- Email: [email protected]
Hyperthyroidism
CORRESPONDENCE
Hyperthyroidism Sir—In his excellent Seminar on hyperthyroidism (Aug 9, p 459),1 David Cooper suggests that elderly individuals with thyrotoxicosis have less obvious symptoms and signs than younger patients, including a higher prevalence of cardiac manifestations, such as atrial fibrillation and, more rarely, congestive heart failure. Up to 35% of elderly people with thyrotoxicosis will develop atrial fibrillation. Cooper does not, however, mention the paramount importance of subclinical hyperthyroidism as a risk factor for atrial fibrillation, especially in elderly individuals. Among older people, in whom atrial fibrillation is common, overt hyperthyroidism is exclusion of uncommon.2 After patients taking thyroid hormone, about 1–2% of these older people have low serum thyrotropin concentrations, few of whom are judged to have clinical hyperthyroidism.3 Thus, subclinical hyperthyroidism is much more common than overt hyperthyroidism in people older than age 60 years3 and does not generally progress to overt hyperthyroidism.4 A low, rather than a normal, serum thyrotropin concentration is associated with a more than five-fold higher likelihood for the presence of atrial fibrillation, with no great difference between subclinical and overt hyperthyroidism.5 Thus, in elderly people, subclinical hyperthyroidism is an important risk factor for atrial fibrillation. In the absence of pre-existing cardiac disease, treatment of subclinical or overt hyperthyroidism usually results in a return to normal cardiac function, including regular sinus rhythm. Perhaps, therefore, individuals with reduced concentrations of serum thyrotropin, irrespective of raised free thyroid hormone concentrations, should be considered for treatment to restore normal thyroid function? *Johann Auer, Robert Berent, Thomas Weber, Bernd Eber Second Medical Department, Division of Cardiology and Intensive Care, General Hospital Wels, 4600 Wels, Austria (e-mail: [email protected]) 1 2
3
4
Cooper DS. Hyperthyroidism. Lancet 2003; 362: 459–68. Peters NS, Schilling RJ, Kanagaratnam P, Markides V. Atrial fibrillation: strategies to control, combat, and cure. Lancet 2002; 359: 593–603. Sawin CT, Geller A, Kaplan MM, Bacharach P, Wilson PW, Hershman JM. Low serum thyrotropin (thyroid-stimulating hormone) in older persons without hyperthyroidism. Arch Intern Med 1991; 151: 165–68. Auer J, Berent R, Weber T, Eber B.
1584
5
Epidemiology of atrial fibrillation. Lancet 2002; 360: 572. 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.
Sir—David Cooper1 refers to the flow chart on laboratory diagnosis of hyperthyroidism in his Seminar numerous times. In the chart, apart from thyroid stimulating hormone, radioiodine uptake has a central place in the diagnosis of hyperthyroidism, which is counterintuitive in view of Cooper’s statement that its measurement lacks both specificity and sensitivity. His choice to assess radioiodine uptake seems to be driven in part by the tendency in the USA to aim for treatment with radioactive iodine (131I) both for toxic multinodular goitre and for Graves’ disease, which are the most prevalent causes of hyperthyroidism. Elsewhere, although most patients with toxic multinodular goitre are offered the option of treatment with 131I, many patients with Graves’ disease are given a course of antithyroid drugs, such as thiamazole, carbimazole, and propylthiouracil, instead. I therefore propose use of a diagnostic work-up in which assessment of thyroid stimulating antibodies (or thyrotropin-receptor stimulating antibodies) is central, although I agree with Cooper that in many patients a diagnosis is apparent from the presence of eye symptoms. Such a work-up would have immediate clinical consequences (choice of antithyroid agents versus work-up with radioiodine uptake). A related point is the late occurrence of hypothyroidism after administration of 131I. Cooper states that permanent hypothyroidism arises in virtually all patients with Graves’ disease, although such a reaction is presumably related to the amount of radioactivity administered. Outside the USA, the prevalence of hypothyroidism varies from 30% to 70% 1–9 years after radioactive treatment.2–5 Since hypothyroidism arises less often after radioactive treatment in patients with toxic multinodular goitre than in those with Graves’ disease,4,5 the dose of 131I given should probably be lower for treatment of Graves’ disease than of toxic multinodular goitre. Timon W van Haeften Department of Internal Medicine, University Medical Center Utrecht, PO Box 85500, NL 3508 GA Utrecht, Netherlands (e-mail: [email protected]) 1
Cooper DS. Hyperthyroidism. Lancet 2003; 362: 459–68.
