DOCSLIB.ORG

Congenital Adrenal Hyperplasia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Congenital Adrenal Hyperplasia Seminar Congenital adrenal hyperplasia Diala El-Maouche, Wiebke Arlt, Deborah P Merke Lancet 2017; 390: 2194–210 Congenital adrenal hyperplasia is a group of autosomal recessive disorders encompassing enzyme deficiencies in the Published Online adrenal steroidogenesis pathway that lead to impaired cortisol biosynthesis. Depending on the type and severity of May 30, 2017 steroid block, patients can have various alterations in glucocorticoid, mineralocorticoid, and sex steroid production that http://dx.doi.org/10.1016/ require hormone replacement therapy. Presentations vary from neonatal salt wasting and atypical genitalia, to adult S0140-6736(17)31431-9 presentation of hirsutism and irregular menses. Screening of neonates with elevated 17-hydroxyprogesterone This online publication has been corrected. The corrected concentrations for classic (severe) 21-hydroxylase deficiency, the most common type of congenital adrenal hyperplasia, version first appeared at is in place in many countries, however cosyntropin stimulation testing might be needed to confirm the diagnosis or thelancet.com on Nov 11, 2017 establish non-classic (milder) subtypes. Challenges in the treatment of congenital adrenal hyperplasia include avoidance National Institutes of Health of glucocorticoid overtreatment and control of sex hormone imbalances. Long-term complications include abnormal Clinical Center, Bethesda, growth and development, adverse effects on bone and the cardiovascular system, and infertility. Novel treatments aim MD 20892, USA (D El-Maouche MD, to reduce glucocorticoid exposure, improve excess hormone control, and mimic physiological hormone patterns. Prof D P Merke MD); Institute of Metabolism and Systems Introduction More than 95% of congenital adrenal hyperplasia cases Research (IMSR), University of In 1865, Luigi De Crecchio, an Italian pathologist, are due to 21OH deficiency,23 characterised by impaired Birmingham & Centre for Endocrinology, Diabetes and described the case of a man who, at autopsy, was found to cortisol and aldosterone production and androgen excess. Metabolism (CEDAM), have female internal anatomy and large adrenal glands, Life-saving neonatal screening for classic congenital Birmingham Health Partners, representing the first known case of presumed congenital adrenal hyperplasia due to 21OH deficiency was first Birmingham, UK adrenal hyperplasia (figure 1).1 However, treatment for done in Alaska in 1977,7 and is currently used worldwide (Prof W Arlt MD); and The Eunice Kennedy Shriver congenital adrenal hyperplasia was not introduced in more than 40 countries, including all 50 US states National Institute of Child for almost another century when cortisone was given for since 2009, although it is yet to be implemented in the Health and Human what was then known as adrenogenital syndrome.18–22 UK.7,23–25 Although all types of classic congenital adrenal Development, Bethesda, MD, Congenital adrenal hyperplasia is a group of seven hyperplasia are rare orphan diseases, the non-classic USA (Prof D P Merke) autosomal recessive diseases caused by mutations in form due to 21OH deficiency is estimated to be one of the Correspondence to: 26,27 Dr Deborah P Merke, National genes encoding enzymes in pathways involved in cortisol most common autosomal recessive disorders. Institutes of Health Clinical biosynthesis: 21-hydroxylase (21OH), 11β-hydroxylase Congenital adrenal hyperplasia remains one of the Center, Bethesda, (11βOH), 17α-hydroxylase (17OH; also known as most challenging endocrine disorders to diagnose, MD 20892–1932, USA 17,20-lyase), 3β-hydroxysteroid dehydrogenase type 2 manage, and treat because of the disorders’ direct and [email protected] (3βHSD2), steroidogenic acute regulatory protein (StAR), indirect effects on steroidogenic pathways and the rarity P450 cholesterol side-chain cleavage enzyme (SCC), and of these conditions. Advances in genetics, metabolomics, P450 oxidoreductase (POR). Multiple hormonal and treatment strategies continue to improve imbalances occur and congenital adrenal hyperplasia understanding of these complex diseases and aim to manifests with a range of clinical and biochemical improve patient outcomes. phenotypes, with or without alterations in glucocorticoid, mineralocorticoid, and