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.

A parathyroid adenoma is a benign tumor of the parathyroid gland. It generally causes hyperparathyroidism; there are very few reports of parathyroid adenomas that were not associated with hyperparathyroidism.

A human being usually has four parathyroid glands located on the back surface of the thyroid in the neck. The parathyroids secrete parathyroid hormone (PTH), which increases the concentration of calcium in the blood by inducing the bones to release calcium into the blood and the kidneys to reabsorb it from the urine into the blood. When a parathyroid adenoma causes hyperparathyroidism, more parathyroid hormone is secreted, causing the calcium concentration of the blood to rise, resulting in hypercalcemia.

The first signs of a parathyroid adenoma and the resulting primary hyperparathyroidism can include bone fractures and urinary calculi such as kidney stones.

Oftentimes parathyroid adenoma is not diagnosed until found on standard blood-tests that reveal high calcium content in the blood, it can appear in urine tests as well. Patients may not be experiencing any noticeable symptoms but could be producing excessive amounts of calcium and eventually experience problems later in life if untreated. However, patients can experience common symptoms that can range from joint, muscle, and abdominal pain to slight discomfort. Additionally patients might be experiencing feelings of depression due to the hormonal imbalance. Constipation and exhaustion can also be experienced as a result of the irregularity in the bloodstream. There is also a potential that the kidneys could be damaged with the excess of calcium in the blood.

Most patients experience moderate to severe hypercalcemia and high parathyroid hormone levels. A large mass in the neck is often seen, and renal and bone abnormalities are common.

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.

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.

Pancreatic islet cell tumors occur in 60 to 70% of patients. Tumors are usually multicentric. Multiple adenomas or diffuse islet cell hyperplasia commonly occurs; such tumors may arise from the small bowel rather than the pancreas. About 30% of tumors are malignant and have local or distant metastases. Malignant islet cell tumors due to MEN 1 syndrome often have a more benign course than do sporadically occurring malignant islet cell tumors.About 40% of islet cell tumors originate from a β-cell, secrete insulin (insulinoma), and can cause fasting hypoglycemia. β-cell tumors are more common in patients 40 years of age. Non-β-cell tumors are somewhat more likely to be malignant.

Most islet cell tumors secrete pancreatic polypeptide, the clinical significance of which is unknown. Gastrin is secreted by many non–β-cell tumors (increased gastrin secretion in MEN 1 also often originates from the duodenum). Increased gastrin secretion increases gastric acid, which may inactivate pancreatic lipase, leading to diarrhea and steatorrhea. Increased gastrin secretion also leads to peptic ulcers in > 50% of MEN 1 patients. Usually the ulcers are multiple or atypical in location, and often bleed, perforate, or become obstructed. Peptic ulcer disease may be intractable and complicated. Among patients presenting with Zollinger-Ellison syndrome, 20 to 60% have MEN 1.

A severe secretory diarrhea can develop and cause fluid and electrolyte depletion with non–β-cell tumors. This complex, referred to as the watery diarrhea, hypokalemia and achlorhydria syndrome (VIPoma) has been ascribed to vasoactive intestinal polypeptide, although other intestinal hormones or secretagogues (including prostaglandins) may contribute. Hypersecretion of glucagon, somatostatin, chromogranin, or calcitonin, ectopic secretion of ACTH resulting in Cushing's syndrome, and hypersecretion of somatotropin–releasing hormone (causing acromegaly) sometimes occur in non–β-cell tumors. All of these are rare in MEN 1.Nonfunctioning pancreatic tumors also occur in patients with MEN 1 and may be the most common type of pancreatoduodenal tumor in MEN 1. The size of the nonfunctioning tumor correlates with risk of metastasis and death.

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 .

Parathyroid carcinoma is a rare malignant neoplasm resulting in parathyroid adenoma to carcinoma progression. It forms in tissues of one or more of the parathyroid glands (four pea-sized glands in the neck that make parathyroid hormone, which helps the body store and use calcium).

It is rare, and much less common than parathyroid adenoma.

It can be difficult to excise.

The signs and symptoms of primary hyperparathyroidism are those of hypercalcemia. They are classically summarized by "stones, bones, abdominal groans, thrones and psychiatric overtones".

- "Stones" refers to kidney stones, nephrocalcinosis, and diabetes insipidus (polyuria and polydipsia). These can ultimately lead to renal failure.

- "Bones" refers to bone-related complications. The classic bone disease in hyperparathyroidism is osteitis fibrosa cystica, which results in pain and sometimes pathological fractures. Other bone diseases associated with hyperparathyroidism are osteoporosis, osteomalacia, and arthritis.

