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.

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.

Craniopharyngiomas are usually successfully managed with a combination of adjuvant chemotherapy and neurosurgery. Recent research describes the rare occurrence of malignant transformations of these normally benign tumors. Malignant craniopharyngiomas can occur at any age, are slightly more common in females, and are usually of the adamantinomatous type.

The malignant transformations can take years to occur (although 1 in 5 of the diagnosed cases were de novo transformations), hence the need for lengthier follow up in patients diagnosed with the more common benign forms.

There was no link found between malignancy and initial chemo-radiotherapy treatment, and the overall survival rate was very poor with median survival being 6 months post diagnosis of malignancy.

A recommend surveillance program for Multiple Endocrine Neoplasia Type 1 has been suggested by the International Guidelines for Diagnosis and Therapy of MEN syndromes group.

There are a few scans and tests that the physician can conduct in order to diagnose a person with craniopharyngioma. Your doctor may order a high-resolution magnetic resonance imaging (MRI) scan. This test is valuable because it allows the neuroradiologist to view the tumor from different angles.

In some cases, a powerful 3T (Tesla) MRI scanner can help define the location of critical brain structures affected by the tumor.The histologic pattern consists of nesting of squamous epithelium bordered by radially arranged cells. It is frequently accompanied by calcium deposition and may have a microscopic papillary architecture.A computed tomography (CT) scan is also a good diagnostic tool as it detects calcification in the tumor.

Two distinct types are recognized:

- Adamantinomatous craniopharyngiomas, which resemble ameloblastomas (the most common type of odontogenic tumor), are characterized by activating CTNNB1 mutations; and,

- Papillary craniopharyngiomas are characterized by BRAFv600E mutations.

In the adamantinomatous type, calcifications are visible on neuroimaging and are helpful in diagnosis.

The papillary type rarely calcifies. A vast majority of craniopharyngiomas in children are adamantiomatous whereas both subtypes are common in adults. Mixed type tumors also occur.

On macroscopic examination, craniopharyngiomas are cystic or partially cystic with solid areas. On light microscopy, the cysts are seen to be lined by stratified squamous epithelium. Keratin pearls may also be seen. The cysts are usually filled with a yellow, viscous fluid which is rich in cholesterol crystals. Of a long list of possible symptoms, the most common presentations include: headaches, growth failure, and bitemporal hemianopsia.

Common diagnostic techniques include:

- MRIs

- CAT scans

- blood samples.

Blood samples are assessed for the absence or presence of aldosterone and cortisol. Physical examinations are also useful in patients in order to examine vision, skin pigmentation, how the body replaces steroids, and the cranial nerves. Recent advancements in high-resolution MRIs allow for adenomas to be detected during the early stages of Nelson syndrome. Physical examination including height, weight, vital signs, blood pressure, eye examination, thyroid examination, abdominal examination, neurological examination, skin examination and pubertal staging needs to be assessed. Through blood pressure and pulse readings can indicate hypothyroidism and adrenal insufficiency. Hyper-pigmentation, hyporeflexia, and loss of vision can also indicate Nelson's syndrome when assessed together. Specifically for a child who might have Nelson's syndrome, the patient should be questioned about the symptoms of the disease, and well as symptoms of other diseases to narrow down which disease the patient presents with. The patient should be questioned about how often and to what degree headaches, visual disturbances, and symptoms associated with pituitary malfunction occur. Additionally, adrenal steroid replacement should be assessed, especially in children who have prior insufficiency associated wit

Fine Needle Aspiration Cytology (FNAC) is a cheap, simple, and safe method in obtaining cytological specimens for diagnosis by using a needle and a syringe. The "Bethesda System for Reporting Thyroid Cytopathology" is the system used to report whether the thyroid cytological specimen is benign or malignant. It can be divided into six categories:

Repeated FNAC is recommended for Category I, followed by clinical follow-up in Category II, repeat FNAC for Category III, and lobectomy for Category IV, near total-thyroidectomy/lobectomy for Category V, and near total thyroidectomy for Category VI. The risk of malignancy in a malignant FNAC report is 93.7% while for suspicious FNAC report, it is 18.9%.

