Adrenal tumor

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Adrenal tumor
Incidences and prognoses of adrenal tumors.png
Incidences and prognoses of adrenal tumors. [1]
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An adrenal tumor or adrenal mass [2] 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.

Contents

Metastasis to the adrenals

Main sites of metastases for some common cancer types. Primary cancers are denoted by "...cancer" and their main metastasis sites are denoted by "...metastases". Lung cancer metastasis to the adrenal glands are mentioned with red arrows. Metastasis sites for common cancers.svg
Main sites of metastases for some common cancer types. Primary cancers are denoted by "...cancer" and their main metastasis sites are denoted by "...metastases". Lung cancer metastasis to the adrenal glands are mentioned with red arrows.

Metastasis to one or both adrenal glands is the most common form of malignant adrenal lesion, and the second most common adrenal tumor after benign adenomas. [4] Primary tumors in such cases are most commonly from lung cancer (39%), breast cancer (35%), malignant melanoma, gastrointestinal tract cancer, pancreas cancer, and renal cancer. [4]

Tumors of the adrenal cortex

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.[ citation needed ]

Adrenocortical adenoma

Adrenocortical adenomas are benign tumors of the adrenal cortex that 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.[ citation needed ] 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.[ citation needed ]

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.[ citation needed ]

Adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare, highly aggressive cancer of adrenal cortical cells, which may occur in children or adults. ACCs may be "functional", producing steroid hormones and consequent endocrine dysfunction similar to that seen in many adrenocortical adenomas, but many are not. Due to their location deep in the retroperitoneum, most adrenocortical carcinomas are not diagnosed until they have grown quite large. They frequently invade large vessels, such as the renal vein and inferior vena cava, as well as metastasizing via the lymphatics and through the blood to the lungs and other organs. The most effective treatment is surgery, although this is not feasible for many patients, and the overall prognosis of the disease is poor. Chemotherapy, radiation therapy, and hormonal therapy may also be employed in the treatment of this disease.[ citation needed ]

Tumors of the adrenal medulla

The adrenal medulla is located anatomically at the center of each adrenal gland, and is composed of neuroendocrine (chromaffin) cells which produce and release epinephrine (adrenaline) into the bloodstream in response to activation of the sympathetic nervous system. Neuroblastoma and pheochromocytoma are the two most important tumors which arise from the adrenal medulla. Both tumors may also arise from extra-adrenal sites, specifically, in the paraganglia of the sympathetic chain.[ citation needed ]

Neuroblastoma

Neuroblastoma is an aggressive cancer of immature neuroblastic cells (precursors of neurons), and is one of the most common pediatric cancers, with a median age at diagnosis of two years. [5] Adrenal neuroblastoma typically presents with a rapidly enlarging abdominal mass. Although the tumor has often spread to distant parts of the body at the time of diagnosis, this cancer is unusual in that many cases are highly curable when the spread is limited to the liver, skin, and/or bone marrow (stage IVS). Related, but less aggressive tumors composed of more mature neural cells include ganglioneuroblastoma and ganglioneuroma. Neuroblastic tumors often produce elevated levels of catecholamine hormone metabolites, such as vanillylmandelic acid (VMA) and homovanillic acid, and may produce severe watery diarrhea through production of vasoactive intestinal peptide. Treatment of neuroblastoma includes surgery and radiation therapy for localized disease, and chemotherapy for metastatic disease. [6]

Pheochromocytoma

Pheochromocytoma is a neoplasm composed of cells similar to the chromaffin cells of the mature adrenal medulla. Pheochromocytomas occur in patients of all ages, and may be sporadic, or associated with a hereditary cancer syndrome, such as multiple endocrine neoplasia (MEN) types IIA and IIB, neurofibromatosis type I, or von Hippel–Lindau syndrome. Only 10% of adrenal pheochromocytomas are malignant, while the rest are benign tumors. The most clinically important feature of pheochromocytomas is their tendency to produce large amounts of the catecholamine hormones epinephrine (adrenaline) and norepinephrine. This may lead to potentially life-threatening high blood pressure, or cardiac arrhythmias, and numerous symptoms such as headache, palpitations, anxiety attacks, sweating, weight loss, and tremor. Diagnosis is most easily confirmed through urinary measurement of catecholamine metabolites such as VMA and metanephrines. Most pheochromocytomas are initially treated with anti-adrenergic drugs to protect against catecholamine overload, with surgery employed to remove the tumor once the patient is medically stable. [7]

Incidentalomas

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. [8]

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. [9] 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. [10]

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, follow-up should be considered with imaging at 6, 12, and 24 months and repeat hormonal evaluation yearly for 4 years [11] .

