DOCSLIB.ORG

Primary Adrenal Insufficiency: Managing Mineralocorticoid Replacement Therapy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Primary Adrenal Insufficiency: Managing Mineralocorticoid Replacement Therapy MINI-REVIEW Primary Adrenal Insufficiency: Managing Mineralocorticoid Replacement Therapy Daniela Esposito,1,2,3 Daniela Pasquali,3 and Gudmundur Johannsson1,2 1Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden; 2Department of Endocrinology, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden; and 3Department of Medical, Surgical, Neurological, Downloaded from https://academic.oup.com/jcem/article/103/2/376/4630430 by guest on 26 September 2021 Metabolic Sciences, and Aging, University of Campania “Luigi Vanvitelli,” 80138 Naples, Italy Context: Mineralocorticoid (MC) replacement therapy in patients with primary adrenal insufficiency (PAI) was introduced more than 60 years ago. Still, there are limited data on how MC substitution should be optimized, because MC dosing regimens have only been systematically investigated in a few studies. We review the management of current standard MC replacement therapy in PAI and its plausible impact on outcome. Design: Using PubMed, we conducted a systematic review of the literature from 1939 to 2017, with the following keywords: adrenal insufficiency, MC deficiency, aldosterone, cardiovascular disease, hypertension, and heart failure. Results: The current standard treatment consists of fludrocortisone (FC) given once daily in the morning, aiming at normotension, normokalemia, and plasma renin activity in the upper normal range. Available data suggest that patients with PAI may be underreplaced with FC as symptoms and signs indicating chronic MC underreplacement, such as salt craving and postural dizziness persist, in many treated patients with PAI. Data acquired from large registry-based studies show that glucocorticoid doses for replacement in PAI are higher than those estimated from endogenous production. Glucocorticoid overreplacement may reduce the need of MC replacement but may also be a consequence of inadequate MC replacement. Conclusions: The commonly used MC replacement in PAI may not be adequate in some patients. Insufficient MC substitution may be responsible for poor cardiometabolic outcome and the failure to restore well-being adequately in patients with PAI. Well-designed studies oriented at optimizing MC replacement therapy are urgently needed. (J Clin Endocrinol Metab 103: 376–387, 2018) rimary adrenal insufficiency (PAI) is a rare disease, Autoimmune PAI may occur either as an isolated entity Pcharacterized by insufficient secretion of glucocorti- (40% of all cases) or as part of an autoimmune poly- coids (GCs), mineralocorticoids (MCs), and androgens endocrine syndrome (60%) (1). Other etiologies to (1). The most common cause of PAI in industrialized mention are infectious, genetic, metastatic, hemorrhagic, countries is autoimmune adrenalitis, which is associated and infiltrative disorders, surgery, and drugs (3–5). Long- with detection of circulating 21-hydroxylase autoanti- chain fatty acids should be investigated to assess adre- bodies (1, 2). Measurement of these autoantibodies is noleukodystrophy in men with PAI without detectable therefore of value to determine the etiology of PAI (3, 4). antibodies (6). ISSN Print 0021-972X ISSN Online 1945-7197 Abbreviations: 11b-HSD2, 11b-hydroxysteroid-dehydrogenase type 2; ACTH, adreno- Printed in USA corticotropic hormone; ANP, atrial natriuretic peptide; BP, blood pressure; FC, flu- Copyright © 2018 Endocrine Society drocortisone; GC, glucocorticoid; GPER, G protein–coupled estrogen receptor; HC, Received 30 August 2017. Accepted 10 November 2017. hydrocortisone; HF, heart failure; HPA, hypothalamic-pituitary-adrenal; LV, left ventricular; First Published Online 15 November 2017 MC, mineralocorticoid; MCU, mineralocorticoid unit; MR, mineralocorticoid receptor; PAI, primary adrenal insufficiency; PRA, plasma renin activity; PRC, plasma renin concentration; PV, plasma volume; QoL, quality of life; RAAS, renin-angiotensin-aldosterone system; SAI, secondary adrenal insufficiency. 