Cortisol secretion in patients on simvastatin

Candrina, R; Balestrieri, G; Salvi, Andrea; Stefano, Ottavio Di; Spandrio, Sara; Giustina, G

doi:10.1016/0140-6736(90)90182-5

Cited by 18 publications

(10 citation statements)

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“…More recently, studies on the effect of simvastatin on adrenocortical function have been reported (22,23), again with conflicting results. Mol et al (22) investigated the response to a short ACTH stimulation test in 21 subjects with heterozygous FH and 3 with unclassified hypercholesterolemia; they found a decrease in stimulated plasma cortisol at peak response (30 and 90 min).…”

Section: Discussionmentioning

confidence: 95%

“…The results of numerous studies in which the effects of inhibitors of cholesterol biosynthesis on adrenal corticosteroid production have been examined have yielded conflicting results (19)(20)(21)(22)(23)(39)(40)(41). Treatment with triparanol (MER-29), which inhibits a late stage of cholesterol synthesis, reduced the urinary excretion of corticosteroids and the serum concentrations of hydrocortisone after ACTH stimulation in hypercholesterolemic patients compared to baseline values (41).…”

Section: Discussionmentioning

confidence: 98%

“…Previous studies (19,20) have indicated that clinically effective doses of lovastatin (40-80 mg/day) do not impair adrenal function in patients with heterozygous FH during either prolonged or short periods of ACTH stimulation (19,20) and do not exacerbate the mild impairment in adrenal function noted in homozygous FH patients under basal conditions (21). In contrast, conflicting results have recently been reported from short term ACTH stimulation tests in heterozygous FH patients treated with simvastatin (22,23); no studies of prolonged ACTH stimulation have been reported. Mevalonic acid (MVA), the immediate product of HMG-CoA reductase, is present in plasma and urine (24)(25)(26).…”

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confidence: 86%

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The Influence of Simvastatin on Adrenal Corticosteroid Production and Urinary Mevalonate during Adrenocorticotropin Stimulation in Patients with Heterozygous Familial Hypercholesterolemia*

Prihoda

Pappu

Smith

et al. 1991

The Journal of Clinical Endocrinology & Metabolism

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The adrenal gland requires a continuous supply of cholesterol for the biosynthesis of adrenal corticosteroids, which can be supplied by low density lipoprotein receptor-mediated uptake or local synthesis. The present study examined whether hypolipidemic therapy with a potent HMG CoA reductase inhibitor, simvastatin, compromises the adrenal response to ACTH stimulation in adult patients with heterozygous familial hypercholesterolemia. The adrenal response to a 36-h continuous ACTH infusion was determined at baseline and after 2 months of simvastatin treatment (40 mg, twice daily) in eight patients. Simvastatin reduced total and low density lipoprotein cholesterol levels by 36% and 45%, respectively. The time course of the increase in serum cortisol concentrations with continuous ACTH infusion was the same before and during simvastatin therapy, as were the rates of urinary excretion of free cortisol, 17-hydroxycorticosteroids, and 17-ketosteroids. Urinary excretion of mevalonate, which correlates with rates of whole body cholesterol synthesis, decreased from 3.8 +/- 0.42 (+/- SEM) mu,ol/24 h at baseline to 2.75 +/- 0.56 on simvastatin; no significant changes were seen in the urinary mevalonate levels before and after simvastatin therapy during ACTH stimulation. We conclude that the hypolipidemic effects of simvastatin in patients with heterozygous familial hypercholesterolemia are paralleled by a decrease in urinary mevalonate, but that the drug does not adversely affect ACTH-stimulated adrenal corticosteroid production.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 86%

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The Influence of Simvastatin on Adrenal Corticosteroid Production and Urinary Mevalonate during Adrenocorticotropin Stimulation in Patients with Heterozygous Familial Hypercholesterolemia*

Prihoda

Pappu

Smith

et al. 1991

The Journal of Clinical Endocrinology & Metabolism

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“…35,36 The impact of statins on adrenal function has been studied in multiple populations with a wide variety of statins. 23,[25][26][27][28][29]31,32,[37][38][39][40][41][42][43][44][45] None of these studies showed clinically relevant impairment of adrenal function, secondary to statin therapy. Patients with heterozygous or homozygous familial hypercholesterolemia could also theoretically be at increased risk of adrenal dysfunction because of their reduced capacity to use LDL receptor-mediated cholesterol uptake.…”

Section: 22mentioning

confidence: 99%

“…[23][24][25][26][27][28][29][30][31][32] Some of this concern was based on studies in isolated patients with abetalipoproteinemia and homozygous hypobetaliproteinemia showing mildly raised ACTH levels, normal cortisol levels, and a blunted response to prolonged ACTH stimulation. 33,34 Further studies of abetalipoproteinemic patients have not always confirmed these early observations, although the endocrine evaluations undertaken have varied substantially.…”

Section: 22mentioning

confidence: 99%

Effects of Evolocumab on Vitamin E and Steroid Hormone Levels

Blom

Djedjos

Monsalvo

et al. 2015

Circulation Research

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Rationale : Vitamin E transport and steroidogenesis are closely associated with low-density lipoproteins (LDLs) metabolism, and evolocumab can lower LDL cholesterol (LDL-C) to low levels. Objective: To determine the effects of evolocumab on vitamin E and steroid hormone levels. Methods and Results: After titration of background lipid-lowering therapy per cardiovascular risk, 901 patients with an LDL-C ≥2.0 mmol/L were randomized to 52 weeks of monthly, subcutaneous evolocumab, or placebo. Vitamin E, cortisol, adrenocorticotropic hormone, and gonadal hormones were analyzed at baseline and week 52. In a substudy (n=100), vitamin E levels were also measured in serum, LDL, high-density lipoprotein, and red blood cell membranes at baseline and week 52. Absolute vitamin E decreased in evolocumab-treated patients from baseline to week 52 by 16% but increased by 19% when normalized for cholesterol. In the substudy, vitamin E level changes from baseline to week 52 mirrored the changes in the lipid fraction, and red blood cell membrane vitamin E levels did not change. Cortisol in evolocumab-treated patients increased slightly from baseline to week 52, but adrenocorticotropic hormone and the cortisol:adrenocorticotropic hormone ratio did not change. No patient had a cortisol:adrenocorticotropic hormone ratio <3.0 (nmol/pmol). Among evolocumab-treated patients, gonadal hormones did not change from baseline to week 52. Vitamin E and steroid changes were consistent across subgroups by minimum postbaseline LDL-C <0.4 and <0.6 mmol/L. Conclusions: As expected, vitamin E levels changed similarly to lipids among patients treated for 52 weeks with evolocumab. No adverse effects were observed in steroid or gonadal hormones, even at very low LDL-C levels. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01516879.

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