Clinical Implications and Management of Sub Clinical Hyperthyroidism: A Review

Parijat De, Terence Pang, Gautam Das

Department of Endocrinology, City Hospital, Birmingham, UK.
Department of Endocrinology, University Hospital of Wales, Cardiff, UK.

DOI: 10.4236/ojemd.2012.23004                

Abstract

Sub clinical hyperthyroidism (SCH) is characterized by normal free thyroid hormone concentrations along with a low or undetectable serum TSH (thyrotropin) level. The increased use of TSH as a screening measure and improved assay sensitivity is contributing to the diagnosis of sub clinical hyperthyroidism more frequently than ever in our clinical practise leading to the increased prevalence of the disease. The significance of SCH remains uncertain for most patients as some will revert to normal thyroid status over time whereas others will either remain static or progress to overt thyroid disease in the future. The detrimental effects of a persistently suppressed TSH has now been extensively studied and its effect on the cardiovascular system, the skeleton, mood disturbance, quality of life is quite significant leading to considerable morbidity and mortality. Majority of the patients are asymptomatic and lack overt features but the relevance of treatment is more focussed in elderly patients where the risk of developing cardiac arrhythmia and loss of bone mineral density is much more than young people in whom a conservative approach is usually preferred. The issue is contentious, the situation is challenging and the benefits of treatment are debatable. The consensus for who, when and how to treat is growing but still hasn’t been universally accepted. We attempt to review the recent literature available for sub clinical hyperthyroidism and suggest an analytical approach to its investigations and management.

Keywords

Sub Clinical; Hyperthyroid; Cardiovascular; Skeleton; Arrhythmia

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	A. D. Toft, “Clinical Practice: Sub Clinical Hyperthyroidism,” The New England Journal of Medicine, Vol. 345, 2001, pp. 512-516. doi:10.1056/NEJMcp010145
[2]	J. V. Parle, P. Maisonneuve, M. C. Sheppard, P. Boyle and J. A. Franklyn, “Prediction of All Cause Mortality in Elderly People from One Low Serum Thyrotropin Result: A 10-Year Cohort Study,” Lancet, Vol. 358, 2001, pp. 861-865. doi:10.1016/S0140-6736(01)06067-6
[3]	H. Gharib, R. M. Tuttle, H. J. Baskin, L. H. Fish, P. A. Singer and M. T. Mcdermott, “Sub Clinical Thyroid Dysfunction: A Joint Statement on Management from the American Association of Clinical Endocrinology, the American Thyroid Association and the Endocrine Society,” Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 1, 2005, pp. 581-585. doi:10.1210/jc.2004-1231
[4]	N. D. Charles, “The Many Causes of Sub Clinical Hyperthyroidism,” Thyroid, Vol. 6, 1996, pp. 391-396.
[5]	S. R. Tollin, E. F. Fallon, M. Mikhail, H. Goldstein and E. Yung, “The Utility of Thyroid Nuclear Imaging and Other Studies in the Detection and Treatment of Underlying Thyroid Abnormalities in Patients with Endogenous Sub Clinical Thyrotoxicosis,” Clinical Nuclear Medicine, Vol. 25, No. 5, 2000, pp. 341-347. doi:10.1097/00003072-200005000-00004
[6]	A. L. Mitchell and S. H. S. Pearce, “How Should We Treat Patients with Low Serum Thyrotropin Concentrations?” Clinical Endocrinology, Vol. 72, No. 3, 2010, pp. 292-296.
[7]	D. J. Stott, A. R. Mclellan, J. Finlayson, P. Chu and W. D. Alexander, “Elderly Patients with Suppressed Serum TSH but Normal Free Thyroid Hormone Levels Usually Have Mild Thyroid over Activity and Are at Increased Risk of Developing Overt Hyperthyroidism,” The Quarterly Journal of Medicine, Vol. 78, No. 1, 1991, pp. 77-84.