- "Abdominal groans" refers to gastrointestinal symptoms of constipation, indigestion, nausea and vomiting. Hypercalcemia can lead to peptic ulcers and acute pancreatitis. The peptic ulcers can be an effect of increased gastric acid secretion by hypercalcemia.

- "Thrones" refers to polyuria and constipation

- "Psychiatric overtones" refers to effects on the central nervous system. Symptoms include lethargy, fatigue, depression, memory loss, psychosis, ataxia, delirium, and coma.

Left ventricular hypertrophy may also be seen.

Other signs include proximal muscle weakness, itching, and band keratopathy of the eyes.

When subjected to formal research, symptoms of depression, pain, and gastric dysfunction seem to correlate with mild cases of hypercalcemia.

The differential diagnoses of pheochromocytoma include:

- Anxiety disorders, including Benzodiazepine withdrawal syndrome

- Paragangliomas

- Von Hippel–Lindau Disease

- Essential hypertension

- Hyperthyroidism

- Insulinoma

- Mercury poisoning

- Paroxysmal supraventricular tachycardia

- Renovascular hypertension

- Carcinoid

An adenoma of a parathyroid gland may secrete inappropriately high amounts of parathyroid hormone and thereby cause primary hyperparathyroidism.

Pituitary adenomas are seen in 10% of neurological patients. A lot of them remain undiagnosed. Treatment is usually surgical, to which patients generally respond well. The most common subtype, prolactinoma, is seen more often in women, and is frequently diagnosed during pregnancy as the hormone progesterone increases its growth. Medical therapy with cabergoline or bromocriptine generally suppresses prolactinomas; progesterone antagonist therapy has not proven to be successful.

Primary hyperparathyroidism is usually caused by a tumor within the parathyroid gland. The symptoms of the condition relate to the elevated calcium levels, which can cause digestive symptoms, kidney stones, psychiatric abnormalities, and bone disease.

The diagnosis is initially made on blood tests; an elevated level of calcium together with a raised level of parathyroid hormone are typically found. To identify the source of the excessive hormone secretion, medical imaging may be performed. Parathyroidectomy, the surgical removal of one or more parathyroid glands, may be required to control symptoms.

The major clinical symptom of metastatic medullary thyroid carcinoma is diarrhea; occasionally a patient will have flushing episodes. Both occur particularly with liver metastasis, and either symptom may be the first manifestation of the disease. The flushing that occurs in medullary thyroid carcinoma is indistinguishable from that associated with carcinoid syndrome. In MTC, the flushing, diarrhea, and itching (pruritis) are all caused by elevated levels of calcitonin gene products (calcitonin or calcitonin gene-related peptide). Alternatively, the flushing and diarrhea observed in carcinoid syndrome is caused by elevated levels of circulating serotonin.

Medullary thyroid carcinoma may also produce a thyroid nodule and enlarged cervical lymph nodes.

Sites of spread of medullary thyroid carcinoma include local lymph nodes in the neck, lymph nodes in the central portion of the chest (mediastinum), liver, lung, and bone. Spread to other sites such as skin or brain occurs but is uncommon.

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.

Medullary thyroid cancer (MTC) is a form of thyroid carcinoma which originates from the parafollicular cells (C cells), which produce the hormone calcitonin.

Medullary tumors are the third most common of all thyroid cancers. They make up about 3% of all thyroid cancer cases.

Approximately 25% of medullary thyroid cancer is genetic in nature, caused by a mutation in the RET proto-oncogene. This form is classified as familial MTC. When MTC occurs by itself it is termed sporadic MTC. When it coexists with tumors of the parathyroid gland and medullary component of the adrenal glands (pheochromocytoma) it is called multiple endocrine neoplasia type 2 (MEN2).It was first characterized in 1959.

The major symptoms of OFC are bone pain or tenderness, bone fractures, and skeletal deformities such as bowing of the bones. The underlying hyperparathyroidism may cause kidney stones, nausea, constipation, fatigue and weakness. X-rays may indicate thin bones, fractures, bowing, and cysts. Fractures are most commonly localized in the arms, legs, or spine.

The addition of weight loss, appetite loss, vomiting, polyuria, and polydipsia to the aforementioned symptoms may indicate that OFC is the result of parathyroid carcinoma. Parathyroid carcinoma, an uncommon cancer of the parathyroid glands, is generally indicated by serum calcium levels higher than usual, even in comparison to the high serum calcium levels that OFC generally presents with. Symptoms are also often more severe. Generally, the presence of a palpable neck mass is also indicative of the cancer, occurring in approximately 50% of sufferers, but virtually nonexistent in individuals with OFC with a different origin.

