Historical Aspects 1898 Bailey –first description 1938 Sheehan – pituitary infarction and panhypopituitarism after obstetrical hemorrhage 1950 Brougham – described 5 cases, recognized and named clinical syndrome
Pituitary Apoplexy is defined clinically –An acute clinical syndrome with the sudden onset of: Headache Vomiting Visual disturbances Ophthalmoplegia Alterations in the state of consciousness –Occurs primarily in patients with pre-existing pituitary adenomas, though also in non- tumorous pituitaries –Caused by extensive pituitary hemorrhage and infarction
True prevalence uncertain – difficulty in recognizing and diagnosing syndrome Surgical series: 10-15% adenomas show hemorrhage-most silent Clinical syndrome estimated at 0.6-10% of adenomas, based on symptoms and sudden decrease or loss of pituitary function Non-adenomatous pituitaries: no data Prevalence
Mean age: 47+15 years (range: 6-88) Males : females - 1.5 : 1 About 2/3 of patients unaware of tumor at time of apoplectic event Relationship to tumor type: no predilection for cell type of adenoma; rare in craniopharyngioma and hamartoma Prevalence (2)
Pathophysiology - theories Ischemic necrosis – Most tumors are not that big Ischemia and infarction 2 o compression of stalk and superior hypophyseal artery. Most vessels from inferior hypophyseal artery Intrinsic vasculopathy of tumors. Pit. tumors >5x more likely to bleed than other intracranial tumors Is primary event hemorrhagic or ischemic? Hemorrhage seen in 100%, ischemic necrosis in 60%
Pathophysiology The anterior pituitary gland is perfused by its portal venous system contributes to frequency of pituitary apoplexy causing ischemia and subsequent necrosis
Signs and Symptoms Variable, depending on which features of apoplexy predominate Tumor expansion - Upward Visual fields and acuity Hypothalamic dysfunction: temp, BP, cardio-resp dysfunc., altered consciousness, other neurol sx. - Lateral Ophthalmoplegia, V nerve dysfunction, internal carotid artery compression - Downward Asymptomatic or epistaxis
Signs and Symptoms Subarachnoid bleeding - Meningeal irritation and photophobia - Aseptic meningitis Endocrine disturbances
Presenting Signs and Symptoms Headache Percent 85 Visual field or acuity reduction63 Ocular palsies49 Nausea and vomiting42 Meningismus17 Decreased level of consciousness16 Photophobia10 Fever7 (9 series over 30 year period; n = 272) Roleh et al,1993; Bills et al, 1993; Bonicki et al,1993; Randeva et al,1999 - Evolution: few hours to 2 days - Symptom severity proportional to tumor size - Headaches generally precede ocular manifestations
headache sudden and postulated to result from stretching and irritation of the dura mater irritation of the trigeminal nerve from the expanding mass retro-orbital in location and may be unilateral at onset, then becomes generalized
Ocular involvement Visual acuity defects (52%) and visual field defects (64%) upward expansion of the tumor, which compresses the optic chiasm, optic tracts, or optic nerve The classic visual field defect is a bitemporal superior quadrantic defect
Ocular involvement Ocular paresis (78%) results from compression of the cavernous sinus the oculomotor nerve (cranial nerve III) is involved most commonly a unilateral dilated pupil, ptosis, and a globe that is deviated inferiorly and laterally The sixth cranial nerve is least commonly involved
Pituitary apoplexy can occur in ectopic sites Hori examined normal adult brains at autopsy and found ectopic pituitary cells in the lepto- meninges of the peri-infundibular region in 75%. Ectopic pituitary adenomas commonly present late because they displace rather than invade vital nervous structures. They may be discovered only after the patient has pituitary apoplexy. Only one case of an ectopic pituitary adenoma that underwent apoplexy has been reported.
