An Unusual Case of Acute Confusion in an Elderly Man: Pituitary Apoplexy With Lateral Rectus Palsy

Often, the provisional diagnosis for an elderly patient who arrives at the hospital with confusion is presumed to be delirium stemming from confusion usually caused by an infectious cause. The famous mnemonic PINCH ME signifies the ruling out of pain, infection (that usually has a urinary cause), constipation, dehydration, medication (particularly narcotics), and the environment (factors triggering confusion in a patient with a background of dementia). However, we report a rare case of sudden confusion in an elderly male with no previous history of cognitive impairment. This is the first ever reported case to the best of our knowledge of a patient that presented with sudden confusion, impaired extraocular mobility, and spontaneous cranial hemorrhage that was ultimately determined to be due to a hypothalamic and/or a pituitary cause. It signifies a need for prompt evaluation to arrive at an early diagnosis. Additionally, we hope this case report would serve as a guide to look beyond the current mnemonic of PINCH ME and instead to a new mnemonic of 'PINCH ME HOT' where the latter most mnemonic connotes the need to look at a hypothalamic/pituitary, ocular, or traumatic origin for the delirium.


Introduction
Apoplexy is defined as 'the sudden loss of the ability to feel or move, normally caused by an injury in the brain' [1]. The incidence of pituitary apoplexy has been reported to range from 1% to 26% with a slight male preponderance in most studies [2]. Ranabir et al. have outlined the precipitating factors for pituitary apoplexy including major surgeries, hypertension, coagulopathies, infection, head injury, or radiation although they clarified most cases occur spontaneously [2]. Pituitary apoplexy in most cases is affiliated with pituitary adenoma associated with hemorrhage or infarction following ischemia and hence a potentially life-threatening event [3]. The non-adenomatous pituitary apoplexy has been reported widely in pregnancy [4]. Findling et al. have reported a case of sub-clinical pituitary apoplexy with a history of increased skin pigmentation and headaches post bilateral adrenalectomy for Cushing's disease associated with increased adrenocorticotropic hormone (ACTH) levels, and pituitary hemorrhagic necrosis from pituitary chromophobe adenoma following transsphenoidal surgery [5].

Case Presentation
An 86-year-old independently mobile man, with a background history of partial color blindness and benign prostatic hypertrophy (BPH), arrived at the emergency department with a collapse witnessed by his wife and the ambulance crew responding to a 111 call (general health information helpline in the United Kingdom). The wife described that the patient had a two-week history of progressive worsening fatigue, lethargy, nausea, vomiting, acute confusion, and feeling cold. During an assessment on arrival, he scored 4/4 for eye movement (spontaneous eye-opening response), 4/5 for verbal response (confused), and 5/6 for motor response (moves to localized pain) with a cumulative Glasgow coma scale (GCS) of 13/15. However, his abbreviated mental test score (AMTS) was 10/10 and this suggested that there was no dementia upon initial screening at the time of the visit to the hospital. His capillary blood glucose was 6.3 mmol/l. Observations recorded a heart rate of 69/minute, lying blood pressure (BP) of 130/77 mmHg while standing BP with assistance was 121/75 mmHg, respiratory rate of 16/minute, oxygen saturation of 100% on air, with a temperature of 36.3-degree Celsius, and normal skin integrity with no bruises or rashes. Clinical examination did not reveal any abnormality apart from left lateral rectus palsy ( Figure 1, Video 1). On inquiry, the patient mentioned that he had been having double vision for the past several years, but he had attributed this to age-related vision changes. The patient had planned to have a review by an optometrist at a later date. An urgent computed tomogram (CT) of the head only showed age-related small vessel ischemic changes. No acute bleeding nor acute ischemic changes were reported ( Figure 2). The chest X-ray (CXR) did not identify any signs of consolidation. His initial blood tests also did not demonstrate any significant abnormality ( Table 1).  Based on the initial assessment and laboratory analysis, a differential diagnosis of stroke or encephalitis with very mild hyponatremia and acute kidney injury (AKI) was made. He was started on intravenous ceftriaxone, acyclovir, and intravenous fluids. The lumbar puncture results showed cerebrospinal fluid (CSF) with a slightly raised protein count of 0.85 grams/litre (reference range: 0.15-0.45 grams/litre), glucose 3.7 millimoles per litre (reference range: 3.3-4.4 mmol/litre) with white cell count (WCC) 12 x106 litre, 100% lymphocytes (reference range: 0-5 x 106 per litre with all lymphocytes with no neutrophils). However, the viral polymerase chain reaction (PCR) on the CSF sample came back negative.

Parameter Unit of measurement
The neurology team evaluated the patient and recommended an MRI brain scan be performed. The brain MRI revealed a pituitary mass lesion with suprasellar extension abutting the optic chiasm with evidence of fresh hemorrhage with high T1 signal and susceptibility artifact peripherally within the mass. The appearances were consistent with a diagnosis of pituitary apoplexy ( Figure 3).

