DOCSLIB.ORG

Steroid-Induced Psychiatric Symptoms: What You Need to Know

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Steroid-Induced Psychiatric Symptoms: What You Need to Know Med/Psych Update STEROIDS AND PSYCHOPATHOLOGY Steroid-induced psychiatric symptoms: What you need to know Early recognition of these symptoms is key to initiating effective interventions s. N, age 30, presents to the emergency department for altered mental status, insomnia, and behavioral Mchanges, which she has experienced for 1 week. On evaluation, she grabs a clinician’s hand and details her busi- ness ideas and life story with no prompting. Ms. N’s mental status examination is significant for hyperverbal speech with increased rate and volume; tangential thought process; and bright, expanded affect. One week earlier, Ms. N was hospitalized for sudden-onset chest pain, weakness, and dizziness. She received 45 minutes of cardiopulmonary resuscitation prior to presentation and was found to have a ST-segment elevation myocardial infarction that required emergent left anterior descending coronary artery AGSANDREW/SHUTTERSTOCK and right coronary artery percutaneous coronary intervention to place drug-eluting stents. Her recovery was complicated by Yvonne Lu, BS acute cardiogenic shock, pulmonary edema, and hypoxic respi- Medical Student ratory failure. Subsequently, she was intubated, admitted to the University of California Irvine School of Medicine Irvine, California ICU, and received high-dose corticosteroids, including IV meth- ylprednisolone, 40 mg every 12 hours, which was tapered prior Lydia Ann, MD PGY-3 Psychiatry Resident to discharge. Her husband reports that since Ms. N came home, Department of Psychiatry she has been more talkative and irritable, ruminating about past University of California Irvine events, unable to sleep (<1 hour/night), and crying frequently. University of California Medical Center Orange, California She has also been endorsing visual and auditory hallucinations, with increased praying and listening to religious music. Robert McCarron, DO Professor and Vice Chair Department of Psychiatry The frequent clinical use of steroids necessitates an under- University of California Irvine standing of these medications’ various adverse effects. University of California Medical Center continued Orange, California Disclosures The authors report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products. Current Psychiatry doi: 10.12788/cp.0104 Vol. 20, No. 4 33 The manifestations of steroid-induced have a rapid onset, possibly within hours psychiatric symptoms are broad and can of starting steroids.1 However, studies have involve affective, behavioral, and cognitive reported a median time to onset of 11.5 days; domains. While the current mechanism is 39% of cases had onset during the first week unknown, this phenomenon may be related and 62% within 2 weeks.3,6 After reducing to decreased levels of corticotropin, norepi- or stopping the steroid, it may take days to nephrine, and beta-endorphin immunoreac- weeks before symptoms start to subside.2 Steroids and tivity, as well as effects on brain regions such psychopathology as the hippocampus and amygdala. The best interventions for steroid-induced psychiatric What to consider in the symptoms are awareness and early diagno- differential Dx sis. There are no FDA-approved treatments Psychiatric symptoms that are induced by for steroid-induced psychiatric symptoms; steroids can mimic metabolic, neurologic, initial measures should include tapering or or toxic disorders. Other factors to consider discontinuing corticosteroids. include drug withdrawal/intoxication, In this article, we review the literature infections, and paraneoplastic syndromes.4,5 Clinical Point on the incidence, characteristics, differen- Although there is no reported correlation Mania/hypomania is tial diagnoses, proposed mechanism, risk between the location of neurologic lesions factors, and proposed treatments of steroid- and the development of specific psychiatric the most common induced psychiatric symptoms. symptoms, manic symptoms appear most steroid-induced commonly with lesions in the right frontal psychiatric symptom lobe. 4 Other factors to note include the pres- A wide range of presentations ence of new-onset psychiatric illnesses such Steroid use has increased over the past 2 as bipolar, mood, or thought disorders,4 as decades, with 10% of medical and surgi- well as psychosocial stressors