Pituitary Apoplexy

Introduction

Pituitary apoplexy (apoplexy: a sudden neurologic impairment) is a neurosurgical and endocrine emergency that constitutes a clinical syndrome caused by the rapid expansion of a pituitary adenoma secondary to ischemia and /or intratumoral hemorrhage which causes compression of the cavernous sinus, chasm,  optic nerves and hormonal imbalance. The diagnosis is often delayed as approximately ~80% of these patients will have no previous history of a pituitary problem. Pituitary apoplexy may also occur in non-adenomatous or even the normal pituitary gland especially during pregnancy. 

Most cases of pituitary apoplexy present in the fifth or sixth decade with a slight male preponderance and the most common presenting symptoms is sudden severe headache, which is frequently retro-orbital in location.

Pathophysiology

Because of the rich and the complex vascular system pituitary adenomas have a greater propensity to bleed in contrast to other brain tumours. The pituitary gland is located in a bony cavity called the sella turcica covered by the diaphragma sellae superiorly. It lies in close proximity with hypothalamus, optic chiasma and the cavernous sinus. 

Possible reasons for a hemmorhage could be:

• Rapid tumor growth that outstrips the arterial supply
• Constriction of the thin vascular network and finally ischemia, necrosis and haemorrhage
• Aggressive and invasive tumoral behaviour and hemorrhage 

Clinical Presentation

• Headache (present in 95% of the cases)
• Nausea and Vomiting
• Diplopia
• Changes in visual fields
• Ptosis

                            

Risk Factors

• Hypertension
• Head Trauma
• Major Surgery (CABG)
• Coagulopathy
• Dynamic testing of pituitary gland

How is pituitary apoplexy different from Sheehan Syndrome?

Sheehan syndrome refers to pituitary apoplexy of a nontumorous gland, presumably due to postpartum arterial spasm of arterioles supplying the anterior pituitary and its stalk. Normally, the pituitary gland hypertrophies in pregnancy and this hypertrophy, combined with locally released factors, mediates vascular spasm and renders the pituitary more susceptible to infarction from compromised blood flow. It typically presents years later or as inability to lactate after delivery due to prolactin deficiency and amenorrhea due to gonadotrophin deficiency. Also, after delivery, pubic hair fail to grow, and waxy skin depigmentation develops. Signs of hypothyroidism and hypoadrenalism may develop.

Differential Diagnosis 

• Subarachnoid haemorrhage
• Meningitis
• Hypertensive encephalopathy
• Brain abscess 
• Cavernous sinus thrombosis
• Intracerebral hematomas
• Ophthalmoplegic migraine

Diagnosis and Management

MRI is the investigation of choice in a patient with suspected pituitary apoplexy. However, if a MRI scan is not possible, a dedicated pituitary CT is another alternative. 

Medical treatment consists of the following:

• IV Fluids and administer high-dose corticosteroids. Corticotropic deficiency is present in most patients with pituitary apoplexy and it may be life-threatening. Hydrocortisone can be administered as 100–200 mg intravenous bolus followed either by continuous intravenous infusion of 2-4 mg/hour. 
• Immediately evaluate electrolytes, glucose, and pituitary hormones (random serum cortisol, TSH, free T4, prolactin, IGF-1, LH, FSH)
• Administer appropriate endocrinologic replacement therapy alone or combined with transsphenoidal surgical decompression.
  
  
  
  
  Clinically, the most important endocrine dysfunction is adrenocorticotroph hormone (ACTH) deficiency. Resolution of hypersecretory states have been reported following apoplexy, also described as ‘auto-hypophysectomy’. 
  

  
  

Management is controversial in terms of surgical intervention as some experts advocate early surgical decompression in all patients, whereas others adopt a more conservative approach for selected patients (without visual acuity or field defects and with normal consciousness). Outcome is similar with either conservative management or surgery in more recent studies. Long term with follow-up with hormonal evaluation is required to replace the deficient hormones.

