Hyperparathyroidism is present in ≥ 90% of patients. Asymptomatic hypercalcemia is the most common manifestation: about 25% of patients have evidence of nephrolithiasis or nephrocalcinosis. In contrast to sporadic cases of hyperparathyroidism, diffuse hyperplasia or multiple adenomas are more common than solitary adenomas.

Pituitary tumors occur in 15 to 42% of MEN 1 patients. From 25 to 90% are prolactinomas. About 25% of pituitary tumors secrete growth hormone or growth hormone and prolactin. Excess prolactin may cause galactorrhea (see Pituitary Disorders: Galactorrhea), and excess growth hormone causes acromegaly clinically indistinguishable from sporadically occurring acromegaly. About 3% of tumors secrete ACTH, producing Cushing's disease. Most of the remainder are nonfunctional. Local tumor expansion may cause visual disturbance, headache, and hypopituitarism. Pituitary tumors in MEN 1 patients appear to be larger and behave more aggressively than sporadic pituitary tumors.

The most common clinical features of MEN2B are:

Unlike Marfan syndrome, the cardiovascular system and the lens of the eye are unaffected.Mucosal neuromas are the most consistent and distinctive feature, appearing in 100% of patients. Usually there are numerous yellowish-white, sessile, painless nodules on the lips or tongue, with deeper lesions having normal coloration. There may be enough neuromas in the body of the lips to produce enlargement and a "blubbery lip" appearance. Similar nodules may be seen on the sclera and eyelids.

Histologically, neuromata contain a characteristic adventitious plaque of tissue composed of hyperplastic, interlacing bands of Schwann cells and myelinated fibers overlay the posterior columns of the spinal cord. Mucosal neuromas are made up of nerve cells, often with thickened perineurium, intertwined with one another in a plexiform pattern. This tortuous pattern of nerves is seen within a background of loose endoneurium-like fibrous stroma.

MEN2 can present with a sign or symptom related to a tumor or, in the case of multiple endocrine neoplasia type 2b, with characteristic musculoskeletal and/or lip and/or gastrointestinal findings.Medullary thyroid carcinoma (MTC) represent the most frequent initial diagnosis. Occasionally pheochromocytoma or primary hyperparathyroidism may be the initial diagnosis.

Pheochromocytoma occurs in 33-50% of MEN2 cases. In MEN2A, primary hyperparathyroidism occurs in 10–50% of cases and is usually diagnosed after the third decade of life. Rarely, it may present in childhood or be the sole clinical manifestation of this syndrome.

MEN2A associates medullary thyroid carcinoma with pheochromocytoma in about 20–50% of cases and with primary hyperparathyroidism in 5–20% of cases.MEN2B associates medullary thyroid carcinoma with pheochromocytoma in 50% of cases, with marfanoid habitus and with mucosal and digestive neurofibromatosis.

In familial isolated medullary thyroid carcinoma the other components of the disease are absent.

In a review of 85 patients 70 had Men2A and 15 had Men2B. The initial manifestation of MEN2 was medullary thyroid carcinoma in 60% of patients, medullary thyroid carcinoma synchronous with pheochromocytoma in 34% and pheochromocytoma alone in 6%. 72% had bilateral pheochromocytomas.

Multiple endocrine neoplasia type 2B (also known as "MEN2B", "Mucosal neuromata with endocrine tumors", "Multiple endocrine neoplasia type 3", and "Wagenmann–Froboese syndrome") is a genetic disease that causes multiple tumors on the mouth, eyes, and endocrine glands. It is the most severe type of multiple endocrine neoplasia, differentiated by the presence of benign oral and submucosal tumors in addition to endocrine malignancies. It was first described by Wagenmann in 1922, and was first recognized as a syndrome in 1965-1966 by E.D. Williams and D.J. Pollock.

MEN 2B typically manifests before a child is 10 years old. Affected individuals tend to be tall and lanky, with an elongated face and protruding, blubbery lips. Benign tumors (neoplasms) develop in the mouth, eyes, and submucosa of almost all organs in the first decade of life.

Medullary thyroid cancer almost always occurs, sometimes in infancy. It is often aggressive. Cancer of the adrenal glands (pheochromocytoma) occurs in 50% of cases.

A variety of eponyms have been proposed for MEN 2B, such as Williams-Pollock syndrome, Gorlin-Vickers syndrome, and Wagenmann-Froboese syndrome. However, none ever gained sufficient traction to merit continued use, and are no longer used in the medical literature.