Usually—depending on the interview of the patient and after a clinical exam which includes a neurological exam, and an ophthalmological exam—a CT scan and or MRI scan will be performed. A special dye may be injected into a vein before these scans to provide contrast and make tumors easier to identify. The neoplasm will be clearly visible.

If a tumor is found, it will be necessary for a neurosurgeon to perform a biopsy of it. This simply involves the removal of a small amount of tumorous tissue, which is then sent to a (neuro)pathologist for examination and staging. The biopsy may take place before surgical removal of the tumor or the sample may be taken during surgery.

Multiple Endocrine Neoplasia type 1 (MEN1) is a rare hereditary endocrine cancer syndrome characterized primarily by tumors of the parathyroid glands (95% of cases), endocrine gastroenteropancreatic (GEP) tract (30-80% of cases), and anterior pituitary (15-90% of cases). Other endocrine and non-endocrine neoplasms including adrenocortical and thyroid tumors, visceral and cutaneous lipomas, meningiomas, facial angiofibromas and collagenomas, and thymic, gastric, and bronchial carcinoids also occur. The phenotype of MEN1 is broad, and over 20 different combinations of endocrine and non-endocrine manifestations have been described. MEN1 should be suspected in patients with an endocrinopathy of two of the three characteristic affected organs, or with an endocrinopathy of one of these organs plus a first-degree relative affected by MEN1 syndrome.

MEN1 patients usually have a family history of MEN1. Inheritance is autosomal dominant; any affected parent has a 50% chance to transmit the disease to his or her progeny. MEN1 gene mutations can be identified in 70-95% of MEN1 patients.

Many endocrine tumors in MEN1 are benign and cause symptoms by overproduction of hormones or local mass effects, while other MEN1 tumors are associated with an elevated risk for malignancy. About one third of patients affected with MEN1 will die early from an MEN1-related cancer or associated malignancy. Entero-pancreatic gastrinomas and thymic and bronchial carcinoids are the leading cause of morbidity and mortality. Consequently, the average age of death in untreated individuals with MEN1 is significantly lower (55.4 years for men and 46.8 years for women) than that of the general population.

Ultrasound imaging is useful as the first-line, non-invasive investigation in determining the size, texture, position, and vascularity of a nodule, accessing lymph nodes metastasis in the neck, and for guiding fine needle aspiration cytology (FNAC) or biopsy. High frequency transducer (7–12 MHz) is used to scan the thyroid nodule, while taking cross-sectional and longitudinal sections during scan. Suspicious findings in a nodule are hypoechoic, ill-defined margins, absence of peripheral halo or irregular margin, fine, punctate microcalcifications, presence of solid nodule, high levels of irregular blood flow within the nodule or "taller-than-wide sign" (anterior-posterior diameter is greater than transverse diameter of a nodule). Features of benign lesion are: hyperechoic, having coarse, dysmorphic or curvilinear calcifications, comet tail artifact (reflection of a highly calcified object), absence of blood flow in the nodule, and presence of cystic (fluid-filled) nodule. However, the presence of solitary or multiple nodules is not a good predictor of malignancy. Malignancy is only diagnosed when ultrasound findings and FNAC report are suggestive of malignancy. Another imaging modality, which is ultrasound elastography, is also useful in diagnosing thyroid malignancy especially for follicular thyroid cancer. However, it is limited by the presence of adequate amount of normal tissue around the lesion, calcified shell around a nodule, cystic nodules, coalescent nodules.

It is important to exclude a tumor which is directly extending into the ear canal from the parotid salivary gland, especially when dealing with an adenoid cystic or mucoepidermoid carcinoma. This can be eliminated by clinical or imaging studies. Otherwise, the histologic differential diagnosis includes a ceruminous adenoma (a benign ceruminous gland tumor) or a neuroendocrine adenoma of the middle ear (middle ear adenoma).

Common treatments for Nelson's syndrome include radiation or surgical procedure. Radiation allows for the limitation of the growth of the pituitary gland and the adenomas. If the adenomas start to affect the surrounding structures of the brain, then a micro-surgical technique can be adapted in order to remove the adenomas in a transsphenoidal (bone at base of the skull) process. Death may result with development of a locally aggressive pituitary tumor. However, does not commonly occur with pituitary diseases. In the rare case, ACTH-secreting tumors can become malignant. Morbidity from the disease can occur due to pituitary tissue compression or replacement, and compression of structures that surround the pituitary fossa. The tumor can also compress the optic apparatus, disturb cerebrospinal fluid flow, meningitis, and testicular enlargement in rare cases.

