Natural history, diagnosis and management of subclinical thyroid dysfunction

Biondi, Bernadette

doi:10.1016/j.beem.2011.12.004

Cited by 98Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryThyroid Cancer Diagnosis and Treatment

Natural history, diagnosis and management of subclinical thyroid dysfunction

Biondi, Bernadette·2012·Best Practice & Research Clinical Endocrinology & Metabolism

DOI 10.1016/j.beem.2011.12.004

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Abstract

Subclinical thyroid dysfunction (STD) represents a condition of slight thyroid hormone excess or deficiency, which may be associated with important adverse effects. This review will focus on the natural history, diagnosis and management of subclinical thyroid dysfunction. Since STD is only detected as a thyroid stimulating hormone (TSH) abnormality, it is essential to exclude transient causes of abnormal serum TSH before treating this disorder. Treatment of subclinical hyperthyroidism (SHyper) is recommended in elderly patients with undetectable serum TSH for the increased risk of atrial fibrillation, osteoporosis and bone fractures and for the higher risk of progression to overt disease. Treatment of subclinical hypothyroidism should be considered in patients with serum TSH above 10 mU/L for the increased risk of progression to overt hypothyroidism and the increased risk of coronary heart disease and heart failure events, which have been documented in patients with TSH increase above 10 mU/L. About 75% of patients with STD have mild dysfunction. The mild form of STD (low but detectable serum TSH in SHyper and mild increased serum TSH between 5 and 9 mU/L in SHypo is associated with a minor risk of disease progression to overt dysfunction. The best treatment for STD remains controversial. Treatment of the mild form of STD should be considered after evaluating the patients' age, the adverse risk factors, the potential beneficial effects of treating this disorder and any underlying co-morbidities. Mild SHypo should be treated in infertile and pregnant women.

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Serum free T4 and free T3 levels are generally normal to low-normal in people with central causes of low serum TSH.
“Serum free T 4 and free T 3 levels are generally normal to low-normal in people with the latter conditions [3,5,18] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [18]
The degree of TSH suppression is the best parameter for predicting the progression from subclinical to overt hyperthyroidism.
“The degree of TSH suppression is the best parameter for predicting the progression from subclinical to overt hyperthyroidism [3,5,18,31] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [18]
Subclinical hyperthyroidism may progress to overt hyperthyroidism and may be associated with increased cardiovascular and skeletal risk.
“SHyper may progress to overt hyperthyroidism and may be associated with increased cardiovascular and skeletal risk [3,5,18] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [18]

