Rare correlation of somatic PRKACA mutations with pregnancy-associated aldosterone- and cortisol-producing adenomas: a case report and literature review

• Published in: BMC endocrine disorders 2024-07, Vol.24 (1), p.116-8, Article 116
• Main Authors: Lin, Jianfan, Li, Yufei, Huang, Zhenxing, Zhu, Yingli, Li, Li, Yang, Haiyan, Liang, Xinghuan, Qin, Yingfen, Zhou, Jia, Xian, Jing, Liu, Deyun, Lu, Decheng, Luo, Zuojie
• Format: Article
• Language: English
• Subjects: Abdomen; Accountants; Adenoma; Adenoma - genetics; Adenoma - metabolism; Adenoma - pathology; Adrenal adenoma; Adrenal Cortex Neoplasms - genetics; Adrenal Cortex Neoplasms - metabolism; Adrenal Cortex Neoplasms - pathology; Adrenal glands; Adrenocortical Adenoma - genetics; Adrenocortical Adenoma - metabolism; Adrenocortical Adenoma - pathology; Adrenocortical Adenoma - surgery; Adult; Aldosterone; Aldosterone - metabolism; Aldosterone synthase; Analysis; Blood pressure; Bone density; Case Report; Chorionic gonadotropin; Co-secretion; Corticosteroids; Cortisol; Cushing Syndrome - genetics; Cushing Syndrome - pathology; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits - genetics; Cytochrome P450; Development and progression; Diabetes; Female; Genetic aspects; Glucose; Gonadotropin; Gonadotropins; Hormones; Humans; Hydrocortisone - metabolism; Hyperaldosteronism - genetics; Hyperaldosteronism - pathology; Hyperaldosteronism - surgery; Hyperplasia; Hypertension; Kinases; Lipids; Literature reviews; Luteinizing hormone; Mutation; Osteoporosis; Patients; Pituitary (anterior); Pregnancy; Pregnancy Complications, Neoplastic - genetics; Pregnancy Complications, Neoplastic - pathology; Pregnant women; PRKACA; Somatic mutations; Steroid 11β-hydroxylase; Tumors; Type 2 diabetes
• ISSN: 1472-6823; 1472-6823
• DOI: 10.1186/s12902-024-01645-x

Somatic mutations have been observed to induce aldosterone-producing adenomas (APAs). These may be accelerated during pregnancy. Somatic PRKACA mutations are common in cortisol-producing adenomas (CPAs). However, their role in APAs, particularly aldosterone- and cortisol-producing adenomas (A/CPAs), is not well understood. This study aims to investigate the association between PRKACA mutations and the accelerated development of A/CPAs during pregnancy. A patient with primary aldosteronism (PA) associated with severe Cushing's syndrome (CS) underwent surgical resection of an adrenal tumor one year after delivery. Pathologic examination revealed an adrenocortical adenoma characterized primarily by zona glomerulosa hyperplasia. Somatic mutation analysis revealed the presence of the somatic PRKACA mutation, which was validated as a deleterious mutation by various computational databases. Immunohistochemical results showed positive staining for cytochrome P450 family 11 subfamily B member 1 (CYP11B1), cytochrome P450 family 11 subfamily B member 2 (CYP11B2), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). Our study included a review of 20 previously documented cases of aldosterone- and cortisol-producing adenomas (A/CPAs), two of which were concurrently positive for both CYP11B1 and CYP11B2, consistent with our findings. Somatic mutations in PRKACA may correlate with the upregulation of LHCGR, which synergistically drives the accelerated growth of co-secretion tumors during pregnancy, thereby exacerbating disease progression.