The silent saboteur: How non-adherence is undermining your patients’ thyroid care

Hypothyroidism is among the most prevalent chronic endocrine disorders worldwide, affecting approximately 5% of the general population in its overt form, with subclinical disease reaching up to 10%.^1,2 Levothyroxine (LT4) monotherapy is the established standard of care with simple once-daily oral treatment.¹ Yet a persistent and clinically significant gap exists between what is prescribed and what is actually taken.

The scale of the problem: Non-adherence to thyroid treatment

Non-adherence to LT4 is quite common. Real-world adherence data consistently show that between 40% and 52% of patients fail to adhere to LT4 within the first year of treatment, and a large retrospective analysis of over 580,000 patients found non-adherence rates of 40.3% at six months, rising to 51.9% at twelve months.³

Adherence rates vary considerably by setting and patient population. The CONTROL Surveillance II study (2025) found that many patients were not following FDA-approved LT4 administration guidance, and that providing multiple dose variations or alternating-day regimens compounded confusion and worsened adherence.⁴ Studies in primary care setting report that only 26–32% of hypothyroid patients demonstrate high adherence, with the majority falling into the low or medium adherence category.^5, A 2025 real-world observational study of 398 patients found that 52% failed to reach TSH goals at their first follow-up check, medication possession ratio was only 66.8%, and just 47.7% demonstrated persistent use at one year.⁶

Clinical consequences of non-adherence

Poor adherence to LT4 directly translates into subtherapeutic thyroid hormone levels, persistent TSH elevation, and an accumulating burden of preventable clinical consequences, from cardiovascular risk to cognitive impairment.⁷

A 2023 narrative review by Feldt-Rasmussen et al. comprehensively characterised the consequences of undertreated hypothyroidism across the life course:⁷

• Cardiometabolic: Persistent hypothyroidism is associated with hypertension and elevated cardiovascular disease risk which is further worsened by an increased tendency to obesity.⁷
• Cognitive and neuropsychiatric: Unresolved cognitive impairment, fatigue, and depression are consistently reported in undertreated patients.^7,8 A cross-sectional study found that 44.1% of hypothyroid patients reported moderate depression, and only 58% demonstrated LT4 adherence. Poor knowledge and depressive symptoms are the strongest predictors of treatment failure.⁹
• Reproductive and obstetric: In women of reproductive age, undertreated hypothyroidism during pregnancy is associated with preterm birth and preterm birth— outcomes with lifelong implications.⁷

What are the barriers to non-adherence to hypothyroid treatment

The five most commonly implicated barriers are:

• Knowledge: Frequently, patients do not understand hypothyroidism and the consequences of its suboptimal treatment very well.¹⁰ Further, this becomes particularly dangerous given that patients with low health literacy are independently more likely to have uncontrolled TSH.¹¹
• Skills: Incorrect administration — particularly taking LT4 with food, supplements of calcium, iron, or other interfering substances — is a pervasive and underdetected form of non-adherence. Many patients are not aware of the 30-minute fasting window or how to navigate it practically.¹¹
• Memory/habit: Forgetfulness is the most commonly self-reported reason for missed LT4 doses across multiple studies.¹² In various studies of thyroidectomized patients, forgetting was the primary driver of non-adherence among solid tablet users.¹³
• Beliefs and motivation: Many times, patients are unaware of the consequences and risks of suboptimal treatment of hypothyroidism, which reduces intrinsic motivation to maintain consistent treatment.¹⁰
• Social and environmental factors: Some of the identified facilitators of non-adherence are lower economic status, poor access to health centres, and busy schedules.^6,12

How to identify non-adherence in clinical practice

Identification of non-adherence is a difficult task as the presentation of symptoms varies with age and sex. TSH remains the primary biochemical proxy which requires continuous monitoring.¹ Clinicians should maintain a structured approach to adherence assessment at every review, which includes:

• Validated self-report: The MMAS-8 is a widely used adherence tool in hypothyroid populations.⁵ It stratifies patients into low, medium, and high adherence categories.¹²
• Pharmacy refill analysis: Gaps between dispensing episodes are a practical, low-burden signal of adherence breakdown that can be integrated into electronic health record surveillance without additional clinical contact.
• TSH pattern analysis: Fluctuating TSH across visits without a clear dose or physiological explanation, or TSH normalisation following a structured medication discussion, are clinically significant indicators of adherence-related instability rather than pharmacological resistance.¹⁴

The 2025 real-world cohort study found that patients aged 40 or over, those with higher education, those with chronic comorbidities, and those who regularly attended TSH monitoring appointments were more likely to be persistent with LT4.⁶ Identifying the inverse profile — younger patients, irregular attenders, those recently initiated — may enable targeted early intervention.