sex steroid production. Both Genetics and pathophysiology severe (classic) and mild (non-classic) forms of congenital Overview adrenal hyperplasia have been described. All types of congenital adrenal hyperplasia are monogenetic and autosomal recessive. Most patients are compound heterozygotes, meaning that they have different mutations Search strategy in two alleles for a particular gene. The clinical We searched the Cochrane Library, MEDLINE, and Embase between Jan 1, 2010, and manifestation follows the allele that results in a more Sept 30, 2016. Keywords and controlled vocabulary and their synonyms were used when functional enzyme, and generally genotype–phenotype 28,29 appropriate. We used variations of the search term “congenital adrenal hyperplasia” in correlation is good. combination with the terms “diagnosis/diagnostics”, “genetics”, “genomics”, “adrenal Adrenal steroidogenesis occurs by a series of steps crisis”, “glucocorticoid”, “mineralocorticoid”, “gene therapy”, “quality of life”, “well-being”, facilitated by adrenal zone-specific enzyme expression, “screening”, “metabolomics”, “prenatal”, “antenatal”, “bone mineral density”, “tumor”, and in different types of congenital adrenal hyperplasia “pregnancy”, “treatment/therapy/ therapeutic”, “fertility/fecundity”, “surgery”, this process is interrupted at distinct points. In addition “management”, “metabolic”, and “complications”. We largely selected publications in the to the classic well established steroidogenesis pathway, past 5 years, but did not exclude commonly referenced and highly regarded older an alternative pathway to active androgen biosynthesis 30,31 publications. We also searched the reference lists of articles identified by this search exists (termed the backdoor pathway), which might strategy and selected those we judged relevant. Review articles and book chapters are play a role in the pathophysiology of congenital adrenal cited to provide readers with more details and more references than this Seminar has hyperplasia (figure 2). The clinical manifestation of room for. The search was restricted to English publications. congenital adrenal hyperplasia is closely related to the type and severity of impairment. 2194 www.thelancet.com Vol 390 November 11, 2017 þÿDownloaded for Anonymous User (n/a) at Consejería de Sanidad de Madrid Biblioteca Virtual from ClinicalKey.com by Elsevier on February 21, 2019. For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved. Seminar 1985: CAH caused by CYPA gene mutations9 1985: CAH caused by 2010 onwards: 1950: Nobel Prize for multiple abnormalities 2001: CAH Genetic advances, 1865: Case report of “discoveries relating of microsomal mixed- caused by biomarker a man with internal to the hormones of function oxidases (later CYPA gene discovery, and female anatomy, the adrenal cortex, 1962: Lipoid known as POR deficiency)10 mutations15 novel treatments hypospadias, enlarged their structure and CAH described5 adrenals, and sudden biological effects”2 1962: CAH 1977: First 1992: CAH caused death1 1950: Cortisone caused by defect neonatal screen by HSDB gene treatment for CAH in 3βHSD26 in Alaska8 mutations13 1800s 1930 1940 1950 1960 1970 1980 1990 2000 2010 1930s: Chemical 1955: CAH 1966: CAH caused 1988: CAH 1995: CAH structure of caused by defect by defect in caused by caused by adrenal steroids in 21-hydroxylation 17α-hydroxylation7 CYPA gene StAR gene and 11-hydroxylation3,4 mutations11 mutations14 1940s: 1991: CAH 2004: CAH Conceptualisation of HPA axis, caused by caused by cortisone treatment for CYPB gene POR gene rheumatoid arthritis (1949) mutations12 mutations16,17 Figure 1: Timeline of important discoveries in adrenal steroidogenesis, treatment landmarks, and gene discovery of congenital adrenal hyperplasia HPA=hypothalamic-pituitary-adrenal. CAH=congenital adrenal hyperplasia. 3βHSD2=3β-hydroxysteroid dehydrogenase type 2 deficiency. POR=P450 oxidoreductase. 