This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huber, G. Articles by Braverman, L. E. Search for Related Content PubMed PubMed Citation Articles by Huber, G. Articles by Braverman, L. E.

Prospective Study of the Spontaneous Course of Subclinical Hypothyroidism: Prognostic Value of Thyrotropin, Thyroid Reserve, and Thyroid Antibodies

Division of Endocrinology (J.J.S., C.M., C.M., M.G.), University Clinic of Medicine B (G.H.), Department of Medicine and Central Laboratories (P.H.), University Hospital Basel, CH-4031 Basel, Switzerland; and Brigham and Women’s Hospital and Harvard Medical School (L.E.B.), Boston, Massachusetts 02118

Address all correspondence and requests for reprints to: Dr. G. Huber, Division of Endocrinology, Department of Medicine, University Hospital, Petersgraben 4, CH-4031 Basel, Switzerland. E-mail: . gerold.huber{at}unibas.ch

Abstract

Subclinical hypothyroidism is a frequent syndrome affecting about 10 million people in the United States. The management of such patients is open to debate. In a long-term prospective study we analyzed the spontaneous course and the value of predictive factors in the development of overt thyroid failure. We studied 82 female patients with subclinical hypothyroidism prospectively over a mean observation period of 9.2 yr. TSH, thyroid hormones, thyroid reserve after TRH administration, thyroid antibodies, and clinical parameters were assessed at yearly intervals. The cumulative incidence of overt hypothyroidism was calculated using life-table analysis and Kaplan-Meier curves. According to the initial serum TSH concentrations (TSH, 4–6/>6–12/>12 mU/liter), Kaplan-Meier estimates of the incidence of overt hypothyroidism were 0%, 42.8%, and 76.9%, respectively, after 10 yr (P < 0.0001). When only patients with TSH levels greater than 6 mU/liter were analyzed, the cumulative incidence was 55.3%. The incidence of overt hypothyroidism increased in patients with impaired thyroid reserve (52.6% vs. 38.1%; P = 0.05) and positive microsomal antibodies (58.5% vs. 23.2%; P = 0.03).

This prospective long-term study demonstrates that only a part of the cohort of patients with subclinical hypothyroidism develops overt hypothyroidism over time and that a major group remains in the subclinical state after 10 yr. The measurement of TSH, microsomal (thyroperoxidase) antibodies, and thyroid reserve allows initial risk stratification for the development of overt thyroid failure (risk ratio ranging from 1.0–15.6). Our study helps to recognize the spontaneous course of subclinical hypothyroidism and in the identification of patients most likely to progress to overt hypothyroidism.

This article has been cited by other articles:

				J. Klubo-Gwiezdzinska and L. Wartofsky Thyrotropin Blood Levels, Subclinical Hypothyroidism, and the Elderly Patient Arch Intern Med, November 23, 2009; 169(21): 1949 - 1951. [Full Text] [PDF]

				L. Lazar, R. B.-D. Frumkin, E. Battat, Y. Lebenthal, M. Phillip, and J. Meyerovitch Natural History of Thyroid Function Tests over 5 Years in a Large Pediatric Cohort J. Clin. Endocrinol. Metab., May 1, 2009; 94(5): 1678 - 1682. [Abstract] [Full Text] [PDF]

				M. Wasniewska, M. Salerno, A. Cassio, A. Corrias, T. Aversa, G. Zirilli, D. Capalbo, M. Bal, A. Mussa, and F. De Luca Prospective evaluation of the natural course of idiopathic subclinical hypothyroidism in childhood and adolescence Eur. J. Endocrinol., March 1, 2009; 160(3): 417 - 421. [Abstract] [Full Text] [PDF]

				H. Cinemre, C. Bilir, F. Gokosmanoglu, and T. Bahcebasi Hematologic Effects of Levothyroxine in Iron-Deficient Subclinical Hypothyroid Patients: A Randomized, Double-Blind, Controlled Study J. Clin. Endocrinol. Metab., January 1, 2009; 94(1): 151 - 156. [Abstract] [Full Text] [PDF]

				J. Karmisholt, S. Andersen, and P. Laurberg Interval between Tests and Thyroxine Estimation Method Influence Outcome of Monitoring of Subclinical Hypothyroidism J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1634 - 1640. [Abstract] [Full Text] [PDF]