that might be cal inpatients and 1% to 3% of the general contributing to the patient’s presentation.5 population taking long-term glucocorti- coids.1 Even with topical application, steroid therapy is often systemically absorbed, and Proposed mechanisms thus may lead to steroid-induced psychiatric Although the exact mechanism by which symptoms. The incidence of steroid-induced steroids induce psychiatric symptoms is psychiatric symptoms is difficult to assess unknown, several mechanisms have been because there can be a wide range of reac- proposed. One hypothesis is that steroid- tions that are dose- and time-related. Three induced psychopathology is related to reviews of a total of 122 cases reports found decreased levels of corticotropin, norepi- that an estimated 5% of patients treated nephrine, and beta-endorphin immuno- with steroids experience severe psychiatric reactivity.4,5,7 This may explain why many reactions.1-3 patients with major depressive disorder Steroid-induced psychopathology can have elevated cortisol production and/ include mood, behavioral, and/or cogni- or lack of suppression of cortisol secre- tive impairments. Mania/hypomania is the tion during a dexamethasone stimulation most common overall psychiatric symptom; test, and why approximately one-half of the most common mood manifestations are patients with Cushing’s disease experience anxiety and depression.4,5 Other possible ste- depressive symptoms.8 This is also likely roid-induced symptoms include psychosis, why antipsychotics, which typically reduce Discuss this article at dementia, panic disorder, delirium, suicidal cortisol, are efficacious treatments for some www.facebook.com/ thinking and behavior, aggressive behav- steroid-induced psychiatric symptoms.9 MDedgePsychiatry ior, insomnia, agitation, depersonalization, Cognitive impairments from steroid and euphoria.5 The most common cogni- use may be related to these agents’ effects tive impairment is verbal or declarative on certain brain regions. One such area is memory deficit; others include distractibil- the hippocampus, an important media- ity and deficits in attention and psychomo- tor in the creation and maintenance of Current Psychiatry 34 April 2021 tor speed.5 These psychiatric symptoms can episodic and declarative memories.5,8,9 Acute glucocorticoid use is associated with may allow hydrophobic steroid molecules decreased activity in the left hippocampus, to more easily penetrate the CNS, lead- reduced hippocampal glucose metabolism, ing to increased neuropsychiatric effects. and reduced cerebral blood flow in the pos- Hypoalbuminemia is another reported MDedge.com/psychiatry terior medial temporal lobe.10 Long-term risk factor, perhaps because lower levels of glucocorticoid exposure is associated with serum albumin are related to higher levels smaller hippocampal volume and lower of free and active glucocorticoids, which levels of temporal lobe N-acetylaspartate, are normally inactive when bound to albu- a marker of neuronal viability.10 Because min.13 There also appears to be an increased working memory depends on the prefron- prevalence of steroid-induced psychopa- tal cortex and declarative memory relies on thology in women, perhaps due to greater the hippocampus, deficits in these functions propensity in women to seek medical care can be attributed to the effect of prolonged or a higher prevalence of women with med- glucocorticoid exposure on glucocorticoid ical disorders that are treated with steroids.5 or mineralocorticoid receptors in the hippo- A previous history of psychiatric disorders campus, reduction of hippocampal volume, may not increase risk.5 or elevated glutamate accumulation in Several methods for reducing risk have Clinical Point 11 that area. In addition, high cortisol levels been proposed, including using a divided- Starting valproate inhibit brain-derived neurotrophic factor, dosing regimens that may lower peak ste- which plays a crucial role in maintaining roid plasma concentrations.13,14 However, while continuing neural architecture in key brain regions the best prevention of steroid-induced corticosteroids may such as the hippocampus and prefrontal psychiatric symptoms are awareness, help lessen mania cortex.11 There is also a correlation between early diagnosis, and intervention. Studies the duration of prednisone treatment and have suggested that N-methyl-d-aspartate atrophy of the right amygdala, which is an (NMDA) antagonists15 and other