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Nonthyroidal illness syndrome

Farwell, Alan P.

Current Opinion in Endocrinology, Diabetes & Obesity:
doi: 10.1097/
THYROID: Edited by Lewis E. Braverman and Angela M. Leung

Purpose of review: The current state of the pathophysiology, diagnosis, and therapeutic implications of the nonthyroidal illness syndrome is reviewed.

Recent findings: Previous studies attributed the development of the nonthyroidal illness syndrome to alterations in three main areas of thyroid hormone metabolism: deiodinase activity, thyroid-stimulating hormone secretion, and hormone binding to serum proteins. New studies suggest that alterations in thyroid hormone transport into tissues and alterations of the nuclear thyroid hormone receptors may also play a role. Therapy of the nonthyroidal illness syndrome remains a controversial topic.

Summary: Multiple factors lead to the development of the nonthyroidal illness syndrome, including alterations in type 1 and 3 deiodinase activity, thyrotropin-releasing hormone and thyroid-stimulating hormone secretion, hormone binding to plasma proteins, thyroid hormone transporter expression and activity, and the thyroid hormone nuclear receptor complex. These data show that acute and chronic illness affect all aspects of thyroid hormone metabolism and action. Some of these changes are physiologic and some are pharmacologic. The mediators of these alterations are still largely unclear. There continues to be no indication for thyroid hormone therapy in the vast majority of patients with the nonthyroidal illness syndrome, although interesting data suggest a possible role for treating a small subset of patients.

Author Information

Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts, USA

Correspondence to Alan P. Farwell, MD, Associate Professor of Medicine, Interim Chief, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Director, Endocrine Clinics, Boston Medical Center, 88 East Newton St, Evans 256, Boston, MA 01583, USA. Tel: +1 617 638 8873; fax: +1 617 638 7221; e-mail:

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