376 https://academic.oup.com/jcem J Clin Endocrinol Metab, February 2018, 103(2):376–387 doi: 10.1210/jc.2017-01928 doi: 10.1210/jc.2017-01928 https://academic.oup.com/jcem 377 If untreated, PAI can be lethal. Before the availability GPER expression is ubiquitous; in vascular cells, it is pres- of GCs, the majority of patients died within 2 years of ent in both endothelial and smooth muscle cells. Activation diagnosis (5, 7). Treatment of PAI consists of lifelong of GPER mediates rapid endothelium-dependent vasodi- replacement therapy with GCs and MCs, whereas an- lation, whereas MR activation produces vasoconstriction. drogen replacement is less frequent and mainly consid- Thus, the effect of aldosterone on endothelial function can ered in women. MC substitution is needed in PAI to vary depending on the balance between MR and GPER correct hypovolemia, hyperkalemia, hyponatremia, and expression (20, 21). hypotension (3). Secondary adrenal insufficiency (SAI) Aldosterone, like angiotensin II, has other endocrine is a different disease entity caused by a pituitary disorder activities essential for circulatory homeostasis. They disrupting adrenocorticotropic secretion that leads to GC contribute to blood coagulation (22) and vasoconstric- deficiency. Patients with SAI do not need MC replace- tion to preserve arterial pressure in case of hypovolemia Downloaded from https://academic.oup.com/jcem/article/103/2/376/4630430 by guest on 26 September 2021 ment because the secretion of aldosterone is mostly and stimulate thirst. They are also involved in regulating stimulated by the renin-angiotensin-aldosterone system inflammatory and reparative processes that follow tissue (RAAS), with only a minor component under the control injury (19, 22, 23) (Fig. 1). of adrenocorticotropic hormone (ACTH) (3, 8). Here, we present a review on MC replacement in PAI, MC Activity of GCs including the outcomes associated with current therapy, to promote further discussions on the safety and effec- MRs and GC receptors have analogous DNA-binding tiveness of conventional treatment. We searched Medline domains (94% homology for amino acids) and similar for articles published in English until 21 May 2017, with ligand-binding domains (57%) (8). Cortisol has high the following keywords: adrenal insufficiency, MC de- affinity for the MR allowing for MC activity. However, a ficiency, aldosterone, cardiovascular disease, hyperten- local enzyme, 11b-hydroxysteroid-dehydrogenase type 2 sion, and heart failure (HF). Studies including a detailed (11b-HSD2), which is colocalized with the MR, converts analysis of MC dosing regimens and monitoring were active cortisol to inactive cortisone, protecting MRs from identified and summarized in Table 1. This review focuses its effects (8). on MC replacement in adult patients with autoimmune Fludrocortisone (FC), a synthetic MC used in PAI for adrenalitis. replacement treatment, has a fluorine atom attached to the carbon 9 position that protects the molecule from b Aldosterone Secretion and Regulation rapid conversion by 11 -HSD2. FC exhibits 10-fold higher MC potency than aldosterone (24, 25). Different Aldosterone was discovered in the adrenal gland more GCs have different MC activity (26). Published compar- than 60 years ago (17). Subsequently, it was recognized ative data on MC potency of steroids are scanty. Hy- as a potent stimulus for sodium reabsorption, acting on drocortisone (HC), the most frequently used short-acting the distal segment of the convoluted tubule in the kidney. GC in PAI, exhibits the highest MC potency (24). Oelkers Aldosterone mediates its effects by the MC receptor et al. (11) defined the MC potency of 1 mg FC as 