Adrenal-dedicated CT and MRI imaging can be performed to distinguish benign adenomas from potentially malignant lesions [12] [13] . Online calculators assist radiologists in calculating the washout of contrast in adrenal nodules on CT [14] and chemical shift on MRI [15] .

Hormonal evaluation can also be helpful, which includes: [11]

Treatment

Surgical

For adrenal carcinomas, the most effective treatment is surgery, although this is not feasible for many patients, and the overall prognosis of the disease is poor. Chemotherapy, radiation therapy, and hormonal therapy may also be employed in the treatment of this disease.

A 2018 Cochrane Systematic review compared two different types of surgery: laparoscopic retroperotenial adrenalectomy and laporoscopic transperitoenal adrenelectomy in different types of adrenal tumors. [16] Laparoscopic retroperotenial adrenalectomy appeared to reduce late morbility, time to oral fluid or food intake and time to ambulation, when compared to laparoscopic transperitoenal adrenalectomy. [16] However there was uncertainty in these findings due to low-quality evidence, as well as inconclusive findings about effects of either surgery on all-cause mortality, early morbidity, socioeconomic effects, duration of surgery, operative blood loss, conversion to open surgery. [16]

Future diagnostic tools

Blood circulating microRNAs (miRNA) has been investigated in the recent years for the potential as a less-invasive biomarker for adrenal diseases. Nine studies have so far investigated the occurrence of circulating miRNAs in blood from patients diagnosed with adrenocortical tumors. [17] [18] MiRNAs can be released into the blood stream by three different types of excretion. [19] Cellular damage with passive release (necrosis, inflammation), active secretion in the form of extracellular vesicles (EV) (microvesicles, exosomes and apoptotic bodies) or in association with high density lipoproteins (HDL) and Argonaute (AGO) proteins. [20] [21] The majority of miRNAs found in blood are in complexes with AGO. [22] [23] Despite the promising results, the sensitivity of potential circulating miRNA markers for adrenocortical tumors appears to be variable. An increase in sensitivity could possibly be achieved by targeting only EV-associated miRNAs as the release of miRNAs into EVs are hypothesized to be a controlled process. [24] EV-associated miRNAs could thereby act as more specific markers of malignancy. [24] However, as there were significant differences in the results of the studies performed, methodological differences and low patient numbers could contribute to this discrepancy. This calls for further studies on larger cohorts with uniform methodological requirements to clarify the applicability of circulating miRNAs as biomarkers of prognosis and malignancy in patients diagnosed with adrenocortical tumors. [17]

Related Research Articles

<span class="mw-page-title-main">Adrenal gland</span> Endocrine gland

The adrenal glands are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which produces steroid hormones and an inner medulla. The adrenal cortex itself is divided into three main zones: the zona glomerulosa, the zona fasciculata and the zona reticularis.

<span class="mw-page-title-main">Thyroid neoplasm</span> Medical condition

Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm, such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected than men. The estimated number of new cases of thyroid cancer in the United States in 2023 is 43,720 compared to only 2,120 deaths. Of all thyroid nodules discovered, only about 5 percent are cancerous, and under 3 percent of those result in fatalities.

