A condition that occurs from exposure to high cortisol levels for a long time.
Fewer than 1 million cases per year (India)
Treatable by a medical professional
Requires a medical diagnosis
Lab tests or imaging always required
Chronic: can last for years or be lifelong
The most common cause is the use of steroid drugs, but it can also occur from overproduction of cortisol by the adrenal glands.
Signs are a fatty hump between the shoulders, a rounded face and pink or purple stretch marks.
Treatment options include reducing steroid use, surgery, radiation and medication.
Congenital Adr Hyperplasia (CAH) can appear at any age from birth to puberty where it can lead to ambiguous genitalia. It is due to absolute or relative deficiency of 17 Hydroxylase or 21 Hydroxylase enzyme.
The adrenal cortex produces three major classes of steroids:
glucocorticoids,
(2) mineralocorticoids, and
(3) adrenal androgens.
Consequently, normal adrenal function is important for
-modulating intermediary metabolism and immune responses through glucocorticoids;
blood pressure, vascular volume, and electrolytes through mineralocorticoids;
secondary sexual characteristics (in females) through androgens.
The adrenal axis plays an important role in the stress response by rapidly increasing cortisol levels.
Adrenal disorders include hyperfunction (Cushing's syndrome) and hypofunction (adrenal insufficiency) as well as a variety of genetic abnormalities of steroidogenesis.
HORMONES OF ADRENAL CORTEX Adrenocortical hormones are steroids in nature. Classification
Based on their functions, corticosteroids are classified into three groups:
Ø1. Glucocorticoids
Ø2. Mineralocorticoids
Ø3. Sex hormones.
Congenital Adr Hyperplasia (CAH) can appear at any age from birth to puberty where it can lead to ambiguous genitalia. It is due to absolute or relative deficiency of 17 Hydroxylase or 21 Hydroxylase enzyme.
The adrenal cortex produces three major classes of steroids:
glucocorticoids,
(2) mineralocorticoids, and
(3) adrenal androgens.
Consequently, normal adrenal function is important for
-modulating intermediary metabolism and immune responses through glucocorticoids;
blood pressure, vascular volume, and electrolytes through mineralocorticoids;
secondary sexual characteristics (in females) through androgens.
The adrenal axis plays an important role in the stress response by rapidly increasing cortisol levels.
Adrenal disorders include hyperfunction (Cushing's syndrome) and hypofunction (adrenal insufficiency) as well as a variety of genetic abnormalities of steroidogenesis.
HORMONES OF ADRENAL CORTEX Adrenocortical hormones are steroids in nature. Classification
Based on their functions, corticosteroids are classified into three groups:
Ø1. Glucocorticoids
Ø2. Mineralocorticoids
Ø3. Sex hormones.
a clinical syndrome that results from inadequate tissue perfusion.
Hypovolemic shock - Blood or fluid loss, both leading to a decreased circulating blood volume, diastolic filling pressure, and volume.
Cardiogenic shock - due to cardiac pump failure related to loss of myocardial contractility/functional myocardium or structural/mechanical failure of the cardiac anatomy and characterized by elevations of diastolic filling pressures and volumes
Extra-cardiac/obstructive shock - due to obstruction to flow in the cardiovascular circuit and characterized by either impairment of diastolic filling or excessive afterload
Distributive shock - caused by loss of vasomotor control resulting in arteriolar/venular dilatation leading to a decrease in preload, with decreased, normal, or elevated cardiac output, depending on the presence of myocardial depression.
The primary treatment goals for patients with hepatitis B (HBV) infection are to prevent progression of the disease, particularly to cirrhosis, liver failure, and hepatocellular carcinoma (HCC).
Risk factors for progression of chronic HBV include the following :
Persistently elevated levels of HBV DNA and, in some patients, alanine aminotransferase (ALT), as well as the presence of core and precore mutations seen most commonly in HBV genotype C and D infections
Male sex
Older age
Family history of HCC
Alcohol use
Elevated alpha-fetoprotein (AFP)
Coinfection with hepatitis D (delta) virus (HDV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
A synergistic approach of suppressing viral load and boosting the patient’s immune response with immunotherapeutic interventions is needed for the best prognosis. The prevention of HCC often includes the use of antiviral treatment using pegylated interferon (PEG-IFN) or nucleos(t)ide analogues.
HBV infection can be self-limited or chronic. No specific therapy is available for persons with acute hepatitis B; treatment is supportive.