[8]	J. V. Parle, J. A. Franklyn, K. W. Cross, S. C. Jones and M. C. Sheppard, “Prevalence and Follow Up of Abnormal TSH Concentrations in the Elderly in the United Kingdom,” Clinical Endocrinology (Oxford), Vol. 34, No. 1, 1991, pp. 77-83. doi:10.1111/j.1365-2265.1991.tb01739.x
[9]	M. P. J. Vanderpump, W. M. G. Turnbridge, J. M. French, D. Appleton, D. Bates, F. Clark, E. J. Grimley, D. M. Hasan, H. Rodges, F. Turnbridge and E. T. Young, “The Incidence of Thyroid Disorders in the Community. A Twenty-Year Follow Up of the Whickham Survey,” Clinical Endocrinology, Vol. 43, No. 1, 1995, pp. 55-68. doi:10.1111/j.1365-2265.1995.tb01894.x
[10]	D. D. Jones, K. E. May and S. A. Geraci, “Subclinical Thyroid Disease, “Subclinical Thyroid Disease,” The American Journal of Medicine, Vol. 123, No. 6, 2010, pp. 502-504. doi:10.1016/j.amjmed.2009.12.023
[11]	B. Biondi, S. Fazio, C. Carella, G. Amato, A. Cittadini, G. Lupoli, L. Sacca, A. Bellastella and G. Lombardi, “Cardiac Effects of Long Term Thyrotropin Suppressive Therapy with Levothyroxine,” Journal of Clinical Endocrinology and Metabolism, Vol. 77, No. 2, 1993, pp. 334338. doi:10.1210/jc.77.2.334
[12]	C. T. Sawin, A. Geller, P. A. Wolf, A. J. Belanger, E. Baker, P. Bacharach, P. W. Wilson, E. J. Benjamin and R. B. D’Agostino, “Low Serum Thyrotropin Concentrations as a Risk Factor for Atrial Fibrillation in Older Persons,” The New England Journal of Medicine, Vol. 331, 1994, pp. 1249-1252. doi:10.1056/NEJM199411103311901
[13]	B. Biondi, S. Fazio, A. Cuocolo, M. Sabatini and L. Sacca, “Impaired Cardiac Reserve and Exercise Capacity in Patients Receiving Long Term Thyrotropin Suppressive Therapy with Levothyroxine,” Journal of Clinical Endocrinology and Metabolism, Vol. 81, No. 12, 1996, pp. 4224-4228. doi:10.1210/jc.81.12.4224
[14]	G. Mercuro, M. G. Panzuto, A. Bina, M. Leom, R. Cabula, L. Petrini, F. Pigliaru and S. Mariotti, “Cardiac Function, Physical Exercise Capacity and Quality of Life during Long Term Thyrotropin Suppressive Therapy with Levothyroxine Effect of Individual Dose Tailoring,” Journal of Clinical Endocrinology and Metabolism, Vol. 85, No. 1, 2000, pp. 159-164. doi:10.1210/jc.85.1.159
[15]	B. Biondi, E. A. Palmieri, S. Fazio, C. Cosco, M. Nocera, L. Sacca, S. Filetti, G. Lombardi and F. Pertisone, “Endogenous Sub Clinical Hyperthyroidism Affects Quality of Life and Cardiac Morphology and Function in Young and Middle Aged Patients,” Journal of Clinical Endocrinology and Metabolism, Vol. 85, No. 12, 2000, pp. 47014705. doi:10.1210/jc.85.12.4701
[16]	M. D. Grammange, J. V. Parle, R. L. Holder, L. M. Roberts, F. D. Hobbs, S. Wilson, M. C. Sheppard and J. A. Franklyn, “Association Between Serum Free Thyroxine Concentration and Atrial Fibrillation,” Archives of Internal Medicine, Vol. 167, No. 9, 2007, pp. 928-934. doi:10.1001/archinte.167.9.928
[17]	A. R. Cappola, L. P. Fried, A. M. Arnold, M. D. Danesse, L. H. Kuller, G. L. Burke, R. P. Tracy and P. W. Ladenson, “Thyroid Status, Cardiovascular Risk and Mortality in Older Adults,” The Journal of the American Medical Association, Vol. 295, No. 9, 2006, pp. 1033-1041. doi:10.1001/jama.295.9.1033
[18]	K. Yasuro, I. Masaki, T. Hidiki, K. Yasuko, M. Tetsuro and N. Yoshiki, “Persistent Increase in Bone Turnover in Grave’s Patients with Sub Clinical Hyperthyroidism,” Journal of Clinical Endocrinology and Metabolism, Vol. 85, No. 11, 2000, pp. 4157-4161. doi:10.1210/jc.85.11.4157
[19]	Z. E. Belaya, G. A. Melnichenko, L. Y. Rozhinskaya, V. V. Fadeev, T. M. Alekseeva, O. K. Dorofeeva, N. I. Sasonova and G. S. Kolesnikova, “Subclinical Hyperthyroidism of Variable Etiology and Its Influence on the Bone in Post Menopausal Women,” Hormones, Vol. 6, No. 1, 2007, pp. 62-70.
