Pituitary apoplexy and associated cranial nerve palsies secondary to bleeding caused by immune thrombocytopaenia in a patient with known pituitary macroadenoma

Abstract

An 84-year-old man presented with a frontal headache and easy bruising. He had a background history of a pituitary macroadenoma, diagnosed incidentally a year earlier. Investigations showed haemorrhage into the pituitary macroadenoma leading to a diagnosis of pituitary apoplexy in the context of low platelet count secondary to immune thrombocytopaenia. He was treated with intravenous hydrocortisone, platelet transfusion, intravenous immunoglobulin and high-dose steroid. Neurosurgical intervention was not indicated initially. Five days into his admission, he developed bilateral ptosis and ophthalmoplegia. MRI confirmed further haemorrhage associated with compression of the optic chiasm. He was transferred to a tertiary neurosurgical centre where he underwent urgent surgical decompression. To date, there has been minor improvement in his neurological symptoms. Management of this patient required considerable multidisciplinary teamwork between the clinics of endocrinology, haematology, neurosurgery, ophthalmology and geriatrics.

Background

Pituitary apoplexy (PA) occurs when bleeding or infarction of a pituitary lesion causes symptoms of headache, visual disturbance or endocrine abnormalities. PA occurs in between 2% and 12% of pituitary tumours, although up to 25% of pituitary tumours have evidence of haemorrhage and/or necrosis at autopsy.¹ Risk factors include use of dopamine agonists, oestrogens or anticoagulants, radiotherapy, trauma, lumbar puncture and angiography.^{2 3}

Immune thrombocytopaenia (ITP) results from immune attack on platelets in the peripheral bloodstream leading to a low platelet count and subsequently increased risk of bleeding. It is a diagnosis of exclusion based on absence of anaemia or leucopaenia and ruling out other secondary causes of thrombocytopaenia. Typically, the syndrome has an acute form in children and a chronic form in adults. The incidence of ITP is reported as between 1 and 6 in 100 000.⁴ Intracranial haemorrhage (ICH) is a known complication, occurring in 1.4% of adults.⁵ Risk factors for ICH include severe thrombocytopaenia (platelet count <10–20×10⁹/L) and increasing age.

We report a case of an elderly patient in whom bleeding due to ITP caused PA associated with bilateral cavernous sinus compression, leading to bilateral ptosis and ophthalmoplegia.

This case highlights a rare presentation of a relatively common acquired disease of haemostasis. It also highlights the increased risk of complications in elderly patients with multiple comorbidities and the importance of communication when working within the multidisciplinary team.

Case presentation

An 82-year-old man with a background history of subdural haematoma and pituitary macroadenoma presented to the emergency department with a 10-day history of headache, nausea and unexplained atraumatic bruising. He had fallen from a ladder a year previously requiring admission for bilateral subdural haematomas, at which point, a pituitary lesion was incidentally diagnosed on his CT scan. The patient was referred to the endocrinology clinic, where further investigations including an MRI brain and hormonal profile were performed. MRI showed a 24 mm×20 mm×26 mm lesion in the sella turcica with radiological findings most likely in keeping with a pituitary macroadenoma (figure 1). As there was no compromise to the hormonal profile (table 1) and an absence of visual symptoms, conservative management was advised at the time.

Figure 1.

MRI brain scan (T1W sagittal view), arrow shows lesion within the pituitary gland. T1W, T1-weighted.

Table 1.

Hormonal profile on investigation of incidental finding of pituitary mass and on admission with PA 1 year later

Laboratory tests
	Ref. range	Incidental finding of pituitary macroadenoma	Admission with PA
Thyroid Stimulating Hormone (TSH) (mIU/L)	0.27–4.20	4.23	1
Free Thyroxine (fT4) (pmol/L)	11.0–22.0	n/a	14.6
Follicle Stimulating Hormone (FSH) (IU/L)	1.5–12.4	6.3	4.4
Leutinizing hormone (LH) (IU/L)	1.7–8.6	1.6	3.2
Prolactin (mIU/L)	86–324	212	40
Insulin-like Growth Factor (IGF-1) (nmol/L)	4.8–23.8	n/a	23.4
Growth Hormone (GH) (µg/L)		n/a	0.41
9am cortisol (nmol/L)		699	449
Sodium (mmol/L)	133–146		147
Potassium (mmol/L)	3.5–5.3		3.5
Creatinine (µmol/L)	62–106		138

PA, pituitary apoplexy.

On examination, the patient was alert and orientated. Conjunctival pallor was noted. There was mild bruising globally, but no evidence of active bleeding. Full neurological examination including cranial nerves revealed no focal deficit.

On the fifth day of admission, the patient presented with an acute onset of visual disturbance. Clinical examination revealed bilateral ptosis and failure of left eye abduction. Visual acuity was 6/12 in the right eye and 6/19 in the left eye. On pin hole, visual acuity was 6/9.5 in the right eye and 6/9.5 in the left eye. There were no abnormalities with colour vision or pupillary reflexes. Funduscopy revealed no optic nerve papilloedema or atrophy. Confrontational visual field testing was only possible with manual elevation of the eyelids; on clinical examination, there was no evidence of bitemporal hemianopia but formal perimetry was not performed. Pupils were fixed and dilated bilaterally. These findings suggested bilateral III nerve palsies with left VI nerve palsy with normal optic nerve function.

