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CASE REPORT
REMISSION OF GRAVES’ DISEASE IN A FEMALE PATIENT WITH ISOLATED METHIMAZOLEDEPENDENT FEBRILE AGRANULOCYTOSIS.
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Vincenzo Bassi
U.O.C. di Medicina Generale, San Giovanni Bosco Hospital -ASLNa-1-, Naples, Italy
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Editorial 2008
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The Author declare no conflict of interest related to this work.
Correpondence to:
Vincenzo Bassi MD, PhD
U.O.C. di Medicina Generale
San Giovanni Bosco Hospital, ASLNa-1, Via F. M. Briganti 255, 80100
Naples, Italy
Phone: +390812545282
Fax: +390812545279
Email: dr_bassi@inwind.it
ABSTRACT
I report the case of a patient affected by Graves’ Disease and treated with an antithyroid drug such
as methimazole. During the drug treatment she presented a methimazole dependent
agranulocytosis and the drug was immediately withdrawn. Amazingly, thyroid hyperstimulation
vanished during withdrawal of anti-thyroid therapy and the patient underwent a remission. The role
that stress factors may exert on the autoimmune process directed against the thyroid gland is
discussed.
INTRODUCTION
Thyrotoxicosis is a common endocrine disorder. It affects mainly women and is approximately five
times more common in females than in males. Usually the patients are treated with antithiroid
drugs such as methimazole and carbimazole. A rare and potentially fatal complication of the
therapy is the agranulocytosis, ranging from 0.3% to 0.6%. The stress factors seem to be important
to trigger the onset of the disease. In literature no role is usually reported of the stress such as a possible cause of hyperthyroidism recovery. We describe an unusual remission of Graves’ Disease
following the onset of a febrile agranulocytosis induced by methimazole.
CASE REPORT
In March 2008 we observed a 52 years old female patient with tachycardia and fine tremor.
Elevated free triiodothyronine (FT3), free thyroxine (FT4) and TSH receptor antibodies (TRAbs)
with suppressed thyrotropin (TSH) were observed. Anti-thyroglobulin and anti-thyreoperoxidase
was slightly positive and no significant time dependent modifications were observed. Thyroid
scintigraphy showed a diffuse 131-I distribution with an increased uptake. No ophtalmopathy was
present. The thyroid ecography showed a slight increase of volume, a hypoechoic gland with an
increased vascularization at Doppler study. The patient started a methimazole (MMI) treatment
with 20 mg/die, after progressively reduced to 15 and 10 mg.
Suddenly, in June, after two months of MMI treatment, the patient showed sore throat and fever
(temperature, 39,5°C), the blood cell count indicated a marked reduction of white blood cells
(WBC) and neuthrophiles (N), compatible with the diagnosis of an isolated agranulocytosis. The
values of the other blood cells were normal. The MMI treatment was immediately withdrawn and
the patient admitted to hospital. No hepatic and kidney failure was observed. Anti-nuclear
antibodies were negative while anti-granulocyte antibodies was not evaluated. The fever and the
sore throat solved after three days of antibiotic and antimycotic treatment and a progressive
improvement of WBC and N was observed. No steroid treatment was started. After nine days the
antibiotic treatment was withdrawn and the patient was discharged. We tested every ten days the
FT3, FT4 and TSH in order to identify the hyperthyroidism relapse. Amazingly, the hormonal status
and the TRAbs levels showed a progressive normalization without MMI treatment (Table 1). The
patient did not attend the subsequent clinical controls (she lives in a rural area), but did not refer
manifestations indicative of hyperthyroidism relapse in the following 3 months. In consideration of
the impossibility to use antithyroid drugs, radiometabolic treatment was recommended in case of
possible future relapse of hyperthyroidism.
DISCUSSION
Many papers discuss the importance of the stress to induce the onset or the worsening of the GD
(1). On the contrary, in the case here reported, the stress dependent on a febrile agranulocytosis,
might represent an unusual cause of GD remission.
