The Interplay of Thyroid and Mind: A Case of Psychosis Secondary to Graves’ Disease

INTRODUCTION

The link between psychiatric disturbances and thyrotoxicosis was initially described by von Basedow in the 19th century.¹ Graves' disease is an autoimmune disorder of the thyroid gland. It is commonly associated with a range of symptoms of hyperthyroidism, such as heat intolerance, palpitation, weight loss, and tremors. However, psychiatric manifestations, including anxiety, depression, delirium, toxic psychosis, and bipolar disorder, can significantly impact a patient's quality of life and complicate the clinical picture. As these psychiatric symptoms are relatively rare, with psychosis occurring in approximately 1% of cases², thus highlighting the importance of recognizing the broader effects of the disease on mental health. Understanding the relationship between thyroid dysfunction and psychiatric conditions can help in early diagnosis and effective management from a multidisciplinary department, ensuring a holistic approach to treating Graves' disease.

CASE REPORT

A 47-year-old unmarried fisherman was diagnosed with hyperthyroidism in 2020 at the primary health care center, presenting with symptoms of palpitation and anxiety. He was staying with his elder sister as his parents had passed away. Laboratory investigation showed evidence of a high level of T4 (thyroxine) with a suppressed thyroid-stimulating hormone (TSH) level. Back in 2020, the TSH level was 0.01 mIU/L, while T4 was 31.6 mIU/L. Thus, the endocrine team started him on carbimazole and propranolol, but he defaulted on his follow-up and medications.

However, the patient presented back in 2022 with palpitations, loose stool, and abdominal pain along with disorganized behavior. He came with worsening stress accompanied by prominent delusions of guilt and persecutory delusions, believing that others intended to harm him. His symptoms deteriorated following non-compliance with his antithyroid medications, significantly affecting his occupational performance and daily life activities. Family members reported that he frequently spoke irrelevantly and laughed to himself while being socially withdrawn. He also experienced intermittent auditory hallucinations, anxiety, and heat intolerance. He persistently refused medications due to the belief that they were poisonous and would cause him harm.

Clinical examination revealed diffuse thyroid swelling that moves with deglutition and fine tremors, but there were no significant eye manifestations of Graves' disease. Laboratory results indicated significantly elevated T4 levels (>100 mIU/L) with suppressed TSH (<0.005 mIU/L). Further workup showed his anti-thyroid peroxidase was high at 163.0 KIU/L, and his thyrotropin receptor antibody (anti-TSH receptor antibody) was 13.5 IU/L. Ultrasound assessment showed heterogeneous enlargement of the thyroid gland with a marked increase in vascularity. A multidisciplinary discussion concluded that this patient had schizophreniform psychosis secondary to thyrotoxicosis due to his underlying Graves’ disease [Figure 1].

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Figure 1: Ultrasound neck image showed hypervascularity of the thyroid gland.

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Despite receiving antipsychotics, the highest dose given was tablet risperidone 2mg daily and thyroid-suppressing medications, his condition deteriorated due to non-compliance, resulting in multiple psychiatric admissions marked by severe psychiatric and physical symptoms, including persecutory delusions and pica.

Subsequently, the patient successfully underwent total thyroidectomy [Figure 2]. Preoperatively, the patient was started on Lugol’s iodine 10 drops daily for 7 days to further suppress his thyroid hormone. Intraoperative findings showed a diffusely enlarged thyroid gland with increased vascularity. Bilateral recurrent laryngeal nerves and bilateral superior and inferior parathyroid glands were identified and preserved during the operation. The patient was discharged well after 3 days post-operation. He was discharged with L-thyroxine 100 mcg daily and calcium supplements. Patient’s condition improved post-operation and doesn’t require further admission. The patient is currently under regular follow-up at the endocrine clinic, and his previous symptoms, including delusions and hallucinations, have resolved, but he is still having minimal anxiety. He was advised to continue taking his L-thyroxine medication and was successfully able to discontinue his antipsychotic medications.

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Figure 2: Total thyroidectomy specimen

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DISCUSSION

Graves’ disease is an autoimmune disorder of the thyroid gland, typically characterized by a diffuse goiter, hyperthyroidism, and circulating thyroid auto-antibodies in the blood, as mentioned in the case presentation.³ While psychosis is now an uncommon presenting feature of thyrotoxicosis, thyroid disorders are prevalent in psychiatric patients: a review of records from one center, which examined 230 patients with schizophrenia or bipolar disorder, revealed that 3% had thyrotoxicosis and 23% were hypothyroid.⁴

The pathophysiology, thyroid hormones can influence the synthesis and release of serotonin (5-HT) by regulating the expression of tryptophan hydroxylase, the enzyme that catalyzes the rate-limiting step in serotonin synthesis.

Hyperthyroidism can cause an overactive serotonin system, leading to symptoms like anxiety, agitation, or even psychosis in extreme cases.^5-7 Thyroid hormones also regulate the expression and function of beta-adrenergic receptors in the brain. Increased thyroid hormone levels can enhance the sensitivity of beta-adrenergic receptors, leading to heightened responses to catecholamines. This can manifest as anxiety, restlessness, or even psychosis.^5-7

Several studies have demonstrated improvement in mental symptoms after the normalization of thyroid function, although it has also been shown that mental symptoms persist in many patients after the normalization of thyroid function.^5-7

Case series reviews have indicated that a combination of antithyroid drugs and beta-blockers is the preferred treatment approach for hyperthyroidism associated with psychotic symptoms.¹ When psychotic symptoms persist after the resolution of thyrotoxicosis, antipsychotic medications are recommended. The introduction of atypical antipsychotics has generated interest in managing thyrotoxic psychosis, with one review suggesting that risperidone should be the first-line choice.¹ In certain instances, the intensity of psychotic symptoms may require the use of antipsychotics as a primary treatment alongside antithyroid medications.¹ Some patients who are non-compliant with medications may undergo surgical treatment. However, in a unique case, psychotic symptoms persisted post-operatively despite evidence of euthyroid and normal PTH and calcium levels.⁸

The connection between psychosis and hyperthyroidism remains poorly understood, as evidenced by the persistence of psychotic symptoms after thyroidectomy and the subsequent need for antipsychotic medications to achieve symptom resolution.⁸

CONCLUSION

This case highlights the critical need for careful monitoring and treatment adherence in patients with Graves' disease and underscores the complex interplay between thyroid dysfunction and psychiatric symptoms. A collaborative approach involving multiple specialties is recommended for optimal outcomes for such Graves' disease with psychiatric manifestations.