This case report details the clinical scenario of a 27-year-old female patient diagnosed with idiopathic refractory hypothyroidism. Despite adherence to prescribed oral levothyroxine therapy, she continued to experience persistent symptoms such as fatigue and cold intolerance. The exploration of her condition delved into the complexities of refractory hypothyroidism, encompassing both its diagnostic challenges and therapeutic management. A critical distinction was made between true levothyroxine malabsorption and pseudo-malabsorption, the latter being attributed to issues with medication adherence. The scarcity of research on intravenous levothyroxine use in such cases was noted, highlighting the novelty of this approach. The patient’s favorable response to intravenous levothyroxine administration, marked by complete symptom resolution and sustained euthyroid state over four years, provides valuable insights. This case contributes significantly to the existing knowledge on the idiopathic etiologies of refractory hypothyroidism and advocates for the consideration of intravenous levothyroxine as an effective alternative when oral administration proves inadequate.