Subclinical Hyperthyroidism

  • Gabriela Brenta
  • José Sgarbi


It is well known that minor elevations in serum thyroid hormone levels, even within the normal range, can have important effects on peripheral tissues. In subclinical hyperthyroidism, a suppressed thyrotropin (TSH) level due to an enhanced negative feedback at the hypothalamus-pituitary-thyroid axis is the clue to this mild excess of thyroid hormones.

Adverse clinical endpoints related to subclinical hyperthyroidism include lower bone mineral density, increased risk of fractures, atrial fibrillation, heart failure, coronary heart disease (CHD), stroke, and cardiovascular mortality as reported in large population studies and meta-analysis. Risk is in general higher for elderly people and TSH levels lower than 0.1 mIU/L. Postmenopausal women and elderly individuals are particularly exposed to the detrimental effects of subclinical hyperthyroidism and are two settings in which aggressive case finding is worthwhile.

TSH is the initial test followed by a determination of thyroid hormones to assure the diagnosis. Although the etiology of subclinical hyperthyroidism is the same as in overt hyperthyroidism, it is always important to discard first other causes of low TSH values or an exogenous source of levothyroxine. Furthermore, a transient form of subclinical hyperthyroidism has to be distinguished from a permanent one.

Once the diagnosis of permanent subclinical hyperthyroidism is done, a clinical decision on treatment has to be taken. Despite the lack of large control trials in the field, treatment is recommended in patients with a higher degree of TSH suppression and older age or exposed to cardiovascular and bone fracture risk.

Treatment options include antithyroid drugs, radioactive iodine therapy, and thyroid surgery. The decision among these options will depend on the individual case and the consensus between the endocrinologist and the affected patient.

In this chapter we shall be discussing the diagnosis, clinical consequences, and treatment modalities of patients with endogenous subclinical hyperthyroidism.


Subclinical hyperthyroidism Thyrotoxicosis Antithyroid drugs Radioactive iodine therapy Graves’ disease Autonomously functioning thyroid nodules 


  1. 1.
    Biondi B, Bartalena L, Cooper DS, Hegedus L, Laurberg P, Kahaly GJ. The 2015 European Thyroid Association guidelines on diagnosis and treatment of endogenous subclinical hyperthyroidism. Eur Thyroid J. 2015;4:149–63.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract. 2011;17:456–520.PubMedCrossRefGoogle Scholar
  3. 3.
    Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012;379:1142–54.CrossRefGoogle Scholar
  4. 4.
    Bartalena L. Diagnosis and management of Graves disease: a global overview. Nat Rev Endocrinol. 2013;9:724–34.CrossRefGoogle Scholar
  5. 5.
    Holzapfel HP, Fuhrer D, Wonerow P, Weinland G, Scherbaum WA, Paschke R. Identification of constitutively activating somatic thyrotropin receptor mutations in a subset of toxic multinodular goiters. J Clin Endocrinol Metab. 1997;82:4229–33.PubMedGoogle Scholar
  6. 6.
    Tonacchera M, Chiovato L, Pinchera A, Agretti P, Fiore E, Cetani F, Rocchi R, Viacava P, Miccoli P, Vitti P. Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma. J Clin Endocrinol Metab. 1998;83:492–8.PubMedGoogle Scholar
  7. 7.
    Yalamanchi S, Cooper DS. Thyroid disorders in pregnancy. Curr Opin Obstet Gynecol. 2015;27:406–15.PubMedCrossRefGoogle Scholar
  8. 8.
    Samuels MH. Subacute, silent, and postpartum thyroiditis. Med Clin North Am. 2012;96:223–33.PubMedCrossRefGoogle Scholar
  9. 9.
    Cohen-Lehman J, Dahl P, Danzi S, Klein I. Effects of amiodarone therapy on thyroid function. Nat Rev Endocrinol. 2010;6:34–41.PubMedCrossRefGoogle Scholar
  10. 10.