[20]	S. Klamijn, K. M. Mehta, H. A. Pols, A. Hofman, H. A. Drexhage and M. M. Breteler, “Subclinical Hyperthyroidism and the Risk of Dementia : The Rotterdam Study,” Clinical Endocrinology (Oxford), Vol. 53, No. 6, 2000, pp. 733-737. doi:10.1046/j.1365-2265.2000.01146.x
[21]	B. Biondi, A. P. Emiliano, M. Klain, M. Schlumberger, S. Filetti and G. Lombardi, “Sub Clinical Hyperthyroidism: Clinical Features and Treatment Options,” European Journal of Endocrinology, Vol. 152, 2005, pp. 1-9. doi:10.1530/eje.1.01809
[22]	M. I. Surks and E. O. Campro, “Sub Clinical Thyroid Disease,” The American Journal Medicine, Vol. 100, No. 2, 1996, pp. 217-223. doi:10.1016/S0002-9343(97)89462-4
[23]	AACE Thyroid Taskforce, “Subclinical Hyperthyroidism: Position Statement from the American Association of Clinical Endocrinologists,” Endocrine Practice, Vol. 5, 1999, pp. 220-221.
[24]	F. C. Nandana, I. S. Marki and H. D. Gilbert, “Subclinical Thyroid Disease,” The Journal of the American Medical Association, Vol. 291, No. 2, 2004, pp. 239-243. doi:10.1001/jama.291.2.239
[25]	P. N. Ladenson, “Thyrotoxicosis and the Heart: Something Old and Something New,” Journal of Clinical Endocrinology and Metabolism,” Vol. 77, No. 2, 1993, pp. 332-333. doi:10.1210/jc.77.2.332
[26]	P. W. Rosario, “Natural History of Sub Clinical Hyperthyroidism in Elderly Patients with TSH Between 0.1 and 0.4 mIU/L: A Prospective Study,” Clinical Endocrinology (Oxford), Vol. 72, No. 5, 2010, pp. 685-688. doi:10.1111/j.1365-2265.2009.03696.x
[27]	G. Das, T. A. Ojewuyi, P. Baglioni, J. Geen, L. D. Premawardhana and O. E. Okosieme, “Baseline Serum Thyrotropin Predicts the Natural Course of Subclinical Hyperthyroidism. Clinical Endocrinology,” Clinical Endocrinology, Vol. 77, No. 1, 2012, pp. 146-151. doi:10.1111/j.1365-2265.2012.04345.x
[28]	J. G. Holowell, N. W. Staehling, W. D. Flanders, W. H. Hannon, E. W. Gunter, C. A. Spencer and L. E. Braverman, “Serum TSH, T4 and Thyroid Antibodies in the United States Population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III),” Journal of Clinical Endocrinology and Metabolism, Vol. 87, No. 2, 2002, pp. 489-499. doi:10.1210/jc.87.2.489
[29]	F. Vahab, “Subclinical Thyroid Disease,” Mayo Clinic Proceedings, Vol. 76, 2001, pp. 413-417.
[30]	C. Spencer, A. Eigen, D. Shen, M. Duda, S. Qualls, S. Weiss and J. Nicoloff, “Specificity of Sensitive Assay of Thyrotropin (TSH) Used to Screen for Thyroid Disease in Hospitalized patients,” Clinical Chemistry, Vol. 33, 1987, pp. 1391-1396.
