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Hashitoxicosis – Three Cases and a Review of the Literature

European Endocrinology, 2008; 4:70-72; DOI:

In young hyperthyroid patients, Graves’ disease is the most likely explanation for the patient’s symptoms; however, there are other reasons that have to be considered. A hyperthyroid metabolic state can also be caused by thyroid cell inflammation and destruction. As thyroid cells die, their stored supplies of thyroid hormone are released into the blood circulation. These bursts of thyroid hormones are responsible for the symptoms of hyperthyroidism. This ‘leakage’ phenomenon has nothing to do with the stimulation of the thyroidstimulating hormone (TSH)-receptor typical of Graves’ disease. It can occur in post-partum thyroiditis, ‘silent thyroiditis’, thyroiditis de Quervain and the initial ‘active’ state of Hashimoto’s thyroiditis.

Hashimoto’s thyroiditis is an autoimmune disease first described by Hakaru Hashimoto in 1912.1 Antibodies against thyroid peroxidase – antithyroid peroxidase antibody (anti-TPO) and/or antithyroglobulin (anti-Tg) – cause a gradual destruction of follicles in the thyroid gland. The diagnosis can be established by measuring these antibodies in the blood. However, a small percentage of patients may have none of these antibodies present. A percentage of the population may also have these antibodies without developing Hashimoto’s thyroiditis. Therefore, it is helpful to establish the diagnosis by the typical picture in ultrasonography. The histological picture of the thyroid gland is characterised by an invasion of the thyroid tissue by leukocytes, mainly T lymphocytes. It occurs far more often in women than in men (10–20:1), and is most prevalent between 45 and 65 years of age. The disease is believed to be the most common cause of primary hypothyroidism.

It should be pointed out that, especially in the US literature, the term ‘hashitoxicosis’ is sometimes used to describe an autoimmune thyroid disease overlap syndrome of Graves’ and Hashimoto’s disease.2 In this article the term is strictly limited to the ‘leakage’ symptoms of active Hashimoto’s disease.

Hashitoxicosis is most likely to present in the early stages of autoimmune hypothyroidism. We will describe three cases from our clinic.

In our first case, a 29-year-old male patient, the diagnosis of hyperthyroidism (in his and the following cases with elevated free triiodothyronine 3 [fT3], free thyroxine 4 [fT4] and suppressed TSH) was established in March 2008 due to tachycardia. From a retrospective viewpoint, prodromi such as tremors, petulance and restlessness had occurred two months earlier. The autoantibody profile was anti-Tg 116U/ml (<60), anti-TPO 69U/ml (<60) and TSH-receptordirected immunoassay kit test (TRAK)-negative. Thyroglobin was elevated at 106ng/ml (<1).

Thyrostatic therapy had been initiated immediately after the diagnosis of hyperthyroidism and before the autoantibodies were available. Euthyroidism was established after two weeks and the thionamides were withdrawn one week later. As expected, ultrasonography showed only minor hypoechoic areas with normal vascularisation in colour Doppler in relation to Hashimoto’s thyroiditis, as the disease was in its initial stage (see Figure 1). The typical signs of Graves’ disease – an enlarged hypoechoic thyroid gland with highly increased vascularisation – could be clearly ruled out. Thyroid hormone replacement therapy has been necessary since May 2008.
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