SUN-314 - Iatrogenic Central Hypothyroidism from Chronic High-Dose Liothyronine

Introduction
Central hypothyroidism is characterized by low free thyroxine (T4) with a low or inappropriately normal thyroid-stimulating hormone (TSH). Chronic exogenous liothyronine (T3) exposure can suppress the hypothalamic-pituitary-thyroid (HPT) axis, resulting in reduced TSH secretion and decreased endogenous T4 production.

Case Presentation
A 72-year-old female was admitted with septic shock secondary to streptococcal pneumonia and bacteremia. Thyroid testing revealed free T4 < 0.10 ng/dL (0.93–1.70), TSH 0.01 mcIU/mL (0.27–4.20), and free T3 0.8 pg/mL (2.0–4.4). Her history included depression, severe osteoporosis, and hypothyroidism. Since her diagnosis over 35 years earlier, she had remained on liothyronine 25 mcg three times daily (75 mcg/day), as prior attempts to switch to levothyroxine were poorly tolerated due to severe fatigue.

The combination of profoundly low free T4 and suppressed TSH in the setting of long-term supraphysiologic T3 exposure was consistent with central hypothyroidism due to HPT-axis suppression. The low T3 level was attributed to interruption of liothyronine during critical illness. She exhibited minimal clinical features of hypothyroidism, and vasopressor requirements were improving with sepsis treatment. AM cortisol was 22.4 mcg/dL, excluding adrenal insufficiency. Additional testing showed total T4 0.8 mcg/dL (5.3–11.6), total T3 31 ng/dL (80–200), free thyroxine index 0.7 mcg/dL (4.4–11.4), and T-uptake 1.07. Thyroid-binding protein levels were likely reduced given hypoalbuminemia (albumin 2.2 g/dL).

We gave an intravenous loading dose of levothyroxine 200 mcg followed by weight-based oral levothyroxine 88 mcg daily. Given uncertainty regarding peripheral T4-to-T3 conversion after decades of high-dose T3 exposure, low-dose liothyronine 5 mcg twice daily was continued temporarily. Free T4 increased to 0.45 ng/dL but remained suboptimal on day 4 (0.47 ng/dL), prompting an increase in levothyroxine to 100 mcg daily. At discharge, free T4 improved to 0.88 ng/dL with clinical stabilization. At four-week follow-up, free T3 was elevated (7.1 pg/mL), total T3 was 283 ng/dL, and free T4 remained low-normal (0.88 ng/dL), leading to further reduction of liothyronine to 2.5 mcg twice daily and an increase in levothyroxine to 112 mcg daily.

Discussion
Our case highlights that prolonged supraphysiologic liothyronine therapy can result in significant HPT-axis suppression with severe T4 depletion. While guidelines recommend titrating levothyroxine to mid-to-upper reference-range free T4 levels in central hypothyroidism, evidence guiding management when the condition is secondary to chronic exogenous T3 exposure is limited. Short-term continuation of low-dose liothyronine may be considered in selected patients during T4 repletion, with close monitoring and a structured taper as free T4 normalizes.

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