Profile, mean residence time of ACTH and cortisol responses after low and standard ACTH tests in healthy volunteers

Alía, Pedro; Villabona, Carmen V.; Giménez, O.; Sospedra, E.; Soler, J.; Navarro, Miguel

doi:10.1111/j.1365-2265.2006.02602.x

Cited by 22 publications

(16 citation statements)

References 33 publications

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“…In a normal individual, an intravenous bolus of ACTH 1-24 disappears from the circulation with a half-life of about 5 min and is eliminated from the circulation rapidly, followed after a delay of 15-30 min later with a sustained secretion of cortisol. Small versus large doses of tetracosactin stimulate the same cortisol production rate, i.e., the same peak level of cortisol and area under the curve (Alia et al, 2006). Simultaneously, a single bolus of this peptide activates the prolonged synthesis of enzymes involved in steroidogenesis (Lehoux et al, 1998).…”

Section: Molecular Mechanisms Of Tissue-protective Effectsmentioning

confidence: 98%

Flipping the molecular switch for innate protection and repair of tissues: Long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin

Collino

Thiemermann

Cerami

et al. 2015

Pharmacology & Therapeutics

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Many disease processes activate a cellular stress response that initiates a cascade of inflammation and damage. However, this process also triggers a tissue protection and repair system mediated by locally-produced hyposialated erythropoietin (hsEPO). Although recombinant EPO is used widely for treating anemia, potential use of recombinant EPO for tissue-protection is limited by rises in hematocrit, platelet activation, and selectin expression resulting in a high risk of thrombosis. Importantly, the erythropoietic and tissue-protective effects of EPO are mediated by different receptors. Whereas EPO stimulates red cell progenitors by binding to an EPO receptor (EPOR) homodimer, a heterodimer receptor complex composed of EPOR and β common receptor (βcR) subunits, termed the innate repair receptor (IRR), activates tissue protection and repair. The IRR is typically not expressed by normal tissues, but instead is rapidly induced by injury or inflammation. Based on this understanding, EPO derivatives have been developed which selectively activate the IRR without interacting with the EPOR homodimer. The latest generation of specific ligands of the IRR includes an 11 amino acid peptide modeled from the three dimensional structure of the EPO in the region of helix B called pyroglutamate helix B surface peptide (pHBSP; ARA-290). Despite a short plasma half-life (~2min), pHBSP activates a molecular switch that triggers sustained biological effects that have been observed in a number of experimental animal models of disease and in clinical trials. This review summarizes pharmacokinetic and pharmacodynamic data and discusses the molecular mechanisms underlying the long-lasting effects of this short-lived peptide.

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Section: Molecular Mechanisms Of Tissue-protective Effectsmentioning

confidence: 98%

Flipping the molecular switch for innate protection and repair of tissues: Long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin

Collino

Thiemermann

Cerami

et al. 2015

Pharmacology & Therapeutics

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“…68 Dorin et al 60 found the synacthen test to have high sensitivity in cases of primary adrenal insufficiency but found no statistically significant difference in sensitivity between the standard-dose (250 mg) and the low-dose (1 mg) tests in secondary adrenal insufficiency. 60 There are conflicting data reporting that the standard-dose (250 mg) synacthen test is more sensitive than the low-dose (1 mg) synacthen test in detecting cases of secondary adrenal insufficiency.…”

Section: Test Comparisonsmentioning

confidence: 99%

“…66,67 Nevertheless the test is challenging to perform, blood concentrations are still supraphysiological and similar diagnostic sensitivities to the standard-dose test were demonstrated by Mayenknecht et al 61 More recently these observations were confirmed by a meta-analysis suggesting that the low-dose test is no more effective than the standard test. 60,68 Using either the low-or standard-dose test, many patients with pituitary disease with marginal responses will require further testing with the insulin tolerance or overnight metyrapone tests. 61 …”

Section: Acth Stimulation Testing (Synacthen Test)mentioning

confidence: 99%

The diagnosis and investigation of adrenal insufficiency in adults

2009

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There is considerable variation in the methods used to diagnose and investigate adrenal insufficiency in clinical practice. These include a range of adrenocorticotropin (ACTH) stimulation and other dynamic testing protocols, serum cortisol cut-off values for diagnosis and tests used for differential diagnosis. With the introduction of modern cortisol and ACTH assays, the interpretation of tests used for diagnosis and differential diagnosis has become more complex and requires local validation. This review examines the basis of normal hypothalamic-pituitary -adrenal axis function and adrenal insufficiency states based upon an evidence base accumulated over the past four decades. The role of the laboratory in the differential diagnosis and interpretation based upon assay methodology is discussed. The accurate identification of patients who may benefit from corticosteroid replacement in special settings such as critical illness is challenging and will be explored.

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“…Its chronic effects to enhance the gland's steroidogenic enzymes in the biosynthetic pathway and to make more cells capable of conducting steroidogenesis have also been studied (Vinson 2003). Although assessment of adrenal function in human patients for diagnostic purposes is carried out by standardized ACTH tests (Alia et al 2006), there is little direct evidence available for the actions of ACTH on the production of aldosterone in rodents. Aldosterone has primarily been studied in the context of its function within the RAAS.…”

Section: Aldosterone and Acth In Micementioning

confidence: 99%

A highly sensitive immunofluorometric assay for the measurement of aldosterone in small sample volumes: validation in mouse serum

Manolopoulou¹,

Bielohuby²,

Caton³

et al. 2007

Journal of Endocrinology

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Data on the involvement of aldosterone in the regulation of the renin-angiotensin-aldosterone system (RAAS) in rodents are still scarce, partly due to the high sample volumes needed by commercially available assays and to the very low aldosterone concentrations present. We have developed a highly sensitive and non-isotopic immunoassay, requiring a volume of only 50 ml serum for a duplicate measurement, employing a highly specific monoclonal antibody against aldosterone. The assay was validated in human and mouse samples and exhibited a linear working range from 10 to 1000 pg/ml. Values obtained after a chromatographic purification step correlated significantly to the dichloromethane extraction ordinarily used. Basal aldosterone values were measured in 75 mouse hybrids and found within the linear range (173G21 pg/ml), with no significant difference between males and females. Additionally, we show an increase in serum aldosterone in mice from 3 to 11 weeks of age. Mice of the same genetic background were treated with dexamethasone intraperitoneally (nZ7), resulting in significantly decreased concentrations (35G3 vs 114G33 pg/ml in controls; P!0 . 001). In contrast, adrenocorticotropic hormone resulted in significantly increased serum aldosterone (603G119 pg/ml; nZ7; P!0 . 001), as did the physiological stimulation of the RAAS by a high K C /low Na C diet (1369G703 vs 172G36 pg/ml). In conclusion, we have developed and validated an extremely sensitive assay for determination of aldosterone concentrations from very small serum samples, which could be especially useful in pharmacological intervention studies in rodent models.

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Profile, mean residence time of ACTH and cortisol responses after low and standard ACTH tests in healthy volunteers

Cited by 22 publications

References 33 publications

Flipping the molecular switch for innate protection and repair of tissues: Long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin

Flipping the molecular switch for innate protection and repair of tissues: Long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin

The diagnosis and investigation of adrenal insufficiency in adults

A highly sensitive immunofluorometric assay for the measurement of aldosterone in small sample volumes: validation in mouse serum

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