Incidentaloma risk factors: Difference between revisions
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==Overview== | ==Overview== | ||
Most [[Adrenocortical carcinoma|adrenocortical carcinomas]] are sporadic, but some occur as a component of hereditary [[cancer]] [[syndromes]] such as [[Li-Fraumeni syndrome]], [[Beckwith-Wiedemann syndrome]], and [[Multiple endocrine neoplasia type 1]]([[MEN1]]). Genetic basis of sporadic incidentaloma | Most [[Adrenocortical carcinoma|adrenocortical carcinomas]] are sporadic, but some occur as a component of hereditary [[cancer]] [[syndromes]] such as [[Li-Fraumeni syndrome]], [[Beckwith-Wiedemann syndrome]], and [[Multiple endocrine neoplasia type 1]]([[MEN1]]). Genetic basis of sporadic incidentaloma includes ''[[TP53 (gene)|TP53]]'' [[gene]]. A role for the ''[[TP53 (gene)|TP53]]'' [[tumor suppressor gene]] in sporadic ACCs is suggested by the frequent finding of [[loss of heterozygosity]] (LOH) at the 17p13 locus in sporadic ACCs. Another [[chromosomal]] [[locus]] that is strongly implicated in the pathogenesis of ACC is 11p, the area of abnormality in [[Beckwith-Wiedemann syndrome]] and the site of the [[Insulin-like growth factor 2|insulin-like growth factor-2]] (IGF-2) [[gene]]. | ||
==Risk Factors== | ==Risk Factors== | ||
Most [[Adrenocortical carcinoma|adrenocortical carcinomas]] are sporadic, but some occur as a component of hereditary [[cancer]] [[syndromes]].< | Most [[Adrenocortical carcinoma|adrenocortical carcinomas]] are sporadic, but some occur as a component of hereditary [[cancer]] [[syndromes]].<ref name="pmid14685087">{{cite journal| author=Sidhu S, Sywak M, Robinson B, Delbridge L| title=Adrenocortical cancer: recent clinical and molecular advances. | journal=Curr Opin Oncol | year= 2004 | volume= 16 | issue= 1 | pages= 13-8 | pmid=14685087 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14685087 }}</ref> | ||
* [[Heredity|Hereditary]] [[cancer]] [[syndromes]]: | * [[Heredity|Hereditary]] [[cancer]] [[syndromes]]: | ||
* [[Li-Fraumeni syndrome]]: [[breast cancer]], soft tissue and [[bone sarcoma]], [[brain tumors]], associated with inactivating mutations of the ''[[TP53 (gene)|TP53]]'' [[tumor suppressor gene]] on chromosome 17p. | * [[Li-Fraumeni syndrome]]: [[breast cancer]], soft tissue and [[bone sarcoma]], [[brain tumors]], associated with inactivating mutations of the ''[[TP53 (gene)|TP53]]'' [[tumor suppressor gene]] on chromosome 17p. | ||
* [[Beckwith-Wiedemann syndrome]]: [[Wilms' tumor]][[Neuroblastoma|, neuroblastoma]], [[hepatoblastoma]], associated with abnormalities in 11p15 | * [[Beckwith-Wiedemann syndrome]]: [[Wilms' tumor]][[Neuroblastoma|, neuroblastoma]], [[hepatoblastoma]], associated with abnormalities in 11p15 | ||
* [[Multiple endocrine neoplasia type 1]] ([[MEN1]]) ([[Parathyroid gland|parathyroid]], [[Pituitary gland|pituitary]], and [[Pancreatic neuroendocrine tumor|pancreatic neuroendocrine tumors]] and [[Adrenal adenoma|adrenal adenomas]], as well as [[Carcinoma|carcinomas]], associated with inactivating mutations | * [[Multiple endocrine neoplasia type 1]] ([[MEN1]]) ([[Parathyroid gland|parathyroid]], [[Pituitary gland|pituitary]], and [[Pancreatic neuroendocrine tumor|pancreatic neuroendocrine tumors]] and [[Adrenal adenoma|adrenal adenomas]], as well as [[Carcinoma|carcinomas]], associated with inactivating mutations in the [[MEN1|''MEN1'' gene]] on chromosome 11q.<ref name="pmid2300390">{{cite journal| author=Lynch HT, Radford B, Lynch JF| title=SBLA syndrome revisited. | journal=Oncology | year= 1990 | volume= 47 | issue= 1 | pages= 75-9 | pmid=2300390 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2300390 }}</ref> | ||