An endocrine gland neoplasm is a neoplasm affecting one or more glands of the endocrine system.

Examples include:

- Adrenal tumor

- Pituitary adenoma

The most common form is thyroid cancer.

Condition such as pancreatic cancer or ovarian cancer can be considered endocrine tumors, or classified under other systems.

Pinealoma is often grouped with brain tumors because of its location.

Microscopically, an astrocytoma is a mass that looks well-circumscribed and has a large cyst. The neoplasm may also be solid.

Under the microscope, the tumor is seen to be composed of bipolar cells with long "hairlike" GFAP-positive processes, giving the designation "pilocytic" (that is, made up of cells that look like fibers when viewed under a microscope). Some pilocytic astrocytomas may be more fibrillary and dense in composition. There is often presence of Rosenthal fibers, eosinophilic granular bodies and microcysts. Myxoid foci and oligodendroglioma-like cells may also be present, though non-specific. Long-standing lesions may show hemosiderin-laden macrophages and calcifications.

In a diagnostic workup individuals with a combination of endocrine neoplasias suggestive of the "MEN1 syndrome" are recommended to have a mutational analysis of the MEN1 gene if additional diagnostic criteria are sufficiently met, mainly including:

- age <40 years

- positive family history

- multifocal or recurrent neoplasia

- two or more organ systems affected

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.

The first step in diagnosing a thyroid neoplasm is a physical exam of the neck area. If any abnormalities exist, a doctor needs to be consulted. A family doctor may conduct blood tests, an ultrasound, and nuclear scan as steps to a diagnosis. The results from these tests are then read by an endocrinologist who will determine what problems the thyroid has.

Hyperthyroidism and hypothyroidism are two conditions that often arise from an abnormally functioning thyroid gland. These occur when the thyroid is producing too much or too little thyroid hormone respectively.

Thyroid nodules are a major presentation of thyroid neoplasms, and are diagnosed by ultrasound guided fine needle aspiration (USG/FNA) or frequently by thyroidectomy (surgical removal and subsequent histological examination). FNA is the most cost-effective and accurate method of obtaining a biopsy sample. As thyroid cancer can take up iodine, radioactive iodine is commonly used to treat thyroid carcinomas, followed by TSH suppression by high-dose thyroxine therapy.

Nodules are of particular concern when they are found in those under the age of 20. The presentation of benign nodules at this age is less likely, and thus the potential for malignancy is far greater.

Serous cystic neoplasms can come to clinical attention in a variety of ways. The most common symptoms are very non-specific and include abdominal pain, nausea and vomiting. In contrast to many of the other tumors of the pancreas, patients rarely develop jaundice (a yellowing of the skin and eyes caused by obstruction of the bile duct), or weight loss. These signs and symptoms are not specific for a serous cystic neoplasm, making it more difficult to establish a diagnosis. Doctors will therefore often order additional tests.

Once a doctor has reason to believe that a patient may have serous cystic neoplasm, he or she can confirm that suspicion using one of a number of imaging techniques. These include computerized tomography (CT), endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP). These tests will reveal a cystic mass within the pancreas. The cysts do not communicate with the larger pancreatic ducts. In some cases a fine needle aspiration (FNA) biopsy can be obtained to confirm the diagnosis. Fine needle aspiration biopsy can be performed through an endoscope at the time of endoscopic ultrasound, or it can be performed through the skin using a needle guided by ultrasound or CT scanning.

A growing number of patients are now being diagnosed before they develop symptoms (asymptomatic patients). In these cases, the lesion in the pancreas is discovered accidentally (by chance) when the patient is being scanned (x-rayed) for another reason.

For the diagnosis of hyperpituitarism it depends on the cell type(s) affected, clinical manifestations of hormone excess may include, gigantism or acromegaly, which can be identified by clinical and radiographic results. Cushing's disease diagnosis is done with a physical examination, laboratory tests and X rays of the pituitary glands (to locate tumors) For prolactinoma, diagnosis comes in the form of the measurement of serum prolactin levels and x-ray of pituitary gland.