FIGURE 3: MRI of the brain
Sagittal T1 pre-contrast reveals a pituitary region mass with suprasellar extension. It has an intrinsic high T1 signal peripherally, in keeping with blood (red arrow).
The patient then had a more targeted MRI of the pituitary confirming these findings ( Figure 4).

FIGURE 4: Coronal T1 post-contrast MRI of the pituitary
The pituitary mass shows heterogenous enhancement (blue arrow). There is the involvement of the cavernous sinuses (more on the left) with internal carotid arteries along the right side (red arrow) and left side (pink arrow). The suprasellar extension is contacting the undersurface of the optic chiasm (yellow arrow) with no overt compression.
The patient was reviewed by the endocrinology team. The pituitary profile blood test was requested which suggested panhypopituitarism ( Table 2).  The patient was commenced on high dose hydrocortisone 50 milligrams (mg) to be taken four times daily for 48 hours then titrated down to a steady dose of hydrocortisone 10 mg in the morning, 5 mg at lunchtime and 5 mg in the evening along with levothyroxine 50 micrograms once a day (OD) until reviewed at the endocrinology clinic. He was also reviewed by the ophthalmology team who confirmed left-sided sixth (abducent nerve) cranial nerve palsy. Humphrey visual field (HVF) analysis showed no defect with exception of a few points missed nasally in the left eye ( Figures 5, 6). The patient felt much better after just 24 hours of steroid treatment and continued to improve. His case was discussed with the neurosurgery team at a tertiary center with advice to continue medical management with outpatient follow-up by the endocrinology team. He was discharged home 16 days after admission. Outpatient follow-up appointments were arranged with endocrinology, ophthalmology, and neurosurgical teams.
The patient was advised not to drive until further notification from the driving and vehicle licensing authority (DVLA). The general practitioner (GP) was advised to arrange for a purple card (to provide support for safe scouting and guidance in the procedures for dealing with an emergency as the patient was on steroids) [6], with periodic blood test analysis in the community. Two weeks after the discharge he was reviewed by the orthoptist team who prescribed prism-corrected spectacles that significantly improved misalignment and resolved diplopia.

Discussion
Common clinical symptoms reported to date associated with pituitary apoplexy include headache, nausea and/or vomiting, decreased visual acuity, variable visual field defect, ophthalmoplegia, altered consciousness, pyrexia, and meningeal signs [7]. Rolih et al. have tabulated anatomical localization with clinical presentation in patients with pituitary tumor expansion and/or apoplexy ( Table 3) [8].  Brain CT can demonstrate sub-arachnoid hemorrhage [9]. However, a cerebral bleed may be missed in CT and may require additional serial CT scans [10]. Special sequence MRI is reported to be more useful than CT scans in characterizing the lesion appropriately [11]. An MRI is useful in the localization and differentiation of tumors and surrounding structures [11]. Dermoid cysts, craniopharyngiomas, lipomas, metastatic melanomas, or any other hemorrhagic tumors are detected with a T1 hyperintense signal [12]. The best advantage of MRI is its usefulness to predict histopathology outcomes in a great majority of patients with pituitary apoplexy [13].

Signs and symptoms of compression
The management of patients with pituitary apoplexy centers around the triad of immediate fluid resuscitation, correction of electrolytes, and steroid replacement. Acute adrenal insufficiency secondary to pituitary apoplexy is reported in two-thirds of patients and is potentially associated with significant mortality and/or morbidity [14]. Hydrocortisone administration up to 100 mg to 200 mg intravenously as a bolus, followed by either continuous infusion of 2 mg to 4 mg/hour or intramuscular administration of 50 mg to 100 mg six hourly (four times a day) is recommended [2]. Other reports of continuous infusion have been recommended due to the saturation kinetics of cortisol-binding globulin [2,15]. Irrespective of the management of the acute phase, following recovery from the acute episode, the recommendations are for quick tapering of the hydrocortisone dose to a maintenance dose of 20 mg to 30 mg per day orally [2,4]. Additional recommendations are for ACTH reserve reassessment in two to three months after the crisis has been resolved [2,4].
The biggest challenge in treating a patient with pituitary apoplexy is involving the specialist teams of endocrinology and neurosurgery as early as possible so that appropriate medical management is initiated with steroids and then proceed to identify patients who would require urgent neurosurgical intervention [2]. The consensus is for patients with hemodynamic compromise and/or worsening eye symptoms from chiasmal compression would require surgical decompression [2,16].
Significant improvement following an early surgical decompression has been reported in patients rendered blind following pituitary apoplexy [6]. However, there are reports of patients with better visual outcomes who were managed conservatively [17,18]. The need for long-term hormone replacement post pituitary apoplexy has been reported to be 40% to 80% for corticosteroids [2,7], 50% to 70% for thyroid hormone [2,7], 6% to 25% for desmopressin [2,7], 40% to 80% for sex steroids, and up to 16% for growth hormone deficiency [2].
The recommendation post four to six weeks of pituitary apoplexy event is to assess pituitary functioning