Adrenocortical carcinoma natural history
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If left untreated, patients with adrenocortical carcinoma may develop diabetes mellitus, osteoporosis, delayed wound healing, hypertension, Cerebrovascular disease, and local or distant metastasis. Prognosis is generally poor, and the 5-year survival rate of patients with adrenocortical carcinoma stage I-III is approximately 30%. Complications may include metastasis, Conn's syndrome and Cushing'a syndrome.
The symptoms of adrenocortical carcinoma usually develop in the fifth to sixth decade of life and start with symptoms of Cushing's syndrome such as weight gain, acne, irritability, insomnia, symptoms of androgen excess such as virilization, deepening of the voice, and coarsening of the facial features.
Without treatment, the patient may develop complications such as diabetes mellitus, osteoporosis, hypertension, hypercoagulable states, metastasis to other organs, cardiovascular and cerebrovascular diseases.
The following are the complications of Adrenocortical carcinoma:
- Cushing's syndrome-related complications
- Conn's syndrome
- Local and distant metastasis
- Paraneoplastic syndrome
- Tumor thrombus formation.
- Adrenocortical carcinoma, generally, carries a poor prognosis.
- The five-year disease-free survival rate for a complete resection of a stage I-III is approximately 30%.
- Survival ranges from a few months to several years.
The most important prognostic factors are:
- Age of the patient 
- Stage of the tumor 
- Mitotic activity 
- Venous invasion
- Weight more than 50 Kg
- Size/Diameter more than 6.5 cm
- Cortisol production is an adverse prognostic factor
- Ki-67/MIB1 labeling index (antigen identified by monoclonal antibody Ki-67).
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- Hermsen IG, Gelderblom H, Kievit J, Romijn JA, Haak HR (2008). "Extremely long survival in six patients despite recurrent and metastatic adrenal carcinoma.". Eur J Endocrinol. 158 (6): 911–9. PMID 18505909. doi:10.1530/EJE-07-0723.
- Libé R, Borget I, Ronchi CL, Zaggia B, Kroiss M, Kerkhofs T; et al. (2015). "Prognostic factors in stage III-IV adrenocortical carcinomas (ACC): an European Network for the Study of Adrenal Tumor (ENSAT) study.". Ann Oncol. 26 (10): 2119–25. PMID 26392430. doi:10.1093/annonc/mdv329.
- Gonzalez RJ, Tamm EP, Ng C, Phan AT, Vassilopoulou-Sellin R, Perrier ND; et al. (2007). "Response to mitotane predicts outcome in patients with recurrent adrenal cortical carcinoma.". Surgery. 142 (6): 867–75; discussion 867–75. PMID 18063070. doi:10.1016/j.surg.2007.09.006.
- Miller BS, Gauger PG, Hammer GD, Giordano TJ, Doherty GM (2010). "Proposal for modification of the ENSAT staging system for adrenocortical carcinoma using tumor grade.". Langenbecks Arch Surg. 395 (7): 955–61. PMID 20694732. doi:10.1007/s00423-010-0698-y.