Psychosis associated with prolactin-secreting pituitary macroadenoma

A pituitary adenoma is prolactin-secreting tumour and is classified based on its size as a microprolactinoma (< 10mm diameter) or a macroprolactinoma (> 10mm diameter).^1,4 Dopamine is the principal prolactin-inhibitory factor; hence dopamine agonists reduce the prolactin level and often will shrink a prolactin-secreting pituitary adenoma. Studies have confirmed that typical and atypical antipsychotics act as dopamine receptor blockers and consequently increase the prolactin level.^8,9

Recent studies revealed aripiprazole, which is a partial dopamine agonist, has little or no effect on the prolactin level.^8,12 These findings have various implications in diagnosing and managing patients with a prolactinoma, psychosis or combination of both conditions. Around 60% of male patients with prolactinomas have macroprolactinomas, and 90% of female counterparts present with microprolactinomas.^4,11 This is likely because the presenting symptom for male patients is typically hypogonadism while female patients present with amenorrhoea, which will be evident much sooner.^4,11 Pituitary macroadenoma space-occupying neurological symptoms are generally headaches and visual problems in the form of field defects. 

The visual problems range from compression of the optic chiasm, causing bitemporal hemianopsia, to the compression of cranial nerves III, IV or VI causing ophthalmoplegia.⁴ Neuroimaging, especially magnetic resonance imaging (MRI), is sensitive in diagnosing pituitary macroadenoma. However, since less than 3% of institutionalised psychiatric patients have intracranial tumours, debates remain between psychiatrists and neurologists about whether all patients with new-onset psychiatric symptoms should undergo routine neuroimaging.⁵

Case report

AZ is a 28-year-old, married, employed, Caucasian male who presents with new-onset psychosis. He suddenly quit his job and engaged in various uncompleted new projects. He denied any history of drug or alcohol abuse and had no significant family history of mental illness, except two uncles with alcohol-related disorders. His only medical history was a motor vehicle accident nine years prior; he was unconscious for few seconds but recovered without any sequelae. 

He reported a two-year history of frontal headaches and a few months of low mood, insomnia, anhedonia, anorexia, anergia, intermittent confusion and poor concentration. On examination he was irritable, perplexed, with disorganised thoughts and pessimism about the future with suicidal thoughts but no specific plan. He had racing thoughts that were tangential and circumstantial, pressured speech, flight of ideas and a labile affect. He also had paranoid/persecutory delusions with second- and third-person auditory hallucinations with the voices running commentary on his actions. Collateral information from wife and sister confirmed bizarre behaviour for two weeks.

Once admitted to the inpatient psychiatric unit he was started on risperidone and escitalopram, and his symptoms improved significantly, however he developed galactorrhoea and a severe headache after three weeks on these medications. An endocrinologist was consulted due to elevated prolactin 21.57 ng/ml (normal level: 2.1-17.7 ng/ml). The hyperprolactinaemia was attributed to the risperidone, which was subsequently discontinued. AZ was then started on aripiprazole and his prolactin level normalised to 0.71 ng/ml, exactly three months after initial level of 21.57 ng/ml. 

However, despite AZ’s normalised prolactin, his headaches persisted, hence an MRI of the brain, T1-weighted, was ordered. The MRI revealed a macroadenoma in the pituitary fossa, which extended into the suprasellar region compressing the chiasma, there was also dilatation of the third and lateral ventricles suggesting some degree of compression at the aqua duct (see Figure 1). AZ was discharged from the psychiatric unit on aripiprazole to follow up with the endocrinologist, who prescribed cabergoline 0.25mg twice weekly.

Figure 1: Pre-surgery, the first MRI, T1-weighted (sagittal) – the pituitary fossa shows a macroadenoma (11 mm)(click to enlarge)

Figure 2: Second MRI T1-weighted (sagittal) – the pituitary fossa shows a macroadenoma. Pre-surgery, almost one year on cabergoline and no significant changes in the size of the macroadenoma(click to enlarge)

MRI findings

Since the psychosis subsided the endocrinologist discontinued aripiprazole causing AZ to have a relapse of his psychosis, as well as acute cognitive impairment (MMSE: 24/30) within one week of drug discontinuation. AZ was again admitted to a psychiatric unit and aripiprazole was restarted, however his psychotic symptoms persisted. Once the aripiprazole was switched to olanzapine his psychotic symptoms quickly resolved. 

However, upon re-evaluation by his endocrinologist it was found that AZ’s pituitary macroadenoma was no longer responsive to cabergoline; therefore the endocrinologist recommended neurosurgery to remove the tumour. AZ successfully had surgical resection of the macroadenoma, his frontal headaches then subsided and his wife became pregnant three months after the neurosurgery. 

After six months on olanzapine, he had another psychotic break, this time with suicidal ideation and a plan. His psychiatrist discontinued the olanzapine and escitalopram and determined the patient’s diagnosis to be schizoaffective disorder and prescribed clozapine. AZ remains stable on clozapine and has been able to return to work.

Discussion

Management of a pituitary adenoma with concomitant psychosis involves a multidisciplinary approach, the psychiatrist needs to work closely with the endocrinologist, neurologist and, if indicated, a neurosurgeon.³ A case report by Filley CM et al, recommended any patient aged 40 or older with a change in mental status, cognitive or emotional, should have brain imaging done. They also recommend brain imaging in patients with specific neurobehavioural or neurological findings and those with unexpected poor response to psychopharmacological treatment.⁵ The first-line treatment for patients with a pituitary macroadenoma is dopamine agonist medications (bromocriptine or cabergoline); these medications normalise serum prolactin levels in 80-90% of cases.³ Typical and atypical antipsychotics which are dopamine antagonists counteract the effects of these medications.²

A case report by Melkersson K et al revealed a good outcome from a combination of clozapine and bromocriptine in management of a patient with a prolactin-secreting pituitary adenoma and a psychotic disorder. Also, a combination of clozapine and a selective D2 receptor agonist like quinagolide have been recommended as the treatment in these complex cases.² Studies revealed clozapine has a high affinity for the D4 receptor and displays relatively weak antagonism at dopamine, D2 receptor, and these may explain its inability to significantly affect the prolactin level.^13,14,15

Conclusions

Management of psychosis in a patient with a comorbid pituitary macroadenoma is complex. The treatment of the psychosis complicates the medical and neurological outcome of the pituitary macroadenoma and vice versa. Evidence-based psychopharmacological management options should be considered at the early phase of treating psychosis; especially schizophrenia-type disorder that is complicated by symptomatic pituitary macroadenoma. Despite low incidence of pituitary adenoma in mental health facilities, patients with new-onset psychosis need comprehensive medical evaluation to rule out organic pathology. 

Finally, we recommend patients with new-onset psychosis after the age of 20 to have a thorough medical assessment including routine laboratory tests and a prolactin level prior to the initiation of neuroleptics. Neuroimaging studies should be considered to definitively rule out organic pathology as this may well serve to avoid pitfalls in ruling out organic pathology in patients with new-onset psychosis.

Declaration of interest: none.

Acknowledgements: The authors would like to thank the following individuals for their assistance with this case report: Drs Brian O’Shea, Branden Youngman and Liam Watters.

References

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