Falsely elevated plasma ACTH levels measured by the Elecsys assay related to heterophilic antibody in a case of secondary adrenocortical insufficiency

Comparisons of resting plasma adrenocorticotropin (ACTH) and corticosterone in the morning and afternoon were made among adult rats bearing regenerated adult adrenal grafts, neonatal (day 1) adrenal grafts, adult adrenal capsule grafts, or intact adrenals. In the morning plasma ACTH and corticosterone were similar in all rats. In the afternoon, plasma ACTH was elevated in rats bearing neonatal adrenal grafts or adult adrenal capsule grafts, but not in rats bearing whole adult adrenal grafts. There was no difference in afternoon plasma corticosterone among rats bearing transplanted adrenals, although afternoon plasma corticosterone was decreased in rats bearing transplants compared with rats with intact adrenals. Thus the increased plasma ACTH after adrenal transplantation cannot be explained entirely by decreases in resting plasma corticosterone. Adrenal responsiveness to ACTH was tested at 5 wk after transplantation in the afternoon by measuring the plasma corticosterone response to submaximal doses of ACTH. The responsiveness was decreased in rats bearing transplants. In addition, responsiveness was inversely related to the age of the grafted adrenal tissue. Adrenals regenerated from adult adrenals were more responsive than adrenals regenerated either from neonatal adrenals or from adult adrenal capsules. The findings suggest that following adrenal transplantation reestablishment of normal pituitary-adrenocortical function does not occur in rats bearing adrenals regenerated from immature adrenal cells. In addition, comparable alterations occur after regeneration of adrenal tissue from neonatal adrenal cells and adult adrenal capsular cells. Elevated plasma ACTH associated with adequate plasma corticosterone in rats bearing adrenals regenerated from immature adrenal cells may result from chronic alteration in responsiveness to steroid feedback.(ABSTRACT TRUNCATED AT 250 WORDS)

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Vasopressin and angiotensin II in reflex regulation of ACTH, glucocorticoids, and renin: effect of water deprivation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.263.4.r762 ◽

1992 ◽

Vol 263 (4) ◽

pp. R762-R769 ◽

Cited By ~ 3

Author(s):

V. L. Brooks ◽

L. C. Keil

Keyword(s):

Angiotensin Ii ◽

Water Deprivation ◽

Adrenocorticotropic Hormone ◽

Renin Secretion ◽

Ang Ii ◽

Elevated Plasma ◽

Plasma Acth ◽

Vasopressin Antagonist ◽

Acth Concentration ◽

V2 Antagonist

Angiotensin II (ANG II) and vasopressin participate in baroreflex regulation of adrenocorticotropic hormone (ACTH), glucocorticoid, and renin secretion. The purpose of this study was to determine whether this participation is enhanced in water-deprived dogs, with chronically elevated plasma ANG II and vasopressin levels, compared with water-replete dogs. The baroreflex was assessed by infusing increasing doses of nitroprusside (0.3, 0.6, 1.5, and 3.0 micrograms.kg-1.min-1) in both groups of animals. To quantitate the participation of ANG II and vasopressin, the dogs were untreated or pretreated with the competitive ANG II antagonist saralasin, a V1-vasopressin antagonist, or combined V1/V2-vasopressin antagonist, either alone or in combination. The findings were as follows. 1) Larger reflex increases in ANG II, vasopressin, and glucocorticoids, but not ACTH, were produced in water-deprived dogs compared with water-replete dogs. 2) ANG II blockade blunted the glucocorticoid and ACTH responses to hypotension in water-deprived dogs, but not water-replete dogs. In contrast, vasopressin blockade reduced the ACTH response only in water-replete dogs. 3) Vasopressin or combined vasopressin and ANG II blockade reduced the plasma level of glucocorticoids related either to the fall in arterial pressure or to the increase in plasma ACTH concentration in water-replete dogs, and this effect was enhanced in water-deprived dogs. 4) In both water-deprived and water-replete animals, saralasin and/or a V1-antagonist increased the renin response to hypotension, but a combined V1/V2-antagonist did not. These results reemphasize the importance of endogenous ANG II and vasopressin in the regulation of ACTH, glucocorticoid, and renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

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Adrenals in Ectopic ACTH Syndrome

