Hashimoto's Encephalopathy Revealed by Hypochondriacal Delusion: A Case Report Involving a Male Patient.

Hashimoto's encephalopathy (HE) is a rare autoimmune disorder. It associates encephalopathy with autoimmune thyroiditis, presenting abnormal elevations of thyroid antibodies. It is more common in females. It can present with various symptoms, including seizures, myoclonus, psychosis, hallucinations, and mood disturbances. Hypochondriacal delusion is an unusual clinical presentation of this disorder. The authors report a case of HE in a male patient whose clinical presentation was dominated by hypochondriacal delusion. The absence of response to antipsychotics, high serum antithyroid peroxidase antibodiesof about 199 UI/ml, the normality of magnetic resonance imaging, and improvement with corticosteroids confirmed the diagnosis. This neuroendocrine disorder is often misdiagnosed and it represents a diagnostic challenge for clinicians. It should be considered in patients presenting a refractory or an atypical neuropsychiatric disorder and having a family history of autoimmune disease.

Hashimoto’s encephalopathy (HE) is a rare autoimmune disorder. It associates encephalopathy with autoimmune thyroiditis, presenting a high serum level of antithyroglobulin antibody (TG Ab) and/or antithyroid peroxidase antibody (TPO Ab; Crotty et al., 2019). It was first described by Brain et al. in 1966 (Menon et al., 2017). The pathophysiology of HE is still unknown. However, it is considered as an autoimmune disease due to the autoantibodies against the antigens shared by the thyroid and the brain, resulting in either vasculitis or damage to the brain cells (Crotty et al., 2019). Diagnosis is often made following the presence of a wide variety of symptoms, including neurological, endocrinological, and psychiatric manifestations and after ruling out all possible infectious etiologies (e.g., Treponema pallidum [causing syphilis] and Borrelia burgdorferi [causing Lyme disease], and viruses such as herpes simplex viruses [HSV-1 and HSV-2] and HIV; Karthik et al., 2017; Zhou et al., 2017). HE is a rare disorder having an estimated prevalence of 2/100,000 (Crotty et al., 2019). An interdisciplinary approach is required for an early diagnosis and an appropriate management of this disorder (Menon et al., 2017). The authors report the case of a young male patient, hospitalized in the psychiatric department of Fattouma Bourguiba University Hospital (Monastir, Tunisia), whose clinical presentation was dominated by hypochondriacal delusion caused by HE.

Case

A 39-year-old male patient (LG) having no personal psychiatric or somatic history and with a family history of dysthyroidism (brother with Basedow’s disease and a maternal cousin with hypothyroidism) was hospitalized in the psychiatric department at the request of a third party for the management of suicidal thoughts and a suicide attempt by the ingestion of household bleach. The family interview revealed that the patient had anxiety, insomnia, and bizarre thinking and reported strange physical sensations (presence of “soap” all over his body). The symptoms were first neglected by the patient and his family and they had been evolving for 2 years before the first consultation. During hospitalization, the psychiatric interviews revealed hypochondriacal delusion with depressive symptomatology (motor retardation, slowing down of thought). Physical examination was normal with no palpable goiter. Biological tests showed macrocytic anemia (hemoglobin = 10 g/dl; mean corpuscular volume [MCV] = 121 fl] and vitamin B12 deficiency [vitamin B12 = 50 pg/ml[normal range: 191–663 pg/mL]). Routine thyroid function tests (e.g., thyroid-stimulating hormone [TSH]) were within the normal range (TSH = 2.8 μU/ml[normal range: 0.25–4 μU/ml]). Fundic biopsy revealed fundic atrophy and intestinal metaplasia compatible with Biermer’s disease. Injection of vitamin B12 was introduced. Brain computerized tomography scan (CT scan) showed no abnormalities. Psychiatric diagnosis was a major depressive disorder with psychotic features (Diagnostic and Statistical Manual of Mental Disorders, 5th edition [DSM-5 code = 296.24; F32.3]) . The patient was treated with a combination of paroxetine (20 mg/day) and risperidone (4 mg/day). A partial improvement was noticed, but delusional thoughts persisted. The patient was discharged and followed up at the outpatient clinic.

One year later, the patient was readmitted to the psychiatric department at the request of a third party (his mother) because he had suicidal thoughts. Psychiatric examination found the same hypochondriacal delusion (“I have soap all over my body”) together with anxiety and delusional ideas of incurability. On examination, vital signs were normal. Neurologic examination revealed an extrapyramidal rigidity in the upper limbs. Biological tests showed a normal range of vitamin B12 in the blood (vitamin B12 = 586 pg/ml[normal range: 191–663 pg/ml]) and hyperprolactinemia (prolactin = 1,349 mUI/L [normal range: 90–330 mUI/L]). Thyroid function tests revealed subclinical hypothyroidism with TSH = 8.44 μU/ml (normal range: 0.25–4 μU/ml) and thyroxine (T4) = 12.78 pmol/L (normal range: 9–20 pmol/L). Serum TPO Ab was high; it was about 199 UI/ml(normal <50 IU/ml). The patient was receiving levothyroxine 25 mg/day with a euthyroid status. Cervical ultrasound showed hypertrophy of the left thyroid lobe with a heterogeneous and hypoechoic parenchymal echo pattern and a moderate increased vascularity of the thyroid parenchyma on color Doppler. Brain magnetic resonance imaging (MRI) showed “a 6*5 mm micro adenoma on the left side of the anterior pituitary gland without signs of complication” (Figure 1). Electroencephalography revealed a characteristic diffuse slowing, suggestive of encephalopathy.