2
3
4
5
Bogazzi F, Bartalena L, Brogioni S, et al. Comparison of radioiodine with radioiodine plus lithium in the treatment of Graves’ hyperthyroidism. J Clin Endocrinol Metab 1999; 84: 499–503. Franklyn JA, Daykin J, Holder R, Sheppard MC. Radioiodine therapy compared in patients with toxic nodular or Graves’ hyperthyroidism. QJM 1995; 88: 175–80. Veneman TF, Weymer M, Tjabbes T, van Haeften TW. Relevance of cause of hyperthyroidism in determining its management. Neth J Med 1989; 35: 303–08. Leary AC, Grealy G, Higgins TM, et al. Long-term outcomes of treatment of hyperthyroidism in Ireland. Ir J Med Sci 1999; 168: 47–52.
Sir—In his Seminar,1 David Cooper discusses treatment options from a very American point of view. In his discussion of the different therapeutic approaches to hyperthyroidism, he mentions alternatives to the American preference for radioactive iodine without assessing the pros and cons of the various treatment options. That the decision about whether ablative therapy is the best option is often affected by availability of surgery or legal restrictions on the use of radioisotopes, could account for the preference for radioactive iodine for Graves’ disease in the USA compared with in several European countries. Cooper states that the worsening of pre-existent endocrine ophthalmopathy under therapy with radioactive iodine can be prevented by adjunctive treatment with prednisolone. There seems, therefore, no medical reason to favour surgery as ablative therapy. Remission rates after administration of antithyroid drugs as first-line treatments can reach 50%,2 so why are drugs not favoured as a primary option? Such treatment would offer patients the chance to regain a permanent euthyroid state without having to undergo an invasive procedure, or the chance of eventual hypothyroidism. In my opinion, ablative therapy should only be undertaken in cases of relapse. Furthermore, I do not believe that radioactive iodine should be used to treat toxic multinodular goitre, since it can hamper or prevent subsequent diagnosis of, and surgery for, thyroid cancer. Even in Graves’ disease, presence scintigraphically cold or nonfunctioning nodules would warrant further diagnostic procedures, since almost all thyroid carcinomas are scintigraphically cold. In the case of multinodular goitre, usually containing hot and cold nodules, cancer cannot be ruled out, since fine-needle aspiration of all nodules is not feasible. Although clinically apparent thyroid cancer is rare, subclinical cancers have been
THE LANCET • Vol 362 • November 8, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
Hyperthyroidism Sir—In his excellent Seminar on hyperthyroidism (Aug 9, p 459),1 David Cooper suggests that elderly individuals with thyrotoxicosis have less obvious symptoms and signs than younger patients, including a higher prevalence of cardiac manifestations, such as atrial fibrillation and, more rarely, congestive heart failure. Up to 35% of elderly people with thyrotoxicosis will develop atrial fibrillation. Cooper does not, however, mention the paramount importance of subclinical hyperthyroidism as a risk factor for atrial fibrillation, especially in elderly individuals. Among older people, in whom atrial fibrillation is common, overt hyperthyroidism is exclusion of uncommon.2 After patients taking thyroid hormone, about 1–2% of these older people have low serum thyrotropin concentrations, few of whom are judged to have clinical hyperthyroidism.3 Thus, subclinical hyperthyroidism is much more common than overt hyperthyroidism in people older than age 60 years3 and does not generally progress to overt hyperthyroidism.4 A low, rather than a normal, serum thyrotropin concentration is associated with a more than five-fold higher likelihood for the presence of atrial fibrillation, with no great difference between subclinical and overt hyperthyroidism.5 Thus, in elderly people, subclinical hyperthyroidism is an important risk factor for atrial fibrillation. In the absence of pre-existing cardiac disease, treatment of subclinical or overt hyperthyroidism usually results in a return to normal cardiac function, including regular sinus rhythm. Perhaps, therefore, individuals with reduced concentrations of serum thyrotropin, irrespective of raised free thyroid hormone concentrations, should be considered for treatment to restore normal thyroid function? *Johann Auer, Robert Berent, Thomas Weber, Bernd Eber Second Medical Department, Division of Cardiology and Intensive Care, General Hospital Wels, 4600 Wels, Austria (e-mail: [email protected]) 1 2
3
4
Cooper DS. Hyperthyroidism. Lancet 2003; 362: 459–68. Peters NS, Schilling RJ, Kanagaratnam P, Markides V. Atrial fibrillation: strategies to control, combat, and cure. Lancet 2002; 359: 593–603. Sawin CT, Geller A, Kaplan MM, Bacharach P, Wilson PW, Hershman JM. Low serum thyrotropin (thyroid-stimulating hormone) in older persons without hyperthyroidism. Arch Intern Med 1991; 151: 165–68. Auer J, Berent R, Weber T, Eber B.
