The major differential to consider in empty sella syndrome is intracranial hypertension, of both unknown and secondary causes, and an epidermoid cyst, which can mimic cerebrospinal fluid due to its low density on CT scans, although MRI can usually distinguish the latter diagnosis.

The diagnosis of ESS, done via examination (and test), may be linked to early onset of puberty, growth hormone deficiency or pituitary gland dysfunction(at an early age). Additionally there is:

Tuber cinereum hamartoma may be associated with Pallister-Hall syndrome, a diagnosis characterized by multiple malformations, including polydactyly and imperforate anus. Neurologic symptoms are less severe in Pallister-Hall than in isolated cases of hamartoma.

The tumor is difficult to detect by CT due to decreased sensitivity of the scan at the level of the sella turcica. MRI is the primary imaging modality for detection, with the lesion being of similar signal intensity to gray matter and non-enhancing with contrast. Lack of enhancement is an important imaging characteristic to help distinguish the tumor from similar masses that can occur in this region. These include germ cell tumors, granulomas of Langerhans cell histiocytosis and hypothalamic astrocytomas, as these lesions usually demonstrate at least partial uptake of contrast.

It is recommended that magnetic resonance imaging (MRI) scan of the pituitary gland is performed if the diagnosis is suspected; this has a sensitivity of over 90% for detecting pituitary apoplexy; it may demonstrate infarction (tissue damage due to a decreased blood supply) or hemorrhage. Different MRI sequences can be used to establish when the apoplexy occurred, and the predominant form of damage (hemorrhage or infarction). If MRI is not suitable (e.g. due to claustrophobia or the presence of metal-containing implants), a computed tomography (CT) scan may demonstrate abnormalities in the pituitary gland, although it is less reliable. Many pituitary tumors (25%) are found to have areas of hemorrhagic infarction on MRI scans, but apoplexy is not said to exist unless it is accompanied by symptoms.

In some instances, lumbar puncture may be required if there is a suspicion that the symptoms might be caused by other problems (meningitis or subarachnoid hemorrhage). This is the examination of the cerebrospinal fluid that envelops the brain and the spinal cord; the sample is obtained with a needle that is passed under local anesthetic into the spine. In pituitary apoplexy the results are typically normal, although abnormalities may be detected if blood from the pituitary has entered the subarachnoid space. If there is remaining doubt about the possibility of subarachnoid hemorrhage (SAH), a magnetic resonance angiogram (MRI with a contrast agent) may be required to identify aneurysms of the brain blood vessels, the most common cause of SAH.

Professional guidelines recommend that if pituitary apoplexy is suspected or confirmed, the minimal blood tests performed should include a complete blood count, urea (a measure of renal function, usually performed together with creatinine), electrolytes (sodium and potassium), liver function tests, routine coagulation testing, and a hormonal panel including IGF-1, growth hormone, prolactin, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, thyroid hormone, and either testosterone in men or estradiol in women.

Visual field testing is recommended as soon as possible after diagnosis, as it quantifies the severity of any optic nerve involvement, and may be required to decide on surgical treatment.

Mainly, the diagnosis of hypophysitis is through exclusion – patients often undergo surgery because they are suspected of having a pituitary adenoma. But, the most accurate diagnosis is using Magnetic Resonance Imaging (MRI) to find any mass or lesions on the Sella Turcica.

Neuroimaging, usually with computed tomography (CT/CAT) or magnetic resonance imaging (MRI), is used to exclude any mass lesions. In IIH these scans typically appear to be normal, although small or slit-like ventricles, dilatation and buckling of the optic nerve sheaths and "empty sella sign" (flattening of the pituitary gland due to increased pressure) and enlargement of Meckel's caves may be seen.

