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Serum TSH, T₄, and Thyroid Antibodies in the United States Population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III)

Centers for Disease Control, National Center for Environmental Health, Division of Emergency and Environmental Services (J.G.H.), Division of Environmental Hazards and Health Effects (N.W.S.), Division of Environmental Laboratory Sciences (W.H.H., E.W.G.), Atlanta, Georgia 30341; Emory University School of Public Health (W.D.F.), Atlanta, Georgia 30324; University of Southern California Medical Center (C.A.S.), Los Angeles, California 90032; and Boston Medical Center (L.E.B.), Boston, Massachusetts 02116

Address all correspondence and requests for reprints to: Joseph G. Hollowell, M.D., MPH 435 North 1500 Road Lawrence, Kansas 66049. E-mail: jgh3{at}mindspring.com

Abstract

NHANES III measured serum TSH, total serum T₄, antithyroperoxidase (TPOAb), and antithyroglobulin (TgAb) antibodies from a sample of 17,353 people aged 12 yr representing the geographic and ethnic distribution of the U.S. population. These data provide a reference for other studies of these analytes in the U.S.

For the 16,533 people who did not report thyroid disease, goiter, or taking thyroid medications (disease-free population), we determined mean concentrations of TSH, T₄, TgAb, and TPOAb. A reference population of 13,344 people was selected from the disease-free population by excluding, in addition, those who were pregnant, taking androgens or estrogens, who had thyroid antibodies, or biochemical hypothyroidism or hyperthyroidism. The influence of demographics on TSH, T₄, and antibodies was examined.

Hypothyroidism was found in 4.6% of the U.S. population (0.3% clinical and 4.3% subclinical) and hyperthyroidism in 1.3% (0.5% clinical and 0.7% subclinical). (Subclinical hypothyroidism is used in this paper to mean mild hypothyroidism, the term now preferred by the American Thyroid Association for the laboratory findings described.) For the disease-free population, mean serum TSH was 1.50 (95% confidence interval, 1.46–1.54) mIU/liter, was higher in females than males, and higher in white non-Hispanics (whites) [1.57 (1.52–1.62) mIU/liter] than black non-Hispanics (blacks) [1.18 (1.14–1.21) mIU/liter] (P < 0.001) or Mexican Americans [1.43 (1.40–1.46) mIU/liter] (P < 0.001). TgAb were positive in 10.4 ± 0.5% and TPOAb, in 11.3 ± 0.4%; positive antibodies were more prevalent in women than men, increased with age, and TPOAb were less prevalent in blacks (4.5 ± 0.3%) than in whites (12.3 ± 0.5%) (P < 0.001). TPOAb were significantly associated with hypo or hyperthyroidism, but TgAb were not. Using the reference population, geometric mean TSH was 1.40 ± 0.02 mIU/liter and increased with age, and was significantly lower in blacks (1.18 ± 0.02 mIU/liter) than whites (1.45 ± 0.02 mIU/liter) (P < 0.001) and Mexican Americans (1.37 ± 0.02 mIU/liter) (P < 0.001). Arithmetic mean total T₄ was 112.3 ± 0.7 nmol/liter in the disease-free population and was consistently higher among Mexican Americans in all populations. In the reference population, mean total T₄ in Mexican Americans was (116.3 ± 0.7 nmol/liter), significantly higher than whites (110.0 ± 0.8 nmol/liter) or blacks (109.4 ± 0.8 nmol/liter) (P < 0.0001). The difference persisted in all age groups.

In summary, TSH and the prevalence of antithyroid antibodies are greater in females, increase with age, and are greater in whites and Mexican Americans than in blacks. TgAb alone in the absence of TPOAb is not significantly associated with thyroid disease. The lower prevalence of thyroid antibodies and lower TSH concentrations in blacks need more research to relate these findings to clinical status. A large proportion of the U.S. population unknowingly have laboratory evidence of thyroid disease, which supports the usefulness of screening for early detection.

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				J. H. Goodman and M. E. Gilbert Modest Thyroid Hormone Insufficiency during Development Induces a Cellular Malformation in the Corpus Callosum: A Model of Cortical Dysplasia Endocrinology, June 1, 2007; 148(6): 2593 - 2597. [Abstract] [Full Text] [PDF]

				G. C. Gonzalez, I. Capel, J. Rodriguez-Espinosa, D. Mauricio, A. de Leiva, and A. Perez Thyroid Autoimmunity at Onset of Type 1 Diabetes as a Predictor of Thyroid Dysfunction Diabetes Care, June 1, 2007; 30(6): 1611 - 1612. [Full Text] [PDF]

				M. D. Gammage, J. V. Parle, R. L. Holder, L. M. Roberts, F. D. R. Hobbs, S. Wilson, M. C. Sheppard, and J. A. Franklyn Association Between Serum Free Thyroxine Concentration and Atrial Fibrillation Arch Intern Med, May 14, 2007; 167(9): 928 - 934. [Abstract] [Full Text] [PDF]