PEDIATRICS ◽

10.1542/peds.48.2.329 ◽

1971 ◽

Vol 48 (2) ◽

pp. 329-330

Author(s):

N. S. Halmi ◽

Gilbert S. Omenn

Keyword(s):

Personal Experience ◽

Ectopic Acth Syndrome ◽

Elevated Plasma ◽

Adrenal Hyperplasia ◽

Plasma Acth ◽

Ectopic Acth ◽

Excellent Review ◽

Bilateral Adrenal Hyperplasia ◽

Crooke’S Hyalinization

In Dr. Gilbert S. Omenn's1 otherwise excellent review of ectopic hormone syndromes associated with tumors in childhood we find the following sentence: "Completely characterized cases of ectopic ACTH syndrome have bilateral adrenal hyperplasia, normal pituitary basophils, positive assay for ACTH in the tumor, and failure of suppression of elevated plasma ACTH by dexamethasone." I have no personal experience with the ectopic ACTH syndrome in childhood, but in three cases seen in adults the basophils (more accurately, the ACTH-MSH cells among them), far from being normal, showed the expected profound Crooke's hyalinization characteristic of severe hypercortisolism.2

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Peripubertal-onset but not adult-onset obesity increases IGF-I and drives development of lean mass, which may lessen the metabolic impairment in adult obesity

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00340.2012 ◽

2012 ◽

Vol 303 (9) ◽

pp. E1151-E1157 ◽

Cited By ~ 9

Author(s):

Jose Cordoba-Chacon ◽

Manuel D. Gahete ◽

Ana I. Pozo-Salas ◽

Antonio Moreno-Herrera ◽

Justo P. Castaño ◽

...

Keyword(s):

Weight Gain ◽

Lean Mass ◽

Obese Mouse ◽

Metabolic Dysfunction ◽

Adult Onset ◽

Adult Obesity ◽

Elevated Plasma ◽

High Fat ◽

Plasma Acth ◽

Igf I

It has been suggested that adult metabolic dysfunction may be more severe in individuals who become obese as children compared with those who become obese later in life. To determine whether adult metabolic function differs if diet-induced weight gain occurs during the peripubertal age vs. if excess weight gain occurs after puberty, male C57Bl/6J mice were fed a low-fat (LF; 10% kcal from fat) or high-fat (HF; 60% kcal from fat) diet starting during the peripubertal period (pHF; 4 wk of age) or as adults (aHF; 12 wk of age). Both pHF and aHF mice were hyperinsulinemic and hyperglycemic, and both showed impaired glucose tolerance and insulin resistance compared with their LF-fed controls. However, despite a longer time on diet, pHF mice were relatively more insulin sensitive than aHF mice, which was associated with higher lean mass and circulating IGF-I levels. In addition, HF feeding had an overall stimulatory effect on circulating corticosterone levels; however, this rise was associated only with elevated plasma ACTH in the aHF mice. Despite the belief that adult metabolic dysfunction may be more severe in individuals who become obese as children, data generated using a diet-induced obese mouse model suggest that adult metabolic dysfunction associated with peripubertal onset of obesity is not worse than that associated with adult-onset obesity.

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OR19-06 Sepsis-Induced Critical Illness in Mice Alters Key Regulators of ACTH Production and Secretion Within the Anterior Pituitary Gland

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.188 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Arno Téblick ◽

Sarah Vander Perre ◽

Lies Langouche ◽

Greet Van den Berghe

Keyword(s):