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Haentjens, P., Van Meerhaeghe, A., Poppe, K., & Velkeniers, B. (2008) · European Journal of Endocrinology · doi:10.1530/eje-08-0110 · Cited by 174 · see citing works
Antithyroperoxidase and Antithyroglobulin Antibodies in a Five-Year Follow-Up Survey of Populations with Different Iodine Intakes
Li, Y., Teng, D., Shan, Z., Teng, X., Guan, H., Yu, X., Fan, C., Chong, W., Yang, F., Dai, H., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2368 · Cited by 170 · see citing works
Initial thyroid status and cardiovascular risk factors: The EPIC‐Norfolk prospective population study
Boekholdt, S. M., Titan, S. M., Wiersinga, W. M., Chatterjee, K., Basart, D. C. G., Luben, R., Wareham, N. J., & Khaw, K. (2010) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03640.x · Cited by 167 · see citing works
Cardiac Function, Physical Exercise Capacity, and Quality of Life during Long-Term Thyrotropin-Suppressive Therapy with Levothyroxine: Effect of Individual Dose Tailoring
Mercuro, G. G., Panzuto, M., Bina, A., Leo, M., Cabula, R., Petrini, L., Pigliaru, F., & Mariotti, S. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.1.6298 · Cited by 162 · see citing works
Cardiovascular Risk and Subclinical Hypothyroidism: Focus on Lipids and New Emerging Risk Factors. What Is the Evidence?
Duntas, L. H., & Wartofsky, L. (2007) · Thyroid · doi:10.1089/thy.2007.0116 · Cited by 157 · see citing works
Does subclinical hypothyroidism affect cardiac pump performance?
Ripoli, A., Pingitore, A., Favilli, B., Bottoni, A., Turchi, S., Osman, N. F., De Marchi, D., Lombardi, M., L'Abbate, A., & Iervasi, G. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.10.044 · Cited by 157 · see citing works
Endogenous subclinical thyroid disorders, physical and cognitive function, depression, and mortality in older individuals
de Jongh, R. T., Lips, P., van Schoor, N. M., Rijs, K. J., Deeg, D. J. H., Comijs, H. C., Kramer, M. H. H., Vandenbroucke, J. P., & Dekkers, O. M. (2011) · European Journal of Endocrinology · doi:10.1530/eje-11-0430 · Cited by 157 · see citing works
Normalization of serum thyrotrophin by means of radioiodine treatment in subclinical hyperthyroidism: effect on bone loss in postmenopausal women
Faber, Jensen, Petersen, Nygaard, Hegedüs, & Siersbæk‐Nielsen (1998) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1998.00427.x · Cited by 156 · see citing works
Increased Cardiovascular and Cancer Mortality after Radioiodine Treatment for Hyperthyroidism
Metso, S., Jaatinen, P., Huhtala, H., Auvinen, A. P., Oksala, H., & Salmi, J. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2321 · Cited by 148 · see citing works
Genetic Predisposition to Elevated Serum Thyrotropin Is Associated with Exceptional Longevity
Atzmon, G., Barzilai, N., Surks, M. I., & Gabriely, I. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0808 · Cited by 145 · see citing works
Subclinical thyroid dysfunctions are independent risk factors for mortality in a 7.5-year follow-up: the Japanese–Brazilian thyroid study
Sgarbi, J. A., Matsumura, L. K., Kasamatsu, T. S., Ferreira, S. R. G., & Maciel, R. M. B. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0845 · Cited by 138 · see citing works
Control of adrenergic overactivity by beta-blockade improves the quality of life in patients receiving long term suppressive therapy with levothyroxine
Biondi, B. (1994) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.78.5.1028 · Cited by 137 · see citing works
Self-citation
Bone metabolism during anti‐thyroid drug treatment of endogenous subclinical hyperthyroidism
Mudde, A. H., Houben, A. J. H. M., & Kruseman, A. C. N. (1994) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1994.tb02571.x · Cited by 135 · see citing works
The Effects of Thyrotropin-Suppressive Therapy on Bone Metabolism in Patients with Well-Differentiated Thyroid Carcinoma
Heemstra, K. A., Hamdy, N. A. T., Romijn, J. A., & Smit, J. W. A. (2006) · Thyroid · doi:10.1089/thy.2006.16.583 · Cited by 134 · see citing works
Subclinical Thyroid Dysfunction and Incident Hip Fracture in Older Adults
Lee, J. S., Bůžková, P., Fink, H. A., Vu, J., Carbone, L., Chen, Z., Cauley, J., Bauer, D. C., Cappola, A. R., & Robbins, J. (2010) · Archives of Internal Medicine · doi:10.1001/archinternmed.2010.424 · Cited by 134 · see citing works
What Is the Evidence?
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Subclinical hypothyroidism and functional mobility in older adults
Simonsick, E. M. (2009) · Archives of Internal Medicine · doi:10.1001/archinternmed.2009.392 · Cited by 129 · see citing works
Cardiac hypertrophy as a result of long-term thyroxine therapy and thyrotoxicosis.
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Thyrotropin Levels and Risk of Fatal Coronary Heart Disease: The HUNT Study
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Reversible Diastolic Dysfunction after Long-Term Exogenous Subclinical Hyperthyroidism: A Randomized, Placebo-Controlled Study
Smit, J. W. A., Eustatia‐Rutten, C. F. A., Corssmit, E. P. M., Pereira, A. M., Frölich, M. A., Bleeker, G. B., Holman, E. R., van der Wall, E. E., Romijn, J. A., & Bax, J. J. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0620 · Cited by 125 · see citing works
Assessment of left ventricular diastolic function by radionuclide ventriculography at rest and exercise in subclinical hypothyroidism, and its response to l-thyroxine therapy
Brenta, G., Mutti, L. A., Schnitman, M., Fretes, O., Perrone, A., & Matute, M. L. (2003) · The American Journal of Cardiology · doi:10.1016/s0002-9149(03)00322-9 · Cited by 118 · see citing works
The Thyroid Epidemiology, Audit, and Research Study (TEARS): the natural history of endogenous subclinical hyperthyroidism
