Treatment of Goitre

S. J. Bonnema; L. Hegedüs

doi:10.1055/s-2005-836758

Der Nuklearmediziner, Table of Contents

Der Nuklearmediziner 2005; 28(2): 96-103
DOI: 10.1055/s-2005-836758

Schilddrüse - Update 2005

Treatment of Goitre

Therapie der StrumaS. J. Bonnema¹ , L. Hegedüs¹

¹Department of Endocrinology and Metabolism, Odense University Hospital, Denmark

Abstract

No consensus exists regarding the optimum treatment of benign non-toxic goitre. L-thyroxine suppressive therapy is widely used for treatment of goitre, but there is poor evidence of its efficacy, and the suppression of serum TSH may have serious adverse effects on health. Iodine supplementation is no better than L-thyroxine in comparative trials. Surgery is first choice in large goitres or if malignancy is suspected. Post-surgery, risk of goitre recurrence is inversely correlated with the extent of the operation. ¹³¹I therapy results in a one-year goitre reduction of around 50 % in multinodular and 70 % in diffuse goitres, usually with a high degree of patient satisfaction and improvement of the inspiratory capacity. The effect is attenuated with increasing goitre size. The risk of hypothyroidism is 22-58 % within 5-8 years. A sufficient thyroid ¹³¹I uptake is mandatory for ¹³¹I therapy to be feasible. Prestimulation with recombinant human TSH (rhTSH) may increase the thyroid ¹³¹I uptake considerably. This leads to an increased absorbed thyroid dose by approx. 75 %, mainly in those patients with the lowest thyroid ¹³¹I uptake. In addition, rhTSH results in a more homogeneous intrathyroidal isotope distribution. Recent studies with rhTSH stimulation before ¹³¹I therapy are encouraging. Pre-stimulation with even a small dose of rhTSH allows a reduction of the ¹³¹I activity while still achieving a mean goitre reduction of approximately 40 % within the first 12 months. A significantly lower extrathyroidal radiation is achieved by this approach. With an unchanged ¹³¹I activity, rhTSH pre-stimulation seems to improve the goitre reduction by up to 50 %. However, this is at the expense of a higher rate of hypothyroidism in addition to other side effects like cervical pain and transient thyrotoxicosis. Of particular concern is the observation made in healthy persons, that rhTSH results in a transient average thyroid volume increase of 35 %. A similar goitre swelling may cause problems in susceptible patients during rhTSH-augmented ¹³¹I therapy. Thus, this concept still needs a closer evaluation before routine use.

Key words

Euthyroid goitre - goitre therapy - levothyroxine therapy - radioiodine therapy - recombinant human TSH