[31]	J. J. Diez and P. Iglesias, “An Analysis of the Natural Course of Sub-Clinical Hyperthyroidism,” The American Journal of Medical Sciences, Vol. 337, No. 4, 2009, pp. 225-232. doi:10.1097/MAJ.0b013e318187e16d
[32]	T. Vadiveloo, P. T. Donnan, L. Cochrane and G. P. Leese, “The Thyroid Epidemiology, Audit and Research Study (TEARS): The Natural History of Endogenous Subclinical Hyperthyroidism,” Journal of Clinical Endocrinology and Metabolism, Vol. 96, No. 1, 2011, pp. E1E8. doi:10.1210/jc.2010-0854
[33]	B. J. Schouten, B. E. Brownie, C. M. Frampton and J. G. Turner, “Subclinical Thyrotoxicosis in an Outpatient Population—Predictors of Outcome,” Clinical Endocrinology (Oxford), Vol. 74, No. 2, 2011, pp. 257-261. doi:10.1111/j.1365-2265.2010.03908.x
[34]	P. W. Rosario, “The Natural History of Subclinical Hyperthyroidism in Patients below the Age of 65 Years,” Clinical Endocrinology (Oxford), Vol. 68, No. 3, 2008, pp. 491-492.
[35]	K. A. Woeber, “Observations Concerning the Natural History of Subclinical Hyperthyroidism,” Thyroid, Vol. 15, No. 7, 2005, pp. 687-691. doi:10.1089/thy.2005.15.687
[36]	B. Biondi, E. A. Palmieri, G. Lombardi and S. Fazio, “Effects of Sub Clinical Thyroid Dysfunction on the Heart,” Annals of Internal Medicine, Vol. 137, 2002, pp. 904-914.
[37]	M. Petretta, D. Bonaduce, L. Spinelli, M. L. E. Vicario, V. Nuzzo, F. Marciaro, P. Camuso, V. De Sanctis and G. Lupoli, “Cardiovascular Haemodynamics and Cardiac Autonomic Control in Patients with Sub Clinical and Overt Hyperthyroidism,” The European Journal of Endocrinology, Vol. 145, 2001, pp. 691-696. doi:10.1530/eje.0.1450691
[38]	J. A. Sgarbi, F. Villaca, B. Gaberline, H. E. Villar and J. H. Romaldini, “The Effects of Early Anti Thyroid Therapy for Endogenous Sub Clinical Hyperthyroidism on Clinical and Heart Abnormalities,” Journal of Clinical Endocrinology and Metabolism, Vol. 88, No. 4, 2003, pp. 1672-1677. doi:10.1210/jc.2002-021046
[39]	H. Yavuz, H. Altunbas, M. K. Baki, F. Demircioglu, M. Cakir and U. Karayalcin, “Normal Systolic Time Intervals in Sub Clinical Hyperthyroidism,” Journal of Endocrinological Investigation, Vol. 23, 2000, pp. 38.
[40]	D. Levy, R. J. Garrison, D. D. Savage, W. B. Kannell and W. Castelli, “Prognostic Implication of Echocardiographically Determined Left Ventricular Mass in the Framingham Heart Study,” The New England Journal of Medicine, Vol. 322, 1990, pp. 1561-1566. doi:10.1056/NEJM199005313222203
[41]	M. Dorr, B. Wolff, D. M. Robinson, V. John, J. Ludemann, W. Meng, S. B. Felix and H. Volzke, “The Association of Thyroid Function with Cardiac Mass and Left Ventricular Hypertrophy,” Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 2, 2005, pp. 673677. doi:10.1210/jc.2004-1554
[42]	N. Ochs, R. Auer, D. C. Bauer, D. Nanchen, J. Gussekloo, J. Cornuz and N. Rodondi, “Meta-Analysis: Subclinical Thyroid Dysfunction and the Risk for Coronary Heart Disease and Mortality,” Annals of Internal Medicine, Vol. 148, No. 11, 2008, pp. 832-845.
