Encephalopathy associated with autoimmune thyroid disease: A grave situation

Charul R Mehta; Aashna Verma; Shashank Bansal

doi:10.4103/ipcares.ipcares_153_22

CASE REPORT

Year : 2023 | Volume : 3 | Issue : 1 | Page : 35-38

Encephalopathy associated with autoimmune thyroid disease: A grave situation

Charul R Mehta, Aashna Verma, Shashank Bansal
Department of Paediatrics, B. J. Medical College, Civil Hospital Campus, Ahmedabad, Gujarat, India

Date of Submission	30-Jun-2022
Date of Decision	11-Jan-2023
Date of Acceptance	23-Jan-2023
Date of Web Publication	27-Feb-2023

Correspondence Address:
Dr. Aashna Verma
Room No. A203, Phase 2, PG Hostel, Civil Hospital, Ahmedabad, Gujarat
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipcares.ipcares_153_22

Abstract

Background: Encephalopathy associated with autoimmune thyroid disease (EAATD) is an uncommon disorder affecting the central nervous system and associated with autoimmune thyroid disorders. It has myriad manifestations. Although most commonly seen with Hashimoto's thyroiditis, it has also been reported with Graves' disease. As it has no pathognomonic features (apart from response to steroids), it is a diagnosis of exclusion, and can be very challenging for the clinician. Clinical Description: An 11-year-old girl presented with a fever and altered sensorium for a few hours. In-depth history was unable to identify any significant history apart from recent weight loss. Salient examination findings were severe thinness, tachycardia, an enlarged thyroid gland, and altered sensorium, but the absence of neurological deficit, meningeal involvement, and increased intracranial tension. The clinical phenotype was acute encephalitis syndrome. Investigations ruled out biomarkers of infection, metabolic acidosis, hypoglycemia, dyselectrolytemia, uremia, hepatic dysfunction, and diabetic ketoacidosis. Neuroimaging was normal. Cerebrospinal fluid abnormalities were lymphocytosis, high protein, and normal glucose. A thyroid function test identified hyperthyroidism. Doppler ultrasonography revealed a diffusely enlarged and hypervascular thyroid gland. Thyrotropin-receptor antibodies were elevated (>10 IU/L). The final diagnosis was EAATD secondary to Graves' disease. Management and Outcome: Intravenous methylprednisolone (30 mg/kg/day), antithyroid drugs, and beta-blockers were started, on which she showed rapid and marked improvement. Conclusions: A detailed history, diligent clinical examination, and rational systemic approach needs to be undertaken to establish a diagnosis of EAATD.

Keywords: Autoimmune, encephalopathy, Graves' disease, Hashimoto's encephalopathy

How to cite this article:
Mehta CR, Verma A, Bansal S. Encephalopathy associated with autoimmune thyroid disease: A grave situation. Indian Pediatr Case Rep 2023;3:35-8

How to cite this URL:
Mehta CR, Verma A, Bansal S. Encephalopathy associated with autoimmune thyroid disease: A grave situation. Indian Pediatr Case Rep [serial online] 2023 [cited 2023 Mar 22];3:35-8. Available from: http://www.ipcares.org/text.asp?2023/3/1/35/370522

Encephalopathy associated with autoimmune thyroid disease (EAATD) is an uncommon manifestation associated with autoimmune thyroid disorders that affects the central nervous system (CNS). The estimated prevalence is 2.1/1 lakh population.^[1] Clinical features include altered sensorium (inflammatory signs of encephalitis and/or meningitis); seizures; stroke-like presentation; cognitive and language impairment; neuropsychiatric manifestations like behavioral changes and hallucinations; abnormal movements such as myoclonus, tremors, and ataxia; sensory deficits; and headache. EAATD may have an acute or subacute presentation and may affect patients with clinical or subclinical autoimmune thyroid disease.^[2],[3] Most patients with EAATD are with Hashimoto's thyroiditis and hypothyroidism^[4] rather than Graves' disease and hyperthyroidism.^[2],[5],[6] Only 7% of patients with EAATD present with Graves' disease as a background autoimmune thyroid disease.^[2] The pathogenesis is still poorly understood. EAATD is rare and has no pathognomonic features, apart from rapid response to corticosteroids. Therefore, establishing the diagnosis may be challenging, unless a diligent clinical evaluation is undertaken.

