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Steroids in the Laboratory and Clinical Practice - 1st Edition - ISBN: 9780128181249

Steroids in the Laboratory and Clinical Practice

1st Edition

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Author: John Honour
Paperback ISBN: 9780128181249
Imprint: Elsevier
Published Date: 1st February 2021
Page Count: 500
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Description

Steroids in the Laboratory and Clinical Practice covers both basic chemistry and therapeutic application of steroids in a single source. The comprehensive reference addresses the specificity of steroid determinations to clarify confusion arising from the laboratory results. The book covers important advancements in the field and is a valuable addition in the literature addressing all existing knowledge gaps. This is a must have reference for pathologists, laboratorians, endocrinologists, analytical/clinical chemists and biochemists.

Key Features

  • Addresses the normal production of steroids and concentrations found in biological fluids and tissues
  • Presents the changes in steroid concentrations at life events as reference points for clinical investigations
  • Reviews the genetic disorders of steroids in relation to specific enzyme changes and clinical presentation

Readership

Researchers, practitioners, endocrinologists, pathologists/laboratorians, analytical chemists, biochemists and chemical pathologists

Table of Contents

Part 1 steroid biochemistry and endocrinology

1.1. Chemistry
Cholesterol
Steroid hormones
Nomenclature

1.2. Synthesis of steroid hormones
Cholesterol availability
Hydroxylation
C-C bond cleavage
3-hydroxysteroid dehydrogenase
Oxidation - ketosteroid reductase
Cytochromes P450
Backdoor path to DHT
retinol dehydrogenase

1.3. Regulation of steroid production.
Control of steroid synthesis - negative/ positive feedback
Cortisol
Aldosterone
Sex steroids

1.4. Steroids in blood and tissues
Binding proteins CBG, SHBG
Physiological changes in binding proteins
Effects of binding proteins on steroid hormone assays
Total steroid measurements
Free steroid measurements
Defects in binding protein production/function

1.5. Mechanism of action
Nuclear receptor superfamily
Membrane receptors
Membrane transporters

1.6. Physiological actions
Carbohydrate metabolism (glucocorticoids) SUGAR
Electrolyte metabolism (mineralocorticoids) SALT
Reproduction (oestrogens and progestogens) SEX
Male hormones (androgens/ anabolic agents) SEX

1.7. Responses of tissues
Muscle
Kidney
Urogenital system
Fat
Skin
Intracrinology

1.8. Breakdown and clearance
Hepatic steroid metabolism - inactivation, conjugation
Cortisol metabolism
Aldosterone metabolism
Sex steroid metabolism
Steroid excretion
Peripheral steroid metabolism: Cortisol to cortisone; T to DHT; DHEA to A4
Aromatase
Inhibitors of steroid metabolism
Microbial metabolism
Effects of changes in the intestinal flora
Effects of thyroid hormones
Effects of vitamin D

1.9.Endocrine disruptors

PART 2 Laboratory investigations
2.1 Steroid determination
Chemical assays
Immunoassays
Chromatographic assays
Physicochemical assays - mass spectrometry
Enzyme assays
Receptor assays
Drug testing in sport

2.2 Tests of endocrine function

2.3 PLASMA STEROIDS
Normal circulating concentrations of total steroids: Age; Sex; Interferences; Free steroids

2.4 URINE STEROIDS
Measurements of metabolites - GC-MS/MS; GC-MS/MS/MS; LC-MS/MS
Urinary steroid profiling: Excretion rates; Metabolite ratios
Interferences

2.5. SALIVA STEROIDS

2.6 TISSUE STEROIDS
Adrenal cortex
Testis
Ovary
Placenta
Liver
Bile
Bone
Brain - neurosteroids
Intestine
Faeces
Skin
Adipose tissue
Heart
Adrenal vein blood
Ovarian vein
Testicular vein

2.7 Provocative tests
CRF
DEX
Insulin
LHRH
ACTH - long, short
Renin/aldo -
Petrosal sinus sampling +/- CRF
Production rates

Part 3. Clinical investigations
3.1 Life events
Mini Puberty
Adrenarche
Puberty
Delayed puberty
Precocious puberty
Pregnancy
Adrenopause
Menopause
Pregnancy
intrahepatic cholestasis
obesity
low oestrogen
tumours
virilisatio
Infertility
Medical problems
Preliminary investigations of partners
Causes, incidence and treatment of female infertility
PCO
CAH
Hypothalamic-pituitary failure
Hyperprolactinaemia
Endometriosis
Anorexia
Bulimia
Ovarian failure
Unexplained infertility
IVF
Male infertility