An MR venogram is also performed in most cases to exclude the possibility of venous sinus stenosis/obstruction or cerebral venous sinus thrombosis. A contrast-enhanced MRV (ATECO) scan has a high detection rate for abnormal transverse sinus stenoses. These stenoses can be more adequately identified and assessed with catheter cerebral venography and manometry. Buckling of the bilateral optic nerves with increased perineural fluid is also often noted on MRI imaging.

Lumbar puncture is performed to measure the opening pressure, as well as to obtain cerebrospinal fluid (CSF) to exclude alternative diagnoses. If the opening pressure is increased, CSF may be removed for transient relief (see below). The CSF is examined for abnormal cells, infections, antibody levels, the glucose level, and protein levels. By definition, all of these are within their normal limits in IIH. Occasionally, the CSF pressure measurement may be normal despite very suggestive symptoms. This may be attributable to the fact that CSF pressure may fluctuate over the course of the normal day. If the suspicion of problems remains high, it may be necessary to perform more long-term monitoring of the ICP by a pressure catheter.

The original criteria for IIH were described by Dandy in 1937.

They were modified by Smith in 1985 to become the "modified Dandy criteria". Smith included the use of more advanced imaging: Dandy had required ventriculography, but Smith replaced this with computed tomography. In a 2001 paper, Digre and Corbett amended Dandy's criteria further. They added the requirement that the patient is awake and alert, as coma precludes adequate neurological assessment, and require exclusion of venous sinus thrombosis as an underlying cause. Furthermore, they added the requirement that no other cause for the raised ICP is found.

In a 2002 review, Friedman and Jacobson propose an alternative set of criteria, derived from Smith's. These require the absence of symptoms that could not be explained by a diagnosis of IIH, but do not require the actual presence of any symptoms (such as headache) attributable to IIH. These criteria also require that the lumbar puncture is performed with patient lying sideways, as a lumbar puncture performed in the upright sitting position can lead to artificially high pressure measurements. Friedman and Jacobson also do not insist on MR venography for every patient; rather, this is only required in atypical cases (see "diagnosis" above).

The prognosis for hypophysitis was variable for each individual. The depending factors for hypophysitis included the advancement of the mass on the Sella Turcica, percentage of fibrosis, and the body's response to corticosteroids. Through the use of Corticosteroids, the vision defects tend to recover when the gland size began to decrease. The prognoses of the limited number of reported cases were usually good.

Diagnosis of a cerebrospinal fluid leak is performed through a combination of measurement of the CSF pressure and a computed tomography myelogram (CTM) scan of the spinal column for fluid leaks. The opening fluid pressure in the spinal canal is obtained by performing a lumbar puncture, also known as a spinal tap. Once the pressure is measured, a radiocontrast agent is injected into the spinal fluid. The contrast then diffuses out through the dura sac before leaking through dural holes. This allows for a CTM with fluoroscopy to locate and image any sites of dura rupture via contrast seen outside the dura sac in the imagery.

In larger case series, the mortality was 1.6% overall. In the group of patients who were unwell enough to require surgery, the mortality was 1.9%, with no deaths in those who could be treated conservatively.

After an episode of pituitary apoplexy, 80% of people develop hypopituitarism and require some form of hormone replacement therapy. The most common problem is growth hormone deficiency, which is often left untreated but may cause decreased muscle mass and strength, obesity and fatigue. 60–80% require hydrocortisone replacement (either permanently or when unwell), 50–60% need thyroid hormone replacement, and 60–80% of men require testosterone supplements. Finally, 10–25% develop diabetes insipidus, the inability to retain fluid in the kidneys due to a lack of the pituitary antidiuretic hormone. This may be treated with the drug desmopressin, which can be applied as a nose spray or taken by mouth.

When cranial CSF leak is suspected because of discharge from the nose or ear that is potentially CSF, the fluid can be collected and tested with a beta-2 transferrin assay. This test can positively identify if the fluid is cerebrospinal fluid.