The prevalence of MEN2B is not well established, but has been derived from other epidemiological considerations as 1 in 600,000 to 1 in 4,000,000. The annual incidence has been estimated at 4 per 100 million per year.

Multiple endocrine neoplasia type 2 (MEN2) (also known as "Pheochromocytoma and amyloid producing medullary thyroid carcinoma", "PTC syndrome," and "Sipple syndrome") is a group of medical disorders associated with tumors of the endocrine system. The tumors may be benign or malignant (cancer). They generally occur in endocrine organs (e.g. thyroid, parathyroid, and adrenals), but may also occur in endocrine tissues of organs not classically thought of as endocrine.

MEN2 is a sub-type of MEN (multiple endocrine neoplasia) and itself has sub-types, as discussed below.

The term multiple endocrine neoplasia (MEN) encompasses several distinct syndromes featuring tumors of endocrine glands, each with its own characteristic pattern. In some cases, the tumors are malignant, in others, benign. Benign or malignant tumors of nonendocrine tissues occur as components of some of these tumor syndromes.

MEN syndromes are inherited as autosomal dominant disorders.

Traditionally, neuroendocrine tumors have been classified by their anatomic site of origin. NETs can arise in many different areas of the body, and are most often located in the intestine, pancreas or the lungs. The various kinds of cells that can give rise to NETs are present in endocrine glands and are also diffusely distributed throughout the body, most commonly Kulchitsky cells or similar enterochromaffin-like cells, that are relatively more common in the gastrointestinal and pulmonary systems.

NETs include certain tumors of the gastrointestinal tract and of the pancreatic islet cells, certain thymus and lung tumors, and medullary carcinoma of the parafollicular cells of the thyroid. Tumors with similar cellular characteristics in the pituitary, parathyroid, and adrenomedullary glands are sometimes included or excluded.

Within the broad category of neuroendocrine tumors there are many different tumor types: this outline is presented to facilitate retrieving information. Neuroendocrine tumors are uncommon in many of these areas, and frequently represent only a very small proportion of the tumors or cancers at these locations.

- Pituitary gland: Neuroendocrine tumor of the anterior pituitary

- Thyroid gland: Neuroendocrine thyroid tumors, particularly medullary carcinoma

- Parathyroid tumors

- Thymus and mediastinal carcinoid tumors

- Pulmonary neuroendocrine tumors

- bronchus

- pulmonary carcinoid tumors: typical carcinoid (TC; low-grade); atypical carcinoid (AC; intermediate-grade)

- small-cell lung cancer (SCLC)

- large cell neuroendocrine carcinoma of the lung (LCNEC)

- Extrapulmonary small cell carcinomas (ESCC or EPSCC)

- Gastroenteropancreatic neuroendocrine tumors (GEP-NET)

- Foregut GEP-NET (foregut tumors can conceptually encompasses not only NETs of the stomach and proximal duodenum, but also the pancreas, and even thymus, lung and bronchus)

- Pancreatic endocrine tumors (if considered separately from foregut GEP-NET)

- Midgut GEP-NET (from distal half of 2nd part of the duodenum to the proximal two-thirds of the transverse colon)

- appendix, including well differentiated NETs (benign); well differentiated NETs (uncertain malignant potential); well differentiated neuroendocrine carcinoma (with low malignant potential); mixed exocrine-neuroendocrine carcinoma (goblet cell carcinoma, also called adenocarcinoid and mucous adenocarcinoid)

- Hindgut GEP-NET

- Liver and gallbladder

- Adrenal tumors, particularly adrenomedullary tumors

- Pheochromocytoma

- Peripheral nervous system tumors, such as:

- Schwannoma

- paraganglioma

- neuroblastoma

- Breast

- Genitourinary tract

- urinary tract carcinoid tumor and neuroendocrine carcinoma

- ovary

- neuroendocrine tumor of the cervix

- testes

- Merkel cell carcinoma of skin (trabecular cancer)

- Several inherited conditions:

- multiple endocrine neoplasia type 1 (MEN1)

- multiple endocrine neoplasia type 2 (MEN2)

- von Hippel-Lindau (VHL) disease

- neurofibromatosis type 1

- tuberous sclerosis

- Carney complex

Although not officially categorized as multiple endocrine neoplasia syndromes, Von Hippel-Lindau disease and Carney complex are two other autosomal dominant endocrine tumor syndromes with features that overlap the clinical features of the MEN syndromes. Although not transmitted in the germline, McCune-Albright syndrome is a genetic disorder characterized by endocrine neoplastic features involving endocrine glands that overlap with those involved in MEN1 or MEN2.

