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PRKACA mutations in cortisol-producing adenomas and adrenal hyperplasia : A single-center study of 60 cases
- Publication Year :
- 2015
-
Abstract
- ObjectiveCortisol excess due to adrenal adenomas or hyperplasia causes Cushing's syndrome. Recent genetic studies have identified a somatic PRKACAL206R mutation as a cause of cortisol-producing adenomas. We aimed to compare the clinical features of PRKACA-mutant lesions with those of CTNNB1 mutations, and to search for similar mutations in unilateral hyperplasia or tumors co-secreting aldosterone.Design, patients, and methodsIn this study, 60 patients with cortisol excess who had adrenalectomies at our institution between 1992 and 2013 were assessed, and somatic mutations were determined by Sanger sequencing. A total of 36 patients had overt Cushing's syndrome, the remainder were subclinical: 59 cases were adenomas (three bilateral) and one was classified as hyperplasia. Four tumors had proven co-secretion of aldosterone.ResultsAmong cortisol-secreting unilateral lesions without evidence of co-secretion (n=52), we identified somatic mutations in PRKACA (L206R) in 23.1%, CTNNB1 (S45P, S45F) in 23.1%, GNAS (R201C) in 5.8%, and CTNNB1+GNAS (S45P, R201H) in 1.9%. PRKACA and GNAS mutations were mutually exclusive. Of the co-secreting tumors, two (50%) had mutations in KCNJ5 (G151R and L168R). The hyperplastic gland showed a PRKACAL206R mutation, while patients with bilateral adenomas did not have known somatic mutations. PRKACA-mutant lesions were associated with younger age, overt Cushing's syndrome, and higher cortisol levels vs non-PRKACA-mutant or CTNNB1-mutant lesions. CTNNB1 mutations were more significantly associated with right than left lesions.ConclusionsPRKACAL206R is present not only in adenomas, but also in unilateral hyperplasia and is associated with more severe autonomous cortisol secretion. Bilateral adenomas may be caused by yet-unknown germline mutations.
- Subjects :
- Cortisol secretion
Adult
Male
medicine.medical_specialty
Hydrocortisone
Endocrinology, Diabetes and Metabolism
Medizin
medicine.disease_cause
chemistry.chemical_compound
Endocrinology
Germline mutation
Internal medicine
KCNJ5
medicine
GNAS complex locus
Humans
Aldosterone
Cushing Syndrome
beta Catenin
Aged
Mutation
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
biology
Adrenal Hyperplasia, Congenital
business.industry
Age Factors
Adrenalectomy
General Medicine
Hyperplasia
Middle Aged
medicine.disease
Adrenal Cortex Neoplasms
PRKACA
Phenotype
chemistry
Adrenocortical Adenoma
biology.protein
Female
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....63c24d3382fc8c2fc88e2a80f5eaedb2