== Genetic basis of risk factors == | == Genetic basis of risk factors == | ||
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==== Sporadic cases genetics ==== | ==== Sporadic cases genetics ==== | ||
* ''[[TP53 (gene)|TP53]]'' [[gene]], located on [[chromosome]] 17p13, is the most frequently mutated [[gene]] in human [[cancers]]. A role for the ''[[TP53 (gene)|TP53]]'' [[tumor suppressor gene]] in sporadic ACCs is suggested by the frequent finding of [[loss of heterozygosity]] (LOH) at the 17p13 locus in sporadic ACCs.<sup>[[Incidentaloma pathophysiology#cite note-pmid11559548-11|[11]]]</sup> | * ''[[TP53 (gene)|TP53]]'' [[gene]], located on [[chromosome]] 17p13, is the most frequently mutated [[gene]] in human [[cancers]]. A role for the ''[[TP53 (gene)|TP53]]'' [[tumor suppressor gene]] in sporadic ACCs is suggested by the frequent finding of [[loss of heterozygosity]] (LOH) at the 17p13 locus in sporadic ACCs.<sup>[[Incidentaloma pathophysiology#cite note-pmid11559548-11|[11]]]</sup> | ||
* | * Although the [[loss of heterozygosity]] at 17p13 is common, only approximately one-third of these [[tumors]] have a [[mutation]] of ''[[TP53 (gene)|TP53]]''. This suggests that another as yet unidentified suppressor gene is present in this [[locus]].<ref name="pmid17289876">{{cite journal| author=Libè R, Groussin L, Tissier F, Elie C, René-Corail F, Fratticci A et al.| title=Somatic TP53 mutations are relatively rare among adrenocortical cancers with the frequent 17p13 loss of heterozygosity. | journal=Clin Cancer Res | year= 2007 | volume= 13 | issue= 3 | pages= 844-50 | pmid=17289876 | doi=10.1158/1078-0432.CCR-06-2085 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17289876 }}</ref> | ||
* Another [[chromosomal]] [[locus]] that is strongly implicated in the pathogenesis of ACC is 11p, the area of abnormality in [[Beckwith-Wiedemann syndrome]] and the site of the [[Insulin-like growth factor 2|insulin-like growth factor-2]] (IGF-2) [[gene]]. LOH at the 11p15 locus and overexpression of [[IGF2|IGF-2]] have been associated with the [[malignant]] [[phenotype]] in sporadic ACCs.<sup>[[Incidentaloma pathophysiology#cite note-pmid9253334-13|[13]]]</sup> However, other growth-related [[Tumor suppressor genes|tumor suppressor gene]]<nowiki/>s at this [[locus]] may also be involved. | * Another [[chromosomal]] [[locus]] that is strongly implicated in the pathogenesis of ACC is 11p, the area of abnormality in [[Beckwith-Wiedemann syndrome]] and the site of the [[Insulin-like growth factor 2|insulin-like growth factor-2]] (IGF-2) [[gene]]. LOH at the 11p15 locus and overexpression of [[IGF2|IGF-2]] have been associated with the [[malignant]] [[phenotype]] in sporadic ACCs.<sup>[[Incidentaloma pathophysiology#cite note-pmid9253334-13|[13]]]</sup> However, other growth-related [[Tumor suppressor genes|tumor suppressor gene]]<nowiki/>s at this [[locus]] may also be involved. | ||
Most adrenocortical tumors are [[Monoclonal antibody|monoclonal]], suggesting that they result from accumulated genetic abnormalities, such as activation of [[Oncogenes|proto-oncogenes]] and inactivation of [[Tumor suppressor genes|tumor suppressor genes.]] | Most adrenocortical tumors are [[Monoclonal antibody|monoclonal]], suggesting that they result from accumulated genetic abnormalities, such as activation of [[Oncogenes|proto-oncogenes]] and inactivation of [[Tumor suppressor genes|tumor suppressor genes.]]<ref name="pmid10634406">{{cite journal| author=Bourcigaux N, Gaston V, Logié A, Bertagna X, Le Bouc Y, Gicquel C| title=High expression of cyclin E and G1 CDK and loss of function of p57KIP2 are involved in proliferation of malignant sporadic adrenocortical tumors. | journal=J Clin Endocrinol Metab | year= 2000 | volume= 85 | issue= 1 | pages= 322-30 | pmid=10634406 | doi=10.1210/jcem.85.1.6303 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10634406 }}</ref> | ||