				J. Karmisholt and P. Laurberg Serum TSH and serum thyroid peroxidase antibody fluctuate in parallel and high urinary iodine excretion predicts subsequent thyroid failure in a 1-year study of patients with untreated subclinical hypothyroidism Eur. J. Endocrinol., February 1, 2008; 158(2): 209 - 215. [Abstract] [Full Text] [PDF]

				B. Biondi and D. S. Cooper The Clinical Significance of Subclinical Thyroid Dysfunction Endocr. Rev., February 1, 2008; 29(1): 76 - 131. [Abstract] [Full Text] [PDF]

				J. Meyerovitch, P. Rotman-Pikielny, M. Sherf, E. Battat, Y. Levy, and M. I. Surks Serum Thyrotropin Measurements in the Community: Five-Year Follow-up in a Large Network of Primary Care Physicians Arch Intern Med, July 23, 2007; 167(14): 1533 - 1538. [Abstract] [Full Text] [PDF]

				G Brabant, P Beck-Peccoz, B Jarzab, P Laurberg, J Orgiazzi, I Szabolcs, A P Weetman, and W M Wiersinga Is there a need to redefine the upper normal limit of TSH? Eur. J. Endocrinol., May 1, 2006; 154(5): 633 - 637. [Abstract] [Full Text] [PDF]

				J. P. Walsh, A. P. Bremner, M. K. Bulsara, P. O'Leary, P. J. Leedman, P. Feddema, and V. Michelangeli Subclinical Thyroid Dysfunction as a Risk Factor for Cardiovascular Disease Arch Intern Med, November 28, 2005; 165(21): 2467 - 2472. [Abstract] [Full Text] [PDF]

				L. Wartofsky and R. A Dickey The Evidence for a Narrower Thyrotropin Reference Range Is Compelling J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5483 - 5488. [Abstract] [Full Text] [PDF]

				M. I. Surks, G. Goswami, and G. H. Daniels The Thyrotropin Reference Range Should Remain Unchanged J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5489 - 5496. [Abstract] [Full Text] [PDF]

				J. J. Diez, P. Iglesias, and K. D. Burman Spontaneous Normalization of Thyrotropin Concentrations in Patients with Subclinical Hypothyroidism J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4124 - 4127. [Abstract] [Full Text] [PDF]

				S. Zoncu, F. Pigliaru, C. Putzu, L. Pisano, S. Vargiu, M. Deidda, S. Mariotti, and G. Mercuro Cardiac function in borderline hypothyroidism: a study by pulsed wave tissue Doppler imaging Eur. J. Endocrinol., April 1, 2005; 152(4): 527 - 533. [Abstract] [Full Text] [PDF]

				J. J. Diez and P. Iglesias Spontaneous Subclinical Hypothyroidism in Patients Older than 55 Years: An Analysis of Natural Course and Risk Factors for the Development of Overt Thyroid Failure J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 4890 - 4897. [Abstract] [Full Text] [PDF]

				M. I. Surks, E. Ortiz, G. H. Daniels, C. T. Sawin, N. F. Col, R. H. Cobin, J. A. Franklyn, J. M. Hershman, K. D. Burman, M. A. Denke, et al. Subclinical Thyroid Disease: Scientific Review and Guidelines for Diagnosis and Management JAMA, January 14, 2004; 291(2): 228 - 238. [Abstract] [Full Text] [PDF]

				S. Fazio, E. A. Palmieri, G. Lombardi, and B. Biondi Effects of Thyroid Hormone on the Cardiovascular System Recent Prog. Horm. Res., January 1, 2004; 59(1): 31 - 50. [Abstract] [Full Text]

				B. Biondi, E. A. Palmieri, G. Lombardi, and S. Fazio Subclinical Thyroid Dysfunction and the Heart Ann Intern Med, November 18, 2003; 139(10): 866 - 867. [Full Text] [PDF]

				E. N. Pearce, A. P. Farwell, and L. E. Braverman Thyroiditis N. Engl. J. Med., June 26, 2003; 348(26): 2646 - 2655. [Full Text] [PDF]