    Tomer Y, Menconi F. Interferon induced thyroiditis. Best Pract Res Clin Endocrinol Metab. 2009;23:703–12.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Somwaru LL, Arnold AM, Joshi N, Fried LP, Cappola AR. High frequency of and factors associated with thyroid hormone over-replacement and under-replacement in men and women aged 65 and over. J Clin Endocrinol Metab. 2009;94:1342–5.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Mammen JS, McGready J, Oxman R, Chia CW, Ladenson PW, Simonsick EM. Thyroid hormone therapy and risk of thyrotoxicosis in community-resident older adults: findings from the Baltimore longitudinal study of aging. Thyroid. 2015;25:979–86.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Kaptein EM, Beale E, Chan LS. Thyroid hormone therapy for obesity and nonthyroidal illnesses: a systematic review. J Clin Endocrinol Metab. 2009;94:3663–75.PubMedCrossRefGoogle Scholar
  14. 14.
    Cooper DS. TSH suppressive therapy: an overview of long-term clinical consequences. Hormones (Athens). 2010;9:57–9.CrossRefGoogle Scholar
  15. 15.
    Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26:1–133.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Collet TH, Gussekloo J, Bauer DC, den Elzen WP, Cappola AR, Balmer P, Iervasi G, Asvold BO, Sgarbi JA, Volzke H, Gencer B, Maciel RM, Molinaro S, Bremner A, Luben RN, Maisonneuve P, Cornuz J, Newman AB, Khaw KT, Westendorp RG, Franklyn JA, Vittinghoff E, Walsh JP, Rodondi N. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med. 2012;172:799–809.CrossRefGoogle Scholar
  17. 17.
    Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87:489–99.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Aghini-Lombardi F, Antonangeli L, Martino E, Vitti P, Maccherini D, Leoli F, Rago T, Grasso L, Valeriano R, Balestrieri A, Pinchera A. The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano survey. J Clin Endocrinol Metab. 1999;84:561–6.PubMedGoogle Scholar
  19. 19.
    Vitti P, Rago T, Tonacchera M, Pinchera A. Toxic multinodular goiter in the elderly. J Endocrinol Investig. 2002;25:16–8.CrossRefGoogle Scholar
  20. 20.
    Woeber KA. Observations concerning the natural history of subclinical hyperthyroidism. Thyroid. 2005;15:687–91.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Iakovou I, Zapandiotis A, Mpalaris V, Goulis DG. Radio-contrast agent-induced hyperthyroidism: case report and review of the literature. Arch Endocrinol Metab. 2016;60(3). Scholar
  22. 22.
    Hamburger JI. Evolution of toxicity in solitary nontoxic autonomously functioning thyroid nodules. J Clin Endocrinol Metab. 1980;50:1089–93.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Parle JV, Franklyn JA, Cross KW, Jones SC, Sheppard MC. Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom. Clin Endocrinol. 1991;34:77–83.CrossRefGoogle Scholar
  24. 24.
    Bjorndal MM, Sandmo Wilhelmsen K, Lu T, Jorde R. Prevalence and causes of undiagnosed hyperthyroidism in an adult healthy population. The Tromso study. J Endocrinol Investig. 2008;31:856–60.CrossRefGoogle Scholar
  25. 25.
    Meyerovitch J, Rotman-Pikielny P, Sherf M, Battat E, Levy Y, Surks MI. Serum thyrotropin measurements in the community: five-year follow-up in a large network of primary care physicians. Arch Intern Med. 2007;167:1533–8.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Rosario PW. Natural history of subclinical hyperthyroidism in elderly patients with TSH between 0.1 and 0.4 mIU/l: a prospective study. Clin Endocrinol. 2010;72:685–8.CrossRefGoogle Scholar
  27. 27.
    Parle JV, Maisonneuve P, Sheppard MC, Boyle P, Franklyn JA. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet. 2001;358:861–5.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Das G, Ojewuyi TA, Baglioni P, Geen J, Premawardhana LD, Okosieme OE. Serum thyrotrophin at baseline predicts the natural course of subclinical hyperthyroidism. Clin Endocrinol. 2012;77:146–51.CrossRefGoogle Scholar
  29. 29.