[[Beta-catenin]] [[mutations]] (CTNNB1) | [[Beta-catenin]] [[mutations]] (CTNNB1) | ||
* Constitutive activation of [[beta-catenin]] in the Wnt [[signaling pathway]] has been identified as a frequent alteration in [[benign]] and [[malignant]] | * Constitutive activation of [[beta-catenin]] in the Wnt [[signaling pathway]] has been identified as a frequent alteration in [[benign]] and [[malignant]] [[Adrenal tumor|adrenocortical tumors]].<ref name="pmid22471738">{{cite journal| author=Mazzuco TL, Durand J, Chapman A, Crespigio J, Bourdeau I| title=Genetic aspects of adrenocortical tumours and hyperplasias. | journal=Clin Endocrinol (Oxf) | year= 2012 | volume= 77 | issue= 1 | pages= 1-10 | pmid=22471738 | doi=10.1111/j.1365-2265.2012.04403.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22471738 }}</ref> | ||
* The increased occurrence of [[Adrenal gland|adrenal]] [[tumors]] in patients with [[mutations]] of [[adenomatous polyposis coli]] ([[APC]]) suggested that the Wnt/[[beta-catenin]] pathway could be involved in [[Adrenal gland|adrenal]] [[tumorigenesis]].< | * The increased occurrence of [[Adrenal gland|adrenal]] [[tumors]] in patients with [[mutations]] of [[adenomatous polyposis coli]] ([[APC]]) suggested that the Wnt/[[beta-catenin]] pathway could be involved in [[Adrenal gland|adrenal]] [[tumorigenesis]].<ref name="pmid11156460">{{cite journal| author=Smith TG, Clark SK, Katz DE, Reznek RH, Phillips RK| title=Adrenal masses are associated with familial adenomatous polyposis. | journal=Dis Colon Rectum | year= 2000 | volume= 43 | issue= 12 | pages= 1739-42 | pmid=11156460 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11156460 }}</ref> | ||
* This pathway is essential for [[embryonic]] development of the [[Adrenal gland|adrenal]], and its [[ectopic]] constitutive activation is associated with [[cancer]] development in a number of tissues.< | * This pathway is essential for [[embryonic]] development of the [[Adrenal gland|adrenal]], and its [[ectopic]] constitutive activation is associated with [[cancer]] development in a number of tissues.<ref name="pmid12824913">{{cite journal| author=Kikuchi A| title=Tumor formation by genetic mutations in the components of the Wnt signaling pathway. | journal=Cancer Sci | year= 2003 | volume= 94 | issue= 3 | pages= 225-9 | pmid=12824913 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12824913 }}</ref> | ||
Aberrant [[Receptor (biochemistry)|receptors]] | Aberrant [[Receptor (biochemistry)|receptors]] | ||
* [[Cortisol]] hypersecretion is the most frequent [[Hormone|hormonal]] abnormality detected in patients with functioning unilateral [[Adrenal adenoma|adrenal adenomas]]. It had been assumed that the mechanism for this was non-[[Adrenocorticotropic hormone|ACTH]]-dependent autonomous [[cortisol]] secretion from the [[adenoma]]. | * [[Cortisol]] hypersecretion is the most frequent [[Hormone|hormonal]] abnormality detected in patients with functioning unilateral [[Adrenal adenoma|adrenal adenomas]]. It had been assumed that the mechanism for this was non-[[Adrenocorticotropic hormone|ACTH]]-dependent autonomous [[cortisol]] secretion from the [[adenoma]]. | ||
