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 (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 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]
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]
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]
1-mg overnight dexamethasone suppression test
24-hour urinary specimen for measurement of fractionated metanephrines and catecholamines
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]
^ abYoung WF (February 2007). "Clinical practice. The incidentally discovered adrenal mass". The New England Journal of Medicine. 356 (6): 601–610. doi:10.1056/NEJMcp065470. PMID17287480.
^Zen K, Zhang CY (March 2012). "Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human cancers". Medicinal Research Reviews. 32 (2): 326–348. doi:10.1002/med.20215. PMID22383180. S2CID13429401.
^ abValadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (June 2007). "Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells". Nature Cell Biology. 9 (6): 654–659. doi:10.1038/ncb1596. PMID17486113. S2CID8599814.
Further reading
Santulli G, ed. (2015). Adrenal Glands: From Pathophysiology to Clinical Evidence. New York, NY: Nova Science. ISBN978-1-63483-570-1.
Cotran R, Kumar V, Collins T (1999). Robbins Pathologic Basis of Disease (Sixth ed.). W.B. Saunders. ISBN978-0-7216-7335-6.
Cote R, Suster S, Weiss L (2003). Noel Weidner (ed.). Modern Surgical Pathology (2 Volume Set). London: W B Saunders. ISBN978-0-7216-7253-3.