Acute psychotic episode in a patient with thyrotoxicosis factitia

Abstract

Psychotic syndromes in the context of hyperthyroidism are seldom mentioned in medical textbooks and only a few cases have been published. Typically, such cases present as an affective psychosis. Schizophrenia-like psychosis is a rare occurrence in hyperthyroidism and the link between these two conditions is still poorly understood.

We report the case of a female patient with a known history of chronic lymphocytic thyroiditis. The patient presented to our emergency department with an acute schizophrenia-like psychosis. Elevated levels of T4 and free T4 were found. These resulted from the patient’s voluntary intake of excess levothyroxine as an attempt to lose weight (thyrotoxicosis factitia). Normalisation of thyroid hormone levels and antipsychotic treatment led to prompt remission of the psychosis. Even though the patient stopped the antipsychotics, she remained free of symptoms during the follow-up. Similar cases are briefly reviewed and some of the data from basic research is also considered.

BACKGROUND

It is estimated that between 9% and 20% of all cases of acute psychosis presenting to emergency departments are due to a general medical condition. The list of possible causes includes such diverse conditions as head trauma, intracranial and structural brain lesions or infections, effects of drugs and toxins, organ failure, nutritional deficiencies and endocrine dysfunction.¹ Within the group of endocrine disorders, conditions involving thyroid function are most commonly associated to psychiatric syndromes.²

Possible causes of elevated thyroid hormone comprise (i) hyperthyroidism, as seen in Graves’ disease, toxic thyroid adenoma, multinodular goiter, some forms of subacute or chronic thyroiditis and rare pituitary thyroid-stimulating hormone (TSH) producing tumours; (ii) extrathyroid origin, such as may occur in ovaric strumma; and (iii) thyrotoxicosis factitia, due to intentional or accidental excessive intake of pharmaceutical thyroid hormone preparations or thyroxin-contaminated ground beef.³ However, it is a well-established fact that acute psychiatric disorders themselves may precipitate hyperthyroxinemia.⁴

Behavioural changes occur commonly in hyperthyroidism. Complaints of fatigue, irritability and mood-instability are frequently reported and may lead to a diagnosis of anxiety disorder.² “Apathetic hyperthyroidism” is an unusual presentation of hyperthyroidism occurring mostly in the elderly. It is characterised by depression, psychomotor slowing and apathy.² Psychotic syndromes in the context of hyperthyroidism occur more rarely and are seldom mentioned in clinical textbooks.⁵ Their exact prevalence is currently unknown but is estimated to lie between 1% and 20% in severe hyperthyroidism.² Most authors describe the “typical” psychosis of hyperthyroidism as similar to an affective psychosis with or without bipolar features. A few cases with schizophrenia-like psychosis, mainly with catatonic or paranoid symptoms, have also been described.

We report the case of a young woman who came to our acute inpatient unit with an acute schizophrenia-like psychosis probably secondary to self-inflicted hyperthyroxinemia.

CASE PRESENTATION

A 28-year-old Caucasian women came to our emergency department complaining that she felt threatened by her mother whom, she suspected, wanted to kill her. She had no previous history of psychiatric disorder and she had been well until 2 months prior to presentation when she abruptly developed insomnia and started to hear the voice of a famous actor inside her head. Over the ensuing weeks these hallucinations gradually became more frequent and intense and the patient felt compelled to obey them. She became increasingly isolated and managed to sleep only for a few hours each night. Finally, in the evening before admission, her mother found her lying on the floor in her sleeping-gown, mute and immobile, with outstretched arms. Shortly thereafter she decided to walk all the way to the hospital where she hoped to meet the famous actor whom she could hear inside her head. The patient and her mother did not describe mood elation or depression throughout the episode.

Although agitated, the patient accepted to be transferred to our acute inpatient unit.

On admission the patient had an increased pulse rate (113 bpm) and a blood pressure of 140/80 mmHg. Mental state examination revealed a vigilant, fully oriented, perplexed patient with flattened mood. No alterations of the thought processes were found. The thought content was dominated by paranoid persecutory and hypochondriac delusional ideas (for example, the patient had a minor wound in her index finger, but she believed that it would develop gangrene and need to be cut off). She was suffering from second-person auditory hallucinations (she heard the voice talking directly to her, as if they were engaged in a conversation). Neurological examination was normal.

