Levothyroxine Dose Changes and Hypothyroid Patient Satisfaction-Results of the CONTROL TS Study

Special Article - Hypothyroidism

Annals Thyroid Res. 2017; 3(2): 109-114.

Levothyroxine Dose Changes and Hypothyroid Patient Satisfaction-Results of the CONTROL TS Study

McMillan M¹*, Sandulli W², Engelken D², Rowe L³ and Bode B³

¹McMillan Survey Research & Statistical Consulting, USA

²Akrimax Pharmaceuticals, USA

³Health Research & Analytics, USA

*Corresponding author: McMillan M, McMillan Survey Research & Statistical Consulting, Memphis, 8428 Arendal Cove, Memphis, TN, USA

Received: June 20, 2017; Accepted: July 24, 2017; Published: August 08, 2017


Introduction: The effects of levothyroxine dose adjustments on patient satisfaction with drug therapy and physician care have not been described previously.

Primary Objective: To measure those effects among: patients who had no changes in levothyroxine dosage within the past year (n = 150), and patients who had = 2 changes in levothyroxine dosage within the past year (n = 150).

Methods: Eligible participants completed a 21-question online survey that employed ThyTSQ, a scientifically-validated instrument designed to assess patient satisfaction with: therapy performance and convenience, and the perceived quality of care provided by physicians. Between-group statistical testing was determined using a Chi-square test to compare proportions.

Results: Compared with those reporting no levothyroxine dose changes in the past year, patients reporting = 2 dose changes were significantly less satisfied with their treatment and treating physician: these patients had lower mean ThyTSQ-Present scores (30.1 vs. 33.2; P=.002); were less likely to be “very satisfied” with their treatment and dose (22% vs. 39%; P=.001); and were less likely to feel their hypothyroid symptoms were well controlled (15% vs. 34%; P<.001). Patients experiencing = 2 dose changes were also less likely to be “very satisfied” with how their physician dealt with their condition since its diagnosis (21% vs. 34%; P=.015), and were more likely to have changed physicians in the past year (23% vs. 14%; P=.054).

Conclusion: Results showed a strong correlation between the frequency of levothyroxine dose changes and reduced patient satisfaction with treatment, treatment convenience, symptom control and physician performance.

Keywords: Dose adjustment; Gastrointestinal; Levothyroxine; Satisfaction; ThyTSQ


FT4: FreeT4; IBS: Irritable Bowel Syndrome; GI: Gastrointestinal; GERD: Gastroesophageal Reflux Disease; TSH: Thyroid Stimulating Hormone


Hypothyroidism is a common endocrine disorder resulting from deficiency of thyroid hormone. It is typically a primary process in which the thyroid gland is unable to produce sufficient amounts of thyroxine [1]. In addition to symptoms that are associated with slowing of patients’ metabolism, such as weight gain or intolerance to cold, psychological symptoms, including reduced cognitive functioning, are also hallmarks of hypothyroidism [2]. In most cases, hypothyroidism can be treated effectively by oral thyroid hormone supplementation, most commonly levothyroxine.

Hypothyroid patients requiring increased doses of levothyroxine have been well documented in the medical literature and are common in clinical practice [3].

The prevalence and frequency of levothyroxine dose changes were recently confirmed in the CONTROL Surveillance Project conducted among 925 patients treated with levothyroxine monotherapy, the majority of whom (94%) had been treated for more than 2 years. Among this population, over 47% reported factors that can affect the performance of levothyroxine. More than 31% reported having experienced one or more levothyroxine dose changes within the past year; 8% reported experiencing 2 or more levothyroxine dose changes in the prior 12 months [4].

Although CONTROL Surveillance was not designed to measure quality of life, nearly 11% of respondents indicated that their thyroid condition ‘‘reduced their quality of life” and “rendered them unable to do the things they used to do.” Overall, 19.6% of patients stated that they were not fully satisfied with their hypothyroid treatment. According to Walsh et al. there are anecdotal reports from clinicians of persistent dissatisfaction with levothyroxine therapy among some patients [5]. These results prompted us to examine the association between levothyroxine dose adjustments and patient satisfaction with drug therapy and physician care.

