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A 76-year-old man was noted by his sister, with whom he lived, to have become increasingly confused for 6 months. He gradually became more dependent on her, even for basic activities of daily living such as dressing, but he remained fully ambulant and was not unsteady. He had no headaches or other specific symptoms, there was no relevant medical history, and he was not receiving any regular medications.
When referred to hospital he was disorientated in time and place. His gait was normal, there was no evidence of cranial nerve or limb deficit. His visual fields and fundal examination were normal, and there were no cardiorespiratory or other abnormalities on physical examination. Full blood count, erythrocyte sedimentation rate, renal and liver function tests were normal, as were thyroid-stimulating hormone (TSH), vitamin B12 and blood glucose levels. Chest X-ray and electrocardiogram were unremarkable. Computed tomography (CT) of the brain suggested a cause for the confusional state which was confirmed by magnetic resonance imaging (MRI) of the brain (figures 1 and2).
- List the causes of acute confusional state.
- What do the MRI scans show?
- Which blood test would confirm the diagnosis?
- What specific medical treatment should the patient receive?
Acute confusional state is the term most commonly used by British psychiatrists. Synonyms include acute psycho-organic syndrome, acute organic reaction, acute brain syndrome and delirium. Lipowski1 defines this state (which he prefers to the name delirium) as an episode of acute onset and transient duration, characterised by global cognitive impairment, and due to widespread disturbance of cerebral metabolism. The very young and the aged are particularly prone to acute confusional states.
There is a framework for tracing the cause of acute confusional states (see box).2
CT scan of the brain showed no intracerebral abnormality and no significant degree of intracerebral atrophy, but there was marked expansion of the pituitary fossa (4 × 4 cm) with destruction of the walls. T1-weighted MRI (figures) confirmed a large pituitary tumour in an expanded sella with lateral extension and destruction of the posterior clinoid and clivus, but no evidence of suprasellar extension.
Measurement of serum prolactin would confirm the diagnosis. In our patient serum prolactin was extremely high at 33 884 mU/l, consistent with prolactinoma (normal level 45–375 mU/l). Basal adrenocorticotropin and serum cortisol levels were normal, with a subnormal synacthen test (basal cortisol 308 nmol/l which increased to 503 nmol/l 30 min after intramuscular injection of 250 μg Synacthen. A normal response should produce a rise in cortisol to 550 nmol/l after 30 min). Free thyroxine and TSH were normal. Follicle-stimulating hormone was low at 2.7 IU/l, and luteinising hormone low at 0.8 IU/l, with a low testosterone level of 2.0 nmol/l and normal growth hormone level.
A diagnosis of megaprolactinoma was made and he was commenced on cabergolin 0.5 mg twice weekly.
To the best of our knowledge this is the oldest individual to be reported with pituitary macroprolactinoma. Our patient improved remarkably with resolution of his confusional state, his serum prolactin level fell to 3373 mU/l within 2 weeks, with normalisation of the hormonal profile, including serum prolactin, after 3 months.
Pituitary tumours in the elderly often present with non-specific symptoms and the diagnosis is commonly missed.3 The majority of large prolactinomas in men are due to rapidly growing tumours which are often invasive and bromocriptine-resistant.4 Prolactinomas in women commonly present as small intrasellar tumours.5
Treatment with the semisynthetic ergot alkaloid bromocriptine, an orally active dopamine agonist, introduced in 1971 for the treatment of hyperprolactinaemia and prolactinomas, may be beneficial, with correction of visual field defects and reduction or disappearance of the adenoma. Cabergoline is a long-acting dopamine agonist specific for D2 receptors and is effective in normalising serum prolactin level in patients with macroprolactinoma.6 Cabergoline may be preferable to bromocriptine because of its effectiveness, low side-effect profile, and being long acting (can be given once a week). Medical treatment with a dopaminergic agonist is the preferred mode of treatment for macroprolactinoma, and surgical excision is only recommended when the tumour is life threatening.
Causes of acute confusional state
space-occupying lesion, eg, tumour
trauma, ie, concussion
infections, eg, meningitis
infections, eg, pneumonia
metabolic, eg, liver failure
anoxic, eg, cardiac or respiratory failure
vascular, eg, giant cell arteritis
endocrine, eg, hypoglycaemia
vitamin deficiency, eg, thiamine
intoxication / withdrawal of alcohol or drugs
psychological / environmental
other, eg, hypothermia