agents important regulator of mood and anxiety.11 that decrease glutamate release (such as Both the hippocampus and amygdala have phenytoin and lamotrigine16) may help dense collections of glucocorticoid recep- prevent corticosteroid-induced hippocam- tors. This may explain why patients who pal volume loss. Lamotrigine has been receive high-dose corticosteroids can have shown to reduce the amount of atrophy in reversible atrophy in the hypothalamus and the amygdala in patients taking corticoste- amygdala, leading to deficits in emotional roids.17 Phenytoin has also been reported to learning and the stress response. reduce the incidence of hypomania associ- ated with corticosteroids, perhaps due to its induction of
Load more

Recommended publications
  • 1 Progesterone: an Enigmatic Ligand for the Mineralocorticoid Receptor
    Progesterone: An Enigmatic Ligand for the Mineralocorticoid Receptor Michael E. Baker1 Yoshinao Katsu2 1Division of Nephrology-Hypertension Department of Medicine, 0735 University of California, San Diego 9500 Gilman Drive La Jolla, CA 92093-0735 2Graduate School of Life Science Hokkaido University Sapporo, Japan Correspondence to: M. E. Baker; E-mail: [email protected] Y. Katsu; E-mail: [email protected] Abstract. The progesterone receptor (PR) mediates progesterone regulation of female reproductive physiology, as well as gene transcription in non-reproductive tissues, such as brain, bone, lung and vasculature, in both women and men. An unusual property of progesterone is its high affinity for the mineralocorticoid receptor (MR), which regulates electrolyte transport in the kidney in humans and other terrestrial vertebrates. In humans, rats, alligators and frogs, progesterone antagonizes activation of the MR by aldosterone, the physiological mineralocorticoid in terrestrial vertebrates. In contrast, in elephant shark, ray-finned fishes and chickens, progesterone activates the MR. Interestingly, cartilaginous fishes and ray-finned fishes do not synthesize aldosterone, raising the question of which steroid(s) activate the MR in cartilaginous fishes and ray-finned fishes. The simpler synthesis of progesterone, compared to cortisol and other corticosteroids, makes progesterone a candidate physiological activator of the MR in elephant sharks and ray-finned fishes. Elephant shark and ray-finned fish MRs are expressed in diverse tissues, including heart, brain and lung, as well as, ovary and testis, two reproductive tissues that are targets for progesterone, which together suggests a multi-faceted physiological role for progesterone activation of the MR in elephant shark and ray-finned fish.
    [Show full text]
  • Mineralocorticoid Receptor Mutations
    234 1 M-C ZENNARO and MR mutations 234:1 T93–T106 Thematic Review F FERNANDES-ROSA 30 YEARS OF THE MINERALOCORTICOID RECEPTOR Mineralocorticoid receptor mutations Maria-Christina Zennaro1,2,3 and Fabio Fernandes-Rosa1,2,3 Correspondence 1INSERM, Paris Cardiovascular Research Center, Paris, France should be addressed 2Université Paris Descartes, Sorbonne Paris Cité, Paris, France to M-C Zennaro 3Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Email Paris, France maria-christina.zennaro@ inserm.fr Abstract Aldosterone and the mineralocorticoid receptor (MR) are key elements for maintaining Key Words fluid and electrolyte homeostasis as well as regulation of blood pressure. Loss-of- f mineralocorticoid function mutations of the MR are responsible for renal pseudohypoaldosteronism type receptor 1 (PHA1), a rare disease of mineralocorticoid resistance presenting in the newborn with f pseudohypoaldosteronism type 1- PHA1 weight loss, failure to thrive, vomiting and dehydration, associated with hyperkalemia f aldosterone and metabolic acidosis, despite extremely elevated levels of plasma renin and f hormone receptors aldosterone. In contrast, a MR gain-of-function mutation has been associated with a f nuclear receptor familial form of inherited mineralocorticoid hypertension exacerbated by pregnancy. In Endocrinology addition to rare variants, frequent functional single nucleotide polymorphisms of the of MR are associated with salt sensitivity, blood pressure, stress response and depression in the general population. This review will summarize our knowledge on MR mutations in Journal PHA1, reporting our experience on the genetic diagnosis in a large number of patients performed in the last 10 years at a national reference center for the disease.
