Adrenocortical carcinoma may present differently in children and adults. Most tumors in children are functional, and virilization is by far the most common presenting symptom, followed by Cushing's syndrome and precocious puberty. Among adults presenting with hormonal syndromes, Cushing's syndrome alone is most common, followed by mixed Cushing's and virilization (glucocorticoid and androgen overproduction). Feminization and Conn syndrome (mineralocorticoid excess) occur in less than 10% of cases. Rarely, pheochromocytoma-like hypersecretion of catecholamines has been reported in adrenocortical cancers. Non-functional tumors (about 40%, authorities vary) usually present with abdominal or flank pain, varicocele and renal vein thrombosis or they may be asymptomatic and detected incidentally.

All patients with suspected adrenocortical carcinoma should be carefully evaluated for signs and symptoms of hormonal syndromes. For Cushing's syndrome (glucocorticoid excess) these include weight gain, muscle wasting, purple lines on the abdomen, a fatty "buffalo hump" on the neck, a "moonlike" face, and thinning, fragile skin. Virilism (androgen excess) is most obvious in women, and may produce excess facial and body hair, acne, enlargement of the clitoris, deepening of the voice, coarsening of facial features, cessation of menstruation. Conn syndrome (mineralcorticoid excess) is marked by high blood pressure which can result in headache and hypokalemia (low serum potassium, which can in turn produce muscle weakness, confusion, and palpitations) low plasma renin activity, and high serum aldosterone. Feminization (estrogen excess) is most readily noted in men, and includes breast enlargement, decreased libido and impotence.

Carcinoids most commonly affect the small bowel, particularly the ileum, and are the most common malignancy of the appendix. Many carcinoids are asymptomatic and are discovered only upon surgery for unrelated causes. These coincidental carcinoids are common; one study found that one person in ten has them. Many tumors do not cause symptoms even when they have metastasized. Other tumors even if very small can produce adverse effects by secreting hormones.

Ten per cent (10%) or less of carcinoids, primarily some midgut carcinoids, secrete excessive levels of a range of hormones, most notably serotonin (5-HT) or substance P, causing a constellation of symptoms called carcinoid syndrome:

- flushing

- diarrhea

- asthma or wheezing

- congestive heart failure (CHF)

- abdominal cramping

- peripheral edema

- heart palpitations

A carcinoid crisis with profound flushing, bronchospasm, tachycardia, and widely and rapidly fluctuating blood pressure can occur if large amounts of hormone are acutely secreted, which is occasionally triggered by factors such as diet, alcohol, surgery chemotherapy, embolization therapy or radiofrequency ablation.

Chronic exposure to high levels of serotonin causes thickening of the heart valves, particularly the tricuspid and the pulmonic valves, and over a long period can lead to congestive heart failure. However, valve replacement is rarely needed. The excessive outflow of serotonin can cause a depletion of tryptophan leading to niacin deficiency, and thus pellagra, which is associated with dermatitis, dementia, and diarrhea. Many other hormones can be secreted by some of these tumors, most commonly growth hormone that can cause acromegaly, or cortisol, that can cause Cushing's syndrome.

Occasionally, haemorrhage or the effects of tumor bulk are the presenting symptoms. Bowel obstruction can occur, sometimes due to fibrosing effects of NET secretory products with an intense desmoplastic reaction at the tumor site, or of the mesentery.

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.

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.

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.

Adrenocortical carcinoma (ACC, adrenal cortical carcinoma, adrenal cortical cancer, adrenal cortex cancer, etc.) is an aggressive cancer originating in the cortex (steroid hormone-producing tissue) of the adrenal gland. Adrenocortical carcinoma is a rare tumor, with incidence of 1–2 per million population annually. Adrenocortical carcinoma has a bimodal distribution by age, with cases clustering in children under 5, and in adults 30–40 years old. Adrenocortical carcinoma is remarkable for the many hormonal syndromes which can occur in patients with steroid hormone-producing ("functional") tumors, including Cushing's syndrome, Conn syndrome, virilization, and feminization. Adrenocortical carcinoma has often invaded nearby tissues or metastasized to distant organs at the time of diagnosis, and the overall 5-year survival rate is only 20–35%. The widely used angiotensin-II-responsive steroid-producing cell line H295R was originally isolated from a tumor diagnosed as adrenocortical carcinoma.

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.

