Abstract
Although subclinical hyperthyroidism (SCH) has been associated with increased risk of osteoporosis and cardiac arrhythmias, its treatment is still controversial. This study was designed as a prospective, randomized, intervention, control-study with a 1-year follow-up in order to investigate whether normalization of serum TSH in SCH using methimazole has favorable bone and heart clinical effects. Fourteen patients with endogenous SCH (not Graves’ disease) were enrolled, 7 (5 women/2 men; group T) were treated with methimazole (2.5–7.5 mg/day), and 7 (5 women/2 men; group C) were followed without treatment; 10 healthy subjects were also included in the study as controls. Serum free-T3 (FT3), free-T4 (FT4) and TSH, thyroid echography, bone stiffness index (SI), as measured by heel ultrasonometry, and 24-h electrocardiography monitoring were obtained. SCH patients exhibited higher systolic and diastolic blood pressure than control subjects. They also had a significantly higher number of both ventricular premature beats (VPB) (mean±SEM: 681 ±238 vs 6±2 beats/24 h; p<0.02) and atrial premature beats (APB) (mean±SEM: 495±331 vs 7±2 beats/24 h; p<0.0001), and a lower SI (66±5 vs 96±3; p<0.001). Twelve months after normalization of TSH with the use of methimazole, the number of VPB decreased significantly (947±443 vs 214±109 beats/24 h; p<0.05) while it remained unchanged in untreated SCH patients (414±163 vs 487±152 beats/24 h; p=ns). An insignificant therapy effect was observed as far as APB were concerned (826±660 vs 144±75 beats/24 h; p=ns), however their number increased significantly in the untreated group (463±49 vs 215±46 beats/ 24 h; p<0.05). The SI increased significantly as a result of therapy in group T (64.1 ±4.8 vs 70.0±5.3; p<0.02) and was further reduced in group C at the end of the study (69.1 ±7.3 vs 62.9±7.1; p<0.001 ). No adverse effect was observed in group T. In conclusion, anti-thyroid therapy seems to have favorable bone and heart clinical effects in subjects with endogenous SCH.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Helfand M. Screening for subclinical thyroid dysfunction in non-pregnant adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2004, 140: 128–41.
Toft AD. Subclinical hyperthyroidism. N Engl J Med 2001, 345: 512–6.
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.
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.
Vanderpump MPJ, Tunbridge WMG, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol 1995, 43: 55–68.
Helfand M, Redfern CC. Clinical guideline, part 2. Screening for thyroid disease: an update. American College of Physicians. Ann Intern Med 1998, 129: 144–58.
AACE Thyroid Task Force. American association of clinical endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 2002, 8: 458–67.
Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease. Scientific review and guidelines for diagnosis and management. JAMA 2004, 291: 228–38.
Brunn J, Block U, Ruf G, Bos I, Kunze WP, Scriba PC. Volumetric analysis of thyroid lobes by real-time ultrasound. Deutsche Medizinische Wochenschrift 1981, 106: 1338–40.
Greenspan SL, Bouxsein ML, Melton ME, et al. Precision and discriminatory ability of calcaneal bone assessment technologies. J Bone Miner Res 1997, 12: 1303–13.
Hans D, Dargent-Molina P, Schott AM, et al. Ultrasonographic heel measurements to predict hip fracture in elderly women: the EPIDOS prospective study. Lancet 1996, 348: 511–4.
Riggs BL, Melton LJ 3rd. Involutional osteoporosis. N Engl J Med 1986, 314: 1676–86.
Lee WY, Oh KW, Rhee EJ, et al. Relationship between subclinical thyroid dysfunction and femoral neck bone mineral density in women. Arch Med Res 2006, 37: 511–6.
Mudde AH, Houben AJ, Nieuwenhuijzen Kruseman AC. Bone metabolism during anti-thyroid drug treatment of endogenous subclinical hyperthyroidism. Clin Endocrinol (Oxf) 1994, 41: 421–4.
Kisakol G, Kaya A, Gonen S, Tunc R. Bone and calcium metabolism in subclinical autoimmune hyperthyroidism and hypothyroidism. Endocr J 2003, 50: 657–61.
Gurlek A, Gedik O. Effect of endogenous subclinical hyperthyroidism on bone metabolism and bone mineral density in premenopausal women. Thyroid 1999, 9: 539–43.
Yönem O, Dökmetas HS, Aslan SM, Erselcan T. Is antithyroid treatment really relevant for young patients with subclinical hyperthyroidism? Endocr J 2002, 49: 307–14.
Britto JM, Fenton AJ, Holloway WR, Nicolson GC. Osteoclast mediate thyroid hormone stimulation of osteoclastic bone resorption. Endocrinology 1994, 134: 169–76.
Eriksen EF. Normal and pathological remodeling of human trabecular bone: three dimensional reconstruction of the remodeling sequence in normals and in metabolic bone disease. Endocr Rev 1986, 7: 379–408.
Inoue M, Tawata M, Yokomori N, Endo T, Onaya T. Expression of thyrotropin receptor on clonal osteoblast-like rat osteosarcoma cells. Thyroid 1998, 8: 1059–64.
Kumeda Y, Inaba M, Tahara H, et al. Persistent increase in bone turnover in Graves’ patients with subclinical hyperthyroidism. J Clin Endocrinol Metab 2000, 85: 4157–61.
Bauer DC, Ettinger B, Nevitt MC, Stone KL. Risk of fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med 2001, 134: 561–8.
Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994, 331: 1249–52.
Auer J, Scheibner P, Mische T, Langsteger W, Eber O, Eber B. Subclinical hyperthyroidism as a risk factor for atrial fibrillation. Am Heart J 2001, 142: 838–42.
Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med 2001, 344: 501–9.
Sgarbi JA, Villaça 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.
Biondi B, Palmieri EA, Fazio S, et al. 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.
Polikar R, Burger AG, Scherrer U, Nicod P. The thyroid and the heart. Circulation 1993, 87: 1435–41.
Klein I, Hong C. Effects of thyroid hormone on cardiac size and myosin content of the heterotopically transplanted rat heart. J Clin Invest 1986, 77: 1694–8.
Col NF, Surks MI, Daniels GH. Subclinical thyroid disease. Clinical applications. JAMA 2004, 291: 239–43.
Faber J, Wiinberg N, Schifter S, Mehlsen J. Haemodynamic changes following treatment of subclinical and overt hyperthyroidism. Eur J Endocrinol 2001, 145; 391–6.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Buscemi, S., Verga, S., Cottone, S. et al. Favorable clinical heart and bone effects of anti-thyroid drug therapy in endogenous subclinical hyperthyroidism. J Endocrinol Invest 30, 230–235 (2007). https://doi.org/10.1007/BF03347430
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03347430