21OH deficiency skeletal growth in children. Patients with the non- The gene for 21OH, CYP21A2, is located within the classic form retain up to 50% of enzyme activity and human leucocyte antigen class III region of mostly do not have adrenal insufficiency, but might chromosome 6 (table 1). CYP21A2 and a homologous have partial glucocorticoid deficiency, and female pseudogene, CYP21A1P, lie about 30 kb apart. Meiotic patients have normal genitalia.41 Patients might recombination events are common in this genomic present with mild androgen excess or have few or region because of the high degree of sequence homology no symptoms. In fact, the term cryptic congenital between duplicated genes. Approximately 95% of adrenal hyperplasia was created to define patients with CYP21A2 disease causing mutations are CYP21A1P- non-classic congenital adrenal hyperplasia who are derived variants or deletions due to recombination identified by family genetic studies, but are otherwise events.28,39 asymptomatic.42 Defective 21OH-hydroxylation results in decreased glucocorticoid and mineralocorticoid synthesis and 11βOH deficiency elevated precursors, most notably 17-hydroxyprogesterone Congenital adrenal hyperplasia caused by 11βOH (17OHP), which is used for congenital adrenal deficiency is due to CYP11B1 mutations
Load more

Recommended publications
  • Congenital Adrenal Hyperplasia in the Newborn
    The Leo Fung Center for CAH and Disorders of Sex Development Congenital Adrenal Hyperplasia in the Newborn Contents Introduction 1 What is congenital adrenal hyperplasia? 1 Types of CAH 3 Diagnosing CAH in newborns 4 Treating CAH 5 Untreated CAH 7 CAH in children and young adults 8 Frequently asked questions 9 Glossary 11 Resources 13 Acknowledgments 14 Congenital Adrenal Hyperplasia in the Newborn 1 Introduction This handbook will provide you and your family information about congenital adrenal hyperplasia (CAH). While this guide will not answer all of your questions, it will provide basic medical facts that will help you to talk to your doctors. It is important to know that CAH cannot be cured but it can be treated. Your child will need to take medicine for the rest of his or her life. If your child takes this medicine, he or she should have a completely normal life in every way. Successful treatment requires teamwork between you and your doctor. The doctor will monitor your child in order to know what dose of medicine is needed. We ask that you give your baby the medication on the schedule recommended by your doctor. Your family is not alone. The Leo Fung Center for CAH and Disorders of Sex Development (DSD) at University of Minnesota Amplatz Children’s Hospital, provides a large network of support, including medical specialists, therapists and counselors who all have expertise in caring for patients with CAH. What is congenital adrenal hyperplasia? Let’s begin by examining each word. • Congenital means existing at birth (inherited). • Adrenal means that the adrenal glands are involved.
    [Show full text]
  • DOI: 10.4274/Jcrpe.Galenos.2021.2020.0175
    DOI: 10.4274/jcrpe.galenos.2021.2020.0175 Case report A novel SCNN1A variation in a patient with autosomal-recessive pseudohypoaldosteronism type 1 Mohammed Ayed Huneif1*, Ziyad Hamad AlHazmy2, Anas M. Shoomi 3, Mohammed A. AlGhofely 3, Dr Humariya Heena 5, Aziza M. Mushiba 4, Abdulhamid AlSaheel3 1Pediatric Endocrinologist at Najran university hospital, Najran Saudi Arabia. 2 Pediatric Endocrinologist at Al yamammah hospital, , Riyadh, Saudi Arabia. 3 Pediatric Endocrinologist at Pediatric endocrine department,. Obesity, Endocrine, and Metabolism Center, , King Fahad Medical City, Riyadh, Saudi Arabia. 4Clinical Geneticist, Pediatric Subspecialties Department, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia. 5 Research Center, King Fahad Medical City, Riyadh , Saudi Arabia What is already known on this topic ? Autosomal-recessive pseudohypoaldosteronism type 1 (PHA1) is a rare genetic disorder caused by different variations in the ENaC subunit genes. Most of these variations appear in SCNN1A mainly in exon eight, which encodes for the alpha subunit of the epithelial sodium channel ENaC. Variations are nonsense, single-base deletions or insertions, or splice site variations, leading to mRNA and proteins of abnormal length. In addition, a few new missense variations have been reported. What this study adds ? We report a novel mutation [ c.729_730delAG (p.Val245Glyfs*65) ] in the exon 4 of the SCNN1A gene In case of autosomal recessive pseudohypoaldosteronism type 1. Patient with PHA1 requires early recognition, proper treatment, and close follow-up. Parents are advised to seek genetic counseling and plan future pregnancies. proof Abstract Pseudohypoaldosteronism type 1 (PHA1) is an autosomal-recessive disorder characterized by defective regulation of body sodium levels.
