Medication-Nonadherent Hypothyroidism Requiring Frequent Primary Care Visits to Achieve Euthyroidism
Background: Nonadherence to medications is a common clinical issue. We describe a case in which weekly visits to assess medication adherence achieved euthyroidism in a patient with persistent primary hypothyroidism and suspected nonadherence to levothyroxine. The patient, however, did not report nonadherence.
Case Presentation: A male aged 67 years with multinodular goiter underwent total thyroidectomy for abnormal thyroid nodule biopsy. Surgical pathology revealed papillary thyroid cancer with lymph node metastasis for which he received radioactive iodine treatment. His plasma thyrotropin (TSH) was noted to be 0.28 uIU/mL (reference range 0.35-4.00 uIU/mL) 7 months postsurgery while taking 224 mcg levothyroxine tablets daily. His plasma TSH remained elevated for about 5 years despite titrations of the levothyroxine dosage, counseling, and multiple follow-up visits. A home care nurse was involved in monitoring the patient taking levothyroxine daily and correctly but was unsuccessful. The patient and his son reported taking levothyroxine daily and correctly. The patient was asked to visit the primary care clinic every week for 6 weeks with all his medications. Repeat plasma TSH normalized to 1.01 uIU/mL. The suspected etiology of previously high plasma TSH was nonadherence to levothyroxine, which was discussed in detail with the patient. The patient verbalized understanding, was willing to follow recommendations and ended the weekly clinic visits. Repeat plasma TSH was again high and the patient claimed adherence, but weekly visits to primary care clinic were resumed, and life-threatening consequences of hypothyroidism were discussed with the patient and his son. After 9 weeks of visits, he was noted to have low plasma TSH (0.23 uIU/mL).
Conclusions: Weekly visits seem impractical but may help in cases of persistent hypothyroidism in which the patient admits to being or is suspected to be nonadherent to levothyroxine. Knowing their medication use will be checked at weekly clinic visits may motivate the patient to be adherent.
Discussion
There are multiple important causes to consider in patients with persistent hypothyroidism. One is medication nonadherence, which was most likely seen in the patient in this case. Missing even 1 day of levothyroxine can affect TSH and thyroid hormone levels for several days due to the long half-life of the medication.2 Hepp and colleagues found that patients with hypothyroidism were significantly more likely to be nonadherent to levothyroxine if they had comorbid conditions such as type 2 diabetes or were obese.3 Another study of levothyroxine adherence found that the most common reason for missing doses was forgetfulness.4 However, memory and cognition impairments can also be symptoms of hypothyroidism itself; Haskard-Zolnierek and colleagues found a significant association between nonadherence to levothyroxine and self-reported brain fog in patients with hypothyroidism.5
Another cause of persistent hypothyroidism is malabsorption. Absorption of levothyroxine can be affected by intestinal malabsorption due to inflammatory bowel disease, lactose intolerance, or gastrointestinal infection, as well as several foods, drinks (eg, coffee), medications, vitamins, and supplements (eg, proton-pump inhibitors and calcium).2,6 Levothyroxine is absorbed mainly at the jejunum and upper ileum, so any pathologies or ingested items that would directly or indirectly affect absorption at those sites can affect levothyroxine absorption.2
A liquid levothyroxine formulation can help with malabsorption.2 Alternatively, weight gain may lead to a need for increasing the dosage of levothyroxine.2,6 Other factors that can affect TSH levels include Addison disease, dysregulation of the hypothalamic-pituitary-thyroid axis, and TSH heterophile antibodies.2
Research describes methods that have effectively treated hypothyroidism in patients struggling with levothyroxine adherence. Two case reports describe weekly visits for levothyroxine administration successfully treating uncontrolled hypothyroidism.7,8 A meta-analysis found that while weekly levothyroxine tablets led to a higher mean TSH level than daily use, weekly use still led to reference-range TSH levels, suggesting that weekly levothyroxine may be a helpful alternative for nonadherent patients.9 Alternatively, patients taking levothyroxine tablets have been shown to forget to take their medication more frequently compared to those taking the liquid formulation.10,11 Additionally, a study by El Helou and colleagues found that adherence to levothyroxine was significantly improved when patients had endocrinology visits once a month and when the endocrinologist provided information about hypothyroidism.12
Another method that may improve adherence to levothyroxine is telehealth visits. This would be especially helpful for patients who live far from the clinic or do not have the time, transportation, or financial means to visit the clinic for weekly visits to assess medication adherence. Additionally, patients may be afraid of admitting to a health care professional that they are nonadherent. Clinicians must be tactful when asking about adherence to make the patient feel comfortable with admitting to nonadherence if their cognition is not impaired. Then, a patient-led conversation can occur regarding realistic ways the patient feels they can work toward adherence.
To our knowledge, the patient in this case report had no symptoms of intestinal malabsorption, and weight gain was not thought to be the issue, as levothyroxine dosage was adjusted multiple times. His plasma TSH levels returned to reference range after weekly pill count visits for 6 weeks and after weekly pill count visits for 9 weeks. Therefore, nonadherence to levothyroxine was suspected to be the cause of frequently elevated plasma TSH levels despite the patient’s insistence on adherence. While the patient did not report memory issues, cognitive impairments due to hypothyroidism may have been contributing to his probable nonadherence. Additionally, he had comorbidities, such as type 2 diabetes mellitus and obesity, which may have made adherence more difficult.
Levothyroxine was also only prescribed in daily tablet form, so the frequency and formulation may have also contributed to nonadherence. While the home nurse was originally sent to assess the patient’s adherence, the care team could have had the nurse start giving the patient weekly levothyroxine once nonadherence was determined to be a likely issue. The patient’s adherence only improved when he went to the clinic for pill counts but not when the home nurse came to his house weekly; this could be because the patient knew he had to invest the time to physically go to clinic visits for pill checks, motivating him to increase adherence.
Conclusions
This case reports a patient with frequently high plasma TSH levels achieving normalization of plasma TSH levels after weekly medication adherence checks at a primary care clinic. Weekly visits to a clinic seem impractical compared to weekly dosing with a visiting nurse; however, after review of the literature, this may be an approach to consider in the future. This strategy may especially help in cases of persistent abnormal plasma TSH levels in which no etiology can be found other than suspected medication nonadherence. Knowing their medication use will be checked at weekly clinic visits may motivate patients to be adherent.