[[Somatic]] [[mutations]] of [[protein kinase A]] (PKA) [[Catalysis|catalytic]] subunit (''PRKACA'') were identified in patients with overt [[Cushing's syndrome]] but not in [[adenomas]] secreting less [[cortisol]]. | [[Somatic]] [[mutations]] of [[protein kinase A]] (PKA) [[Catalysis|catalytic]] subunit (''PRKACA'') were identified in patients with overt [[Cushing's syndrome]] but not in [[adenomas]] secreting less [[cortisol]]. | ||
* In additional reports, the same [[mutation]] was found in over 50 percent of patients with [[Cushing's syndrome]] due to [[Adrenal adenoma|adrenal adenomas]].< | * In additional reports, the same [[mutation]] was found in over 50 percent of patients with [[Cushing's syndrome]] due to [[Adrenal adenoma|adrenal adenomas]].<ref name="pmid24571724">{{cite journal| author=Beuschlein F, Fassnacht M, Assié G, Calebiro D, Stratakis CA, Osswald A et al.| title=Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome. | journal=N Engl J Med | year= 2014 | volume= 370 | issue= 11 | pages= 1019-28 | pmid=24571724 | doi=10.1056/NEJMoa1310359 | pmc=4727447 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24571724 }}</ref> | ||
* The most frequent hotspot p.Leu206Arg [[mutation]] is located in the active cleft of the [[catalytic]] subunit, inactivating the site where the regulatory subunit RII-beta usually binds, thus causing a constitutive [[Protein kinase A|PKA]] activation. | * The most frequent hotspot p.Leu206Arg [[mutation]] is located in the active cleft of the [[catalytic]] subunit, inactivating the site where the regulatory subunit RII-beta usually binds, thus causing a constitutive [[Protein kinase A|PKA]] activation.<ref name="pmid27389594">{{cite journal| author=Ronchi CL, Di Dalmazi G, Faillot S, Sbiera S, Assié G, Weigand I et al.| title=Genetic Landscape of Sporadic Unilateral Adrenocortical Adenomas Without PRKACA p.Leu206Arg Mutation. | journal=J Clin Endocrinol Metab | year= 2016 | volume= 101 | issue= 9 | pages= 3526-38 | pmid=27389594 | doi=10.1210/jc.2016-1586 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27389594 }}</ref> | ||
==== Mutations in [[aldosterone]]-producing adenomas | ==== Mutations in [[aldosterone]]-producing adenomas (APA) ==== | ||
* The most frequent causes of primary [[Hyperaldosteronism|aldosteronism]] include bilateral idiopathic [[hyperplasia]] and unilateral aldosterone-producing adenoma. | * The most frequent causes of primary [[Hyperaldosteronism|aldosteronism]] include bilateral idiopathic [[hyperplasia]] and unilateral aldosterone-producing adenoma.<ref name="pmid25958045">{{cite journal| author=Monticone S, Castellano I, Versace K, Lucatello B, Veglio F, Gomez-Sanchez CE et al.| title=Immunohistochemical, genetic and clinical characterization of sporadic aldosterone-producing adenomas. | journal=Mol Cell Endocrinol | year= 2015 | volume= 411 | issue= | pages= 146-54 | pmid=25958045 | doi=10.1016/j.mce.2015.04.022 | pmc=4474471 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25958045 }}</ref> | ||
* Somatic [[mutations]] in ''[[KCNJ5]]'' have been identified in patients with primary [[Hyperaldosteronism|aldosteronism]] due to | * Somatic [[mutations]] in ''[[KCNJ5]]'' have been identified in patients with primary [[Hyperaldosteronism|aldosteronism]] due to APA. | ||
* These [[mutation]]<nowiki/>s are more common in women than men; APAs with ''[[KCNJ5]]'' [[mutations]] are larger than those without [[mutation]]<nowiki/>s. | * These [[mutation]]<nowiki/>s are more common in women than men; APAs with ''[[KCNJ5]]'' [[mutations]] are larger than those without [[mutation]]<nowiki/>s. | ||