Vadiveloo, T., Donnan, P. T., Cochrane, L., & Leese, G. P. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0854 · Cited by 118 · see citing works
Cardiovascular Effects of Mild Hypothyroidism
Biondi, B. (2007) · Thyroid · doi:10.1089/thy.2007.0158 · Cited by 106 · see citing works
Self-citation
Haemodynamic changes following treatment of subclinical and overt hyperthyroidism
Faber, J., Wiinberg, N., Schifter, S., & Mehlsen, J. (2001) · European Journal of Endocrinology · doi:10.1530/eje.0.1450391 · Cited by 104 · see citing works
Thyroid Disease and Vascular Function
Owen, P. J. D., Sabit, R., & Lazarus, J. H. (2007) · Thyroid · doi:10.1089/thy.2007.0051 · Cited by 101 · see citing works
Effects of thyroxin therapy on cardiac function in patients with subclinical hypothyroidism: index of myocardial performance in the evaluation of left ventricular function
Yazici, M., Gorgulu, S., Sertbas, Y., Erbilen, E., Albayrak, S., Yildiz, O., & Uyan, C. (2004) · International Journal of Cardiology · doi:10.1016/j.ijcard.2003.05.015 · Cited by 99 · see citing works
Natural history of the transition from euthyroidism to overt autoimmune hypo- or hyperthyroidism: a prospective study
Effraimidis, G., Strieder, T. G. A., Tijssen, J. G. P., & Wiersinga, W. M. (2011) · European Journal of Endocrinology · doi:10.1530/eje-10-0785 · Cited by 99 · see citing works
Natural history of subclinical hyperthyroidism in elderly patients with TSH between 0·1 and 0·4 mIU/l: a prospective study
Rosario, P. W. (2010) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03696.x · Cited by 88 · see citing works
Variation in thyroid function in subclinical hypothyroidism: importance of clinical follow-up and therapy
Karmisholt, J., Andersen, S., & Laurberg, P. (2011) · European Journal of Endocrinology · doi:10.1530/eje-10-1021 · Cited by 86 · see citing works
Risk for Progression to Overt Hypothyroidism in an Elderly Japanese Population with Subclinical Hypothyroidism
Imaizumi, M., Sera, N., Ueki, I., Horie, I., Ando, T., Usa, T., Ichimaru, S., Nakashima, E., Hida, A., Soda, M., et al. (2011) · Thyroid · doi:10.1089/thy.2010.0411 · Cited by 73 · see citing works
Thyroid Hormone Use, Hyperthyroidism and Mortality in Older Women
Bauer, D. C., Rodondi, N., Stone, K. L., & Hillier, T. A. (2007) · The American Journal of Medicine · doi:10.1016/j.amjmed.2006.04.034 · Cited by 71 · see citing works
Subclinical Hypothyroidism and Cardiovascular Risk
Palmieri, E. A., Fazio, S., Lombardi, G., & Biondi, B. (2004) · Treatments in Endocrinology · doi:10.2165/00024677-200403040-00005 · Cited by 68 · see citing works
Self-citation
Decreased serum TSH levels are not associated with mortality in the adult northeast German population
Ittermann, T., Haring, R., Sauer, S., Wallaschofski, H., Dörr, M., Nauck, M. A., & Völzke, H. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0566 · Cited by 68 · see citing works
Effects of TSH-suppressive therapy on cardiac morphology and function: beneficial effects of the addition of beta-blockade on diastolic dysfunction
Gullu, S., Altuntas, F., Dincer, I., Erol, C., & Kamel, N. (2004) · European Journal of Endocrinology · doi:10.1530/eje.0.1500655 · Cited by 57 · see citing works
Endothelial-mediated coronary flow reserve in patients with mild thyroid hormone deficiency
Biondi, B., Galderisi, M., Pagano, L., Sidiropulos, M., Pulcrano, M., Errico, A. D., Ippolito, S., Rossi, A., DIVITIIS, O. D., & Lombardi, G. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0196 · Cited by 48 · see citing works
Self-citation
Prospective echocardiographic evaluation of patients with endogenous subclinical hyperthyroidism and after restoring euthyroidism: Subclinical hyperthyroidism and the heart
Kaminski, G., Michalkiewicz, D., Makowski, K., Podgajny, Z., Szalus, N., Ruchala, M., Szczepanek, E., & Gielerak, G. (2011) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2010.03957.x · Cited by 45 · see citing works
The Management of Subclinical Hyperthyroidism by Thyroid Specialists
McDermott, M. T., Woodmansee, W. W., Haugen, B. R., Smart, A., & Ridgway, E. C. (2003) · Thyroid · doi:10.1089/10507250360731532 · Cited by 45 · see citing works
Patient Guide to Vitamin D Deficiency
Holick, M. F., & Gordon, C. M. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.96.7.zeg33a · Cited by 32 · see citing works
Management of Subclinical Hyperthyroidism
Wartofsky, L. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-2409 · Cited by 31 · see citing works
Abnormal Left Ventricular Longitudinal Functional Reserve Assessed by Exercise Pulsed Wave Tissue Doppler Imaging in Patients with Subclinical Hypothyroidism
Akçakoyun, M., Kaya, H., Kargın, R., Pala, S., Emiroğlu, Y., Esen, Ö., Karapınar, H., Kaya, Z., & Esen, A. M. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0117 · Cited by 28 · see citing works
Should we treat all subjects with subclinical thyroid disease the same way?
Biondi, B. (2008) · European Journal of Endocrinology · doi:10.1530/eje-08-0527 · Cited by 25 · see citing works
Self-citation
Factors Influencing Clinical Decisions to Initiate Thyroxine Therapy for Patients With Mildly Increased Serum Thyrotropin (5.1-10.0 mIU/L)
Fatourechi, V., Lankarani, M., Schryver, P. G., Vanness, D. J., Long, K. H., & Klee, G. G. (2003) · Mayo Clinic Proceedings · doi:10.4065/78.5.554 · Cited by 22 · see citing works
Invited Commentary: Cardiovascular mortality in subclinical hyperthyroidism: an ongoing dilemma
Biondi, B. (2010) · European Journal of Endocrinology · doi:10.1530/eje-09-1095 · Cited by 17 · see citing works
Self-citation
Ripoli A, Pingitore A, Favilli B, Bottoni A, Turchi S, Osman NF, De Marchi D, Lombardi M, L'Abbate A, Iervasi G. Does subclinical hypothyroidism affect cardiac pump performance? Evidence from a magnetic resonance imaging study
(2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.02.032 · Cited by 12 · see citing works

