RAI and Thyroid Eye Disease: Some studies

In a very recent study (dated 1997) by Vitti et al., it is stated that patients with thyroids under 40 gm weight, with low TRAb levels, and age over 40, were most likely to enter remission with anti-thyroid drugs (in up to 80%).

However, in the United States, RAI (I-131, radioiodine) is the therapy of choice selected by members of the ATA (American Thyroid Association) for the management of uncomplicated Graves' disease in adult women. (Solomon et al. 1990).

 

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I-131 therapy causes an increase in titers of TSH-RAbs, and anti-TG or TPO antibodies, which reflects an activation of autoimmunity, probably due to release of thyroid antigens by cell damage, or destruction of T cells inside the thyroid.

Many endocrinologists believe that I-131 therapy can lead to worsening of infiltrative eye disease because of this immune response.

Many works have been published on this subject:

In 1979, Fenzi, DeGroot and others state: "In contrast to the experience with antithyroid drugs or surgery, antithyroid antibodies, including TSH-RSAb levels, increase after RAI".

In 1980 Teng and colleagues arrive at the same conclusion.

In 1989, Sridama and DeGroot in another study titled “Treatment of Graves' disease and the course of ophthalmopathy “ give a similar opinion and add that "Coincident with this condition, exophthalmos may be worsened" They continue, "Although we believe that this change is an immunologic reaction to discharged thyroid antigens, this is conjecture, and the relationship of radiation therapy and exacerbation of exophthalmos remains uncertain".

However, DeGroot concedes that "Recent data indicate that there is a significant correlation" alluding to Tallstedt et al. and Escobar et al., whose works were published in 1992 and 1993.

This work, dated 1992 by Tallstedt and associates, The Thyroid Study Group from Sweden, provides us with the results of a randomised control trial on the occurrence of TED after treatment, indicating that "131-I therapy may cause development or worsening of infiltrative eye disease in nearly 33% of patients, while surgery only does it in about 16% -half as many- and antithyroid drugs in 10%".

The 1993 study by Fernandez Sanchez and colleagues, concludes that "the ophthalmopathy of Graves' disease improves to a greater extent after subtotal thyroidectomy than after radioiodine therapy". It refers to different tests showing improvement in eye disease after surgery, compared to improvement after RAI which was only noted in the Feldon score. Take a look at it here.

Some years later, in 1996, Thyroid Swedish Group published a prospective randomised study which showed, "increased risk of ophthalmopathy in patients with high serum T3 levels, especially when treated with iodine", and also indicated a risk of relapse of 21%, while it was 3%-8% for surgery and 34%-42% for drugs.

In April 1997, again Tallstedt et al., published another paper regarding a prospective study they performed, in which patients were randomized to either antithyroid drugs, subtotal thyroidectomy, or 131I. They said:

"We found that 33% of the patients treated with I-131 deteriorated, compared with 10% and 16% of patients treated with antithyroid drugs and surgery, respectively (p = 0.02). The risk was greater when patients had very high pretreatment thyroid hormone levels".

 

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There are quite a number of papers on TED and Graves’ therapies. Very few of these don’t conclude that RAI is the causative factor for the development of eye disease or its worsening when already present.

The authors of one of the papers, even after admitting that RAI contributes to triggering eye disease, ended up saying "Nevertheless, we consider 'bad eyes' to be a relative contraindication to RAI".

Consequently, many doctors continued and continue to push patients towards RAI. In order to prevent the development or worsening of eye disease different measures were taken:

Administration of corticosteroids along with I-131 was suggested to be followed for one month and tapering over in three months in patients who had significative TED at the time of treatment. In the case of worsening of eye disease, doses of prednisone should be doubled and therapy lasting over several months.

Other physicians gave anti-thyroid drugs prior RAI in order to deplete the gland of stored hormone and to restore the FTI to normal before radioiodine therapy.

Antithyroid drugs have immunosuppressive effect. They inhibit thyroid peroxidase. Moreover, conversion of T4 to T3 in peripheral tissues is prevented by PTU.

