Subclinical hyperthyroidism: diagnostic criteria and principles of treatment

В. В. Галицкая

Abstract


This article presents the European Thyroid Association guidelines for diagnosis and treatment of subclinical hyperthyroidism, 2015. Determination of thyroid-stimulating hormone levels can help to diagnose a variety of pathological conditions: disorders of sexual development, amenorrhea (primary or secondary), infertility, miscarriage, which require specific treatment after detection the functional changes of thyroid taking into account the patient’s age.

Diagnosis of endogenous subclinical hyperthyroidism is based solely on the results of laboratory tests, not clinical criteria. Endogenous subclinical hyperthyroidism is defined by the presence of sub-normal levels of thyroid-stimulating hormone with normal levels of free thyroxine, total triiodothyronine, and/or free triiodothyronine. There are two categories of endogenous subclinical hyperthyroidism: grade 1 – the level of thyroid-stimulating hormone is 0.1–0.39 mIU/l; grade 2 – the level of thyroid-stimulating hormone is < 0.1 mIU/l. The levels of free thyroxine and free triiodothyronine, as a rule, are medium-high value at a subclinical level of thyroid hormone and can help differentiate between endogenous subclinical hyperthyroidism from overt hyperthyroidism.

Recommended to study the thyroid-stimulating hormone level as the first test for the diagnosis of subclinical hyperthyroidism. In identifying low levels of thyroid-stimulating hormone it is necessary to investigate the level of free thyroxine, free and bound triiodothyronine.

Patients with primary sub-normal levels of thyroid-stimulating hormone with concentration of thyroid hormones in the upper limit or in normal range should be evaluated within 2–3 months.

It is recommended to perform scintigraphy and possible 24-hour test the absorption of radioactive iodine if in patient with 2nd degree endogenous subclinical hyperthyroidism there is nodular goiter to determine treatment strategy.

Ultrasonography with color Doppler can be informative in patients with endogenous subclinical hyperthyroidism and nodular goiter.

Determining the level of antibodies to thyroid-stimulating hormone receptors can confirm the etiology of autoimmune hyperthyroidism.


Keywords


thyroid; thyroid stimulating hormone; hyperthyroidism; thyrotoxicosis; subclinical hyperthyroidism; Graves’ disease; toxic multinodular goiter

References


Biondi, В., Bartalena, L., Cooper, D.S., et al. “The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism.” Eur Thyroid J 4 (2015): 149–63.

Surks, M.I., Ortiz, E., Daniels, G.H., et al. “Subclinical thyroid disease: scientific review and guidelines for diagnosis and management.” JAMA 291 (2004): 228–38.

Biondi, B., Palmieri, E.A., Klain, M., et al. “Subclinical hyperthyroidism: clinical features and treatment options.” Eur J Endocrinol 152 (2005: 1–9.

Biondi, B., Cooper, D.S. “The clinical significance of subclinical thyroid dysfunction.” Endocr Rev 29 (2008): 76–131.

Bahn, R.S., Burch, H.B., Cooper, D.S., et al. “Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists.” Thyroid 21 (2011): 593–646.

Cooper, D.S., Biondi, B. “Subclinical thyroid disease.” Lancet 379 (2012): 1142–54.

Mitchell, A.L., Pearce, S.H. “How should we treat patients with low serum thyrotropin concentrations?” Clin Endocrinol (Oxf) 72 (2010): 292–6.

Bulow Pedersen, I., Knudsen, N., Jorgensen, T., et al. “Large differences in incidences of overt hyper- and hypothyroidism associated with a small difference in iodine intake: a prospective comparative register-based population survey.” J Clin Endocrinol Metab 87 (2002): 4462–9.

Marqusee, E., Haden, S.T., Utiger, R.D. “Subclinical thyrotoxicosis.” Endocrinol Metab Clin North Am 27 (1998): 37–49.

Canaris, G.J., Manowitz, N.R., Mayor, G., Ridgway, E.C. “The Colorado thyroid disease prevalence study.” Arch Intern Med 160 (2000): 526–34.