Conceptually, there are two main types of NET within this category: those which arise from the gastrointestinal (GI) system and those that arise from the pancreas. In usage, the term "carcinoid" has often been applied to both, although sometimes it is restrictively applied to NETs of GI origin (as herein), or alternatively to those tumors which secrete functional hormones or polypeptides associated with clinical symptoms, as discussed.

Hormone secreting pituitary adenomas cause one of several forms of hyperpituitarism. The specifics depend on the type of hormone. Some tumors secrete more than one hormone, the most common combination being GH and prolactin, which present as unexpected bone growth and unexpected lactation (in both men and women).

A patient with pituitary adenoma may present with visual field defects, classically bitemporal hemianopsia. It arises from the compression of the optic nerve by the tumor. The specific area of the visual pathway at which compression by these tumours occurs is at the optic chiasma.

The anatomy of this structure causes pressure on it to produce a defect in the temporal visual field on both sides, a condition called bitemporal hemianopsia. If originating superior to the optic chiasm, more commonly in a craniopharyngioma of the pituitary stalk, the visual field defect will first appear as bitemporal inferior quadrantanopia, if originating inferior to the optic chiasm the visual field defect will first appear as bitemporal superior quadrantanopia. Lateral expansion of a pituitary adenoma can also compress the abducens nerve, causing a lateral rectus palsy.

Also, a pituitary adenoma can cause symptoms of increased intracranial pressure.

Prolactinomas often start to give symptoms especially during pregnancy, when the hormone progesterone increases the tumor's growth rate.

Various types of headaches are common in patients with pituitary adenomas. The adenoma may be the prime causative factor behind the headache or may serve to exacerbate a headache caused by other factors. Amongst the types of headaches experienced are both chronic and episodic migraine, and more uncommonly various unilateral headaches; primary stabbing headache, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) - another type of stabbing headache characterized by short stabs of pain -, cluster headache, and hemicrania continua (HS).

Non-secreting adenomas can go undetected for an extended time because no obvious abnormalities are seen; the gradual reduction in normal activities due to decreased production of hormones is rather less evident. For example, insufficient adrenocorticotropic hormone means that the adrenal glands will not produce sufficient cortisol, resulting in slow recovery from illness, inflammation and chronic fatigue; insufficient growth hormone in children and adolescents leads to diminished stature but which can have many other explanations.

An adrenal tumor or adrenal mass is any benign or malignant neoplasms of the adrenal gland, several of which are notable for their tendency to overproduce endocrine hormones. Adrenal cancer is the presence of malignant adrenal tumors, and includes neuroblastoma, adrenocortical carcinoma and some adrenal pheochromocytomas. Most adrenal pheochromocytomas and all adrenocortical adenomas are benign tumors, which do not metastasize or invade nearby tissues, but may cause significant health problems by unbalancing hormones.

Various psychiatric manifestations have been associated with pituitary disorders including pituitary adenomas. Psychiatric symptoms such as depression, anxiety apathy, emotional instability, easy irritability and hostility have been noted.

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.

The adrenal cortex is composed of three distinct layers of endocrine cells which produce critical steroid hormones. These include the glucocorticoids which are critical for regulation of blood sugar and the immune system, as well as response to physiological stress, the mineralcorticoid aldosterone, which regulates blood pressure and kidney function, and certain sex hormones. Both benign and malignant tumors of the adrenal cortex may produce steroid hormones, with important clinical consequences.

Carney triad (CT) is characterized by the coexistence of three types of neoplasms, mainly in young women, including gastric gastrointestinal stromal tumor, pulmonary chondroma, and extra-adrenal paraganglioma. The underlying genetic defect remains elusive. CT is distinct from Carney complex, and the Carney-Stratakis syndrome.

