Comorbidities, Concomitant Medications, and Diet as Factors Affecting Levothyroxine Therapy: Results of the CONTROL Surveillance Project

Drugs R D. 2016 Mar;16(1):53-68. doi: 10.1007/s40268-015-0116-6.


Background: The CONTROL Surveillance Project was a comprehensive patient-based survey conducted among hypothyroid patients undergoing treatment. The primary objective of the study was to specifically quantify the prevalence of factors adversely affecting levothyroxine therapy.

Methods: Participants were selected from a large proprietary database. Those eligible for the study completed a 21-question survey.

Results: Of the eligible hypothyroid patients, 925 (92.5%) were being treated with levothyroxine monotherapy. The mean age was 60.4 years; 755 (81.6%) were female and 168 (18.2%) were male. Almost half of those receiving levothyroxine (435, 47.0%) had at least one comorbid condition that could adversely affect its absorption: gastroesophageal reflux disease (33.8% of patients), irritable bowel syndrome (9.7%), lactose intolerance (7.8%), or a history of gastric bypass surgery or bowel resection (3.0%). Other factors reported by many patients that could adversely affect levothyroxine absorption included use of prescription medications (20.6%) and over-the-counter medications (34.3%) used to treat comorbid gastrointestinal (GI) conditions; use of dietary supplements (51.8%, primarily calcium and iron); and intake of foods/beverages high in fiber, iodine, or soy (68.0%). Of the 13.4% who reported difficulty controlling their hypothyroid symptoms, significantly more patients with comorbid GI conditions reported such difficulty (7.8 versus 5.6%, P < 0.01). Frequent changes in levothyroxine dosing (two or more dose changes in the past year) were reported by 8.0% of survey participants. Those with GI comorbidities were nearly twice as likely to have such changes (5.0 versus 3.0%, P < 0.01).

Conclusion: Better initial workup of patients, including identification of relevant GI comorbidities and allergies, may help in the early detection of factors that may affect the performance of levothyroxine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Comorbidity*
  • Diet / adverse effects*
  • Dietary Supplements / adverse effects
  • Female
  • Humans
  • Hypothyroidism / drug therapy*
  • Male
  • Middle Aged
  • Surveys and Questionnaires
  • Thyroxine / therapeutic use*


  • Thyroxine