Features that result from high level of GH or expanding tumor include:

- Soft tissue swelling visibly resulting in enlargement of the hands, feet, nose, lips and ears, and a general thickening of the skin

- Soft tissue swelling of internal organs, notably the heart with attendant weakening of its muscularity, and the kidneys, also the vocal cords resulting in a characteristic thick, deep voice and slowing of speech

- Generalized expansion of the skull at the fontanelle

- Pronounced brow protrusion, often with ocular distension (frontal bossing)

- Pronounced lower jaw protrusion (prognathism) with attendant macroglossia (enlargement of the tongue) and teeth spacing

- Hypertrichosis, hyperpigmentation and hyperhidrosis may occur in these patients.

- Acrochordon (skin tags)

- Carpal tunnel syndrome

Many conditions are associated with disorders of the function of the parathyroid gland. Parathyroid diseases can be divided into those causing hyperparathyroidism, and those causing hypoparathyroidism.

Osteitis fibrosa cystica is defined as the classic skeletal manifestation of advanced hyperparathyroidism. Under the ICD-10 classification system, established by the World Health Organization, OFC is listed under category E21.0, primary hyperparathyroidism.

Brown tumours consist of fibrous tissue, woven bone and supporting vasculature, but no matrix. The osteoclasts consume the trabecular bone that osteoblasts lay down and this front of reparative bone deposition followed by additional resorption can expand beyond the usual shape of the bone, involving the periosteum thus causing bone pain. The characteristic brown coloration results from hemosiderin deposition into the osteolytic cysts. Hemosiderin deposition is not a distinctive feature of brown tumors; it may also be seen in giant cell tumors of the bone.

Brown tumors may be rarely associated with ectopic parathyroid adenomas or end stage renal osteodystrophy.

Symptoms depend on whether the hyperparathyroidism is the result of parathyroid overactivity or secondary.

In primary hyperparathyroidism about 75% of people have no symptoms. The problem is often picked up during blood work for other reasons via a raised calcium. Many other people only have non-specific symptoms. Symptoms directly due to hypercalcemia are relatively rare, being more common in patients with malignant hypercalcemia. If present, common manifestations of hypercalcemia include weakness and fatigue, depression, bone pain, muscle soreness (myalgias), decreased appetite, feelings of nausea and vomiting, constipation, polyuria, polydipsia, cognitive impairment, kidney stones (See Foot Note) and osteoporosis. A history of acquired racquet nails (brachyonychia) may be indicative of bone resorption. Parathyroid adenomas are very rarely detectable on clinical examination. Surgical removal of a parathyroid tumor eliminates the symptoms in most patients.

In secondary hyperparathyroidism the parathyroid gland is behaving normally; clinical problems are due to bone resorption and manifest as bone syndromes such as rickets, osteomalacia and renal osteodystrophy.

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.

Acromegaly is a disorder that results from excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There may also be enlargement of the forehead, jaw, and nose. Other symptoms may include joint pain, thicker skin, deepening of the voice, headaches, and problems with vision. Complications of the disease may include type 2 diabetes, sleep apnea, and high blood pressure.

Acromegaly is typically due to the pituitary gland producing too much growth hormone. In more than 95% of cases the excess production is due to a benign tumor, known as a pituitary adenoma. The condition is not inherited from a person's parents. Rarely acromegaly is due to tumors in other parts of the body. Diagnosis is by measuring growth hormone after a person has drunk glucose or by measuring insulin-like growth factor I in the blood. After diagnosis, medical imaging of the pituitary is carried out to look for an adenoma. If excess growth hormone is produced during childhood the result is gigantism.

Treatment options include surgery to remove the tumor, medications, and radiation therapy. Surgery is usually the preferred treatment and is most effective when the tumor is smaller. In those in whom surgery is not effective, medications of the somatostatin analogue or GH receptor antagonist type may be used. The effects of radiation therapy are more gradual than that of surgery or medication. Without treatment those affected live on average 10 years less; however, with treatment life expectancy is typically normal.

Acromegaly affects about 6 per 100,000 people. It is most commonly diagnosed in middle age. Males and females are affected with equal frequency. The first medical description of the disorder occurred in 1772 by Nicolas Saucerotte. The term is from Greek "akron" meaning "extremity" and "mega" meaning "large".