Hollowell, J.G., Staehling, N.W., Flanders, W.D., et al. “Serum TSH, T(4), and thyroid antibodies in the United States population (1988–1994): National Health and Nutrition Examination Survey (NHANES III).” J Clin Endocrinol Metab 87 (2002): 489–99.

Aghini-Lombardi, F., Antonangeli, L., Martino, E., et al. “The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano survey.” J Clin Endocrinol Metab 84 (1999): 561–6.

Paschke, R., Hegedus, L., Alexander, E., et al. “Thyroid nodule guidelines: agreement, disagreement and need for future research.” Nat Rev Endocrinol 7 (2011): 354–61.

Baloch, Z., Carayon, P., Conte-Devolx, B., et al.; Guidelines Committee, National Academy of Clinical Biochemistry. “Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease.” Thyroid 13 (2003): 3–126.

Figge, J., Leinung, M., Goodman, A.D., et al. “The clinical evaluation of patients with subclinical hyperthyroidism and free triiodothyronine (free T3) toxicosis.” Am J Med 96 (1994): 229–34.

Cooper, D.S., Laurberg, P. “Hyperthyroidism in pregnancy.” Lancet Diabetes Endocrinol 1 (2013): 238–49.

Harman, S.M., Wehmann, R.E., Blackman, M.R. “Pituitary-thyroid hormone economy in healthy aging men: basal indices of thyroid function and thyrotropin responses to constant infusions of thyrotropin releasing hormone.” J Clin Endocrinol Metab 58 (1984): 320–326.

Mariotti, S., Franceschi, C., Cossarizza, A., Pinchera, A. “The aging thyroid.” Endocr Rev 16 (1995): 686–715.

Surks, M.I., Boucai, L. “Age- and race-based serum thyrotropin reference limits.” J Clin Endocrinol Metab 95 (2010): 496–502.

Magri, F., Muzzoni, B., Cravello, L., et al. “Thyroid function in physiological aging and in centenarians: possible relationships with some nutritional markers.” Metabolism 51 (2002): 105–9.

Mariotti, S., Barbesino, G., Caturegli, P., et al. “Complex alteration of thyroid function in healthy centenarians.” J Clin Endocrinol Metab 77 (1993): 1130–4.

Belin, R.M., Astor, B.C., Powe, N.R., Ladenson, P.W. “Smoke exposure is associated with a lower prevalence of serum thyroid autoantibodies and thyrotropin concentration elevation and a higher prevalence of mild thyrotropin concentration suppression in the Third National Health and Nutrition Examination Survey (NHANES III).” J Clin Endocrinol Metab 89 (2004): 6077–86.

Diana, T., Kanitz, M., Lehmann, M., et al. “Standardization of a bioassay for thyrotropin receptor stimulating autoantibodies.” Thyroid 25 (2015): 169–75.

Pedersen, I.B., Knudsen, N., Perrild, H., et al. “TSH-receptor antibody measurement for differentiation of hyperthyroidism into Graves’ disease and multinodular toxic goitre: a comparison of two competitive binding assays.” Clin Endocrinol (Oxf) 55 (2001): 381–90.


GOST Style Citations


1. Biondi, В., Bartalena, L., Cooper, D.S., et al. “The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism.” Eur Thyroid J 4 (2015): 149–63.

2. Surks, M.I., Ortiz, E., Daniels, G.H., et al. “Subclinical thyroid disease: scientific review and guidelines for diagnosis and management.” JAMA 291 (2004): 228–38.

3. Biondi, B., Palmieri, E.A., Klain, M., et al. “Subclinical hyperthyroidism: clinical features and treatment options.” Eur J Endocrinol 152 (2005: 1–9.

4. Biondi, B., Cooper, D.S. “The clinical significance of subclinical thyroid dysfunction.” Endocr Rev 29 (2008): 76–131.

5. Bahn, R.S., Burch, H.B., Cooper, D.S., et al. “Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists.” Thyroid 21 (2011): 593–646.

6. Cooper, D.S., Biondi, B. “Subclinical thyroid disease.” Lancet 379 (2012): 1142–54.

7. Mitchell, A.L., Pearce, S.H. “How should we treat patients with low serum thyrotropin concentrations?” Clin Endocrinol (Oxf) 72 (2010): 292–6.