    [Show full text]
  • 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]
  • ACUTE ADRENAL INSUFFICIENCY by PAUL FOURMAN, M.D., M.R.C.P
    Postgrad Med J: first published as 10.1136/pgmj.29.330.215 on 1 April 1953. Downloaded from 215 ACUTE ADRENAL INSUFFICIENCY By PAUL FOURMAN, M.D., M.R.C.P. Nuffield Department of Clinical Medicine, University of Oxford In acute adrenal insufficiency we are faced with common in patients whose adrenal insufficiency is the interaction of many factors ; if in trying to due to hypopituitarism than in patients with disentangle them I have cut some knots it is for Addison's disease. the sake of brevity. Addison's disease is characterized by a failure to Acute adrenal insufficiency may result from conserve sodium and we usually think of the crisis sudden loss of adrenal function by haemorrhage, of acute adrenal insufficiency as a condition of thrombosis or ablation. More often it-occurs in a shock brought about by salt depletion. This patient with chronic adrenal insufficiency, either might be true in a patient with Addison's disease in the natural course of the illness or following who is in crisis when he first presents ; in him the an injury such as'infection, operation or exposure. crisis is the climax of a long illness during which Acute adrenal insufficiency is characterized by there has been time for the sodium stores to by copyright. prostration and collapse with low blood pressure become depleted. The sodium depletion may and rapid pulse. It is usually accompanied by represent a stress that released the crisis rather gastro-intestinal symptoms: anorexia, vomiting than the immediate cause of the shock-like state. and diarrhoea, and sometimes abdominal pain and Sodium depletion is not an essential feature of hiccup.
    [Show full text]
  • Lyase Deficiency Due to P.R96W Mutation in the CYP17 Gene in a Brazilian Patient
    clinical case report Combined 17α-hydroxylase/17,20- lyase deficiency due to p.R96W mutation in the CYP17 gene in a Brazilian patient Deficiência combinada de 17α-hidroxilase/17,20 liase devido à mutação p.R96W no gene CYP17 em um paciente brasileiro Fabíola Costenaro1, Ticiana C. Rodrigues1, Claudio E. Kater2, Richard J. Auchus3, Mahboubeh Papari-Zareei3, Mauro A. Czepielewski1 SUMMARY 1 Division of Endocrinology, Congenital adrenal hyperplasia (CAH) resulting from 17α-hydroxylase/17,20-lyase deficiency is Hospital de Clínicas de Porto a rare autosomal recessive disease and the second most common form of CAH in Brazil. We Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), describe the case of a Brazilian patient with CYP17 deficiency (17α-hydroxylase/17,20-lyase de- Porto Alegre, RS, Brazil ficiency) caused by a homozygous p.R96W mutation on exon 1 of the CYP17 gene, an unusual 2 Division of Endocrinology genotype in Brazilian patients with this form of CAH. The patient, raised as a normal female, and Metabolism, Department of Medicine, Escola Paulista sought medical care for lack of pubertal signs and primary amenorrhea at the age of 16 years. At de Medicina, Universidade evaluation, the presence of a 46,XY karyotype, hypertension and hypokalemia were observed. Federal de São Paulo (Unifesp/ We emphasize the recognition of CYP17 deficiency in the differential diagnosis of cases of hy- EPM), São Paulo, SP, Brazil 3 Division of Endocrinology and pergonadotrophic hypogonadism and hypertension in young patients who need specific treat- Metabolism, Department of Internal ment for both situations. Arq Bras Endocrinol Metab. 2010;54(8):744-8 Medicine, University of Texas Southwestern Medical Center, USA SUMÁRIO Correspondence to: A hiperplasia adrenal congênita (HAC), em razão da deficiência de 17α-hidroxilase/17,20-liase, Mauro A.