Patients with acute hepatitis C virus (HCV) infection appear to have an excellent chance of responding to 6 months of standard therapy with interferon (IFN). Because spontaneous resolution is common, no definitive timing of therapy initiation can be recommended; however, waiting 2-4 months after the onset of illness seems reasonable.
Treatment for chronic HCV is based on guidelines from the Infectious Diseases Society of America (IDSA) and the American Associations for the Study of Liver Diseases (AASLD), in collaboration with the International Antiviral Society-USA (IAS-USA). These guidelines are constantly being updated. For more information, see HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C.
The guidelines propose that because all patients cannot receive treatment immediately upon the approval of new agents, priority should be given to those with the most urgent need.
The recommendations include the following :
Patients with advanced fibrosis, those with compensated cirrhosis, liver transplant recipients, and those with severe extraheptic hepatitis are to be given the highest priority for treatment
Based on available resources, patients at high risk for liver-related complications and severe extrahepatic hepatitis C complications should be given high priority for treatment
Treatment decisions should balance the anticipated reduction in transmission versus the likelihood of reinfection in patients whose risk of HCV transmission is high and in whom HCV treatment may result in a reduction in transmission (eg, men who have high-risk sex with men, active injection drug users, incarcerated persons, and those on hemodialysis)
Interstitial Lung Diseases [ILD] Approach to ManagementArun Vasireddy
Diffuse (interstitial) lung disease includes a wide variety of relatively uncommon conditions presenting with characteristic clusters of clinical features and marked by an immune response. There are over 200 specific diffuse lung diseases, many of unknown etiology. The combined incidence is 50 per 100,000, or 1 in 2000 people. Because these conditions cause aberrant lung function, morbidity and mortality due to lung injury and fibrosis are not uncommon. Both environmental and genetic factors are believed to contribute to the development of diffuse lung disease. Antigen processing and presentation are important in the development of the immune response seen in the disease, and it is thought that the likely candidate genes predisposing patients to this category of disease are those of the major histocompatibility complex. Genes that affect the immune, inflammatory, and fibrotic processes may also influence who develops the disease. If we can identify the genes that cause diseases characterized by lung injury and fibrosis, we can eventually develop genetic interventional approaches to treatment.
Amniotic Fluid Embolism [AFE] Approach to ManagementArun Vasireddy
Amniotic fluid embolism (AFE) is a life threatening obstetric emergency characterized by sudden cardiorespiratory collapse and disseminated intravascular coagulation.
Steiner and Luschbaugh first described AFE in 1941, after they found fetal debris in the pulmonary circulation of women who died during labor. Data from the National Amniotic Fluid Embolus Registry (USA) suggest that the process is more similar to anaphylaxis than to embolism, and the term anaphylactoid syndrome of pregnancy has been suggested because fetal tissue or amniotic fluid components are not universally found in women who present with signs and symptoms attributable to AFE.
The diagnosis of AFE has traditionally been made at autopsy when fetal squamous cells are found in the maternal pulmonary circulation; however, fetal squamous cells are commonly found in the circulation of laboring patients who do not develop the syndrome. The diagnosis is essentially one of exclusion based on clinical presentation. Other causes of hemodynamic instability should not be neglected.
Approach to Management of Upper Gastrointestinal (GI) BleedingArun Vasireddy
Upper gastrointestinal bleeding is gastrointestinal bleeding in the upper gastrointestinal tract, commonly defined as bleeding arising from the esophagus, stomach, or duodenum. Blood may be observed in vomit (hematemesis) or in altered form in the stool (melena). Depending on the severity of the blood loss, there may be symptoms of insufficient circulating blood volume and shock. As a result, upper gastrointestinal bleeding is considered a medical emergency and typically requires hospital care for urgent diagnosis and treatment. Upper gastrointestinal bleeding can be caused by peptic ulcers, gastric erosions, esophageal varices, and some rarer causes such as gastric cancer.
The initial assessment includes measurement of the blood pressure and heart rate, as well as blood tests to determine hemoglobin concentration. In significant bleeding, fluid replacement is often required, as well as blood transfusion, before the source of bleeding can be determined by endoscopy of the upper digestive tract with an esophagogastroduodenoscopy. Depending on the source, endoscopic therapy can be applied to reduce rebleeding risk. Specific medical treatments (such as proton pump inhibitors for peptic ulcer disease) or procedures (such as TIPS for variceal hemorrhage) may be used. Recurrent or refractory bleeding may lead to need for surgery, although this has become uncommon as a result of improved endoscopic and medical treatment.