A adrenocortical adenoma (or adrenal cortical adenoma, or sometimes simply adrenal adenoma) is a benign tumor of the adrenal cortex.

It can present with Cushing's syndrome or primary aldosteronism. They may also secrete androgens, causing hyperandrogenism. Also, they are often diagnosed incidentally as incidentalomas.

Is a well circumscribed, yellow tumour in the adrenal cortex, which is usually 2–5 cm in diameter. The color of the tumour, as with adrenal cortex as a whole, is due to the stored lipid (mainly cholesterol), from which the cortical hormones are synthesized. These tumors are frequent incidental findings at post mortem examination, and appear to have produced no significant metabolic disorder; only a very small percentage lead to Cushing's syndrome. Nevertheless, these apparently non-functioning adenomas are most often encountered in elder obese people. There is some debate that they may really represent nodules in diffuse nodular cortical hyperplasia.

Very occasionally, a true adrenal cortical adenoma is associated with the clinical manifestations of Conn's syndrome, and can be shown to be excreting mineralocorticoids.

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.

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

An adenoma (from Greek αδένας, "", "gland" + -ώμα, "", "tumor") (; plural adenomas or adenomata ) is a benign tumor of epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organs, including the adrenal glands, pituitary gland, thyroid, prostate, and others. Some adenomas grow from epithelial tissue in nonglandular areas but express glandular tissue structure (as can happen in familial polyposis coli). Although adenomas are benign, over time they may transform to become malignant, at which point they are called adenocarcinomas. Most adenomas do not transform. But even while benign, they have the potential to cause serious health complications by compressing other structures (mass effect) and by producing large amounts of hormones in an unregulated, non-feedback-dependent manner (causing paraneoplastic syndromes). Some adenomas are too small to be seen macroscopically but can still cause clinical symptoms.

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".

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.

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.

Signs and symptoms include: hypoglycemia, dehydration, weight loss, and disorientation. Additional signs and symptoms include weakness, tiredness, dizziness, low blood pressure that falls further when standing (orthostatic hypotension), cardiovascular collapse, muscle aches, nausea, vomiting, and diarrhea. These problems may develop gradually and insidiously. Addison's disease can present with tanning of the skin that may be patchy or even all over the body. Characteristic sites of tanning are skin creases (e.g. of the hands) and the inside of the cheek (buccal mucosa). Goitre and vitiligo may also be present. Eosinophilia may also occur.

There are three major types of adrenal insufficiency.

- Primary adrenal insufficiency is due to impairment of the adrenal glands.

- 80% are due to an autoimmune disease called Addison's disease or autoimmune adrenalitis.

- One subtype is called idiopathic, meaning of unknown cause.

- Other cases are due to congenital adrenal hyperplasia or an adenoma (tumor) of the adrenal gland.

- Secondary adrenal insufficiency is caused by impairment of the pituitary gland or hypothalamus. Its principal causes include pituitary adenoma (which can suppress production of adrenocorticotropic hormone (ACTH) and lead to adrenal deficiency unless the endogenous hormones are replaced); and Sheehan's syndrome, which is associated with impairment of only the pituitary gland.

- Tertiary adrenal insufficiency is due to hypothalamic disease and a decrease in the release of corticotropin releasing hormone (CRH). Causes can include brain tumors and sudden withdrawal from long-term exogenous steroid use (which is the most common cause overall).

An "Addisonian crisis" or "adrenal crisis" is a constellation of symptoms that indicates severe adrenal insufficiency. This may be the result of either previously undiagnosed Addison's disease, a disease process suddenly affecting adrenal function (such as adrenal hemorrhage), or an intercurrent problem (e.g., infection, trauma) in someone known to have Addison's disease. It is a medical emergency and potentially life-threatening situation requiring immediate emergency treatment.

Characteristic symptoms are:

- Sudden penetrating pain in the legs, lower back, or abdomen

- Severe vomiting and diarrhea, resulting in dehydration

- Low blood pressure

- Syncope (loss of consciousness and ability to stand)

- Hypoglycemia (reduced level of blood glucose)

- Confusion, psychosis, slurred speech

- Severe lethargy

- Hyponatremia (low sodium level in the blood)

- Hyperkalemia (elevated potassium level in the blood)

- Hypercalcemia (elevated calcium level in the blood)

- Convulsions

- Fever

Causes of adrenal insufficiency can be categorized by the mechanism through which they cause the adrenal glands to produce insufficient cortisol. These are adrenal dysgenesis (the gland has not formed adequately during development), impaired steroidogenesis (the gland is present but is biochemically unable to produce cortisol) or adrenal destruction (disease processes leading to glandular damage).

