Hypothyroidism is a common condition affecting many individuals.  Symptoms of hypothyroidism can be very non-specific and include the following: fatigue, cold intolerance, constipation, and weight gain. According to Up-to-date (accessed on May 6, 2017), primary hypothyroidism is characterized by a high serum thyroid-stimulating hormone (TSH) concentration and a low serum free thyroxine (T4) concentration, whereas subclinical hypothyroidism is defined biochemically as a normal free T4 concentration with an elevated TSH concentration.

Given we tend to only screen with TSH, we often cannot differentiate between primary hypothyroidism and subclinical hypothyroidism.  Yet in the elderly population, subclinical hypothyroidism is very common.  Some clinicians would argue that treatment with levothyroxine may not be necessary.

This question was evaluated in the Trust Thyroid Trial, of which the results were published recently in the New England Journal of Medicine here.

Here are some highlights of the study:

Study Objective:

  • To determine whether there are clinical benefits from levothyroxine replacement in older persons with subclinical hypothyroidism.


  • A double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persistent subclinical hypothyrodism (TSH 4.6-19.99mIU/L, free thyroxine level within the reference range).
  • The main exclusion criteria were a current prescription for levothyroxine, antithyroid drugs, amiodarone or lithium; thyroid surgery or receipt of radioactive iodine within the previous 12 months, dementia, hospitalization for a major illness or an elective surgery within the previous 4 weeks, an acute coronary syndrome within the previous 4 weeks and terminal illness.
  • 368 adults were assigned to treatment group; 369 adults were assigned to placebo group.
  • Two primary outcomes were measured at baseline and at 1 year for the following:
    • the change in the Hypothyoridism symptoms score and
    • The Tiredness score on a thyroid-related quality-of-life questionnaire

Main Results

  • Hypothyroidism Symptoms Score at 1 year
    • Placebo group: 16.7± 17.5
    • Levothyroxine group: 16.6± 16.9
    • Difference (0.0 [-2.0 to 2.1]), p =0.99
  • Tiredness Score at 1 year
    • Placebo group: 28.6± 19.5
    • Levothyroxine group: 28.7± 20.2
    • Difference (0.4 [-2.1 to 2.9]), p = 0.77


  • Given there were no differences in the primary outcomes, the authors concluded that there was no apparent benefit in levothyroxine replacement therapy in older persons with subclinical hypothroidism.

Here are some of my thoughts:

In practice, I do see some elderly individuals present with elevated TSH but the repeat TSH with T4 results often confirm subclinical hypothyroidism.  I do agree that not everyone requires levothyroxine replacement, nor an increase in their existing levothyroxine dose. However, repeat monitoring every 3-6months may be warranted as some individuals do eventually develop primary hypothyroidism for which levothyroxine replacement would be indicated.

I don’t always jump to recommend increasing levothyroxine dose for an elevated TSH in the following scenarios:

  • New admission to a long term care facility due to progressive dementia. In this situation, the patient’s history is not reliable including the compliance history. Hence there is a good chance that the TSH is elevated because of non-compliance and may self-correct when the medication will be reliably administered in the long term care facility by registered staff.
  • Concurrent levothyroxine with calcium, iron or other multivitamin supplements. Levothyroxine may not be well absorbed if administered at the same time with these supplements. Hence, the first thing is to try changing the timing of administration as this may resolve the concern and correct for the TSH gradually.

What do you think? Do you encounter patients with hypothyroidism in your practice? How do you manage individuals with subclinical hypothyroidism?

Looking forward to hearing your thoughts. As always, thank you for dropping by and reading my post.