Research · PMID 41938307

PubMed sourcedAbstract-based analysis

Reviewed by Neal Rouzier, MD, Preventive Medicine · Sep 2026

Use of Thyroid Hormones in Patients with Hypothyroidism and Euthyroidism in the United States: American Association of Clinical Endocrinology International Collaboration with the THESIS Investigators.

AACE endocrinology and diabetes · January 2026 · Leslie S Eldeiry, Roberto Attanasio, Laszlo Hegedüs, Roberto Negro, Enrico Papini, et al.

What this study found

LT4 monotherapy is overwhelmingly employed as first line therapy for hypothyroidism by U.S. However, the high usage of thyroid hormones for patients whose symptoms were considered to be unrelated to hypothyroidism is at odds with current international guidelines for the management of hypothyroidism.

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How RAGMD uses this study

Clinical questions this paper informs

Synthesis lives on the evidence question — this page shows where the study sits in that analysis.

Primary study

Is desiccated thyroid extract superior to levothyroxine for hypothyroidism?

Levothyroxine is standard first-line therapy with the strongest outcome evidence. Desiccated thyroid extract lacks modern RCT data demonstrating superiority and has variable hormone content between batches.

Open evidence analysis

Core study

What factors interfere with levothyroxine absorption?

Levothyroxine absorption is reduced by concurrent iron, calcium, PPIs, and some foods including coffee and fiber. Consistent fasting dosing separated from interfering substances improves TSH stability.

Open evidence analysis

Supporting literature

Does combination T3/T4 therapy improve symptoms versus levothyroxine alone?

Randomized trials and meta-analyses show inconsistent symptom benefit from adding liothyronine to levothyroxine compared with levothyroxine monotherapy. Guidelines generally recommend levothyroxine as first-line therapy.

Open evidence analysis

Supporting literature

Should subclinical hypothyroidism be treated with levothyroxine?

The TRUST trial found no meaningful symptom or quality-of-life benefit from levothyroxine in older adults with subclinical hypothyroidism. Treatment may still be considered with very high TSH, pregnancy plans, or specific clinical contexts.

Open evidence analysis

Supporting literature

What TSH target is appropriate for treated hypothyroidism?

Most guidelines suggest maintaining TSH within the reference range on levothyroxine, often near the lower half for many patients. Pregnancy and specific comorbidities require tighter targets.

Open evidence analysis

Supporting literature

Does treated hypothyroidism fully explain difficulty losing weight?

Hypothyroidism can contribute to weight gain, but levothyroxine normalization typically yields modest weight loss rather than resolving obesity. Persistent weight difficulty usually involves additional metabolic and behavioral factors.

Open evidence analysis