If one of these tests shows a deficiency of hormones produced by the pituitary, magnetic resonance imaging (MRI) scan of the pituitary is the first step in identifying an underlying cause. MRI may show various tumors and may assist in delineating other causes. Tumors smaller than 1 cm are referred to as "microadenomas", and larger lesions are called "macroadenomas". Computed tomography with radiocontrast may be used if MRI is not available. Formal visual field testing by perimetry is recommended, as this would show evidence of optic nerve compression by a tumor.

Other tests that may assist in the diagnosis of hypopituitarism, especially if no tumor is found on the MRI scan, are ferritin (elevated in hemochromatosis), angiotensin converting enzyme (ACE) levels (often elevated in sarcoidosis), and human chorionic gonadotropin (often elevated in tumor of germ cell origin). If a genetic cause is suspected, genetic testing may be performed.

Multiple endocrine neoplasia type 1 (MEN-1 syndrome) or Wermer's syndrome is part of a group of disorders, the multiple endocrine neoplasias, that affect the endocrine system through development of neoplastic lesions in pituitary, parathyroid gland and pancreas.

Pituicytoma is a rare brain tumor. It grows at the base of the brain from the pituitary gland. This tumor is thought to be derived from the parenchymal cells of the posterior lobe of the pituitary gland, called pituicytes. Some researchers believe that they arise from the folliculostellate cells in the anterior lobe of the pituitary. As such, it is a low-grade glioma. It occurs in adults and symptoms include visual disturbance and endocrine dysfunction. They are often mistaken for pituitary adenomas which have a similar presentation and occur in the same location. The treatment consists of surgical resection, which is curative in most cases.

If acromegaly is suspected, medical imaging and medical laboratory investigations are generally used together to confirm or rule out the presence of this condition.

IGF1 provides the most sensitive lab test for the diagnosis of acromegaly, and a GH suppression test following an oral glucose load, which is a very specific lab test, will confirm the diagnosis following a positive screening test for IGF1. A single value of the GH is not useful in view of its pulsatality (levels in the blood vary greatly even in healthy individuals). GH levels taken 2 hours after a 75- or 100-gram glucose tolerance test are helpful in the diagnosis: GH levels are suppressed below 1 μg/l in normal people, and levels higher than this cutoff are confirmatory of acromegaly.

Other pituitary hormones must be assessed to address the secretory effects of the tumor, as well as the mass effect of the tumor on the normal pituitary gland. They include thyroid stimulating hormone (TSH), gonadotropic hormones (FSH, LH), adrenocorticotropic hormone, and prolactin.

An MRI of the brain focusing on the sella turcica after gadolinium administration allows for clear delineation of the pituitary and the hypothalamus and the location of the tumor. A number of other overgrowth syndromes can result in similar problems.

A doctor will test for prolactin blood levels in women with unexplained milk secretion (galactorrhea) or irregular menses or infertility, and in men with impaired sexual function and, in rare cases, milk secretion. If prolactin is high, a doctor will test thyroid function and ask first about other conditions and medications known to raise prolactin secretion. The doctor will also request a magnetic resonance imaging (MRI), which is the most sensitive test for detecting pituitary tumors and determining their size. MRI scans may be repeated periodically to assess tumor progression and the effects of therapy. Computed Tomography (CT scan) also gives an image of the pituitary, but it is less sensitive than the MRI.

In addition to assessing the size of the pituitary tumor, doctors also look for damage to surrounding tissues, and perform tests to assess whether production of other pituitary hormones is normal. Depending on the size of the tumor, the doctor may request an eye exam with measurement of visual fields.

Diagnosis is made first by diagnosing Cushing's syndrome, which can be difficult to do clinically since the most characteristic symptoms only occur in a minority of patients. Some of the biochemical diagnostic tests used include salivary and blood serum cortisol testing, 24-hour urinary free cortisol (UFC) testing, the dexamethasone suppression test (DST), and bilateral inferior petrosal sinus sampling (BIPSS). No single test is perfect and multiple tests should always be used to achieve a proper diagnosis. Diagnosing Cushing's disease is a multidisciplinary process involving doctors, endocrinologists, radiologists, surgeons, and chemical pathologists.

