Synonyms: pituitary apoplexy, hypopituitary coma

Acute pituitary failure is a rare, life-threatening condition of sudden onset which is both difficult to diagnose and to treat. It occurs most often in patients with pituitary tumours but can occur when there is no pituitary gland tumour.

• It is usually caused by haemorrhage or infarction of the pituitary gland and a variety of pathophysiological processes may cause this.
• It is characterised by the sudden onset of hormonal dysfunction often with important accompanying symptoms.

Aetiology

• This usually occurs because of an acute expansion of a pituitary adenoma. Less often it occurs from haemorrhage or infarction in a nonadenomatous gland. These changes compromise the unusual blood supply of the anterior pituitary and pituitary stalk.
• It can occur in otherwise healthy patients where the pituitary gland is damaged by trauma,¹ surgery or haemorrhage.
• It may be associated with an acute medical episode such as hypertension, diabetes mellitus, bleeding disorders, infection, trauma, hypothermia, or sedative therapy.
• It may be precipitated by medical interventions such as endocrine stimulation tests, treatment with bromocriptine, surgery² and pituitary irradiation.

Epidemiology

• Acute pituitary failure is rare. It occurs:
  • In between 1 and 10% of pituitary tumours.
  • Twice as often in men, usually between age 37 and 57 years.
• Postpartum pituitary necrosis is also known as Sheehan's syndrome:
  • This usually presents progressively with a variety of developing symptoms (starting commonly with failure to lactate, breast involution and then amenorrhoea), rather than the more dramatic and acute presentation.
  • The more dramatic acute presentation of pituitary apoplexy only occurs in a minority of patients with Sheehan's syndrome.³
  • Sheehan's syndrome occurs in as many as 1-2% of women with a significant postpartum haemorrhage apart from cases developing at other stages of pregnancy and the puerperium.

Presentation⁴

History

The onset of symptoms is sudden and may occur in patients known to have a pituitary adenoma.

• Headache occurs in 95% of patients. It often starts suddenly^5,6 as a unilateral, retro-orbital headache before becoming more generalised. It is thought to be caused by stretching of the dura mater in the sella.⁷
• Vomiting occurs in 69% of cases. It often accompanies the headache and may be caused by elevation of intracranial pressure or irritation of meninges.
• Diplopia may occur in the conscious patient from involvement of different cranial nerves.
• Visual field defects occur in 64% of patients, by compression of the optic chiasm. Defects in acuity may result from optic nerve compression.
• Ptosis may occur.

Examination findings

There may be rapid progression to coma, suggesting stroke, subarachnoid haemorrhage and with accompanying meningism, even meningitis. Careful and early examination may detect a variety of findings. These may include:

• Bitemporal superior quadrantic field defect, which is classic. There may be a contralateral homonymous hemianopia if the optic chiasm is affected differently.
• Compression of the cavernous sinus may impair cranial nerves III, IV and VI causing ocular paresis and hence diplopia (in the conscious patient).
• Horner syndrome, which may develop if sympathetic fibres are damaged.
• Stroke, which can occur if the carotid syphon is compressed against the anterior clinoid process. This may be associated with meningism, stupor and coma.
• Thermal regulation, which may be impaired by hypothalamic involvement. Hypothermia can result.
• Endocrine deficiencies, which can result from destruction of adenohypophyseal tissue.
• Complete ophthalmoplegia, which may result.⁸
• More difficult to diagnose pituitary apoplexy, which can arise from ectopic pituitary adenomas. These are usually found at autopsy.

