MON-444 - A Case of Refractory Hypothyroidism, Call for A Systematic Approach in the Management.

Background: Difficult to control hypothyroidism remains a diagnostic and therapeutic challenge, particularly in patients with complex gastrointestinal comorbidities. This frequently leads to empiric escalation to alternative costly levothyroxine (LT4) formulations or parenteral therapy without objective confirmation of mechanism. We present a case highlights the value of structured reassessment in apparent refractory hypothyroidism.

Case: A 76-year-old frail woman with long-standing symptomatic hypothyroidism and persistently elevated TSH despite escalating LT4 therapy, including standard tablets, soft-gel (Tirosint), liquid LT4, and intramuscular LT4 at 500 mcg weekly for over two years. Her history included severe underweight (BMI 14) and distal pancreatectomy, pancreatic enzyme replacement was optimized. Interfering factors, including biotin supplementation and heterophile antibody interference, were systematically excluded.

A supervised LT4 absorption test demonstrated a ≥67% absorption, effectively excluding clinically significant malabsorption. Consumptive hypothyroidism due to excess type 3 deiodinase activity was considered but lacked clinical or laboratory support. Management was reframed to focus on pharmacokinetic optimization rather than non-oral therapy.

LT4 was reintroduced orally with a fixed bedtime dosing schedule, titrated to 200 mcg daily (2.6 mcg/kg/day). After this adjustment, the patient’s TSH declined steadily and normalized to 2.17 mIU/L, representing the first sustained biochemical control in several years. The patient reported no thyroid-specific hyper- or hypothyroid symptoms, though baseline fatigue persisted and was deemed multifactorial.

Conclusion: Levothyroxine malabsorption is primarily associated with gastric or intestinal pathology rather than pancreatic disease. In a four-year Mayo Clinic study, true malabsorption was uncommon (8%), with most cases reflecting pseudomalabsorption. This case highlights the value of a structured, stepwise approach to apparent refractory hypothyroidism: verifying adherence, excluding assay and medication interference, optimizing LT4 dosing timing, and performing formal absorption testing before escalating to alternative formulations or parenteral therapy. Such approach provides a cost-effective approach in the management of refractory hypothyroidism

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