Reviewed by Dr. Mehwish Ismaily
Stott, David J., et al. New England Journal of Medicine (2017)
Subclinical Hypothyroidism is defined as an elevated TSH and a free T4 within normal limits. Patients with this entity usually do not have symptoms of hypothyroidism such as fatigue. However given the broad range of effects of the thyroid hormone on multiple organ systems such as the heart, the bone, the brain and skeletal muscle, this study was undergone to understand the role of supplementation in the elderly population.
This trial was a randomized, double-blinded, parallel group trial that involved patients over the age of 65 years old (n=797) with subclinical hypothyroidism. The control group involved patients (n= 369) receiving a placebo and the experimental group involved patients (n=368) receiving levothyroxine with up-titration from a starting dose of 50ug (or 25 ug depending on history of heart failure and weight). Excluded patients included those using antithyroid medication, patients with ACS, adrenal insufficiency and recent thyroid surgery. The primary end points over the course of a year were changes in scores on a “Hypothyroid Symptoms” questionnaire and a “Tiredness” questionnaire. These questionnaires are well-studied measurement tools to assess quality of life in those with subclinical hypothyroidism. The scores range from 0 to 100 and a score of 0 denotes no symptoms from subclinical hypothyroidism.
In regards to thyroid function tests, the mean baseline TSH was 6.40±2.01 mIU per liter. After 1 year, the TSH was lower in the group on levothyroxine therapy with a mean of 3.63 mIU per liter (median dose 50 ug) vs. 5.48 mIU per liter in the placebo group (p<0.001). In regards to the primary outcomes, there was no statistically significant difference at 1 year in the Hypothyroid Symptoms and Tiredness scores. The mean scores on the Hypothyroid Symptoms questionnaire was 16.7±17.5 placebo group vs. 16.6±16.9 levothyroxine group (p=0.99). The mean Tiredness score was 28.6±19.5 placebo group vs. 28.7±20.2 levothyroxine group (p =0.77). The adverse events in the placebo and levothyroxine group were similar including new onset atrial fibrillation, heart failure, fracture, and new diagnosis of osteoporosis.
Despite the lack of difference in symptomatic scores among the elderly population in this study, the current literature suggests treating a TSH level above 10 mIU/L in patients who either test positive for antithyroid antibodies or are symptomatic have the benefit of preventing progression to hypothyroidism. A limitation of this particular study was that the mean baseline TSH was 6.40±2.01 mIU per liter and that antithyroid antibodies were not checked in each of the groups. In addition the baseline symptom scores were on the low end to start with, which may make it difficult to detect any significant symptom differences with levothyroxine treatment.
Proper diagnosis of subclinical hypothyroidism can also be challenging and require reassessment at 6-12 months as there are several factors that can affect TSH level including natural increase with age (age adjusted TSH levels are often not reported in the lab results), lithium use, amiodarone use, those recently receiving iodine contrast etc. In addition, there are also adverse events associated with those that are overtreated leading to a low TSH and a hyperthyroid state.