No treatment is required, but neoplastic processes (metastatic maliganancy to the submandibular lymph nodes and/or salivary gland tumours) should be ruled out. This is usually done with clinical exam and imaging. Very rarely, since the defect contains salivary gland tissue, salivary gland tumors can occur within an established defect but there is likely no difference in the risk of neoplasia in salivary gland tissue at other sites.

Stafne's defect is usually discovered by chance during routine dental radiography. Radiographically, it is a well-circumscribed, monolocular, round, radiolucent defect, 1–3 cm in size, usually between the inferior alveolar nerve (IAN) and the inferior border of the posterior mandible between the molars and the angle of the jaw. It is one of the few radiolucent lesions that can occur below the IAN. The border is well corticated and it will have no effect on the surrounding structures. Computed tomography (CT) will show a shallow defect through the medial cortex of the mandible with a corticated rim and no soft tissue abnormalities, with the exception of a portion of the submandibular gland. Neoplasms, such as metastatic squamous cell carcinoma to the submandibular lymph nodes or a salivary gland tumour, could create a similar appearance but rarely have such well defined borders and can usually be palpated in the floor of the mouth or submandibular triangle of the neck as a hard mass. CT and clinical exam is typically sufficient to distinguish between this and a Stafne defect. The Stafne defect also tends to not increase in size or change in radiographic appearance over time (hence the term "static bone cyst"), and this can be used to help confirm the diagnosis. Tissue biopsy is not usually indicated, but if carried out, the histopathologic appearance is usually normal salivary gland tissue. Sometimes attempted biopsy of Stafne defects reveals an empty cavity (possibly because the gland was displaced at the time of biopsy), or other contents such as blood vessels, fat, lymphoid or connective tissues. Defects of the anterior lingual mandible may require biopsy for correct diagnosis at this unusual location. The radiolucent defect here may be superimposed on the lower anterior teeth and be mistaken for an odontogenic lesion. Sometimes the defect may interrupt the contour of the lower border of the mandible, and may be palpable. Sialography may be sometimes used to help demonstrate the salivary gland tissue within the bone.

Pituitary incidentalomas are pituitary tumors that are characterized as an incidental finding. They are often discovered by computed tomography (CT) or magnetic resonance imaging (MRI), performed in the evaluation of unrelated medical conditions such as suspected head trauma, in cancer staging or in the evaluation of nonspecific symptoms such as dizziness and headache. It is not uncommon for them to be discovered at autopsy. In a meta-analysis, adenomas were found in an average of 16.7% in postmortem studies, with most being microadenomas (<10mm); macrodenomas accounted for only 0.16% to 0.2% of the decedents. While non-secreting, noninvasive pituitary microadenomas are generally considered to be literally as well as clinically benign, there are to date scant studies of low quality to support this assertion.

It has been recommended in the current Clinical Practice Guidelines (2011) by the Endocrine Society - a professional, international medical organization in the field of endocrinology and metabolism - that all patients with pituitary incidentalomas undergo a complete medical history and physical examination, laboratory evaluations to screen for hormone hypersecretion and for hypopituitarism. If the lesion is in close proximity to the optic nerves or optic chiasm, a visual field examination should be performed. For those with incidentalomas which do not require surgical removal, follow up clinical assessments and neuroimaging should be performed as well follow-up visual field examinations for incidentalomas that abut or compress the optic nerve and chiasm and follow-up endocrine testing for macroincidentalomas.

A pineal gland cyst is a usually benign (non-malignant) cyst in the pineal gland, a small endocrine gland in the brain. Historically, these fluid-filled bodies appeared on of magnetic resonance imaging (MRI) brain scans, but were more frequent at death, seen in of autopsies. A 2007 study by Pu "et al". found a frequency of 23% in brain scans (with a mean diameter of 4.3 mm).

