TSH‐receptor antibody measurement for differentiation of hyperthyroidism into Graves' disease and multinodular toxic goitre: a comparison of two competitive binding assays

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357

231

Introduction: Autoimmunity against the TSH receptor is a key pathogenic element in Graves' disease. The autoimmune aberration may be modified by therapy of the hyperthyroidism. Objective: To compare the effects of the common types of therapy for Graves' hyperthyroidism on TSHreceptor autoimmunity. Methods: Patients with newly diagnosed Graves' hyperthyroidism aged 20-55 years were randomized to medical therapy, thyroid surgery, or radioiodine therapy (radioiodine was only given to patients R35 years of age). L-thyroxine (L-T 4 ) was added to therapy as appropriate to keep patients euthyroid. Anti-thyroid drugs were withdrawn after 18 months of therapy. TSH-receptor antibodies (TRAb) in serum were measured before and for 5 years after the initiation of therapy. Results: Medical therapy (nZ48) and surgery (nZ47) were followed by a gradual decrease in TRAb in serum, with the disappearance of TRAb in 70-80% of the patients after 18 months. Radioiodine therapy (nZ36) led to a 1-year long worsening of autoimmunity against the TSH receptor, and the number of patients entering remission of TSH-receptor autoimmunity with the disappearance of TRAb from serum during the following years was considerably lower than with the other types of therapy. Conclusion: The majority of patients with Graves' disease gradually enter remission of TSH-receptor autoimmunity during medical or after surgical therapy, with no difference between the types of therapy. Remission of TSH-receptor autoimmunity after radioiodine therapy is less common.

Section: Discussionmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

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TSH-receptor autoimmunity in Graves' disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study

Laurberg

Wallin²,

Tallstedt³

et al. 2008

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357

231

“…This conservative handling of data did not alter any of our conclusions: we still found a statistically significant difference in incidence ratio between Aalborg and Copenhagen with regards to MNTG (P!0.001), 'mixed-type' (P!0.001), STA (PZ0.003), and no regional difference in occurrence of GD (PZ0.10). We previously reported that up to 15-20% of hyperthyroid patients with a multinodular scintigraphic pattern are TRAb positive (28). Even higher frequencies of TRAb positivity have been reported in clinic-based studies from Germany (51).…”

Section: Study Strengths and Limitationsmentioning

confidence: 93%

Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study

Carlé

Pedersen

Knudsen

et al. 2011

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176

125

Objective: Few population-based studies have described the epidemiology of subtypes of hyperthyroidism. Design: A prospective population-based study, monitoring two well-defined Danish cohorts in Aalborg with moderate iodine deficiency (nZ311 102) and Copenhagen with only mild iodine deficiency (nZ227 632). Methods: A laboratory monitoring system identified subjects with thyroid function tests suggesting overt hyperthyroidism (low s-TSH combined with high s-thyroxine or s-triiodothyronine). For all subjects, we collected information on medical history, thyroid scintigraphy and thyroid hormone receptor antibody (TRAb) measurement. Information was used to disprove or verify primary overt hyperthyroidism and to subclassify hyperthyroidism into nosological disorders. Results: From 1997 to 2000 (2 027 208 person-years of observation), we verified 1682 new cases of overt hyperthyroidism. The overall standardized incidence rate (SIR) per 100 000 person-years was 81.6, and was higher in Aalborg compared with Copenhagen (96.7 vs 60.0, P!0.001), giving an SIR ratio (SIRR (95% confidence interval (CI))) between moderate versus mild iodine-deficient areas of 1.6 (1.4-1.8). Nosological types of hyperthyroidism (percentage/SIRR (95% CI)): multinodular toxic goitre (MNTG) 44.1%/1.9 (1.6-2.2), Graves' disease (GD) 37.6%/1.2 (0.99-1.4), solitary toxic adenoma (STA) 5.7%/2.4 (1.3-3.5), 'mixed type' hyperthyroidism (TRAb-positive, scintigraphicly multinodular) 5.4%/6.0 (3.0-12), subacute thyroiditis 2.3%/0.9 (0.4-1.4), postpartum thyroid dysfunction 2.2%/1.6 (0.8-3.0), amiodarone-associated hyperthyroidism 0.8%/7.1 (1.1-65), hyperthyroidism after thyroid radiation 0.7%/12.3 (0.8-50), lithium-associated hyperthyroidism 0.7%/0.97 (0.4-4.8) and hyperthyroidism caused by various other factors 0.7%. Lifetime risk for overt hyperthyroidism was 10.5%/6.5%/2.4% (females/all/males). Conclusion: Hyperthyroidism was common in Denmark with MNTG and GD as dominating entities. The higher incidence of hyperthyroidism in the most iodine-deficient region was caused by higher frequency of MNTG, 'mixed-type', STA and amiodarone-associated hyperthyroidism.

“…GD, Graves' disease; ophthalmopathy (TAO; nZ10) was used as the base for the diagnosis of GD. We considered TRAb as positive above the lower cut-off of the TRAb assays (including borderline positive results), as it was considered so in clinical practice, and it has been shown that either cut-off is highly specific for GD (21). In routine health care, patients were instructed to leave blood samples for white blood cell counts during ATD treatment when they experienced signs of infection.…”

Section: Methodsmentioning

confidence: 99%

Long-term prognosis after medical treatment of Graves' disease in a northern Swedish population 2000–2010

Mohlin

Nyström

Eliasson

2014

Objective: To investigate the long-term prognosis of patients with Graves' disease (GD) after antithyroid drug (ATD) treatment and follow-up outside of highly specialised care. Design and methods: Medical records of all patients diagnosed with first-time GD in 2000-2010 with at least 6 months ATD treatment at a central hospital and follow-up in primary health care in the county of Norrbotten in northern Sweden were retrospectively reviewed. Patients were followed for relapse until 31st December 2012. We included 219 patients (mean age 46 years, 82.5% women) with follow-up of maximum 10 years and 829 observed patient years. Data were analysed using Kaplan-Meier estimates and log-rank test. Results: During the observation period, 43.5% of the patients had relapsed into active GD. The cumulative relapse rates were 22.6, 30.2, 36.9 and 41.5% after 6 months, 1, 3 and 5 years respectively. The presence of goitre (PZ0.014) predicted relapse. Previous smoking was protective against relapse (PZ0.003). The levels of free thyroxine or free tri-iodothyronine, age, gender, current smoking and ophthalmopathy did not predict relapse. Agranulocytosis was found in 1.7% (95% CI 0.7-4.0%). Conclusion: A long-term remission of 56.5%, in an iodine-sufficient area where ATD is offered to most patients in the real world of central and district hospitals, is higher than in most studies. Relapse was most common during the first year, and prognosis was excellent after 4 years without relapse. The protective effect of previous smoking merits further research.