Tachy Arrhythmias - Approach to ManagementArun Vasireddy
Tachyarrhythmias are disorders of heart rhythm which may present with a tachycardia i.e. a heart rate >100 bpm.
This article provides an overview of tachyarrhythmias in general and goes on to cover the most common tachyarrhythmias in more detail. The acute management of tachyarrhythmias, in an emergency setting, will be covered in the 'Acute' section of the fastbleep website.
Tachyarrhythmias are clinically important as they can precipitate cardiac arrest, cardiac failure, thromboembolic disease and syncopal events. As such, they crop up time and time again in exam papers and on the wards.
Tachyarrhythmias are classified based on whether they have broad or narrow QRS complexes on the ECG. Broad is defined as >0.12s (or more than 3 small squares on the standard ECG). Narrow is equal to or less than 0.12s. Broad QRS complexes are slower ventricular depolarisations that arise from the ventricles. Narrow complexes are ventricular depolarisations initiated from above the ventricles (known as supraventricular). One important exception is when there is a supraventricular depolarisation conducted through a diseased AV node. This will produce wide QRS complexes despite the rhythm being supraventricular in origin.
Scrub typhus is a mite-borne disease caused by Orientia tsutsugamushi (formerly Rickettsia tsutsugamushi). Symptoms are fever, a primary lesion, a macular rash, and lymphadenopathy. (See also Overview of Rickettsial and Related Infections.) Scrub typhus is related to rickettsial diseases.
Pulmonary edema is often caused by congestive heart failure. When the heart is not able to pump efficiently, blood can back up into the veins that take blood through the lungs. As the pressure in these blood vessels increases, fluid is pushed into the air spaces (alveoli) in the lungs.
The jugular venous pressure (JVP, sometimes referred to as jugular venous pulse) is the indirectly observed pressure over the venous system via visualization of the internal jugular vein. It can be useful in the differentiation of different forms of heart and lung disease.
A treadmill exercise stress test is used to determine the effects of exercise on the heart. Exercise allows doctors to detect abnormal heart rhythms (arrhythmias) and diagnose the presence or absence of coronary artery disease.
This test involves walking in place on a treadmill while monitoring the electrical activity of your heart. Throughout the test, the speed and incline of the treadmill increase. The results show how well your heart responds to the stress of different levels of exercise.
Description
A technologist will explain the test to you, take a brief medical history, and answer any questions you may have. Your blood pressure, heart rate, and electrocardiogram (ECG) will be monitored before, during, and after the test.
You will be asked to sign a consent form. This form is required before the test can proceed.
You will be asked to remove all upper body clothing, and to put on a gown with the opening to the front.
Adhesive electrodes will be put onto your chest to capture an ECG. The sites where the electrodes are placed will be cleaned with alcohol and shaved if necessary. A mild abrasion may also be used to ensure a good quality ECG recording.
Your resting blood pressure, heart rate, and ECG will be recorded.
You will be asked to walk on a treadmill. The walk starts off slowly, then the speed and incline increases at set times. It is very important that you walk as long as possible because the test is effort-dependent.
You will be monitored throughout the test. If a problem occurs, the technologist will stop the test right away. It is very important for you to tell the technologist if you experience any symptoms, such as chest pain, dizziness, unusual shortness of breath, or extreme fatigue.
Following the test, you will be asked to lie down. Your blood pressure, heart rate, and ECG will be monitored for three to five minutes after exercise.
The data will be reviewed by a cardiologist after the test is completed. A report will be sent to the doctor(s) involved in your care.
A mosquito-borne viral disease occurring in tropical and subtropical areas.
Spreads by animals or insects
Requires a medical diagnosis
Lab tests or imaging often required
Short-term: resolves within days to weeks
Those who become infected with the virus a second time are at a significantly greater risk of developing severe disease.
Symptoms include high fever, headache, rash and muscle and joint pain. In severe cases there is serious bleeding and shock, which can be life threatening.
Treatment includes fluids and pain relievers. Severe cases require hospital care.
Osteoporosis is a progressive systemic skeletal disease characterized by low bone mass and microarchitecture deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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3. History of Events
1563 Eustachius describes the adrenals (published by Lancisi in 1714).
1855 Thomas Addison describes the clinical features and autopsy findings in 11 cases of diseases of the
suprarenal capsules, at least 6 of which were tuberculous in origin.
