Adrenal insufficiency in phytosterolaemia

Mushtaq, Talat; Wales, Jerry; Wright, Neil

doi:10.1530/eje-07-0222

Cited by 21 publications

(15 citation statements)

References 20 publications

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“…Clinically, sitosterolemia (also known as phytosterolemia) manifests either in children as tendon and tuberous xanthomas (67)(68)(69)(70)(71) or in young adults with severe CHD attributable to massive accumulation of sterols and stanols in monocyte-derived macrophages ( 25,68,(72)(73)(74)(75). Other clinical manifestations include arthralgia and intermittent arthritis ascribed to sitosterol deposits ( 45,70 ); liver disease ( 45 ); and hematological abnormalities ( 45,69,76,77 ), including abnormally shaped, fragile erythrocytes and large platelets. In one patient, adrenal insuffi ciency was present ( 76 ).…”

Section: Abcg5/8 Geneticsmentioning

confidence: 99%

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Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk

Calandra

Tarugi

Speedy

et al. 2011

Journal of Lipid Research

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This review covers the dietary and biochemical origins and fates of key classes of sterol molecules in humans, namely, cholesterol and the relatively under-recognized and often unappreciated noncholesterol sterols and stanols; the intra-and intercellular systems that govern their transport; and the contribution of innate genetic programs to the biochemically observed levels of plasma LDL-cholesterol (LDL-C). The reasons for these foci are both biological and medical. The former is the burgeoning knowledge of the normal physiological roles that cholesterol performs within cell membranes in supporting receptor-mediated signaling activities ( 1-4 ), the movement of diverse molecules through different membranebound compartments (5)(6)(7)(8), and multiple other cell functions (9)(10)(11), including myelination ( 12 ). The latter, Abstract This review integrates historical biochemical and modern genetic fi ndings that underpin our understanding of the low-density lipoprotein (LDL) dyslipidemias that bear on human disease. These range from life-threatening conditions of infancy through severe coronary heart disease of young adulthood, to indolent disorders of middle-and oldage. We particularly focus on the biological aspects of those gene mutations and variants that impact on sterol absorption and hepatobiliary excretion via specifi c membrane transporter systems ( NPC1L1 , ABCG5/8 ); the incorporation of dietary sterols ( MTP ) and of de novo synthesized lipids ( HMGCR, TRIB1 ) into apoB-containing lipoproteins ( APOB ) and their release into the circulation ( ANGPTL3, SARA2, SORT1 ); and receptor-mediated uptake of LDL and of intestinal and hepatic-derived lipoprotein remnants ( LDLR, APOB, APOE, LDLRAP1, PCSK9, IDOL ).The insights gained from integrating the wealth of genetic data with biological processes have important implications for the classifi cation of clinical and presymptomatic diagnoses of traditional LDL dyslipidemias, sitosterolemia, and newly emerging phenotypes, as well as their management through both nutritional and pharmaceutical means. -Calandra, S., P. Tarugi Abbreviations: ABCG5, ATP-binding cassette, subfamily G, member 5; ABCG8, ATP-binding cassette, subfamily G, member 8; ABL, abetalipoproteinemia; ADH, autosomal dominant hypercholesterolemia; ANGPTL3, angiopoietin-like 3; ARH, autosomal recessive hypercholesterolemia; BMI, body mass index; CAC, coronary artery calcifi cation; CAD, coronary artery disease; CHD, coronary heart disease; CMRD, chylomicron retention disease; CYP7A1 , cholesterol 7 ␣ -hydroxylase; EGF, epidermal growth factor; ER, endoplasmic reticulum; FCHL, familial combined hyperlipidemia; FDB, familial defective apoB; FH, familial hypercholesterolemia; FHBL, familial hypobetalipoproteinemia; GWAS, genome-wide association study; HMGCR, HMGCoA reductase; IDOL, inducible degrader of LDLR; LD, linkage disequilibrium; LDL-C, LDL-cholesterol; LDLR, LDL receptor; LRP1, LDLRAP1, LDLR-associated protein 1; LDLR-related protein 1; LXR, liver X receptor; MI, myocardial infarction; MTP, m...

