An adrenal "incidentaloma" is an adrenal tumor found by coincidence without clinical symptoms or suspicion. It is one of the more common unexpected findings revealed by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasonography.

In these cases, a dexamethasone suppression test is often used to detect cortisol excess, and metanephrines or catecholamines for excess of these hormones. Tumors under 3 cm are generally considered benign and are only treated if there are grounds for a diagnosis of Cushing's syndrome or pheochromocytoma. Radiodensity gives a clue in estimating malignancy risk, wherein a tumor with 10 Hounsfield units or less on an unenhanced CT is probably a lipid-rich adenoma.

Hormonal evaluation includes:

- 1-mg overnight dexamethasone suppression test

- 24-hour urinary specimen for measurement of fractionated metanephrines and catecholamines

- Blood plasma aldosterone concentration and plasma renin activity, "if hypertension is present"

On CT scan, benign adenomas typically are of low radiographic density (due to fat content) and show rapid washout of contrast medium (50% or more of the contrast medium washes out at 10 minutes). If the hormonal evaluation is negative and imaging suggests benign, followup should be considered with imaging at 6, 12, and 24 months and repeat hormonal evaluation yearly for 4 years

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.

Management of MEN2 patients includes thyroidectomy including cervical central and bilateral lymph nodes dissection for MTC, unilateral adrenalectomy for unilateral pheochromocytoma or bilateral adrenalectomy when both glands are involved and selective resection of pathologic parathyroid glands for primary hyperparathyroidism.

Familial genetic screening is recommended to identify at risk subjects who will develop the disease, permitting early management by performing prophylactic thyroidectomy, giving them the best chance of cure.

Prognosis of MEN2 is mainly related to the stage-dependant prognosis of MTC indicating the necessity of a complete thyroid surgery for index cases with MTC and the early thyroidectomy for screened at risk subjects.

CT-scans, MRIs, sonography (ultrasound), and endoscopy (including endoscopic ultrasound) are common diagnostic tools. CT-scans using contrast medium can detect 95 percent of tumors over 3 cm in size, but generally not tumors under 1 cm.

Advances in nuclear medicine imaging, also known as molecular imaging, has improved diagnostic and treatment paradigms in patients with neuroendocrine tumors. This is because of its ability to not only identify sites of disease but also characterize them. Neuronedocrine tumours express somatostatin receptors providing a unique target for imaging. Octreotide is a synthetic modifications of somatostatin with a longer half-life. OctreoScan, also called somatostatin receptor scintigraphy (SRS or SSRS), utilizes intravenously administered octreotide that is chemically bound to a radioactive substance, often indium-111, to detect larger lesions with tumor cells that are avid for octreotide.

Somatostatin receptor imaging can now be performed with positron emission tomography (PET) which offers higher resolution, three-dimensional and more rapid imaging. Gallium-68 receptor PET-CT is much more accurate than an OctreoScan.

Imaging with fluorine-18 fluorodeoxyglucose (FDG) PET may be valuable to image some neuroendocrine tumors. This scan is performed by injected radioactive sugar intravenously. Tumors that grow more quickly use more sugar. Using this scan, the aggressiveness of the tumor can be assessed.

The combination of somatostatin receptor and FDG PET imaging is able to quantify somatostatin receptor cell surface (SSTR) expression and glycolytic metabolism, respectively. The ability to perform this as a whole body study is highlighting the limitations of relying on histopathology obtained from a single site. This is enabling better selection of the most appropriate therapy for an individual patient.

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.

While the increased serum concentration of calcitonin is not harmful, it is useful as a marker which can be tested in blood.

A second marker, carcinoembryonic antigen (CEA), also produced by medullary thyroid carcinoma, is released into the blood and it is useful as a serum or blood tumor marker. In general, measurement of serum CEA is less sensitive than serum calcitonin for detecting the presence of a tumor, but has less minute to minute variability and is therefore useful as an indicator of tumor mass.

Diagnosis is primarily performed via fine needle aspiration of the lesion of the thyroid to distinguish it from other types of thyroid lesions. Microscopic examination will show amyloid and hyperplasia of parafollicular C cells.

Before gene testing was available, the type and location of tumors determined which type of MEN2 a person had. Gene testing now allows a diagnosis before tumors or symptoms develop.

A table in the multiple endocrine neoplasia article compares the various MEN syndromes. MEN2 and MEN1 are distinct conditions, despite their similar names. MEN2 includes MEN2A, MEN2B and familial medullary thyroid cancer (FMTC).

The common feature among the three sub-types of MEN2 is a high propensity to develop medullary thyroid carcinoma.

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.

A physician's response to detecting an adenoma in a patient will vary according to the type and location of the adenoma among other factors. Different adenomas will grow at different rates, but typically physicians can anticipate the rates of growth because some types of common adenomas progress similarly in most patients. Two common responses are removing the adenoma with surgery and then monitoring the patient according to established guidelines.

One common example of treatment is the response recommended by specialty professional organizations upon removing adenomatous polyps from a patient. In the common case of removing one or two of these polyps from the colon from a patient with no particular risk factors for cancer, thereafter the best practice is to resume surveillance colonoscopy after 5–10 years rather than repeating it more frequently than the standard recommendation.