Study objectives

The primary objective of our study was to measure the effect of levothyroxine dose adjustments among two groups of subjects using a validated treatment satisfaction instrument developed specifically for hypothyroid patients. The first group (n = 150) had not experienced any change in levothyroxine dosage or formulation in the prior 12 months (No Dose Change Group). The second group (n = 150) had experienced = 2 levothyroxine dose or formulation changes in the prior 12 months. Based on decades of clinical experience and studies such as CONTROL Surveillance, we concluded that 2 or more dose changes within the period of a year would be a better indicator of suboptimal therapy than only 1 dose change, which routinely occurs with levothyroxine.

Secondary objectives of the study included a comparison of patient satisfaction between the two groups on several dimensions including overall satisfaction with care, satisfaction with drug therapy and satisfaction with the perceived quality of care provided by treating physicians. The number of study subjects who had changed healthcare providers in the past 12 months was also measured. Patient characteristics were collected for both groups.


Sample size calculation

It was determined that a sample size of 300 would provide 80% power to detect a difference of 25% for all satisfaction scores. Statistical testing to compare the two study groups included a Chisquare test to compare proportions.

Selection of patients and exclusion/inclusion criteria: Eligible patients were selected from a proprietary database and asked to complete a 21-question online survey. Patients were excluded from the study if they were < 19 years old, pregnant or taking levothyroxine for less than one year. For the reasons described under Study Objectives, patients with 1 levothyroxine dose change in the prior year were also excluded. Patients received modest compensation for study participation.

Survey instrument: In order to measure patient satisfaction with hypothyroid treatment, the Underactive Thyroid Treatment Satisfaction Questionnaire (ThyTSQ) was used. This is the first scientifically-validated survey instrument developed to measure treatment satisfaction among hypothyroid patients [6]*. The ThyTSQ survey is divided into two parts, which have been validated as separate instruments: 4 questions measuring treatment and provider satisfaction at the beginning of hypothyroid treatment (ThyTSQPast). An additional 7 questions measure current treatment and provider satisfaction (ThyTSQ-Present). An Overall Satisfaction Score is derived by combining the results of both sections of the survey. The full list of survey questions can be found in the Appendix. For each survey question, the scale is 0-6, with higher scores representing higher satisfaction. As described above, the scores for all questions are then summed to create the Overall Satisfaction Score.

Data collection

Responses from 300 survey respondents were stored in an electronic database from which they were abstracted and analyzed. The study database was created and maintained by Health Research & Analytics (Parsippany, NJ).

Statistical analysis

Statistically significant differences between the two groups were determined using a Chi-square test to compare proportions. Results were calculated for both sections of the survey (ThyTSQ-Past and ThyTSQ-Present questions) as well as for overall results.

Study ethics/institutional review board information

The study protocol and methods used in CONTROL TS, including use of the Thy-TSQ survey instrument, were reviewed and approved by the IntegReview IRB in Austin, TX. To ensure that the research was in compliance with the Health Insurance and Accountability Act of 1996 (HIPPA), a waiver of authorization was obtained according to 45 CFR 164.512 (i)(l)(i), which allowed the collection and analysis of protected health data without the authorization of research participants. Survey results for individual patients were blinded to the study sponsor.



Mean age of patients receiving levothyroxine monotherapy was 53.2 years. Respondents were mostly female: 270 (90%). Nearly threequarters of respondents were Caucasian (Table 1). Although the demographic characteristics were similar between the two treatment groups, participants in the Dose Change Group were, on average, 9.5 years younger than those in the No Dose Change Group (P < .001). In terms of gender, both study groups were comparable, and reflect the composition of the general hypothyroid population.