It was once believed that smaller cysts (less than 5.0 mm) were usually asymptomatic, but for larger cysts (greater than 5.0 mm), symptoms could include headache, unexpected seizures, visual disturbances, memory loss, cognitive decline, muscle fasciculations, nausea, weakness, fatigue, light sensitivity, tinnitus, circadian rhythm dysfunction, or hydrocephalus if the cyst impinged on the superior colliculi or caused obstruction of the cerebral aqueduct. Newer research shows that the size of the cyst does not necessarily correlate to the presence of symptoms. In some cases, it will need to be removed before life-threatening situations occur.

Despite the pineal gland being in the center of the brain, due to recent advancements in endoscopic medicine, endoscopic brain surgery to drain and/or remove the cyst can be done with the patient spending 1-3 nights in the hospital, and being fully recovered in weeks, rather than a year, as is the case with open-skull brain surgery.

The National Organization for Rare Disorders states that pineal cysts larger than 5.0 mm are "rare findings" and are possibly symptomatic. If narrowing of the cerebral aqueduct occurs, many neurological symptoms may exist, including headaches, vertigo, nausea, muscle fasciculations, eye sensitivity, and ataxia. Continued monitoring of the cyst might be recommended to monitor its growth, and surgery may be necessary.

In a small population of people with larger, symptomatic cysts, the following comorbid conditions have been noted: Pseudotumor cerebri (elevated intracranial pressure), empy sella, hormonal disturbances, flattened optic discs, chiari malformation, sjogren's, POTS, dysautonomia, PCOS.

Visual fields associated with chiasmal syndrome usually leads to an MRI. Contrast can delineate arterial aneurysms and will enhance most intrinsic chiasmal lesions. If a mass is confirmed on MRI, an endocrine panel can help determine if a pituitary adenoma is involved.

In patients with functional adenomas diagnosed by other means, visual field tests are a good screen to test for chiasmal involvement. Visual fields tests will delinate chiasmal syndromes because the missing fields will not cross the midline. Junctional scotomas classically show ipsilateral optic disc neuropathy with contralateral superotemporal defects. Bitemporal hemianopia with or without central scotoma is present if the lesions have affected the body of the chiasm. A posterior chiasm lesion should only produce defects on the temporal sides of the central visual field.

Although GH can be readily measured in a blood sample, testing for GH deficiency is constrained by the fact that levels are nearly undetectable for most of the day. This makes simple measurement of GH in a single blood sample useless for detecting deficiency. Physicians therefore use a combination of indirect and direct criteria in assessing GHD, including:

- Auxologic criteria (defined by body measurements)

- Indirect hormonal criteria (IGF levels from a single blood sample)

- Direct hormonal criteria (measurement of GH in multiple blood samples to determine secretory patterns or responses to provocative testing), in particular:

- Subnormal frequency and amplitude of GH secretory peaks when sampled over several hours

- Subnormal GH secretion in response to at least two provocative stimuli

- Increased IGF1 levels after a few days of GH treatment

- Response to GH treatment

- Corroborative evidence of pituitary dysfunction

"Provocative tests" involve giving a dose of an agent that will normally provoke a pituitary to release a burst of growth hormone. An intravenous line is established, the agent is given, and small amounts of blood are drawn at 15 minute intervals over the next hour to determine if a rise of GH was provoked. Agents which have been used clinically to stimulate and assess GH secretion are arginine, levodopa, clonidine, epinephrine and propranolol, glucagon and insulin. An insulin tolerance test has been shown to be reproducible, age-independent, and able to distinguish between GHD and normal adults, and so is the test of choice.

Severe GH deficiency in childhood additionally has the following measurable characteristics:

- Proportional stature well below that expected for family heights, although this characteristic may not be present in the case of familial-linked GH deficiency

- Below-normal velocity of growth

- Delayed physical maturation

- Delayed bone age

- Low levels of IGF1, IGF2, IGF binding protein 3

- Increased growth velocity after a few months of GH treatment

In childhood and adulthood, the diagnosing doctor will look for these features accompanied by corroboratory evidence of hypopituitarism such as deficiency of other pituitary hormones, a structurally abnormal pituitary, or a history of damage to the pituitary. This would confirm the diagnosis; in the absence of pituitary pathology, further testing would be required.