<span class="mw-page-title-main">Pheochromocytoma</span> Type of neuroendocrine tumor

Pheochromocytoma is a rare tumor of the adrenal medulla composed of chromaffin cells and is part of the paraganglioma (PGL) family of tumors, being defined as an intra-adrenal PGL. These neuroendocrine tumors can be sympathetic, where they release catecholamines into the bloodstream which cause the most common symptoms, including hypertension, tachycardia, sweating, and headaches. Some PGLs may secrete little to no catecholamines, or only secrete paroxysmally (episodically), and other than secretions, PGLs can still become clinically relevant through other secretions or mass effect. PGLs of the head and neck are typically parasympathetic and their sympathetic counterparts are predominantly located in the abdomen and pelvis, particularly concentrated at the organ of Zuckerkandl at the bifurcation of the aorta.

<span class="mw-page-title-main">Multiple endocrine neoplasia</span> Group of genetic conditions

Multiple endocrine neoplasia is a condition which 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.

<span class="mw-page-title-main">Adrenal medulla</span> Central part of the adrenal gland

The adrenal medulla is the inner part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cells that secrete catecholamines, including epinephrine (adrenaline), norepinephrine (noradrenaline), and a small amount of dopamine, in response to stimulation by sympathetic preganglionic neurons.

<span class="mw-page-title-main">Adenoma</span> Type of benign tumor

An adenoma 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. Although adenomas are benign, they should be treated as pre-cancerous. Over time adenomas may transform to become malignant, at which point they are called adenocarcinomas. Most adenomas do not transform. However, even though benign, they have the potential to cause serious health complications by compressing other structures and by producing large amounts of hormones in an unregulated, non-feedback-dependent manner. Some adenomas are too small to be seen macroscopically but can still cause clinical symptoms.

<span class="mw-page-title-main">Chromaffin cell</span> Neuroendocrine cells found in adrenal medulla in mammals

Chromaffin cells, also called pheochromocytes, are neuroendocrine cells found mostly in the medulla of the adrenal glands in mammals. These cells serve a variety of functions such as serving as a response to stress, monitoring carbon dioxide and oxygen concentrations in the body, maintenance of respiration and the regulation of blood pressure. They are in close proximity to pre-synaptic sympathetic ganglia of the sympathetic nervous system, with which they communicate, and structurally they are similar to post-synaptic sympathetic neurons. In order to activate chromaffin cells, the splanchnic nerve of the sympathetic nervous system releases acetylcholine, which then binds to nicotinic acetylcholine receptors on the adrenal medulla. This causes the release of catecholamines. The chromaffin cells release catecholamines: ~80% of adrenaline (epinephrine) and ~20% of noradrenaline (norepinephrine) into systemic circulation for systemic effects on multiple organs, and can also send paracrine signals. Hence they are called neuroendocrine cells.

In medical or research imaging, an incidental imaging finding is an unanticipated finding which is not related to the original diagnostic inquiry. As with other types of incidental medical findings, they may represent a diagnostic, ethical, and philosophical dilemma because their significance is unclear. While some coincidental findings may lead to beneficial diagnoses, others may lead to overdiagnosis that results in unnecessary testing and treatment, sometimes called the "cascade effect".

<span class="mw-page-title-main">Pituitary adenoma</span> Human disease

Pituitary adenomas are tumors that occur in the pituitary gland. Most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas. Pituitary adenomas represent from 10% to 25% of all intracranial neoplasms and the estimated prevalence rate in the general population is approximately 17%.

<span class="mw-page-title-main">Adrenocortical carcinoma</span> Medical condition

Adrenocortical carcinoma (ACC) is an aggressive cancer originating in the cortex of the adrenal gland.

<span class="mw-page-title-main">Benign tumor</span> Mass of cells which cannot spread throughout the body

A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize. Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have relatively well differentiated cells. They are often surrounded by an outer surface or stay contained within the epithelium. Common examples of benign tumors include moles and uterine fibroids.

<span class="mw-page-title-main">Multiple endocrine neoplasia type 1</span> Medical condition

Multiple endocrine neoplasia type 1 (MEN-1) is one 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. Individuals suffering from this disorder are prone to developing multiple endocrine and nonendocrine tumors. It was first described by Paul Wermer in 1954.