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The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism
Biondi, B., Bartalena, L., Cooper, D. S., Hegedüs, L., Laurberg, P., & Kahaly, G. J. (2015) · European Thyroid Journal · doi:10.1159/000438750 · Cited by 323 · see citing works
Self-citation
MECHANISMS IN ENDOCRINOLOGY: Heart failure and thyroid dysfunction
Biondi, B. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0627 · Cited by 291 · see citing works
Self-citation
Effects of thyroid hormones on the heart
Vargas‐Uricoechea, H., Bonelo, A., & Sierra-Torres, C. H. (2014) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/j.arteri.2014.07.003 · Cited by 193 · see citing works
Hypothyroidism and Thyroiditis
Brent, G. A., & Davies, T. F. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4377-0324-5.00013-4 · Cited by 115 · see citing works
Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts
Segna, D., Bauer, D. C., Feller, M., Schneider, C., Fink, H. A., Aubert, C. E., Collet, T. ‐., da Costa, B. R., Fischer, K., Peeters, R. P., et al. (2018) · Journal of Internal Medicine · doi:10.1111/joim.12688 · Cited by 87 · see citing works
A double-blind placebo-controlled trial of liquid thyroxine ingested at breakfast: results of the TICO study
Cappelli, C., Pirola, I., Daffini, L., Formenti, A., Iacobello, C., Cristiano, A., Gandossi, E., Agabiti Rosei, E., & Castellano, M. (2016) · Thyroid · doi:10.1089/thy.2015.0422 · Cited by 80 · see citing works
Age- and gender-specific reference intervals of TSH and free T4 in an iodine-replete area: Data from Korean National Health and Nutrition Examination Survey IV (2013–2015)
Park, S. Y., Kim, H. I., Oh, H.-K., Kim, T. H., Jang, H. W., Chung, J. H., Shin, M.-H., & Kim, S. W. (2018) · PLOS ONE · doi:10.1371/journal.pone.0190738 · Cited by 79 · see citing works
Subclinical thyroid dysfunction and cardiovascular consequences: An alarming wake-up call?
Manolis, A. S., Manolis, T. A., Melita, H., & Manolis, A. S. (2019) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2019.02.011 · Cited by 81 · see citing works
Subclinical hypothyroidism in older individuals
Biondi, B., & Cappola, A. R. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00285-0 · Cited by 80 · see citing works
Self-citation
Thyroxine softgel capsule in patients with gastric-related T4 malabsorption
Santaguida, M. G., Virili, C., Duca, S. C. D., Cellini, M., Gatto, I., Brusca, N., De Vito, C., Gargano, L., & Centanni, M. (2015) · Endocrine · doi:10.1007/s12020-014-0476-7 · Cited by 68 · see citing works
The lipid‐lowering effect of levothyroxine in patients with subclinical hypothyroidism: A systematic review and meta‐analysis of randomized controlled trials
Li, X., Wang, Y., Guan, Q., Zhao, J., & Gao, L. (2017) · Clinical Endocrinology · doi:10.1111/cen.13338 · Cited by 66 · see citing works
Respiratory Manifestations of Hypothyroidism: A Systematic Review
Sørensen, J. R., Winther, K. H., Bonnema, S. J., Godballe, C., & Hegedűs, L. D. (2016) · Thyroid · doi:10.1089/thy.2015.0642 · Cited by 66 · see citing works
Thyroid hormones and the heart
Vargas‐Uricoechea, H., & Sierra-Torres, C. H. (2014) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2013-0059 · Cited by 65 · see citing works
Subclinical Thyroid Dysfunction and Frailty Among Older Men
Virgini, V. S., Rodondi, N., Cawthon, P. M., Harrison, S. L., Hoffman, A. R., ORWOLL, E. S., Ensrud, K. E., & Bauer, D. C. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3191 · Cited by 55 · see citing works
Inadequate levothyroxine replacement for primary hypothyroidism is associated with poor health-related quality of life-a Brazilian multicentre study
Vigário, P. D. S., Vaisman, F., Coeli, C. M., Ward, L., Graf, H., Carvalho, G., Júnior, R. M., & Vaisman, M. (2013) · Endocrine · doi:10.1007/s12020-013-9886-1 · Cited by 54 · see citing works