    Spencer CA, LoPresti JS, Patel A, Guttler RB, Eigen A, Shen D, Gray D, Nicoloff JT. Applications of a new chemiluminometric thyrotropin assay to subnormal measurement. J Clin Endocrinol Metab. 1990;70:453–60.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Figge J, Leinung M, Goodman AD, Izquierdo R, Mydosh T, Gates S, Line B, Lee DW. The clinical evaluation of patients with subclinical hyperthyroidism and free triiodothyronine (free T3) toxicosis. Am J Med. 1994;96:229–34.PubMedCrossRefGoogle Scholar
  31. 31.
    Wallaschofski H, Kuwert T, Lohmann T. TSH-receptor autoantibodies—differentiation of hyperthyroidism between Graves’ disease and toxic multinodular goitre. Exp Clin Endocrinol Diabetes. 2004;112:171–4.PubMedCrossRefGoogle Scholar
  32. 32.
    Pedersen IB, Knudsen N, Perrild H, Ovesen L, Laurberg P. TSH-receptor antibody measurement for differentiation of hyperthyroidism into Graves’ disease and multinodular toxic goitre: a comparison of two competitive binding assays. Clin Endocrinol. 2001;55:381–90.CrossRefGoogle Scholar
  33. 33.
    Shigemasa C, Abe K, Taniguchi S, Mitani Y, Ueda Y, Adachi T, Urabe K, Tanaka T, Yoshida A, Mashiba H. Lower serum free thyroxine (T4) levels in painless thyroiditis compared with Graves’ disease despite similar serum total T4 levels. J Clin Endocrinol Metab. 1987;65:359–63.PubMedCrossRefGoogle Scholar
  34. 34.
    Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruf J, Smyth PP, Spencer CA, Stockigt JR. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003;13:3–126.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Brenta G, Schnitman M, Gurfinkiel M, Damilano S, Pierini A, Sinay I, Pisarev MA. Variations of sex hormone-binding globulin in thyroid dysfunction. Thyroid. 1999;9:273–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Brenta G, Schnitman M, Fretes O, Facco E, Gurfinkel M, Damilano S, Pacenza N, Blanco A, Gonzalez E, Pisarev MA. Comparative efficacy and side effects of the treatment of euthyroid goiter with levo-thyroxine or triiodothyroacetic acid. J Clin Endocrinol Metab. 2003;88:5287–92.PubMedCrossRefGoogle Scholar
  37. 37.
    Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegedus L, Vitti P. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules: executive summary of recommendations. J Endocrinol Investig. 2010;33:51–6.CrossRefGoogle Scholar
  38. 38.
    Verburg FA, Aktolun C, Chiti A, Frangos S, Giovanella L, Hoffmann M, Iakovou I, Mihailovic J, Krause BJ, Langsteger W, Luster M. Why the European Association of Nuclear Medicine has declined to endorse the 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2016;43:1001.PubMedCrossRefGoogle Scholar
  39. 39.
    Ianni F, Perotti G, Prete A, Paragliola RM, Ricciato MP, Carrozza C, Salvatori M, Pontecorvi A, Corsello SM. Thyroid scintigraphy: an old tool is still the gold standard for an effective diagnosis of autonomously functioning thyroid nodules. J Endocrinol Investig. 2013;36:233–6.Google Scholar
  40. 40.
    Treglia G, Trimboli P, Verburg FA, Luster M, Giovanella L. Prevalence of normal TSH value among patients with autonomously functioning thyroid nodule. Eur J Clin Investig. 2015;45:739–44.CrossRefGoogle Scholar
  41. 41.
    Reschini E, Ferrari C, Castellani M, Matheoud R, Paracchi A, Marotta G, Gerundini P. The trapping-only nodules of the thyroid gland: prevalence study. Thyroid. 2006;16:757–62.PubMedCrossRefGoogle Scholar
  42. 42.
    Donkol RH, Nada AM, Boughattas S. Role of color Doppler in differentiation of Graves’ disease and thyroiditis in thyrotoxicosis. World J Radiol. 2013;5:178–83.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Kim TK, Lee EJ. The value of the mean peak systolic velocity of the superior thyroidal artery in the differential diagnosis of thyrotoxicosis. Ultrasonography. 2015;34:292–6.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Pazaitou-Panayiotou K, Michalakis K, Paschke R. Thyroid cancer in patients with hyperthyroidism. Horm Metab Res. 2012;44:255–62.PubMedCrossRefGoogle Scholar
  45. 45.