1856 In adrenalectomy experiments, Brown-Séquard demonstrates that the adrenal glands are essential for
life.
1896 William Osler demonstrated clinical benefits in patients with Addison’s disease.
1929 Liquid extracts of cortical tissue are used to keep adrenalectomized cats alive indefinitely (Swingle and
Pfiffner); subsequently, this extract was used successfully to treat a patient with Addison’s disease
1932 Harvey Cushing associates the “polyglandular syndrome” of pituitary basophilism, which he first
described in 1912, with hyperactivity of the pituitary-adrenal glands.
1950 Hench, Kendall, and Reichstein share Nobel Prize in Medicine for describing the anti-inflammatory
effects of cortisone in patients with rheumatoid arthritis.
1980-present The “molecular era”: cloning and functional characterization of steroid receptors, steroidogenic
enzymes, and adrenal transcription factors are reported, and the molecular basis for human adrenal diseases
is defined.
5. Anatomy
There are 2 adrenal glands each weighing about 4
gms
They lie at the superior poles of the two kidneys
Each gland is composed of two distinct parts
adrenal cortex and adrenal medulla
Blood supplied by superior ,inferior and middle
adrenal arteries
6.
7. Adrenal cortex
Three distinct layers-
Zona glomerulosa- thin layer under the capsule 15% of
the cortex. The cells here capable of secreting significant
amount of aldosterone
Zona fasiculata- middle widest layer 75%of cortex
secreting glucocorticoids, cortisol and corticosterone as
well as small amount of adrenal androgens and estrogen
Zona reticularis- deep layer secretes adrenal androgens
dehydroepiandrosterone(DHEA) and androstenedione as
well as small amount of estrogen and glucocorticoid
8. Adrenal medulla
It occupies the central 20 % of the adrenal gland
It secretes the hormones epinephrine and nor
epinephrine in response to sympathetic stimulation
they are referred to as catecholamines
9. Biosynthesis of adrenal steroids
Important steroid products of adrenal cortex are aldosterone , cortisol and
androgens
All the steps of synthesis occurs in mitochondria and endoplasmic
reticulum
Approx 90-95% of cortisol in plasma binds to plasma protein globulin
called transcortin and to albumin
Binding serves as a reservoir to lessen rapid fluctuations in free hormone
concentration
Adrenal steroids are degraded mainly by liver and conjugated to
glucoronic acid or sulphates
25% of these conjugates are excreted in the bile and then in feces and
remaining in urine
10.
11. The adrenal cortex produces three major classes of steroids:
• Glucocorticoids,
• mineralocorticoids, and
• adrenal androgens.
Consequently, normal adrenal function is important for
-modulating intermediary metabolism and immune responses through
glucocorticoids;
- blood pressure, vascular volume, and electrolytes through
mineralocorticoids;
- secondary sexual characteristics (in females) through androgens.
- The adrenal axis plays an important role in the stress response by rapidly
increasing cortisol levels.
- Adrenal disorders include hyperfunction (Cushing's syndrome) and
hypofunction (adrenal insufficiency) as well as a variety of genetic
abnormalities of steroidogenesis.
12. Glucocorticoids
95% of glucocorticoid activity occurs from secretion
of cortisol known as hydrocortisone
Cortisol has effects on
Carbohydrate metabolism
Protein metabolism
Fat metabolism
Antiinfammatory effects
13.
14. Regulation of cortisol secretion
• Hypothalamic-pituitary-adrenal axis.
• Adrenocorticotropic hormone (ACTh) is
secreted from the anterior pituitary
under the influence of two principal
secretagogues, corticotropin-releasing
hormone (Crh) and arginine vasopressin;
other factors, including cytokines, also
play a role.
• Crh secretion is regulated by an inbuilt
circadian rhythm and by additional
stressors operating through the
hypothalamus.
• Secretion of Crh and ACTh is inhibited by
cortisol, highlighting the importance of
negative feedback control.
15.
16. Principal pathways of cortisol metabolism
• The Interconversion of hormonally
active cortisol to inactive cortisone is
catalyzed by two isozymes of 11β-
hydroxysteroid dehydrogenase (11β-
hSd), with hSd11B1 principally
converting cortisone to cortisol and
hSd11B2 doing the reverse.
• Cortisol can be hydroxylated at the C6
and C20 positions.
• A ring reduction is undertaken by 5α-
reductase or 5β-reductase and 3α-
hSd.
