The three general practices (comprising 18 physicians) served a combined registered population of 33 933 (with a similar age–sex structure to the general population of England). The trial flow chart shows the identification and progress of patients in the study (). A total of 497 patients prescribed thyroxine for primary hypothyroidism (autoimmune thyroiditis, thyroidectomy, radio-iodine therapy, both thyroidectomy and radio-iodine therapy) were identified. The point prevalence for treated primary hypothyroidism was 1.5% (95% CI = 1.3 to 1.6%). A total of 332 (67%) patients participated in the trial. Participants were on average 8 years younger than non-participants, were more likely to have had their TSH checked within the previous 12 months as part of their routine medical care, and were more likely to have had a recent TSH level within the reference range.
Baseline characteristics of patients at randomisation
The two groups were comparable at baseline (). Although the prescribed dose of thyroxine was similar in both groups (1.7mcg/kg in the intervention group versus 1.6mcg/kg for controls), more patients in the intervention group had undetectable TSH at baseline compared with the control group (20% versus 13%). A total of 329 (99%) participants had biochemically confirmed hypothyroidism, the three patients lacking biochemical confirmation had all undergone total thyroidectomy in the past.
Baseline characteristics of patients randomised with primary hypothyroidism (n = 332).
The time interval between baseline and follow-up assessments was a median of 96 days for both groups. On average only 2 days elapsed between telephone contacts and home visits. Most patients remained on the same dose of thyroxine throughout the trial (89% intervention; 92% control). Only two control group patients were completely lost to follow-up (one patient died and one developed severe depression). Baseline and follow-up TSH was available for 330 patients and completed questionnaires available for 328 patients (an additional two patients failed to complete the final questionnaire due to depression and confusion).
At the second assessment 22% of patients in both groups admitted to knowing another trial participant; however, no patients reported showing or being shown the intervention booklet by another participant in the trial.
Change in TSH (n = 330)
The mean within-subject change in TSH was −0.11mIU/L in the intervention group and −0.12mIU/L in the control group with an absolute difference between groups of 0.01mIU/L (95% CI = −0.93 to 0.94mIU/L) (). At baseline more patients in the intervention than the control group had undetectable TSH levels (). Baseline TSH also demonstrated regression to the mean, being negatively correlated with change in TSH over follow-up (Pearson correlation coefficient −0.42; 95% CI = −0.34 to −0.51). Consequently analysis of covariance (ANCOVA)16
was employed to adjust for differences in TSH at baseline. The absolute difference in mean within-subject change in TSH, (adjusted for baseline TSH using ANCOVA) was −0.12mIU/L (95% CI = −1.97 to 1.95).
Main outcome measures of mean ‘within-subject’ change in TSH, SF-36, and Hypothyroid Index (n = 330).
The overall results remained essentially the same with analysis restricted to patients remaining on the same thyroxine dose and also in those with detectable levels of TSH at baseline.
Patients who received the booklet showed some symptomatic improvement when compared to those receiving routine care. This improvement was seen for both vitality and general health on the SF-36 and also on the hypothyroid index. However, all these changes were small and not statistically significant ().
Subgroup analysis by baseline TSH
As the overall comparison failed to demonstrate any difference, a subgroup analysis should be interpreted cautiously. For patients with elevated TSH at baseline (TSH ≥4.8mIU/L), the mean reduction in TSH was 3.09mIU/L (95% CI = −2.57 to 8.76mIU/L) higher in the control than the intervention group (), although this is based on data from only 38 patients. Changes in TSH in the other three subgroups were much smaller (). None of the changes in TSH in subgroup analysis were statistically significant.
Subgroup analysis of mean ‘within-subject’ change in TSH categorised by baseline TSH (n = 330).
Hypothyroid information booklet
At follow-up, 153 (92%) patients in the intervention group recalled receiving the booklet and 148 (89%) recalled reading it; 70% read it more than once. In response to a satisfaction questionnaire administered at the end of the trial, almost all the patients who recalled reading the booklet had found it easy to read (99%) and understand (99%). Most found the booklet personally relevant (82%) and many had kept it for future reference (88%).