1 MC unit (MR), a member of the nuclear receptor superfamily (MCU). Because the MC potency of HC is about 1/400th widely expressed in tissues not only involved with salt that of FC, 0.4 mg HC may be regarded as 1 MCU (11). balance, including kidney, brain, lung, colon, and sali- Therefore, 15 to 25 mg of HC, the current recommended vary and sweat glands (18). daily dose in PAI (9), corresponds to approximately 0.04 Aldosterone secretion is mainly regulated by the RAAS to 0.06 mg of FC (11, 24). and the potassium ion, whereas ACTH and other pro- A study that investigated the effect of higher vs lower opiomelanocortin peptides are minor modulators (8, 19) GC replacement dose (30 to 40 vs 15 to 20 mg HC/d) on (Fig. 1). Therefore, aldosterone secretion is not impaired the RAAS and blood pressure (BP) in patients with SAI in SAI (4, 19). The MR, upon binding with aldosterone, is showed an increase in BP and a decrease in renin, al- transferred to the cell nucleus where the ligand-receptor dosterone, and potassium levels in the group on the complex interacts with hormone-responsive elements, higher dose (27). These findings are consistent with modulating transcription (8, 18). activation of the MR by HC, suggesting that MC Aldosterone, however, mediates its actions not only substitution may be superfluous in patients using via the “classic” transcriptional mechanisms but also higher doses of HC (30 to 40 mg/d). By contrast, pa- through “rapid” (,15-minute) mechanisms, described as tients treated with synthetic GCs require higher FC nongenomic signaling of MC (20). Therefore, these ef- doses as prednisolone exhibits fourfold lower MC fects seem to be independent of MRs and are mediated by activity than HC and dexamethasone does not exert Gprotein–coupled estrogen receptors (GPERs) (20, 21). any MC activity (26).
Load more

Recommended publications
  • Conduct Protocol in Emergency: Acute Adrenal Insufficiency
    ORIGINAL ARTICLE FARES AND SANTOS Conduct protocol in emergency: Acute adrenal insufficiency ADIL BACHIR FARES1*, RÔMULO AUGUSTO DOS SANTOS2 1Medical Student, 6th year, Faculdade de Medicina de São José do Rio Preto (Famerp), São José do Rio Preto, SP, Brazil 2Degree in Endocrinology and Metabology from Sociedade Brasileira de Endocrinologia e Metabologia (SBEM). Assistant Physician at the Internal Medicine Service of Hospital de Base. Researcher at Centro Integrado de Pesquisa (CIP), Hospital de Base, São José do Rio Preto. Endocrinology Coordinator of the Specialties Outpatient Clinic (AME), São José do Rio Preto, SP, Brazil SUMMARY Introduction: Acute adrenal insufficiency or addisonian crisis is a rare comor- bidity in emergency; however, if not properly diagnosed and treated, it may progress unfavorably. Objective: To alert all health professionals about the diagnosis and correct treatment of this complication. Method: We performed an extensive search of the medical literature using spe- cific search tools, retrieving 20 articles on the topic. Results: Addisonian crisis is a difficult diagnosis due to the unspecificity of its signs and symptoms. Nevertheless, it can be suspected in patients who enter the emergency room with complaints of abdominal pain, hypotension unresponsive to volume or vasopressor agents, clouding, and torpor. This situation may be associated with symptoms suggestive of chronic adrenal insufficiency such as hyperpigmentation, salt craving, and association with autoimmune diseases such as vitiligo and Hashimoto’s thyroiditis. Hemodynamically stable patients Study conducted at Faculdade may undergo more accurate diagnostic methods to confirm or rule out addiso- de Medicina de São José do nian crisis. Delay to perform diagnostic tests should be avoided, in any circum- Rio Preto (Famerp), São José do Rio Preto, SP, Brazil stances, and unstable patients should be immediately medicated with intravenous glucocorticoid, even before confirmatory tests.