[43]	P. Haentjens, A. Van Meerhaeghe, K. Poppe and B. Velkeniers, “Subclinical Thyroid Dysfunction and Mortality: An Estimate of Relative and Absolute Excess All Cause Mortality Based on Time to Event Data from Cohort Studies,” European Journal of Endocrinology, Vol. 159, No. 3, 2008, pp. 329-341. doi:10.1530/EJE-08-0110
[44]	J. Gussekloo, E. Van Excel, A. J. De Craen, A. E. Meinders, M. Frolich and R. G. J. Westendrop, “Thyroid Status, Disability and Cognitive Function, and Survival in Old Age,” The Journal of the American Medical Association, Vol. 292, No. 21, 2004, pp. 2591-2599. doi:10.1001/jama.292.21.2591
[45]	A. W. Van den Beld, T. J. Visser, R. A. Feelders, D. E. Grobbee and S. W. J. Lamberts, “Thyroid Hormone Concentrations, Disease, Physical Function and Mortality in Elderly Men,” Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 12, 2005, pp. 6403-6409. doi:10.1210/jc.2005-0872
[46]	T. Ittermann, R. Haring, S. Sauer, H. Wallaschofski, M. Dorr, M. Nauck and H. Volzke, “Decreased Serum TSH Levels Are Not Associated with Mortality in the Adult Northeast German Population,” European Journal of Endocrinology, Vol. 162, No. 3, 2010, pp. 579-585. doi:10.1530/EJE-09-0566
[47]	J. Auer, P. Scheibner, T. Mische, W. Langsteger, O. Eber and B. Eber, “Sub Clinical Hyperthyroidism as a Risk Factor for Atrial Fibrillation,” American Heart Journal, Vol. 142, No. 5, 2001, pp. 838-842. doi:10.1067/mhj.2001.119370
[48]	P. Petersen and J. M. Hensen, “Stroke in Thyrotoxicosis with Atrial Fibrillation,” Stroke, Vol. 19, 1988, pp. 15-18. doi:10.1161/01.STR.19.1.15
[49]	C. F. Presti and R. G. Hart, “Thyrotoxicosis, Atrial Fibrillation and Embolism Revisited,” American Heart Journal, Vol. 117, No. 4, 1989, pp. 976-977. doi:10.1016/0002-8703(89)90642-X
[50]	J. Faber, N. Wiinberg, S. Schifter and J. Mehisen, “Hemodynamic Changes Following Treatment of Sub Clinical and Overt Hyperthyroidism,” European Journal of Endocrinology,” Vol. 145, 2001, pp. 391-396. doi:10.1530/eje.0.1450391
[51]	M. Helfand and C. C. Redfern, “Screening for Thyroid Disease: An Update,” Annals of Internal Medicine, Vol. 129, No. 2, 1999, pp. 144-158.
[52]	J. C. Forfar, C. M. Feek, H. C. Miller and A. D. Toft, “Atrial Fibrillation and Isolated Suppression of the Pituitary Thyroid Axis: Response to Specific Anti Thyroid Therapy,” International Journal of Cardiology, Vol. 1, No. 1, 1981, pp. 43-48. doi:10.1016/0167-5273(81)90047-4
[53]	A. H. Muddle, F. J. L. Reijnders and A. C. Kruseman, “Peripheral Bone Density in Women with Untreated Multinodular Goitre,” Clinical Endocrinology (Oxford), Vol. 37, No. 1, 1992, pp. 35-39. doi:10.1111/j.1365-2265.1992.tb02280.x
[54]	J. C. Foldes, G. Tarjan, M. Szathmari, F. Varga, I. Krasznai and C. S. Horvath, “Bone Mineral Density in Patients with Endogenous Sub Clinical Hyperthyroidism: Is This Thyroid Status a Risk Factor for Osteoporosis,” Clinical Endocrinology (Oxford), Vol. 39, No. 5, 1993, pp. 521-527. doi:10.1111/j.1365-2265.1993.tb02403.x
[55]	A. H. Muddle, A. J. Houben and K. A. C. Nieuwenhuijzen, “Bone Metabolism during Anti Thyroid Drug Treatment of Endogenous Sub Clinical Hyperthyroidism,” Clinical Endocrinology (Oxford), Vol. 41, No. 4, 1994, pp. 421-424. doi:10.1111/j.1365-2265.1994.tb02571.x
