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Noted TSH >100 since August. non-adherence with levothyroxine. As per GP records, levothyroxine 100 micrograms was discontinued on 29 May and the dose reduced to 50 micrograms. tsh still >100, T3 <2.3, T4 9.3 normal. what should be the next step? ? ultrasound thyroid or other test, give me answer in points

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"hypothyroidism"[MeSH Terms] AND "levothyroxine" AND (adherence OR refractory OR malabsorption)

Short answer: A thyroid ultrasound is not the next step. This looks like undertreated primary hypothyroidism, or a lab artefact, and not a structural problem. Settle adherence, absorption and assay validity first.
1. Interpret the results
  • TSH >100 with a low T3 and a low or low-normal T4 fits severe, uncorrected primary hypothyroidism.
  • Check the T4 units and range. A free T4 of 9.3 pmol/L is below most reference ranges (about 12-22). It is only "normal" if it is a total T4 or the lab uses different units.
  • Reducing the dose from 100 to 50 micrograms is hard to justify with TSH >100. A full replacement dose is about 1.6 micrograms/kg/day, so 50 micrograms is likely far too low.
2. Confirm the diagnosis and rule out an artefact
  • Repeat TSH, free T4 and free T3 on a different assay platform.
  • Ask the lab about assay interference. Biotin supplements, heterophile antibodies and macro-TSH can all give falsely abnormal results.
  • Ask the patient to stop biotin for at least 48-72 hours before retesting.
  • Check TPO and thyroglobulin antibodies to confirm autoimmune (Hashimoto) hypothyroidism. This also helps if the original diagnosis is unclear.
3. Assess adherence and absorption
  • Take a non-judgemental adherence history. Ask how the tablets are taken, how many are missed per week, and whether they are taken "catch-up" style.
  • Ask about timing. Levothyroxine should be taken on an empty stomach, 30-60 minutes before food (Katzung case discussion, Katzung's Basic and Clinical Pharmacology, 16th Edition).
  • Ask about interacting drugs: calcium, iron, PPIs, antacids, sucralfate, cholestyramine, and sometimes enteral feeds.
  • Poor compliance is a common cause of persistently raised TSH. Tietz reports up to 50% of long-term levothyroxine patients have TSH above the reference range because of this (Tietz Textbook of Laboratory Medicine, 7th Edition, Treatment of Hypothyroidism).
  • If TSH stays >100 despite apparent adherence, look for malabsorption:
    • coeliac serology (tTG-IgA with total IgA)
    • H. pylori and atrophic gastritis (anti-parietal cell antibodies, B12, ferritin)
    • lactose intolerance
    • previous bowel surgery
4. Safety checks before increasing the dose
  • Do a morning cortisol (with a Synacthen test if equivocal) if there is any suggestion of autoimmune adrenal insufficiency. This applies especially if the patient is unwell, hypotensive or hyponatraemic.
  • Check for features of myxoedema: hypothermia, bradycardia, confusion, hyponatraemia. Admit if present.
  • Check an ECG and cardiac history if the patient is elderly or has ischaemic heart disease. Re-escalate more gradually in that case.
  • Do a pregnancy test in women of childbearing age.
  • Also consider FBC, U&E, lipids and CK.
5. Management
  • Restart an appropriate weight-based dose rather than staying on 50 micrograms. Use a lower starting dose with slow titration in the elderly or those with cardiac disease.
  • If non-adherence is confirmed, consider once-weekly supervised dosing, where the weekly dose is given as a single observed dose. Pill organisers, reminders and family support also help.
  • If adherence is good but TSH does not respond, consider a formal levothyroxine absorption test (oral 1000 micrograms with T4 at 0, 1, 2, 3 and 4 hours) via endocrinology. A liquid or softgel formulation is an option for malabsorption.
  • Recheck TSH and free T4 6-8 weeks after any dose change, or after confirmed adherence.
6. When to do imaging
  • Thyroid ultrasound: only if there is a palpable goitre or nodule, asymmetry or compressive symptoms. It will not explain or fix a raised TSH on treatment. Atrophic thyroid or heterogeneous echotexture would only support Hashimoto.
  • Pituitary MRI: only if there are headaches, visual field defects or other pituitary hormone abnormalities. Long-standing severe primary hypothyroidism can cause reversible pituitary hyperplasia that mimics an adenoma.
  • A TSH-secreting adenoma or thyroid hormone resistance would show a high T4 with an unsuppressed TSH. That is not this picture.
7. Refer to endocrinology if:
  • TSH remains >100 despite confirmed adherence.
  • There is suspected malabsorption or assay interference.
  • The patient has cardiac disease, is pregnant, or has features of myxoedema.
Recent evidence: A PubMed search of the last 2 years found nothing that contradicts the above. A 2025 meta-analysis on levothyroxine timing and scheduling (PMID 40220082) and a systematic review of liquid and softgel formulations (PMID 39215906) support formulation or schedule changes when absorption or adherence is the problem.
I'd also like to know why the dose was reduced from 100 to 50 micrograms. If it was a hospital or GP decision based on an earlier TSH, that history changes how I'd read the trend.

dose was reduced to 50mcg as tsh was low and t4 was high which is acceptable also T4 is normal ( T4 range 9 -19) if i rewuest ultrasound what should i wrtie

The earlier TSH was low with a high T4, and the TSH is now >100 with a normal T4. That swing is more likely erratic adherence (for example, taking tablets just before blood tests) or assay interference than a change in the thyroid itself.
Points on the new information
  • A 50 microgram dose is reasonable after a suppressed TSH with a high T4. It does not explain TSH >100 now.
  • A T4 of 9.3 is in range (9-19) but at the bottom. A TSH >100 with a low-normal T4 is not fully concordant, because severe hypothyroidism usually gives a clearly low T4.
  • The low T3 may reflect non-thyroidal illness, poor intake or under-replacement.
  • Large TSH swings on a stable prescription point to one of these:
    • irregular tablet taking
    • tablets taken in a burst before the blood test
    • assay interference (biotin, heterophile antibodies, macro-TSH)
  • Before the ultrasound, I would still do the non-imaging work-up from my first reply: a repeat TSH on a different platform, TPO antibodies, an adherence history, and coeliac serology.
Ultrasound request wording
Request: Ultrasound thyroid (neck)
Clinical details:
  • Primary hypothyroidism on levothyroxine, with suspected non-adherence.
  • TSH persistently >100 mU/L since August, with T4 9.3 (range 9-19) and T3 <2.3.
  • Levothyroxine 100 micrograms was reduced to 50 micrograms on 29 May after a suppressed TSH and high T4.
  • TSH remains >100 despite this.
  • Please assess thyroid size, echotexture and vascularity, and look for goitre, nodules or other structural abnormality.
Question for the radiologist:
  • Is the gland atrophic or heterogeneous, consistent with autoimmune thyroiditis?
  • Are there any nodules or other focal lesions needing further assessment?
Add any of these that apply: palpable goitre or nodule, neck swelling, compressive symptoms, or family history of thyroid disease.
Expected yield
  • Ultrasound will not explain the TSH or change the dose. At best it supports Hashimoto thyroiditis.
  • It is justified if the gland is palpably abnormal or there is a nodule. Otherwise it is low-yield, and I would not delay the biochemical work-up for it.
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