Presentation and Outcome of Severe Graves’ Disease

Introduction: Subjects with “severe” Graves’ disease (GD) are known to have adverse outcomes. They have multisystem involvement (orbitopathy, dermopathy), more severe clinical features, large goitres and a higher relapse rate. Also, their response to thionamides is slower. There is a developing consensus that early definitive treatment improves prognosis in them. Methods: We retrospectively analysed the electronic case records and biochemistry databases of all subjects seen in our University Health Board between January 2017 and October 2019 with GD. Severe GD was defined by (1) a thyrotropin receptor antibody (TRAb) value greater than 10U/l (normal range: less than 0.9), (2) with any one of the following - (a) free thyroxine (T4) above 50pmol/l (reference range 9-19.1), (b) a combination of T4 more than 40 pmol/l with triiodothyronine (T3) above the detection range of the assay (46.1 pmol/l), (c) the presence of a large goitre, (d) active Graves’ orbitopathy (GO) or (e) dermopathy. We compared subjects with severe GD to those who did not fulfil the above criteria i.e. non-severe GD. Results: 176 GD subjects were seen during this period - 52 (29.5%) with severe and 124 (70.5%) with non-severe GD. However, 19 severe and 26 non-severe GD subjects were on active thionamide treatment at the time of analysis, and complete details were unavailable in 41 subjects. There was a significant difference in the following features between the severe and non-severe GD groups respectively (1) their median age (39 vs.52 years), (2) median TRAb levels (25.5 vs.18.5 U/l) (3) higher prevalence of GO (38.5 vs.13.3%) and active GO (15.4 vs.0%), (4) the presence of moderate/large goitre (51.3 vs.3.3%), (5) higher number failing to normalize biochemically within the first 6 months after treatment initiation (53.9 vs.39%), (6) the presence of a family history, and (8) a higher number requiring definitive treatment within 12 months of starting treatment (9.6vs.0.81%)(p=0.001-0.026 for the above). There was no difference between the two groups in gender, treatment regime i.e. dose titration regime or block and replacement regime, number biochemically normalizing within 12 months, and those who had more than 18 months of treatment and their relapse rates (55 vs. 59.1%, p=0.84). Conclusions: We have shown that those with severe GD were younger, have higher TRAb concentrations with multisystem involvement, and delayed initial normalization of thyroid hormones. A greater number of them require definitive treatment within 12 months of treatment initiation. However, the majority in both groups normalize thyroid hormones within 12 months irrespective of the treatment regime used. Early definitive treatment is required in a significantly higher percentage of subjects with severe GD and needs to be considered in them.

Accuracy of Fine Needle Aspiration Cytology in Solitary or Dominant Nodular Goitre: A Single Centre Study

Background: Thyroid swelling or goitre is a common condition, either asymptomatic or symptomatic. The diagnosis is usually established by ultrasound or fine needle aspiration cytology (FNAC) as a gold standard. The sensitivity of the test is inversely related to increasing size of the nodule. The objective of this study is to evaluate the accuracy of FNAC especially in cases of large goitre. Material and methods: This is a retrospective study on patients who underwent thyroidectomy between January 2000 to December 2007 for solitary or dominant nodular goitre. The analysis was made only on those patients with complete data on FNAC and histology. Result: There were 235 patients, but only 161 patients were analysed after excluding the suspicious and inadequate sample. The patients’ mean age was 42.1 year old (21 to 60). The size of the thyroid nodule ranged from 2.1 to 5.0 cm (mean = 3.9 cm). The overall sensitivity was 67.4% and the overall accuracy was 86.3%. The accuracy of FNAC according to the sizes above and below the value were as follows; 2 cm (72.2% vs. 88.1%); 3 cm (88.0% vs. 87.4%) ; 4 cm (86.6% vs. 84.4%) ; 5 cm (87.3% vs. 78.8%). This was most obvious in the sensitivity of the FNA which also showed reducing trend as the nodules increased in size. Conclusion: FNAC is an essential diagnostic tool in the management of nodular goitre. Our study showed that the accuracy of FNAC decreased as the size of the nodule getting bigger. Cautious approach should be taken in the management of large goitre and decision should not be based only on the result of FNAC.

Factors influencing the outcome of thyrostatic drug therapy in Graves' disease

In patients with Graves' disease, thyrostatic drug treatment may induce definitive remission without the need of more aggressive measures such as surgery or radioiodine. Following drug therapy, however, relapses often occur. In the present study, a multivariate analysis of pretreatment variables was performed, in order to identify individuals running a high risk of an unfavourable outcome of thyrostatic drug therapy. We studied 109 consecutive patients with a mean age of 38 years, range 20–70, over a mean follow-up period of 5.3 years after cessation of therapy. The analysis showed that goitre size, age, thyroid hormone levels, HLA-DR 3 haplotype, and TSH receptor antibody levels were of prognostic significance, whereas HLA-B8 haplotype, a lymphocytic infiltrate at fine needle biopsy, thyroglobulin, and microsomal antibodies had no such value. In particular, patients characterized by young age, large goitre and high hormone values were found to be associated with an unfavourable course.

Goitre size and outcome of medical treatment of Graves' disease

One hundred and twenty-four patients with newly diagnosed hyperthyroidism received a combined thionamid-thyroxine medical therapy for approximately 2 years. According to the estimated goitre size before therapy and the type of goitre the patients were divided into 4 groups: Graves' disease no goitre (n = 19). Graves' disease small goitre (n = 57), Graves' disease medium or large goitre (n = 23), multinodular goitre (n = 25). The median follow-up period after cessation of medication was 64 (range 11–141) months. The remission rates in the different groups during follow-up were calculated using life table analysis. Graves' patients with no goitre or a small goitre had a significantly better outcome (remission % after 5 years 82.5 ± 15.4 (se) and 71.5 ± 7.8, respectively) than Graves' patients with a medium size or large goitre (remission % after 5 years 37.0 ± 11.1) (P <0.025). Most patients with multinodular goitre had a relapse within the first year after stop of medication (remission % after 5 years 15.5 ± 10.1). Hence patients with Graves' disease having a small thyroid gland should be treated medically while surgery or radioiodine may be a more reasonable choice in Graves' patients with medium size or large goitres. Medically treated patients with toxic multinodular goitres have a very small chance of prolonged remission if medication is stopped.