1584
5
Epidemiology of atrial fibrillation. Lancet 2002; 360: 572. 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.
Sir—David Cooper1 refers to the flow chart on laboratory diagnosis of hyperthyroidism in his Seminar numerous times. In the chart, apart from thyroid stimulating hormone, radioiodine uptake has a central place in the diagnosis of hyperthyroidism, which is counterintuitive in view of Cooper’s statement that its measurement lacks both specificity and sensitivity. His choice to assess radioiodine uptake seems to be driven in part by the tendency in the USA to aim for treatment with radioactive iodine (131I) both for toxic multinodular goitre and for Graves’ disease, which are the most prevalent causes of hyperthyroidism. Elsewhere, although most patients with toxic multinodular goitre are offered the option of treatment with 131I, many patients with Graves’ disease are given a course of antithyroid drugs, such as thiamazole, carbimazole, and propylthiouracil, instead. I therefore propose use of a diagnostic work-up in which assessment of thyroid stimulating antibodies (or thyrotropin-receptor stimulating antibodies) is central, although I agree with Cooper that in many patients a diagnosis is apparent from the presence of eye symptoms. Such a work-up would have immediate clinical consequences (choice of antithyroid agents versus work-up with radioiodine uptake). A related point is the late occurrence of hypothyroidism after administration of 131I. Cooper states that permanent hypothyroidism arises in virtually all patients with Graves’ disease, although such a reaction is presumably related to the amount of radioactivity administered. Outside the USA, the prevalence of hypothyroidism varies from 30% to 70% 1–9 years after radioactive treatment.2–5 Since hypothyroidism arises less often after radioactive treatment in patients with toxic multinodular goitre than in those with Graves’ disease,4,5 the dose of 131I given should probably be lower for treatment of Graves’ disease than of toxic multinodular goitre. Timon W van Haeften Department of Internal Medicine, University Medical Center Utrecht, PO Box 85500, NL 3508 GA Utrecht, Netherlands (e-mail: [email protected]) 1
Cooper DS. Hyperthyroidism. Lancet 2003; 362: 459–68.
2
3
4
5
Bogazzi F, Bartalena L, Brogioni S, et al. Comparison of radioiodine with radioiodine plus lithium in the treatment of Graves’ hyperthyroidism. J Clin Endocrinol Metab 1999; 84: 499–503. Franklyn JA, Daykin J, Holder R, Sheppard MC. Radioiodine therapy compared in patients with toxic nodular or Graves’ hyperthyroidism. QJM 1995; 88: 175–80. Veneman TF, Weymer M, Tjabbes T, van Haeften TW. Relevance of cause of hyperthyroidism in determining its management. Neth J Med 1989; 35: 303–08. Leary AC, Grealy G, Higgins TM, et al. Long-term outcomes of treatment of hyperthyroidism in Ireland. Ir J Med Sci 1999; 168: 47–52.
Sir—In his Seminar,1 David Cooper discusses treatment options from a very American point of view. In his discussion of the different therapeutic approaches to hyperthyroidism, he mentions alternatives to the American preference for radioactive iodine without assessing the pros and cons of the various treatment options. That the decision about whether ablative therapy is the best option is often affected by availability of surgery or legal restrictions on the use of radioisotopes, could account for the preference for radioactive iodine for Graves’ disease in the USA compared with in several European countries. Cooper states that the worsening of pre-existent endocrine ophthalmopathy under therapy with radioactive iodine can be prevented by adjunctive treatment with prednisolone. There seems, therefore, no medical reason to favour surgery as ablative therapy. Remission rates after administration of antithyroid drugs as first-line treatments can reach 50%,2 so why are drugs not favoured as a primary option? Such treatment would offer patients the chance to regain a permanent euthyroid state without having to undergo an invasive procedure, or the chance of eventual hypothyroidism. In my opinion, ablative therapy should only be undertaken in cases of relapse. Furthermore, I do not believe that radioactive iodine should be used to treat toxic multinodular goitre, since it can hamper or prevent subsequent diagnosis of, and surgery for, thyroid cancer. Even in Graves’ disease, presence scintigraphically cold or nonfunctioning nodules would warrant further diagnostic procedures, since almost all thyroid carcinomas are scintigraphically cold. In the case of multinodular goitre, usually containing hot and cold nodules, cancer cannot be ruled out, since fine-needle aspiration of all nodules is not feasible. Although clinically apparent thyroid cancer is rare, subclinical cancers have been
THE LANCET • Vol 362 • November 8, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.