Take Home:

• Pituitary Apoplexy is a life threatening cause of acute onset headache
• Maintain a high index of suspicion in any patient with acute headache and a negative conventional CT scan
• Steroid replacement and maintaining the hemodynamic stability for the cornerstone of management

References:

1. Ranabir, Salam, and Manash P. Baruah. “Pituitary Apoplexy.” Indian Journal of Endocrinology and Metabolism 15.Suppl3 (2011): S188–S196. PMC. Web. 17 Apr. 2016.
2. Rajasekaran, S., Vanderpump, M., Baldeweg, S. et al. (2011) UK guidelines for the management of pituitary apoplexy. Clinical Endocrinology, 74, 9-20. 
3. Solomon, Adriana Elena, et al. "Pituitary apoplexy: clinical features, management and outcome. Clinical study and review of the literature." Romanian Neurosurgery 22.1 (2015): 69-77.

The Intracerebral Bleeder

Intracerebral haemorrhage (ICH) is a subtype of stroke AKA Haemorrhagic stroke. Often the outcome turns out to be dismal and unfortunately we cannot do much about it. But luckily ICH makes up only about 10-15% of the total strokes and it is a neurosurgical emergency where we need to act fast and do the best to at least prevent the secondary brain injury. There are two schools of thought about this depending on the circumstances in which you are working. Some physicians go all out and do everything possible for these patients while others have a pretty nihilistic attitude about this. 

Regardless of these, there are some things that we must do in the initial few hours of intracranial haemorrhage that can possibly change the outcome of these patients. Let us go through each one of them.

Rapid and accurate diagnosis using neuroimaging

First and foremost, we should always suspect ICH in anyone presenting with acute CNS symptoms. Some patients might walk into the ED if they have a small bleed but usually they have other worrisome symptoms like acute onset weakness, headache, vomiting, seizures, altered mental status. It is not reliable to distinguish between an Acute Ischemic Stroke (AIS) and Intracerebral Haemorrhage (ICH) based on the history and clinical examination alone and this is the sole reason why a Non-Contrast head CT is ordered for these symptoms. 

If CT shows blood --> ICH

CT Normal --> Probable AIS 

Other information that a CT can give us:

• Based on the location of blood

Classical hypertensive ICH - seen at basal ganglia, thalamus, pons, cerebellum 

Amyloid Antipathy bleeds/ AVM bleeds - Lobar bleed

Common causes that lead to ICH are chronic hypertension leading to charcot bouchard aneurysms, cerebral amyloid angiopathy, AV malformations, Berry Aneurysms (SAH).

• Calculate the ICH Volume

Concise clinical assessment regarding ICH characteristics and patient condition

We will one again start with the mantra of emergency medicine and start off with ABCs. These patients are often comatose and require RSI. 

Avoid ketamine here if they already have a high blood pressure. I prefer using rocorunium with a sedative. This eases the process of intubation and also brings down the blood pressure a bit. Remember with succinyl choline (sux), there is a concern for transient rise in ICP. Though some physicians are of the opinion that this transient bump in ICP with sux in insignificant, I don't recommend using sux here. 

A full neuro exam is hard to perform in these patients but we can do a ICH score to assess the mortality. Each point increase in the ICH score is associated with an increased risk of mortality and a decreased likelihood of good functional outcome. 

Targeted assessment for potential early interventions including:

1. Control of elevated blood pressure
   The exact number to which the blood pressure should be reduced remains unclear. But a reduction SBP of 140mmHg appress safe. There has been a concern that acutely lowering blood pressure could lead to ischemic brain injury in the peri-hematoma region, but this risk has not been supported by recent studies. 
   
   
   American Heart Association/American Stroke Association Guidelines for the Management of Intracerebral Hemorrhage suggest reducing the blood pressure to <160/90 mmHg or a mean arterial pressure (MAP) <110 mmHg. In patients with potential for elevated ICP, a cerebral perfusion pressure (CPP) of >60 mmHg should be maintained.
   
   
   Go for quick acting and titratable agents like IV calcium channel blocker infusions (nicardipine or clevidipine) or Labetalol. The worst thing that you can do for these patients is to start them on a nitroprusside or nitroglycerine drip. These dugs cause cerebral vasodilation and can further increase the ICP. 
   
   
2. Correction of coagulopathy
   For some reason, we tend to forget this. But reversing blood thinners and anticoagulants is one of the most crucial steps while managing these patients. A quick guide on reversing these medication is mentioned in the table below:
   
   
   
   
   
   
   
   
   
3. Need for early surgical intervention and hematoma evacuation

Current AHA ICH guidelines recommend surgical intervention if:

• Patients with cerebellar hemorrhage who are deteriorating neurologically 
• Brainstem compression  
• Lobar ICH with hematoma volume >30 cc and within 1 cm of the cortical surface 
• Significant life-threatening mass effect

Always correct coagulopathy in patients undergoing surgical hematoma evacuation.  