    Hegedus L, Bonnema SJ. Approach to management of the patient with primary or secondary intrathoracic goiter. J Clin Endocrinol Metab. 2010;95:5155–62.PubMedCrossRefGoogle Scholar
  46. 46.
    Mercante G, Gabrielli E, Pedroni C, Formisano D, Bertolini L, Nicoli F, Valcavi R, Barbieri V. CT cross-sectional imaging classification system for substernal goiter based on risk factors for an extracervical surgical approach. Head Neck. 2011;33:792–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Biondi B, Palmieri EA, Fazio S, Cosco C, Nocera M, Sacca L, Filetti S, Lombardi G, Perticone F. Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middle-aged patients. J Clin Endocrinol Metab. 2000;85:4701–5.PubMedGoogle Scholar
  48. 48.
    Sgarbi JA, Villaca FG, Garbeline B, Villar HE, Romaldini JH. The effects of early antithyroid therapy for endogenous subclinical hyperthyroidism in clinical and heart abnormalities. J Clin Endocrinol Metab. 2003;88:1672–7.CrossRefGoogle Scholar
  49. 49.
    Goichot B, Caron P, Landron F, Bouee S. Clinical presentation of hyperthyroidism in a large representative sample of outpatients in France: relationships with age, aetiology and hormonal parameters. Clin Endocrinol. 2016;84:445–51.CrossRefGoogle Scholar
  50. 50.
    Bell RJ, Rivera-Woll L, Davison SL, Topliss DJ, Donath S, Davis SR. Well-being, health-related quality of life and cardiovascular disease risk profile in women with subclinical thyroid disease - a community-based study. Clin Endocrinol. 2007;66:548–56.Google Scholar
  51. 51.
    Kalmijn S, Mehta KM, Pols HA, Hofman A, Drexhage HA, Breteler MM. Subclinical hyperthyroidism and the risk of dementia. The Rotterdam study. Clin Endocrinol. 2000;53:733–7.CrossRefGoogle Scholar
  52. 52.
    Bensenor IM, Lotufo PA, Menezes PR, Scazufca M. Subclinical hyperthyroidism and dementia: the Sao Paulo Ageing & Health Study (SPAH). BMC Public Health. 2010;10:298.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Moon JH, Park YJ, Kim TH, Han JW, Choi SH, Lim S, Park do J, Kim KW, Jang HC. Lower-but-normal serum TSH level is associated with the development or progression of cognitive impairment in elderly: Korean longitudinal study on health and aging (KLoSHA). J Clin Endocrinol Metab. 2014;99:424–32.PubMedCrossRefGoogle Scholar
  54. 54.
    Yeap BB, Alfonso H, Chubb SA, Puri G, Hankey GJ, Flicker L, Almeida OP. Higher free thyroxine levels predict increased incidence of dementia in older men: the health in men study. J Clin Endocrinol Metab. 2012;97:E2230–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Vadiveloo T, Donnan PT, Cochrane L, Leese GP. The thyroid epidemiology, audit, and research study (TEARS): morbidity in patients with endogenous subclinical hyperthyroidism. J Clin Endocrinol Metab. 2011;96:1344–51.PubMedCrossRefGoogle Scholar
  56. 56.
    Virgini VS, Wijsman LW, Rodondi N, Bauer DC, Kearney PM, Gussekloo J, den Elzen WP, Jukema JW, Westendorp RG, Ford I, Stott DJ, Mooijaart SP. Subclinical thyroid dysfunction and functional capacity among elderly. Thyroid. 2014;24:208–14.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Wijsman LW, de Craen AJ, Trompet S, Gussekloo J, Stott DJ, Rodondi N, Welsh P, Jukema JW, Westendorp RG, Mooijaart SP. Subclinical thyroid dysfunction and cognitive decline in old age. PLoS One. 2013;8:e59199.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Formiga F, Ferrer A, Padros G, Contra A, Corbella X, Pujol R. Thyroid status and functional and cognitive status at baseline and survival after 3 years of follow-up: the OCTABAIX study. Eur J Endocrinol. 2014;170:69–75.PubMedCrossRefGoogle Scholar
  59. 59.