Treatment with methimazole before and for three months after undertaking RAI, appears to prevent the RAI-induced rise in TSH-R antibodies.

It has also been noted that antithyroid drugs have the following beneficial effects:

--prompt reduction in circulating antibody titers
--prompt reduction in anti-receptor antibodies
--inhibit their synthesis
--prompt reduction in high levels of activated T-lymphocites
--prompt and transient elevation of activated T suppressor lymphocites
--the reduced number of T suppressor cells, return to normal while on antithyroid drugs.
--do not directly inhibit T cell function

To sum up: Antithyroid drugs have a powerful beneficial immuno-suppressive effect on Graves’ disease sufferers.

For patients with serious eye involvement, or high TRAb levels, antithyroid drugs followed by total thyroidectomy were prescribed. Using this protocol the University of Chicago Clinics report that euthyroid state has been achieved by surgery in 82%; 6% became hypothyroid, and the recurrence rate was 12%.

After surgery, TSAb tend to disappear from the blood in the following 3 to 12 months.

Recurrence rates are higher in patients with progressive eye disease or positive TRAb.

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 2009:  Graves’ Orbitopathy Activation after Radioactive Iodine Therapy with and without Steroid Prophylaxis

Conclusions: GO may occur after RAI in approximately 15% of patients also in the absence of signs of active GO. Prophylactic OGC did not prevent GO activation in a large proportion of patients, compared to IVGC.

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The AtomicWomen agree to disagree with one important researcher and notorious thyroid expert, Dr. DeGroot, who said:
"Nevertheless, we consider 'bad-eyes' to be a relative contraindication to RAI".

Some of us have developed "bad eyes" within a few months after RAI, undoubtedly as a consequence of having TED, where no eye signs were present. So we know from experience every kind of NOSPECS classification –blindness excepted… so far! We also know from experience what a decompression surgery is. That’s why we would never dare to consider all these sufferings "a relative contraindication to RAI".

We would like to say:

1) - We have no doubt that RAI is a trigger for orbitopathy. Therefore we can hardly believe that, despite the many studies pointing out to RAI, there is still so much reluctance to accept these facts. Very important prospective randomized studies, like Tallsted’s (1992) one, were discounted because "patients became hypothyroid and thyroxine therapy was slightly delayed”.

2) - Regarding prescription of glucocorticoids along with RAI therapy, we would like to point out two things:

-- Glucocorticoids are given to people that ALREADY show signs of eye disease. But, as stated above, some among us have developed eye disease right after having RAI, where NO PREVIOUS SIGNS were present. Of course, in these cases prednisone it is not given, neither is it advisable to give it.

-- Glucocorticoids are strong medicines with very serious side effects. Sometimes they help bad eyes, sometimes they don’t. But even when they help, isn’t it paradoxical to mix their potential benefits, plus their side effects, to the real damage that RAI will cause?. Why does this sound to us like kissing and punching at the same time?. What’s the REAL benefit?

3) - Prominent, knowlegeable thyroidologists, keep on on keeping on not agreeing (not exactly disagreeing…) with other peers' investigations, just for the sake of the present medical dogmas(?) on RAI.

4) - Patients’ symptoms and signs are systematically disregarded.  We all very well know the it’s all in your head medical principle, as well as messages like this --hormone readings are normal, maybe you’re sensitive in excess, or comments of this kind:
--you could get TED anyway. Really? Could we? What are the chances without RAI? And what are the chances WITH the help of RAI?
--maybe it’s the underlying disease
--"These differences could be due to genetic or environmental factors". But "A search for genetic markers specifically linked to susceptibility to Graves' opththalmopathy has so far been unsuccessful".

These last two sentences have been posed in an editorial by Dr Wiersinga, commenting Bartalena’s 1998 research, re. patients who developed TED after RAI when it was not previously present.

Dr Wiersinga is a famous and excellent endocrinologist, and the editorial is very interesting and worth a lengthy reading, in spite of two or three "tics" of this kind.

Some doctors may still rely on discussing theories. In the meantime, many among us can show them PROVEN FACTS!.

For how long will people have to go through what we have?

And, again, what is the point of RAI?