Full Text

References

1 Hegedüs L. The thyroid nodule. N Engl J Med. 2004; 351 1764-1771
2 Brix T H, Kyvik K O, Hegedüs L. Major role of genes in the etiology of simple goiter in females: a population-based twin study. J Clin Endocrinol Metab. 1999; 84 3071-3075
3 Knudsen N, Bülow I, Jørgensen T, Laurberg P, Ovesen L, Perrild H. Goitre prevalence and thyroid abnormalities at ultrasonography: a comparative epidemiological study in two regions with slightly different iodine status. Clin Endocrinol (Oxf). 2000; 53 479-485
4 Bonnema S J, Nielsen V E, Hegedüs L. Long-term effects of radioiodine on thyroid function, size and patient satisfaction in non-toxic diffuse goitre. Eur J Endocrinol. 2004; 150 439-445
5 Hegedüs L, Bonnema S J, Bennedbæk F N. Management of simple nodular goiter: current status and future perspectives. Endocr Rev. 2003; 24 102-132
6 Gittoes N J, Miller M R, Daykin J, Sheppard M C, Franklyn J A. Upper airways obstruction in 153 consecutive patients presenting with thyroid enlargement. Br Med J. 1996; 312 484
7 Elte J W, Bussemaker J K, Haak A. The natural history of euthyroid multinodular goitre. Postgrad Med J. 1990; 66 186-190
8 Hamburger J I. Evolution of toxicity in solitary nontoxic autonomously functioning thyroid nodules. J Clin Endocrinol Metab. 1980; 50 1089-1093
9 Wiener J D, de Vries A A. On the natural history of Plummer's disease. Clin Nucl Med. 1979; 4 181-190
10 Bonnema S J, Bennedbæk F N, Wiersinga W M, Hegedüs L. Management of the nontoxic multinodular goitre: a European questionnaire study. Clin Endocrinol (Oxf). 2000; 53 5-12
11 Bonnema S J, Bennedbæk F N, Ladenson P W, Hegedüs L. Management of the nontoxic multinodular goiter: a North American survey. J Clin Endocrinol Metab. 2002; 87 112-117
12 Bhagat M C, Dhaliwal S S, Bonnema S J, Hegedüs L, Walsh J P. Differences between endocrine surgeons and endocrinologists in the management of non-toxic multinodular goitre. Br J Surg. 2003; 90 1103-1112
13 Soestbergen M J van, der Vijver J C van, Graafland A D. Recurrence of hyperthyroidism in multinodular goiter after long-term drug therapy: a comparison with Graves' disease. J Endocrinol Invest. 1992; 15 797-800
14 Vanderpump M P, Ahlquist J A, Franklyn J A, Clayton R N. 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. Br Med J. 1996; 313 539-544
15 Andrade V A, Gross J L, Maia A L. The effect of methimazole pretreatment on the efficacy of radioactive iodine therapy in Graves' hyperthyroidism: one-year follow-up of a prospective, randomized study. J Clin Endocrinol Metab. 2001; 86 3488-3493
16 Bonnema S J, Bennedbæk F N, Veje A, Marving J, Hegedüs L. Propylthiouracil before ¹³¹I therapy of hyperthyroid diseases: effect on cure rate evaluated by a randomized clinical trial. J Clin Endocrinol Metab. 2004; 89 4439-4444
17 Braga M, Walpert N, Burch H B, Solomon B L, Cooper D S. The effect of methimazole on cure rates after radioiodine treatment for Graves' hyperthyroidism: a randomized clinical trial. Thyroid. 2002; 12 135-139
18 Bonnema S J, Bennedbæk F N, Gram J, Veje A, Marving J, Hegedüs L. Resumption of methimazole after ¹³¹I therapy of hyperthyroid diseases: effect on thyroid function and volume evaluated by a randomized clinical trial. Eur J Endocrinol. 2003; 149 485-492
19 Kahaly G, Dienes H P, Beyer J, Hommel G. Randomized, double blind, placebo-controlled trial of low dose iodide in endemic goiter. J Clin Endocrinol Metab. 1997; 82 4049-4053
20 Hintze G, Kobberling J. Treatment of iodine deficiency goiter with iodine, levothyroxine or a combination of both. Thyroidology. 1992; 4 37-40
21 Roti E, Uberti E D. Iodine excess and hyperthyroidism. Thyroid. 2001; 11 493-500
22 Bongers H, Hotze L A, Schmitz R, Joseph K. LT4-monopreparation versus LT4-LT3-compound preparation in the treatment of diffuse endemic goitre. Acta Endocrinol (Copenh). 1986; 113 242-248