    [Show full text]
  • GLOWM.414493 23/09/2021 This Chapter Should Be Cited As Follows: Lust K, Tellam J, Glob
    The Continuous Textbook of Women\'s Medicine Series ISSN: 1756-2228; DOI 10.3843/GLOWM.414493 23/09/2021 This chapter should be cited as follows: Lust K, Tellam J, Glob. libr. women's med., ISSN: 1756-2228; DOI 10.3843/GLOWM.414493 The Continuous Textbook of Women’s Medicine Series – Obstetrics Module Volume 8 MATERNAL MEDICAL HEALTH AND DISORDERS IN PREGNANCY Volume Editor: Clinical Associate Professor Sandra Lowe, University of New South Wales, Australia Chapter Adrenal Disorders in Pregnancy First published: February 2021 AUTHORS Karin Lust, MBBS, FRACP Director Women’s and Newborn Services, General & Obstetric Physician, Royal Brisbane and Women’s Hospital, Herston, Australia Jane Tellam, MBBS Endocrinology and Obstetric Medicine Advanced Trainee, Department of Endocrinology and Obstetric Medicine, Royal Brisbane and Women’s Hospital, Herston, Australia PHYSIOLOGY OF ADRENAL GLAND FUNCTION IN PREGNANCY There are two major components to the adrenal glands: the cortex and medulla. The adrenal cortex consists of the outermost zona glomerulosa (ZG) which produces mineralocorticoids (aldosterone), the middle zona fasciculata (ZF) which produces glucocorticoids (cortisol) and the zona reticularis which produces androgens (dehydroepiandrosterone, DHEA, and the sulfated version DHEA-S).1,2 The adrenal medulla produces adrenaline and noradrenaline. Cortisol Cortisol is essential for maintaining blood pressure, electrolyte physiology and glycemic control. Ten to fteen per cent circulates freely in non-pregnant women, with the remainder bound to cortisol binding globulin (CBG) and albumin.3 Both free and bound cortisol are elevated throughout pregnancy and spike at delivery. By the third trimester, cortisol levels have increased by 2–3 fold. Diurnal variation is preserved, characterized by high levels of cortisol in the morning and low levels at night.4 Multiple mechanisms are involved (Figure 1):5 1.
    [Show full text]
  • The Adrenal Glands
    The Adrenal Glands Thomas Jacobs, M.D. Diane Hamele-Bena, M.D. I. Normal adrenal gland A. Gross & microscopic B. Hormone synthesis, regulation & measurement II. Hypoadrenalism III. Hyperadrenalism; Adrenal cortical neoplasms IV. Adrenal medulla 1 Normal Adrenal Gland • Nldltdlld3545Normal adult adrenal gland: 3.5 - 4.5 grams Adrenal Cortex Morphology • Cortex: 3 zones: – Glomerulosa – Fasciculata – Reticularis 2 Hypoadrenalism 3 Hypoadrenalism • Primary Adrenocortical Insufficiency • Secondary Adrenocortical Insufficiency Hypoadrenalism Clinical Manifestations Primary adrenal insufficiency: Deficiency of glucocorticoids, mineralocorticoids, and androgens 4 Hypoadrenalism Clinical Manifestations Primary adrenal insufficiency: Concomitant hypersecretion of ACTH Hyperpigmentation Hypoadrenalism Clinical Manifestations Secondary adrenal insufficiency: Deficiency of ACTH NO hyperpigmentation 5 Pathology of Hypoadrenalism • PiPrimary Adrenocort ica l IffiiInsufficiency –Acute – Chronic = Addison Disease • Secondary Adrenocortical Insufficiency Pathology of Hypoadrenalism • PiPrimary Adrenocort ica l IffiiInsufficiency –Acute – Chronic = Addison Disease •Autoimmune adrenalitis 6 Addison Disease Clinical findings Mineralocorticoid deficiency Glucocorticoid deficiency •Hypotension •Weakness and fatigue •Hyponatremia •Weight loss •Hyperkalemia •Hyponatremia •Hypoglycemia •Pigmentation Androgenic deficiency •Abnormal H2O metabolism •Loss of pubic and axillary •Irritability and mental hair in women sluggishness Autoimmune Adrenalitis Three settings:
    [Show full text]
  • Does Pseudohypoaldosteronism Mask the Diagnosis of Congenital Adrenal Hyperplasia?
