Pituitary apoplexy differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Overview

Pituitary apoplexy must be differentiated from other diseases that cause severe headache such as subarachnoid hemorrhage, meningitis, intracranial mass, cerebral hemorrhage, cerebral infarction, intracranial venous thrombosis, migraine, head injury, and lymphocytic hypophysitis.

Differentiating Pituitary apoplexy From Other Diseases

Pituitary apoplexy should be differentiated from other diseases causing severe headache for example:

Onset	Disease	Symptoms		Gold Standard Test	CT/MRI Findings	Other Investigation Findings
		Headache Characteristics	Associated Features
Sudden	Pituitary apoplexy	Severe headache	Nausea and vomiting Paralysis of eye muscles (diplopia) Changes in vision	MRI	CT scan without contrast is the initial test of choice. Pituitary hemorrhage on CT presents as a hyper-dense lesion MRI is done in cases of inconclusive CT. An MRI is more sensitive in identifying intrasellar mass and soft tissue changes	Blood tests may be done to check: PT/INR and aPTT Pituitary hormonal assay
	Subarachnoid hemorrhage	Severe headache Thunderclap Described as the worst headache of life	Double vision Nausea and vomiting Symptoms of meningeal irritation Sudden decreased level of consciousness	Digital subtraction angiography	The modality of choice for diagnosis of subarachnoid hemorrhage is non-contrast head computed tomography (CT), with or without lumbar puncture.[1] CT shows hyperattenuating material filling the subarachnoid space	Lumbar puncture (LP) is necessary when there is a strong suspicion of subarachnoid hemorrhage. LP will show: Elevated opening pressure Elevated red blood cell (RBC) Xanthochromia
	Meningitis	Headache is associated with: Fever Neck stiffness	Photophobia    Phonophobia  Irritability Altered mental status	Lumbar puncture for CSF	CT scan of the head may be performed before LP to determine the risk of herniation	Diagnosis is based on clinical presentation in combination with CSF analysis CSF analysis is the investigation of choice For more information on CSF analysis in meningitis please click here
	Cerebral hemorrhage	Rapidly progressing headache	Nausea Vomiting Diplopia Focal neurological deficits	CT without contrast (differentiates ischemic stroke from hemorrhagic stroke)	CT is highly sensitive for identifying acute hemorrhage which appears as a hyperattenuating clot. Gradient echo and T2 susceptibility-weighted MRI are as sensitive as CT for detection of acute hemorrhage and are more sensitive for identification of prior hemorrhage	PT/INR and aPTT should be checked to rule out coagulopathy
	Migraine	Severe to moderate headache One-sided Pulsating Lasts between several hours to three days	Nausea and vomiting Preceding aura Photophobia Phonophobia	---	CT and MRI may be needed to rule out other suspected possible causes of headache	Migraine is a clinical diagnosis that does not require any laboratory tests. Laboratory tests may be ordered to rule out any suspected coexistent metabolic problems
	Head injury (Epidural hematoma)	Dull Throbbing One sided or all around	Confusion Drowsiness Personality change Seizures Nausea and vomiting Loss of consciousness Lucid interval	CT scan without contrast	CT scan is the first test performed and identifies cerebral hemorrhage (appears as a hyperattenuating clot) following head injury MRI is more sensitive, takes more time, and is done in patients with symptoms unexplained by CT scan	The Glasgow Coma Scale is a tool for measuring degree of unconsciousness and is a useful tool for determining severity of injury The Pediatric Glasgow Coma Scale is used in young children
	Lymphocytic hypophysitis	Generalized headache Retro-orbital or Bitemporal pain	Most often seen in late pregnancy or the postpartum period Mass lesion effect such as visual field defects Hypopituitarism	Pituitary biopsy	CT & MRI typically reveal features of a pituitary mass	The most accurate test is a pituitary biopsy which will show lymphocytic infiltration
Gradual	Intracranial mass	Morning headache	Nausea Vomiting Change in mental status Seizures Focal neurological deficits	MRI	CT or MRI is the initial test to detect intracranial lesions (ring enhancing lesions) These imaging tests determine the location of intracranial mass lesion(s) and help in guiding therapy	Biopsy of the lesion may be done to identify the nature of the lesion such as: Tumor Abscess X-ray of the skull is a non specific test, but useful if any of the lesions are calcified
	Intracranial venous thrombosis	Diffuse headache Headache can be the only symptom of cerebral venous thrombosis	Focal neurological deficits Seizures Depressed level of consciousness	Digital subtraction angiography	The classic finding of sinus thrombosis on unenhanced CT images is a hyperattenuating thrombus in the occluded sinus CT and MRI may identify Cerebral edema and venous infarction may be apparent	CT venography detects the thrombus, computed tomography with radiocontrast in the venous phase (CT venography or CTV) has a detection rate that in some regards exceeds that of MRI Cerebral angiography may demonstrate smaller clots, and obstructed veins may give the "corkscrew appearance"

Pituitary apoplexy should be differentiated from other diseases causing hypopituitarism.