    de Jongh RT, Lips P, van Schoor NM, Rijs KJ, Deeg DJ, Comijs HC, Kramer MH, Vandenbroucke JP, Dekkers OM. Endogenous subclinical thyroid disorders, physical and cognitive function, depression, and mortality in older individuals. Eur J Endocrinol. 2011;165:545–54.PubMedCrossRefGoogle Scholar
  60. 60.
    Gan EH, Pearce SH. Clinical review: the thyroid in mind: cognitive function and low thyrotropin in older people. J Clin Endocrinol Metab. 2012;97:3438–49.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Annerbo S, Lokk J. A clinical review of the association of thyroid stimulating hormone and cognitive impairment. ISRN Endocrinol. 2013;2013:856017.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Duntas LH, Brenta G. The effect of thyroid disorders on lipid levels and metabolism. Med Clin North Am. 2012;96:269–81.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Peppa M, Betsi G, Dimitriadis G. Lipid abnormalities and cardiometabolic risk in patients with overt and subclinical thyroid disease. J Lipids. 2011;2011:575840.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Parle JV, Franklyn JA, Cross KW, Jones SR, Sheppard MC. Circulating lipids and minor abnormalities of thyroid function. Clin Endocrinol. 1992;37:411–4.CrossRefGoogle Scholar
  65. 65.
    Berghout A, van de Wetering J, Klootwijk P. Cardiac and metabolic effects in patients who present with a multinodular goitre. Neth J Med. 2003;61:318–22.PubMedGoogle Scholar
  66. 66.
    Brenta G. Why can insulin resistance be a natural consequence of thyroid dysfunction? J Thyroid Res. 2011;2011:152850.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Yavuz DG, Yuksel M, Deyneli O, Ozen Y, Aydin H, Akalin S. Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH-suppressed nodular goitre patients. Clin Endocrinol. 2004;61:515–21.CrossRefGoogle Scholar
  68. 68.
    Maratou E, Hadjidakis DJ, Peppa M, Alevizaki M, Tsegka K, Lambadiari V, Mitrou P, Boutati E, Kollias A, Economopoulos T, Raptis SA, Dimitriadis G. Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism. Eur J Endocrinol. 2010;163:625–30.PubMedCrossRefGoogle Scholar
  69. 69.
    Rezzonico J, Niepomniszcze H, Rezzonico M, Pusiol E, Alberto M, Brenta G. The association of insulin resistance with subclinical thyrotoxicosis. Thyroid. 2011;21:945–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Heemstra KA, Smit JW, Eustatia-Rutten CF, Heijboer AC, Frolich M, Romijn JA, Corssmit EP. Glucose tolerance and lipid profile in longterm exogenous subclinical hyperthyroidism and the effects of restoration of euthyroidism, a randomised controlled trial. Clin Endocrinol. 2006;65:737–44.CrossRefGoogle Scholar
  71. 71.
    Nicholls JJ, Brassill MJ, Williams GR, Bassett JH. The skeletal consequences of thyrotoxicosis. J Endocrinol. 2012;213:209–21.PubMedCrossRefGoogle Scholar
  72. 72.
    Wartofsky L. Subclinical hyperthyroidism and fracture risk in women. J Clin Endocrinol Metab. 2014;99:2654–6.PubMedCrossRefGoogle Scholar
  73. 73.
    Faber J, Galloe AM. Changes in bone mass during prolonged subclinical hyperthyroidism due to L-thyroxine treatment: a meta-analysis. Eur J Endocrinol. 1994;130:350–6.PubMedCrossRefGoogle Scholar
  74. 74.
    Uzzan B, Campos J, Cucherat M, Nony P, Boissel JP, Perret GY. Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis. J Clin Endocrinol Metab. 1996;81:4278–89.PubMedGoogle Scholar
  75. 75.