Gene Expression ◽

Critical Illness ◽

Protein Expression ◽

Critically Ill ◽

Annexin A1 ◽

Elevated Plasma ◽

Plasma Acth ◽

Mediated Action ◽

Free Cortisol ◽

Pomc Gene

Abstract Introduction Critical illness is hallmarked by high plasma cortisol without elevated ACTH. This is partly explained by low cortisol-binding proteins and reduced binding affinity and by suppressed cortisol metabolism, 3 peripheral drivers of increased free cortisol (corticosterone (CORT) in rodents).1 We hypothesized that lack of elevated plasma ACTH is explained by CORT-induced feed-back inhibition either due to suppressed CRH or AVP pituitary signaling or to direct glucocorticoid receptor (GR)-mediated action within corticotrophs. To test this hypothesis, we documented alterations in ACTH precursors and key enzymes controlling ACTH maturation and secretion in a mouse model of sepsis-induced critical illness. Methods C57Bl/6 mice were randomly allocated to a healthy control group or to 4 critically ill groups sacrificed after increasing illness duration (30 hours (H), 3 days (D), 5D or 7D). Critical illness was induced by sepsis brought about by cecal-ligation and puncture followed by fluid-resuscitation and antibiotics treatment. The study was continued until 15 surviving animals per time cohort were reached (n=120). We quantified pituitary pro-opiomelanocortin (POMC) gene/protein expression and POMC plasma concentrations, pituitary POMC intracellular trafficking and cleavage via intracellular POMC sorting/trafficking receptor Carboxypeptidase E (CPE) and prohormone convertase 1 (PC1/3) gene/protein expression. Gene expression of Annexin A1, an inhibitor of mature ACTH secretion, was quantified as marker of GR-mediated CORT-induced feedback inhibition at corticotroph level. Results Plasma CORT concentrations were median 3-fold increased during critical illness (p<0.001 for all time cohorts) in the face of normal (for 30H, 3D and 5D cohorts) to low (7D time cohort; p=0.01) plasma ACTH concentrations. Plasma POMC concentrations were higher in critically ill than in control mice (p=0.05). POMC gene expression (but not protein, P=0.8) was a median 55% higher in critically ill mice than in controls (p<0.05 for all time cohorts). In contrast, pituitary mature ACTH protein concentration was median 61% lower in critically ill than in control mice (p<0.01). CPE gene expression was only increased in 30H time cohort (p<0.001). PC1/3 gene and protein expression were positively correlated (R2 0.1; p=0.001) and were reduced (by 37% and 43%, respectively) during the entire course of critical illness (p<0.01). Annexin A1 gene expression was increased during critical illness (p<0.05 for all time cohorts). Conclusion Suppressed CRH or AVP signaling and GR-mediated action within corticotrophs explained lack of elevated plasma ACTH in critical illness, as indicated by impaired POMC processing and ACTH maturation. However, increased POMC gene expression suggests ongoing corticotroph activation, the driver of which needs to be identified. 1. Teblick A et al. Nat Rev Endocrinol 2019

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A case of small-cell lung cancer complicated with elevated plasma ACTH level, cryptococcal meningitis and cryptococcosis of the skin.

Haigan ◽

10.2482/haigan.30.575 ◽

1990 ◽

Vol 30 (4) ◽

pp. 575-581 ◽

Cited By ~ 1

Author(s):

Tsuyoshi Hasegawa ◽

Hiroko Sakamoto ◽

Hitoshi Nakai

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cryptococcal Meningitis ◽

Small Cell ◽

Acth Level ◽

Elevated Plasma ◽

Small Cell Lung ◽

Plasma Acth ◽

Plasma Acth Level

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Endocrinological and Behavioural Effects of Chronic Fluxilan Administration in Rats

Journal of Medical Biochemistry ◽

10.2478/v10011-007-0033-5 ◽

2007 ◽

Vol 26 (4) ◽

pp. 274-279 ◽

Cited By ~ 1

Author(s):

Nataša Spasojević ◽

Ljubica Gavrilović ◽

Ivan Kovačević ◽

Slađana Dronjak

Keyword(s):

Adrenocorticotropic Hormone ◽

Plasma Catecholamines ◽

Selective Inhibitor ◽

Mild Stress ◽

Neuronal System ◽

Elevated Plasma ◽

Plasma Acth ◽

Behavioural Effects ◽

Initial Depression ◽

Hpa Axis Activity

Endocrinological and Behavioural Effects of Chronic Fluxilan Administration in RatsChronic stress induces changes in the neuroendocrine and neuronal system, including elevation of catecholamines and corticosterone (CORT) levels, and could be an important factor in initial depression. Antidepressants affect monoaminergic neurotransmission and modulate central neuropeptides involved in the coordination of stress response and the control of HPA axis activity. We studied the effects of chronic treatment with fluxilan, a selective inhibitor of serotonin reuptake, in unstressed controls and chronic unpredictable mild stress (CUMS) rats, on behaviour and plasma noradrenaline (NA), adrenaline (A), corticosterone (CORT) and adrenocorticotropic hormone (ACTH). CUMS did not affect plasma NA, A and ACTH, but elevated plasma CORT content. Plasma concentration of catecholamines after fluxilan administration was significantly increased in control and CUMS group. On the other hand, fluxilan expressed no effect on plasma ACTH and CORT concentrations in control animals, but decreased ACTH and CORT levels in CUMS animals. Behaviourally, fluxilan treated animals displayed enhanced anxiety. The results demonstrate that the anxiogenic effects of chronic fluxilan administration are similar to those reported by many other studies. The findings described here suggest that elevated plasma catecholamines may contribute to an adverse effect of this drug on cardiovascular parameters during antidepressant therapy.