Medical history was remarkable only for chronic lymphocytic thyroiditis, for which she had been prescribed levothyroxine 0.1 mg twice daily. Family history was positive for schizophrenia (maternal grandmother).

The patient was started on risperidone 2 mg three times a day and levothyroxine 0.1 mg twice a day. Twenty-four hours after her admission, agitation and anxiety improved and it was possible to collect a better clinical history. She complained of heat intolerance, fatigue and also added that she had been losing weight in spite of a normal appetite. Physical examination remained remarkable for tachycardia (130–150 bpm) and an elevated blood pressure (150/100 mmHg), as well as warm and moist skin.

By then, iatrogenic hyperthyroidism was suspect but it could only be confirmed the next day when laboratory values were available.

INVESTIGATIONS

Blood analysis revealed a TSH level of 0.07 μU/ml (0.35–4.94), a total T4 of 235 nmol/L (62.68–150.85) and a free T4 level of 22.0 pmol/L (9.01–19.05; enzyme immunoassay method). The antithyroglobulin antibody level was 6.8 UI/ml (normal <4.1) and the antithyroid peroxidase antibody level was 12.5 UI/ml (normal <5.6; microparticle enzyme immunoassay).

TREATMENT

The patient eventually acknowledged that she had been doubling the levothyroxine dose for at least 3 months in order to lose weight. Levothyroxine was suspended and later reintroduced when the T4 and free T4 levels became low.

OUTCOME AND FOLLOW-UP

The psychotic symptoms subsided within 4 days. The patient was discharged 2 weeks after admission, on risperidone 3 mg once a day, levothyroxine 0.1 mg once a day and with normal values for thyroid function. The preliminary diagnosis was psychosis due to a general medical condition. She was by now asymptomatic, with full insight into her illness.

Just a few days after leaving the hospital, the patient stopped the risperidone on her own initiative. Despite this, 16 months after discharge she was still doing well, free of psychotic symptoms and with good insight.

DISCUSSION

We described a patient with no previous history of psychiatric disorder and a known history of hypothyroid lymphocytic thyroiditis who suddenly developed an acute schizophrenia-like psychosis. Elevated levels of T4 and free T4 were found. These resulted from the patient’s voluntary intake of excess levothyroxine as an attempt to lose weight (thyrotoxicosis factitia). Interruption of levothyroxine intake and antipsychotic treatment led to prompt remission of the psychotic syndrome. Sixteen months later the patient remained well in spite of having stopped her antipsychotic medication shortly after discharge.

Although elevated thyroid hormone levels are a common finding in acute psychiatric inpatients, in such cases the TSH level is usually in the upper “normal” range. In fact, it is the non-suppression of TSH in spite of elevated hormone levels that distinguishes this phenomenon from “true” hyperthyroidism.⁴

The literature on thyrotoxicosis factitia is scarce. Notwithstanding, the phenomenon is consistently reported to occur in patients suffering from some form of mental illness. This has led some authors to suggest that it is the psychiatric disorder that leads to the thyroxine abuse and not the inverse.^6,7 However, others maintain that besides the usual side effects like tachycardia and elevated systolic blood pressure, the use of levothyroxine for slimming purposes occasionally leads to severe psychiatric syndromes.³

In our patient, the simultaneous onset of psychotic symptoms and levothyroxine abuse, as well as the coincidence of thyroid function normalisation and remission of the psychotic symptoms, strongly suggests a role for the thyrotoxicosis factitia in the aetiology of the psychotic syndrome. The quick remission of the psychotic syndrome after only 4 days of antipsychotic treatment further reinforces this hypothesis. Finally, the fact that the patient abandoned her antipsychotic treatment just a few days after leaving the hospital and still remained well 16 months after argues vehemently in favour of a secondary psychosis.

Nevertheless, the hypothesis of a mere chance association between psychosis and thyrotoxicosis or the possibility that thyrotoxicosis resulted from psychotic behaviour cannot be totally dismissed.

