Hashitoxicosis is an initial, transient, hyperthyroid phase that rarely affects patients with Hashimoto thyroiditis. We present here an unusual case of a child with Hashimoto thyroiditis and recurrent hyperthyroidism. A 4 yr 6/12 old male was diagnosed by us with autoimmune subclinical hypothyroidism (normal free T4, slightly elevated TSH, and elevated TG antibody titer). Two years and 6/12 later he experienced increased appetite and poor weight gain; a laboratory evaluation revealed suppressed TSH, elevated free T4, and normal TSI titer. In addition, an I123 thyroid uptake was borderline-low. A month later, the free T4 had normalized. After remaining asymptomatic for 3 years, the patient presented again with increased appetite, and he was found with low TSH and high free T4. Within the following 3 months, his free T4 and TSH normalized. At his most recent evaluation, his TSH was normal and the free T4 was borderline-high; the TG antibody titer was still elevated and the TSI titer was negative. To our knowledge, this is the first patient reported with Hashimoto thyroiditis and recurrent hyperthyroidism. This case exemplifies the variability of the manifestations and natural history of Hashimoto thyroiditis and supports the need for a long-term evaluation of patients with autoimmune thyroid disease.
Hashitoxicosis is considered to be an initial hyperthyroid phase of Hashimoto thyroiditis, caused by the release of preformed thyroid hormones from the thyroid follicles. It is biochemically characterized by elevated titer(s) of anti-thyroglobulin (anti-TG) and/or anti-thyroid peroxidase (anti-TPO) antibodies, suppressed TSH, and elevated T4 and T3. Hashitoxicosis is distinguished from Graves disease by the absence of thyroid stimulating immunoglobulins (TSI) and by a diminished radioiodine uptake. We present an unusual case of recurrent hyperthyroidism in a child with positive anti-thyroglobulin antibodies and negative TSI. This case illustrates the need for continued follow-up of patients with autoimmune thyroid disease and supports the evidence of a very wide spectrum of clinical and biochemical features in children with autoimmune thyroid disease.
A 4 yr 6/12 old male was first seen at our clinic in 2006, after his primary physician found him with a slightly elevated TSH (Table
Initial and follow-up laboratory studies.
Date | Age |
Free T4 |
TSH |
T3 |
TPO |
TG Ab |
TSI |
---|---|---|---|---|---|---|---|
07/17/2006 | 4 |
1.1 | 7.94 | 140 | |||
08/24/2006 | 4 |
1.1 | 9.26 | <10 | 85 | ||
08/29/2007 | 5 |
1.05 | 4.49 | ||||
10/23/2008 | 6 |
1.39 | 3.21 | ||||
03/6/2009 | 7 |
2.8 | <0.01 | <10 | 312 | 90 | |
04/30/2009 | 7 |
1.2 | 128 | <10 | 279 | 107 | |
12/2/2009 | 7 |
1.0 | 3.34 | 112 | <10 | 96 | |
06/16/2010 | 8 |
1.3 | 2.23 | 110 | <10 | 61 | 100 |
12/28/2011 | 9 |
2.1 | 0.02 | 39 | |||
03/9/2012 | 10 |
1.0 | 0.24 | 77 | 12 | 399 | |
07/5/2012 | 10 |
1.1 | 6.32 | ||||
02/6/2014 | 11 |
1.5 | 1.77 | 102 | <10 | 59 | 43 |
Normal ranges in parentheses.
In the following year, the patient was maintained on the same dose of L-thyroxine, but he continued to experience hyperactivity, poor appetite, and speech delay. In addition to L-thyroxine, the patient was placed on Atomoxetine (40 mg QD) for ADHD. At age 5 yrs 7/12 (13 months after the initial visit), the patient and his mother returned to our clinic for follow-up with complaints of insomnia, aggressiveness, heat intolerance, and persistent constipation. His mother admitted being nonadherent to the recommended treatment, giving her son L-thyroxine only 3-4 times a week. Height and weight had remained within normal limits, and his thyroid size was normal. A month prior to the follow-up visit, the TSH was 4.49 mIU/dL (normal range, 0.5–4.3) and the free T4 1.05 ng/dL (normal range, 0.9–1.4). At the end of the follow-up visit, we advised his mother to discontinue the L-thyroxine treatment and repeat the thyroid hormone measurements 6 weeks later; however, this laboratory evaluation was never obtained.