    J Clin Res Pediatr En docrinol 2011;3(4):219-221 DO I: 10.4274/jcrpe.369 Case Report Does Pseudohypoaldosteronism Mask the Diagnosis of Congenital Adrenal Hyperplasia? Sebahat Yılmaz Ağladıoğlu1, Zehra Aycan1, Havva Nur Peltek Kendirci1, Nilgün Erkek2, Veysel Nijat Baş1 1Dr. Sami Ulus Obstetrics and Gynecology, Pediatric Health and Disease Training and Research Hospital, Clinics of Pediatric Endocrinology, Ankara, Turkey 2Dr. Sami Ulus Obstetrics and Gynecology, Pediatric Health and Disease Training and Research Hospital, Clinics of Pediatrics, Ankara, Turkey In tro duc ti on Hyperpotassemia together with severe hyponatremia is rare in infancy but important as it can be life-threatening. Congenital adrenal hyperplasia (CAH) should be considered first among adrenal diseases in the differential diagnosis of hyponatremia if no gastrointestinal salt loss is present. Adrenal hypoplasia, isolated aldosterone deficiency, drug effects and pseudohypoaldosteronism (PHA) are other conditions that should be kept in mind in the differential diagnosis (1). A congenital renal anomaly can cause PHA due to a lack of response to aldosterone in the distal tubule in male infants under 3 months of age in the presence of obstructive uropathy, vesicoureteral reflux (VUR) and/or urinary tract infection (UTI) (2) and this can be confused with CAH. ABS TRACT Compensated salt-losing CAH (SL-CAH) is accompanied Hyponatremia and hyperpotassemia occurring in the first few weeks of by increased androgen production, inadequate cortisol life primarily indicate aldosterone deficiency due to salt-losing production and also increased renin and aldosterone levels; congenital adrenal hyperplasia (SL-CAH), while mineralocorticoid deficiency and insensitivity are the main causes of hyponatremia and serum electrolytes are normal in this condition (3).
    [Show full text]
  • Revisitation of Autoimmune Addison's Disease
    International Journal of Clinical Endocrinology Review Article Revisitation of Autoimmune Addison’s Disease: known and Open Pathophysiologic and Clinical Aspects - Annamaria De Bellis*, Giuseppe Bellastella, Maria Ida Maiorino, Vlenia Pernice, Miriam Longo, Carmen Annunziata, Antonio Bellastella and Katherine Esposito Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy *Address for Correspondence: Annamaria De Bellis, Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy, Tel/Fax: 0039-081-566-5245; E-mail: Submitted: 30 January 2019; Approved: 21 March 2019; Published: 22 March 2019 Cite this article: Bellis AD, Bellastella G, Maiorino MI, Pernice V, Longo M, et al. Revisitation of Autoimmune Addison’s Disease: known and Open Pathophysiologic and Clinical Aspects. Int J Clin Endocrinol. 2019;3(1): 001-0013. Copyright: © 2019 Bellis AD, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ISSN: 2640-5709 International Journal of Clinical Endocrinology ISSN: 2640-5709 ABSTRACT Addison’s Disease (AD) or primary adrenal insuffi ciency has been thought a rare disease for a long time, but recent epidemiological studies have reported a rising prevalence in developed countries. Among the causes of apparently idiopathic forms, autoimmunity plays a relevant role. This review will be focused on several aspects of autoimmune AD, which may manifest either as an isolated disorder or associated with other autoimmune diseases among the autoimmune polyglandular syndromes. HLA plays a key role in determining T cell responses to antigens, and various HLA alleles have been shown to be associated with many T cell-mediated autoimmune disorders, but the mechanism by which the adrenal cortex is destroyed in AD is still discussed.