Despite reports supporting the idea that psychotic syndromes may be a direct manifestation of thyrotoxicosis,^2,5,8,9 schizophrenia-like psychoses in particular have only rarely been described in this context. For instance, Brownlie et al,⁵ in a retrospective study of 18 thyrotoxic patients with associated psychosis, only found two patients with schizophrenia-like psychosis. Lazarus et al also described a case of schizophrenia-like psychosis in a patient with Graves’ disease. In this case, psychiatric symptoms remitted promptly after subtotal thyroidectomy.⁹ Finally, Gruber et al reported a case of recurrent schizophrenia-like psychosis in a 63-year-old woman with hyperthyroid Graves’ thyroiditis.⁸

The differential diagnosis between affective psychosis and schizophrenia-like psychosis is not always straightforward. Sometimes the patients with psychotic depression or mania present with symptoms that are considered more typical of schizophrenia.¹⁰ The key resides in the evaluation of mood. To obtain an accurate mood history one should at least interview one member of the patient’s family. In this case, the mental state evaluation together with the history provided by the patient’s mother was negative for depression or elation of mood. The patient did not exhibit other symptoms suggestive of depression (for example, anhedonia, loss of energy, fatigue or suicidal ideation). Likewise she did not present symptoms that could suggest mania with psychotic symptoms (for example, grandiosity, increase in goal-directed activity, pressure of speech and increase in pleasurable activities with potential risk).

It remains unclear which mechanism underlies the association between hyperthyroidism and psychosis in general, and for what reason a minority of these patients tend to develop schizophrenia-like syndromes closely mimicking primary schizophrenia. As to the first question, a variety of mechanisms are likely to be involved. One of the main effects of thyroid hormone in the central nervous system is to modulate noradrenergic transmission. Hyperthyroidism enhances β-adrenergic neurotransmission, while hypothyroidism seems to increase α-adrenergic activity.¹¹ Adrenergic function has been classically implicated in affective disorders,¹¹ which is in accordance with the fact that the majority of patients with psychosis and thyrotoxicosis develop affective-like psychotic syndromes.⁵ However, a new groundbreaking noradrenaline hypothesis of schizophrenia has recently been forwarded, with noradrenaline dysfunction playing a central role in both positive and negative symptoms.¹²

Why some patients develop psychotic syndromes and others do not, and why only a minority of those who do so develop a schizophrenia-like phenotype, remains open to speculation. A tempting hypothesis would be that both unspecific psychosis and schizophreniform syndromes emerge in those patients who bear a genetically increased risk for either primary functional psychosis or primary schizophrenia. This would seem to be the case in our patient, whose grandmother had schizophrenia, and agrees with the view that there may be liability genes for psychosis, common to schizophrenia and psychotic affective disorders, and liability genes that are specific for schizophrenia.¹³ Moreover, recent work on candidate genes for schizophrenia has shown increased vulnerability associated with genes that are regulated by thyroid hormones.¹⁴ However, in contrast to our patient, the two patients with schizophreniform psychosis in the study by Brownlie et al⁵ did not have a family history of psychosis, nor did the patient described by Gruber et al.⁸ This suggests that various non-genetic factors may also have played a decisive role in these cases. Then again, the complex, polygenetic multifactorial, mode of transmission of schizophrenia also means that genetic vulnerability may exist even in patients with a negative family-history of full-blown schizophrenia. Clearly, data on the interaction between psychosis and hyperthyroidism are too scarce and too scattered for any relevant conclusions to be drawn about aetiological mechanisms.

Hyperthyroidism, whatever its cause, is definitely a condition to consider in any patient with first-episode psychosis or whenever a psychotic syndrome secondary to a general medical condition is suspected. Particular attention should be paid to thyroid function not only in those patients with a known history of thyroid disorder and thyroid hormone supplementation, but also in those patients who are attempting to lose weight and may be taking slimming compounds containing levothyroxine. We need more in-depth studies of similar cases, as well as more basic research data, to learn more about the association between hyperthyroidism and schizophrenia-like psychosis.

LEARNING POINTS

• Hyperthyroidism can present as an affective psychosis and, rarely, as a schizophrenia-like psychosis.

• It is definitely a condition to consider in any patient with first-episode psychosis, and particular attention should be paid not only in those patients with a known history of thyroid disorder but also in those who are attempting to lose weight and may be taking slimming compounds.

• Data on the interaction between psychosis and hyperthyroidism are still too scarce and too scattered for any relevant conclusions to be drawn about aetiological mechanisms.