    [Show full text]
  • Mifepristone
    1. NAME OF THE MEDICINAL PRODUCT Mifegyne 200 mg tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains 200-mg mifepristone. For the full list of excipients, see section 6.1 3. PHARMACEUTICAL FORM Tablet. Light yellow, cylindrical, bi-convex tablets, with a diameter of 11 mm with “167 B” engraved on one side. 4. CLINICAL PARTICULARS For termination of pregnancy, the anti-progesterone mifepristone and the prostaglandin analogue can only be prescribed and administered in accordance with New Zealand’s abortion laws and regulations. 4.1 Therapeutic indications 1- Medical termination of developing intra-uterine pregnancy. In sequential use with a prostaglandin analogue, up to 63 days of amenorrhea (see section 4.2). 2- Softening and dilatation of the cervix uteri prior to surgical termination of pregnancy during the first trimester. 3- Preparation for the action of prostaglandin analogues in the termination of pregnancy for medical reasons (beyond the first trimester). 4- Labour induction in fetal death in utero. In patients where prostaglandin or oxytocin cannot be used. 4.2 Dose and Method of Administration Dose 1- Medical termination of developing intra-uterine pregnancy The method of administration will be as follows: • Up to 49 days of amenorrhea: 1 Mifepristone is taken as a single 600 mg (i.e. 3 tablets of 200 mg each) oral dose, followed 36 to 48 hours later, by the administration of the prostaglandin analogue: misoprostol 400 µg orally or per vaginum. • Between 50-63 days of amenorrhea Mifepristone is taken as a single 600 mg (i.e. 3 tablets of 200 mg each) oral dose, followed 36 to 48 hours later, by the administration of misoprostol.
    [Show full text]
  • Agonistic and Antagonistic Properties of Progesterone Metabolites at The
    European Journal of Endocrinology (2002) 146 789–800 ISSN 0804-4643 EXPERIMENTAL STUDY Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor M Quinkler, B Meyer, C Bumke-Vogt, C Grossmann, U Gruber, W Oelkers, S Diederich and V Ba¨hr Department of Endocrinology, Klinikum Benjamin Franklin, Freie Universita¨t Berlin, Hindenburgdamm 30, 12200 Berlin, Germany (Correspondence should be addressed to M Quinkler; Email: [email protected]) Abstract Objective: Progesterone binds to the human mineralocorticoid receptor (hMR) with nearly the same affinity as do aldosterone and cortisol, but confers only low agonistic activity. It is still unclear how aldosterone can act as a mineralocorticoid in situations with high progesterone concentrations, e.g. pregnancy. One mechanism could be conversion of progesterone to inactive compounds in hMR target tissues. Design: We analyzed the agonist and antagonist activities of 16 progesterone metabolites by their binding characteristics for hMR as well as functional studies assessing transactivation. Methods: We studied binding affinity using hMR expressed in a T7-coupled rabbit reticulocyte lysate system. We used co-transfection of an hMR expression vector together with a luciferase reporter gene in CV-1 cells to investigate agonistic and antagonistic properties. Results: Progesterone and 11b-OH-progesterone (11b-OH-P) showed a slightly higher binding affinity than cortisol, deoxycorticosterone and aldosterone. 20a-dihydro(DH)-P, 5a-DH-P and 17a-OH-P had a 3- to 10-fold lower binding potency. All other progesterone metabolites showed a weak affinity for hMR. 20a-DH-P exhibited the strongest agonistic potency among the metabolites tested, reaching 11.5% of aldosterone transactivation.
    [Show full text]
  • The Novel Progesterone Receptor
    0013-7227/99/$03.00/0 Vol. 140, No. 3 Endocrinology Printed in U.S.A. Copyright © 1999 by The Endocrine Society The Novel Progesterone Receptor Antagonists RTI 3021– 012 and RTI 3021–022 Exhibit Complex Glucocorticoid Receptor Antagonist Activities: Implications for the Development of Dissociated Antiprogestins* B. L. WAGNER†, G. POLLIO, P. GIANGRANDE‡, J. C. WEBSTER, M. BRESLIN, D. E. MAIS, C. E. COOK, W. V. VEDECKIS, J. A. CIDLOWSKI, AND D. P. MCDONNELL Department of Pharmacology and Cancer Biology (B.L.W., G.P., P.G., D.P.M.), Duke University Medical Center, Durham, North Carolina 27710; Molecular Endocrinology Group (J.C.W., J.A.C.), NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709; Department of Biochemistry and Molecular Biology (M.B., W.V.V.), Louisiana State University Medical School, New Orleans, Louisiana 70112; Ligand Pharmaceuticals, Inc. (D.E.M.), San Diego, California 92121; Research Triangle Institute (C.E.C.), Chemistry and Life Sciences, Research Triangle Park, North Carolina 27709 ABSTRACT by agonists for DNA response elements within target gene promoters. We have identified two novel compounds (RTI 3021–012 and RTI Accordingly, we observed that RU486, RTI 3021–012, and RTI 3021– 3021–022) that demonstrate similar affinities for human progeste- 022, when assayed for PR antagonist activity, accomplished both of rone receptor (PR) and display equivalent antiprogestenic activity. As these steps. Thus, all three compounds are “active antagonists” of PR with most antiprogestins, such as RU486, RTI 3021–012, and RTI function. When assayed on GR, however, RU486 alone functioned as 3021–022 also bind to the glucocorticoid receptor (GR) with high an active antagonist.