Other issues:

Prophylactic AEDs

Current guidelines do not recommend routine use of prophylactic anticonvulsants though some practitioners still use a short course in patients with lobar ICH and those undergoing hematoma evacuation. Clinical seizures should be treated.  

Need for intracranial pressure (ICP) or other neuromonitoring

ICP monitoring is recommended in patients with GCS < 9, large hematomas with mass effect suggestive of elevated ICP, or hydrocephalus. As a goal, an ICP <20 mmHg and a CPP> 60 should be maintained.

  

Patient disposition from emergency department (ED):

‘‘I have a 62 year man with known DM/HTN/A fib who was on warfarin. He was found at home this morning at 7 AM by his wife who last saw him normal at 5 AM. He had left-sided weakness, pre hospital GCS was 12, and BP was 190/100.’’

‘‘On arrival to the ED, he was the same, so we took labs and sent him for a head CT.’’

‘‘CT completed at 10 AM showed a 20-mL right thalamic ICH with mild IVH, but no hydrocephalus. There is about 4 mm of right-to-left midline shift. CTA/CTP showed no AVM or aneurysm."

‘‘When he returned to the ED, he was comatose with a GCS of 10, and his left-sided weakness was worse. So he has an ICH Score of 2. His labs came back with an INR of 2.8.’’

‘‘We intubated him using rocuronium and etomidate and transfused PCC. He also had 10 mg of IV vitamin K.’’

‘‘Neurosurgery has been called, and they are on their way to see him. He is in ED, intubated and sedated now on propofol drip. His BP is 150/85 with no other treatment.’’

‘‘They are ready to take him in Bed 2 in the ICU in 5 min.

The first 24 h are critical for blood pressure management, identification of seizures, ICP management, and maintaining a secure airway. Avoidance of fever, hyperglycemia/hypoglycemia, and hypoxia are also important, as these may affect outcomes. In addition, patients with ICH are at increased risk for the development of deep venous thrombosis (DVT); current guidelines recommend use of compression stockings and pneumatic compression devices at hospital admission, as well as initiation of prophylaxis-dose UFH/LMWH within 1–4 days following onset (assuming cessation of bleeding).

Take Home

• DNR is a self fulfilling prophecy. Give them the best chance.
• Do the ABCs, reverse blood thinners/anticoags and control BP (140 SBP is acceptable)
• Get neurosurgery involved ASAP
• When you handover, make sure to convey the volume, location, medication reversal.

References:

1. www.neurocriticalcare.org
2. Morgenstern LB, Hemphill JC 3rd, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2010;41: 2108–29. 
3. Kothari RU, Brott T, Broderick JP, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke. 1996;27:1304–5.
4. Hemphill JC 3rd, Newman J, Zhao S, Johnston SC. Hospital usage of early do-not-resuscitate orders and outcome after intracerebral hemorrhage. Stroke. 2004;35:1130–4.
5. Hemphill JC 3rd, White DB. Clinical nihilism in neuroemer- gencies. Emerg Med Clin North Am. 2009;27:27–37. vii-viii. Qureshi AI, Wilson DA, Hanley DF, Traystman RJ. No evidence for an ischemic penumbra in massive experimental intracerebral hemorrhage. Neurology. 1999;52:266–72.
6. Zazulia AR, Diringer MN, Videen TO, et al. Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage. J Cereb Blood Flow Metab. 2001;21:804–10.
7. Antihypertensive Treatment of Acute Cerebral Hemorrhage Investigators. Antihypertensive treatment of acute cerebral hemorrhage. Crit Care Med. 2010;38:637–48.
8. Anderson CS, Huang Y, Wang JG, et al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol. 2008;7:391–9.
9. Kirollos RW, Tyagi AK, Ross SA, van Hille PT, Marks PV.Management of spontaneous cerebellar hematomas: a prospective treatment protocol. Neurosurgery. 2001;49:1378–86. Discussion: 86–7. 
10. Frontera, Jennifer A., et al. "Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage." Neurocritical care (2015): 1-41.