Investigations

Blood tests identified thrombocytopaenia (platelet count=5×10⁹/L), with no evidence of anaemia or leucopaenia. The patient’s serum electrolytes, glucose, cortisol, prolactin, thyroid hormone and growth hormone levels were within the normal limits (table 1). HIV and hepatitis screen test results were negative. Blood film confirmed thrombocytopaenia, with no other abnormalities noted. Coagulation screen including direct antiglobulin test was normal.

Admission CT head was performed on admission and showed resolution of previous subdural haematomas; however, there was a hyperdense area surrounding the pituitary macroadenoma suggesting possible haemorrhage (figure 2). MRI pituitary and MRI brain scans were performed on day 5 after the patient developed clinical evidence of neurological deficit (figure 3). MRI confirmed haemorrhage within the pituitary macroadenoma causing compression of the optic chiasm (figure 4) and extension of blood into the surrounding basal cisterns as well as ventricles bilaterally.

Figure 2.

CT brain scan (sagittal view), arrow shows hyperdensity around pituitary macroadenoma.

Figure 3.

MRI brain scan (T1W sagittal view), arrow shows haemorrhage into enlarged pituitary macroadenoma. T1W, T1-weighted.

Figure 4.

MRI brain scan (T1W coronal view), arrow shows pituitary adenoma causing upwards displacement of optic chiasm. There are areas of high T1 signal within the lesion suggesting haemorrhage. T1W, T1-weighted.

Differential diagnosis

Diagnosis of ITP was made in line with the guidelines for investigation and management of ITP recommended by the British Society of Haematology (BSH). BSH guidance suggests blood film to exclude pseudothrombocytopaenia along with non-immune causes of thrombocytopaenia such as acute or chronic leukaemia, and blood tests to screen for other autoimmune disease. In this situation, the history, examination, blood counts and blood film were sufficient for a diagnosis of ITP, and in the absence of any atypical findings, the guidelines do not warrant further investigations such as bone marrow biopsy.⁶

Diagnosis of PA was suspected based on a suggestive history along with consistent radiology findings.

Treatment

In view of the findings of PA, intravenous hydrocortisone was given. In the context of intracranial bleeding, urgent platelet transfusion was organised on advice of haematologists, along with intravenous methylprednisolone, intravenous immunoglobulin and oral folic acid. Initially, the neurosurgical team advised conservative management as there were no neurological deficits and the risks of surgery outweighed the benefits. Cranial diabetes insipidus was suspected due to high urine output and desmopressin was administered; however, subsequent urine and serum osmolarities did not support the diagnosis. After further questioning, it was felt the high urine output was secondary to urinary frequency and the patient was treated for a urinary tract infection with antibiotics. The patient was managed on an elderly care ward with regular input from haematology, endocrinology and ophthalmology clinics. Platelet count showed good response to treatment and remained stable >100×10⁹/L so the patient was switched to a tapering dose of prednisolone starting at 75 mg.

On the fifth day of admission, the patient developed worsening ptosis and ophthalmoplegia. MRI confirmed that there was compression of the optic chiasm so he was re-referred for a neurosurgical opinion and transferred to a tertiary referral centre, where he underwent endoscopic endonasal resection of pituitary adenoma and PA. Histology of the tissue showed features suggesting a necrotic neoplasm, but the sample was entirely necrotic prohibiting an exact histological diagnosis. Following surgery, the patient was repatriated back to his local hospital and discharged home with an appropriate care package and plan for eye physiotherapy in the community.

Outcome and follow-up

Following surgery, there was some improvement of the ptosis in both eyes, but bilateral ophthalmoplegia persists. Currently, the patient remains on a reducing dose of prednisolone with a plan from endocrinology clinic to further assess pituitary function and consider switching to oral hydrocortisone. He will be followed up in haematology clinic to monitor his platelet count and ophthalmology clinic will review regarding his cranial nerve palsies.

Discussion

PA occurs after bleeding or infarction of the pituitary gland and leads to headache, visual symptoms or endocrine abnormalities. According to epidemiological studies, PA is rare with incidence of around 0.17 episodes per 100 000 per year. Between 2% and 12% of patients with pituitary tumours experience apoplexy, although up to 75% of patients with PA will not have had a prior diagnosis of a pituitary tumour. PA can occur at all ages but is most common in fifth and sixth decade of life.⁶ Tumour size appears to increase risk of apoplexy, with macroadenomas more likely to undergo apoplexy than microadenomas. Similarly, certain tumour types increase likelihood of apoplexy with non-functioning macroadenomas at higher risk than other tumour types.⁶

