Audit of Long-Term Treatment Outcomes of Thyrotoxicosis in a Single-Centre Virtual Clinic

The Utility of Long-Term Antithyroid Drugs

Miles J. Levy; Narendra Reddy; David Price; Ragini Bhake; Emma Bremner; Mary Barrowcliffe; Veronica Kieffer; Carole Robinson; Francesco Zaccardi; Trevor A. Howlett

Disclosures

Clin Endocrinol. 2022;97(5):643-653. 

In This Article

Abstract and Introduction

Abstract

Objective: To investigate the long-term outcomes and prognosis of thyrotoxicosis in a large number of patients in a single UK county (Leicestershire).

Design: Retrospective cohort analysis of 56,741 thyroid function test (TFT) results, treatment modalities and outcomes in a well-established virtual thyrotoxicosis clinic database.

Patients: One thousand four hundred and eighty-nine patients were included with a median length of follow-up of 10.9 years. The aetiology of thyrotoxicosis was autoimmune (85.9%), nodular (9.1%) and mixed (5.0%). Treatment modalities included antithyroid drugs (ATDs), radioiodine (RAI; 555 MBq fixed dose) and thyroidectomy.

Methods: We analysed both individual TFTs and groups of sequential TFTs on or after the same thyroid treatment(s), which we describe as 'phase of thyroid care' (POTC). Patients studied entered the virtual clinic between 1 January 1995 and 1 January 2010; we exported data on every TFT sample up to April 2020.

Results: ATD had been used in 99.2% (median 2, maximum seven courses) with long-term ATD (>2 years) in 48%. RAI and thyroidectomy were used more commonly with nodular and mixed aetiology. Overall, T4 was more often controlled than thyroid-stimulating hormone (TSH), and at the latest follow-up, T4 was normal in >96%, TSH in >79% and both in >76% of different aetiologies. The mean percentage control of T4 was 85% and TSH 50%; in long-term ATD courses, this improved to 89% and 62%, respectively. In the latest POTC, control of T4 and TSH was best in cases off treatment (95%/87%) and on T4 without ablative therapy (94%/72%), but was broadly similar in patients on long-term ATD (90%/68%), after RAI (92%/60%) or after thyroidectomy (91%/58%). After the first course of ATD, remission or hypothyroidism was seen in 47.3% autoimmune, 20.9% nodular and 32.5% mixed, with 90% relapses seen within 4 years. Relapse was more common in patients with ophthalmopathy, but there was no difference between the sexes.

Conclusions: Thyrotoxicosis can be well controlled with minimal specialist clinic attendance using a software-supported virtual shared-care scheme. Long-term ATD appears to be a valid patient choice achieving TFT control comparable to that seen after RAI or surgery. In patients with autoimmune disease, relapse is more common in patients with ophthalmopathy, and hypothyroidism is common after RAI. In nodular disease, we found that spontaneous remission may occur.

Introduction

Despite the fact that thyrotoxicosis is one of the most common conditions treated in a secondary care endocrine clinic, there is a relative lack of long-term outcome studies in a large number of patients. UK NICE guidelines have given a comprehensive evidence-based approach to the diagnosis, management and follow-up of thyrotoxicosis[1] alongside the American Thyroid Association (ATA) Guidelines.[2] Such guidelines are largely based on the meta-analysis of existing data and consensus opinion, rather than on long-term observational cohort studies.

Endocrinologists have different ways of confirming the aetiology of thyrotoxicosis, as well as individual approaches to management, which have changed over time and therefore comparisons between different centres are difficult. A small single-centre prospective study showed a remission rate of 30% after 5 years follow-up, although this was seen only in 26 patients.[3] The ATA estimates the remission rate of thyrotoxicosis to be 20%–30% after 18 months of ATD treatment.[2] Relapse rates are thought to be higher in patients with significantly elevated fT4 and fT3 levels at presentation and in patients with strongly positive thyroid antibodies, large goitres, thyroid eye disease and persistently suppressed thyroid-stimulating hormone (TSH) levels.[4]

North America traditionally use early definitive treatment relative to their counterparts in Europe and Japan.[2,5] Definitive treatment for thyrotoxicosis has typically been considered preferable to long-term antithyroid treatment to prevent long-term complications of thyrotoxicosis.[1] Young women are advocated early definitive treatment to reduce the potential risk of congenital malformations in pregnant women on carbimazole (CBZ).[6] There is a relative lack of data regarding the safety of long-term ATD treatment.

The Endocrine Unit in Leicester (UK) has run a long-established virtual thyrotoxicosis clinic since 1995. We are in a relatively unique position to look at a single-centre outcome in a large number of patients over a long period of time. We were interested in attempting to answer some of the big questions regarding the long-term follow-up and prognosis of thyrotoxicosis. We have a unified approach in the management of thyrotoxicosis, making the comparison of the different groups more reliable than comparing different centres. Nevertheless, this is a real-life retrospective observational study, and the methods of diagnosis and treatment of thyrotoxicosis have evolved over time as new investigation modalities have become available.

Since 1988, we have prospectively recorded diagnosis, treatment and major outcomes on all cases of thyrotoxicosis in our department in a comprehensive clinical information system, and since 1995 we have managed a majority of patients with thyrotoxicosis via a shared-care scheme administered using the same software, with storage of the results of all thyroid function tests (TFTs) obtained during monitoring. We, therefore, reviewed these data to obtain insights on treatment choice, treatment outcomes and degree of control of TFTs on treatment and during long-term follow-up in routine clinical practice, comparing various treatment modalities and strategies and seeking markers that might predict outcomes for future patients. We were particularly interested to look at the remission rates and prognosis of patients with hyperthyroidism depending on the likely aetiology.

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