A genetic risk score for thyroid peroxidase antibodies associates with clinical thyroid disease in community-based populations
Schultheiss, U. T., Teumer, A., Medici, M., Li, Y., Daya, N., Chaker, L., Homuth, G., Uitterlinden, A. G., Nauck, M., Hofman, A., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-4352 · Cited by 50 · see citing works
Hypothyroidism and Risk of Cardiovascular Disease
Gluvic, Z. M., Zafirovic, S. S., Obradovic, M. M., Sudar-Milovanovic, E. M., Rizzo, M., & Isenović, E. R. (2022) · Current Pharmaceutical Design · doi:10.2174/1381612828666220620160516 · Cited by 54 · see citing works
Subclinical Thyroid Dysfunction and Functional Capacity Among Elderly
Virgini, V. S., Wijsman, L. W., Rodondi, N., Bauer, D. C., Kearney, P. M., Gussekloo, J., den Elzen, W. P. J., Jukema, J. W., Westendorp, R. G. J., Ford, I., et al. (2014) · Thyroid® · doi:10.1089/thy.2013.0071 · Cited by 44 · see citing works
Relationship between subclinical thyroid dysfunction and the risk of fracture: a meta-analysis of prospective cohort studies
Yan, Z., Huang, H., Li, J., & Wang, J. (2016) · Osteoporosis International · doi:10.1007/s00198-015-3221-z · Cited by 43 · see citing works
Clinical and subclinical maternal hypothyroidism and their effects on neurodevelopment, behavior and cognition
Batistuzzo, A., & Ribeiro, M. O. (2020) · Archives of Endocrinology and Metabolism · doi:10.20945/2359-3997000000201 · Cited by 44 · see citing works
Dementia and osteoporosis in a geriatric population: Is there a common link?
Downey, C. L., Young, A., Burton, E., Graham, S. M., MacFarlane, R. J., Tsapakis, E.-M., & Tsiridis, E. E. (2017) · World Journal of Orthopedics · doi:10.5312/wjo.v8.i5.412 · Cited by 42 · see citing works
Bone health in children with long–term idiopathic subclinical hypothyroidism
Mase, R. D., Cerbone, M., Improda, N., Esposito, A., Capalbo, D., Mainolfi, C. G., Santamaria, F., Pignata, C., & Salerno, M. (2012) · The Italian Journal of Pediatrics/Italian journal of pediatrics · doi:10.1186/1824-7288-38-56 · Cited by 35 · see citing works
Acute and chronic effects of kisspeptin‐54 administration on GH , prolactin and TSH secretion in healthy women
Jayasena, C. N., Comninos, A. N., Narayanaswamy, S., Bhalla, S., Abbara, A., Ganiyu‐Dada, Z., Busbridge, M., Ghatei, M. A., Bloom, S. R., & Dhillo, W. S. (2014) · Clinical Endocrinology · doi:10.1111/cen.12512 · Cited by 32 · see citing works
Thyroid And Aging
Jasim, S., & Gharib, H. (2017) · Endocrine Practice · doi:10.4158/ep171796.ra · Cited by 35 · see citing works
Natural history of mild subclinical hypothyroidism in a middle-aged and elderly Chinese population: a prospective study
Li, X., Zhen, D., Zhao, M., Liu, L., Guan, Q., Zhang, H., Ge, S., Tang, X., & Gao, L. (2017) · Endocrine Journal · doi:10.1507/endocrj.ej16-0549 · Cited by 29 · see citing works
Thyroid Disorders in Older Adults
Visser, W. E., Visser, T. J., & Peeters, R. P. (2013) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.02.008 · Cited by 29 · see citing works
Risks and safety of combination therapy for hypothyroidism
Jonklaas, J. (2016) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2016.1182019 · Cited by 27 · see citing works
Associations between thyroid hormones and serum metabolite profiles in an euthyroid population
Jourdan, C., Linseisen, J., Meisinger, C., Petersen, A.-K., Gieger, C., Rawal, R., Illig, T., Heier, M., Peters, A., Wallaschofski, H., et al. (2013) · Metabolomics · doi:10.1007/s11306-013-0563-4 · Cited by 26 · see citing works
Association of subclinical thyroid dysfunction with bone mineral density and fracture: a meta-analysis of prospective cohort studies
Zhu, H., Zhang, J., Wang, J., Zhao, X., & Gu, M. (2020) · Endocrine · doi:10.1007/s12020-019-02110-9 · Cited by 28 · see citing works
Subclinical thyroid dysfunction, bone mineral density, and osteoporosis in a middle-aged Korean population
