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The Journal of Clinical Endocrinology & Metabolism Vol. 87, No. 2 489-499
Copyright © 2002 by The Endocrine Society

Endocrine Care

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

Joseph G. Hollowell, Norman W. Staehling, W. Dana Flanders, W. Harry Hannon, Elaine W. Gunter, Carole A. Spencer and Lewis E. Braverman

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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G. Y. Gandhi, R. Basu, A. Dispenzieri, A. Basu, V. M. Montori, and M. D. Brennan
Endocrinopathy in POEMS Syndrome: The Mayo Clinic Experience
Mayo Clin. Proc., July 1, 2007; 82(7): 836 - 842.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
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]

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 Diabetes CareHome page
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]

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 Arch Intern MedHome page
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]

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 J. Clin. Endocrinol. Metab.Home page
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]

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 Clin. Chem.Home page
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]

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 QJMHome page
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]

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 J. Clin. Endocrinol. Metab.Home page
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]

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 J. Clin. Endocrinol. Metab.Home page
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]

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 J. Clin. Endocrinol. Metab.Home page
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]

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 Postgrad. Med. J.Home page
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]

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 J. Clin. Endocrinol. Metab.Home page
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]

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 Eur J EndocrinolHome page
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]

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 J Am Psychiatr Nurses AssocHome page
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]

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

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 J. Clin. Endocrinol. Metab.Home page
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]

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 Eur J EndocrinolHome page
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]

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 JAMAHome page
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]

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 JAMAHome page
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]

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 J. Am. Coll. Nutr.Home page
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]

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 J. Clin. Endocrinol. Metab.Home page
M. Dorr, D. M. Robinson, H. Wallaschofski, C. Schwahn, U. John, S. B. Felix, and H. Volzke
Low Serum Thyrotropin Is Associated with High Plasma Fibrinogen
J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 530 - 534.
[Abstract] [Full Text] [PDF]

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 Clin. Chem.Home page
K. Zophel, G. Wunderlich, and J. Kotzerke
Should We Really Determine a Reference Population for the Definition of Thyroid-Stimulating Hormone Reference Interval?
Clin. Chem., February 1, 2006; 52(2): 329 - 330.
[Full Text] [PDF]

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 Clin. Chem.Home page
D. Giavarina, R. M. Dorizzi, and G. Soffiati
Indirect Methods for Reference Intervals Based on Current Data
Clin. Chem., February 1, 2006; 52(2): 335 - 337.
[Full Text] [PDF]

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 Clin. Chem.Home page
E. Grossi, R. Colombo, S. Cavuto, and C. Franzini
Indirect Methods for Reference Intervals Based on Current Data: The authors of the article cited above respond:
Clin. Chem., February 1, 2006; 52(2): 337 - 338.
[Full Text] [PDF]

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 Eur J EndocrinolHome page
A. Carle, P. Laurberg, I. B. Pedersen, N. Knudsen, H. Perrild, L. Ovesen, L. B. Rasmussen, and T. Jorgensen
Epidemiology of subtypes of hypothyroidism in Denmark
Eur. J. Endocrinol., January 1, 2006; 154(1): 21 - 28.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. Jorde, K. Waterloo, H. Storhaug, A. Nyrnes, J. Sundsfjord, and T. G. Jenssen
Neuropsychological Function and Symptoms in Subjects with Subclinical Hypothyroidism and the Effect of Thyroxine Treatment
J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 145 - 153.
[Abstract] [Full Text] [PDF]

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 Pediatr. Rev.Home page
C. P. Dobson, M. Neuwirth, R. E. Frye, and M. Gorman
Index of Suspicion
Pediatr. Rev., January 1, 2006; 27(1): 29 - 33.
[Full Text] [PDF]

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 Clin. Chem.Home page
E. H. Hoogendoorn, A. R. Hermus, F. de Vegt, H. A. Ross, A. L.M. Verbeek, L. A.L.M. Kiemeney, D. W. Swinkels, F. C.G.J. Sweep, and M. den Heijer
Thyroid Function and Prevalence of Anti-Thyroperoxidase Antibodies in a Population with Borderline Sufficient Iodine Intake: Influences of Age and Sex
Clin. Chem., January 1, 2006; 52(1): 104 - 111.
[Abstract] [Full Text] [PDF]

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 Arch Intern MedHome page
N. Rodondi, A. B. Newman, E. Vittinghoff, N. de Rekeneire, S. Satterfield, T. B. Harris, and D. C. Bauer
Subclinical Hypothyroidism and the Risk of Heart Failure, Other Cardiovascular Events, and Death
Arch Intern Med, November 28, 2005; 165(21): 2460 - 2466.
[Abstract] [Full Text] [PDF]

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 Arch Intern MedHome page
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]

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 J. Clin. Endocrinol. Metab.Home page
O. Gumieniak, S. Hurwitz, T. S. Perlstein, U. C. Ngumezi, P. N. Hopkins, X. Jeunemaitre, and G. H. Williams
Aggregation of High-Normal Thyroid-Stimulating Hormone in Hypertensive Families
J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 5985 - 5990.
[Abstract] [Full Text] [PDF]


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