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Endocrine and metabolic characteristics of polyoma large T transgenic mice that develop ACTH-producing pituitary tumors

Journal of Neurosurgery ◽

10.3171/jns.1995.82.5.0879 ◽

1995 ◽

Vol 82 (5) ◽

pp. 879-885 ◽

Cited By ~ 3

Author(s):

Are Helseth ◽

Egil Haug ◽

Jahn M. Nesland ◽

Gene P. Siegal ◽

Øystein Fodstad ◽

...

Keyword(s):

Transgenic Mice ◽

Adrenocorticotropic Hormone ◽

Plasma Concentrations ◽

Pituitary Tumors ◽

Secondary Effect ◽

Elevated Plasma ◽

Plasma Acth ◽

Content Type ◽

Metabolic Characteristics ◽

Pituitary Macroadenomas

✓ The authors have analyzed several endocrine and metabolic parameters in polyoma large T transgenic mice (PyLT-1) that develop adrenocorticotropic hormone (ACTH)-immunoreactive pituitary tumors and in nontransgenic mice with tumor transplants. All clinically ill PyLT-1 mice (13 to 16 months of age) had pituitary macroadenomas and elevated plasma ACTH levels. Compared to PyLT-1 transgenic mice, the ACTH plasma concentrations in immunocom-petent mice with transplant tumors were markedly raised. In these animals, a secondary effect of hypercorticotropism was documented by a moderate hyperglycemia. Furthermore, mice with transplant tumors had a pathological weight increase from the time the tumor was palpable. The present study supports and extends the authors' previous morphological documentation of the similarity between the ACTH-producing tumors in this mouse model and human Cushing's disease.

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Changes in the glomerulosa cell phenotype during adrenal regeneration in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.276.5.r1374 ◽

1999 ◽

Vol 276 (5) ◽

pp. R1374-R1382 ◽

Cited By ~ 3

Author(s):

W. C. Engeland ◽

B. K. Levay-Young

Keyword(s):

Cellular Differentiation ◽

Zona Glomerulosa ◽

Cell Phenotype ◽

Zona Fasciculata ◽

Elevated Plasma ◽

Plasma Acth ◽

Acth Treatment ◽

Glomerulosa Cells ◽

Cytochrome P 450

In situ hybridization was used to examine cellular differentiation during rat adrenal regeneration, defining zona glomerulosa [cytochrome P-450 aldosterone synthase ( P-450aldo) mRNA positive], zona fasciculata [cytochrome P-450 11β-hydroxylase ( P-45011β) mRNA positive], or zona intermedia [negative for both but 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA positive]. After unilateral adrenal enucleation with contralateral adrenalectomy (ULE/ULA), the expression of all mRNA was reduced at 2 days. From 5 to 10 days, P-45011β and 3β-HSD mRNA increased while P-450aldo remained low; at 20 days, all mRNA were increased. From 2 to 10 days, cells adjacent to the capsule showed intermedia cell differentiation; by 20 days, the subcapsular glomerulosa cells reappeared. This suggests that after enucleation the glomerulosa dedifferentiates to zona intermedia. The experiment was repeated in rats where the postenucleation ACTH rise was prevented. Rats underwent ULE with sham ULA (ULE/SULA) or ULE/SULA with ACTH treatment. Adrenals from ULE/SULA rats expressed increased P-450aldo mRNA at 10 days and reduced P-45011β mRNA and adrenal weight at 30 days. ACTH treatment reversed the pattern toward that seen in ULE/ULA. These findings show that the enucleation-induced dedifferentitation of the glomerulosa cell may result in part from elevated plasma ACTH and that prevention of dedifferentiation may result in impaired regeneration.

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