Lee, K., Lim, S., Park, H. H., Woo, H., Chang, Y., Sung, E., Jung, H. S., Yun, K. E., Kim, C., Ryu, S., et al. (2019) · Osteoporosis International · doi:10.1007/s00198-019-05205-1 · Cited by 26 · see citing works
Levothyroxine treatment and gastric juice pH in humans: the proof of concept
Virili, C., Bruno, G., Santaguida, M. G., Gargano, L., Stramazzo, I., De Vito, C., Cicenia, A., Scalese, G., Porowska, B., Severi, C., et al. (2022) · Endocrine · doi:10.1007/s12020-022-03056-1 · Cited by 22 · see citing works
Thyroid hormonal profile in elderly patients treated with two different levothyroxine formulations: A single institute survey
Cappelli, C., Pirola, I., Daffini, L., Gandossi, E., Agosti, B., & Castellano, M. (2014) · European Geriatric Medicine · doi:10.1016/j.eurger.2014.09.006 · Cited by 22 · see citing works
The Management of Thyroid Abnormalities in Chronic Heart Failure
Biondi, B. (2019) · Heart Failure Clinics · doi:10.1016/j.hfc.2019.02.008 · Cited by 20 · see citing works
Self-citation
Surgical management of hyperthyroidism
Quérat, C., Germain, N., Dumollard, J., Estour, B., Péoc’h, M., & Prades, J. M. (2015) · European Annals of Otorhinolaryngology Head and Neck Diseases · doi:10.1016/j.anorl.2014.04.005 · Cited by 18 · see citing works
Is an Isolated TSH Elevation in Chronic Nonthyroidal Illness “Subclinical Hypothyroidism”?
Kaptein, E. M., LoPresti, J. S., & Kaptein, M. J. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1850 · Cited by 17 · see citing works
Hypothyroidism and Thyroiditis
Brent, G. A., & Weetman, A. P. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-29738-7.00013-7 · Cited by 16 · see citing works
The longitudinal effect of subclinical hypothyroidism on urine microalbumin-to-urine creatinine ratio in patients with type 2 diabetes mellitus
Xie, J., Wang, X., Zhang, Y., Li, H., Xu, Y., & Zheng, D. (2019) · BMC Endocrine Disorders · doi:10.1186/s12902-019-0405-0 · Cited by 16 · see citing works
Liquid levothyroxine and its potential use
Formenti, A. M., Daffini, L., Pirola, I., Gandossi, E., Cristiano, A., & Cappelli, C. (2015) · HORMONES · doi:10.14310/horm.2002.1579 · Cited by 15 · see citing works
Liquid levothyroxine formulations in patients taking drugs interfering with L-T4 absorption
Gatta, E., Bambini, F., Buoso, C., Gava, M., Maltese, V., Anelli, V., Delbarba, A., Pirola, I., & Cappelli, C. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1080108 · Cited by 13 · see citing works
Non-autoimmune subclinical hypothyroidism due to a mutation in TSH receptor: report on two brothers
Cerbone, M., Agretti, P., Marco, G. D., Improda, N., Pignata, C., Santamaria, F., Tonacchera, M., & Salerno, M. (2013) · The Italian Journal of Pediatrics/Italian journal of pediatrics · doi:10.1186/1824-7288-39-5 · Cited by 13 · see citing works
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Additional file 4 of Management strategies for patients with subclinical hypothyroidism: a protocol for an umbrella review
Bauer, B. S., Azcoaga-Lorenzo, A., Agrawal, U., & McCowan, C. (2021) · Figshare · doi:10.6084/m9.figshare.16916436
Additional file 3 of Management strategies for patients with subclinical hypothyroidism: a protocol for an umbrella review
Bauer, B. S., Azcoaga-Lorenzo, A., Agrawal, U., & McCowan, C. (2021) · Figshare · doi:10.6084/m9.figshare.16916433
Additional file 1 of Management strategies for patients with subclinical hypothyroidism: a protocol for an umbrella review
Bauer, B. S., Azcoaga-Lorenzo, A., Agrawal, U., & McCowan, C. (2021) · Figshare · doi:10.6084/m9.figshare.16916427
Additional file 2 of Management strategies for patients with subclinical hypothyroidism: a protocol for an umbrella review
Bauer, B. S., Azcoaga-Lorenzo, A., Agrawal, U., & McCowan, C. (2021) · Figshare · doi:10.6084/m9.figshare.16916430

