Adrenocortical Carcinoma

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 disease is associated with neoplastic processes. The incidence rate of the disease is set at a value of about 1 / 100.000.

Presentation

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

Workup

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.

Treatment

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.

Prognosis

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

Etiology

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

Epidemiology

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

Pathophysiology

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.

Prevention

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.

Summary

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.

Search symptoms now!

References

  1. Angeli A, Osella G, Terzolo M. Adrenal incidentaloma: an overview of clinical and epidemiological data from the National Italian Study Group. Horm Res. 1997;47(4-6):279-83.
  2. Villelli NW, Jayanti MK, Zynger DL. Use and Usefulness of Adrenal Core Biopsies Without FNA or On-site Evaluation of Adequacy: A Study of 204 Cases for a 12-Year Period. Am J Clin Pathol. Jan 2012;137(1):124-31.
  3. Lau SK, Weiss LM. The Weiss system for evaluating adrenocortical neoplasms: 25 years later. Hum Pathol. Jun 2009;40(6):757-68.
  4. Soon PS, Gill AJ, Benn DE, Clarkson A, Robinson BG, McDonald KL, et al. Microarray gene expression and immunohistochemistry analyses of adrenocortical tumors identify IGF2 and Ki-67 as useful in differentiating carcinomas from adenomas. Endocr Relat Cancer. Jun 2009;16(2):573-83.
  5. Miller BS, Gauger PG, Hammer GD, et al. Proposal for modification of the ENSAT staging system for adrenocortical carcinoma using tumor grade. Langenbecks Arch Surg 2010; 395:955.
  6. Allolio B, Hahner S, Weismann D, Fassnacht M. Management of adrenocortical carcinoma. Clin Endocrinol (Oxf) 2004; 60:273
  7. Reibetanz J, Jurowich C, Erdogan I, et al. Impact of lymphadenectomy on the oncologic outcome of patients with adrenocortical carcinoma. Ann Surg 2012; 255:363.
  8. Bertagna C, Orth DN. Clinical and laboratory findings and results of therapy in 58 patients with adrenocortical tumors admitted to a single medical center (1951 to 1978). Am J Med 1981; 71:855.
  9. Stojadinovic A, Ghossein RA, Hoos A, et al. Adrenocortical carcinoma: clinical, morphologic, and molecular characterization. J Clin Oncol 2002; 20:941.
  10. Hough AJ, Hollifield JW, Page DL, Hartmann WH. Prognostic factors in adrenal cortical tumors. A mathematical analysis of clinical and morphologic data. Am J Clin Pathol 1979; 72:390.

  • Adrenal gland and adrenal mass calcification - N Hindman, GM Israel - European radiology, 2005 - Springer
  • GROWTH FACTOR II IN RELATION TO SUPPRESSED INSULIN‐LIKE GROWTH FACTOR I IN THE DIAGNOSIS OF NON‐ISLET CELL TUMOUR HYPOGLYCAEMIA - JD Teale, V Marks - Clinical endocrinology, 2008 - Wiley Online Library
  • Adrenal cortical carcinoma producing solely mineralocorticoid effect - LV Foye, TV Feichtmeir - The American journal of medicine, 1955 - Elsevier
  • Adrenocortical carcinoma responded to treatment withoff, p'-DDD-A case report - T Naruse, A Koike, K Kato, T Ishii, K Suzumura - Endocr. jap, 1984 - ukpmc.ac.uk
  • Adrenal cortical carcinoma: clinical features of 138 patients - AM Hutter, DE Kayhoe - The American journal of medicine, 1966 - Elsevier
  • ACTH-independant macronodular adrenal hyperplasia: imaging findings of a rare condition - A Verma, S Mohan, A Gupta - Abdominal imaging, 2008 - Springer
  • Adrenal cortical carcinoma - APB Dackiw, JE Lee, RF Gagel, DB Evans - World journal of surgery, 2001 - Springer
  • 891TiPPHASE II STUDY OF DOVITINIB IN FIRST LINE METASTATIC OR (NON RESECTABLE PRIMARY) ADRENOCORTICAL CARCINOMA (ACC). SOGUG STUDY - A Ravaud, C Barrios, Ö Anak, D Pelov - Annals of , 2012 - Eur Soc Med Oncology
  • A case of Cushing's syndrome due to adrenocortical carcinoma with recurrence 19 months after laparoscopic adrenalectomy. - T Ushiyama, K Suzuki, S Kageyama, K Fujita - The Journal of , 1997 - ukpmc.ac.uk
  • Adrenal lesion in multiple endocrine neoplasia type 1 - B Skogseid, J Rastad, A Gobl, C Larsson, K Backlin - Surgery, 1995 - Elsevier
  • Canine hyperadrenocorticism due to adrenocortical neoplasia: pretreatment evaluation of 41 dogs - CE Reusch, EC Feldman - Journal of Veterinary Internal , 2008 - Wiley Online Library
  • Adrenocortical carcinoma - BL Wajchenberg, MA Albergaria Pereira - Cancer, 2000 - Wiley Online Library
  • Analysis in the differential diagnosis of hepatocellular carcinoma, metastatic adenocarcinoma, renal cell carcinoma, and adrenal cortical carcinoma - TJ Wieczorek, JL Pinkus, JN Glickman - American journal of , 2002 - 171.67.112.51
  • A rare cause of Cushing's syndrome demonstrates analytical discrepancies between the Roche E170 and Bayer Centaur testosterone assays - S Hancock, RA Still, AM Fielding - Annals of clinical , 2008 - acb.rsmjournals.com
  • A possible mechanism for the erythrocytosis associated with hepatocellular carcinoma in man - AS GORDON, ED ZANJANI - Blood, 1970 - bloodjournal.hematologylibrary.org
  • A survey on adrenal incidentaloma in Italy - F Mantero, M Terzolo, G Arnaldi, G Osella - Journal of Clinical , 2000 - Endocrine Soc
  • Adrenocortical hyperactivity in a patient with bronchial carcinoma and diabetes mellitus - FD Rosenthal - British medical journal, 1957 - bmj.com
  • A case of non-functioning huge adrenocortical carcinoma extending into inferior vena cava and right atrium - KH Kim, JC Park, SY Lim, IS Sohn - Journal of Korean , 2006 - synapse.koreamed.org
  • Adrenal myelolipoma: report of a case and review of the literature - VG Patel, OA Babalola, JK Fortson - The American , 2006 - ingentaconnect.com
  • Profiling of human adrenocortical tumors using complementary deoxyribonucleic acid microarrays identifies several candidate genes as markers of malignancy - F De Fraipont, M El Atifi, N Cherradi - Journal of Clinical , 2005 - Endocrine Soc
  • ACTH-Independent Cushing's Syndrome: Adrenocortical Tumors - MCBV Fragoso, S Domenice, AC Latronico - Cushing's , 2011 - Springer
  • Acute Budd-Chiari syndrome as first manifestation of adrenocortical carcinoma - F Carbonnel, D Valla, Y Menu, Y Lecompte - J Clin , 1988 - ukpmc.ac.uk
  • Adrenocortical carcinoma in children: a study of 40 cases. - RC Ribeiro, RSS Neto, MJ Schell - Journal of Clinical , 1990 - jco.ascopubs.org
  • Adjunctive treatment of adrenocortical carcinoma - M Terzolo, A Berruti - Current Opinion in Endocrinology, Diabetes , 2008 - journals.lww.com
Search symptoms now!