Adrenocortical Carcinoma (Adrenal Cortical Carcinomas)

Adrenal cortical carcinoma - low mag[1]

Adrenocortical carcinoma (ACC) is a rare malignancy that arises from the adrenal cortex. Adrenocortical masses are common, but only approximately 1 per 1500 adrenal tumors are malignant.


The findings during examination are variable and dependent on the endocrine syndromes that occur (if any exist) [6]. The majority of patients with functional tumors shows symptoms of Cushing syndrome including truncal obesity, striae, malar flushing, supraclavicular and dorsocervical fat pads. Hypertension with weakness and ileus resulting from hypokalemia (Conn syndrome), virilization, precocity, feminization and combined hormone excess also may be present. For nonfunctional tumors, signs and symptoms include fever, weight loss, abdominal, flank and back pain.

Adrenocortical carcinomas may be classified as [7]:

  • Functional
  • Nonfunctional
  • Well differentiated
  • Intermediate
  • Poorly differentiated to anaplastic


All hormonal syndromes need to be confirmed with laboratory testing. In Cushing syndrome, the laboratory findings include increased urine cortisol and serum glucose. Adrenal virilism is confirmed by the finding of an excess of low serum potassium, low plasma renin activity and also high serum aldosterone. Exces serum estrogen depicts feminization [8]. To identify the site of the tumor, imaging studies of the abdomen, such as CT scans and magnetic resonance imaging are useful. They aid in differentiating ACC from other masses and in determining the extent of invasion of the tumor into surrounding tissues and organs. CT scans of the chest and bone scans are routinely performed to examine for metastases to the bones or lungs.


Presently, the major treatment is total surgical excision of the tumor. This can be done even if the tumor has invaded large blood vessels like inferior vena cava or the renal vein. The 5-year survival rate after a successful surgery is around 60% however, majority of the patients are not surgical candidates [9]. For patients who are not surgical candidates, radiation therapy and radiofrequency ablation are used as palliation. For chemotherapy regimens, the drug mitotane and other standard cytotoxic drugs are used. Mitotane is an inhibitor of steroid synthesis and this is toxic to the cells of the adrenal cortex.


The efficacy of treatment is largely dependent on the stage of the cancer. Therefore early detection is paramount if the individual is to survive.


Although the mutation-induced inactivation of tumor suppressor genes appears to be a plausible mechanism for ACC development, other potential mechanisms, including activation of various protooncogenes (eg, ras, PKC), inhibition of apoptosis, or changes in various adrenocortical tissue-specific factors (eg, the steroidogenic acute regulatory protein (StaR)) are possible [3]. Potential mechanisms for adrenocortical tumorigenesis are as follows:

  • Activation of various protooncogenes -Ras, PKC, C myc, C fos, G proteins, G protein-coupled receptors (eg, for vasoactive intestinal peptide (VIP), gastric-inhibitory peptide (GIP), luteinizing hormone (LH), and catecholamines)
  • Inactivation of tumor suppressor genes (antioncogenes) -TP53, TP57, TP16, H19, retinoblastoma gene, APC gene, various DNA repair enzyme genes
  • Inhibition of senescence and/or apoptosis - Mutations involving telomerase and/or BCL-2 genes
  • Changes in adrenocortical tissue-specific factors - Mutations involving the genes for StaR, SF-1 (steroidogenic factor), and Dax-1 transcription factor
  • Aberrant expression of receptors to normal adrenocortical trophic agents and ligands - Adrenocorticotropic hormone, angiotensin 2, catecholamines, and endorphins
  • Ectopic expression of receptors on adrenocortical cells to atypical trophic factors and ligands - Cytokines, growth factors, and neurotransmitters


Internationally, the tumors are uncommon [1] [2]. With approximately 0.6-1.67 cases per 1 million people each year, the incidence is relatively low. Some reports say that incidence is ten times higher in southern Brazilian children for reasons unknown. Overall however, ACC accounts for 0.02-0.2% of all cancer-related deaths so the disease is rightly adjudged as rare.

ACC does not have any racial predilection and the female to male ration is 2.5-3.1. The male patients tend to be older than the females and the prognosis is better for females. However, the females are more likely than the male counterparts to have an associated endocrine syndrome. Nonfunctional ACCs occur equally between both sexes. ACC has two major periods of occurrence, the first decade of life and the fourth and fifth decade of life. 75% of children who have ACC are younger than 5 years of ages. Nonfunctional tumors are more common in adults but functional tumors are common in children.

Sex distribution
Age distribution


Although some reports point to an increased predilection for the left adrenal, majority of reports show no side preference. The exact etiopathogenesis of sporadic ACC is unclear but analysis of the syndromic variants of the condition provides some insight [4]. The role of tumor suppressor gene mutations is suggested by their association with Li-Fraumeni syndrome, which is characterized by inactivating germline mutations of the TP53 gene (a vital tumor suppressor gene or antioncogene) on chromosome 17. This syndrome also is associated with a predisposition to other malignancies, including breast carcinoma, leukemia, osteosarcoma, and soft-tissue sarcoma.

A few reports describe an association between AC and familial adenomatous polyposis, which also is due to a germline inactivating mutation of a tumor suppressor gene (in this case, the adenomatous polyposis coli gene, APC) [5]. However, such mutations have not been found in sporadic APC cases.

Suggestions have been made that adrenal hyperplasia predisposes patients to develop ACC. A few cases of congenital adrenal hyperplasia are associated with functional adrenocortical adenomas but not carcinoma.


Majority of adrenal gland tumors are not linked to family history but some are linked to genetic defects. This means that there is really no way to prevent the disease. The best bet is to focus on early detection.


Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex and can be equally referred to as adrenal cortical carcinoma. The adrenal cortex represents the outer layer of the adrenal glands which are located at the upper poles of the kidneys. The adrenal cortex secretes mineralocorticoids, glucocorticoids and adrenal androgen. The presentation varies depending on hormone excess or local tumor growth and adrenal incidentalomas are common [1].

Patient Information

Adrenocortical carcinoma is a rare cancerous growth in the adrenal cortex. Patients have to be on the lookout for reoccurrence of growth. This will be dealt with by surgery as well [10]. For healthy individuals or people in a family with history of ACC, family members around the peak years for ACC occurrence should be monitored for symptoms like lump in the abdomen, pain in the abdomen or back, unusual hair growth, irregular menstrual cycles, irregular sexual behavior and in children, early puberty.


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