Authors: Biondi, B.
Affiliations: Federico II University Hospital (IT)
Corresponding author: Biondi, Bernadette
ORCID: Biondi, Bernadette
Venue: Best Practice & Research Clinical Endocrinology & Metabolism
Publisher: Elsevier BV
Published: 2012-08
Volume: 26
Issue: 4
Pages: 431-446
ISSN: 1521-690X (ISSN-L)
DOI: 10.1016/j.beem.2011.12.004
OpenAlex: W2129395029
Cited by: 98
References: 120
Citations by year: 2025: 2 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 9 · 2020: 7 · 2019: 13 · 2018: 3 · 2017: 8 · 2016: 3 · 2015: 12 · 2014: 12 · 2013: 11 · 2012: 2
FWCI: 1.64
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Best Practice & Research Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords: subclinical thyroid dysfunction, subclinical hyperthyroidism, subclinical hypothyroidism, thyroid-stimulating hormone, natural history (disease), disease progression, overt hypothyroidism, overt hyperthyroidism, atrial fibrillation, osteoporosis, coronary artery disease, heart failure, treatment thresholds, pregnancy, infertility
MeSH terms: Humans, Thyroid Diseases, Thyroid Function Tests, Thyrotropin, Thyroxine, Triiodothyronine

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Natural history, diagnosis and management of subclinical thyroid dysfunction

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