    Lee JS, Buzkova P, Fink HA, Vu J, Carbone L, Chen Z, Cauley J, Bauer DC, Cappola AR, Robbins J. Subclinical thyroid dysfunction and incident hip fracture in older adults. Arch Intern Med. 2010;170:1876–83.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Garin MC, Arnold AM, Lee JS, Robbins J, Cappola AR. Subclinical thyroid dysfunction and hip fracture and bone mineral density in older adults: the cardiovascular health study. J Clin Endocrinol Metab. 2014;99:2657–64.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Leader A, Ayzenfeld RH, Lishner M, Cohen E, Segev D, Hermoni D. Thyrotropin levels within the lower normal range are associated with an increased risk of hip fractures in euthyroid women, but not men, over the age of 65 years. J Clin Endocrinol Metab. 2014;99:2665–73.PubMedCrossRefGoogle Scholar
  78. 78.
    Abrahamsen B, Jorgensen HL, Laulund AS, Nybo M, Brix TH, Hegedus L. Low serum thyrotropin level and duration of suppression as a predictor of major osteoporotic fractures—the OPENTHYRO register cohort. J Bone Miner Res. 2014;29:2040–50.PubMedCrossRefGoogle Scholar
  79. 79.
    Wirth CD, Blum MR, da Costa BR, Baumgartner C, Collet TH, Medici M, Peeters RP, Aujesky D, Bauer DC, Rodondi N. Subclinical thyroid dysfunction and the risk for fractures: a systematic review and meta-analysis. Ann Intern Med. 2014;161:189–99.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Blum MR, Wijsman LW, Virgini VS, Bauer DC, den Elzen WP, Jukema JW, Buckley BM, de Craen AJ, Kearney PM, Stott DJ, Gussekloo J, Westendorp RG, Mooijaart SP, Rodondi N. Subclinical thyroid dysfunction and depressive symptoms among elderly: a prospective cohort study. Neuroendocrinology. 2016;103(3-4):291–9.PubMedCrossRefGoogle Scholar
  81. 81.
    Yan Z, Huang H, Li J, Wang J. Relationship between subclinical thyroid dysfunction and the risk of fracture: a meta-analysis of prospective cohort studies. Osteoporos Int. 2016;27:115–25.PubMedCrossRefGoogle Scholar
  82. 82.
    Sawin CT, Geller A, Wolf PA, Belanger AJ, Baker E, Bacharach P, Wilson PW, Benjamin EJ, D’Agostino RB. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med. 1994;331:1249–52.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Cappola AR, Fried LP, Arnold AM, Danese MD, Kuller LH, Burke GL, Tracy RP, Ladenson PW. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA. 2006;295:1033–41.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Selmer C, Olesen JB, Hansen ML, Lindhardsen J, Olsen AM, Madsen JC, Faber J, Hansen PR, Pedersen OD, Torp-Pedersen C, Gislason GH. The spectrum of thyroid disease and risk of new onset atrial fibrillation: a large population cohort study. BMJ. 2012;345:e7895.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Biondi B. Mechanisms in endocrinology: heart failure and thyroid dysfunction. Eur J Endocrinol. 2012;167:609–18.CrossRefGoogle Scholar
  86. 86.
    Rodondi N, Bauer DC, Cappola AR, Cornuz J, Robbins J, Fried LP, Ladenson PW, Vittinghoff E, Gottdiener JS, Newman AB. Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The cardiovascular health study. J Am Coll Cardiol. 2008;52:1152–9.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Nanchen D, Gussekloo J, Westendorp RG, Stott DJ, Jukema JW, Trompet S, Ford I, Welsh P, Sattar N, Macfarlane PW, Mooijaart SP, Rodondi N, de Craen AJ. Subclinical thyroid dysfunction and the risk of heart failure in older persons at high cardiovascular risk. J Clin Endocrinol Metab. 2012;97:852–61.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Gencer B, Collet TH, Virgini V, Bauer DC, Gussekloo J, Cappola AR, Nanchen D, den Elzen WP, Balmer P, Luben RN, Iacoviello M, Triggiani V, Cornuz J, Newman AB, Khaw KT, Jukema JW, Westendorp RG, Vittinghoff E, Aujesky D, Rodondi N. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation. 2012;126:1040–9.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Frey A, Kroiss M, Berliner D, Seifert M, Allolio B, Guder G, Ertl G, Angermann CE, Stork S, Fassnacht M. Prognostic impact of subclinical thyroid dysfunction in heart failure. Int J Cardiol. 2013;168:300–5.PubMedCrossRefGoogle Scholar
  90. 90.