Self-limited transient forms of GD are described after delivery, surgery of Cushing’s disease, the
withdrawal of antithyroid drugs or such as the spontaneous transient Graves’ thyrotoxicosis (2). But
the clinical characteristics could not assign this patient to one of these categories. Indeed, the longlasting
duration of MMI withdrawal guaranteed that the resolution of the hyperthyroidism was not
dependent upon a drug effect. However, other factors, such as the TRAbs levels, the age and the
goiter size, indicated that our patient was more prone to undergo a remission of hyperthyroidism,
according to Vitti et al (3).
Table 1. Laboratory values detected at different times and laboratory normal ranges (n.r.). In bold
the values at the moment of the hospital admission and MMI suspension. Not done (n.d.)
Usually, an immunosuppressive mechanism of the antithyroid drugs has been hypothesized to
explain the remission in GD (4). Anyway, many evidences does not support this point of view,
evidencing that the remission (secondary to TRAbs normalization) in GD is independent of dose,
kind of antithyroid drug or surgical treatment (5). The restored euthyroidism, independently if
secondary to the drug or surgical treatment, seems to be the main factor inducing the remission of
GD, breaking the vicious circle existing between autoimmunity and hyperthyroidism (6).
It is well known that a significant stress, such as a sepsis, can induce a decrease in thyroid
hormone bioavailability (7) and a severe immunosuppression (8). Conceptually, the decreased
bioavailability, mainly, of FT3 and the immunosuppression are, theoretically, able to induce the
normalization of TRAbs with consequent remission of the autoimmune process and
hyperthyroidism in GD.
Moreover, in consideration that antithyroid drug-induced agranulocytosis and aplastic anemia are
dependent on autoantibodies directed, respectively, against granulocyte and bone marrow (4),
another possible hypothesis is that a similar autoimmune process could suppress the source of
TRAbs responsible of the hyperthyroidism.
CONCLUSIONS
On the basis of the reported findings, it is tempting to speculate that the stress of the febrile
agranulocytosis could have played an important role in disrupting the vicious circle between
hyperthyroidism and autoimmunity in this patient. Then, should we consider that stress factors may
potentially be able to induce opposite (negative or positive) effects on the autoimmune processes
affecting the thyroid gland?
REFERENCES
1) Fukao A, Takamatsu J, Murakami Y, Sakane S, Miyauchi A, Kuma K, Hayashi S, Hanafusa T. The
relationship of psychological factors to the prognosis of hyperthyroidism in antithyroid drug-treated patients
with Graves' disease. Clin Endocrinol (Oxf). 58:550-555, 2003
2) Hidaka Y., Tatsumi K. Spontaneous Transient Graves' Thyrotoxicosis. Thyroid. 18: 1133-1134, 2008
3) Vitti P, Rago T, Chiovato L, Pallini S, Santini F, Fiore E, Rocchi R, Martino E, Pinchera A. Clinical features of patients with Graves' disease undergoing remission after antithyroid drug treatment. Thyroid. 7:369-375, 1997
4) Cooper D.S. Antithyroid drugs. N Engl J Med. 352:905-917, 2005
5) Torring O., Tallstedt L.,Wallin G., Lundell G., Ljunggren J.G., Taube A,. Saaf M., Hamberger B. Graves’ hyperthyroidism: treatment with antithyroid drugs, surgery, or radio iodine – a prospective, randomized study. J Clin Endocrinol Metab. 81: 2986–2993, 1996
6) Laurberg P. Remission of Graves' disease during anti-thyroid drug therapy. Time to reconsider the
mechanism? Eur J Endocrinol. 155: 783-786, 2006
7) Rodriguez-Perez A., Palos-Paz F., Kaptein E., Visser T. J., Dominguez-Gerpe L., Alvarez-Escudero J.,
Lado-Abeal J. Identification of molecular mechanisms related to nonthyroidal illness syndrome in skeletal
muscle and adipose tissue from patients with septic shock. Clin Endocrinol (Oxf) 68: 821–827, 2008
8) Lyn-Kew K, Standiford TJ. Immunosuppression in sepsis. Curr Pharm Des.14:1870-1881, 2008. |
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Address:
CASE REPORT
Remission of Graves’ Disease in a female patient with isolated methimazoledependent febrile agranulocytosis. |
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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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