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Background and Importance Oral levothyroxine is the standard treatment for hypothyroidism. However, some patients present refractory disease despite high oral doses. Intramuscular (IM) administration of levothyroxine may provide a therapeutic alternative to these patients; nonetheless, its evidence is very limited. We present a case of difficult to control hypothyroidism, successfully treated with a weekly regimen of IM levothyroxine.Aim and Objectives To describe the clinical course of a 31-year-old woman with hypothyroidism refractory to high oral doses of levothyroxine. The patient had a history of Graves’ disease treated with iodine-131.Material and Methods Routine analytical tests were performed, revealing elevated thyroid-stimulating hormone (TSH) levels (>200 mU/L) despite treatment with oral levothyroxine at a dose of up to 1000 µg/week, with adequate adherence and administration technique. The levothyroxine absorption test showed an increase in free thyroxine (FT4) >100% after administration of 900 µg orally, ruling out malabsorption. After administration of 400 µg of intravenous (IV) levothyroxine, the patient reported significant clinical improvement, so it was decided to start treatment with IM levothyroxine, with clinical and biochemical monitoring every 6-8 weeks.Results Treatment began in June 2024 with 200 µg/week of IM levothyroxine. Doses were progressively titrated (250 → 375 → 500 → 650 → 800 µg/week) based on symptoms and biochemical findings. The patient reported substantial improvement in energy, mood, and functional capacity. Serial laboratory monitoring confirmed a gradual TSH reduction and stabilisation of FT4 in the low-normal range:18/06/2024:TSH 192.98;FT4 0.304/10/2024:TSH 127;FT4 0.5431/01/2025:TSH 23;FT4 0.8825/08/2025:TSH 17;FT4 1The treatment was well tolerated, with no adverse reactions observed. Adherence was excellent, supervised by healthcare professionals and family members.Conclusion and Relevance Weekly IM levothyroxine successfully stabilised thyroid function and improved clinical status in a patient with refractory hypothyroidism. Although not included in current clinical guidelines, this approach may serve as a valuable option in selected cases. Further studies are required to establish long-term safety, efficacy, and standardised treatment protocols.References and/or Acknowledgements 1. Grebe SK, Cooke RR, Ford HC, Fagerström JN, Cordwell DP, Lever NA, et al. Treatment of hypothyroidism with once weekly thyroxine. J Clin Endocrinol Metab. 1997;82(3):870–5.2. Koulouri O, Auldin MA, Agarwal R, Murray RD. Intramuscular and subcutaneous levothyroxine: a successful treatment for non-compliance. Endocrinol Diabetes Metab Case Rep. 2013;2013:130060.Conflict of Interest No conflict of interest