Benign tumors are very diverse, and may be asymptomatic or may cause specific symptoms depending on their anatomic location and tissue type. They grow outwards, producing large rounded masses, which can cause what is known as a "mass effect". This growth can cause compression of local tissues or organs, which can cause many effects such as blockage of ducts, reduced blood flow (ischaemia), tissue death (necrosis) and nerve pain or damage. Some tumors also produce hormones that can lead to life-threatening situations. Insulinomas can produce large amounts of insulin leading to hypoglycemia. Pituitary adenomas can cause elevated levels of hormones such as growth hormone and insulin-like growth factor-1, which cause acromegaly; prolactin; ACTH and cortisol, which cause Cushings disease; TSH, which causes hyperthyroidism; and FSH and LH. Bowel intussusception can occur with various benign colonic tumors. Cosmetic effects can be caused by tumors, especially those of the skin, possibly causing psychological effects on the person with the tumor. Vascular tumors can bleed, which in some cases can be substantial, leading to anemia.

The spotty skin pigmentation and lentigines occur most commonly on the face, especially on the lips, eyelids, conjunctiva and oral mucosa. Cardiac myxomas may lead to embolic strokes and heart failure and may present with fever, joint pain, shortness of breath, diastolic rumble and tumor plop. Myxomas may also occur outside the heart, usually in the skin and breast. Endocrine tumors may manifest as disorders such as Cushing syndrome. The most common endocrine gland manifestation is an ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD).

The LAMB acronym refers to lentigines, atrial myxomas, and blue nevi. NAME refers to nevi, atrial myxoma, myxoid neurofibromas, and ephelides.

Testicular cancer, particularly Sertoli cell type, is associated with Carney syndrome. Thyroid and pancreas cancer may also occur.

Although J Aidan Carney also described Carney's triad it is entirely different.

The signs and symptoms of a pheochromocytoma are those of sympathetic nervous system hyperactivity, including:

- Skin sensations

- Flank pain

- Elevated heart rate

- Elevated blood pressure, including paroxysmal (sporadic, episodic) high blood pressure, which sometimes can be more difficult to detect; another clue to the presence of pheochromocytoma is orthostatic hypotension (a fall in systolic blood pressure greater than 20 mmHg or a fall in diastolic blood pressure greater than 10 mmHg upon standing)

- Palpitations

- Anxiety often resembling that of a panic attack

- Diaphoresis (excessive sweating)

- Headaches – most common symptom

- Pallor

- Weight loss

- Localized amyloid deposits found microscopically

- Elevated blood glucose level (due primarily to catecholamine stimulation of lipolysis (breakdown of stored fat) leading to high levels of free fatty acids and the subsequent inhibition of glucose uptake by muscle cells. Further, stimulation of beta-adrenergic receptors leads to glycogenolysis and gluconeogenesis and thus elevation of blood glucose levels).

A pheochromocytoma can also cause resistant arterial hypertension. A pheochromocytoma can be fatal if it causes a hypertensive emergency, that is, severely high blood pressure that impairs one or more organ systems (formerly called "malignant hypertension"). This hypertension is not well controlled with standard blood pressure medications.

Not all patients experience all of the signs and symptoms listed. The most common presentation is headache, excessive sweating, and increased heart rate, with the attack subsiding in less than one hour.

Tumors may grow large, but most are smaller than .

Pheochromocytoma (PCC) is a neuroendocrine tumor of the medulla of the adrenal glands (originating in the chromaffin cells), or extra-adrenal chromaffin tissue that failed to involute after birth, that secretes high amounts of catecholamines, mostly norepinephrine, plus epinephrine to a lesser extent. Extra-adrenal paragangliomas (often described as extra-adrenal pheochromocytomas) are closely related, though less common, tumors that originate in the ganglia of the sympathetic nervous system and are named based upon the primary anatomical site of origin. The term is from Greek "phaios" "dark", "chroma" "color", "kytos" "cell", "-oma" "tumor".

Benign neoplasms are typically but not always composed of cells which bear a strong resemblance to a normal cell type in their organ of origin. These tumors are named for the cell or tissue type from which they originate, followed by the suffix "-oma" (but not -carcinoma, -sarcoma, or -blastoma, which are generally cancers). For example, a lipoma is a common benign tumor of fat cells (lipocytes), and a chondroma is a benign tumor of cartilage-forming cells (chondrocytes). Adenomas are benign tumors of gland-forming cells, and are usually specified further by their cell or organ of origin, as in hepatic adenoma (a benign tumor of hepatocytes, or liver cells). Teratomas contain many cell types such as skin, nerve, brain and thyroid, among others, because they are derived from germ cells. Hamartomas are a group of benign tumors that have relatively normal cellular differentiation but the architecture of the tissue is disorganised. There are a few cancers with 'benign-sounding' names which have been retained for historical reasons, including melanoma (a cancer of pigmented skin cells, or melanocytes) and seminoma (a cancer of male reproductive cells). Skin tags, vocal chord polyps and hyperplastic polyps of the colon are often referred to as benign but they are actually overgrowths of normal tissue rather than neoplasms.