8. Bulow Pedersen, I., Knudsen, N., Jorgensen, T., et al. “Large differences in incidences of overt hyper- and hypothyroidism associated with a small difference in iodine intake: a prospective comparative register-based population survey.” J Clin Endocrinol Metab 87 (2002): 4462–9.

9. Marqusee, E., Haden, S.T., Utiger, R.D. “Subclinical thyrotoxicosis.” Endocrinol Metab Clin North Am 27 (1998): 37–49.

10. Canaris, G.J., Manowitz, N.R., Mayor, G., Ridgway, E.C. “The Colorado thyroid disease prevalence study.” Arch Intern Med 160 (2000): 526–34.

11. Hollowell, J.G., Staehling, N.W., Flanders, W.D., et al. “Serum TSH, T(4), and thyroid antibodies in the United States population (1988–1994): National Health and Nutrition Examination Survey (NHANES III).” J Clin Endocrinol Metab 87 (2002): 489–99.

12. Aghini-Lombardi, F., Antonangeli, L., Martino, E., et al. “The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano survey.” J Clin Endocrinol Metab 84 (1999): 561–6.

13. Paschke, R., Hegedus, L., Alexander, E., et al. “Thyroid nodule guidelines: agreement, disagreement and need for future research.” Nat Rev Endocrinol 7 (2011): 354–61.

14. Baloch, Z., Carayon, P., Conte-Devolx, B., et al.; Guidelines Committee, National Academy of Clinical Biochemistry. “Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease.” Thyroid 13 (2003): 3–126.

15. Figge, J., Leinung, M., Goodman, A.D., et al. “The clinical evaluation of patients with subclinical hyperthyroidism and free triiodothyronine (free T3) toxicosis.” Am J Med 96 (1994): 229–34.

16. Cooper, D.S., Laurberg, P. “Hyperthyroidism in pregnancy.” Lancet Diabetes Endocrinol 1 (2013): 238–49.

17. Harman, S.M., Wehmann, R.E., Blackman, M.R. “Pituitary-thyroid hormone economy in healthy aging men: basal indices of thyroid function and thyrotropin responses to constant infusions of thyrotropin releasing hormone.” J Clin Endocrinol Metab 58 (1984): 320–326.

18. Mariotti, S., Franceschi, C., Cossarizza, A., Pinchera, A. “The aging thyroid.” Endocr Rev 16 (1995): 686–715.

19. Surks, M.I., Boucai, L. “Age- and race-based serum thyrotropin reference limits.” J Clin Endocrinol Metab 95 (2010): 496–502.

20. Magri, F., Muzzoni, B., Cravello, L., et al. “Thyroid function in physiological aging and in centenarians: possible relationships with some nutritional markers.” Metabolism 51 (2002): 105–9.

21. Mariotti, S., Barbesino, G., Caturegli, P., et al. “Complex alteration of thyroid function in healthy centenarians.” J Clin Endocrinol Metab 77 (1993): 1130–4.

22. Belin, R.M., Astor, B.C., Powe, N.R., Ladenson, P.W. “Smoke exposure is associated with a lower prevalence of serum thyroid autoantibodies and thyrotropin concentration elevation and a higher prevalence of mild thyrotropin concentration suppression in the Third National Health and Nutrition Examination Survey (NHANES III).” J Clin Endocrinol Metab 89 (2004): 6077–86.

23. Diana, T., Kanitz, M., Lehmann, M., et al. “Standardization of a bioassay for thyrotropin receptor stimulating autoantibodies.” Thyroid 25 (2015): 169–75.

24. Pedersen, I.B., Knudsen, N., Perrild, H., et al. “TSH-receptor antibody measurement for differentiation of hyperthyroidism into Graves’ disease and multinodular toxic goitre: a comparison of two competitive binding assays.” Clin Endocrinol (Oxf) 55 (2001): 381–90.





DOI: http://dx.doi.org/10.18370/2309-4117.2016.31.107-110

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