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Section: Abcg5/8 Geneticsmentioning

confidence: 99%

“…Other clinical manifestations include arthralgia and intermittent arthritis ascribed to sitosterol deposits ( 45,70 ); liver disease ( 45 ); and hematological abnormalities ( 45,69,76,77 ), including abnormally shaped, fragile erythrocytes and large platelets. In one patient, adrenal insuffi ciency was present ( 76 ).…”

Section: Abcg5/8 Geneticsmentioning

confidence: 99%

Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk

Calandra

Tarugi

Speedy

et al. 2011

Journal of Lipid Research

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“…The authors concluded that Mediterranean stomatocytosis/macrothrombocytopenia is caused by an excess of phytosterols, that phytosterolemia can be diagnosed based on the distinctive hematology findings including unexplained hemolysis and macrothrombocytopenia, and that phytosterolemia should be considered in the differential diagnosis of all patients with large platelets 35 . A subsequent follow up study of one of these families showed that sitosterolemia was also associated with adrenal and ovarian failure, suggesting that build up of non-cholesterol sterols can lead to disruption of steroid hormone pathway synthesis, although it should be emphasized that these features are not classically present in most cases of sitosterolemia 36 .…”

Section: Are There Other Clinical Features That May Indicate Sitostermentioning

confidence: 99%

Plant sterols and stanols: Their role in health and disease

Patel

2008

Journal of Clinical Lipidology

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Mammalian physiological processes, and likely any organism with a biliary tree, can distinguish between dietary cholesterol and non-cholesterols, retaining very little of the non-cholesterol in their bodies. Historically, the distinction between plant sterols and cholesterol has been known about for a century or more. That plants sterols were not 'absorbed' has been investigated for almost half a century. Indeed, the oral of plant sterols in gram quantities was shown to interfere with cholesterol absorption and is one of the oldest pharmacological therapies for hypercholesterolemia. Although the basis for the latter was shown to be caused by exclusion of cholesterol from intestinal micelles by plant sterols, it was not until the identification of the a rare genetic disease, sitosterolemia, first described in 1974, that led to the hypothesis that specific molecular mechanism(s) governed both the entry and excretion of sterols by the body. This talk will cover the physiology of dietary sterol metabolism, genetics and pathophysiology of sitosterolemia. Additionally, the role of plant sterols in normal and abnormal metabolism in humans as well as selected animal models will be discussed.

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“…Comparable results were previously reported for juvenile male Japanese quails (Liu et al, 2012). Except for one study in humans (Mushtaq et al, 2007), evidence regarding PS induced adrenal insufficiency is lacking. Liu et al (2012) suggested that as PS reduced circulating cholesterol (LDL-C) levels, adrenal glands likely used PS as precursors for steroidogenesis; alternatively, endogenous LDL-C was sufficient for adrenal corticosterone production.…”

Section: Discussionmentioning

confidence: 45%

Effects of Phytosterols as Food Additives on Adrenal and Reproductive Endocrine Function during Sexual Maturation in Male Japanese Quail (<i>Coturnix coturnix japonica</i>)

et al. 2018

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Varying amounts of phytosterols (PS) occur naturally in several foods of plant origin. PS, which are structurally and functionally similar to cholesterol, have been shown to reduce plasma total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels.Moreover, PS disrupts endocrine function in certain animals. In the present study, we investigated the effects of high doses of PS on adrenal and reproductive endocrine function during sexual maturation in Japanese male quails. Two experiments were conducted; in the first experiment, quail chicks were subjected to long-term chronic feeding of PS (8, 80, and 800 mg/kg body weight [BW]) and the chemicals were gavaged into the crop sac from 7-50 days post-hatching. From the forty-fourth day, half of the animals in each group were subjected to a 6-day adrenocorticotropic hormone (ACTH) challenge for artificial stimulation of the adrenal gland and evaluation of long-term PS effects; in the second experiment, single doses of PS were subcutaneously injected (SC) into adult males (10-weeks-old) to assess the acute direct effect. Results indicated that chronically PS-fed animals showed a better adrenal response to ACTH challenge, and the corticosterone levels were higher (P < 0.05) than those of the controls. Moreover, corticosterone levels were also high (P < 0.05) 3 h after SC injection of PS. In contrast, testosterone levels and the testes weights were significantly lower (P < 0.05) in the groups chronically administered with PS. No differences were observed in the testosterone levels in the acute experiment or luteinizing hormone (LH) levels in either experiment. In conclusion, the differential effects of PS on the adrenal gland and testis might be due to preferential use of different lipoprotein-cholesterol forms for steroid production. In addition, PS might locally perturb testosterone production by its accumulation or delay in testicular maturation.

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Adrenal insufficiency in phytosterolaemia

Cited by 21 publications

References 20 publications

Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk

Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk

Plant sterols and stanols: Their role in health and disease

Effects of Phytosterols as Food Additives on Adrenal and Reproductive Endocrine Function during Sexual Maturation in Male Japanese Quail (<i>Coturnix coturnix japonica</i>)

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