    [Show full text]
  • King's Research Portal
    King’s Research Portal DOI: 10.1016/j.psyneuen.2019.104420 Document Version Peer reviewed version Link to publication record in King's Research Portal Citation for published version (APA): Lombardo, G., Enache, D., Gianotti, L., Schatzberg, A. F., Young, A., Pariante, C. M., & Mondelli, V. (2019). Baseline cortisol and the efficacy of antiglucocorticoid treatment in mood disorders: a meta-analysis. Psychoneuroendocrinology, 110, [104420]. https://doi.org/10.1016/j.psyneuen.2019.104420 Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rights Copyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights. •Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research. •You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim.
    [Show full text]
  • The Molecular Biology of RU486. Is There a Role for Antiprogestins in the Treatment of Breast Cancer?*
    0163-769X/92/1302-0146$03.00/0 Endocrine Reviews Vol. 13, No. 2 Copyright 0 1992 by The Endocrine Society Printed in U.S.A. The Molecular Biology of RU486. Is There a Role for Antiprogestins in the Treatment of Breast Cancer?* KATHRYN B. HORWITZ DeDartments of Medicine and Patholot!v. Universitv of Colorado Health Sciences Center, Division of Endocrinology,. Denuer, Colorado 8026~ ’ I. Introduction spread use of tamoxifen reflects its efficacy and low II. Progesterone and the Normal Breast toxicity, and the fact that it makes good physiological III. Progesterone and Breast Cancer sense to block the local proliferative effects of estrogens A. Progestin agonists and tumor induction directly at the breast. But are estrogens the only hor- B. Progestin agonists and growth of established tumors mones with a proliferative impact on the breast and on IV. Molecular Mechanisms of Progesterone Antagonists A. Progesterone receptors breast cancers? This review focuses on evidence that B. Molecular mechanisms of progesterone antagonists progesterone also has proliferative actions in the breast; 1. Affinity for inactive PR - on the role of synthetic progestins in breast cancer 2. PR activation treatment; on the molecular biology of progesterone an- 3. DNA binding tagonists; and on the preliminary data showing that 4. Dimerization progesterone antagonists may be powerful new tools for 5. Transcription the management of metastatic breast cancer, because 6. PR “processing” or down-regulation they block the local effects of endogenous progesterone V. Progesterone Antagonists and the Treatment of Breast on breast cell proliferation. The reader is also referred Cancer to the excellent general review on progestin regulation A.
    [Show full text]
  • Improvements in Neurocognitive Function and Mood Following Adjunctive Treatment with Mifepristone (RU-486) in Bipolar Disorder
    Neuropsychopharmacology (2004) 29, 1538–1545 & 2004 Nature Publishing Group All rights reserved 0893-133X/04 $30.00 www.neuropsychopharmacology.org Improvements in Neurocognitive Function and Mood Following Adjunctive Treatment with Mifepristone (RU-486) in Bipolar Disorder ,1 1 1 1 1 1 Allan H Young* , Peter Gallagher , Stuart Watson , Dolores Del-Estal , Bruce M Owen and I Nicol Ferrier 1Stanley Research Centre, School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, UK High cortisol levels are found in severe mood disorders, particularly bipolar disorder. Hypercortisolaemia may cause or exacerbate both neurocognitive impairment and depressive symptoms. We hypothesized that antiglucocorticoid treatments, particularly corticosteroid receptor antagonists, would improve neurocognitive functioning and attenuate depressive symptoms in this disorder. To test this hypothesis, 20 bipolar patients were treated with 600 mg/day of the corticosteroid receptor antagonist mifepristone (RU-486) or placebo for 1 week in a double-blind crossover design. Over the total 6 weeks of the study, neurocognitive and neuroendocrine function were evaluated at baseline, days 21 and 42. Mood symptoms were evaluated weekly. Nineteen subjects completed the protocol; there were no drop-outs due to adverse events. Following treatment with mifepristone, selective improvement in neurocognitive functioning was observed. Spatial working memory performance was significantly improved compared to placebo (19.8% improvement over placebo). Measures of verbal fluency and spatial recognition memory were also improved after mifepristone. Beneficial effects on mood were found; Hamilton Depression Rating Scale scores were significantly reduced compared to baseline (mean reduction of 5.1 points) as were Montgomery–Asberg Depression Rating Scale scores (mean reduction of 6.05 points).
