Target level for TSH during thyroxine therapy

Primary hypothyroidism in a non-pregnant adult

Thyroid function test should be done at least after 6-8 weeks of therapy.

• fine tuning of the dose could be necessary in some patients
  • aim of levothyroxine treatment is to make the patient feel better, and the dose should be adjusted to maintain the level of thyroid stimulating hormone within the lower half of the reference range, around 0.4 to 2.5 mU/l. If the patient feels perfectly well with a level in the upper half of the reference range, then adjustment is unnecessary (1)
    • in a small prospective study of initiating levothyroxine treatment for newly diagnosed primary hypothyroidism, there was no difference in lipid profile, body composition, or bone mineral density in patients maintained on low TSH (0.4-2.0 mIU/L) as compared with those maintained on higher TSH (2-4 mIU/L) for 12 months (2)
      
      
  • TSH level below the reference range may be acceptable in younger patients who require a higher dose of levothyroxine to fully control symptoms but over treatment should be avoided (3)
    • a serum TSH level of less than 0.1 mU/l (fully suppressed) should always be avoided.
      • low levels (0.1 to 0.4 mU/l) may be tolerated in young individuals who require a higher dose of levothyroxine to fully control symptoms (1)
      • low TSH levels in older people (>60 years) should prompt a small dose reduction of 25 µg daily, or on alternate days
        
        
      • maintaining TSH concentrations below 0.1 mU/l is poor practice due to the increased risk of osteoporosis and atrial fibrillation (1,3,4). The exception to this is after thyroidectomy for thyroid cancer, when TSH values may need to be suppressed to and maintained at a concentration <0.1 mU/l (1,3,4)
        
        
  • a persistently abnormal serum TSH level during levothyroxine treatment may be seen in (1):
    • situations where levothyroxine is taken only on the day of the blood test - thyroid function test will typically show raised TSH level but normal or raised free thyroxine levels
    • situation where absorption of levothyroxine in prevented e.g. - by drugs, malabsorption (think about excluding coeliac disease and autoimmune gastritis)

Hypothyroidism in pregnancy

• Requires specialist advice. Maintenance of the euthyroid state is the aim of management during pregnancy:
  • in women with hypothyroidism diagnosed before pregnancy and who are already taking thyroxine
    • for hypothyroid women planning pregnancy, levothyroxine dose ideally should be adjusted to keep TSH less than 2.5 mIU/L before conception (4,5)
    • thyroid function should be checked as soon as the pregnancy is confirmed to adjust the dose of levothyroxine further
    • at the first prenatal visit the dose is usually increased by 30-50% (as early as four to eight weeks' of gestation)
      • some studies have suggested an increase by 30% as soon as the woman finds out that she is pregnant (before evaluation) to minimize early maternal hypothyroidism
      • an alternative approach is to advise the woman to increase the dose of levothyroxine by 30%-50% as soon as pregnancy is confirmed to avoid any delay in dose increment (4)
    • the increase in dose varies with the cause of hypothyroidism e.g. - in women without any residual thyroid tissue, the dose should be increased more rapidly to a greater amount and than those with Hashimoto's thyroiditis (3)
    • thyroid function should be monitored at regular intervals (every 4-6 weeks) to adjust the dose of levothyroxine to keep TSH under 2.5 mIU/L in the first trimester and under 3.0 mIU/L in the second and third trimesters (5)
      • patients will need a reduction of their levothyroxine dose after pregnancy (4)
        
        
  • in women with overt hypothyroidism diagnosed during pregnancy
    
    • aim is to normalise the thyroid function test as soon as possible (3)
    • thyroxine dose should be adjusted to reach and maintain serum TSH concentrations in the low normal range (0.4-2.0mU/L) in the first trimester (or trimester specific normal TSH values) (5)
    • thyroid function test should be repeated during therapy - four to five weeks after the onset and every six weeks thereafter (3)
      
  • in women with subclinical hypothyroidism
    • thyroxin therapy is associated with improved obstetrical outcome but does not modify long-term neurological development of the fetus
    • the American Endocrine Society recommends thyroxine replacement in pregnant women with subclinical hypothyroidism (3)
    • there is general consensus that subclinical hypothyroidism in pregnant women should also be treated with levothyroxine (4,5)

Reference:

• Vaidya B, Pearce SH. Management of hypothyroidism in adults. BMJ. 2008;337:a801
• Boeving A, Paz-Filho G, Radominski RB, Graf H, de Carvalho GA. Low-normal or high-normal thyrotropin target levels during treatment of hypothyroidism: a prospective, comparative study. Thyroid. 2011;21(4):355-360
• Association for Clinical Biochemistry (ACB), British Thyroid Association (BTA), British Thyroid Foundation (BTF) 2006. UK guidelines for the use of thyroid function tests
• Todd CH. Management of thyroid disorders in primary care: challenges and controversies. Postgrad Med J. 2009;85(1010):655-9
• Chakera AJ et al. Treatment for primary hypothyroidism: current approaches and future possibilities. Drug Des Devel Ther. 2012; 6: 1-11.
• Abalovich M et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2007 Aug; 92(8 Suppl):S1-47.