    [Show full text]
  • Preventable Deaths: Panhypopituitarism and Adrenal Insufficiency
    Preventable Deaths: Panhypopituitarism and adrenal insufficiency. What you need to know What is panhypopituitarism? Your child has been diagnosed with a big scary sounding word, and all you can think is: 'What does this mean? and 'Why have I never heard of this?' Simply put, panhypopituitarism means that your child's pituitary gland does not function properly and as a result, your child is deficient in one or several hormones. Some children have congenital panhypopituitarism, meaning they are born with it. Others have acquired panhypopituitarism following an event such as head trauma, brain tumor surgery, or brain radiation. It is rare enough that is entirely possible, in fact, probable, that you will not initially know anyone else with this disorder. What will my child need? Although the diagnosis and condition can seem intimidating, it is very manageable once you understand what is needed. Unfortunately the condition cannot be cured or reversed, but again, it can be effectively managed. Your child will need to take medications to replace the missing hormones. These might include thyroid hormone, growth hormone, cortisol, and/or possibly others. Your doctor will go over these with you, as dosages vary from child to child. Most medications are taken orally, but growth hormone must be taken by daily injection. Your endocrinologist will work with you and your child to achieve the proper dosages and will guide you in how to administer any necessary medications. Why is it sometimes life threatening? What is adrenal insufficiency? Of the hormone deficiencies your child may have, the most critical is cortisol, also known as the 'stress hormone.' Cortisol is essential for life , and is therefore the central focus of this guide.
    [Show full text]
  • Disorders of the Adrenal Glands
    Disorders of the Adrenal Glands Presley Regional Trauma Center Department of Surgery University of Tennessee Health Science Center Memphis, Tennessee Physiology Cortex • Steroid hormones cortisol, aldosterone and androgens are synthesized • Derived from cholesterol • Three histologic zones – glomerulosa (aldosterone), fasiculata and reticularis Cortisol • Secretion is regulated by hypothalamus (CRH) and the pituitary (ACTH) • Exerts effects on intermediary metabolism through variety of cells and tissues • Stimulates hepatic gluconeogenesis and glycogen synthesis Cortisol • Inhibits protein synthesis, increases protein catabolism and fat lipolysis • Inhibits peripheral uptake of glucose in most tissues (liver, brain and RBCs) • Promote collagen loss and impairment of wound healing (inhibit fibroblast activity) Cortisol • Inhibit bone formation • Inhibit numerous anti-inflammatory actions • Critical for cardiovascular stability Androgens • Synthesized primarily in zona reticularis – DHEA • Peripheral conversion to testosterone and dihydrotestosterone • Account for less than 5% of normal male testosterone production Aldosterone • Regulation of ECF volume • Regulation of Na and K balance • Release is stimulated by renin through renin-angiotensin-aldosterone pathway Adrenal Medulla • Derived from neural crest cells • Principal site for catecholamine synthesis • Only site for the enzyme PNMT • Converts NE to EPI Disorders of the Adrenal Cortex Primary Hyperaldosteronism • Conn syndrome • Responsible for HTN in 8 to 12% of pts • Characterized
    [Show full text]
  • Adrenal Crisis: Still a Deadly Event in the 21St Century Troy H.K
    REVIEW Adrenal Crisis: Still a Deadly Event in the 21st Century Troy H.K. Puar, MBBS, MRCP (UK),a,b Nike M.M.L. Stikkelbroeck, MD, PhD,a Lisanne C.C.J. Smans, MD, PhD,c Pierre M.J. Zelissen, MD, PhD,c Ad. R.M.M. Hermus, MD, PhDa aDivision of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; bDepartment of Endocrinology, Changi General Hospital, Singapore; cDepartment of Internal Medicine and Endocrinology, University Medical Center Utrecht, Utrecht, The Netherlands. ABSTRACT Adrenal crisis is a life-threatening medical emergency, associated with a high mortality unless it is appropriately recognized and early treatment is rendered. Despite it being a treatable condition for almost 70 years, failure of adequate preventive measures or delayed treatment has often led to unnecessary deaths. Gastrointestinal illness is the most common precipitant for an adrenal crisis. Although most patients are educated about “sick day rules,” patients, and physicians too, are often reluctant to increase their gluco- corticoid doses or switch to parenteral injections, and thereby fail to avert the rapid deterioration of the patients’ condition. Therefore, more can be done to prevent an adrenal crisis, as well as to ensure that adequate acute medical care is instituted after a crisis has occurred. There is generally a paucity of studies on adrenal crisis. Hence, we will review the current literature, while also focusing on the incidence, pre- sentation, treatment, prevention strategies, and latest recommendations in terms of steroid dosing in stress situations. Ó 2015 Elsevier Inc. All rights reserved. The American Journal of Medicine (2015) -, --- KEYWORDS: Adrenal crisis; Adrenal insufficiency; Crisis; Emergency DEFINITION AND EPIDEMIOLOGY only if metastatic disease is bilateral, with extensive damage 4 In 1855, Thomas Addison first described patients with to the adrenal glands.
