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CASE REPORT
EUTHYROID GRAVES’ OPHTHALMOPATHY PATIENTS REMAINING STABLE ON MORE THAN 20 MONTHS FOLLOW UP – A REPORT OF 9 PATIENTS.
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Anirban Mazumdar
Vivekananda Institute of Medical Sciences, Kolkata, India
Sudip Chatterjee
Vivekananda Institute of Medical Sciences, Kolkata, India
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 printed version |
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Editorial 2009
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The Authors have nothing to declare.
Correspondence to:
Dr. Sudip Chatterjee
Vivekananda Institute of Medical Sciences
Kolkata, India
Email: drsudip.chatterjee@gmail.com
ABSTRACT
Thyroid Associated Ophthalmopathy (TAO) is generally associated with altered thyroid function.
Patients who are euthyroid, generally become hyperthyroid within 6-12 months of diagnosis. We
report a group of patients who have remained euthyroid for more than 20 months following diagnosis
of TAO. The diagnosis of TAO was supported by the presence of TSH receptor antibody and graded
clinically by the ‘NO SPECS’ system of the American Thyroid Association. Free T3, Free T4 and TSH
were measured every 4 months using a chemiluminescence technique. Out of 78 patients with TAO,
six patients were euthyroid and were followed for more than 20 months and remained euthyroid.
Additionally, 3 patients seen earlier, all of whom had visual loss secondary to TAO, remained
euthyroid for more than 39 months. In the present study, a subset of patients were identified who did
not develop hyperthyroidism by 20 months. These patients are unlikely to be referred to an
endocrinologist, are at risk of visual loss and warrant further study.
INTRODUCTION
Thyroid-associated orbitopathy (TAO), is an organ-specific autoimmune process that is
strongly associated with dysthyroidism. In the medical literature, TAO was formally described by
Graves in 1835 and by von Basedow in 1840. Twenty percent of patients indicate that the ocular
morbidity of TAO is more troublesome than the thyroid problems. It may result in eyelid retraction,
proptosis, chemosis, periorbital edema, and altered ocular motility with significant functional, social,
and cosmetic consequences. Although most cases of TAO can be managed medically and without
visual loss, it may result in vision-threatening exposure keratopathy, troublesome diplopia, and
compressive optic neuropathy. TAO may precede, but more frequently coincide or follow the onset of
dysthyroidism (1).
Many patients with TAO are hyperthyroid, but the following also are associated with
TAO: Hashimoto thyroiditis, thyroid carcinoma, neck irradiation and hypothyroidism (2). In
patients who are hyperthyroid, the eye signs of TAO usually develop within 18 months of
dysthyroidism; very often, they develop concurrently (3). We describe here 9 cases of TAO,
who did not develop hyper-thyroidism on more than 20 months of follow up.
METHODS
Patients
The study was conducted at the Endocrine clinic of Ram Krishna Mission Seva Pratisthan
Hospital. All patients with TAO attending the clinic of between Jan 2006 to Dec 2007 were included
into the study if they satisfied the following criteria.
Inclusion criteria:
TAO with normal thyroid function for more than 18 months. All were TRAb positive except 3 patients
who were seen 4 to 6 years earlier, as the test was not available to us at that time. The patients were
diagnosed and TAO was graded following the “NO SPECS” classification (4) (see Table 1 and photos
in the appendix)
Exclusion criteria:
1. Thyroid associated orbitopathy with thyrotoxicosis
2. Anti-TSH receptor antibody negative
3. Development of hyperthyroidism within 18 months of TAO.
Photographs of patients have been included in an appendix at the end of the report with their written
consent. Patient No. 7 has died and consent was received from her son. This patient had ennucleation
of her right eye with fitment of prosthesis. Permission was given by Patient No. 8 to include
his MRI scan.
Methods
TSH receptor antibodies were measured by a competitive binding radioreceptor assay
manufactured by Immunotech, SA, Marseille, France. Free T3, Free T4 and TSH were measured by
sensitive chemiluminescence microplate assays (Monobind Inc, Lake Forest CA, USA). A thyroid
scan with 99m Technetium pertechnetate (99Tc scan) was performed on all patients. All patients also
had CT or MRI scans of their orbits
RESULTS
We reviewed all retrievable charts of patients seen at our institution for Graves’
ophthalmopathy between January 2006-December 2007. TAO was diagnosed by a combination of
clinical symptoms and signs and CT scans. CT scans of the orbits were performed on all patients,
primarily to exclude other pathology. All showed enlargement of the external ocular muscles in
varying degrees. The 99Tc scans were normal in all patients. Most patients with TAO had some form
of thyroid dysfunction (dysthyroid group), as evidenced by a history of abnormal thyroid function tests,
previous diagnosis of thyroid dysfunction by an outside physician, or current or past use of thyroid
medications. Nine patients (9/78 total patients; 11.5%) were found to be euthyroid for over a minimum
of 18-months of follow-up., based on consistently normal thyroid function tests, lack of hyperthyroid
clinical features, absence of medical or surgical treatment for thyroid dysfunction, and a negative
history of any thyroid associated abnormalities (see Table 1). These patients were seen every four
months in our clinic and their thyroid function tests were continuously monitored. Patients who subsequently developed thyroid dysfunction were excluded from our follow up. However, we cannot
exclude the possibility that some of these patients had an undetected, transient episode of
asymptomatic hyperthyroidism. In 3 patients (Pts no. 7,8,9), TRAbs could not be done as this test was
not available in our centre at that time.