    [Show full text]
  • Common Adrenal Diseases
    Common Adrenal Diseases Rachel Mast, D.O. February 7, 2014 Outline • Pre-test Questions • Topics: • Cases • Primary AI • Anatomy/physiology • Central AI • Cushing’s syndrome • Symptoms/Signs • Incidentaloma • Diagnosis/Treatment • Pheochromocytoma • Post-test Questions • Primary Aldosteronism • Questions Pre-Test Question #1 The primary cause of central adrenal insufficiency is 20% 1. Pituitary adenoma 20% 2. Sheehan’s syndrome 20% 3. Exogenous glucocorticoids 20% 4. Tuberculosis 20% 5. Metastatic cancer Case #1 • Mr. Smith is a 34 yo wm presents to your office to establish care. He is a manual laborer and has noticed worsening fatigue that is interfering with his job. He also reports nausea, decreased appetite and progressive, unintentional weight loss. No night sweats, diarrhea, or blood in his stool. No chest pain or SOB. He admits to some recent problems with memory and depression. • He has no known medical problems and is a non-drinker, never smoker. • His family history is unknown as he is adopted. • He takes no prescribed medications.. Case #1 continued • On physical exam you note a blood pressure of 100/60, and general, diffuse tenderness on palpation of his abdomen • He has some areas of vitiligo and otherwise looks tan Case #1 Continued • Laboratory evaluation shows a normal TSH, normal LFTs, normal CBC except for eosinophilia • His BMP shows mild hyponatremia and hyperkalemia Primary Adrenal Insufficiency • AKA Addison’s Disease • First described by Thomas Addison in 1855 • First synthesized cortisone did not become available
    [Show full text]
  • Adrenal Disorders
    ADRENAL DISEASE Dr. Kareithi Adrenal anatomy and function £ Wt 8-10 g £ Outer - cortex with 3 zones producing steroids § Zona reticularis § Zona fasciculata § Zona glomerulosa , £ Inner - medulla that synthesizes, stores and secretes catecholamines £ adrenal steroids grouped into 3 classes based on their predominant physiological effects. § Glucocorticoids § Mineralocorticoids § Androgens Corticosteroids -Effects Increased or stimulated £ Decreased or inhibited £ Gluconeogenesis £ Protein synthesis £ Glycogen deposition £ Host response to £ Protein catabolism infection £ Fat deposition £ Lymphocyte transformation £ Sodium retention £ Delayed hypersensitivity £ Potassium loss £ Circulating lymphocytes £ Free water clearance £ Circulating eosinophils £ Uric acid production £ Circulating neutrophils Mineralocorticoids £ Their predominant effect is on the EC balance of Na ⁺⁺⁺ and K⁺⁺⁺ in the distal tubule of the kidney. £ Aldosterone , § solely from zona glomerulosa , § is the predominant mineralocorticoid in humans £ corticosterone makes a small contribution £ mineralocorticoid activity of cortisol is weak but it is present in considerable excess Androgens £ Have only relatively weak intrinsic androgenic activity until metabolized peripherally to testosterone or dihydrotestosterone. Biochemistry Physiology £ Glucocorticoid production by the adrenal is under hypothalamic-pituitary control. £ Corticotropin-releasing hormone (CRH): § secreted in the hypothalamus in response to circadian rhythm &stress. § It travels down the portal system to stimulate ACTH release from the anterior pituitary § is derived from the prohormone pro-opiomelanocortin, which also produce a number of other peptides including beta-lipotrophin and beta-endorphin. £ Many of these peptides, including ACTH , contain melanocyte-stimulating hormone (MSH )-like sequences which cause pigmentation when levels of ACTH are markedly raised. £ ACTH stimulates cortisol production in the adrenal gland £ Cortisol causes negative feedback on the hypothalamus and pituitary to inhibit further CRH/ACTH release.