Once Cushing's syndrome has been diagnosed, the first step towards finding the cause is measuring plasma corticotropin concentrations. A concentration consistently below 1.1 pmol/L is classified as corticotropin-independent and does not lead to a diagnosis of Cushing's disease. In such cases, the next step is adrenal imaging with CT. If plasma corticotropin concentrations are consistently above 3.3 pmol/L, then corticotropin-dependent Cushing's syndrome is most likely. Any intermediate values need to be cautiously interpreted and a corticotropin-releasing hormone (CRH) test is advised in order to confirm corticotropin dependency. If corticotropin-dependent Cushing's syndrome is determined then the next step is to distinguish between Cushing's disease and ectopic corticotropin syndrome. This is done via a combination of techniques including CRH, high-dose DST, BIPSS, and pituitary MRI.

Two dexamethasone suppression tests (DSTs) are generally used, the overnight and 48-h DSTs. For both tests, a plasma cortisol level above 50 nmol/L is indicative of Cushing's disease. However, 3-8% of patients with Cushing's disease will test negative due to a retention of dexamethasone suppression abilities. For non-Cushing or healthy patients, the false-positive rate is 30%. The 48-h DST is advantageous since it is more specific and can be done by outpatients upon proper instruction. In the high-dose 48-h DST, 2 mg of dexamethasone is given every 6 hours for 48 hours or a single dose of 8 mg is given. This test is not needed if the 48-h low-dose DST has shown suppression of cortisol by over 30%. These tests are based on the glucocorticoid sensitivity of pituitary adenomas compared to non-pituitary tumors.

Administration of corticotropin releasing hormone (CRH) can differentiate this condition from ectopic ACTH secretion. In a patient with Cushing's disease, the tumor cells will be stimulated to release corticotropin and elevated plasma corticotropin levels will be detected. This rarely occurs with ectopic corticotropin syndrome and thus is quite useful for distinguishing between the two conditions. If ectopic, the plasma ACTH and cortisol levels should remain unchanged; if this is pituitary related, levels of both would rise. The CRH test uses recombinant human or bovine-sequence CRH, which is administered via a 100μg intravenous bolus dose. The sensitivity of the CRH test for detecting Cushing's disease is 93% when plasma levels are measured after fifteen and thirty minutes. However, this test is used only as a last resort due to its high cost and complexity.

A CT or MRI of the pituitary may also show the ACTH secreting tumor if present. However, in 40% of Cushing's disease patients MRI is unable to detect a tumor. In one study of 261 patients with confirmed pituitary Cushing's disease, only 48% of pituitary lesions were identified using MRI prior to surgery. The average size of tumor, both those that were identified on MRI and those that were only discovered during surgery, was 6 mm.

A more accurate but invasive test used to differentiate pituitary from ectopic or adrenal Cushing's syndrome is inferior petrosal sinus sampling. A corticotropin gradient sample via BIPSS is required to confirm diagnosis when pituitary MRI imaging and biochemical diagnostic tests have been inconclusive. A basal central:peripheral ratio of over 3:1 when CRH is administered is indicative of Cushing’s disease. This test has been the gold standard for distinguishing between Cushing's disease and ectopic corticotropin syndrome. The BIPSS has a sensitivity and specificity of 94% for Cushing's disease but it is usually used as a last resort due to its invasiveness, rare but serious complications, and the expertise required to perform it.

Another diagnostic test used is the urinary free cortisol (UFC) test, which measures the excess cortisol excreted by the kidneys into the urine. Results of 4x higher cortisol levels than normal are likely to be Cushing's disease. This test should be repeated three times in order to exclude any normally occurring periods of hypercortisolism. The UFC test has a specificity of 81% and thus has a high rate of false-positives that are due to pseudo-Cushing states, sleep apnea, polycystic ovary syndrome, familial glucocorticoid resistance, and hyperthyroidism.

The late-night or midnight salivary cortisol test has been gaining support due to its ease of collection and stability at room temperature, therefore it can be assigned to outpatients. The test measures free circulating cortisol and has both a sensitivity and specificity of 95-98%. This test is especially useful for diagnosing children.