Pituitary apoplexy and cerebral infarction

Abstract

Pituitary apoplexy (PA) is a possible complication of pituitary adenoma but is rarely followed by cerebral infarction. The mechanism by which this occurs is not totally understood but is believed to have multiple aetiologies such as arterial compression due to mass effect, vasospasm induced by the presence of blood or by vasoactive agents. In this report, we present a man in his 80s with known pituitary adenoma with a sudden onset of left central facial palsy, left hemiparesis, paresis of the VI left pair and previously unrecognised atrial fibrillation in the ECG. At first, the signs of haemorrhage on imaging were unnoticed, which led to a diagnosis of ischaemic stroke that was submitted to thrombolysis. Due to complications during hospitalisation, the team suspected of PA with panhypopituitarism, confirmed by brain MRI and blood tests. The patient underwent conservative management with glucocorticoids with resolution of the acute adrenal insufficiency related symptoms.

Background

Pituitary apoplexy (PA) is a rare endocrine emergency which can occur due to infarction or haemorrhage of the pituitary gland. It complicates 2%–7% of pituitary adenomas and is the first symptom of a previously unknown neoplasm in up to 80% of the cases.¹ The incidence reported varies from 0.6% to 10.5%.² Headache is the earliest and most frequent symptom, but the presentation varies greatly and up to 20% of cases can be subclinical.³ Other common symptoms include nausea and vomiting, ocular palsies, visual field defects and decreased visual acuity.³ Hypopituitarism may occur in 50%–87% of cases.⁴ The pathophysiological mechanisms of PA remain incompletely understood. The pituitary gland is a highly vascular organ and pituitary adenomas are the intracranial tumours that most frequently bleed.⁵ A precipitating factor is identified in up to 40% of patients, mainly hypertension, major surgery, pregnancy and anticoagulation therapy.⁴ Some reports of stroke caused by PA have been reported.^{6 7}

Case presentation

A man in his 80s, with a Clinical Frailty Scale of 5, uncontrolled dyslipidaemia and known pituitary adenoma with supplemented central hypothyroidism (with levothyroxine 0.50 μg), presented to the emergency department with left central facial palsy, mild left hemiparesis and dysarthria which started 2 hours before hospital admission. Paresis of the VI left pair was also noted. The NIH Stroke Scale was 8. The remaining physical examination was unremarkable. Atrial fibrillation (AF) was documented on the ECG. The cerebral CT scan with angiography showed no acute lesions and two calcified atherosclerotic plaques in the left and right carotid bifurcations, leading to a very significant focal stenosis in the carotid bulb. Ischaemic stroke was diagnosed, and the patient underwent thrombolysis.

Initial evolution was favourable, with improvement of motor deficits. Repeated brain CT showed a hypodensity in the areas of the right middle cerebral artery (MCA) and posterior cerebral artery, compatible with a recent ischaemic stroke (figure 1). Ten days after the stroke, hypocoagulation with apixaban was started.

Figure 1.

Cerebral CT scan 24 hours post-thrombolysis revealed hypodensities in the right parietal, occipital and temporal lobes, compatible with a recent infarct (*).

Nineteen days after being admitted, the patient developed an aspiration pneumonia, de novo hyponatraemia with a minimum sodium of 116 mEq/L, hypotension (blood pressure of 90/50 mm Hg), prostration and motor deficits aggravation. PA with panhypopituitarism was suspected. The study performed is shown in table 1. Blood test was collected during an active infection and after initiation of glucocorticoids, due to sustained symptomatic hypotension with altered mental status.

Table 1.

Blood test study performed

	Value	Normal range
Serum osmolality	257 mOsm/Kg	275–295 mOsm/Kg
Urine osmolality	108 mOsm/Kg	300–800 mOsm/Kg
Morning cortisol	6.8 ug/dL	3.7–19.4 ug/dL
Adrenocorticotropic hormone	26.55 pg/mL	7.2–63.3 pg/mL
Thyroid-stimulating hormone	0.090 uU/mL	0.35–4.94 uU/mL
Free T4	1.01 ng/dL	0.70–1.48 ng/dL
Testosterone	107 ng/mL	142.39–923.14 ng/mL
Prolactin	2.45 ng/mL	3.46–19.40 ng/mL

Brain MRI confirmed haemorrhage within pituitary gland and a cerebral infarction in the MCA (figure 2). We reviewed previous CT scans, and a mild hyperdensity in the sellar region was already noticeable at admission. Hypocoagulation was suspended and glucocorticoid in a substitute dose was continued and progressively reduced. Resolution of hyponatraemia and hypotension was achieved. Repeated brain CT scan revealed stabilisation of the haemorrhage size, even after anticoagulation. The patient was discharged after 30 days to a rehabilitation facility, on prednisolone 5 mg/day. Hypocoagulation with apixaban was re-introduced, due to the high risk of new ischaemic events in a patient with AF and the stability of the haemorrhage. At 1 year follow-up, the patient remained asymptomatic.

Figure 2.