    [Show full text]
  • Anemia LECTURE in INTERNAL MEDICINE for IV COURSE
    Essentials of Diagnosis, Treatment and Prevention of Major Endocrine Diseases: Diseases of the Adrenal Glands. Adrenal Insufficiency. Adrenal Hyperfunction. Hormonally Active Tumors. LECTURE IN INTERNAL MEDICINE FOR IV COURSE STUDENTS M. Yabluchansky, L. Bogun, L. Martymianova, O. Bychkova, N. Lysenko, N. Makienko V.N. Karazin National University Medical School’ Internal Medicine Dept. Plan of the Lecture • Definition • Epidemiology • Risk factors • Etiology • Mechanisms • Classification • Clinical presentation • Diagnosis • Treatment • Prognosis • Prophylaxis • Abbreviations • Diagnostic guidelines http://www.thelancet.com/pb/assets/raw/pb/assets/raw/Lancet/clinical/diseases/Cushing's.jpg http://peninsulamassage.com.au/wp-content/uploads/2012/08/Adrenal_Glands_1.jpg Definition Diseases of the Adrenal Glands • Diseases of the Adrenal Glands are conditions that interfere with the normal functioning of the adrenal glands and may cause hyperfunction (Overactive Adrenal Glands) or hypofunction (Underactive Adrenal Glands), and may be congenital or acquired. • There are two parts of the adrenal glands, the cortex, derived from mesenchymal cells, and the medulla, derived from neuroectodermal cells; first one produces mineralocorticoids, glucocorticoids, and androgens; and second one produces epinephrine (adrenaline) and norepinephrine(noradrenaline). https://en.wikipedia.org/wiki/Adrenal_gland_disorder Epidemiology Epidemiologic study of adrenal gland disorders in Japan • The total numbers of patients in Japan in 1997 were estimated as 1,450
    [Show full text]
  • A Case of Waterhouse-Friderichsen Syndrome in a Patient with Streptococcus Pyogenes Bacteremia
    A Case of Waterhouse-Friderichsen Syndrome in a Patient with Streptococcus Pyogenes Bacteremia D. I. BACAL, B. E. CATALDO, P. M. LUCERI, G. VARALLO Rowan University School of Osteopathic Medicine, and Jefferson University Hospital System, NJ INTRODUCTION Waterhouse-Friderichsen Syndrome (WFS) is a rare condition of adrenal insufficiency (AI) due to adrenal hemorrhage after a severe infection. The incidence of WFS has been estimated at 0.14-1.8% based on post-mortem studies.1 It has been associated with a 55-60% mortality rate.2 Meningococcal disease comprises up to 80% of WFS, but additional causative agents continue to be identified.3 This is the case of a 52-year-old female with toxic shock syndrome from Group A Streptococcal (GAS) bacteremia who developed bilateral adrenal hemorrhage & subsequent AI. Septic shock occurred during an initial hospitalization & resolved. Four weeks after discharge she presented with evidence of an adrenal crisis. CT scans demonstrated bilateral adrenal enlargement concerning for adrenal hemorrhage. Primary AI was confirmed via ACTH stimulation testing. A literature search found fewer than ten cases of WFS described due to streptococcal bacteremia. BACKGROUND OF WATERHOUSE-FRIDERICHSEN SYNDROME CONCLUSIONS • Bilateral adrenal hemorrhage has multiple causes: coagulopathies, sepsis from infection, hypotension (i.e. MI), severe volume loss, or surgical WFS is a rare, often fatal, clinical condition that can develop after a intervention 4 severe infection & leads to adrenal hemorrhage. Many factors • Signs include pallor, weakness, fatigue, anorexia, nausea, vomiting, and lethargy 5,6 & labs often depict hyponatremia & hyperkalemia contribute to the pathogenicity of WFS, including coagulopathy, • Increased skin pigmentation develops due to an increase in proopiomelanocortin (POMC), Bacterial ischemia & bacterial toxins.