DNA testing is now the preferred method of establishing a diagnosis for MEN 2B, and is thought to be almost 100% sensitive and specific. Gordon et al. reported cases of a difference disease—the "multiple mucosal neuroma syndrome"—having the physical phenotype of MEN2B, but without variations in the RET gene and without malignancy.

MEN2B should be entertained as a diagnosis whenever a person is found to have either medullary thyroid carcinoma or pheochromocytoma. Before DNA testing became available, measurement of serum calcitonin was the most important laboratory test for MEN2B. Calcitonin is produced by the "C" cells of the thyroid, which, because they are always hyperplastic or malignant in MEN2B, produce more calcitonin than normal. Calcitonin levels remain a valuable marker to detect recurrence of medullary thyroid carcinoma after thyroidectomy.

Luxol fast blue staining identifies myelin sheathing of some fibers, and lesional cells react immunohistochemically for S-100 protein, collagen type IV, vimentin, NSE, and neural filaments. More mature lesions will react also for EMA, indicating a certain amount of perineurial differentiation. Early lesions, rich in acid mucopolysaccharides, stain positively with alcian blue. When medullary thyroid cancer is present, levels of the hormone calcitonin are elevated in serum and urine. Under the microscope, tumors may closely resemble traumatic neuroma, but the streaming fascicles of mucosal neuroma are usually more uniform and the intertwining nerves of the traumatic neuroma lack the thick perineurium of the mucosal neuroma. Inflammatory cells are not seen in the stroma and dysplasia is not present in the neural tissues.

The MACIS system of estimating the prognosis of papillary thyroid cancer was developed by Clive S. Grant at the Mayo Clinic, and was based on careful evaluation of a large group of patients. It is probably the most reliable staging method available.

It assigns scores to the main factors involved, and uses the sum of this score to calculate the prognosis:

Most patients fall into the low-risk category (MACIS score less than 6.0) and are cured of the cancer at the time of surgery.

Children with multiple lung metastases and/or a miliary aspect still have an excellent long-term prognosis if given adequate treatment.

Without treatment, persons with MEN2B die prematurely. Details are lacking, owing to the absence of formal studies, but it is generally assumed that death in the 30s is typical unless prophylactic thyroidectomy and surveillance for pheochromocytoma are performed (see below). The range is quite variable, however: death early in childhood can occur, and it is noteworthy that a few untreated persons have been diagnosed in their 50s. Recently, a larger experience with the disease "suggests that the prognosis in an individual patient may be better than previously considered."

Thyroidectomy is the mainstay of treatment, and should be performed without delay as soon as a diagnosis of MEN2B is made, even if no malignancy is detectable in the thyroid. Without thyroidectomy, almost all patients with MEN2B develop medullary thyroid cancer, in a more aggressive form than MEN 2A. The ideal age for surgery is 4 years old or younger, since cancer may metastasize before age 10.

Pheochromocytoma - a hormone secreting tumor of the adrenal glands - is also present in 50% of cases. Affected individuals are encouraged to get yearly screenings for thyroid and adrenal cancer.

Because prophylactic thyroidectomy improves survival, blood relatives of a person with MEN2B should be evaluated for MEN2B, even if lacking the typical signs and symptoms of the disorder.The mucosal neuromas of this syndrome are asymptomatic and self-limiting, and present no problem requiring treatment. They may, however, be surgically removed for aesthetic purposes or if they are being constantly traumatized.

Symptoms from secreted hormones may prompt measurement of the corresponding hormones in the blood or their associated urinary products, for initial diagnosis or to assess the interval change in the tumor. Secretory activity of the tumor cells is sometimes dissimilar to the tissue immunoreactivity to particular hormones.

Given the diverse secretory activity of NETs there are many other potential markers, but a limited panel is usually sufficient for clinical purposes. Aside from the hormones of secretory tumors, the most important markers are:

- chromogranin A (CgA), present in 99% of metastatic carcinoid tumors

- urine 5-hydroxyindoleacetic acid (5-HIAA)

- neuron-specific enolase (NSE, gamma-gamma dimer)

- synaptophysin (P38)

Newer markers include N-terminally truncated variant of Hsp70 is present in NETs but absent in normal pancreatic islets. High levels of CDX2, a homeobox gene product essential for intestinal development and differentiation, are seen in intestinal NETs. Neuroendocrine secretory protein-55, a member of the chromogranin family, is seen in pancreatic endocrine tumors but not intestinal NETs.

There are many diagnostic methods that can be used to determine the type of salivary gland tumour and if it is benign or malignant. Examples of diagnostic methods include:

Physical exam and history: An exam of the body to check general signs of health. The head, neck, mouth, and throat will be checked for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.

Endoscopy: A procedure to look at organs and tissues inside the body to check for abnormal areas. For salivary gland cancer, an endoscope is inserted into the mouth to look at the mouth, throat, and larynx. An endoscope is a thin, tube-like instrument with a light and a lens for viewing.

MRI

Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer.

