A 72-year-old man who ran a beef cattle farm presented in 2008 with severe-sudden onset headache, nausea and vomiting. His blood pressure was 118/55 mmHg, with heart rate 59 b.p.m., oxygen saturations 97% on room air. He had hazy vision but no visual field deficit at initial presentation. The computed tomography (CT) scan of head demonstrated a 2.5 cm sellar and suprasellar mass compressing the optic chiasma.
The mass was hyperdense and the pituitary fossa was expanded, indicating haemorrhage into a pituitary tumour. The pituitary lesion measured 17×14 mm, extending to the surface of the optic chiasm with haemorrhage. He had a CT angiogram which ruled out aneurysm. His vision worsened a day after his initial presentation, with development of a bitemporal haemianopia, worse on the left than the right. There were no symptoms or signs of anterior pituitary hormone insufficiency or excess.
Q From this history alone, what is your inference ?
We are probably dealing with Pituitary apoplexy
Q What is the clinical presentation of Pituitary apoplexy ?
Pituitary apoplexy occurs from hemorrhage or infarction of the pituitary. The patient presents with complaints of
- Headache- most common symptom +/- Vomiting
- Oculomotor nerve palsy
- Loss of consciousness
- Visual impairment (bitemporal hemianopia)
Q What kind of headache is seen in Pituitary apoplexy ?
Headache is often sudden and can be retroorbital, bifrontal or diffuse headache
Q What is the pathogenesis of headache ?
It is because of increase intrasellar pressure
Q Which cranial nerve is most commonly affected in Pituitary apoplexy ?
Third cranial nerve
Q What causes loss of consciousness ?
Pressure on Hypothalamus or midbrain causes loss of consciousness
Q What is the pathogenesis behind pituitary apoplexy ?
- Pituitary outgrowing its own vascular supply leading to ischemia
- Kinking of superior hypophyseal artery against the diaphragmatic sella
- Entrapment of inferior hypophyseal artery against the diaphragmatic notch because of enlarging tumor
Q Name an important iatrogenic cause for pituitary apoplexy ?
Dynamic testing for anterior pituitary can lead to pituitary apoplexy. This must be kept in mind while testing for anterior pituitary functions.
He underwent urgent trans-sphenoidal surgery. Pre-operative evaluation of pituitary function were difficult to interpret given they were drawn at 2130 h and in light of probable exogenous steroids given earlier. However, there was evidence of hypogonadotrophic hypogonadism and hypoprolactinaemia. The biochemical parameters included cortisol 496 nmol/l, adrenocorticotropin (ACTH) <10 ng/l, testosterone 0.5 nmol/l (9–35), follicle-stimulating hormone (FSH) 3.1 IU/l, luteinising hormone 0.9 IU/l (1–9), thyroid-stimulating hormone 2.4 mIU/l, free thyroxine (T4) 9.9 pmol/l, free tri-iodothyronine 3.8 pmol/l, growth hormone (GH) 2.9 mIU/l, insulin-like growth factor1 10 nmol/l, prolactin 36 mIU/l (56–278).
Q How common is ACTH deficiency in patient with Pituitary apoplexy ?
It is seen in 70% of cases and hence must always be factored in while dealing with such a case. Hence treatment of secondary adrenal insufficiency must be the first priority in such a case of Pituitary apoplexy.
Q What is the importance of low serum prolactin in such a case ?
Low serum prolactin denotes more extensive pituitary damage and suggests less likelihood of improvement in the anterior pituitary function following pituitary decompressive surgery.
Q Which electrolyte imbalance is common in such a case ?
Hyponatremia is common
Histological examination demonstrated haemorrhagic infarction of the pituitary (Figure 1). Reticulin stain was difficult to interpret to ascertain the presence of a neoplasm, but ultimately it was concluded that there was a partially infarcted pituitary adenoma, with positive immunohistochemistry staining for FSH (weak), thyrotrophin and luteinizing hormone. There was no staining with ACTH, GH, prolactin
Visual fields postoperatively improved to a left superior quadrantanopia to confrontation, with normal extraocular movements. Formal visual fields 4 months postoperatively showed improved but residual upper temporal quadrant loss and right inferior quadrant loss. This continued to improve with minimal deficit at 1 year post operation. He developed postoperative panhypopituitarism, requiring replacement therapy with T4 100 μg daily, cortisone acetate 12.5/5 mg daily, testosterone gel 50 mg daily via the transdermal route
Q What do studies say about visual outcome in patients of Pituitary apoplexy treated surgically vs those treated conservatively ?
Retrospective studies have shown no difference in visual outcome amongst those treated surgically vs those treated medically. However the studies suffer from a selection bias and those patients who were more likely to have more visual loss preoperatively, were more likely to have undergone a surgery.
Q Surgical intervention is suggested in which patients with Pituitary apoplexy ?
- Loss of consciousness
- Severe visual field defects
- Severe reduction in visual acuity
Q Is oculomotor nerve palsy an indication for surgery by itself ?
No. It generally resolves on its own in a few days.
Q Is there any difference in Endocrine outcomes in patients managed medically vs surgically ?
Studies do not show a difference in endocrine outcomes in the two groups.
Q What is Pituitary apoplexy score and which parameters are assessed in the same ?
It is a score developed by Rajasekaran et al . It is based on the following parameters:
- Glasgow coma scale
- Visual acuity
- Visual field defect
- Ocular paresis
The score ranges from 0 to 10 and higher the score, more likely to have extensive neuropthalmic involvement. (Click here for the complete guidelines)
Q What would be the Pituitary apoplexy score in this case ?
