ArticleThe Journal of clinical endocrinology and metabolism2012
Phosphodiesterase 11A (PDE11A) gene defects in patients with acth-independent macronodular adrenal hyperplasia (AIMAH): functional variants may contribute to genetic susceptibility of bilateral adrenal tumors.
Article in The Journal of clinical endocrinology and metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 80 citations in OpenAlex.
- Primary Pigmented Nodular Adrenocortical Disease Presenting as Osteonecrosis of the Femoral Head: A Case Report.Cureus · 2026Article
- Preventing Cushing Syndrome: Adrenalectomy inJCEM case reports · 2026Article
- cAMP/PKA signaling in endocrine hypertension: genetic mechanisms and pathophysiological insights.Frontiers in endocrinology · 2026Review
- PDE11A Is a Phenotype Modulator of Primary Bilateral Macronodular Adrenal Hyperplasia: Results of a 334-Patient Series.The Journal of clinical endocrinology and metabolism · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- PDE10A as a novel diagnostic and therapeutic target in cancer: insights and challenges.Frontiers in oncology · 2025Review
- Germline targeted next-generation sequencing in patients with adrenal incidentalomas.Frontiers in endocrinology · 2025Article
- Molecular and Genetics Perspectives on Primary Adrenocortical Hyperfunction Disorders.International journal of molecular sciences · 2024Review
- New pathogenic variants in ARMC5 gene in a series of Italian patients affected by primary bilateral macronodular adrenocortical hyperplasia (PBMAH).Molecular genetics & genomic medicine · 2023Article
- Gene Mutations in Cushing's Syndrome.Molecular syndromology · 2023Review
- Primary bilateral macronodular adrenal hyperplasia: definitely a genetic disease.Nature reviews. Endocrinology · 2022Review
- Functional characteristics and research trends of PDE11A in human diseases (Review).Molecular medicine reports · 2022Article
- An Overview of the Heterogeneous Causes of Cushing Syndrome Resulting From Primary Macronodular Adrenal Hyperplasia (PMAH).Journal of the Endocrine Society · 2022Review
- Genetic Alterations in Benign Adrenal Tumors.Biomedicines · 2022Review
- The cAMP-signaling cancers: Clinically-divergent disorders with a common central pathway.Frontiers in endocrinology · 2022Review
- Disorders of the adrenal cortex: Genetic and molecular aspects.Frontiers in endocrinology · 2022Review
- Bilateral Adrenal Hyperplasia: Pathogenesis and Treatment.Biomedicines · 2021Review
- Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway.Biomedicines · 2021Review
- A novel nonsense mutation in ARMC5 causes primary bilateral macronodular adrenocortical hyperplasia.BMC medical genomics · 2021Article
- Review
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11 authors at 6 institutions in 2 countries.
Funding
Abstract
contextPhosphodiesterases (PDEs) are key regulatory enzymes of intracellular cAMP levels. PDE11A function has been linked to predisposition to adrenocortical tumors.
objectiveThe aim of the study was to study the PDE11A gene in a large cohort of patients with ACTH-independent macronodular adrenal hyperplasia (AIMAH) and in control subjects.
designThe PDE11A entire coding region was sequenced in 46 patients with AIMAH and 192 controls. Two variants found in AIMAH patients were transiently expressed in HEK 293 and adrenocortical H295R cells for further functional studies.
resultsThe frequency of all PDE11A variants was significantly higher among patients with AIMAH (28%) compared to controls (7.2%) (P = 5 × 10(-5)). Transfection of the two PDE11A variants found in AIMAH patients only (D609N or M878V) showed that cAMP levels were higher, after forskolin stimulation, in cells transfected with the PDE11A mutants, compared to cells transfected with the wild-type PDE11A in HEK 293 cells (P < 0.05). Moreover, transfection with mutants PDE11A increased transcriptional activity of a cAMP-response element reporter construct compared to wild-type PDE11A in HEK 293 cells (P < 0.0004 for D609N and P < 0.003 for M878V) and in the adrenocortical H295R cells (P < 0.05 for D609N and M878V). In addition, analysis of cAMP levels in intact living culture cells by fluorescence resonance energy transfer probes showed increased cAMP in forskolin-treated cells transfected with PDE11A variants compared with wild-type PDE11A (P < 0.05).
conclusionWe conclude that PDE11A genetic variants may increase predisposition to AIMAH.
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