How to manage overt severe hypothyroidism?

Management of Overt Severe Hypothyroidism

Levothyroxine (T4) is the first-line treatment for overt severe hypothyroidism, with dosing tailored to patient age, comorbidities, and severity of disease. 1

Initial Assessment and Diagnosis

• Overt hypothyroidism is defined by elevated TSH with low free T4 levels, indicating significant thyroid hormone deficiency 2
• Common symptoms include fatigue (68-83%), weight gain (24-59%), cognitive issues (45-48%), cold intolerance, constipation, hoarseness, and menstrual irregularities (23%) 2
• Untreated severe hypothyroidism can progress to myxedema coma, a life-threatening condition with hypothermia, hypotension, and altered mental status, carrying up to 30% mortality 2

Treatment Algorithm

Initial Dosing Strategy

• For patients <70 years without cardiac disease or multiple comorbidities:

  • Start with full replacement dose of approximately 1.6 mcg/kg/day 1
  • This approach is appropriate for most young adults with severe hypothyroidism 3

• For patients >70 years or with cardiac disease/multiple comorbidities:

  • Start with a lower dose of 25-50 mcg/day and titrate gradually 1, 4
  • This conservative approach reduces risk of cardiac complications 3

Special Considerations

• If adrenal insufficiency is suspected or confirmed, adrenal replacement must be initiated BEFORE thyroid hormone replacement to prevent precipitating adrenal crisis 4
• Severe and prolonged hypothyroidism can lead to decreased adrenocortical activity; supplemental adrenocortical steroids may be necessary 4
• For patients with angina pectoris or elderly patients with suspected coronary artery disease, initiate therapy at low doses (12.5-25 mcg/day) and increase by no more than 5 mcg increments at 2-week intervals 4

Monitoring and Dose Adjustment

• Monitor TSH and free T4 every 6-8 weeks while titrating hormone replacement 1
• Target TSH level should be within the reference range (0.5-4.5 mIU/L) 1, 5
• Once adequately treated, repeat testing every 6-12 months or if symptoms change 1
• Dose adjustments should only be considered after 6-12 weeks due to the long half-life of levothyroxine 6

Common Pitfalls and Considerations

• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses high enough to fully suppress TSH, increasing risk for osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy 7, 1
• Avoid excessive dose increases that could lead to iatrogenic hyperthyroidism 1
• Certain medications reduce levothyroxine absorption (iron, calcium) or efficacy (enzyme inducers) 6
• Levothyroxine should be taken on an empty stomach to maximize absorption 5
• Untreated hypothyroidism can increase risk for cardiovascular events, insulin resistance, and reproductive health issues 2

Alternative Treatment Considerations

• While levothyroxine monotherapy remains the standard treatment, some patients with persistent symptoms despite optimal levothyroxine therapy may benefit from combination therapy with liothyronine (T3) 8
• The decision to start liothyronine should be made after optimizing levothyroxine therapy for 3-6 months with TSH in the 0.3-2.0 mU/L range 8
• Liothyronine should be used with great caution in patients with cardiovascular disease or the elderly, starting at very low doses (5 mcg daily) with increases of no more than 5 mcg at 2-week intervals 4

Monitoring for Treatment Success

• Clinical improvement should be assessed alongside biochemical normalization 3
• Most symptoms improve within 4-8 weeks of achieving normal thyroid hormone levels 2
• Persistent symptoms despite normalized TSH may warrant evaluation for other conditions or consideration of alternative treatment approaches 8