We report a patient presenting with altered sensorium and the clinical phenotype of acute encephalopathy syndrome (AES). She was eventually diagnosed with EAATD associated with a newly diagnosed Graves' disease. We wish to highlight this case, as Grave's disease is uncommon in children and the typical findings of Grave's disease, such as exophthalmos and goiter, may be missed in a patient presenting in altered sensorium if they are in a recumbent position and the eyes are closed. Awareness of this condition and a high index of suspicion by the clinician are important to establish the diagnosis and initiate timely management.

Clinical Description

An 11-year-old Hindu girl, residing in Kheda, Gujarat, was referred to our department from a peripheral center for the evaluation and management of sudden-onset alteration of the sensorium. The patient had a history of fever and altered sensorium for 1 day. The fever was high grade, associated with chills and rigors, and transiently relieved by medication. It was associated with redness of the eyes but not with any rash. The altered sensorium was in the form of progressively increasing lethargy that had started 5–6 h before presenting to our institute. When she arrived, she was not responding to her parents at all. There was no concurrent vomiting, headache, convulsions, behavioral changes, alteration in the sleep–wake cycle, abnormal vision, squint, facial asymmetry, hearing loss, difficulty in chewing or swallowing, sudden loss of function of limbs, or intolerance to light. There was no preceding history of ear discharge, respiratory or gastrointestinal symptoms, jaundice, bleeding from any site, exposure to any toxins, poisons, or medication, recent dog bite, immunization, or head trauma. The parents reported some recent loss of weight (not documented), though her appetite had been preserved. There was no significant past, antenatal or perinatal history. She was second by birth order, born out of a nonconsanguineous marriage, and the family history was noncontributory. The acquisition of developmental milestones had been normal for age. She was currently studying in 6^th standard with average scholastic performance, according to her mother. There were no cases of similar manifestations in the neighborhood.

On initial examination, the patient appeared drowsy but could be transiently aroused on being given physical stimulus, but she was not oriented to time, place, or person. Her temperature was 100°F. She was normotensive with a blood pressure of 94/56 mm Hg, had tachycardia (pulse rate 140 beats/min), respiratory rate of 28 breaths/min, and O₂ saturation of 100% on room air. She displayed severe thinness with a body mass index of 12.3 kg/m² (< −3 Z score). On general physical examination, the patient had a midline neck swelling, clinically appearing to be an enlarged thyroid gland. It was approximately 6 cm × 4 cm in size, soft, nontender, and not fixed to the underlying tissue. Movement with deglutition and peripheral signs for thyrotoxicosis could not be checked due to the altered sensorium. There was some pallor, hyperpigmentation of the knuckles, and no jaundice. There were no rashes, mucosal involvement, or conjunctivitis. CNS examination revealed a Glasgow Coma score of 9 (E2V3M4); the absence of cranial or focal neurological deficit; normal fundus; normal tone, power, and reflexes; and absence of signs indicating meningeal involvement or increased intracranial tension. The only abnormality detected in the cardiovascular system was an systolic ejection murmur. There was no hepatosplenomegaly. Other systemic examination findings were normal. Keeping a clinical diagnosis of AES, the patient was started on empirical antibiotics and supportive therapy.

Management and outcome

Routine investigations were ordered. The hemogram showed hemoglobin of 9.2 g/dL, normal total leukocyte (11,700/mm³), differential leukocyte, and platelet (262,000/mm³) count. The blood glucose, serum electrolytes, and renal/liver function tests were normal. The arterial blood gas analysis was normal. The C-reactive protein was not elevated, and the blood culture was sterile. The blood dengue antigen test was negative, and the peripheral smear did not show any malarial parasites. Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis with 20 cells/mm³ and high protein (103 mg/dl), but normal glucose levels. CSF culture and serology for Herpes simplex 1 and 2, cytomegalovirus, and Japanese encephalitis were negative. Plain and contrast magnetic resonance imaging (MRI) of the brain was normal. Tuberculosis workup (chest roentgenogram and sonography of the abdomen and pelvis) was negative. The electrocardiography displayed sinus tachycardia with the left ventricular strain pattern. Keeping in mind, the young age, female sex, history of weight loss, tachycardia, and enlarged thyroid, a thyroid profile was ordered. This detected a high free T3 level of 22.6 pg/ml (normal 2.73–4.69 pg/ml), free T4 level of 3.36 ng/dl (normal 1–2.1 ng/dl) with nearly undetectable (0.00032 uIU/ml) thyroid-stimulating hormone (TSH) levels; suggestive of hyperthyroidism. Investigations were planned to determine the underlying etiology of hyperthyroidism. The anti-TSH receptor antibody was positive (>10 IU/L; normal <1.75 IU/L). The color flow Doppler ultrasonography of the neck revealed a markedly enlarged thyroid gland with hypoechoic and heterogeneous echotexture and diffuse hypervascularity [Figure 1].