DISCUSSION
The diagnosis of TAO was based on the presence of ophthalmopathy and confirmed in 6 out
of 9 cases by positive serum TSH receptor antibodies, both specific indicators of Graves' disease. In
one of the largest series reported in the literature (3), eye disease was associated with
hyperthyroidism in more than 90 % of patients with active Graves' ophthalmopathy. Another recent
review (5) reported that 10% of Graves’ ophthalmopathy patients are euthyroid, but made no comment as to the natural history of the euthyroid state. In the present series, ophtalmopathy and was not accompanied by thyroid hyperfunction (euthyroid Graves' disease) in 10% of the patients and
did not evolve toward thyroid dysfunction during a follow-up of >20 months in 9 patients.
TRAbs detected with the Dynotest TRAK human have the highest diagnostic power to
differentiate Graves disease from other thyrotoxic conditions and should be obtained for all patients
with non-typical Graves disease (6). However, euthyroid Graves' ophthalmopathy with negative
autoantibodies (including TRAb) has also been described (7,8). Graves' ophthalmopathy as a rule
develops at a time when thyroid autoimmunity also exists. Hyperthyroidism precedes the eye disease
or occurs simultaneously in most of the cases and in only minority of cases it develops after the eye
disease and usually within one year after the onset of eye disease (9).
In our study, 9 patients with euthyroid TAO were identified who did not develop thyrotoxicosis
when followed for more than 20 months. However at least one patient (no. 6) developed
hypothyroidism. In comparison to a series of patients with dysthyroid ophthalmopathy (10), most of
our patients were males (6 out of 9), they were younger (mean age±SD: 44.6±15.9 vs 56±13.5 years),
had less severe ophthalmopathy and a similar body mass index (mean BMI±SD: 26.5±2.1 vs 26±0.8).
CONCLUSION
A large body of evidence suggests that when TAO occurs in euthyroid Graves’ disease
patients, hyperthyroidism supervenes within 12 months of diagnosis. In the present study, a subset of
patients were identified who did not develop hyperthyroidism by more than 20 months. These patients
were referred fairly late to our clinic, after having ineffective treatment for glaucoma and various eye
problems. It is important to be aware of the connection of TAO to thyroid disease and early
endocrinology referral should be mandatory. |
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1. Burch HB, Wartofsky L. Graves’ ophthalmopathy: Current concepts regarding pathogenesis and management. Endocr Rev 14:747-793,1993.
2. Maciá-Bobes C, Ronzón-Fernández A. Dysthyroid ophthalmopathy associated with hypothyroidism. Arch Soc Esp Oftalmol. 82:765-768, 2007
3. Marcocci C, Bartalena L, Bogazzi F, Panicucci M, Pinchera A. Studies on the occurrence of ophthalmopathy in Graves' disease. Acta Endocrinol (Copenh). 120:473-478, 1989
4. Werner SC. Modification of the classification of the eye changes of Graves’ disease. Recommendations of the ad hoc committee of the American Thyroid Association. J Clin Endocrinol Metab 44 (1) 203-204, 1977.
5. Bartalena L, Tanda ML. Graves’ Ophthalmopathy. N Engl J Med. 360 994-1001, 2009
6. Wallaschofski H, Orda C, Georgi P, Miehle K, Paschke R. Distinction between autoimmune and non-autoimmune hyperthyroidism by determination of TSH-receptor antibodies in patients with the initial diagnosis of toxic multinodular goiter. Horm Metab Res. 33:504-507, 2001
7. Cakir M. Euthyroid Graves' ophthalmopathy with negative autoantibodies. J Natl Med Assoc. 97:1547-1549, 2005.
8. Paunkovic J, Paunkovic N. Does autoantibody-negative Graves' disease exist? A second evaluation of the clinical diagnosis. Horm Metab Res.38:53-56, 2006.
9. Wiersinga WM, Smit T, van der Gaag R, Koornneef L. Temporal relationship between onset of Graves' ophthalmopathy and onset of thyroidal Graves' disease. J Endocrinol Invest. 11:615-619, 1988
10. Kim JM, LaBree L, Levin L, Feldon SE. The relation of Graves' ophthalmopathy to circulating thyroid hormone status. Br J Ophthalmol.88:72-74, 2004.
APPENDIX: Photographs of the 9 patients and MRI scan of patient 8.
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Address:
Case Report
Euthyroid Graves’ Ophthalmopathy patients remaining stable on more than 20 months follow up – a report of 9 patients. |
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Title: Hot Thyroidology; Abbreviated key title: Hot Thyroidol.; Online ISSN: 2075-2202
Legal Note: © All rights reserved European Thyroid Association 2009
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