    Sgarbi JA, Matsumura LK, Kasamatsu TS, Ferreira SR, Maciel RM. Subclinical thyroid dysfunctions are independent risk factors for mortality in a 7.5-year follow-up: the Japanese-Brazilian thyroid study. Eur J Endocrinol. 2010;162:569–77.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Ochs N, Auer R, Bauer DC, Nanchen D, Gussekloo J, Cornuz J, Rodondi N. Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med. 2008;148:832–45.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Haentjens P, Van Meerhaeghe A, Poppe K, Velkeniers B. Subclinical thyroid dysfunction and mortality: an estimate of relative and absolute excess all-cause mortality based on time-to-event data from cohort studies. Eur J Endocrinol. 2008;159:329–41.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Rugge JB, Bougatsos C, Chou R. 2015. Screening and treatment of thyroid dysfunction: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 162(1):35-45. Scholar
  94. 94.
    Bengtsson D, Brudin L, Wanby P, Carlsson M. Previously unknown thyroid dysfunction in patients with acute ischemic stroke. Acta Neurol Scand. 2012;126:98–102.PubMedCrossRefGoogle Scholar
  95. 95.
    Wollenweber FA, Zietemann V, Gschwendtner A, Opherk C, Dichgans M. Subclinical hyperthyroidism is a risk factor for poor functional outcome after ischemic stroke. Stroke. 2013;44:1446–8.PubMedCrossRefGoogle Scholar
  96. 96.
    Schultz M, Kistorp C, Raymond I, Dimsits J, Tuxen C, Hildebrandt P, Faber J. Cardiovascular events in thyroid disease: a population based, prospective study. Horm Metab Res. 2011;43:653–9.PubMedCrossRefGoogle Scholar
  97. 97.
    Selmer C, Olesen JB, Hansen ML, von Kappelgaard LM, Madsen JC, Hansen PR, Pedersen OD, Faber J, Torp-Pedersen C, Gislason GH. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. J Clin Endocrinol Metab. 2014;99:2372–82.PubMedCrossRefGoogle Scholar
  98. 98.
    Chaker L, Baumgartner C, Ikram MA, Dehghan A, Medici M, Visser WE, Hofman A, Rodondi N, Peeters RP, Franco OH. Subclinical thyroid dysfunction and the risk of stroke: a systematic review and meta-analysis. Eur J Epidemiol. 2014;29:791–800.CrossRefGoogle Scholar
  99. 99.
    Vescovi PP, Favaloro EJ, Lippi G, Garofano M, Montagnana M, Manzato F, Franchini M. The spectrum of coagulation abnormalities in thyroid disorders. Semin Thromb Hemost. 2011;37:7–10.PubMedCrossRefGoogle Scholar
  100. 100.
    Stuijver DJ, van Zaane B, Romualdi E, Brandjes DP, Gerdes VE, Squizzato A. The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors: a systematic review and meta-analysis. Thromb Haemost. 2012;108:1077–88.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Segna D, Mean M, Limacher A, Baumgartner C, Blum MR, Beer JH, Kucher N, Righini M, Matter CM, Frauchiger B, Cornuz J, Aschwanden M, Banyai M, Osterwalder J, Husmann M, Egloff M, Staub D, Lammle B, Angelillo-Scherrer A, Aujesky D, Rodondi N. Association between thyroid dysfunction and venous thromboembolism in the elderly: a prospective cohort study. J Thromb Haemost. 2016;14:685–94.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Lerstad G, Enga KF, Jorde R, Brodin EE, Svartberg J, Braekkan SK, Hansen JB. Thyroid function, as assessed by TSH, and future risk of venous thromboembolism: the Tromso study. Eur J Endocrinol. 2015;173:83–90.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Rugge JB, Bougatsos C, Chou R. Screening and treatment of thyroid dysfunction: an evidence review for the U.S. preventive services task force. Ann Intern Med. 2015;162:35–45.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Hennessey JV, Klein I, Woeber KA, Cobin R, Garber JR. Aggressive case finding: a clinical strategy for the documentation of thyroid dysfunction. Ann Intern Med. 2015;163:311–2.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Vanderpump MP. Should we treat mild subclinical/mild hyperthyroidism? No. Eur J Intern Med. 2011;22:330–3.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Wiersinga WM. Should we treat mild subclinical/mild hyperthyroidism? Yes. Eur J Intern Med. 2011;22:324–9.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Ward L, Sgarbi JA. When to treat a suppressed TSH ICE/Endo 2014 meet-the-professor endocrine case management. Washington, DC: Endocrine Society; 2014. p. 247–50.Google Scholar
  108. 108.
