How to manage a patient with hypothyroidism and elevated TSH?

Management of Hypothyroidism with TSH 6 and Low Cortisol

Critical First Step: Address Adrenal Insufficiency Before Thyroid Replacement

You must start corticosteroid replacement immediately and wait at least one week before initiating levothyroxine, as starting thyroid hormone in the setting of untreated adrenal insufficiency can precipitate a life-threatening adrenal crisis. 1, 2

A serum cortisol of 96 (assuming nmol/L, approximately 3.5 mcg/dL) indicates significant adrenal insufficiency that requires urgent evaluation and treatment. 1

Why This Sequence Matters

• Thyroid hormone increases metabolic rate and cortisol clearance, which can unmask or worsen adrenal insufficiency when cortisol reserves are already depleted 1
• This is particularly critical in patients with suspected central hypothyroidism or hypophysitis, where both pituitary axes may be affected 1
• Physiologic dose corticosteroids (typically hydrocortisone 15-25 mg daily in divided doses) should be initiated for at least 7 days before thyroid replacement 1

Evaluation of the Hypothyroidism

Confirm the Diagnosis

• Repeat TSH measurement in 3-6 weeks along with free T4 to confirm the diagnosis, as 30-60% of elevated TSH levels normalize spontaneously 1, 3
• Measure free T4 to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4) 1
• Check anti-TPO antibodies to identify autoimmune etiology, which predicts higher progression risk (4.3% per year vs 2.6% in antibody-negative individuals) 1

Assess for Central vs Primary Hypothyroidism

• The combination of low cortisol and elevated TSH suggests possible dual pituitary/hypothalamic dysfunction requiring further workup 1
• If central hypothyroidism is suspected (inappropriately normal or low TSH with low free T4), evaluate other pituitary hormones including prolactin, LH, FSH, and IGF-1 4
• In central hypothyroidism, TSH cannot be used for monitoring—free T4 must be maintained in the upper half of normal range 2, 4

Levothyroxine Initiation After Cortisol Replacement

Starting Dose Selection

For patients under 60 years without cardiac disease:

• Start with full replacement dose of approximately 1.6 mcg/kg/day 1, 2, 5
• This rapidly normalizes thyroid function and prevents prolonged hypothyroid symptoms 1

For patients over 60 years or with cardiac disease:

• Start with 25-50 mcg daily and titrate gradually 1, 6, 5
• Elderly patients and those with coronary disease are at increased risk of cardiac decompensation, angina, or arrhythmias even with therapeutic doses 1, 3
• Use 12.5 mcg increments for dose adjustments in this population 1

Monitoring and Titration

• Recheck TSH and free T4 in 6-8 weeks after initiating therapy or any dose change 1, 6, 2
• Target TSH within the reference range (0.5-4.5 mIU/L) with normal free T4 1, 6
• Increase dose by 12.5-25 mcg increments based on patient age and cardiac status 1, 6
• Once stable, monitor TSH every 6-12 months or with symptom changes 1, 2

Special Considerations for TSH Level of 6 mIU/L

Treatment Decision Based on TSH Magnitude

• TSH of 6 mIU/L falls in the 4.5-10 mIU/L range, which represents subclinical hypothyroidism if free T4 is normal 1, 4
• Treatment is reasonable and recommended for patients already requiring evaluation for adrenal insufficiency, as they are symptomatic and at higher risk 1
• The presence of positive anti-TPO antibodies would further support treatment, given 4.3% annual progression risk 1

Evidence for Treatment at This TSH Level

• Randomized controlled trials show limited benefit for treating TSH <10 mIU/L in asymptomatic patients 7
• However, symptomatic patients (which this patient likely is, given low cortisol) may benefit from a 3-4 month trial with clear evaluation of benefit 1
• Treatment may improve symptoms and lower LDL cholesterol, though evidence is rated as "fair" quality 1

Critical Pitfalls to Avoid

• Never start levothyroxine before ruling out and treating adrenal insufficiency—this is the most dangerous error in management 1, 4
• Do not treat based on a single elevated TSH value without confirmation 1, 3
• Avoid overtreatment, which occurs in 14-21% of patients and increases risk for atrial fibrillation, osteoporosis, and fractures 1, 4
• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, increasing cardiovascular and bone risks 1
• Do not adjust doses more frequently than every 6-8 weeks, as steady state is not reached sooner 1, 2

Long-Term Management Considerations

• If both adrenal insufficiency and hypothyroidism are confirmed, lifelong replacement of both hormones will likely be necessary 1
• Consider endocrinology referral for complex management of potential hypopituitarism 4
• Ensure adequate calcium (1200 mg/day) and vitamin D (1000 units/day) intake if TSH becomes suppressed during treatment 1
• Monitor for symptoms of overtreatment including tachycardia, tremor, heat intolerance, or weight loss 1