[56]	J. Faber, I. W. Jensen, L. Petersen, B. Nygaard, L. Hegedus and K. Siersbaek-Nielsen, “Normalization of Serum Thyrotropin by Means of Radioiodine Treatment in Subclinical Hyperthyroidism: Effect of Bone Loss in Postmenopausal Women,” Clinical Endocrinology (Oxford), Vol. 48, No. 3, 1998, pp. 285-290. doi:10.1046/j.1365-2265.1998.00427.x
[57]	A. D. Toft, “Thyroxine Therapy,” The New England Journal of Medicine, Vol. 331, 1994, pp. 174-180. doi:10.1056/NEJM199407213310307
[58]	B. Uzzan, J. Campos, P. Cucherat, P. Nony, J. P. Boissel and G.Y. Perret, “Effects on Bone Mass of Long Term Treatment with Thyroid Hormone: A Meta-Analysis,” Journal of Clinical Endocrinology and Metabolism, Vol. 81, No. 12, 1996, pp. 4278-4289. doi:10.1210/jc.81.12.4278
[59]	P. W. Rosario, “Bone and Heart Abnormalities of Subclinical Hyperthyroidism in Women below the Age of 65 Years,” Arquivos Brasileiros de Endocrinologia & Metabologia, Vol. 52, No. 9, 2008, pp. 1448-1451. doi:10.1590/S0004-27302008000900007
[60]	D. C. Bauer, B. Ettinger, M. C. Nevitt and K. L. Stone, “Risk for Fracture in Women with Low Serum Levels of Thyroid Stimulating Hormone,” Annals of Internal Medicine, Vol. 134, No. 7, 2001, 134, pp. 561-568.
[61]	J. A. Franklyn, J. Betterridge, J. Daykin, R. Holder, G. D. Oates, J. V. Parle, J. Lilley, D. A. Heath and M. C. Sheppard, “Long Term Thyroxine Treatment and Bone Mineral Density,” Lancet, Vol. 340, 1992, pp. 9-13. doi:10.1016/0140-6736(92)92423-D
[62]	L. J. Greenlund, K. S. Nair and M. D. Brennan, “Changes in Body Composition in Women Following Treatment of Overt and Subclinical Hyperthyroidism,” Endocrine Practice, Vol. 14, No. 8, 2008, pp. 973-978.
[63]	H. A. Oomen, A. J. Schipperijn and H. A. Drexhage, “The Prevalence of Affective Disorder and in Particular of a Rapid Cycling of Bipolar Disorder in Patients with Abnormal Thyroid Function Tests,” Clinical Endocrinology (Oxford), Vol. 45, No. 2, 1996, pp. 215-223. doi:10.1046/j.1365-2265.1996.d01-1558.x
[64]	M. Rockel, J. Teuber, R. Schmidt, S. Kaumeier, H. Hafner and K. H. Usadel, “Correlation of ‘Latent’ Hyperthyroidism with Psychological and Somatic Changes,” Journal of Klin Wochenschr, Vol. 65, 1987, pp. 264-273.
[65]	G. Ceresini, F. Lauretani, M. Maggio, G. P. Ceda, S. Morganti, E. Usberti, C. Chezzi, R. Valcavo, S. Bandinelli, J. M. Guralnik, A. R. Cappola, G. Valenti and L. Ferrucci, “Thyroid Function Abnormalities and Cognitive Impairment in Elderly People: Results of the Invecchiare in Chianti Study,” Journal of the American Geriatrics Society, Vol. 57, No. 1, 2009, pp. 89-93. doi:10.1111/j.1532-5415.2008.02080.x
[66]	N. Dober, N. Hamscho, C. Menzel, J. Peters, L. Frolich, A. Tsolakis, K. Zaplatnikov, T. Kratzsch, J. Diener, K. Maurer and F. Grunwald, “Subclinical Hyperthyroidism in Dementia and Correlation of the Metabolic Index in FDG-PET,” Acta medica Austriaca, Vol. 30, 2003, pp. 130-133.
[67]	L. M. Roberts, H. Pattison, A. Roalfe, J. Franklyn, S. Wilson, F. D. Hobbs and J. V. Parle, “Is Subclinical Thyroid Dysfunction in the Elderly Associated with Depression or Cognitive Dysfunction?” Annals of Internal Medicine, Vol. 145, 2006, pp. 573-581.
