Further analysis of the disturbed adrenocortical function in the cerebro‐hepato‐renal syndrome of zellweger

Govaerts, L.; Sippell, Wolfgang G.; Monnens, L.A.H.

doi:10.1007/bf01802037

Cited by 11 publications

(4 citation statements)

References 29 publications

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“…Several studies, including studies on post mortem material, suggest that elevated (i.e. toxic) concentrations of VLCFA cause adrenal cell dysfunction leading to decreased cortisol response and thus adrenal insufficiency [7-13]. We found a correlation between the occurrence of an adrenal insufficiency and the concentration of C26:0 in plasma.…”

Section: Discussionsupporting

confidence: 49%

High prevalence of primary adrenal insufficiency in Zellweger spectrum disorders

Berendse

Engelen

Linthorst

et al. 2014

Orphanet J Rare Dis

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Zellweger spectrum disorders are a group of autosomal recessive disorders characterized by impaired peroxisome functions. The clinical spectrum is broad, ranging from the classical most severe Zellweger syndrome to patients with a relatively mild phenotype. Treatment options are limited to symptomatic and supportive therapy. During routine follow-up we discovered patients with asymptomatic primary adrenal insufficiency. It is important to detect impaired adrenal function because it has treatment implications. Primary adrenal insufficiency was found in 7/24 patients examined, with 4/7 being asymptomatic. Systematic evaluation of adrenal function, through a Synacthen test, should be included in the clinical management of these patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-014-0133-5) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 49%

High prevalence of primary adrenal insufficiency in Zellweger spectrum disorders

Berendse

Engelen

Linthorst

et al. 2014

Orphanet J Rare Dis

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“…transport. However, a complete lack of SCP2 due to peroxisome-deficient disorders, including Zellweger syndrome and adrenoleukodystrophy, may cause adrenal insufficiency (33,34). Further studies are needed to establish the functional significance of SCP2 in steroidogenic tissue.…”

Section: Discussionmentioning

confidence: 97%

Expression of sterol carrier protein 2 (SCP2) in human adrenocortical tissue

Yanase

Hara²,

Sakai

et al. 1996

European Journal of Endocrinology

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Sterol carrier protein 2 (SCP2) has been implicated in adrenal steroidogenesis by in vitro studies. In order to clarify the clinical significance of SCP2 in human steroidogenesis, we investigated the expression of SCP2 mRNA in various types of adrenocortical tissue and one testis and examined the correlation between the amounts of SCP2 and other values such as the free cholesterol content and the cholesterol side-chain cleavage (SCC) activity in the tissue mitochondria. The types of adrenocortical tissue examined included adrenocortical carcinomas (N = 3), adrenocortical adenomas from patients with Conn's syndrome (N = 3) and from patients with Cushing's syndrome (N = 3), non-functioning adrenocortical adenomas (N = 2) and normal adrenal glands (N = 2). Northern blot hybridization predominantly revealed a 1.8-kb SCP2 mRNA in all tissue specimens examined. The mRNA concentrations of SCP2 in two out of three adrenocortical carcinomas were relatively lower than those in other types of tissue. No other special tendency was observed regarding the mRNA expression levels in various tissue specimens. The mRNA concentrations of SCP2 correlated significantly with mitochondrial contents of free cholesterol (r = 0.67, p < 0.01), but was not correlated with the SCC activities in mitochondria measured by an in vitro enzyme assay. The mitochondrial SCC activities, however, were correlated significantly with the protein levels of mitochondrial P-450 scc determined by a Western blot analysis (r = 0.79, p < 0.01). The significant positive correlation between mRNA concentrations of SCP2 and the mitochondrial content of free cholesterol suggests that the central role of SCP2 in human steroidogenic tissues may be in part a translocation of cytoplasmic free cholesterol to the mitochondria, as demonstrated previously by in vitro studies.

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“…Pathophysiology of adrenal insufficiency in PD is different from the classic primary adrenal insufficiency described in Addison’s disease; i.e., it is thought to be secondary to the inability of the adrenocorticotrophs to respond to ACTH, compared to the autoimmune destruc-tion of the cells seen in Addison’s disease [11‒15]. It has been postulated that oxidative stress from elevated VLCFA has the potential to damage adrenocortical cells.…”

Section: Discussionmentioning

confidence: 99%

“…The prevalence of adrenal insufficiency in patients with PD in these reports highlights the need for performing a Cortrosyn stimulation test in all patients with PD including asymptomatic cases. Pathophysiology of adrenal insufficiency in PD is different from the classic primary adrenal insufficiency described in Addison's disease; i.e., it is thought to be secondary to the inability of the adrenocorticotrophs to respond to ACTH, compared to the autoimmune destruction of the cells seen in Addison's disease [11][12][13][14][15]. It has been postulated that oxidative stress from elevated VL-CFA has the potential to damage adrenocortical cells.…”

Section: Presentation Of Adrenal Insufficiencymentioning

confidence: 99%

Adrenal Insufficiency in Peroxisomal Disorders: A Single Institution Case Series

Gagnon¹,

Hurst²,

Ashraf³

2023

Horm Res Paediatr

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Introduction: There are two major categories of peroxisomal disorders (PD): Peroxisomal biogenesis disorders (PBD) due to defects in peroxisomal (PEX) genes and deficiency of other peroxisomal enzymes (such as D-bifunctional enzyme deficiency due to HSD17B4). PD are characterized by abnormal elevations of very long-chain fatty acids (VLCFA). We aim to evaluate the clinical phenotype of adrenal insufficiency in patients with PD and to assess any genotype-phenotype correlations with adrenal insufficiency. Methods: We performed a retrospective electronic medical record review at a single University Medical Center, of data over 12 years and identified seven patients with PD. Cases: Of the seven patients identified, six patients had a diagnosis of PBD and one had a single peroxisomal enzyme deficiency, HSD17B4. The average age of the patients at diagnosis were 0.61 ± 0.66 years. Four patients (66.7%) had primary adrenal insufficiency: three, out of the four, patients had elevated baseline ACTH. Three patients failed to have increased response after Cortrosyn™ stimulation test. Three patients were on daily hydrocortisone replacement and one patient was on stress dose hydrocortisone only as needed. Specific genetic variant analysis revealed that, all the three patients with PBD and adrenal insufficiency who were on steroid supplementation had compound heterozygous pathogenic variant in exon 13 of PEX1 c.2097dupT (p.Ile700Tyrfs*42) and c.2528G>A (p.Gly843Asp) while the one patient with peroxisomal enzyme deficiency and adrenal insufficiency had compound heterozygous pathogenic variants in HSD17B4 c. 1369A>T (p.Asn457Tyr) and c.1210-1G>A (Splice Acceptor). Two of these patients with PEX1 variants also required mineralocorticoid supplementation. The three PBD patients without adrenal insufficiency did not have a PEX1 variant. Conclusions: Primary adrenal insufficiency is common in patients with peroxisomal disorder. Based on our data, patients with the compound heterozygous PEX1 pathogenic variants of exon 13 (c.2097dupT and c.2528G>A) tend to have adrenal insufficiency. Aldosterone deficiency, though rare, can occur in PD.

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Further analysis of the disturbed adrenocortical function in the cerebro‐hepato‐renal syndrome of zellweger

Cited by 11 publications

References 29 publications

High prevalence of primary adrenal insufficiency in Zellweger spectrum disorders

High prevalence of primary adrenal insufficiency in Zellweger spectrum disorders

Expression of sterol carrier protein 2 (SCP2) in human adrenocortical tissue

Adrenal Insufficiency in Peroxisomal Disorders: A Single Institution Case Series

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