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- Kobayashi, Hiroki, et al.
(författare)
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Assessing Lateralization Index of Adrenal Venous Sampling for Surgical Indication in Primary Aldosteronism
- 2024
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Ingår i: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM. - 0021-972X .- 1945-7197.
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Tidskriftsartikel (refereegranskat)abstract
- Context Clinical practice guidelines recommend the lateralization index (LI) as the standard for determining surgical eligibility in primary aldosteronism (PA).Objective Our goal was to identify the optimal LI cutoffs in adrenal venous sampling (AVS) for diagnosing PA that is amenable to surgical cure.Methods We conducted a retrospective international cohort study across 16 institutions in 11 countries, including 1550 patients with PA who underwent AVS, with and/or without adrenocorticotropin (ACTH) stimulation. The establishment of optimal cutoffs was informed by a survey of 82 patients with PA in Japan, aimed at determining the LI cutoff aligned with patient expectations for a surgical cure rate.Results The survey revealed that a median cure rate expectation of 80% would motivate patients with PA towards undergoing adrenalectomy. The optimal LI cutoffs achieving an adjusted positive predictive value (PPV) of 80% were identified as 3.8 for unstimulated AVS and 3.4 for ACTH-stimulated AVS. Furthermore, a contralateral ratio of less than 0.4 and the detection of an adrenal nodule on computed tomography imaging were identified as independent predictors of surgically curable PA. Incorporating these factors with the optimal LI cutoffs, the adjusted PPV increased to 96.6% for unstimulated AVS and 89.6% for ACTH-stimulated AVS. No clear differences in predictive ability between unstimulated and ACTH-stimulated LI were found.Conclusion The present study clarified the optimal LI cutoffs for without and with ACTH stimulation. The presence of contralateral suppression and adrenal nodule on CT imaging seems to provide additional available information besides LI for surgical indication.
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| 2. |
- Naruse, Mitsuhide, et al.
(författare)
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International multicenter survey on screening and confirmatory testing in primary aldosteronism.
- 2023
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Ingår i: European journal of endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 188:1
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Tidskriftsartikel (refereegranskat)abstract
- Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized.In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated.We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers.Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA.
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| 3. |
- Zhou, Junhua, et al.
(författare)
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Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1360-1372
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Tidskriftsartikel (refereegranskat)abstract
- Sequence analysis identifies gain-of-function somatic mutations in GNA11 or GNAQ in CTNNB1-mutant aldosterone-producing adenomas. Most patients with these mutations presented during puberty, pregnancy or menopause, with elevated LHCGR expression. Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1.
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