Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. EDITORIAL Subclinical hypothyroidism Giampaolo Papi a , Ettore degli Uberti b , Corrado Betterle c , Cesare Carani a , Elizabeth N. Pearce d , Lewis E. Braverman d and Elio Roti e Purpose of review Mild or subclinical hypothyroidism is characterized by normal serum free thyroxine concentrations with elevated serum thyroid-stimulating hormone concentrations. Subclinical hypothyroidism is relatively prevalent in the general population, especially among women and the elderly. The main cause of subclinical hypothyroidism is autoimmune chronic thyroiditis. The present report reviews the most important and recent studies on subclinical hypothyroidism, and discusses the most controversial aspects of this topic. Recent findings Several studies have demonstrated that subclinical hypothyroidism may affect both diastolic and systolic cardiac function. It may also worsen many risk factors for cardiovascular disease, including hypertension, abnormal endothelial function, and elevated low-density lipoprotein cholesterol concentrations. Furthermore, a growing body of evidence suggests that subclinical hypothyroidism may cause symptoms or progress to symptomatic overt hypothyroidism. Summary Prompt treatment of subclinical hypothyroidism in pregnant women is mandatory to decrease risks for pregnancy complications and impaired cognitive development in offspring. Children with subclinical hypothyroidism should be treated to prevent growth retardation. Whether nonpregnant adult patients with subclinical hypothyroidism should be treated, and at what thyroid-stimulating hormone values, is debatable. Keywords diagnosis, etiology, mild hypothyroidism, subclinical hypothyroidism, therapy Curr Opin Endocrinol Diabetes Obes 14:197–208. ß 2007 Lippincott Williams & Wilkins. a Department of Internal Medicine, University of Modena and Reggio Emilia, Italy, b Department of Biochemical Sciences and Advanced Therapies, Section of Endocrinology, University of Ferrara, Italy, c Department of Medical and Surgical Sciences, University of Padova, Italy, d Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA and e Institute of Endocrinology, University of Milan, Italy Correspondence to Lewis E. Braverman, MD, Boston University Medical Center, 88 East Newton Street, Evans 201, Boston, MA 02118, USA Tel: +1 617 638 7211; fax: +1 617 638 7221; e-mail: lewis.braverman@bmc.org Current Opinion in Endocrinology, Diabetes & Obesity 2007, 14:197–208 Abbreviations AACE American Association of Clinical Endocrinologists ATA American Thyroid Association HDL-C high-density lipoprotein-cholesterol LDL-C low-density lipoprotein-cholesterol SCH subclinical hypothyroidism TPO-Ab thyroperoxidase antibody TSH thyroid-stimulating hormone ß 2007 Lippincott Williams & Wilkins 1752-296X Introduction Patients with overt thyroid dysfunction should be treated [1,2]. However, whether and when treatment should be started in patients with subclinical hyperthyroidism or subclinical hypothyroidism (SCH) is still debatable [3–11]. Although the Endocrine Society, the American Association of Clinical Endocrinologists (AACE) and the American Thyroid Association (ATA) have stated their position about the appropriate management of subclinical thyroid disorders, the controversy still remains unre- solved, especially related to SCH [12]. In the last few years, several groups have investigated whether SCH may be associated with symptoms, may represent a risk factor for cardiovascular disease, or may evolve to overt hypothyroidism. The role of L-thyroxine therapy in reducing or reversing the adverse effects of SCH has also been evaluated. The present report reviews the most important and recent studies related to SCH and attempts to draw literature-based conclusions about the management of this condition. Definition A recent consensus committee defined SCH as a serum thyroid-stimulating hormone (TSH) concentration above the statistically defined upper limit of the reference range and the serum free thyroxine within the reference range [13]. The third National Health and Nutrition Examination Survey (NHANES III) [14] screened 13 344 disease-free, euthyroid subjects who were thyroid antibody negative. In this population, the median TSH concentration was 1.39 mIU/l, with the 95% TSH reference limits between 197