23 Gullu S, Gurses M A, Baskal N, Uysal A R, Kamel A N, Erdogan G. Suppressive therapy with levothyroxine for euthyroid diffuse and nodular goiter. Endocr J. 1999; 46 221-226
24 Kreissl M, Tiemann M, Hanscheid H, Rendl J, Reiners C. [Comparison of the effectiveness of two different dosages of levothyroxine-iodide combinations for the therapy of euthyroid diffuse goiter]. Dtsch Med Wochenschr. 2001; 126 227-231
25 Perrild H, Hansen J M, Hegedüs L. et al . Triiodothyronine and thyroxine treatment of diffuse non-toxic goitre evaluated by ultrasonic scanning. Acta Endocrinol (Copenh). 1982; 100 382-387
26 Peters H, Hackel D, Schleusener H. [Treatment of euthyroid struma. Comparable volume reduction with 400 micrograms iodine, 100 micrograms levothyroxine combined with 100 micrograms iodine or individually dosed levothyroxine]. Med Klin. 1997; 92 63-67
27 Wilders-Truschnig M M, Warnkross H, Leb G. et al . The effect of treatment with levothyroxine or iodine on thyroid size and thyroid growth stimulating immunoglobulins in endemic goitre patients. Clin Endocrinol (Oxf). 1993; 39 281-286
28 Hansen J M, Kampmann J, Madsen S N. et al . L-thyroxine treatment of diffuse non-toxic goitre evaluated by ultrasonic determination of thyroid volume. Clin Endocrinol (Oxf). 1979; 10 1-6
29 Berghout A, Wiersinga W M, Drexhage H A, Smits N J, Touber J L. Comparison of placebo with L-thyroxine alone or with carbimazole for treatment of sporadic non-toxic goitre. Lancet. 1990; 336 193-197
30 Wesche M F, Tiel-Van Buul M M, Lips P, Smits N J, Wiersinga W M. A randomized trial comparing levothyroxine with radioactive iodine in the treatment of sporadic nontoxic goiter. J Clin Endocrinol Metab. 2001; 86 998-1005
31 Uzzan B, Campos J, Cucherat M, Nony P, Boissel J P, Perret G Y. Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis. J Clin Endocrinol Metab. 1996; 81 4278-4289
32 Parle J V, Maisonneuve P, Sheppard M C, Boyle P, Franklyn J A. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet. 2001; 358 861-865
33 Ozbas S, Kocak S, Aydintug S, Cakmak A, Demirkiran M A, Wishart G C. Comparison of the complications of subtotal, near total and total thyroidectomy in the surgical management of multinodular goitre. Endocr J. 2005; 52 199-205
34 Thomusch O, Machens A, Sekulla C. et al . Multivariate analysis of risk factors for postoperative complications in benign goiter surgery: prospective multicenter study in Germany. World J Surg. 2000; 24 1335-1341
35 al Suliman N N, Ryttov N F, Qvist N, Blichert-Toft M, Graversen H P. Experience in a specialist thyroid surgery unit: a demographic study, surgical complications, and outcome. Eur J Surg. 1997; 163 13-20
36 Geelhoed G W. Tracheomalacia from compressing goiter: management after thyroidectomy. Surgery. 1988; 104 1100-1108
37 Abdel Rahim A A, Ahmed M E, Hassan M A. Respiratory complications after thyroidectomy and the need for tracheostomy in patients with a large goitre. Br J Surg. 1999; 86 88-90
38 Torre G, Borgonovo G, Amato A. et al . Surgical management of substernal goiter: analysis of 237 patients. Am Surg. 1995; 61 826-831
39 Netterville J L, Coleman S C, Smith J C, Smith M M, Day T A, Burkey B B. Management of substernal goiter. Laryngoscope. 1998; 108 1611-1617
40 Berghout A, Wiersinga W M, Drexhage H A. et al . The long-term outcome of thyroidectomy for sporadic non-toxic goitre. Clin Endocrinol (Oxf). 1989; 31 193-199
41 Röjdmark J, Järhult J. High long term recurrence rate after subtotal thyroidectomy for nodular goitre. Eur J Surg. 1995; 161 725-727
42 Hegedüs L, Nygaard B, Hansen J M. Is routine thyroxine treatment to hinder postoperative recurrence of nontoxic goiter justified?. J Clin Endocrinol Metab. 1999; 84 756-760