    [Show full text]
  • Aldosterone SYMPTOMS
    Unless otherwise noted, the content of this course material is licensed under a Creative Commons Attribution - Non-Commercial - Share Alike 3.0 License. Copyright 2008, Arno Kumagai, Gary Hammer The following information is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. You should speak to your physician or make an appointment to be seen if you have questions or concerns about this information or your medical condition. You assume all responsibility for use and potential liability associated with any use of the material. Material contains copyrighted content, used in accordance with U.S. law. Copyright holders of content included in this material should contact [email protected] with any questions, corrections, or clarifications regarding the use of content. The Regents of the University of Michigan do not license the use of third party content posted to this site unless such a license is specifically granted in connection with particular content objects. Users of content are responsible for their compliance with applicable law. Adrenal Physiology & Steroid Pharmacology Logo: All Rights Reserved Regents of the University of Michigan. 2008 Gary D. Hammer, M.D., Ph.D. University of Michigan Ann Arbor, Michigan USA Learning Objectives After this lecture you should have an understanding of: • The feedback loops regulating cortisol secretion. • The physiologic actions of glucocorticoids (cortisol) + mineralocorticoids
    [Show full text]
  • Adrenal Dysfunction
    e & M tabo gy li o c Speiser, Endocrinol Metab Synd 2015, 4:1 l S o y n i n r d c r o o m DOI: 10.4172/2161-1017.1000164 d n e E Endocrinology & Metabolic Syndrome ISSN: 2161-1017 Review Article Open Access Adrenal Dysfunction Phyllis W Speiser* Division of Pediatric Endocrinology, Cohen Children’s Medical Center of New York, School of Medicine, Hofstra-North Shore LIJ, USA Abstract Adrenal cortical disease, especially adrenal insufficiency, is more common than adrenal medullary disease and often goes unrecognized for extended periods. Physicians should consider the diagnosis of adrenal insufficiency in any patient with non-specific unexplained signs or symptoms including hypoglycemia, growth failure, weight loss, vomiting, or lethargy. The clinical features may be mistaken for, and should be differentiated from, infection, malnutrition, and gastrointestinal disease, inborn errors of metabolism, anorexia, chronic fatigue syndrome, and depression. Keywords: Adrenal dysfunction; malnutrition; hypoglycemia; pressors. At high concentrations, cortisol acts as a mineralocorticoid anorexia agonist, causing sodium and water retention. Cortisol and/or aldosterone deficiencies often result in shock if unrecognized and Anatomy and Physiology untreated [3]. The adrenal glands each weigh about 4 grams in full-term infants Adrenal Insufficiency at birth, which is equivalent to that of adult glands; however, adrenal size decreases by about 50% to 60% within the first week of life and then History and physical examination enlarges in mid-childhood at the time of adrenarche. There is an inner The symptoms of cortisol deficiency include lethargy, fatigue, medulla and an outer cortex, linked by vascular supply and hormonal weakness, dizziness, and anorexia.