    [Show full text]
  • Case 1: 54-Year-Old Woman with Adrenal Insufficiency
    ENDORAMA March 22, 2012 54-year-old woman with adrenal insufficiency Celeste Thomas, MD Case 1 Chief Complaint Adrenal crisis in Dec 2011 I didn’t know what was going on When I finally reached my doctor she told me a story of one of her patients who has a crisis every time her grandchildren visit What do you think? History of Present Illness Feeling Horrible – Dermatologist recommended she see an Intolerable myalgias endocrinologist, Diagnosed with diagnosed with fibromyalgia panhypopituitarism 2004 2009 2011 Viral illness: 2007 2010 myalgias, weakness, 2012 fatigue Adrenal Needed Help: Not returned to Crisis fibroandfatigue.com previous state of health since Started natural supplements History Past Medical History Medications Raynaud’s phenomena Synthroid 50 mcg daily diagnosed in 2000 Hydrocortisone 12.5 mg Fibromyalgia in 2007 8AM, 5 mg at noon, 2.5 Hypopituitarism in 2010 mg at 4pm, 2.5 mg at 8pm Allergies Omnitrope (recombinant human growth hormone) Iodinated contrast causes 0.3 mg subcutaneous anaphylaxis daily Hydroxychloroquine Clonazepam 0.5 mg 2- causes a rash 3x/night Nexium Calcium Vitamin D Probiotics History Family History Social History Mother is 80 years old Lives with her husband with history of ER+ and youngest son breast cancer Spends her days in Father is 80 years old pajamas due to fatigue with T2DM and obesity and weakness 1 sibling, brother who Smoked cigarettes for is well two years in college 3 children, all are well Does not drink alcohol or use illicit drugs Review of Systems Constitutional:
    [Show full text]
  • Steroid-Induced Iatrogenic Adrenal Insufficiency in Children
    Review Steroid-Induced Iatrogenic Adrenal Insufficiency in Children: A Literature Review Shogo Akahoshi * and Yukihiro Hasegawa Division of Endocrinology and Metabolism, Tokyo Metropolitan Children’s Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo 183-8561, Japan; [email protected] * Correspondence: [email protected]; Tel.: +81-42-300-5111 Received: 12 October 2020; Accepted: 5 December 2020; Published: 9 December 2020 Abstract: The present review focuses on steroid-induced adrenal insufficiency (SIAI) in children and discusses the latest findings by surveying recent studies. SIAI is a condition involving adrenocorticotropic hormone (ACTH) and cortisol suppression due to high doses or prolonged administration of glucocorticoids. While its chronic symptoms, such as fatigue and loss of appetite, are nonspecific, exposure to physical stressors, such as infection and surgery, increases the risk of adrenal crisis development accompanied by hypoglycemia, hypotension, or shock. The low-dose ACTH stimulation test is generally used for diagnosis, and the early morning serum cortisol level has also been shown to be useful in screening for the condition. Medical management includes gradually reducing the amount of steroid treatment, continuing administration of hydrocortisone corresponding to the physiological range, and increasing the dosage when physical stressors are present. Keywords: adrenal insufficiency; children; endocrinology; glucocorticoids; hypothalamic–pituitary –adrenal axis; therapeutics 1. Mainstem Concepts of Adrenal Insufficiency 1.1. Primary, Secondary, and Tertiary Adrenal Insufficiency Adrenal insufficiency (AI) is defined as the inability of the adrenal cortex to produce sufficient amounts of glucocorticoid hormone. It can also be associated with mineralocorticoid deficiency, depending on the pathophysiology of the disease [1]. Severe AI, or adrenal crisis, can be life-threatening because glucocorticoids and mineralocorticoids play a central role in maintaining energy, salt, and fluid homeostasis [2].
    [Show full text]