43 Miccoli P, Antonelli A, Iacconi P, Alberti B, Gambuzza C, Baschieri L. Prospective, randomized, double-blind study about effectiveness of levothyroxine suppressive therapy in prevention of recurrence after operation: result at the third year of follow-up. Surgery. 1993; 114 1097-1101
44 Feldkamp J, Seppel T, Becker A. et al . Iodide or L-thyroxine to prevent recurrent goiter in an iodine-deficient area: prospective sonographic study. World J Surg. 1997; 21 10-14
45 Pappalardo G, Guadalaxara A, Frattaroli F M, Illomei G, Falaschi P. Total compared with subtotal thyroidectomy in benign nodular disease: personal series and review of published reports. Eur J Surg. 1998; 164 501-506
46 Bennedbæk F N, Hegedüs L. Treatment of recurrent thyroid cysts with ethanol: a randomized double-blind controlled trial. Journal of Clinical Endocrinology and Metabolism. 2003; 88 5773-5777
47 Døssing H, Bennedbæk F N, Karstrup S, Hegedüs L. Benign solitary solid cold thyroid nodules: US-guided interstitial laser photocoagulation - initial experience. Radiology. 2002; 225 53-57
48 Le Moli R, Wesche M F, Tiel-Van Buul M M, Wiersinga W M. Determinants of longterm outcome of radioiodine therapy of sporadic non- toxic goitre. Clin Endocrinol (Oxf). 1999; 50 783-789
49 Nygaard B, Hegedüs L, Gervil M, Hjalgrim H, Søe-Jensen P, Hansen J M. Radioiodine treatment of multinodular non-toxic goitre. Br Med J. 1993; 307 828-832
50 Nygaard B, Hegedüs L, Ulriksen P, Nielsen K G, Hansen J M. Radioiodine therapy for multinodular toxic goiter. Arch Intern Med. 1999; 159 1364-1368
51 Huysmans D A, Hermus A R, Corstens F H, Barentsz J O, Kloppenborg P W. Large, compressive goiters treated with radioiodine. Ann Intern Med. 1994; 121 757-762
52 Bonnema S J, Bertelsen H, Mortensen J. et al . The feasibility of high dose iodine 131 treatment as an alternative to surgery in patients with a very large goiter: effect on thyroid function and size and pulmonary function. J Clin Endocrinol Metab. 1999; 84 3636-3641
53 Bonnema S J, Knudsen D U, Bertelsen H. et al . Does radioiodine therapy have an equal effect on substernal and cervical goiter volumes? Evaluation by magnetic resonance imaging. Thyroid. 2002; 12 313-317
54 Jarløv A E, Hegedüs L, Kristensen L Ø, Nygaard B, Hansen J M. Is calculation of the dose in radioiodine therapy of hyperthyroidism worth while?. Clin Endocrinol (Oxf). 1995; 43 325-329
55 Nygaard B, Knudsen J H, Hegedüs L, Veje A, Hansen J E. Thyrotropin receptor antibodies and Graves' disease, a side-effect of ¹³¹I treatment in patients with nontoxic goiter. J Clin Endocrinol Metab. 1997; 82 2926-2930
56 Nygaard B, Faber J, Veje A, Hegedüs L, Hansen J M. Transition of nodular toxic goiter to autoimmune hyperthyroidism triggered by ¹³¹I therapy. Thyroid. 1999; 9 477-481
57 Nygaard B, Metcalfe R A, Phipps J, Weetman A P, Hegedüs L. Graves' disease and thyroid associated ophthalmopathy triggered by ¹³¹I treatment of non-toxic goiter. J Endocrinol Invest. 1999; 22 481-485
58 Nygaard B, Faber J, Hegedüs L. Acute changes in thyroid volume and function following ¹³¹I therapy of multinodular goitre. Clin Endocrinol (Oxf). 1994; 41 715-718
59 Ron E, Doody M M, Becker D V. et al . Cancer mortality following treatment for adult hyperthyroidism. Cooperative Thyrotoxicosis Therapy Follow-up Study Group. JAMA. 1998; 280 347-355
60 Franklyn J A, Maisonneuve P, Sheppard M, Betteridge J, Boyle P. Cancer incidence and mortality after radioiodine treatment for hyperthyroidism: a population-based cohort study. Lancet. 1999; 353 2111-2115
61 Duick D S, Baskin H J. Utility of recombinant human thyrotropin for augmentation of radioiodine uptake and treatment of nontoxic and toxic multinodular goiters. Endocrine Practice. 2003; 9 204-209
62 Albino C C, Mesa C O, Olandoski M. et al . Recombinant human thyrotropin as adjuvant in the treatment of multinodular goiters with radioiodine. J Clin Endocrinol Metab. 2005; 90 2775-2780