    [Show full text]
  • Antiprogestins, a New Form of Endocrine Therapy for Human Breast Cancer1
    [CANCER RESEARCH 49, 2851-2856, June 1, 1989] Antiprogestins, a New Form of Endocrine Therapy for Human Breast Cancer1 Jan G. M. Klijn,2Frank H. de Jong, Ger H. Bakker, Steven W. J. Lamberts, Cees J. Rodenburg, and Jana Alexieva-Figusch Department of Medical Oncology (Division of Endocrine Oncology) [J. G. M. K., G. H. B., C. J. K., J. A-F.J, Dr. Daniel den Hoed Cancer Center, and Department of Endocrinology ¡F.H. d. J., S. W. ]. L.J, Erasmus University, Rotterdam, The Netherlands ABSTRACT especially pronounced effects on the endometrium, decidua, ovaries, and hypothalamo-pituitary-adrenal axis. With regard The antitumor, endocrine, hematological, biochemical, and side effects of chronic second-line treatment with the antiprogestin mifepristone (RU to clinical practice, the drug has currently been used as a contraceptive agent or abortifacient as a result of its antipro 486) were investigated in 11 postmenopausal patients with metastatic breast cancer. We observed one objective response, 6 instances of short- gestational properties (2, 22-24). Based on its antiglucocorti term stable disease, and 4 instances of progressive disease. Mean plasma coid properties, this drug has been used or has been proposed concentrations of adrenocorticotropic hormone (/' < 0.05), cortisol (/' < for treatment of conditions related to excess corticosteroid 0.001), androstenedione (/' < 0.01), and estradici (P < 0.002) increased production such as Cushing's syndrome (19, 25-27) and for significantly during treatment accompanied by a slight decrease of sex treatment of lymphomas (24) and glaucoma (28); because of its hormone binding globulin levels, while basal and stimulated gonadotropi effects on the immune system, the drug has been suggested to levels did not change significantly.
    [Show full text]
  • Aldosterone and Mineralocorticoid Receptors—Physiology and Pathophysiology
    International Journal of Molecular Sciences Conference Report Aldosterone and Mineralocorticoid Receptors—Physiology and Pathophysiology John W. Funder Hudson Institute of Medical Research, Monash University, 27–31 Wright St., Clayton 3168, Australia; [email protected] Academic Editors: Anastasia Susie Mihailidou, Jan Danser, Sadayoshi Ito, Fumitoshi Satoh and Akira Nishiyama Received: 8 March 2017; Accepted: 4 May 2017; Published: 11 May 2017 Abstract: Aldosterone is a uniquely terrestrial hormone, first appearing in lungfish, which have both gills and lungs. Mineralocorticoid receptors (MRs), on the other hand, evolved much earlier, and are found in cartilaginous and bony fish, presumptive ligand cortisol. MRs have equivalent high affinity for aldosterone, progesterone, and cortisol; in epithelia, despite much higher cortisol circulating levels, aldosterone selectively activates MRs by co-expression of the enzyme 11β-hydroxysteroid dehydrogenase, Type 11. In tissues in which the enzyme is not expressed, MRs are overwhelmingly occupied but not activated by cortisol, which normally thus acts as an MR antagonist; in tissue damage, however, cortisol mimics aldosterone and acts as an MR agonist. The risk profile for primary aldosteronism (PA) is much higher than that in age-, sex-, and blood pressure-matched essential hypertensives. High levels of aldosterone per se are not the problem: in chronic sodium deficiency, as seen in the monsoon season in the highlands of New Guinea, plasma aldosterone levels are extraordinarily high, but cause neither hypertension nor cardiovascular damage. Such damage occurs when aldosterone levels are out of the normal feedback control, and are inappropriately elevated for the salt status of the individual (or experimental animal). The question thus remains of how excess salt can synergize with elevated aldosterone levels to produce deleterious cardiovascular effects.
