To the Editor:
Classical pituitary apoplexy is a medical emergency, and rapid replacement with hydrocortisone may be lifesaving. It is a clinical syndrome characterized by sudden onset of headache, vomiting, visual impairment, and decreased consciousness caused by hemorrhage or infarction of the pituitary gland. The headache may or may not be accompanied by neurologic symptoms involving the second, third, fourth, and sixth cranial nerves. 1 The diagnosis is frequently missed because of its rarity. A high index of suspicion is required to diagnose these cases, as illustrated by this case report.
A 29-year-old man with no prior history of high altitude exposure ascended to 5200 m over the course of 14 days. Soon after arrival he experienced a severe headache that was associated with nausea, difficulty sleeping, loss of appetite, and fatigue. With this constellation of symptoms he was diagnosed with acute mountain sickness (AMS) and treated with ibuprofen 400 mg 3 times daily, acetazolamide 250 mg twice daily, and rest. During the next 4 days at 5200 m, he failed to improve and was subsequently evacuated to 1800 m for further management. The patient denied any history of drug abuse, visual disturbance, double vision, ptosis, or head trauma. Evaluation revealed a temperature of 37.0°C (98.6°F), regular pulse of 44 beats/min, blood pressure (BP) of 90/60 mm Hg, respiratory rate of 16 breaths/min, and pulse oximetry of 98% on room air. There was no neck rigidity. Eye movements were full and unrestricted, and the fundus examination was normal. The remainder of the general physical and systemic examination was within normal limits. Routine hematologic and biochemical investigations were normal. The electrocardiogram showed sinus bradycardia, and a computed tomographic (CT) scan of the brain was normal.
Persistent hypotension, sinus bradycardia, and headache gave a strong clinical clue of an acute adrenocortical insufficiency likely owing to secondary cause. The patient was started on hydrocortisone 100 mg IV every 6 hours. Within 12 hours, his BP normalized to 120/80 mm Hg and pulse to 68 beats/min. Hormonal assays were performed along with a magnetic resonance imaging (MRI) of the brain. The MRI revealed enlargement of the anterior pituitary gland with altered signal intensity in the sella extending into the suprasellar region. It measured 8.9 mm in height, 12.7 mm in anteroposterior dimension, and 14 mm in transverse plane. The gland was closely abutting the optic chiasma. There was a focal area of altered signal intensity, which was heterogeneously hyperintense on T1 and hypointense on T2, suggestive of early subacute hemorrhage. On postcontrast scans there was moderate enhancement of the gland with focal nonenhancing area within. Hormonal analysis revealed normal levels of thyroxine, thyroid-stimulating hormone, serum testosterone, prolactin, luteinizing hormone, and follicle-stimulating hormone, and a serum cortisol of 9.65 μg/dL (basal value) and 14.24 μg/dL (during hypoglycemia; range, 20–70 μg/dL). The patient went on to make a complete recovery and has not required regular hormonal therapy.
Pituitary adenomas predispose to apoplexy; however, the condition is usually not known or suspected at the time of the event. Numerous other medical conditions have been linked to pituitary apoplexy but many times it occurs without any predisposing factor.2,3 If present, the main predisposing factors are medication (bromocriptine and cabergoline), radiotherapy, pituitary function tests, diabetes mellitus, trauma, thrombocytopenia, or recent surgery. 4 High blood pressure is also considered as a risk factor for pituitary apoplexy, although this association is not always observed.5,6 High altitude could be a risk factor in this patient as increased risk of cerebrovascular accidents at high altitude is known. 7 Elsässer Imboden et al 8 have underlined the superiority of MRI over CT imaging in detecting pituitary apoplexy as is demonstrated by this report as well.
Pituitary apoplexy can be a masquerader for AMS or high altitude cerebral edema (HACE) if it presents at high altitude. The astute physician may distinguish these diagnoses by examining the signs and symptoms carefully. AMS occurs in a setting of recent gain in altitude, and presents with headache and at least 1 of the following symptoms: gastrointestinal (anorexia, nausea, or vomiting), fatigue or weakness, dizziness or lightheadedness, and difficulty sleeping. AMS may cause headache and nausea whereas HACE may cause diplopia, cranial nerve signs, loss of consciousness, or signs similar to stroke. AMS and HACE can be differentiated from pituitary apoplexy by looking at the signs and symptoms of an acute adrenal crisis (hypotension, hypopituitarism). Those with HACE will typically not have abdominal pain, hypotension, hypoglycemia, or hyponatremia. Pituitary apoplexy does not cause cerebellar signs (ataxia) like HACE. In pituitary apoplexy, the headache typically presents rapidly and without altered mental status. Altered visual acuity because of involvement of the third, fourth, and sixth cranial nerves and ipsilateral mydriasis and ptosis owing to involvement of the third cranial nerve may be present (Table).
The diagnostic criteria for pituitary apoplexy 9
This patient presented with signs and symptoms suggestive of AMS. But hypotension eventually gave a clue to the diagnosis of pituitary apoplexy and was finally confirmed with biochemical evidence of adrenocortical insufficiency on dynamic testing and pituitary hemorrhage on MRI. In the final analysis, the trigger for apoplexy could have been a rise in blood pressure at high altitude. A high index of suspicion by the intensive care and high altitude physician should be maintained when evaluating these cases.