    [Show full text]
  • Adrenal Disorders for the USMLE, Step One
    Adrenal Disorders for the USMLE, Step One: Abnormalities of the Fasciculata: Hypocortisolism Howard Sachs, MD Patients Course, 2017 Associate Professor of Clinical Medicine UMass Medical School Manifestations Aldosterone Cortisol Response Anything else Etiologies Normal Physiology Etiololgy of Hypocortisolism Acute, Shock Chronic: HPA axis failure • Pituitary • Hypothalamus – Apoplexy • Infiltrative disorders • Adrenal • Pituitary – Hemorrhage • Sheehan’s • HPA Failure • Adenoma/Mass effect – Acute cessation+ • Adrenal • Autoimmune • Infiltrative (bait-switch) • Tumor • Infection • CAH (enzyme deficiency) • HPA Failure • Cessation: exogenous CCS Etiololgy of Hypocortisolism Acute, Shock Chronic: HPA axis failure • Pituitary • Hypothalamus – Apoplexy • Infiltrative disorders • Adrenal • Pituitary – Hemorrhage • Sheehan’s • HPA Failure • Adenoma/Mass effect – Acute cessation+ • Adrenal • Autoimmune • Infiltrative (bait-switch) • Tumor • Infection • CAH (enzyme deficiency) • HPA Failure • Cessation: exogenous CCS Etiololgy of Hypocortisolism Acute, Shock Chronic: HPA axis failure • Pituitary • Hypothalamus – Apoplexy • Infiltrative disorders • Adrenal • Pituitary – Hemorrhage • Sheehan’s • HPA Failure • Adenoma/Mass effect – Acute cessation+ • Adrenal • Autoimmune • Infiltrative (bait-switch) • Tumor • Infection • CAH (enzyme deficiency) • HPA Failure • Cessation: exogenous CCS Etiololgy of Hypocortisolism Acute, Shock Chronic: HPA axis failure • Pituitary • Hypothalamus – Apoplexy • Infiltrative disorders • Adrenal • Pituitary – Hemorrhage
    [Show full text]
  • MOLECULAR BASIS of ADRENAL INSUFFICIENCY 63R Density Lipoproteins (LDL)
    0031-3998/05/5705-0062R PEDIATRIC RESEARCH Vol. 57, No. 5, Pt 2, 2005 Copyright © 2005 International Pediatric Research Foundation, Inc. Printed in U.S.A. Molecular Basis of Adrenal Insufficiency KENJI FUJIEDA AND TOSHIHIRO TAJIMA Department of Pediatrics [K.J.], Asahikawa Medical College, Asahikawa 078-8510, Japan, Department of Pediatrics [T.T.], Hokkaido University School of Medicine, Sapporo 060-0835, Japan ABSTRACT Defective production of adrenal steroids due to either primary Abbreviations adrenal failure or hypothalamic-pituitary impairment of the cor- ABS, Antley-Bixler syndrome ticotrophic axis causes adrenal insufficiency. Depending on the AHC, adrenal hypoplasia congenita etiologies of adrenal insufficiency, clinical manifestations may be AIRE, autoimmune regulator severe or mild, have gradual or sudden onset, begin in infancy or CAH, congenital adrenal hyperplasia childhood/adolescence. Adrenal crisis represents an endocrine DAX-1(NR0B1), dosage-sensitive sex reversal-adrenal emergency, and thus the rapid recognition and prompt therapy hypoplasia congenita critical region on the X-chromosome, for adrenal crisis are critical for survival even before the diag- gene-1 nosis is made. The recognition of various disorders that cause P450scc, cholesterol desmolase (cholesterol side chain adrenal insufficiency, either at a clinical or molecular level, often cleavage enzyme) has implications for the management of the patient. Recent POR, P450-oxidoreductase molecular-genetic analysis for the disorder that causes adrenal SF-1(NR5A1), steroidogenic
    [Show full text]
  • Diagnosis and Management of Adrenal Insufficiency Bancos, Irina; Hahner, Stefanie; Tomlinson, Jeremy; Arlt, Wiebke
    University of Birmingham Diagnosis and management of adrenal insufficiency Bancos, Irina; Hahner, Stefanie; Tomlinson, Jeremy; Arlt, Wiebke DOI: 10.1016/S2213-8587(14)70142-1 License: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) Document Version Peer reviewed version Citation for published version (Harvard): Bancos, I, Hahner, S, Tomlinson, J & Arlt, W 2015, 'Diagnosis and management of adrenal insufficiency', The Lancet Diabetes and Endocrinology, vol. 3, no. 3, pp. 216-26. https://doi.org/10.1016/S2213-8587(14)70142-1 Link to publication on Research at Birmingham portal General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. •User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) •Users may not further distribute the material nor use it for the purposes of commercial gain. Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version. Take down policy While the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive.
    [Show full text]