    [Show full text]
  • The Necessity and Effectiveness of Mineralocorticoid Receptor Antagonist in the Treatment of Diabetic Nephropathy
    Hypertension Research (2015) 38, 367–374 & 2015 The Japanese Society of Hypertension All rights reserved 0916-9636/15 www.nature.com/hr REVIEW The necessity and effectiveness of mineralocorticoid receptor antagonist in the treatment of diabetic nephropathy Atsuhisa Sato Diabetes mellitus is a major cause of chronic kidney disease (CKD), and diabetic nephropathy is the most common primary disease necessitating dialysis treatment in the world including Japan. Major guidelines for treatment of hypertension in Japan, the United States and Europe recommend the use of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, which suppress the renin-angiotensin system (RAS), as the antihypertensive drugs of first choice in patients with coexisting diabetes. However, even with the administration of RAS inhibitors, failure to achieve adequate anti-albuminuric, renoprotective effects and a reduction in cardiovascular events has also been reported. Inadequate blockade of aldosterone may be one of the reasons why long-term administration of RAS inhibitors may not be sufficiently effective in patients with diabetic nephropathy. This review focuses on treatment in diabetic nephropathy and discusses the significance of aldosterone blockade. In pre-nephropathy without overt nephropathy, a mineralocorticoid receptor antagonist can be used to enhance the blood pressure-lowering effects of RAS inhibitors, improve insulin resistance and prevent clinical progression of nephropathy. In CKD categories A2 and A3, the addition of a mineralocorticoid receptor antagonist to an RAS inhibitor can help to maintain ‘long-term’ antiproteinuric and anti-albuminuric effects. However, in category G3a and higher, sufficient attention must be paid to hyperkalemia. Mineralocorticoid receptor antagonists are not currently recommended as standard treatment in diabetic nephropathy.
    [Show full text]
  • Differential Effects of Glucocorticoid and Antiglucocorticoid Treatment on Ovarian Progesterone and Relaxin Secretion in the Pig
    Iowa State University Breeding/Physiology Differential Effects of Glucocorticoid and Antiglucocorticoid Treatment on Ovarian Progesterone and Relaxin Secretion in the Pig L. L. Anderson, professor, from aging corpora lutea of pigs are regulated through Department of Animal Science separate mechanisms, and adrenal glucocorticoids may be involved in such a regulation process. ASL-R1569 Introduction Relaxin (RLX), a peptide hormone with partial Summary and Implications structural homology to insulin, and progesterone are Pregnancy lasts about 114 days in pigs. Porcine corpora produced by corpora lutea of pigs during pregnancy and lutea on the ovaries produce not only progesterone but also after hysterectomy. Although the normal duration of the relaxin (RLX), a peptide hormone that plays a critical role in estrous cycle is about 21 days in the pig, the corpora lutea suppressing uterine motility during pregnancy and in secrete progesterone and small amounts of RLX. During a remodeling connective tissues in preparation for imminent normal pregnancy of 114 days, circulating progesterone parturition. Progesterone concentrations in peripheral blood concentrations peak by day 8 and remain high (≈25 ng ml-1) remain elevated (_25 ng ml-1) for the major part of pregnancy and decrease just before parturition. The decrease until they decrease just before parturition. Relaxin in progesterone coincides with peak prepartum RLX release. accumulates in electron dense granules of luteal tissue and Glucocorticoid or antiglucocorticoid steroid, RU 486, increases gradually during pregnancy, and it is released into administration during late pregnancy can induce parturition the blood in peak amounts just before parturition. After in the pig. Peak release of RLX and a coincident decrease of hysterectomy of unmated gilts, the corpora lutea are progesterone in the circulating blood also can occur in the maintained to day 150; these aging corpora lutea continue to complete absence of fetuses and uterus (hysterectomy) in secrete RLX and progesterone.
    [Show full text]