(A) Brain MRI showing cerebral infarction in the right MCA territory (*) on diffusion-weighted images; (B) Spontaneous pituitary hyperintensity (arrow) on T1 weighted images; C: T2* sequences revealed an hypointensity in the pituitary (arrow head), confirming the haemorrhage. MCA, middle cerebral artery.

Outcome and follow-up

On hospital discharge, physical examination showed left hemiparesis, dysphagia and dysarthria sequelae. He was observed by physical medicine and rehabilitation and referred to a convalescence unit. The patient ended up dying from an infectious complication 1 year and 3 months later at the hospital.

Discussion

We present a rare case of simultaneous stroke and PA. On first assessment, signs of haemorrhage on imaging went unnoticed and the stroke was managed as a cardioembolic event. The respiratory tract infection was probably the trigger that elicited acute adrenal insufficiency, characterised by hypotension and hyponatraemia.

When PA develops, a rise in intrasellar pressure leads to necrosis of the gland and subsequent panhypopituitarism. Growth hormone deficiency is present in almost all patients, but adrenocorticotropic hormone (ACTH) deficiency is the most clinically relevant deficiency, followed by central hypothyroidism.⁸ Whenever possible, evaluation of the adrenocorticotropic axis should be performed before administration of steroids to correctly interpret the results. In our case, symptomatic hypotension led to glucocorticoid introduction before the blood samples were collected, which probably explains the normal morning cortisol and ACTH levels.

Secondary adrenal insufficiency is the main cause of death and glucocorticoid replacement therapy is the most effective medical treatment.⁹ Surgical approach, with transsphenoidal decompression, is reserved for patients with severe neuro-ocular signs or impaired consciousness.³ Nearly 80% of patients will need some type of hormone replacement therapy, namely glucocorticoids in 60%–80%, thyroid hormone in 50%–60%, desmopressin in 10%–25% of patients and testosterone in 60%–80% of men.³

The mechanism of stroke associated with PA is not fully understood. It is thought that this might be due to the compression of the arteries secondary to the mass effect of the tumour,¹⁰ which can be demonstrated by brain CT scan or MRI. Other authors argue that ischaemia might result from vasospasm induced by the presence of blood in the subarachnoid space or by vasoactive agents released from the tumour.¹¹ In order to diagnose PA-associated brain infarction, a cerebral angiography in the acute phase of the stroke is needed. Previous reports state that this presentation is more common in men and usually involves the internal carotid or middle cerebral arteries, which is the case of our patient.¹²

In this case, left eye adduction was not justified by the stroke and it was more likely caused by the compression of the VI cranial nerve palsy by the tumour. The aetiology of the cerebral infarct is difficult to establish. It could have been a coincidence that the patient had a cardioembolic stroke associated with de novo AF, in addition to a pituitary haemorrhage that became clinically significant due to previous thrombolysis. Another hypothesis to take into account is the cerebral infarction induced by vasospasm related to the apoplexy.

Management of these patients is particularly challenging. Generally, treatment of the acute phase of the stroke involves reperfusion. Intra-axial intracranial neoplasms are an absolute contraindication for thrombolysis, but not extra-axial neoplasms such as pituitary adenomas.¹³ However, intracranial haemorrhage such as PA is a contraindication.¹³ When the patient presents with classic symptoms of PA associated with neurological deficits suggestive of stroke, emergent cranial MRI should be performed to rule out pituitary haemorrhage. When the stroke is caused by tumour compression of the vessels, surgical decompression has shown some positive results, but due to the reduced number of cases published, this is not a clear indication for surgery.¹⁴ When the main mechanism is vasospasm, hormone replacement therapy and supportive therapy are indicated.¹⁴ However, in this case, the patient did not report headache or visual disturbances and the pituitary haemorrhage was missed in the first CT scan, so the patient underwent thrombolysis. Comparing brain CT scans at admission and 17 days after the event, haemorrhage size remained stable, even after thrombolysis and oral anticoagulation.

Previous intracerebral haemorrhage (ICH) is usually considered a contraindication to anticoagulation. Recently, Pennlert et al published a study reporting that anticoagulant treatment is not associated with a significant increase in haemorrhagic event risk in patients with ICH and AF, but it is associated with a significant reduction in 3 year thrombotic event risk and in the combined event of risk of vascular death and non-fatal stroke.¹⁵ This decision should be individualised. In our case, we decided to restart anticoagulation and the patient remained stable, without evidence of new haemorrhagic complications. To our knowledge this is the first report of anticoagulation introduction after PA.

Learning points.

• The imaging of pituitary tumours should not focus only on the tumour itself but also include assessment of its vascular complication—such as pituitary haemorrhage.

• The overlap of pituitary haemorrhage with ischaemic stroke may be an example of a complication of a pituitary adenoma or an unfortunate coincidence.

• Any acute cerebral event, when being evaluated with imaging, should also focus on pituitary, especially in a patient with preexisting adenoma.

• The management of these diseases is challenging and should be individualised to each patient with changes in prognosis and treatment.

Ethics statements

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