Fine needle aspiration (FNA) biopsy: The removal of tissue or fluid using a thin needle. An FNA is the most common type of biopsy used for salivary gland cancer, and has been shown to produce accurate results when differentiating between benign and malignant tumours.

Radiographs: An OPG (orthopantomogram) can be taken to rule out mandibular involvement. A chest radiograph may also be taken to rule out any secondary tumours.

Ultrasound: Ultrasound can be used to initially assess a tumour that is located superficially in either the submandibular or parotid gland. It can distinguish an intrinsic from an extrinsic neoplasm. Ultrasonic images of malignant tumours include ill defined margins.

Based on overall cancer staging into stages I to IV, papillary thyroid cancer has a 5-year survival rate of 100 percent for stages I and II, 93 percent for stage III and 51 percent for stage IV.

Parathyroid carcinoma is sometimes diagnosed during surgery for primary hyperparathyroidism. If the surgeon suspects carcinoma based on severity or invasion of surrounding tissues by a firm parathyroid tumor, aggressive excision is performed, including the thyroid and surrounding tissues as necessary.

Agents such as calcimimetics (for example, cinacalcet) are used to mimic calcium and are able to activate the parathyroid calcium-sensing receptor (making the parathyroid gland "think" we have more calcium than we actually do), therefore lowering the calcium level, in an attempt to decrease the hypercalcemia.

Detection of any metastases of thyroid cancer can be performed with a full body scintigraphy using iodine-131.

The diagnosis can be established by measuring catecholamines and metanephrines in plasma (blood) or through a 24-hour urine collection. Care should be taken to rule out other causes of adrenergic (adrenalin-like) excess like hypoglycemia, stress, exercise, and drugs affecting the catecholamines like stimulants, methyldopa, dopamine agonists, or ganglion blocking antihypertensives. Various foodstuffs (e.g. coffee, tea, bananas, chocolate, cocoa, citrus fruits, and vanilla) can also affect the levels of urinary metanephrine and VMA (vanillylmandelic acid).

Imaging by computed tomography or a T2 weighted MRI of the head, neck, and chest, and abdomen can help localize the tumor. Tumors can also be located using an MIBG scan, which is scintigraphy using iodine-123-marked metaiodobenzylguanidine. Even finer localization can be obtained in certain PET scan centers using PET-CT or PET-MRI with [18F] fluorodopamine or FDOPA.

Pheochromocytomas occur most often during young-adult to mid-adult life.

These tumors can form a pattern with other endocrine gland cancers which is labeled multiple endocrine neoplasia (MEN). Pheochromocytoma may occur in patients with MEN 2 and MEN 3 (MEN 2B). Von Hippel Lindau patients may also develop these tumors.

Patients experiencing symptoms associated with pheochromocytoma should be aware that it is rare. However, it often goes undiagnosed until autopsy; therefore patients might wisely choose to take steps to provide a physician with important clues, such as recording whether blood pressure changes significantly during episodes of apparent anxiety.

There is increased life-time risk of secondary cancers (relative risk 3.63), with a slightly increased mortality risk (1.21) according to a 2004 Swedish study of 481 patients.

Adrenal adenomas are common, and are often found on the abdomen, usually not as the focus of investigation; they are usually incidental findings. About one in 10,000 is malignant. Thus, a biopsy is rarely called for, especially if the lesion is homogeneous and smaller than 3 centimeters. Follow-up images in three to six months can confirm the stability of the growth.

While some adrenal adenomas do not secrete hormones at all, often some secrete cortisol, causing Cushing's syndrome, aldosterone causing Conn's syndrome, or androgens causing hyperandrogenism.

Cancer staging is the process of determining the extent of the development of a cancer. The TNM staging system is usually used to classify stages of cancers but not of the brain.

"Adrenocortical adenomas" are benign tumors of the adrenal cortex which are extremely common (present in 1-10% of persons at autopsy). They should not be confused with adrenocortical "nodules", which are not true neoplasms. Adrenocortical adenomas are uncommon in patients younger than 30 years old, and have equal incidence in both sexes.

The clinical significance of these neoplasms is twofold. First, they have been detected as incidental findings with increasing frequency in recent years, due to the increasing use of CT scans and magnetic resonance imaging in a variety of medical settings. This can result in expensive additional testing and invasive procedures to rule out the slight possibility of an early adrenocortical carcinoma. Second, a minority (about 15%) of adrenocortical adenomas are "functional", meaning that they produce glucocorticoids, mineralcorticoids, and/or sex steroids, resulting in endocrine disorders such as Cushing's syndrome, Conn's syndrome (hyperaldosteronism), virilization of females, or feminization of males. Functional adrenocortical adenomas are surgically curable.

Most of the adrenocortical adenomas are less than 2 cm in greatest dimension and less than 50 gram in weight. However, size and weight of the adrenal cortical tumors are no longer considered to be a reliable sign of benignity or malignancy. Grossly, adrenocortical adenomas are encapsulated, well-circumscribed, solitary tumors with solid, homogeneous yellow-cut surface. Necrosis and hemorrhage are rare findings.

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.

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