Endocrine Disturbances Sudden onset – features of adrenal insufficiency predominate Other abnormalities reflect underlying tumor: hormone hypersecretion (GH, Prl, ACTH, TSH) and hypopituitarism GH deficiency88% Gonadal deficiency Male86% Female52% Adrenal insufficiency Hypothyroidism 71% 46% Hyperprolactinemia12% Diabetes insipidus2-3% - and - resolution of hypersecretory syndromes Data from Veldhuis & Hammond, 1980 and Randeva et al, 1999
Precipitating Events In half of cases (from series), no precipitating event recorded Publications in past 15 years (300) Irradiation – no evidence Sudden changes in BP or ICP, often associated with procedures - Angiography, LP, PEG, repetitive coughing, surgical procedures - primarily cardiac (15) Head trauma (4) Anticoagulation and clotting disorders (5) Releasing hormones – for dx (31) and rx (6) Bromocriptine (8)
Sheehan syndrome pituitary apoplexy of a nontumorous gland presumably due to postpartum arterial spasm of arterioles supplying the anterior pituitary and its stalk. In 1937, Sheehan reported 11 cases of women who died in the puerperium all of whom had necrosis of the anterior pituitary gland (adenohypophysis). Nine of the 11 cases had severe hemorrhage at delivery. The other 2 cases had no hemorrhage but were gravely ill prior to delivery
Sheehan syndrome Normally, the pituitary gland hypertrophies in pregnancy from diffuse nodular hyperplasia of prolactin secreting cells Usually, at least 1-2 liters of blood loss and hypovolemic shock 1-2% of women suffering significant postpartum hemorrhage inability to lactate after delivery due to prolactin deficiency occurs and amenorrhea due to gonadotrophin deficiency classically develops
Sheehan syndrome after delivery, shaved pubic hair or axillary pubic hair fails to regrow, and waxy skin depigmentation develops Signs of hypothyroidism and hypoadrenalism may develop posterior pituitary (neurohypophysis) involvement with diabetes insipidus may occur clinical presentation of acute pituitary apoplexy has only been reported case
CT Findings in Pituitary Apoplexy Non-contrast CT is hyperdense in acute stage and may be more specific than MRI which is often isodense Ring sign, if present is diagnostic Useful to exclude subarachnoid hemorrhage acutely However, no pathognomonic findings
3 weeks later 6 months later MacCagnan P et al, JCEM 80:2190, 1995 Time of diagnosis 5 days
Therapy Medical – Acute –Glucocorticoids in doses to cover acute stress at time dx made or suspected: hydrocortisone, 300mg/d –Use of larger doses in presence of severe neurologic deficits, i.e., decreased states of consciousness; rationale anecdotal –Fluid and electrolyte replacement as needed Medical – Chronic –Replacement therapy for hypopituitarism, as appropriate upon testing
Therapy Surgical –Considerable controversy in literature –In early reports, recommended for all patients –Subsequent reports suggested many patients can be managed medically –Two major endpoints to consider: Recovery of visual acuity, visual fields, and oculomotor fx. Preservation / recovery of pituitary function
<8 days>8 days<8 days>8 days<8 days>8 days Percent 0 20 40 60 80 100 Complete recovery Partial recovery No improvement Visual AcuityVisual FieldsOcular Paresis Randeva et al, 1999 Visual Outcome and Timing of Surgery
Mean Days to Surgery 2.2 6.0 7.7 Percent requiring replacement 0 20 40 60 80 100 Arafah et al, 90 n=8 Randeva et al, 99 n=35 Bills et al, 93 n=37 Glucocorticoids Thyroxine Testosterone Vasopressin/DDAVP Hormone Replacement and Timing of Surgery
Summary Classical pituitary apoplexy is an acute clinical syndrome that has life-threatening consequences, requiring immediate medical and frequently surgical therapy. Although hemorrhage into a pituitary macroadenoma is the typical setting, it may be the first manifestation of the tumor. In more than half of the cases clinical manifestations are milder or nonexistent.
Summary (2) Immediate institution of glucocorticoid therapy is essential when the diagnosis is suspected because of the high frequency of adrenal insufficiency. Controversy exists concerning the need for surgical therapy in all cases. However, in patients with oculoparesis and visual field impairment, early surgical intervention results in better functional recovery.
Summary (3) Early surgical intervention also appears to improve the retention and/or recovery of pituitary function. Re-bleeding commonly occurs irrespective of previous therapy and careful follow-up is important.