[68]	US Preventive Services Task Force, “Screening Thyroid Disease: Summary of Recommendations,” 2004. www.ahrg.gov/clinic/usptf/uspsthyr.htm
[69]	M. P. Vanderpump, J. A. Ahlquist, J. A. Franklyn and R. N. Clayton, “Consensus Statement for Good Practice and Audit Measures in the Management of Hypothyroidism and Hyperthyroidism. The Research Unit of the Royal College of Physicians of London, The Endocrinology and Diabetes Committee of the Royal College of Physicians of London and the Society for Endocrinology,” British Medical Journal, Vol. 313, 1996, pp. 539-544. doi:10.1136/bmj.313.7056.539
[70]	M. Helfand and C. C. Redfern, “Clinical Guideline, Part 2 Screening for Thyroid Disease: An Update, American College of Physicians,” Annals of Internal Medicine, Vol. 129, 1998, pp. 144-158.
[71]	I. Donangelo and G. D Braustein, “Update on Subclinical Hyperthyroidism,” American Family Physicians, Vol. 83, No. 8, 2011, pp. 933-938.
[72]	American Academy of Family Physicians, “Recommendations for Clinical Preventive Services, Rev 5.7,” 2005. www.aafp.org/x24973.xml
[73]	P. W. Ladenson, P. A. Singer, K. B. Ain, N. Bagchi, S. T. Bigos, E. G. Levy, S. A. Smith, G. H. Daniels and H. D. Cohen, “American Thyroid Association Guidelines for Detection of Thyroid Dysfunction,” Archives of Internal Medicine, Vol. 160, 2000, pp. 1573-1575. doi:10.1001/archinte.160.11.1573
[74]	R. S. Bahn, H. B. Buch, D. S. Cooper, J. R. Garber, M. C. Greenlee, I. Klein, P. Laurberg, I. R. Mcdougall, V. M. Montori, S. A. Rivkees, D. S. Ross, J. A. Sosa and M. N. Stan, “Hyperthyroidism and Other Causes of Thyrotoxicosis: Management Guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists,” Endocrine Practice, Vol. 17, No. 3, 2011, pp. e1-e65.
[75]	AACE Thyroid Task Force, “American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Hyperthyroidism and Hypothyroidism,” Endocrine Practice, Vol. 8, 2002, pp. 457-469.
[76]	R. C. Smallridge, “Disclosing Sub Clinical Thyroid Disease: An Approach to Mild Laboratory Abnormalities and Vague and Absent Symptoms,” Postgraduate Medicine, Vol. 107, 2000, pp. 143-146. doi:10.3810/pgm.2000.01.812
[77]	M. H. Samuels, “Sub Clinical Thyroid Disease in the Elderly,” Thyroid, Vol. 8, No. 9, 1998, pp. 803-813. doi:10.1089/thy.1998.8.803
[78]	B. Biondi, S. Fazio, C. Carella, D. Sabatini, G. Amato, A. Cittadini, A. Bellastella, G. Lombardi and L. Sacca, “Control of Adrenergic over Activity by ? Blockade Improves Quality of Life in Patients Receiving Long-Term Suppressive Therapy with Levothyroxine,” Journal of Clinical Endocrinology and Metabolism, Vol. 78, No. 5, 1994, pp. 1028-1033. doi:10.1210/jc.78.5.1028
[79]	N. Hemandy and D. Shah, “Sub Clinical Thyroid Disorders: Current Screening and Treatment Recommendations,” Resident and Staff Physician, Vol. 52, No. 1, 2006, pp. 1.
[80]	E. H. Hoogendoorn, M. D. Heijer, A. P. J. Van Dijk and A. R. Hermus, “Subclinical Hyperthyroidism: To Treat or Not to Treat?” Post Graduate Medical Journal, Vol. 80, No. 945, 2004, pp. 394-398. doi:10.1136/pgmj.2003.017095
[81]	D. S. Cooper, “Anti-Thyroid Drugs,” The New England Journal of Medicine, Vol. 352, 2005, pp. 905-917. doi:10.1056/NEJMra042972