63 Huysmans D A, Nieuwlaat W, Erdtsieck J. et al . Administration of a single low dose of recombinant human thyrotropin significantly enhances thyroid radioiodine uptake in nontoxic nodular goiter. J Clin Endocrinol Metab. 2000; 85 3592-3596
64 Nielsen V E, Bonnema S J, Boel-Jørgensen H, Veje A, Hegedüs L. Recombinant human thyrotropin markedly changes the ¹³¹I kinetics during ¹³¹I therapy of patients with nodular goiter: an evaluation by a randomized double-blinded trial. J Clin Endocrinol Metab. 2005; 90 79-83
65 Nieuwlaat W A, Hermus A R, Sivro-Prndelj F, Corstens F H, Huysmans D A. Pretreatment with recombinant human TSH changes the regional distribution of radioiodine on thyroid scintigrams of nodular goiters. J Clin Endocrinol Metab. 2001; 86 5330-5336
66 Silva M N, Rubio I G, Romao R. et al . Administration of a single dose of recombinant human thyrotrophin enhances the efficacy of radioiodine treatment of large compressive multinodular goitres. Clin Endocrinol (Oxf). 2004; 60 300-308
67 Nieuwlaat W A, Huysmans D A, Den Bosch H C Van. et al . Pretreatment with a single, low dose of recombinant human thyrotropin allows dose reduction of radioiodine therapy in patients with nodular goiter. J Clin Endocrinol Metab. 2003; 88 3121-3129
68 Nielsen V E, Bonnema S J, Hegedüs L. The effects of recombinant human thyrotropin, in normal subjects and patients with goitre. Clin Endocrinol (Oxf). 2004; 61 655-663
69 Nieuwlaat W A, Hermus A R, Ross H A. et al . Dosimetry of radioiodine therapy in patients with nodular goiter after pretreatment with a single, low dose of recombinant human thyroid-stimulating hormone. J Nucl Med. 2004; 45 626-633
70 Lawrence J E, Emerson C H, Sullaway S L, Braverman L E. The effect of recombinant human TSH on the thyroid ⁽¹²³⁾I uptake in iodide treated normal subjects. J Clin Endocrinol Metab. 2001; 86 437-440
71 Torres M S, Ramirez L, Simkin P H, Braverman L E, Emerson C H. Effect of various doses of recombinant human thyrotropin on the thyroid radioactive iodine uptake and serum levels of thyroid hormones and thyroglobulin in normal subjects. J Clin Endocrinol Metab. 2001; 86 1660-1664
72 Braga M, Ringel M D, Cooper D S. Sudden enlargement of local recurrent thyroid tumor after recombinant human TSH administration. J Clin Endocrinol Metab. 2001; 86 5148-5151
73 Giovanni V, Arianna L G, Antonio C. et al . The use of recombinant human TSH in the follow-up of differentiated thyroid cancer: experience from a large patient cohort in a single centre. Clin Endocrinol (Oxf). 2002; 56 247-252
74 Goffman T, Ioffe V, Tuttle M, Bowers J T, Mason M E. Near-lethal respiratory failure after recombinant human thyroid-stimulating hormone use in a patient with metastatic thyroid carcinoma. Thyroid. 2003; 13 827-830
75 Vargas G E, Uy H, Bazan C, Guise T A, Bruder J M. Hemiplegia after thyrotropin alfa in a hypothyroid patient with thyroid carcinoma metastatic to the brain. J Clin Endocrinol Metab. 1999; 84 3867-3871
76 Nielsen V E, Bonnema S J, Hegedüs L. Effects of 0.9 mg recombinant human thyrotropin on thyroid size and function in normal subjects: a randomized, double-blind, cross-over trial. J Clin Endocrinol Metab. 2004; 89 2242-2247
77 Hegedüs L, Hansen B M, Knudsen N, Hansen J M. Reduction of size of thyroid with radioactive iodine in multinodular non-toxic goitre. Br Med J. 1988; 297 661-662
78 Wesche M F, Buul M M, Smits N J, Wiersinga W M. Reduction in goiter size by ¹³¹I therapy in patients with non-toxic multinodular goiter. Eur J Endocrinol. 1995; 132 86-87
79 Verelst J, Bonnyns M, Glinoer D. Radioiodine therapy in voluminous multinodular non-toxic goitre. Acta Endocrinol (Copenh). 1990; 122 417-421
80 De Klerk J M, Isselt J W Van, Dijk A van. et al . Iodine-131 therapy in sporadic nontoxic goiter. J Nucl Med. 1997; 38 372-376

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