Diseases	Onset	Manifestations					Diagnosis
		History and Symptoms				Physical examination	Laboratory findings	Gold standard	Imaging	Other investigation findings
		Traumatic delivery	Lactation failure	Menstrual irregularities	Other features
Sheehan's syndrome	Acute	++	++	Oligo/amenorrhea	Symptoms of: Adrenal insufficiency Hypothyroidism	Breast tissue atrophy Decreased axillary and pubic hair growth	Pancytopenia Eosinophilia Hyponatremia Low fasting plasma glucose Decreased levels of anterior pituitary hormones in blood	Clinical diagnosis Most senitive test: Low baseline prolactin levels w/o response to TRH	CT/MRI: Sequential changes of pituitary enlargement followed by: Shrinkage and necrosis leading to decreased sellar volume or empty sella	Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Lymphocytic hypophysitis	Acute	+/-	+	Oligo/amenorrhea	Associated with autoimmune conditions Generalized headache Retro-orbital or Bitemporal pain Mass lesion effect such as visual field defects	DI Autoimmune thyroiditis	Decreased pituitary hormones(Gonadotropins most common) Hyperprolactinemia(40%) GH excess	Pituitary biopsy: lymphocytic infiltration	CT & MRI: Features of a pituitary mass Diffuse and homogeneous contrast enhancement	Assays for: Anti-TPO Anti-Tg Ab
Pituitary apoplexy	Acute	+/-	++	Oligo/amenorrhea	Severe headache Nausea and vomiting Paralysis of eye muscles (diplopia) Changes in vision	Visual acuity defects CN palsies (nerves III, IV, V , and VI)	Decreased levels of anterior pituitary hormones in blood.	MRI	CT scan without contrast: Hemorrhage on CT presents as a hyperdense lesion MRI: If inconclusive CT	Blood tests may be done to check: PT/INR and aPTT Pituitary hormonal assay
Empty sella syndrome	Chronic	-	+	Oligo/amenorrhea	Erectile dysfunction Headache Low libido	Signs of raised intracranial pressure may be present Nipple discharge	Decreased levels of pituitary hormones in blood.	MRI	Empty sella containing CSF	Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Simmonds' disease/Pituitary cachexia	Chronic	+/-	+	Oligo/amenorrhea	Cachexia Premature aging	Progressive emaciation Loss of body hair	Decreased levels of anterior pituitary hormones in blood.	MRI	Done to rule out any pituitary cause	Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Hypothyroidism	Chronic	+/-	-	Oligomenorrhea/menorrhagia	Cold intolerance Constipation	Dry skin Bradycardia Hair loss Myxedema Delayed relaxation phase of deep tendon reflexes	Low T3,T4 Normal/ low TSH Rest of pituitary hormone levels WNL	TSH levels	Done to rule out any pituitary cause	Assays for anti-TPO and anti-Tg Ab FNA biopsy
Hypogonadotropic hypogonadism	Chronic	-	-	Oligo/amenorrhea	Hot flushes Energy and mood changes Decreased libido	Breast tissue atrophy Decreased maturation of vaginal mucosa	Low estrogen, testosterone High FSH/LH	FSH LH	Done to rule out any pituitary cause	Genetic tests  (karyotype) Measurement of total and free testosterone and 17-hydroxyprogesterone concentrations
Hypoprolactinemia	Chronic	-	+	-	Infertility Subfertiliy	Puerperal agalactogenesis	No workup is necessary	Decreased prolactin levels	Done to rule out any pituitary cause	Prolactin assay in 3rd trimester LH, FSH Thyrotropin and free thyroxine
Panhypopituitarism	Chronic	-	+	Oligo/amenorrhea	Polyuria Polydipsia Features of hypothyroidism and hypoadrenalism	Growth failure B/L hemianopsia Papilledema	All pituitary hormones decreased	MRI	Done to rule out any pituitary cause	Left hand and wrist radiograph for bone age
Primary adrenal insufficiency/Addison's disease	Chronic	-	-	-	Hypoglycemia Hypotension	Dehydration Hyperpigmentation loss of pubic and axillary hair	Hyponatremia with/without hyperkalemia Plasma renin activity to aldosterone ratio	Abdominal CT	Abdominal CT	Serum cortisol testing Serum ACTH testing Anti-adrenal Ab testing
Menopause	Chronic	-	+/-	Oligo/amenorrhea	Hot flashes Insomnia Weight gain and bloating Mood changes	Vaginal atrophy Loss of pelvic muscle tone	↑ FSH ↓ Estradiol and inhibin	FSH > LH	Normal	Endometrial biopsy