Figure 1.

Brain magnetic resonance imaging obtained from (a) coronal plane and (b) sagittal plane illustrating microadenoma on the left side of the anterior pituitary gland (arrows).

The presence of refractory hypochondriacal delusion associated with depressive symptoms and high serum anti-TPO antibodies, and the exclusion of other possible causes of encephalopathy, led to the diagnosis of HE. Thus, a corticosteroid treatment (prednisone) was initiated at a dose of 1 mg/kg/day. It was prescribed for 6 months and was gradually reduced, and then it was stopped. A significant improvement in the patient’s clinical condition was observed within 1 week. Risperidone was slowly reduced and then stopped. The patient was followed up in both the psychiatric and internal medicine departments. No relapse occurred during 5 months without any medication.

Discussion

HE is a rare condition (Crotty et al., 2019). Its prevalence is estimated to be 2/100,000. The average age of patients for this disease is 55 years. It ismore commonly reported in females (sex ratio = 4:1; Zhou et al., 2017). The first case was reported in 1966 and it involved a 58-year-old male patient treated for Hashimoto’s thyroiditis and presenting psychiatric manifestations (severe heart attack, altered mental state, and somnolence; Szydełko et al., 2019). Since then, more than 230 cases have been reported (Menon et al., 2017; Szydełko et al., 2019; Zhou et al., 2017).

The clinical features are various, with a wide spectrum ranging from weakness to severe psychiatric disorders (Fiore et al., 2019; Netuluri et al., 2018). To the best of the authors’ knowledge, this is the first reported case of HE with hypochondriacal delusions as a sole manifestation.

Three potential organic causes have been suspected to generate the patient’s hypochondriacal delusion:

Biermer’s disease: Several cases with psychiatric signs, namely, somatic delusion, in association with vitamin B12 deficiency have been reported (Rajkumar & Jebaraj, 2008; Tufan et al., 2012). Psychiatric symptoms can occur in the absence of characteristic hematological or neurological symptoms of Biermer’s disease (Dogan et al., 2012). The pathophysiology of this relationship remains unknown. This may be due to the excitotoxic effects of glutamate on the brain neurons with destroyed myelin sheaths secondary to vitamin B12 deficiency (Akaike et al., 1993; Silva et al., 2019). Given the lack of improvement of the patient’s symptoms after vitamin substitution, this hypothesis was unlikely.

Prolactin adenoma: Prolactinoma can induce psychotic features (hallucinations, delusions etc; Ali et al., 2010). This is explained by the dopaminergic hyperactivity caused by prolactin adenoma. In fact, excessive secretion of unregulated prolactin could induce an increase in dopamine by positive feedback (Liu et al., 2019). In the present case, this type of adenoma was most likely due to the iatrogenic effects of the neuroleptic treatments received by the patient. Indeed, antipsychotics drugs constitute the most involved pharmacological class in the occurrence of hyperprolactinemia. Neuroleptics proceed by blocking D2 dopamine receptors; therefore, they decrease the dopamine. They consequently cause a lifting of inhibition on the secretion of prolactin (Besnard et al., 2014). As the brain CT scan performed during the first hospitalization when the patient had the same symptomatology was normal, this hypothesis was also unlikely.

HE: After excluding the other possible etiologies of encephalopathy, the clinical resolution of psychiatric symptoms with prednisone was in favor of this diagnosis. HE is often successfully treated with corticosteroids (Szydełko et al., 2019). About half of the cases respond completely to this therapy (Berger et al., 2010; Netuluri et al., 2018; Zimmermann & Stranzinger, 2012).

The pathogenesis of hypochondriacal delusion remains unclear (Feusner et al., 2008). It involves a complex interplay of damages to several brain networks including the dorsal striatum, the frontal, parietal, and temporal cortices, and the thalamus as areas of structural dysfunctions (Huber et al., 2018). According to the literature (Chang & Chang, 2014; Lee & House, 2017; Mazzù et al., 2012), hallucinations and psychotic symptoms can be seen in HE. The inducing mechanism can be an autoimmune reaction creating antibodies directed against specific brain cell receptors in the above-mentioned territories (Iglesias-Alonso & Iglesias-García, 2017).

Treatment of HE is specific (Szydełko et al., 2019; Zhou et al., 2017). Most patients respond favorably to corticosteroid therapy (Berger et al., 2010; Tang et al., 2012). Prednisone (50 to 150 mg per day or 1 to 2 mg/kg per day) is recommended (Zhou et al., 2017).

Conclusion

HE is a challenging diagnosis for clinicians. It can present with variable clinical manifestations. This case study highlights the importance of considering the diagnosis of HE when patients present some refractory or atypical psychotic signs associated with an autoimmune disease. Although rare, HE is one of the few completely treatable causes of psychosis.