* Somatic [[mutations]] in other important [[genes]] implicated in regulation of [[aldosterone]] synthesis [[ATP1A1|(''ATP1A1'']]'', [[ATP2B3]], CACNA1D'', ''CTNNB1'', ''ARMC5'') have also been identified. | * Somatic [[mutations]] in other important [[genes]] implicated in the regulation of [[aldosterone]] synthesis [[ATP1A1|(''ATP1A1'']]'', [[ATP2B3]], CACNA1D'', ''CTNNB1'', ''ARMC5'') have also been identified. | ||
==References== | ==References== | ||
Revision as of 14:22, 26 September 2017
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]
Overview
Most adrenocortical carcinomas are sporadic, but some occur as a component of hereditary cancer syndromes such as Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, and Multiple endocrine neoplasia type 1(MEN1). Genetic basis of sporadic incidentaloma includes TP53 gene. A role for the TP53 tumor suppressor gene in sporadic ACCs is suggested by the frequent finding of loss of heterozygosity (LOH) at the 17p13 locus in sporadic ACCs. Another chromosomal locus that is strongly implicated in the pathogenesis of ACC is 11p, the area of abnormality in Beckwith-Wiedemann syndrome and the site of the insulin-like growth factor-2 (IGF-2) gene.
Risk Factors
Most adrenocortical carcinomas are sporadic, but some occur as a component of hereditary cancer syndromes.[1]
- Li-Fraumeni syndrome: breast cancer, soft tissue and bone sarcoma, brain tumors, associated with inactivating mutations of the TP53 tumor suppressor gene on chromosome 17p.
- Beckwith-Wiedemann syndrome: Wilms' tumor, neuroblastoma, hepatoblastoma, associated with abnormalities in 11p15
- Multiple endocrine neoplasia type 1 (MEN1) (parathyroid, pituitary, and pancreatic neuroendocrine tumors and adrenal adenomas, as well as carcinomas, associated with inactivating mutations in the MEN1 gene on chromosome 11q.[2]
Genetic basis of risk factors
Sporadic cases genetics
- TP53 gene, located on chromosome 17p13, is the most frequently mutated gene in human cancers. A role for the TP53 tumor suppressor gene in sporadic ACCs is suggested by the frequent finding of loss of heterozygosity (LOH) at the 17p13 locus in sporadic ACCs.[11]
- Although the loss of heterozygosity at 17p13 is common, only approximately one-third of these tumors have a mutation of TP53. This suggests that another as yet unidentified suppressor gene is present in this locus.[3]
- Another chromosomal locus that is strongly implicated in the pathogenesis of ACC is 11p, the area of abnormality in Beckwith-Wiedemann syndrome and the site of the insulin-like growth factor-2 (IGF-2) gene. LOH at the 11p15 locus and overexpression of IGF-2 have been associated with the malignant phenotype in sporadic ACCs.[13] However, other growth-related tumor suppressor genes at this locus may also be involved.
Most adrenocortical tumors are monoclonal, suggesting that they result from accumulated genetic abnormalities, such as activation of proto-oncogenes and inactivation of tumor suppressor genes.[4]
Beta-catenin mutations (CTNNB1)
- Constitutive activation of beta-catenin in the Wnt signaling pathway has been identified as a frequent alteration in benign and malignant adrenocortical tumors.[5]
- The increased occurrence of adrenal tumors in patients with mutations of adenomatous polyposis coli (APC) suggested that the Wnt/beta-catenin pathway could be involved in adrenal tumorigenesis.[6]
- This pathway is essential for embryonic development of the adrenal, and its ectopic constitutive activation is associated with cancer development in a number of tissues.[7]
Aberrant receptors
- Cortisol hypersecretion is the most frequent hormonal abnormality detected in patients with functioning unilateral adrenal adenomas. It had been assumed that the mechanism for this was non-ACTH-dependent autonomous cortisol secretion from the adenoma.