				J. E. Haddow, M. R. McClain, G. E. Palomaki, and J. G. Hollowell Urine Iodine Measurements, Creatinine Adjustment, and Thyroid Deficiency in an Adult United States Population J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1019 - 1022. [Abstract] [Full Text] [PDF]

				E. Jensen, O. Blaabjerg, P. H. Petersen, and L. Hegedus Sampling Time Is Important but May Be Overlooked in Establishment and Use of Thyroid-Stimulating Hormone Reference Intervals Clin. Chem., February 1, 2007; 53(2): 355 - 356. [Full Text] [PDF]

				O.E. Okosieme, R.C. Taylor, A.E. Ohwovoriole, A.B. Parkes, and J.H. Lazarus Prevalence of thyroid antibodies in Nigerian patients QJM, February 1, 2007; 100(2): 107 - 112. [Abstract] [Full Text] [PDF]

				D. S. Cooper Approach to the Patient with Subclinical Hyperthyroidism J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 3 - 9. [Abstract] [Full Text] [PDF]

				S. Wilson, J. V. Parle, L. M. Roberts, A. K. Roalfe, F. D. R. Hobbs, P. Clark, M. C. Sheppard, M. D. Gammage, H. M. Pattison, J. A. Franklyn, et al. Prevalence of Subclinical Thyroid Dysfunction and Its Relation to Socioeconomic Deprivation in the Elderly: A Community-Based Cross-Sectional Survey J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4809 - 4816. [Abstract] [Full Text] [PDF]

				K. Boelaert, J. Horacek, R. L. Holder, J. C. Watkinson, M. C. Sheppard, and J. A. Franklyn Serum Thyrotropin Concentration as a Novel Predictor of Malignancy in Thyroid Nodules Investigated by Fine-Needle Aspiration J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4295 - 4301. [Abstract] [Full Text] [PDF]

				S G S Krishnan, R Pathalapati, L Kaplan, and R K Cobbs Falsely raised TSH levels due to human anti-mouse antibody interfering with thyrotropin assay Postgrad. Med. J., November 1, 2006; 82(973): e27 - e27. [Abstract] [Full Text] [PDF]

				J.-M. Fernandez-Real, A. Lopez-Bermejo, A. Castro, R. Casamitjana, and W. Ricart Thyroid Function Is Intrinsically Linked to Insulin Sensitivity and Endothelium-Dependent Vasodilation in Healthy Euthyroid Subjects J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3337 - 3343. [Abstract] [Full Text] [PDF]

				P. Laurberg, T. Jorgensen, H. Perrild, L. Ovesen, N. Knudsen, I. B. Pedersen, L. B Rasmussen, A. Carle, and P. Vejbjerg The Danish investigation on iodine intake and thyroid disease, DanThyr: status and perspectives. Eur. J. Endocrinol., August 1, 2006; 155(2): 219 - 228. [Abstract] [Full Text] [PDF]

				K. H. Archbold Sleep Disorders and Attention-Deficit Hyperactivity Disorder in Children: A Missing Differential Diagnosis Journal of the American Psychiatric Nurses Association, August 1, 2006; 12(4): 216 - 224. [Abstract] [PDF]

				J. L. Johnson Diabetes Control in Thyroid Disease Diabetes Spectr, July 1, 2006; 19(3): 148 - 153. [Abstract] [Full Text] [PDF]

				J. M. Barker Type 1 Diabetes-Associated Autoimmunity: Natural History, Genetic Associations, and Screening J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1210 - 1217. [Abstract] [Full Text] [PDF]

				K Poppe, D Glinoer, H Tournaye, U Maniewski, P Haentjens, and B Velkeniers Is systematic screening for thyroid disorders indicated in subfertile men? Eur. J. Endocrinol., March 1, 2006; 154(3): 363 - 366. [Abstract] [Full Text] [PDF]

				M. Imaizumi, T. Usa, T. Tominaga, K. Neriishi, M. Akahoshi, E. Nakashima, K. Ashizawa, A. Hida, M. Soda, S. Fujiwara, et al. Radiation Dose-Response Relationships for Thyroid Nodules and Autoimmune Thyroid Diseases in Hiroshima and Nagasaki Atomic Bomb Survivors 55-58 Years After Radiation Exposure JAMA, March 1, 2006; 295(9): 1011 - 1022. [Abstract] [Full Text] [PDF]

				A. R. Cappola, L. P. Fried, A. M. Arnold, M. D. Danese, L. H. Kuller, G. L. Burke, R. P. Tracy, and P. W. Ladenson Thyroid Status, Cardiovascular Risk, and Mortality in Older Adults JAMA, March 1, 2006; 295(9): 1033 - 1041. [Abstract] [Full Text] [PDF]

				S. A. H. Cann Hypothesis: dietary iodine intake in the etiology of cardiovascular disease. J. Am. Coll. Nutr., February 1, 2006; 25(1): 1 - 11. [Abstract] [Full Text] [PDF]