Figure 1: Doppler ultrasonogram of the neck revealed markedly enlarged thyroid gland with heterogeneous echotexture and diffuse hypervascularity

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We reviewed the possible causes of a rapidly progressive AES in conjunction with available clinical clues (history and examination) and investigations. Metabolic causes (hypoglycemia, dyselectrolytemia, uremia, hepatic, or diabetic ketoacidosis); toxic (poisons), and; intracranial space-occupying lesions, malformations, cerebrovascular disease, tumors, or vasculitis; were ruled out. Although the CSF analysis displayed pleocytosis and elevated protein levels, there was no other supportive evidence of any bacterial, viral, or parasitic CNS infection. Thus, based on hyperthyroidism in the presence of an enlarged and hypervascular thyroid, elevated TSH receptor antibodies, and an inflammatory CSF profile, we kept the final diagnosis of EAATD secondary to Graves disease.

The patient was started on intravenous (IV) methylprednisolone (30 mg/kg/day), antithyroid drugs, and beta-blockers. Within a day, the patient showed a significant response and her sensorium markedly improved. By the 5^th day, she was oriented to time, place, and person, had become afebrile and displayed a normal pulse rate. Once her sensorium normalized the typical examination findings associated with exophthalmos [Figure 2] and thyroid gland swelling [Figure 3] became apparent. She was shifted to oral medications and discharged on the 10^th day with the plan to repeat the thyroid function test on follow-up.

Figure 2: Exophthalmos became apparent once the sensorium had improved and the best eye opening was 5

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Figure 3: A midline thyroid swelling (that became more apparent when consciousness was regained)

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Discussion

The symptoms of EAATD vary from tremors, headaches, and sleep abnormalities to hallucinations, transient aphasia, cognitive impairment, hemiplegia, coma, and status epilepticus. The clinical presentation is heterogeneous, frequently being insidious (75%), with cognitive and behavioral disturbance that may be associated with tremors, myoclonus, or ataxia. Less often, clinical onset may be acute (25%) as stroke-like episodes, epilepsy, or psychosis.^[7],[8] The pathophysiology remains unknown. No relationship has been observed between the antibody titer and the severity of the disease.^[9],[10] Laboratory investigations are nonspecific. The majority of patients of EAATD are euthyroid (18%–45%) or hypothyroid (clinical in 25%–35% and subclinical in 17%–20%) and less commonly present with hyperthyroidism (7%).^[1],[11] In our case, the patient was found to be hyperthyroid. Antithyroid peroxidase antibodies are found in around 85%–100% of the patients, whereas 50% of the patients may have antithyroglobulin antibodies.^[7],[12] CSF analysis is mostly nonspecific (as seen in the case) and may show mild inflammation with mononuclear pleocytosis or slightly increased proteins.^[1],[12] MRI brain is usually normal and is important primarily to exclude other diagnoses.^[2],[13]

In general, EAATD responds well to treatment. Fifty percent of the patients show complete remission after initiation of corticosteroids; IV methylprednisolone (500–1000 mg/day for 3–5 days) combined with oral therapy (1–2 mg/kg/day). Oral steroids can be administrated concomitantly with IV therapy or initiated afterward. Some patients appear to be steroid resistant. If steroid monotherapy fails, or dose reduction is desired, other immunomodulators such as azathioprine, methotrexate, cyclophosphamide, rituximab, or mycophenolate may be initiated.^[9],[10]

EAATD still represents a diagnostic challenge as the clinical presentation varies widely, and there are no reliable diagnostic markers. In the setting of the heterogeneous clinical manifestations of EAATD, it should be kept in mind when diagnosing any patient of chronic, subacute, or even acute-onset neurological or psychiatric complaints, particularly in females with personal or familial history of autoimmune disorders, independent of thyroid functional status. Immunosuppressive therapy must be given early for complete remission and a favorable prognosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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