Severe headache as the initial manifestation of painless thyroiditis: a pediatric case report

Abstract

Painless thyroiditis is a potential cause of thyrotoxicosis, typically presenting with weakness, fatigue, irritability, palpitations, and tremors; however, headache is an uncommon manifestation. Herein, we report two pediatric cases of painless thyroiditis in which headache was the initial presenting symptom. Two 14-yr-old boys presented to our emergency department with chief complaints of severe migraine-like headaches. They did not exhibit typical symptoms of thyrotoxicosis. Head imaging findings revealed no abnormalities, and blood test results indicated elevated thyroid hormone and suppressed thyroid-stimulating hormone levels. Both patients were diagnosed with painless thyroiditis based on the absence of thyroid pain and increased blood flow on thyroid ultrasonography, and were monitored on an outpatient basis with only symptomatic treatment. One patient experienced palpitations and required treatment with propranolol. Within a few months, thyroid hormone levels normalized spontaneously in both patients, and their headaches improved accordingly. Although the mechanism by which thyroid hormones cause headaches remains unclear, these two cases suggest that thyrotoxicosis may be associated with headaches. Thus, it is important to measure thyroid hormone levels in patients with severe headaches without an obvious cause. Furthermore, early detection of thyrotoxicosis may be possible, leading to appropriate treatment, prediction of the future course of the patient’s headache, and relief of the patients’ and parents’ anxiety levels.

Highlights

● We report two cases of painless thyroiditis in which headache was the initial presenting symptom.

● Headache could be one of the symptoms of thyrotoxicosis.

● Measuring thyroid hormone levels in patients with unexplained severe headaches may aid in proper diagnosis.

Introduction

Classically, thyrotoxicosis includes all conditions involving excess thyroid hormones, whereas hyperthyroidism specifically refers to excess thyroid hormone levels from increased thyroid hormone synthesis. Thyrotoxicosis may result from follicular destruction due to thyroiditis or excessive exogenous thyroid hormone intake, and may encompass hyperthyroidism (1, 2). Although hyperthyroidism and thyrotoxicosis are used interchangeably sometimes (3), we have adhered to the classic definitions outlined above.

Painless thyroiditis is a condition in which the thyroid gland cells deteriorate for some reason, leading to the release of thyroid hormone into the bloodstream, resulting in transient thyrotoxicosis (1). It is termed “painless thyroiditis,” because of the absence of pain during cellular breakdown. Hypothyroidism may occur temporarily following a transient increase in thyroid hormone levels; however, thyroid function normalizes within a few months. Rarely, some patients develop permanent hypothyroidism (2, 3). Patients usually exhibit thyrotoxicosis with symptoms such as weakness, fatigue, irritability, palpitations, tachycardia, and tremor. Patients present with an acute onset of these symptoms that often pinpoint the most recent onset. These symptoms generally disappear within a few months along with thyroid hormone level normalization (2, 3).

In the International Classification of Headache Disorders, 3^rd edition (ICHD-3), hyperthyroidism is barely mentioned in the appendix as one of the many other metabolic and systemic diseases that can cause headache, although this has not been adequately validated in previous studies (4). Furthermore, no other form of thyrotoxicosis has been documented in the ICHD-3. While a few adult cases of thyrotoxicosis unrelated to hyperthyroidism have presented with headache as the primary complaint (5,6,7), to our knowledge, no such cases have been reported in children. In this report, we describe two pediatric cases in which severe headache prompted the diagnosis of painless thyroiditis, with symptoms resolving after normalization of thyroid hormone levels. Our experience may aid in the management of such pediatric headaches in the future.