The course of PA is highly variable and as such decisions regarding definitive treatment are difficult. Management of patients with PA is best achieved in collaboration by a multidisciplinary team involving endocrinology, neurosurgery and ophthalmology clinics. PA can be considered a spectrum of disease ranging from patients presenting with chronic mild symptoms to acute onset visual loss and cranial nerve palsies. As corticosteroid deficiency is the main source of mortality among the patients with PA and present in the vast majority of PA, steroid replacement is mandatory and should be administered intravenously as soon as diagnosis is suspected.⁷

Historically, acute PA is considered a medical emergency but a more conservative approach to management has been adopted by some specialists. Cases of patients treated conservatively with steroid-based management have shown recovery of visual defects and endocrine abnormalities. Surgery also poses risk of harm such as postsurgical cerebrospinal fluid rhinorrhoea and posterior pituitary damage, which in turn can lead to diabetes insipidus. Hypopituitarism due to removing too much pituitary tissue is also a risk. With regards to timing of surgery, retrospective studies have shown that there is clinical benefit when surgery is performed within 1 week of symptom development in patients with PA and visual defects.¹ There have been no randomised controlled trials to answer the questions over conservative versus neurosurgical management and it remains the principle controversy of treating PA. Current UK guidance for management of PA suggests surgical management for patients with ‘severe neuroophthalmic signs such as severely reduced visual acuity, severe and persistent or deteriorating visual field defects or deteriorating level of consciousness’.⁷

PA in the context of ITP has been previously reported in just three cases. Lenthall et al⁸ report the first known case of a patient with PA and ITP. A 70-year-old man presenting with headache and bitemporal hemianopia that progressed to binocular blindness. The patient underwent surgery with no postoperative improvement in his vision. Maïza et al⁹ report the case of a patient who presented with headache and right eye ophthalmoplegia which progressed to bilateral ophthalmoplegia on the next day. Decompressive surgery was performed after normalisation of platelet count with total recovery of the left oculomotor nerve dysfunction and facial hypoesthesia while palsy of the right oculomotor nerve partially subsided. The patient required long-term hormonal replacement for hypopituitarism. Tsuji et al¹⁰ report the case of a patient with known ITP and PA who was treated conservatively.

In summary, the decision-making around whether and when to perform surgery in patients presenting with ITP and PA remains difficult. The risks of operating on patients with a proven disorder of haemostasis must be weighed against the benefits of neurological recovery. The decision should be made with support from a multidisciplinary team, at least consisting of an endocrinologist, neurosurgeon and an ophthalmologist and input from therapy colleagues is essential so that consideration can be made for how the neurological impairment is affecting quality of life. Timing of surgery should also be considered, with studies suggesting patients with visual defects and PA have better outcomes if intervention is performed within 1 week of symptoms.

Patient’s perspective.

Things haven’t been quite right since I had my fall December last year. I fell from quite a height which resulted in admission into hospital, where I found out I had two bleeds in the brain and a tumour in my pituitary gland. Obviously I was worried when tumour was mentioned, however, it was explained to me that with close monitoring and regular follow-ups, I still should be able to lead a good quality of life.

Prior to my second admission, I was still able to lead a relatively independent lifestyle. Although sometimes my balance was off, I was still about to get around without my frame and aid my wife around the house.

To be honest, I cannot remember a large chunk of time before and during my hospital admission. My wife tells me I was rather muddled and kept asking repetitive questions on the phone (as families were unable to visit due to the COVID-19 pandemic). From what I can remember, most days merged into one; I’d be washed and dressed by the nursing staff, have my meals, sit out in a chair in the afternoon and be put back for bedtime. It was really disorientating being sight impaired. I had to rely on others to tell the time—I’ve never previously had to rely on anyone before. I’d never dreamed of being a burden to anyone!

Having been previously independent, I left hospital with carers four times a day. This was quite a difficult adjustment, however, I knew it was necessary because of my decreased mobility and lack of eyesight. Now my care has reduced to two times a day as my wife is able to manage meals.

My eyesight has been quite hard to come to terms with. I really struggled when I was unable to open both eyes. Over time, my left eye has opened fully, so I was able to attain some normality to my life. Since my right eye has now opened, I am seeing double (images one on top of the other) which is very disorientating and can induce headaches and sickness. I am hoping to get new corrective glasses to aid me with this difficulty.

Thankfully all the healthcare professionals were extremely helpful and caring. I was always kept updated regarding my progress and my family also. I didn’t realise how many different specialisms were integrated in my care, seeing as my contact with my general practitioner was previously so infrequent. I seem to be a medical marvel!

Learning points.

• Pituitary apoplexy is an important, life-threating diagnosis and if suspected, clinicians should initiate intravenous steroid replacement therapy without delay.

• New neurological symptoms in a patient with pituitary apoplexy may point to further bleeding.

• Timing of surgery remains important, with better outcomes proven if surgery is performed within 1 week of symptoms onset.

• When treating elderly patients, Hickam’s dictum—that ‘patients can have as many diseases as they damn well please’ is often more relevant than Occam’s razor. Our case highlights that elderly, frail patients often present with multiple interrelating problems and teamwork within the multidisciplinary team is key to their management.