Hashimoto’s encephalopathy: an under diagnosed entity

Abstract

We describe a 60-year-old woman with Hashimoto’s thyroiditis who presented with neuropsychiatric manifestations even on optimal and stable doses of levothyroxine replacement therapy. She had high anti-thyroid peroxidase antibody and responded to glucocorticoid treatment

BACKGROUND

Hashimoto’s encephalopathy is an under recognised entity and should be considered in patients with unexplained altered sensorium.

CASE PRESENTATION

A 60-year-old retired government official, who has had type 2 diabetes mellitus since she was 48 years old was detected to have hypothyroidism 2 years ago when her thyroid function tests showed serum-free T3 2.14 pg/ml (normal: 2.3–4.2), free T4 1.01 ng/dl (normal: 0.89–1.76) and thyroid stimulating hormone (TSH) 10.83 IU/ml (normal: 0.27–4.2).

She was on 100 μg/day of levothyroxine replacement for 1 year, but started developing recurrent altered behaviour in the form of agitation, memory disturbances, urinary incontinence and episodes of running away from home, which was associated with incoordination and tremor a year later. Initially these episodes were occurring once every 3–4 weeks but later the frequency increased to weekly episodes. These episodes would last for 3–4 days and would spontaneously improve. Her blood glucose levels were stable on oral anti-diabetic drugs (glimepride 2 mg/day and metformin 2000 mg/day) during these episodes.

On examination, she was 155 cm tall and weighed 67 kg and her body mass index was 27.9. Her blood pressure was 120/84 mmHg without any postural drop. Goitre was absent and deep tendon reflexes were normal. Her neurological examination revealed normal higher mental functions and cranial nerves. She had coarse tremor and ataxia. Motor and sensory examination was otherwise unremarkable. Fundus was showing mild non-proliferative diabetic retinopathy. The rest of the systemic examination was normal. She did not have history of nephropathy, coronary artery disease or cerebrovascular accident and was not a hypertensive.

Her haemogram showed haemoglobin 10.2 gm/dl with normal white blood and platelet counts. Biochemical parameters, including electrolytes renal parameters and liver function tests, were within normal limits. Her thyroid function tests were T3 1.8 nmol/L (normal: 1.2–3.0), T4 99.03 nmol/L (normal: 61.8–163.4, TSH 0.82 μU/L (normal: 0.27–4.2) and anti-thyroid peroxidase antibody (TPO Ab) 1515.2 U/m l (normal: <34). Serum vitamin B12 levels were 420.0 pg/ml (normal: 193–982 pg/ml). HbA1c was 8.7%.

Her chest x ray, electrocardiogram and echocardiogram were normal. Brain imaging showed multifocal non-specific white matter abnormalities (fig 1). Cerebrospinal fluid cytology, biochemistry and microbiological studies were normal.

Figure 1.

T1W MR brain imaging showing multifocal non-specific white matter abnormalities.

She was diagnosed to have Hashimoto’s encephalopathy and was started on prednisolone 60 mg/day by the neurologist along with continuation of levothyroxine 100 μg/day. With prednisolone she had marked improvement in her symptoms—the episodes of altered sensorium subsided and incoordination improved. Since the glycaemic control worsened after starting prednisolone, she was initiated on insulin. She developed recurrence of her neurological symptoms after 4 months when the prednisolone dose was tapered from 60 mg to 40 mg. So she has continued on 60 mg prednisolone for the last 6 months. On admission, her prednisolone dose was reduced to 40 mg/day as she had become overtly Cushingoid and she was continued on levothyroxine 100 μg/day along with calcium and 1,25(OH)₂ Vitamin D supplementation 0.75 μg/day. Insulin dosage was adjusted to intensify her glycaemic control. She was also given iron and multivitamin supplementations and physiotherapy. Steroid dose was gradually tapered at the rate of 5 mg reduction per week. She was also started on azathroprine 150 mg/day because of her repeated relapse while tapering steroids.

OUTCOME AND FOLLOW-UP

Two months later, azathroprine had to be stopped as the patient developed hepatotoxicity and pancytopenia. Prednisolone dose had to be increased to 20 mg/day and the patient is now doing fine.

DISCUSSION

Hashimoto’s encephalopathy was described in 1966 by Professor Brain and his colleagues with a case of a 63-year-old man who presented with seizures, disorientation and frequent alternating hemiparesis simulating a vascular disorder.¹ The episodes were transient and were associated with increased cerebrospinal fluid protein and transient electroencephalographic abnormalities. The patient had clinical hypothyroidism, positive anti-thyroid antibodies and biopsy proven Hashimoto’s thyroiditis. The episodes occurred while he was receiving adequate thyroxine treatment. This was described as either a sign of Hashimoto’s encephalopathy or a coincidence. Our patient, despite being on optimal dose of levothyroxine treatment had altered behaviour in the form of agitation, episodes of running away from home along with tremor and incoordination. The majority of patients with Hashimoto’s encephalopathy are reported to have tremor, transient aphasia, myoclonus, gait ataxia, seizures and sleep abnormalities. These manifestations may occur episodically, as was seen in our patient.

Pathogenesis of Hashimoto’s encephalopathy is not clearly defined. However, the postulations are that it may be an autoimmune brain disease as a part autoimmune predisposition in the background² or it may be a manifestation of delayed cerebral tissue responsiveness to levothyroxine replacement therapy as different tissues in the body attain euthyroidism at variable times. However, the autoimmune basis is substantiated by the presence of other autoimmune disorders and response to immunosuppressive treatment. This is further strengthened by the presence of α-enolase antibody,³ antineuronal autoantibody and TPO Ab in sera and demonstration of lymphocytic infiltrates into the perivascular space in the central nervous system.⁴ The term “corticosteroid-responsive encephalopathy associated with autoimmune thyroiditis” has been suggested to be more accurate and descriptive than Hashimoto’s encephalopathy.⁵ The differential diagnoses include Creutzfeldt–Jakob disease (CJD), Alzheimer’s disease and myxedematous encephalopathy.⁶ Slower onset and progressive nature along with non-responsiveness to corticosteroids differentiate CJD and Alzheimer’s disease from Hashimoto’s encephalopathy.^5,7

The treatment of Hashimoto’s encephalopathy is prednisolone in doses of 60–100 mg per day for at least 2–4 weeks. The majority of the patients have a prolonged remission to this initial treatment.⁸ The rest may have recurrent disease, which either requires reintroduction of glucocorticoids or addition of other immunosuppressives that may have to be continued lifelong. Our patient had two episodes of recurrent neuropsychiatric manifestations whenever prednisolone dose was tapered; therefore, azathioprine was added to facilitate the reduction of prednisolone dose.

LEARNING POINTS

• In a patient presenting with neuropsychiatric manifestations in the background of autoimmune thyroid disease, a possibility of Hashimoto's encephalopathy should be considered.

• Glucocorticoid treatment in such situations is rewarding.