Evidence-based strategies that can help to improve adherence

Following are some evidence-supported behavior change techniques (BCTs) that can provide actionable strategies in clinical practice:

Formulation-based interventions

Switching from standard tablets to liquid or softgel formulations is one of the most evidence-supported adherence interventions available. These formulations can be taken with meals without loss of therapeutic efficacy, directly removing the fasting requirement that underpins a large proportion of missed and incorrectly timed doses.¹² In a prospective study of 106 thyroidectomized patients, liquid LT4 users had significantly better MMAS scores and lower TSH levels than solid tablet users (p = 0.0085).^12,13 For patients who regularly struggle with the fasting window, or who identify co-administration with food or supplements as unavoidable, formulation switching should be an early, not last-resort, clinical decision.¹²

Tailored patient education

Education-based interventions include, providing information on the consequences of non-adherence, tailoring messages to individual patient beliefs and concerns, and addressing myths about long-term medication use.¹³ The 2025 health literacy study highlights the importance of assessing literacy level before choosing educational materials — complex written information has a demonstrably lower impact in patients with limited health literacy, where verbal teach-back and visual aids are more effective.¹¹ Family-centred education — involving partners or caregivers — emerged as one of the most consistently impactful social support interventions.

Pharmacist-led and multidisciplinary support

Individualised pharmacist counselling at the point of dispensing, particularly for newly initiated patients, has been repeatedly identified as an underutilised but high-impact strategy. Pharmacists are optimally positioned to identify administration errors, review potential drug–food interactions, and provide practical advice on fitting LT4 into daily routines. For patients with comorbid depression, onward coordination with mental health services should be considered as both a clinical need and an adherence intervention, given the well-documented bidirectionality of depression and non-adherence in this population.⁹

Digital tools and structured monitoring

Smartphone-based reminder applications, habit-anchoring strategies, and digital platforms linked to pharmacy refill records have demonstrated efficacy in targeting forgetfulness-driven non-adherence. The 2025 real-world cohort confirmed that regular TSH monitoring appointment attendance was independently predictive of LT4 persistence⁶ — suggesting that the act of scheduled biochemical monitoring itself functions as an adherence intervention. Building TSH review into proactive recall systems, rather than relying on patient-initiated attendance, should be standard practice.

The 2025 European Thyroid Association guidelines on LT4 monotherapy optimisation address adherence explicitly as a clinical priority. The guidelines emphasise the importance of individualising treatment — acknowledging that a single prescribing approach cannot accommodate the diverse barriers encountered across patient populations — and provide specific recommendations on formulation selection, dosing flexibility, and the clinical management of interfering factors including nutritional supplements, concomitant medications, and gastrointestinal comorbidities.¹⁵ Critically, the ETA guidelines note that switching between LT4 brands or formulations has caused adverse effects in some European patients, including fatigue, depression, hair loss, and TSH variability — reinforcing the recommendation for consistent preparation use once a patient is stable, as part of an adherence-supportive prescribing strategy.

Clinical Takeaways

Levothyroxine non-adherence is prevalent, clinically consequential, and largely preventable. For HCPs, the following principles should anchor routine practice:

• Assume adherence assessment is incomplete until you have asked — structured, non-judgmental inquiry at every review is more reliable than waiting for TSH failure to prompt the conversation.
• Distinguish non-adherence from treatment failure before escalating dose — TSH fluctuation without a clear physiological explanation should trigger an adherence review, not a prescription change.
• Match the intervention to the barrier — formulation switching for food/timing constraints, educational BCTs for knowledge deficits, psychological support referral for comorbid depression, digital reminders for forgetfulness.
• Liquid and softgel LT4 formulations offer a well-evidenced adherence advantage for patients who struggle with the fasting administration requirement, and should be considered early rather than as a last resort.¹²
• Health literacy assessment should inform how education is delivered — not just what is delivered — given its independent association with TSH control outcomes.¹²

This article was written with the assistance of generative AI technology and reviewed for accuracy.

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