Genetic aspects of adrenocortical tumours and hyperplasias

Mazzuco, Tânia Longo; Durand, José Carlos Garcia; Chapman, Arnold; Crespigio, Jefferson; Bourdeau, Isabelle

doi:10.1111/j.1365-2265.2012.04403.x

Cited by 41 publications

(32 citation statements)

References 72 publications

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“…However, no data are available regarding the progressive transformation of Cushing's disease in BAI. However, bilateral masses may be the result of a genetic predisposition to adrenocortical cell proliferation (6). If this was the case, the disease duration could be longer in BAI than in UAI patients.…”

Section: Discussionmentioning

confidence: 99%

“…Acquired somatic genetic changes (i.e. B-catenin gene mutations) have been described in sporadic adrenal tumours, while the activation of the cAMP signalling pathway has been found in macronodular adrenal hyperplasia (4,5,6). In addition, the N363S variant of the glucocorticoid receptor gene, associated with an increased sensitivity to glucocorticoids, seems to be more frequent in BAI than in UAI patients, suggesting a possible role of this polymorphism in the formation of bilateral adrenal masses (7).…”

Section: Introductionmentioning

confidence: 99%

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Bilateral and unilateral adrenal incidentalomas: biochemical and clinical characteristics

Morelli

Palmieri

Salcuni

et al. 2013

European Journal of Endocrinology

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Objective: The possible different prevalence of arterial hypertension (AH), type 2 diabetes mellitus (T2DM), dyslipidaemia (DL) and vertebral fractures (FX) between patients with bilateral and unilateral adrenal incidentalomas (BAI and UAI, respectively) with and without subclinical hypercortisolism (SH) is unknown. In this study we compared the prevalence of AH, T2DM, DL and FX in BAI and UAI patients in relation to SH. Design: Prospective study. Methods: In 175 UAI and 38 BAI patients, we evaluated BMI, spinal and femoral bone mineral density (LS and FN BMD, respectively) and the presence of AH, T2DM, DL and FX. SH was diagnosed in the presence of R2 of the following: urinary free cortisol levels O193 nmol/24 h, serum cortisol levels after 1 mg dexamethasone suppression test O83 nmol/l or ACTH levels !2.2 pmol/l. Results: Age, BMI and cortisol secretion were comparable, while FN BMD was lower in BAI than in UAI patients (K0.45G0.86 vs 0.09G1.07, PZ0.004). The prevalence of SH, AH, T2DM, and DL was comparable, while the prevalence of FX was higher in BAI than in UAI (52.6 vs 28%, PZ0.007). The presence of FX was associated with BAI (odds ratio (OR) 2.6, 95% confidence interval (95% CI) 1.2-5.6, PZ0.016), after adjusting for SH (OR 1.77, 95% CI 0.85-3.7, PZ0.12), BMI (OR 1.06, 95% CI 0.98-1.13, PZ0.1), age (OR 1.07, 95% CI 1.04-1.11, PZ0.0001) and LS BMD (OR 1.31, 95% CI 1.03-1.67, PZ0.03). Conclusion: BAI patients have an increased FX risk than UAI ones. Further studies should investigate the causes of bone involvement in BAI patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bilateral and unilateral adrenal incidentalomas: biochemical and clinical characteristics

Morelli

Palmieri

Salcuni

et al. 2013

European Journal of Endocrinology

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“…Although BMAH may be associated with McCune-Albright syndrome (GNAS1), only a few cases of sporadic BMAH with somatic GNAS1 mutations were reported (16,17). BMAH was also found in patients with familial colon polyps and adenomatous polyposis coli (APC) gene mutation (14,16).…”

Section: Introductionmentioning

confidence: 99%

“…A limited number of cases of BMAH were described in association with the multiple endocrine neoplasia type 1 syndrome (14,15) and the hereditary leiomyomatosis and renal cancer syndrome (14,16). Although BMAH may be associated with McCune-Albright syndrome (GNAS1), only a few cases of sporadic BMAH with somatic GNAS1 mutations were reported (16,17).…”

Section: Introductionmentioning

confidence: 99%

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ARMC5 mutations in a large French-Canadian family with cortisol-secreting β-adrenergic/vasopressin responsive bilateral macronodular adrenal hyperplasia

Bourdeau

Oble²,

Magne³

et al. 2016

European Journal of Endocrinology

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Background: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare cause of Cushing's syndrome (CS) and its familial clustering has been described previously. Recent studies identified that ARMC5 mutations occur frequently in BMAH, but the relation between ARMC5 mutation and the expression of aberrant G-protein-coupled receptor has not been examined in detail yet. Methods: We studied a large French-Canadian family with BMAH and sub-clinical or overt CS. Screening was performed using the 1-mg dexamethasone suppression test (DST) in 28 family members. Screening for aberrant regulation of cortisol by various hormone receptors were examined in vivo in nine individuals. Sequencing of the coding regions of ARMC5 gene was carried out. Results: Morning ambulating cortisol post 1 mg DST were O50 nmol/l in 5/8 members in generation II (57-68 years old), 9/22 in generation III (26-46 years old). Adrenal size was enlarged at different degrees. All affected patients increased cortisol following upright posture, insulin-induced hypoglycemia and/or isoproterenol infusion. b-blockers led to the reduction of cortisol secretion in all patients with the exception of two who had adrenalectomies because of b-blockers intolerance. We identified a heterozygous germline variant in the ARMC5 gene c.327_328insC, (p.Ala110Argfs*9) in nine individuals with clinical or subclinical CS, in four out of six individuals with abnormal suppression to dexamethasone at initial investigation and one out of six individuals with current normal clinical screening tests. Conclusions: Systematic screening of members of the same family with hereditary BMAH allows the diagnosis of unsuspected subclinical CS associated with early BMAH. The relation between the causative ARMC5 mutation and the reproducible pattern of aberrant b-adrenergic and V 1 -vasopressin receptors identified in this family remains to be elucidated.

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Case report of adrenocortical carcinoma associated with double germline mutations in MSH2 and RET

Raygada

Bernstein

Miettinen

et al. 2021

American J of Med Genetics Pt A

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Adrenocortical carcinoma (ACC) is a rare aggressive malignancy that originates in the outer layer of the adrenal gland. Most ACCs are sporadic, but a small percentage of cases are due to hereditary cancer syndromes such as Li‐Fraumeni syndrome (LFS), Lynch syndrome (LS), and familial adenomatous polyposis (FAP). Multiple endocrine neoplasia type 2A (MEN2A) is an inherited disorder that predisposes to medullary thyroid cancer, pheochromocytoma, and parathyroid hyperplasia. We present here a case of ACC with both LS and MEN2A; the family and medical history were consistent with Lynch. This is, to our knowledge, the first report of a patient with ACC associated with germline mutations in RET and MSH2, and no phenotypical characteristics of MEN2A.

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Genetic aspects of adrenocortical tumours and hyperplasias

Cited by 41 publications

References 72 publications

Bilateral and unilateral adrenal incidentalomas: biochemical and clinical characteristics

Bilateral and unilateral adrenal incidentalomas: biochemical and clinical characteristics

ARMC5 mutations in a large French-Canadian family with cortisol-secreting β-adrenergic/vasopressin responsive bilateral macronodular adrenal hyperplasia

Case report of adrenocortical carcinoma associated with double germline mutations in MSH2 and RET

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