Carney complex and its subsets LAMB syndrome and NAME syndrome are autosomal dominant conditions comprising myxomas of the heart and skin, hyperpigmentation of the skin (lentiginosis), and endocrine overactivity. It is distinct from Carney's triad. Approximately 7% of all cardiac myxomas are associated with Carney complex.

The Carney complex is a distinct entity, characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue nevus.

While most carcinoids are asymptomatic through the natural lifetime and are discovered only upon surgery for unrelated reasons (so-called "coincidental carcinoids"), all carcinoids are considered to have malignant potential.

About 10% of carcinoids secrete excessive levels of a range of hormones, most notably serotonin (5-HT), causing:

- Flushing (serotonin itself does not cause flushing). Potential causes of flushing in carcinoid syndrome include bradykinins, prostaglandins, tachykinins, substance P, and/or histamine, diarrhea, and heart problems. Because of serotonin's growth-promoting effect on cardiac myocytes,[14] a serotonin-secreting carcinoid tumour may cause a tricuspid valve disease syndrome, due to the proliferation of myocytes onto the valve.

- Diarrhea

- Wheezing

- Abdominal cramping

- Peripheral edema

The outflow of serotonin can cause a depletion of tryptophan leading to niacin deficiency. Niacin deficiency, also known as pellagra, is associated with dermatitis, dementia, and diarrhea.

This constellation of symptoms is called "carcinoid syndrome" or (if acute) "carcinoid crisis". Occasionally, haemorrhage or the effects of tumor bulk are the presenting symptoms. The most common originating sites of carcinoid is the small bowel, particularly the ileum; carcinoid tumors are the most common malignancy of the appendix. Carcinoid tumors may rarely arise from the ovary or thymus.

They are most commonly found in the midgut at the level of the ileum or in the appendix. The next most common affected area is the respiratory tract, with 28% of all cases — per PAN-SEER data (1973 – 1999). The rectum is also a common site.

Some PanNETs do not cause any symptoms, in which case they may be discovered incidentally on a CT scan performed for a different purpose. Symptoms such as abdominal or back pain or pressure, diarrhea, indigestion, or yellowing of the skin and whites of the eyes can arise from the effects of a larger PanNET tumor, either locally or at a metastasis. About 40% of PanNETS have symptoms related to excessive secretion of hormones or active polypeptides and are accordingly labeled as "functional"; the symptoms reflect the type of hormone secreted, as discussed below. Up to 60% of PanNETs are nonsecretory or nonfunctional, in which there is no secretion, or the quantity or type of products, such as pancreatic polypeptide (PPoma), chromogranin A, and neurotensin, do not cause a clinical syndrome although blood levels may be elevated. In total, 85% of PanNETs have an elevated blood marker.

Functional tumors are often classified by the hormone most strongly secreted, for example:

- gastrinoma: the excessive gastrin causes Zollinger–Ellison syndrome (ZES) with peptic ulcers and diarrhea

- insulinoma: hypoglycemia occurs with concurrent elevations of insulin, proinsulin and C peptide

- glucagonoma: the symptoms are not all due to glucagon elevations, and include a rash, sore mouth, altered bowel habits, venous thrombosis, and high blood glucose levels

- VIPoma, producing excessive vasoactive intestinal peptide, which may cause profound chronic watery diarrhea and resultant dehydration, hypokalemia, and achlorhydria (WDHA or pancreatic cholera syndrome)

- somatostatinoma: these rare tumors are associated with elevated blood glucose levels, achlorhydria, cholelithiasis, and diarrhea

- less common types include ACTHoma, CRHoma, calcitoninoma, GHRHoma, GRFoma, and parathyroid hormone–related peptide tumor

In these various types of functional tumors, the frequency of malignancy and the survival prognosis have been estimated dissimilarly, but a pertinent accessible summary is available.