ArticleJCI insight2017
Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing's syndrome.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 56 citations in OpenAlex.
- Molecular pathology of primary aldosteronism and hypercortisolism: Impact on adrenal surgery.iScience · 2026Review
- Advancements in the research of the structure, function, and disease-related roles of ARMC5.Frontiers of medicine · 2025Review
- Cushing syndrome.Nature reviews. Disease primers · 2025Review
- Molecular and Genetics Perspectives on Primary Adrenocortical Hyperfunction Disorders.International journal of molecular sciences · 2024Review
- Potential role of tirzepatide towards Covid-19 infection in diabetic patients: a perspective approach.Inflammopharmacology · 2023Review
- Decreased steroidogenic enzyme activity in benign adrenocortical tumors is more pronounced in bilateral lesions as determined by steroid profiling in LC-MS/MS during ACTH stimulation test.Endocrine connections · 2022Article
- Bilateral Adrenal Hyperplasia: Pathogenesis and Treatment.Biomedicines · 2021Review
- Aldosterone is Aberrantly Regulated by Various Stimuli in a High Proportion of Patients with Primary Aldosteronism.The Journal of clinical endocrinology and metabolism · 2021Article
- Molecular Genetic and Genomic Alterations in Cushing's Syndrome and Primary Aldosteronism.Frontiers in endocrinology · 2021Review
- ARMC5 variants in PRKAR1A-mutated patients modify cortisol levels and Cushing's syndrome.Endocrine-related cancer · 2020Article
- Molecular Basis of Primary Aldosteronism and Adrenal Cushing Syndrome.Journal of the Endocrine Society · 2020Review
- Adrenocortical tumorigenesis: Lessons from genetics.Best practice & research. Clinical endocrinology & metabolism · 2020Review
- Cushing syndrome: Old and new genes.Best practice & research. Clinical endocrinology & metabolism · 2020Review
- The pathogenic role of the GIP/GIPR axis in human endocrine tumors: emerging clinical mechanisms beyond diabetes.Reviews in endocrine & metabolic disorders · 2020Review
- High expression of adrenal P450 aromatase (CYP19A1) in association with ARMC5-primary bilateral macronodular adrenocortical hyperplasia.The Journal of steroid biochemistry and molecular biology · 2019Article
- Coexistence of Myelolipoma and Primary Bilateral Macronodular Adrenal Hyperplasia With GIP-Dependent Cushing's Syndrome.Frontiers in endocrinology · 2019Article
- An update on adrenal endocrinology: significant discoveries in the last 10 years and where the field is heading in the next decade.Hormones (Athens, Greece) · 2018Review
- Advances in adrenal tumors 2018.Endocrine-related cancer · 2018Review
- Genetics of Cushing's Syndrome.Endocrinology and metabolism clinics of North America · 2018Review
Corrections and comments
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Authors and funding
31 authors at 9 institutions in 5 countries.
Funding
Abstract
GIP-dependent Cushing's syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Here we performed molecular analyses on adrenocortical adenomas and bilateral macronodular adrenal hyperplasias obtained from 14 patients with GIP-dependent adrenal Cushing's syndrome and one patient with GIP-dependent aldosteronism. GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had a 19q duplication only. We demonstrated that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in adenoma cells. Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing's syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.