A case of neurofibromatosis type 1 with an aldosterone‐producing adenoma of the adrenal

Biagi, Pierluigi; Alessandri, Michael; Campanella, G; Castro, Rodrigo F.; Totteri, A; Fanciullacci, M

doi:10.1046/j.1365-2796.1999.00577.x

Cited by 6 publications

(3 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the data presented in this manuscript support the importance of neurofibromin as a causative factor in adrenal nodular hyperplasia in patients with NF1. Biallelic inactivation of NF1 had been previously reported in one case of adrenal cortical tumor [23], and adrenal adenoma have been described in association with NF1 in several reports [21–23]. …”

Section: Discussionmentioning

confidence: 99%

“…Inactivating mutations in NF1 are frequent in adrenal medullary tumors (pheochromocytomas) and it has been shown that NF1 is required for control of proliferation and differentiation in chromaffin cells [20]. While medullary tumors are frequent in NF1, only several cases of adrenal cortex adenoma associated with NF1 have been described in the literature [21–23]. However, these cases of sporadic cortical hyperplasia suggest that NF1 might have yet unidentified roles in control of adrenocortical homeostasis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Double NF1 Inactivation Affects Adrenocortical Function in NF1Prx1 Mice and a Human Patient

et al. 2015

View full text Add to dashboard Cite

BackgroundNeurofibromatosis type I (NF1, MIM#162200) is a relatively frequent genetic condition, which predisposes to tumor formation. Apart from tumors, individuals with NF1 often exhibit endocrine abnormalities such as precocious puberty (2,5–5% of NF1 patients) and some cases of hypertension (16% of NF1 patients). Several cases of adrenal cortex adenomas have been described in NF1 individuals supporting the notion that neurofibromin might play a role in adrenal cortex homeostasis. However, no experimental data were available to prove this hypothesis.Materials and MethodsWe analysed Nf1Prx1 mice and one case of adrenal cortical hyperplasia in a NF1patient.ResultsIn Nf1Prx1 mice Nf1 is inactivated in the developing limbs, head mesenchyme as well as in the adrenal gland cortex, but not the adrenal medulla or brain. We show that adrenal gland size is increased in NF1Prx1 mice. Nf1Prx1 female mice showed corticosterone and aldosterone overproduction. Molecular analysis of Nf1 deficient adrenals revealed deregulation of multiple proteins, including steroidogenic acute regulatory protein (StAR), a vital mitochondrial factor promoting transfer of cholesterol into steroid making mitochondria. This was associated with a marked upregulation of MAPK pathway and a female specific increase of cAMP concentration in murine adrenal lysates. Complementarily, we characterized a patient with neurofibromatosis type I with macronodular adrenal hyperplasia with ACTH-independent cortisol overproduction. Comparison of normal control tissue- and adrenal hyperplasia- derived genomic DNA revealed loss of heterozygosity (LOH) of the wild type NF1 allele, showing that biallelic NF1 gene inactivation occurred in the hyperplastic adrenal gland.ConclusionsOur data suggest that biallelic loss of Nf1 induces autonomous adrenal hyper-activity. We conclude that Nf1 is involved in the regulation of adrenal cortex function in mice and humans.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Double NF1 Inactivation Affects Adrenocortical Function in NF1Prx1 Mice and a Human Patient

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Mid-aortic syndrome [13], aldosterone producing tumor [14], aortic coarctations [15] and stretching of the renal artery by neural tumor have also been described as possible determinants. The vascular lesions of renal artery stenosis were characterized by fibromuscular dysplasia [10,16], intramural renal artery Schwann cell proliferation [17], or vascular lesions characterized by an intimal proliferation of spindle cells with destruction of the internal elastic membrane, frequently accompanied by loss or attenuation of the media and fibrosis of the 195 Fig.…”

Section: Discussionmentioning

confidence: 99%

Renal artery stenosis and aneurysmatic dilatation of arteria carotis interna in tuberous sclerosis complex

2002

View full text Add to dashboard Cite

Hypertension in children with neurocutaneous disorders (phacomatoses) is a well-recognized complication of these diseases and the cause of hypertension is fairly specific within each group. In patients with neurofibromatosis, hypertension is mainly caused by renovascular disease, whereas in tuberous sclerosis (TSC) reasons for hypertension are renoparenchymal lesions, such as angiomyolipoma or cysts. We report on a girl with TSC and hypertension due to unilateral renal artery stenosis associated with aneurysmatic changes of internal carotid artery. This unusual combination of symptoms in our patient supports the importance of thorough and complete investigation of hypertension in children with phacomatoses.

show abstract

Pediatric Adrenal Cortical Carcinoma: Brain Metastases and Relationship to NF-1, Case Reports and Review of the Literature

Wagner

Fleitz

Kleinschmidt-DeMasters

2005

J Neurooncol

View full text Add to dashboard Cite

Adrenal cortical carcinoma (ACC) is a rare childhood neoplasm that seldom manifests brain metastases; hence few papers in the literature focus on neurological manifestations associated with ACC. Although ACC is known to be a signature tumor type in several inherited cancer predisposition syndromes, particularly Li Fraumeni, ACC has not been previously associated with neurofibromatosis, type 1 (NF-1), an inherited disorder with frequent CNS lesions that might prompt concern for metastatic disease by neuroimaging studies. We present two pediatric patients with ACC and unusual CNS findings. The first child developed metastasis to the brain 4 years after resection of his adrenal primary and 2 and 1 years, respectively, after metastases to the liver and lungs. Soon after our experience with this patient, a girl with known NF-1 presented with virilization; adrenalectomy disclosed an ACC and systemic metastases were found within months. Disseminated disease prompted concern that her complex intracranial lesions identified by neuroimaging studies might represent brain metastases, but this proved to be NF1-related hamartomatous lesions. We review the literature on ACCs in pediatric patients regarding brain metastases and previous associations with NF-1.

show abstract

A case of neurofibromatosis type 1 with an aldosterone‐producing adenoma of the adrenal

Cited by 6 publications

References 19 publications

Double NF1 Inactivation Affects Adrenocortical Function in NF1Prx1 Mice and a Human Patient

Double NF1 Inactivation Affects Adrenocortical Function in NF1Prx1 Mice and a Human Patient

Renal artery stenosis and aneurysmatic dilatation of arteria carotis interna in tuberous sclerosis complex

Pediatric Adrenal Cortical Carcinoma: Brain Metastases and Relationship to NF-1, Case Reports and Review of the Literature

Contact Info

Product

Resources

About