Hashitoxicosis, three cases and a review of the literature

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.

Hashitoxicosis – Three cases and a review of the literature
Igor A Harsch, Eckhart G Hahn, Deike Strobel

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

Hashimoto’s thyroiditis is an autoimmune disease first described by Hakaru Hashimoto in 1912. 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.


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. 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.

The first patient

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 116 U/ml (normal less than 60), anti-TPO 69 U/ml (normal less than 60) and TSH-receptordirected immunoassay kit test (TRAK)-negative. Thyroglobin was elevated at 106 ng/ml (normal less than 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. 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.

The second patient

The second patient was a 42-year-old female presenting with tachycardia and mood swings who was diagnosed with hyperthyroidism in February 2008. Thyrostatic therapy was initiated immediately after the diagnosis and before the autoantibodies were available. The autoantibody status was anti-Tg antibodies 47 U/ml (normal less than 60), anti-TPO 137 U/ml (normal less than 60) and TRAK 1.21 U/l (normal less than 1.5). Thyroglobulin was elevated at 42.9 ng/ml (normal less than 1).

Due to elevated liver enzymes, thyrostatic therapy was performed for only one month and therapy with beta-blockers was continued. A euthyroid metabolic status was observed in July 2008. At that time, ultrasound showed a normal-sized thyroid with multiple hypoechoic 3–15mm areas and slightly increased vascularisation.

The third patient

In October 2007, the third patient, a 41-year-old female, was diagnosed with hyperthyroidism after presenting with tachycardia, mood swings and fatigue. The autoantibody profile was anti-Tg less than 20 U/ml (normal less than 60), anti-TPO 518 U/ml (less than 60) and TRAK less than 1.0 U/l (normal less than 1.5). Thyroglobulin was elevated 89.3 ng/ml (normal less than 1).

After the onset of thyrostatic therapy, she became euthyroid after one month and did not develop hypothyroidism.

Interestingly, in this patient the diagnosis of hyperthyroidism was simultaneously accompanied by a diagnosis of Addison’s disease. The adrenocorticotropic hormone (ACTH) test showed cortisol basal 0.5 μg/dl 30 minutes after stimulation: 0.6 μg/dl (normal greater than 21μg/dl), ACTH 1,036 pg/ml (10–60) and dehydroepiandrosterone (DHEA) 55 ng/ml (400–2,170). The patient is under steady surveillance for early detection of other features of the autoimmune polyendocrine syndrome.


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