Differential diagnosis

• Subarachnoid haemorrhage⁹
• Meningitis
• Brain tumours
• Demyelinating disease
• Cerebrovascular disease

Investigations

• Blood tests:
  • Urea and electrolytes (hyponatraemia)¹⁰
  • Creatinine
  • Blood glucose urgently (risk of hypoglycaemia)¹⁰
  • Pituitary hormones
• Imaging to assess the pituitary:
  • Computerised tomography (CT) scan
  • Magnetic resonance imaging (MRI) is preferable to visualise haemorrhage not seen on CT scans

Management¹¹

Acute management

This is one of a small but important group of endocrine emergencies. It is so rare that there is little evidence on which to plan optimum care.¹²

• Resuscitation and stabilisation of the patient with particular attention to management of fluids.
• High-dose corticosteroids (hypopituitarism is usual).
• Hormonal treatment of any adrenocortical hormone deficiency.
• Surgical decompression of pituitary may be required.¹³
• Some patients can be managed conservatively.^12,14

Long-term management

Patients should be followed up for:

• Regrowth of tumour
• Endocrine abnormalities^12,15

Prognosis

It is a life-threatening condition with a high mortality. It is difficult to diagnose and difficult to treat.^13,14 However, with rapid diagnosis, followed by prompt correct management, it is possible to achieve complete recovery.^15,16

Document references

1. Behan LA, Phillips J, Thompson CJ, et al; Neuroendocrine disorders after traumatic brain injury. J Neurol Neurosurg Psychiatry. 2008 Jul;79(7):753-9. [abstract]
2. Dev R, Singh SK, Sharma MC, et al; Post traumatic pituitary apoplexy with contiguous intra cerebral hematoma operated through endonasal route-a case report. Pituitary. 2007 Feb 22;. [abstract]
3. Kelestimur F; Sheehan's syndrome. Pituitary. 2003;6(4):181-8. [abstract]
4. Vaphiades M; Pituitary apoplexy; eMedicine (2009)
5. Dodick DW, Wijdicks EF; Pituitary apoplexy presenting as a thunderclap headache. Neurology. 1998 May;50(5):1510-1.
6. Garza I, Kirsch J; Pituitary apoplexy and thunderclap headache. Headache. 2007 Mar;47(3):431-2.
7. Matharu MS, Schwedt TJ, Dodick DW; Thunderclap headache: an approach to a neurologic emergency. Curr Neurol Neurosci Rep. 2007 Mar;7(2):101-9. [abstract]
8. Keane JR; Bilateral ocular paralysis: analysis of 31 inpatients. Arch Neurol. 2007 Feb;64(2):178-80. [abstract]
9. Sergides IG, Minhas PS, Anotun N, et al; Pituitary apoplexy can mimic subarachnoid haemorrhage clinically and radiologically. Emerg Med J. 2007 Apr;24(4):308.
10. Bunch TJ, Dunn WF, Basu A, et al; Hyponatremia and hypoglycemia in acute Sheehan's syndrome. Gynecol Endocrinol. 2002 Oct;16(5):419-23. [abstract]
11. Kearney T, Dang C; Diabetic and endocrine emergencies. Postgrad Med J. 2007 Feb;83(976):79-86. [abstract]
12. Ayuk J, McGregor EJ, Mitchell RD, et al; Acute management of pituitary apoplexy--surgery or conservative management? Clin Endocrinol (Oxf). 2004 Dec;61(6):747-52. [abstract]
13. Randeva HS, Schoebel J, Byrne J, et al; Classical pituitary apoplexy: clinical features, management and outcome. Clin Endocrinol (Oxf). 1999 Aug;51(2):181-8. [abstract]
14. Sibal L, Ball SG, Connolly V, et al; Pituitary apoplexy: a review of clinical presentation, management and outcome in 45 cases. Pituitary. 2004;7(3):157-63. [abstract]
15. Lubina A, Olchovsky D, Berezin M, et al; Management of pituitary apoplexy: clinical experience with 40 patients. Acta Neurochir (Wien). 2005 Feb;147(2):151-7; discussion 157. [abstract]
16. Dubuisson AS, Beckers A, Stevenaert A; Classical pituitary tumour apoplexy: clinical features, management and outcomes in a series of 24 patients. Clin Neurol Neurosurg. 2007 Jan;109(1):63-70. Epub 2006 Feb 20. [abstract]

Acknowledgements