Unlike tumors of the posterior Pituitary, Pituitary adenomas are classified as endocrine tumors (not brain tumors). Pituitary adenomas are classified based upon anatomical, histological and functional criteria.

- Anatomically pituitary tumors are classified by their size based on radiological findings; either microadenomas (less than <10 mm) or macroadenomas (equal or greater than ≥10 mm).

- Histological classification utilizes an immunohistological characterization of the tumors in terms of their hormone production. Historically they were classed as either basophilic, acidophilic, or chromophobic on the basis of whether or not they took up the tinctorial stains hematoxylin and eosin. This classification has fallen into disuse, in favor of a classification based on what type of hormone is secreted by the tumor. Approximately 20-25% of adenomas do not secrete any readily identifiable active hormones ('non-functioning tumors') yet they are still sometimes referred to as 'chromophobic'.

- Functional classification is based upon the tumors endocrine activity as determined by serum hormone levels and pituitary tissue cellular hormone secretion detected via immunohistochemical staining. The "Percentage of hormone production cases" values are the fractions of adenomas producing each related hormone of each tumor type as compared to all cases of pituitary tumors, and does not directly correlate to the percentages of each tumor type because of smaller or greater incidences of absence of secretion of the expected hormone. Thus, nonsecretive adenomas may be either "null cell adenomas" or a more specific adenoma that, however, remains nonsecretive.

Though outwardly similar to cluster headaches, chronic paroxysmal hemicrania is rather different, and the two headaches are not a subset of one or the other. Key differences include:

- Different gender distributions – CPH is more common in women than men, with opposite occurring with cluster headaches.

- CPH attacks occur more frequently, but are shorter.

- Individuals with CPH are far more responsive to indomethacin than individuals with cluster headaches.

- CPH attacks can be provoked by neck movement.

- In a study conducted by Sjaastad, heating a patient's body will cause the painful side of the forehead to sweat more in CPH patients, while there will be less sweating on that side for those suffering from cluster headaches.

A ten-patient study conducted by Pareja et al. found that all patients diagnosed with CPH were responsive to indomethacin and were able to completely control their symptoms. Doses of the drug ranged from 25 mg per day to 150 mg per day with a median dose of 75 mg per 24-hour period.

Almost all cases of CPH respond positively and effectively to indometacin, but as much as 25 percent of patients discontinued use of the drug due to adverse side effects, namely complications in the gastrointestinal tract.

According to a case study by Milanlioglu et al., 100mg of lamotrigine, an antiepileptic drug, administered twice daily alleviated all painful symptoms. No side effects were noted after two months of treatment. Dosage of lamotrigine was decreased to 50mg a day after the first two months, and no symptoms or side-effects were recorded after a three-month followup.

Use of topiramate has also been found to be an effective treatment for CPH, but cluster headache medications have been found to have little effect.

No consensus criteria exist for the diagnosis of ENS; it is typically diagnosed by ruling out other conditions, with ENS remaining the likely diagnosis if the signs and symptoms are present. A "cotton test" has been proposed, in which moist cotton is held where a turbinate should be, to see if it provides relief; while this has not been validated nor is it widely accepted, it may be useful to identify which people may benefit from surgery.

As of 2015, protocols for using rhinomanometry to diagnose ENS and measure response to surgery were under development, as was a standardized clinical instrument (a well defined and validated questionnaire) to obtain more useful reporting of symptoms.

GH deficiency is treated by replacing GH with daily injections under the skin or into muscle. Until 1985, growth hormone for treatment was obtained by extraction from human pituitary glands collected at autopsy. Since 1985, recombinant human growth hormone (rHGH) is a recombinant form of human GH produced by genetically engineered bacteria, manufactured by recombinant DNA technology. In both children and adults, costs of treatment in terms of money, effort, and the impact on day-to-day life, are substantial.