<span class="mw-page-title-main">Multiple endocrine neoplasia type 2</span> Medical condition

Multiple endocrine neoplasia type 2 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, but may also occur in endocrine tissues of organs not classically thought of as endocrine. MEN2 is a sub-type of MEN and itself has sub-types, as discussed below. Variants in MEN2A have been associated with Hirschsprung disease. Screening for this condition can begin as young as eight years old for Pheochromocytoma.

Nelson's syndrome is a disorder that occurs in about one in four patients who have had both adrenal glands removed to treat Cushing's disease. In patients with pre-existing adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas, loss of adrenal feedback following bilateral adrenalectomy can trigger the rapid growth of the tumor, leading to visual symptoms and hyperpigmentation. The severity of the disease is dependent upon the effect of ACTH release on the skin, pituitary hormone loss from mass compression, as well as invasion into surrounding structures around the pituitary gland.

<span class="mw-page-title-main">Adrenalectomy</span> Surgical removal of adrenal glands

Adrenalectomy is the surgical removal of one or both adrenal glands. It is usually done to remove tumors of the adrenal glands that are producing excess hormones or is large in size. Adrenalectomy can also be done to remove a cancerous tumor of the adrenal glands, or cancer that has spread from another location, such as the kidney or lung. Adrenalectomy is not performed on those who have severe coagulopathy or whose heart and lungs are too weak to undergo surgery. The procedure can be performed using an open incision (laparotomy) or minimally invasive laparoscopic or robot-assisted techniques. Minimally invasive techniques are increasingly the gold standard of care due to shorter length of stay in the hospital, lower blood loss, and similar complication rates.

<span class="mw-page-title-main">Paraganglion</span>

A paraganglion is a group of non-neuronal cells derived of the neural crest. They are named for being generally in close proximity to sympathetic ganglia. They are essentially of two types: (1) chromaffin or sympathetic paraganglia made of chromaffin cells and (2) nonchromaffin or parasympathetic paraganglia made of glomus cells. They are neuroendocrine cells, the former with primary endocrine functions and the latter with primary chemoreceptor functions.

<span class="mw-page-title-main">Endocrine disease</span> Medical condition

Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology.

<span class="mw-page-title-main">Adrenocortical adenoma</span> Medical condition

An adrenocortical adenoma or adrenal adenoma is commonly described as a benign neoplasm emerging from the cells that comprise the adrenal cortex. Like most adenomas, the adrenocortical adenoma is considered a benign tumor since the majority of them are non-functioning and asymptomatic. Adrenocortical adenomas are classified as ACTH-independent disorders, and are commonly associated with conditions linked to hyperadrenalism such as Cushing's syndrome (hypercortisolism) or Conn's syndrome (hyperaldosteronism), which is also known as primary aldosteronism. In addition, recent case reports further support the affiliation of adrenocortical adenomas with hyperandrogenism or florid hyperandrogenism which can cause hyperandrogenic hirsutism in females. "Cushing's syndrome" differs from the "Cushing's disease" even though both conditions are induced by hypercortisolism. The term "Cushing's disease" refers specifically to "secondary hypercortisolism" classified as "ACTH-dependent Cushing's syndrome" caused by pituitary adenomas. In contrast, "Cushing's syndrome" refers specifically to "primary hypercortisolism" classified as "ACTH-independent Cushing's syndrome" caused by adrenocortical adenomas.

<span class="mw-page-title-main">Iobenguane</span> Chemical compound

Iobenguane, or MIBG, is an aralkylguanidine analog of the adrenergic neurotransmitter norepinephrine (noradrenaline), typically used as a radiopharmaceutical. It acts as a blocking agent for adrenergic neurons. When radiolabeled, it can be used in nuclear medicinal diagnostic and therapy techniques as well as in neuroendocrine chemotherapy treatments.

<span class="mw-page-title-main">Adrenal gland disorder</span> Medical condition

Adrenal gland disorders are conditions that interfere with the normal functioning of the adrenal glands. Your body produces too much or too little of one or more hormones when you have an adrenal gland dysfunction. The type of issue you have and the degree to which it affects your body's hormone levels determine the symptoms.

References

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  3. ↑ List of included entries and references is found on main image page in Commons: File:Metastasis sites for common cancers.svg
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