Somatic mutations of protein kinase A (PKA) catalytic subunit (PRKACA) were identified in patients with overt Cushing's syndrome but not in adenomas secreting less cortisol.
- In additional reports, the same mutation was found in over 50 percent of patients with Cushing's syndrome due to adrenal adenomas.[8]
- The most frequent hotspot p.Leu206Arg mutation is located in the active cleft of the catalytic subunit, inactivating the site where the regulatory subunit RII-beta usually binds, thus causing a constitutive PKA activation.[9]
Mutations in aldosterone-producing adenomas (APA)
- The most frequent causes of primary aldosteronism include bilateral idiopathic hyperplasia and unilateral aldosterone-producing adenoma.[10]
- Somatic mutations in KCNJ5 have been identified in patients with primary aldosteronism due to APA.
- These mutations are more common in women than men; APAs with KCNJ5 mutations are larger than those without mutations.
- Somatic mutations in other important genes implicated in the regulation of aldosterone synthesis (ATP1A1, ATP2B3, CACNA1D, CTNNB1, ARMC5) have also been identified.
References
- ↑ Sidhu S, Sywak M, Robinson B, Delbridge L (2004). "Adrenocortical cancer: recent clinical and molecular advances". Curr Opin Oncol. 16 (1): 13–8. PMID 14685087.
- ↑ Lynch HT, Radford B, Lynch JF (1990). "SBLA syndrome revisited". Oncology. 47 (1): 75–9. PMID 2300390.
- ↑ Libè R, Groussin L, Tissier F, Elie C, René-Corail F, Fratticci A; et al. (2007). "Somatic TP53 mutations are relatively rare among adrenocortical cancers with the frequent 17p13 loss of heterozygosity". Clin Cancer Res. 13 (3): 844–50. doi:10.1158/1078-0432.CCR-06-2085. PMID 17289876.
- ↑ Bourcigaux N, Gaston V, Logié A, Bertagna X, Le Bouc Y, Gicquel C (2000). "High expression of cyclin E and G1 CDK and loss of function of p57KIP2 are involved in proliferation of malignant sporadic adrenocortical tumors". J Clin Endocrinol Metab. 85 (1): 322–30. doi:10.1210/jcem.85.1.6303. PMID 10634406.
- ↑ Mazzuco TL, Durand J, Chapman A, Crespigio J, Bourdeau I (2012). "Genetic aspects of adrenocortical tumours and hyperplasias". Clin Endocrinol (Oxf). 77 (1): 1–10. doi:10.1111/j.1365-2265.2012.04403.x. PMID 22471738.
- ↑ Smith TG, Clark SK, Katz DE, Reznek RH, Phillips RK (2000). "Adrenal masses are associated with familial adenomatous polyposis". Dis Colon Rectum. 43 (12): 1739–42. PMID 11156460.
- ↑ Kikuchi A (2003). "Tumor formation by genetic mutations in the components of the Wnt signaling pathway". Cancer Sci. 94 (3): 225–9. PMID 12824913.
- ↑ Beuschlein F, Fassnacht M, Assié G, Calebiro D, Stratakis CA, Osswald A; et al. (2014). "Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome". N Engl J Med. 370 (11): 1019–28. doi:10.1056/NEJMoa1310359. PMC 4727447. PMID 24571724.
- ↑ Ronchi CL, Di Dalmazi G, Faillot S, Sbiera S, Assié G, Weigand I; et al. (2016). "Genetic Landscape of Sporadic Unilateral Adrenocortical Adenomas Without PRKACA p.Leu206Arg Mutation". J Clin Endocrinol Metab. 101 (9): 3526–38. doi:10.1210/jc.2016-1586. PMID 27389594.
- ↑ Monticone S, Castellano I, Versace K, Lucatello B, Veglio F, Gomez-Sanchez CE; et al. (2015). "Immunohistochemical, genetic and clinical characterization of sporadic aldosterone-producing adenomas". Mol Cell Endocrinol. 411: 146–54. doi:10.1016/j.mce.2015.04.022. PMC 4474471. PMID 25958045.