About a year after the follow-up visit, the patient, now 6 yr 8/12 old, was brought again to our clinic. Meanwhile, he had been placed in special education due to his developmental delay and behavioral difficulties; Risperidone was added to his treatment regimen (still taking Atomoxetine). The child complained of occasional headaches but was otherwise asymptomatic. His weight and height remained at the 50th percentile, and he was found to be clinically and biochemically euthyroid (Table
Approximately four months later, he was referred back to us by his primary physician. Due to worsening hyperactivity, increased appetite, and poor weight gain (1 kg in 4 months), he requested thyroid function tests. The child’s TSH was suppressed (<0.01 mIU/L) and the free T4 elevated (2.8 ng/dL), with a normal TSI of 90% (normal, <140%). Anti-TPO antibodies remained undetectable, while the anti-TG antibodies were elevated (Table
At the age of 7 yr 10/12 (3 yrs 4/12 after the initial diagnosis of autoimmune thyroid disease and 11/12 after his short-lived hyperthyroidism), he presented to our clinic with complaints of constipation and occasional headaches. Upon examination in our clinic, his thyroid was not palpable and his thyroid hormone levels were normal (Table
At 9 yr 10/12 he was again noted by his mother to be more hyperactive, with increased appetite and thirst. When evaluated by us, he was found with a normal thyroid size, shape, and contour. An ultrasound revealed heterogeneous appearance of the thyroid and confirmed its normal size; no discrete nodules were identified. The TSH was low and the free T4 was high (Table
At his most recent visit at our center (11 yr 11/12 of age; 6 yrs 5/12 after his initial presentation), his TSH and total T3 were normal, while the free T4 was borderline-high (Table
Chronic autoimmune thyroiditis is the most common thyroid disorder in children. Also known as Hashimoto thyroiditis, it is typically characterized by elevated titers of thyroid autoantibodies. Thyroid peroxidase (TPO) antibodies are detectable in ~95% of patients with Hashimoto’s thyroiditis, and thyroglobulin TG antibodies are positive in approximately 60% of adult patients with chronic thyroiditis (less often in children with thyroid autoimmune disease). Clinically and biochemically, chronic thyroiditis is characterized by a variable presentation in childhood: children of younger age are most often symptomatic [
The clinical history and laboratory findings of our patient are surely atypical for a child with thyroid disease. First, unlike most children with chronic thyroiditis, the only thyroid autoantibodies that have been persistently positive are the anti-thyroglobulin antibodies. Furthermore, the patient has experienced recurrent hyperthyroidism, preceded and followed by years of normal thyroid function. Although some psychotropic medications (like lithium) are sometimes associated with impaired thyroid function, Risperidone and Atomoxetine are not typically implicated in drug-related thyroid dysfunction. Lastly, some of the symptoms experienced by this patient, such as his behavioural difficulties, are often associated with a hyperthyroid state; however, in this case they also occurred when the patient was biochemically euthyroid.
There is now genetic [
It has also been reported that Graves disease is sometimes associated with negative TSI [
Our patient’s persistently negative TSI titer was associated with borderline-low radioiodine thyroid uptake, which argues against the diagnosis of Graves disease. Low thyroid autoantibody titers and hyperthyroidism may also occur in patients with subacute or viral thyroiditis; yet, in this thyroid disorder, markers of autoimmunity are usually transiently elevated, and signs and symptoms of hyperthyroidism present at diagnosis and do not recur years later. The short-lived occurrence of hyperthyroidism and reduced iodine uptake in our patient most resemble the typical presentation of Hashitoxicosis; on the other hand, we are not aware of any previous report of Hashitoxicosis in children that occurred long after the diagnosis of autoimmune thyroid disease and then recurred years later. Indeed, Wasniewska et al. [
In conclusion, our patient represents a further example of the variability of the clinical and biochemical manifestations of autoimmune thyroid disease in children. In addition, it confirms how little we know about the natural history and the outcome of children with chronic thyroiditis. As a result, we believe that a long-term, periodical evaluation of patients with autoimmune thyroid disease (despite the lack of clinical and biochemical manifestations of an overt thyroid dysfunction for many years) is always warranted.
Thyroid peroxidase
Thyroglobulin
Thyroid stimulating immunoglobulins.
Written informed consent was obtained from the patient’s parents for publication of this case report.
The authors declare that there is no conflict of interests regarding the publication of this paper.