<i>KDM1A</i> genotyping and expression in 146 sporadic somatotroph pituitary adenomas

Chasseloup, Fanny; Regazzo, Daniela; Tosca, Lucie; Proust, Alexis; Kuhn, Emmanuelle; Hage, Mirella; Jublanc, Christel; Mokhtari, Karima; Dalle Nogare, Mattia; Avallone, Serena; Ceccato, Filippo; Tachdjian, Gerard; Salenave, Sylvie; Young, Jacques; Gaillard, Stephan; Parker, Fabrice; Boch, Anne-Laure; Chanson, Philippe; Bouligand, Jerome; Occhi, Gianluca; Kamenický, Peter

doi:10.1093/ejendo/lvae013

Cited by 2 publications

(1 citation statement)

References 26 publications

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“…However, they observed recurrent 1p LOH and monoallelic KDM1A expression in the somatic DNA from 27.9 % of adenomas, with a more frequent increase in GIPR expression in these adenomas, but this was neither constant nor exclusive, including with regard to the paradoxical response to oral glucose load. They concluded that KDM1A is not the molecular cause of GIPR expression in somatotropinomas [76].…”

Section: Molecular Causes Of Food-dependent Cushing's Syndromementioning

confidence: 99%

From the First Case Reports to KDM1A Identification: 35 Years of Food (GIP)-Dependent Cushing’s Syndrome

Bouys,

Bertherat

2024

Exp Clin Endocrinol Diabetes

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Food-dependent Cushing’s syndrome (FDCS) is a rare presentation of hypercortisolism from adrenal origin, mostly observed in primary bilateral macronodular adrenal hyperplasia (PBMAH) but also in some cases of unilateral adrenocortical adenoma. FDCS is mediated by the aberrant expression of glucose-dependent insulinotropic peptide (GIP) receptor (GIPR) in adrenocortical cells. GIP, secreted by duodenal K cells after food intake, binds to its ectopic adrenal receptor, and stimulates cortisol synthesis following meals. FDCS was first described more than 35 years ago, and its genetic cause in PBMAH has been recently elucidated: KDM1A inactivation by germline heterozygous pathogenic variants is constantly associated with a loss-of-heterozygosity of the short arm of chromosome 1, containing the KDM1A locus. This causes biallelic inactivation of KDM1A, resulting in the GIPR overexpression in the adrenal cortex. These new insights allow us to propose the KDM1A genetic screening to all PBMAH patients with signs of FDCS (low fasting cortisol that increases after a mixed meal or oral glucose load) and to all first-degree relatives of KDM1A variant carriers. Given that KDM1A is a tumor suppressor gene that has also been associated with monoclonal gammopathy of uncertain significance and multiple myeloma, the investigation of FDCS in the diagnostic management of patients with PBMAH and further genetic testing and screening for malignancies should be encouraged.

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Section: Molecular Causes Of Food-dependent Cushing's Syndromementioning

confidence: 99%

From the First Case Reports to KDM1A Identification: 35 Years of Food (GIP)-Dependent Cushing’s Syndrome

Bouys,

Bertherat

2024

Exp Clin Endocrinol Diabetes

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The Preoperative Paradoxical GH Response to Oral Glucose Load Predicts a Low Risk of Recurrence in Acromegaly

Losa,

Garbin,

Calcagnile

et al. 2024

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context A paradoxical growth hormone (GH) response to oral glucose load (oral glucose tolerance test [OGTT]) in acromegaly is associated with a milder phenotype. Objective To study whether the GH response to the OGTT predicts the risk of recurrence after initial surgical cure. Methods Retrospective, observational study at 2 tertiary care centers. We investigated 254 patients with acromegaly who were cured by surgery. All patients underwent an OGTT at diagnosis before pituitary surgery. A peak to basal GH ratio ≥120% within 90 minutes was used to distinguish paradoxical (GH-Par) from nonparadoxical responses (GH-NPar) in patients with acromegaly. Cox analysis was used to investigate whether the paradoxical GH response to OGTT was associated with the risk of disease recurrence Results A paradoxical GH response to OGTT occurred in 87 patients (34.3%, termed GH-Par group). Recurrence of acromegaly occurred in 3 patients in the GH-Par group (3.4%) and in 20 patients in the GH-NPar group (12.0%). In the multivariate analysis, the paradoxical GH response to OGTT was significantly associated with a low risk of recurrence (HR 0.18, 95% CI 0.05-0.63; P = .007). Basal GH level at diagnosis was the only other variable associated with the risk of disease recurrence (HR 1.58, 95% CI 1.01-2.47; P = .04). Conclusion Our study demonstrates that a paradoxical GH response to OGTT in the preoperative setting predicts a lower risk of disease recurrence after initial surgical cure. The pattern of GH responsiveness to OGTT is, therefore, useful to predict the long-term outcome of patients with acromegaly.

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KDM1A genotyping and expression in 146 sporadic somatotroph pituitary adenomas

Cited by 2 publications

References 26 publications

From the First Case Reports to KDM1A Identification: 35 Years of Food (GIP)-Dependent Cushing’s Syndrome

From the First Case Reports to KDM1A Identification: 35 Years of Food (GIP)-Dependent Cushing’s Syndrome

The Preoperative Paradoxical GH Response to Oral Glucose Load Predicts a Low Risk of Recurrence in Acromegaly

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