, abnormal cardiac output, or ventricular hypertrophy 1
• Starting thyroid hormone in patients with adrenal insufficiency without first correcting the adrenal deficiency can precipitate adrenocortical crisis 6
• Levothyroxine should be used with great caution in patients with angina pectoris or the elderly, where there is a greater likelihood of occult cardiac disease 6