Case Presentation

Case 1

A 14-yr-old boy presented to our hospital in an ambulance because of a severe headache during a meeting at school. The headache was described as a throbbing frontal pain, which relieved slightly in a dark room but aggravated with head movement. The pain was rated 10 on the Numerical Rating Scale (NRS), an 11-point pain scale ranging from 0 (no pain) to 10 (worst pain imaginable), with the patient visibly writhing with discomfort. Further, the pain was accompanied by blurred vision and multiple episodes of vomiting. He had not previously complained of headaches, and his medical history was unremarkable. The patient had no history of medication overuse or excessive iodine intake. His father had a history of migraines, and his mother had Hashimoto’s disease. His vital signs were generally within normal limits, with a heart rate of 97 beats/min; however, his blood pressure (128/67 mmHg) was slightly elevated. The patient did not experience weight loss, other symptoms of thyrotoxicosis, or thyroid gland tenderness. The neurological and head computed tomography findings were unremarkable. His blood test results showed no abnormalities in inflammatory markers and coagulation but revealed thyrotoxicosis: thyroid-stimulating hormone (TSH), <0.005 μIU/mL (reference range, 0.500–5.000 μIU/mL); free thyroxine (T4), 3.13 ng/dL (reference range, 0.90–1.70 ng/dL); and free triiodothyronine (T3), 10.74 pg/mL (reference range, 2.3–4.0 pg/mL) (Fig. 1). Tests for TSH receptor and thyroid peroxidase antibodies yielded negative results, and the thyroglobulin antibody level was slightly elevated (6.10 IU/mL [reference range, <4.11 IU/mL]). Thyroid ultrasonography revealed the gland at the upper limit of normal size, a hypovascular thyroid gland (Fig. 2A), and no increased blood flow in the superior thyroid artery. Thyroid scintigraphy indicated a decreased 3-h radioiodine uptake rate (2.2% [reference range, 5–15% (8)]) (Fig. 2B). Based on these findings, a diagnosis of painless thyroiditis was made. The patient was administered symptomatic treatment only for the headache. His blood pressure ranged from 100–120 mmHg systolic and 40–60 mmHg diastolic at outpatient visits and at home, with no history of chronic hypertension. One month after the initial headache episode, the patient returned to the emergency department (ED) with an incapacitating headache equivalent to 10 on the NRS. At the time, his blood pressure was high (131/74 mmHg), and other vital signs were normal. Thyroid hormone levels remained high (Fig. 1). In addition to the headache, palpitations were observed; thus, 20 mg of propranolol was initiated, which was continued until his thyroid hormone levels gradually normalized approximately 4 mo after his first visit. Seven months after his first visit, TSH suppression resolved. Overall, he developed a headache thrice before his thyroid hormone and TSH levels normalized. The third headache occurred after swimming but was not severe enough to require visiting the ED or other clinics; it was rated 4 on the NRS. However, it remains unclear whether the third occurrence of headache was similar to the previous two. After complete normalization of the TSH, free T4, and free T3 levels, the patient remained free of headaches throughout the subsequent 9 mo.

Fig. 1.

Clinical course of Case 1. The shadow indicates the normal range for the following thyroid parameters: TSH (0.500–5.000 µIU/mL), FT4 (0.90–1.70 ng/dL), FT3 (2.3–4.0 pg/mL), and TG (≤ 33.7 ng/mL). Pain intensity was assessed using the Numerical Rating Scale, an 11-point scale ranging from 0 (no pain) to 10 (worst pain imaginable). Thyroid function improved and reached the normal range approximately 7 mo after the first headache. The patient experienced three headache episodes, and after the thyrotoxicosis resolved, he no longer experienced headaches. Propranolol was administered for 3 mo. TSH, thyroid-stimulating hormone; FT4, free thyroxine; FT3, free triiodothyronine; TG, thyroglobulin; ED, emergency department.

Fig. 2.

Thyroid ultrasonography and thyroid scintigraphy findings of Cases 1. 2A: Thyroid ultrasonography of Case 1 shows a hypovascular thyroid gland. 2B: Thyroid scintigraphy of Case 1 reveals a decreased 3-h radioiodine uptake rate (2.2% [reference range, 5–15% (8)]).