Adrenal gland disorders (or diseases) are conditions that interfere with the normal functioning of the adrenal glands. Adrenal disorders may cause hyperfunction or hypofunction, and may be congenital or acquired.

The adrenal gland produces hormones that affects growth, development and stress, and also helps to regulate kidney function. There are two parts of the adrenal glands, the adrenal cortex and the adrenal medulla. The adrenal cortex produces mineralocorticoids, which regulate salt and water balance within the body, glucocorticoids (including cortisol) which have a wide number of roles within the body, and androgens, hormones with testosterone-like function. The adrenal medulla produces epinephrine (adrenaline) and norepinephrine (noradrenaline). Disorders of the adrenal gland may affect the production of one or more of these hormones.

People often have few or no symptoms. They may get occasional muscular weakness, muscle spasms, tingling sensations, or excessive urination.

High blood pressure, manifestations of muscle cramps (due to hyperexcitability of neurons secondary to low blood calcium), muscle weakness (due to hypoexcitability of skeletal muscles secondary to hypokalemia), and headaches (due to low blood potassium or high blood pressure) may be seen.

Secondary hyperaldosteronism is often related to decreased cardiac output which is associated with elevated renin levels.

PPNAD is a rare cause of high cortisol levels in the blood and often manifests as ACTH-independent Cushing's syndrome. The effects of PPNAD can often be cyclical so the symptoms of Cushing's syndrome will not always be as severe, which may complicate diagnosis. The classic symptoms of Cushing's syndrome include rapid central weight gain, a puffy red face and a buffalo hump at the back of the neck due to fat deposits. Skin changes in Cushing's syndrome include thinning and bruising easily, developing striae and hyperpigmentation at skin folds. The hormonal changes can lead to hirsuitism, males developing breast tissue, females no longer having periods and both sexes may become infertile. High cortisol levels can lead to psychological disturbances such as anxiety or depression and insomnia. Bone health can deteriorate, leading to an increased fracture risk in people with Cushing's syndrome. PPNAD is unique as it often causes Cushing's at a young age, in children and adolescents. In addition to the other symptoms of Cushing's syndrome, the patient may have a short stature due to interrupted growth because of ACTH suppression.

In 90% of people with PPNAD it is associated with Carney Complex. Carney Complex is usually inherited, however it can also occur sporadically. A visible sign of Carney complex is abnormal skin hyperpigmentation. There may also be myxomas which can appear as lumps in the skin and breast as well as often being present in the heart, which can lead to multiple cardiovascular problems. The majority of people with PPNAD will have some of these signs/symptoms due to the strong association between PPNAD and Carney Complex.

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.

The most common clinical manifestations are related to mental status and gastrointestinal function; they include lethargy, anorexia, vomiting, weight loss, and weakness. Additional findings may include dehydration, bradycardia, weak femoral pulses, and abdominal pain. Polyuria and polydipsia, diarrhea, and shivering are occasionally reported.

Symptoms of hypoadrenocorticism can include vomiting, diarrhea, lethargy, lack of appetite, tremors or shaking, muscle weakness, low body temperature, collapse, low heart rate, and pain in the hind quarters. Hypoglycemia can also be present, and initially may be confused with seizure disorders, insulin-secreting pancreatic tumor (insulinoma), food poisoning, parvovirus enteritis, gastric volvulus, spinal or joint problems, earning hypoadrenocorticism the nicknames of "the Great Mimic" and "the Great Imitator". It is possible not to see any signs of the disease until 90% of the adrenal cortex is no longer functioning.

The condition is due to:

- Bilateral idiopathic (micronodular) adrenal hyperplasia (66%)

- Adrenal adenoma (Conn's syndrome) (33%)

- Primary (unilateral) adrenal hyperplasia—2% of cases

- Aldosterone-producing adrenocortical carcinoma—<1% of cases

- Familial Hyperaldosteronism (FH)

- Glucocorticoid-remediable aldosteronism (FH type I)—<1% of cases

- FH type II (APA or IHA)—<2% of cases

- Ectopic aldosterone-producing adenoma or carcinoma—< 0.1% of cases