    Biondi B, Fazio S, Carella C, Sabatini D, Amato G, Cittadini A, Bellastella A, Lombardi G, Sacca L. Control of adrenergic overactivity by beta-blockade improves the quality of life in patients receiving long term suppressive therapy with levothyroxine. J Clin Endocrinol Metab. 1994;78:1028–33.PubMedPubMedCentralGoogle Scholar
  109. 109.
    Gullu S, Altuntas F, Dincer I, Erol C, Kamel N. Effects of TSH-suppressive therapy on cardiac morphology and function: beneficial effects of the addition of beta-blockade on diastolic dysfunction. Eur J Endocrinol. 2004;150:655–61.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Cooper DS. Antithyroid drugs. N Engl J Med. 2005;352:905–17.PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    McDermott MT, Woodmansee WW, Haugen BR, Smart A, Ridgway EC. The management of subclinical hyperthyroidism by thyroid specialists. Thyroid. 2003;13:1133–9.PubMedCrossRefGoogle Scholar
  112. 112.
    Walter MA, Briel M, Christ-Crain M, Bonnema SJ, Connell J, Cooper DS, Bucher HC, Muller-Brand J, Muller B. Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials. BMJ. 2007;334:514.PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Bonnema SJ, Hegedus L. Radioiodine therapy in benign thyroid diseases: effects, side effects, and factors affecting therapeutic outcome. Endocr Rev. 2012;33:920–80.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Graf H. Recombinant human TSH and radioactive iodine therapy in the management of benign multinodular goiter. Eur J Endocrinol. 2015;172:R47–52.PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    Stokkel MP, Handkiewicz Junak D, Lassmann M, Dietlein M, Luster M. EANM procedure guidelines for therapy of benign thyroid disease. Eur J Nucl Med Mol Imaging. 2010;37:2218–28.PubMedCrossRefGoogle Scholar
  116. 116.
    Bartalena L, Macchia PE, Marcocci C, Salvi M, Vermiglio F. Effects of treatment modalities for Graves’ hyperthyroidism on Graves’ orbitopathy: a 2015 Italian Society of Endocrinology Consensus Statement. J Endocrinol Investig. 2015;38:481–7.CrossRefGoogle Scholar
  117. 117.
    Nygaard B, Faber J, Veje A, Hegedus L, Hansen JM. Transition of nodular toxic goiter to autoimmune hyperthyroidism triggered by 131I therapy. Thyroid. 1999;9:477–81.PubMedCrossRefGoogle Scholar
  118. 118.
    Cirocchi R, Trastulli S, Randolph J, Guarino S, Di Rocco G, Arezzo A, D’Andrea V, Santoro A, Barczynski M, Avenia N. Total or near-total thyroidectomy versus subtotal thyroidectomy for multinodular non-toxic goitre in adults. Cochrane Database Syst Rev. 2015;(8):CD010370.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  • Gabriela Brenta
    • 1
  • José Sgarbi
    • 2
  1. 1.Thyroid Unit, Division of Endocrinology and MetabolismUnidad Asistencial Dr. César MilsteinBuenos AiresArgentina
  2. 2.Thyroid Unit, Division of Endocrinology and MetabolismFaculdade Estadual de Medicina de MariliaMariliaBrazil

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