Case 2

The second case involved a 14-yr-old boy with epilepsy, who regularly visited a nearby neurological hospital and received valproic acid and clobazam. He had no other medical history or medications and had never experienced headaches in the past. His mother had a history of cancer, and his father had a history of migraines. He visited our ED in an ambulance because of frontal pain and nausea during a class at school. His blood pressure (113/71 mmHg) was normal; however, his heart rate (113 beats/min) was slightly elevated. The patient remained conscious and was neurologically intact. Therefore, acetaminophen was prescribed, and he was discharged. The next day, because of a persistent headache, he visited his neurologist and underwent head computed tomography and blood tests. No abnormalities were detected in either examination. Thus, the patient was prescribed ibuprofen. A day later, his headache developed into intermittent pulsating occipital pain for a few tens of seconds, which did not improve even after the administration of acetaminophen or ibuprofen. The pain was considerably severe, and he flailed uncontrollably at home, resulting in damage to his surroundings. Therefore, the patient was transferred to our hospital via ambulance (Fig. 3). The headache recurred every few tens of minutes with mild nausea, but no visual field abnormalities. The headache improved when he sat down and lowered his head. His vital signs, including heart rate (90 beats/min), were normal except for the high blood pressure (130/58 mmHg). No abnormal neurological findings or symptoms, other than headaches, were observed. No weight loss was observed. We performed brain magnetic resonance imaging, which showed no abnormalities, including no vascular stenosis on magnetic resonance angiography and no blood flow changes on arterial spin labeling. Thus, we measured his thyroid hormone levels as part of his blood tests, as in Case 1, which revealed the presence of thyrotoxicosis: TSH, 0.061 μIU/mL; free T4, 3.74 ng/dL; and free T3, 16.74 pg/mL (Fig. 3). Tests for TSH receptor, thyroid peroxidase, and thyroglobulin antibodies yielded negative results. Thyroid ultrasonography revealed a normal thyroid size, reduced blood flow in the thyroid gland (Fig. 4), and no increase in blood flow in the superior thyroid artery. After a 3-wk outpatient follow-up, his headache completely resolved, and thyroid hormone levels normalized (Fig. 3). Thereafter, the patient had no episodes of headache, and during the subsequent 4 mo, his thyroid hormone levels remained normal. Based on this course, the patient was diagnosed with suspected painless thyroiditis.

Fig. 3.

Clinical course of Case 2. The shadow indicates the normal range for the following thyroid parameters: TSH (0.500–5.000 µIU/mL), FT4 (0.90–1.70 ng/dL), FT3 (2.3–4.0 pg/mL), and TG (≤ 33.7 ng/mL). On days when the headaches occurred but the attack frequency was unknown, bar graphs are shown in gray. His headaches, which occurred 18 times a day, completely disappeared within 2 wk. Thyroid function improved and reached the normal range approximately 3 wk after the first headache episode. TSH, thyroid-stimulating hormone; FT4, free thyroxine; FT3, free triiodothyronine; TG, thyroglobulin; ED, emergency department.

Fig. 4.

Thyroid ultrasonography findings of Cases 2. Thyroid ultrasonography of Case 2 reveals reduced blood flow in the thyroid gland.

Discussion

We encountered two pediatric cases of painless thyroiditis identified through acute severe headache. In both cases, headache frequency and severity improved with thyroid hormone normalization. These two cases suggest a possible association between thyrotoxicosis and headache, consistent with previous reports in adults (5,6,7, 9,10,11,12,13).

The prevalence of headache in children ranges from 37% to 51% (14, 15). Headache is one of the most common symptoms in the ED, and is sometimes difficult to diagnose or treat. Of non-traumatic headache occurrences in pediatric ED visits, secondary headaches account for 35.4–63.2% of cases (16). One report lists hyperthyroidism as a cause of acute recurrent secondary headache (17), although only 2% (markedly rare) of pediatric patients with hyperthyroidism present with headaches as the chief complaint (18). Therefore, headache is an under-recognized symptom of thyrotoxicosis (1,2,3). However, based on these two cases, thyrotoxicosis should be considered in the differential diagnosis of acute headache, and its potential association with headache warrants further discussion in the context of previous reports.