Foroozen divides the causes of chiasmal syndromes into intrinsic and extrinsic causes. Intrinsic implies thickening of the chiasm itself and extrinsic implies compression by another structure. Other less common causes of chiasmal syndrome are metabolic, toxic, traumatic or infectious in nature.

Intrinsic etiologies include gliomas and multiple sclerosis. Gliomas of the optic chiasm are usually derived from astrocytes. These tumors are slow growing and more often found children. However, they have a worse prognosis, especially if they have extended into the hypothalamus. They are frequently associated with neurofibromatosis type 1 (NF-1). Their treatment involves the resection of the optic nerve. The supposed artifactual nature of Wilbrand's knee has implications for the degree of resection that can be obtained, namely by cutting the optic nerve immediately at the junction with the chiasm without fear of potentially resulting visual field deficits.

The vast majority of chiasmal syndromes are compressive. Ruben et al. describe several compressive etiologies, which are important to understand if they are to be successfully managed. The usual suspects are pituitary adenomas, craniopharyngiomas, and meningiomas.

Pituitary tumors are the most common cause of chiasmal syndromes. Visual field defects may be one of the first signs of non-functional pituitary tumor. These are much less frequent than functional adenomas. Systemic hormonal aberrations such as Cushing’s syndrome, galactorrhea and acromegaly usually predate the compressive signs. Pituitary tumors often encroach upon the middle chiasm from below. Pituitary apoplexy is one of the few acute chiasmal syndromes. It can lead to sudden visual loss as the hemorrhagic adenoma rapidly enlarges.

The embryonic remnants of Rathke’s pouch may undergo neoplastic change called a craniopharyngioma. These tumors may develop at any time but two age groups are most at risk. One peak occurs during the first twenty years of life and the other occurs between fifty and seventy years of age. Craniopharyngiomas generally approach the optic chiasm from behind and above. Extension of craniopharyngiomas into the third ventricle may cause hydrocephalus.

Meningiomas can develop from the arachnoid layer. Tuberculum sellae and sphenoid planum meningiomas usually compress the optic chiasm from below. If the meningioma arises from the diaphragma sellae the posterior chiasm is damaged. Medial sphenoid ridge types can push on the chiasm from the side. Olfactory groove subfrontal types can reach the chiasm from above. Meningiomas are also associated with neurofibromatosis type 1. Women are more prone to develop meningiomas.

Initial treatment is similar to atrophic rhinitis, namely keeping the nasal mucosa moist with saline or oil-based lubricants and treating pain and infection as they arise; adding menthol to lubricants may be helpful in ENS, as may be use of a cool mist humidifer at home. For people with anxiety, depression, or who are obsessed with the feeling that they can't breathe, psychiatric or psychological care may be helpful.

In some people, surgery to restore missing or reduced turbinates may be beneficial.

A 2015 meta-analysis identified 128 people treated with surgery from eight studies that were useful to pool, with an age range of 18 to 64, most of whom had been suffering ENS symptoms for many years. The most common surgical approach was creating a pocket under the mucosa and implanting material - the amount and location were based on the judgement of the surgeon. In about half the cases a filler such as noncellular dermis, a medical-grade porous high-density polyethylene, or silastic was used and in about 40% cartilage taken from the person or from a cow was used. In a few cases hyaluronic acid was injected and in a few others tricalcium phosphate was used. There were no complications caused by the surgery, although one person was over-corrected and developed chronic rhinosinusitis and two people were under-corrected. The hyaluronic acid was completely resorbed in the three people who received it at the one year follow up, and in six people some of the implant came out, but this did not affect the result as enough remained. About 21% of the people had no or marginal improvement but the rest reported significant relief of their symptoms. Since none of the studies used placebo or blinding there may be a strong placebo effect or bias in reporting.