Why is my levothyroxine not working?

When levothyroxine appears not to be working, there are three separate questions to answer in order. Is the TSH actually in range, is the tablet being absorbed, and if both are true, is the thyroid still the explanation for the symptom. Most cases resolve at the second question, because levothyroxine absorption is disrupted easily and quietly.

Absorption is the most common reason

The prescribing information instructs taking levothyroxine on an empty stomach, one half to one hour before breakfast, and separating it by at least four hours from drugs known to interfere with absorption. Beyond timing, several conditions raise the dose requirement measurably. A 2019 Endocrine Reviews review of gastrointestinal thyroxine malabsorption reports that Helicobacter pylori related gastritis increases the daily thyroxine requirement by about one third, that proven atrophic gastritis raises it by 32 percent, that omeprazole is associated with a 37 percent higher dose requirement, and that lactose intolerance raises it by 31 percent. Untreated coeliac disease also increases requirement, and the same review notes the effect was partially or completely reversed by a gluten-free diet.

Dose, formulation and consistency

Levothyroxine is a narrow therapeutic index drug. Switching between manufacturers at the pharmacy, splitting tablets unevenly, or alternating between morning and bedtime dosing can all move TSH enough to matter. Weight change, pregnancy, and starting oestrogen therapy all increase requirement. Some medications increase clearance, including carbamazepine, phenytoin, rifampicin and sertraline.

When the thyroid is no longer the problem

If TSH is in range on a stable dose taken correctly, further levothyroxine rarely helps and suppressing TSH below the reference range carries real risk of atrial fibrillation and bone loss. The joint American, British and European Thyroid Association consensus is explicit that patients with persistent symptoms should be considered for further intervention "once other causes for these symptoms have been excluded." Iron deficiency, B12 deficiency, sleep apnoea, perimenopause, depression and insulin resistance account for most of what remains.

Before asking for a dose increase, write down exactly how and when you take the tablet for one week, including supplements and coffee. Bring that record and your last two TSH results with dates. That single page changes more outcomes in my clinic than any additional test.