We have summarized 12 cases of thyrotoxicosis with headache as the chief complaint in Table 1 (5,6,7, 9,10,11,12,13). There was little commonality in the headache locations, and in many cases (75%), nausea and vomiting accompanied the headaches. In some patients, visual abnormalities also occurred, leading to the initial diagnosis of migraine. Additionally, painless thyroiditis and subacute thyroiditis tended to have shorter diagnostic periods (a few days vs. several months) and fewer accompanying symptoms than Graves’ disease (Table 1). Generally, in Graves’ disease, thyroid hormone levels increase gradually over weeks to months, whereas in painless thyroiditis, they rise rapidly within days to weeks because of thyroid tissue destruction (19). Consequently, thyroiditis symptoms develop and are diagnosed more rapidly than in Graves’ disease, typically within a few days to weeks (20). Moreover, as thyroiditis improves before the appearance of other symptoms, fewer accompanying symptoms are expected. Furthermore, we speculate that rapid exposure to high levels of thyroid hormone may contribute to headache onset. Therefore, it is important to carefully differentiate thyroiditis, especially in patients presenting with acute-onset headaches. In a previous study, all three cases of painless thyroiditis occurred in adolescent males. Generally, painless thyroiditis is more common in females than in males (female-to-male ratio: 1.5:1.0) (21). Epidemiological data on painless thyroiditis are limited (22), and it is unclear whether it is more common in teenage males. Further case studies are warranted to determine the correlation among severe headache, painless thyroiditis, and male sex. Accordingly, some cases may have been diagnosed as migraines and overlooked because painless thyroiditis presents with few accompanying symptoms and resolves spontaneously within a few months.

Table 1. Review of previous case reports on headaches associated with thyrotoxicosis.

The mechanism by which thyroid hormones cause headache remains unclear. Three possible mechanisms are proposed. First, thyroid hormones increase oxidative stress in the brain and upregulate cortical excitability by reducing the synthesis of γ-aminobutyric acid (23). Thyroid hormones also appear to alter the redox state of the mitochondrial respiratory chain, favoring the leakage of electrons from complexes I and III to form superoxides (23). Thyrotoxicosis has been associated with high levels of lipid peroxides and low levels of antioxidants in the rat brain and human plasma (23). Second, thyroid hormones may induce cerebral vasospasms and have been shown to increase the sensitivity of vessels that are resistant to the vasoconstrictive action of norepinephrine (24). Vasospasms associated with hyperthyroidism leading to cerebral infarction have been previously reported (24). Third, thyroid hormones inhibit the absorption of spinal fluid by arachnoid granules and increase intracranial pressure (7, 25). In some reports, thyrotoxicosis and idiopathic intracranial hypertension (IIH) were simultaneously observed (25,26,27). Moreover, studies have documented IIH and excessive thyroid hormone levels following levothyroxine treatment for hypothyroidism and total thyroidectomy (27, 28). Further studies are necessary to elucidate the exact mechanism by which thyroid hormones cause headache.

This report has a few limitations. First, the patient in Case 1 experienced markedly fewer headache episodes, whereas the patient in Case 2 had a limited observation period. Consequently, establishing a clear relationship between headache and thyrotoxicosis is difficult. Nonetheless, to date, no patient has presented to the ED or other clinics with headaches following the normalization of thyroid function. Further follow-up of these cases, along with additional case reports, is required to better understand this relationship. Second, the causes of the headaches were so diverse that they were difficult to distinguish. The headaches in Case 1 resembled migraines; thus, a migraine diagnosis may be considered depending on the patient’s future headache pattern. Conversely, the headaches in Case 2 were less likely to be migraines, as they developed while the patient was receiving valproic acid, a prophylactic drug for migraines. In addition, although hypertension in both cases was not considered severe enough to directly cause headaches, considering their age, the potential involvement of intracranial hypertension or cerebral blood flow changes cannot be excluded. It is unknown whether papilledema was present. In Case 2, the improvement in headache with changes in body position suggested the possibility of transient cerebral ischemia. Although MRI showed no abnormalities in Case 2, a single scan may have missed some findings, depending on the timing. More detailed blood pressure monitoring, ophthalmological examinations, and repeated MRI scans can provide additional useful information.

Conclusion

A recent review of pediatric headache in the ED highlighted that blood tests are rarely useful, as the most common causes of secondary headache are upper respiratory tract infections and sinusitis (16). Our two case reports highlight the importance of performing blood tests to exclude thyrotoxicosis in patients with severe headaches without an obvious cause. In particular, thyroid function should be assessed in cases of sudden-onset, first-time migraine-like headaches that are severe enough to impair daily life activities and lead to an ED visit. Early detection of thyrotoxicosis can facilitate appropriate management, help predict the clinical course of headache, and provide reassurance to both patients and their parents.

Conflict of interests

The authors declare no conflict of interest.