3.2 Steroid disorders
3.2.1 defects of cortisol synthesis
3.2.1. 1. Adrenal insufficiency -
Congenital adrenal hyperplasia
CYP21
CYP11B1
CYP11B2
CYP17
HS3B2
Molecular biology of steroid disorders
Mutations causing defects of CYP21 etc
Phenotype and genotype
Prenatal diagnosis
Adrenal hypoplasia and adrenoleucodystrophy
Addisons disease
3.2.2 Excess cortisol production
Cushings syndrome
Cushings disease
3.2.3 Defects of aldosterone synthesis - Salt losing conditions, hypertension
Mineralocorticoid excess
Apparent mineralocorticoid excess
Primary aldosteronism
Dex suppressible hyperaldosteronism
Bartters syndrome
Gitelmans
True and apparent
Hypoaldosteronism
Pseuddohypoaldosteronism
3.2.4 Defects of testosterone synthesis - ambiguous genitalia, precocious puberty, hypogonadism
Androgen excess
Newborn girls ambiguous genitalia
Precocious puberty
Premature adrenarche
Acne, hirsutism, menstrual disturbance
Androgen deficiency
Newborn infants
Delayed puberty
3.2.5. Defects of oestrogen production - sulphatase, aromatase, gynaecomastia
3.2.6. Defects of cholesterol - SLO, hypercholesterolaemia

3.3. Disorders of hormone action
Androgen resistance
Pseudohypoaldosteronism
GCH resistance
Tubulopathies

3.4. Clinical scenarios
Hyponatraemia
Hypertension
PMS premenstrual syndrome, dysphoria
OBESITY
Metabolic syndrome
BARKER hypothesis
CRITICAL ILLNESS
SEPTIC SHOCK
DIABETES
MENTAL ILLNESS
Depression
CANCER
Prostate
Breast
IMMUNE SYSTEM/INFLAMMATION
STEROID PRODUCING TUMOURS
Adrenal, ovary, testis
Pituitary tumours
AIDS

Part 4. Pharmacological use of steroids
Anti-inflammatory steroids - use in asthma , RA
Contraceptives
Growth promoters
Hormone replacement therapy - oestrogens, testosterone
Treatment of hormone dependent cancers
Glucocorticoids - pred etc
Mineralocorticoids - 9-alphaF, DOC
MCH antagonists
Androgens - anaemia, impotence
Anaesthetics
Steroid enzyme inhibitors - metyrapone, Aldosterone synthase inhibitors, aromatase, ketoconazole
Receptor modulators -
SERMS
SARMS
SPRMS
Prostate cancer
Breast cancer
Abuse of steroids
Androgens
Corticosteroids
Drug testing 

Details

No. of pages:
500
Language:
English
Copyright:
© Elsevier 2021
Published:
1st February 2021
Imprint:
Elsevier
Paperback ISBN:
9780128181249

About the Author

John Honour

Dr. Honour has 45 years of experience in analyzing steroids mainly by gas chromatography and mass spectrometry and applying these results to the investigation of patients with endocrine disorders. His work has included the diagnosis of inherited disorders of blood pressure, sex determination, infertility, osteoporosis, and salt balance in the body. He has long had an interest in the ability of bacteria to change steroids in the body and has used bacteria in test-tubes to achieve some changes in steroid structure which could not be easily achieved with chemicals. Several research projects have examined the safety of inhaled steroids with respect to effects on the hypothalamic-pituitary-adrenal axis. Dr. Honour is an Honorary Senior Research Associate at the Institute for Women's Health at University College London and formerly a Consultant Clinical Scientist in Clinical Biochemistry at UCLH and Head of the specialist service for Steroid Endocrinology. The steroid laboratory maintains strong links with the clinical endocrinologists at UCL and the Hospital for Children at Great Ormond Street. Research in the unit covered the validation and use of mass spectrometry in steroid analysis for disorders of sex determination, adrenal diseases, polycystic ovary syndrome, safety of corticosteroids in treatment of asthma, links between birthweight and cardiovascular risk, and the enterohepatic circulation of steroids. Dr. Honour has more than 170 refereed publications and 19 book chapters covering a range of analytical, genetic and clinical aspects of steroids. He presented 175 papers at scientific conferences. He was scientific adviser to UKNEQAS for immunoassays, steroid accuracy and pediatric investigations. He served on two working parties for the European Society for Pediatric Endocrinology with the Lawson Wilkins Pediatric Society that produced guidelines on congenital adrenal hyperplasia and newborn screening. An EQA scheme for urinary steroids was operated from UCL globally with the collaboration of the Dutch Foundation for Quality in Clinical Chemistry (SKML). Dr Honour has maintained an interest in the detection of abuse of anabolic steroids in sport and has acted as an expert witness in cases of drug abuse in sport. He is an Associate Editor of the Annals of Clinical Biochemistry.

Affiliations and Expertise

Senior Research Associate, Institute for Women’s Health, University College London, UK

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