Since the patient had reduced visual acuity, developed bitemporal hemianopia, no loss of consciousness and no ocular paraeseis the patient’s Pituitary apoplexy score would be 4.
Magnetic resonance imaging (MRI) scanning 3 months postoperatively demonstrated removal of the tumour with minor residual soft tissue in the sellar floor, which remained stable on and follow up imaging for 2 successive years, with a plan for another MRI after a further 3 year interval. He continued to report reasonable energy levels, and felt well on hormone replacement therapy.
Q When is MRI repeated after the event of Pituitary apoplexy ?
After 3 months (12 weeks)
The patient had no remarkable medical history before the initial presentation, but in the succeeding years was diagnosed with type 2 diabetes mellitus, hypertension, obesity (BMI 31 kg/m2), hypercholesterolaemia, bilateral cataracts, for which he underwent surgery on the right eye in 2012, transient ischaemic attack requiring unilateral carotid angioplasty and a single-tonic clonic seizure. Medications included metformin, atorvastatin, sodium valproate and an antihypertensive.
In 2013, nearly 5 years after his initial presentation he presented with a 3-day history of a mild occipital headache with vomiting and visual disturbance.
Q Can Pituitary apoplexy recur ?
Yes. A retrospective study by Pal et al showed that in a mean follow up of 6.6 years after surgery , 11.1% of the patient had recurrence of pituitary apoplexy.
Examination demonstrated a partial right oculomotor nerve palsy, with partial ptosis, diplopia but pupil sparing. Visual fields were intact to confrontation. Other cranial nerves were normal.
MRI demonstrated T1 hyperintensity and abnormal soft tissue in the sella and right cavernous sinus, suggesting haemorrhage, possibly into underlying tumour. The differential included an inflammatory or infective lesion. Follow-up imaging demonstrated resolution of the T1 hyperintensity, consistent with evolution of blood products. There was also noted to be a depressed optic chiasm, which was not different to previous imaging. The cranial nerve signs resolved on dexamethasone.
Three weeks later, the man re-presented with a 2-day history of severe headache, vomiting, tunnel vision and diplopia. The right partial oculomotor nerve palsy had returned, but there also developed bilateral abducens nerve palsies. MRI demonstrated a mild increase in the sellar soft tissue mass, and notably increased tumour invading the right cavernous sinus compared with the scan 3 weeks earlier. At the time, the most likely diagnosis was thought to be further evolution of previous haemorrhage in underlying recurrent pituitary adenoma, but because of the atypical presentation, the differential remained wide.
Nearly 2 months after the first presentation in 2013, he presented again, this time with 3 weeks of worsening epistaxis and with a significant drop in haemoglobin level from 149 g/l a month earlier to 91 g/l. He also had a 1 week history of diplopia, with worsening headaches, vomiting and falls. Cortisone acetate was increased by the patient with no improvement in his symptoms. Examination demonstrated bilateral ptosis, bilateral ophthalmoplegia on all movements, complete on the right, dyscoria and only finger counting for acuity. The visual fields were not documented. Thus, there was a bilateral optic, oculomotor and trochlear nerve palsy, as a right and likely also left abducens nerve palsies. CT head, MRI head and CT-angiogram were performed. The imaging demonstrated an atypical, rapidly growing lesion with now bilateral cavernous sinus involvement, with extension posteriorly into the pre-pontine cistern. There was subtle reduction in calibre of the cavernous internal carotid arteries, suggesting extrinsic compression by the sellar mass. The patient underwent debulking left sphenoidotomy 1800 h later. Operative notes documented a tumour arising from the pituitary fossa eroding through the floor of the sella, filling the right sphenoid sinus, destroying the clivus or posterior wall of the sphenoid sinus and encasement of bilateral parasellar carotids.
Histopathology gave the diagnosis of malignant spindle and round cell neoplasm, without clear evidence of any specific line of differentiation
Following debulking sphenoidotomy, the patient underwent radiotherapy with 54 Gray over 30 fractions, aiming for local control and haemostasis.
Review 1 month after radiotherapy demonstrated some recovery of cranial nerve function, but with residual partial right oculomotor, complete right abducens and mild left abducens palsies. MRI was repeated immediately after radiotherapy, but was essentially unchanged in light of its temporal proximity to surgery
He reported progressive right scapula pain, and CT chest demonstrated seven rounded soft tissue masses in the lungs, the largest measuring 13-mm diameter, most likely metastases, but no apparent lymph node involvement, no effusions and no evidence of bony metastases. He died 2 months after this review.
Q Which cranial nerve of the cavernous sinus is least likely to be affected by a pituitary tumor ?
Q What are reasons for epistaxis following transsphenoidal surgery ?
Transient epistaxis can occur after transsphenoidal surgery. However a possibility of pseudoaneurysm following a damage to a vessel during surgery must be kept in mind while dealing with delayed epistaxis.
LEARNING POINTS FROM THIS CASE
- Pituitary apoplexy score is an important tool for evaluating cases of Pituitary apoplexy
- Recurrence of pituitary apoplexy is noted in 11% of cases over 6 year of follow up
- Oculomotor nerve palsy must be looked for in a case of Pituitary apoplexy.
- Worsening of visual acuity, visual fields and loss of consciousness are indications for surgery in a case of Pituitary apoplexy.