Ziekte van Graves. Kan het worden genezen?

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Ziekte van Graves. Kan het worden genezen?

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Received Feb 19, 2019; Revised Feb 28, 2019; Accepted Mar 05, 2019

Endocrinol Metab. 2019 Mar;34(1):29-38. English.
Published online Mar 21, 2019.

Graves' Disease: Can It Be Cured?

Wilmar M. Wiersinga
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Corresponding author: Wilmar M. Wiersinga. Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Room F5-169, Meibergdreef 9, Amsterdam 1105AZ, The Netherlands. Tel: +31-20-5666071, Fax: +31-20-6183468, Email: w.m.wiersinga@amc.uva.nl

Whether or not Graves' hyperthyroidism can be really cured, depends on the definition of “cure.”
If eradication of thyroid hormone excess suffices for the label “cure,” then all patients can be cured because total thyroidectomy or high doses of 131I will abolish hyperthyroidism albeit at the expense of creating another disease (hypothyroidism) requiring lifelong medication with levothyroxine. I would not call this a “cure,” which I would like to define as a state with stable thyroid stimulating hormone (TSH), free thyroxine, and triiodothyronine serum concentrations in the normal range in the absence of any thyroid medication. Surgery and radioiodine are unlikely to result in so-defined cures, as their preferable aim as stated in guidelines is to cause permanent hypothyroidism. Discontinuation of antithyroid drugs is followed by 50% recurrences within 4 years; before starting therapy the risk of recurrences can be estimated with the Graves' Recurrent Events After Therapy (GREAT) score. At 20-year follow-up about 62% had developed recurrent hyperthyroidism, 8% had subclinical hypothyroidism, and 3% overt hypothyroidism related to TSH receptor blocking antibodies and thyroid peroxidase antibodies. Only 27% was in remission, and might be considered cured. If the definition of “cure” would also include the disappearance of thyroid antibodies in serum, the proportion of cured patients would become even lower.

Keywords: Graves hyperthyroidism; Cure; Thyroidectomy; Radioactive iodine; Antithyroid agents; Remission; Long term outcome

Fig. 1
Hypothetical curves reflecting the natural history of Graves' hyperthyroidism. A minority of patients (green line) have a single episode of hyperthyroidism. The majority (blue line) has a prolonged course following a relapsing and remitting course over many years. In some patients (red line) the disease never remits but continues to express herself clinically. In the long-term the natural course along the green and blue curves could evolve towards spontaneous development of hypothyroidism.



Table 1
A Predictive Score (Called the GREAT Score) for the Outcome of Therapy with Antithyroid Drugs in Graves' Hyperthyroidism Based on Four Baseline Characteristics [23]

Table 2
Long-Term Follow-up Studies in Patients with Graves' Hyperthyroidism Who Were in Stable Remission after a Course of Antithyroid Drugs


Whether or not Graves' hyperthyroidism can be cured, depends on the definition of ‘cure.’
If cure is defined as just disappearance of thyroid hormone excess, then cure is possible in almost all cases by either Tx, RAI, or ATD. Cure defined as ‘restitutio ad integrum’ implies maintenance of the euthyroid state like it was before the illness, that is without any medication and without thyroid antibodies in the circulation. Guidelines state the aim of Tx or RAI in Graves' hyperthyroidism should be permanent hypothyroidism, which requires lifelong levothyroxine medication for maintaining euthyroidism. Creating another disease in order to treat the original disease, is no cure. ATDs leave open the possibility of cure, defined as maintenance of the euthyroid state (normal TSH, FT4, and T3) without the use of any medication.

The average remission rate after a course of ATD is about 50% [21]. Most recurrences occur within 4 years after discontinuation of ATD [3]. Although prognosis is excellent after 4 years without relapse [30], late recurrences do occur and only one in three patients experiences permanent remission [21]. Remission rate after 10 years is in the order of 30% to 40%, and hypothyroidism has developed in 10% to 15% 15 years after ATD [59]. Taken into account the above reviewed literature, permanent cure of Graves' hyperthyroidism is possible albeit at a low rate of about 27% (Fig. 2). The cure rate would be even lower if cure also supposes the absence of TSH receptor antibodies.

Fig. 2
Chance of remission of Graves' hyperthyroidism after a course of antithyroid drugs. ATD, antithyroid drug.

CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.

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