17. Regulation of cortisol secretion
ACTH stimulates cortisol secretion
Secretion of cortisol is controlled
entirely by ACTH
ACTH activates by increase in
cAMP
ACTH acts on adrenaocortical
cells to activate adeny cyclase
Long term activation can cause
hypertrophy
Inhibitory effect of cortisol
Cortisol sends negative feedback
to hypothalamus and pituitary to
regulate cortisol levels
18. B. General effects:
1.On C.V.S.
a) Cortisol increases blood pressure
because of increased production of
angiotensionogen.
b) Increased sensibility of vascular smooth
muscle to nor-adrenaline and
adrenaline.
19. 2. On blood cells:
a) Increases the platelet count.
b) Decreases blood clotting time.
c) Increases total WBCs.
d) Decreases lymphocytes, eosinophils and basophils.
e) Increases neutrophils, monocytes and RBC count.
20. 3. On C.N.S. :
a) Low cortisol levels cause restlessness, insomnia, and inability
to concentrate.
b) Causes excitation of the CNS.
4. On GIT:
a) Increases gastric acidity and may cause a peptic ulcer.
21. 5. On bone:
a) Excess cortisol may cause a defect in the
synthesis of protein matrix.
b) It decreases the deposition of calcium.
c) It increases the loss of calcium in urine.
d) It decreases absorption of calcium from the
GIT.
22. 6. On infection, inflammation, and trauma:
a) Large doses of cortisol decrease the formation of antibodies
due to its destructive effect on lymphoid tissues.
b) It decreases tissue response to bacteria.
c) It is anti- inflammatory.
d) It is anti- allergic.
e) It delays wound healing.
23. Effect of cortisol in preventing
inflammation
Cortisol stabilizes the lysosomal membrane
Cortisol decreases the permeability of the capillaries
preventing loss of plasma into tissues
Cortisol decreases migration of WBCs into inflamed area
and phagocytosis of damaged cells
Cortisol suppresses the immune system causing
lymphocyte reproduction to decrease
Cortisol attenuates fever as it reduces the release of
interleukin-1
27. A constellation of clinical abnormalities due to
chronic exposure to inappropriately elevated levels
of free plasma glucocorticoids.
described by Harvey Cushing in 1932
Cushing’s Syndrome
28.
29. COMMON CAUSES OF ECTOPIC ACTH SECRETION
Small cell carcinoma of the lung 50%
Endocrine tumors of foregut origin 35%
Thymic carcinoid
Islet cell tumor
Medullary carcinoma thyroid
Bronchial carcinoid
Pheochromocytoma 5%
Ovarian tumors 2%
30. Hyperadrenalism- Cushing’s syndrome
Hypercorticolism can occur due to-
Adenomas of the anterior pitutary secreting increased ACTH
Abnormal function of hypothalamus causing increased CRH
and thereby increased ACTH
Ectopic secretion of ACTH by a tumor somewhere else in the
body
Adenomas of the adrenal cortex
When cushing’s syndrome is secondary to excess secretion of
ACTH by the anterior pituitary this is called Cushing’s disease
35. Ectopic ACTH Syndrome
In 15% of cases, Cushing’s syndrome is associated with nonpituitary
tumors secreting ACTH—the ectopic ACTH syndrome
Circulating ACTH concentrations and cortisol secretion rates can be
extremely high.
As a result, duration of symptoms from onset to presentation is short
(<3 months); patients are commonly pigmented, and the metabolic
manifestations of glucocorticoid excess are often rapid and
progressive.
Weight loss, myopathy, and glucose intolerance are prominent
symptoms and signs.
The association of these features with hypokalemic alkalosis and
peripheral edema should alert the clinician to the diagnosis.
36. Ectopic Corticotropin-Releasing
Hormone Syndrome
Ectopic production of CRH is a very rare cause of pituitary-
dependent Cushing’s.
Pituitary histology has revealed corticotroph hyperplasia but
not adenoma formation.
Biochemically, these patients, like those with ectopic ACTH
syndrome, lose the normal negative glucocorticoid feedback
mechanism—50% have resistance to high-dose dexamethasone
therapy.
Ectopic CRH production may explain the suppression of cortisol
secretion after high- dose dexamethasone that is observed in
some patients with the “ectopic” ACTH syndrome.
37. Macronodular Adrenal Hyperplasia
In 10% to 40% of patients with Cushing’s disease, there is bilateral
adrenocortical hyperplasia associated with one or more nodules,
which may be up to several centimeters in diameter.
Pathologically, the nodules are lobulated and can be markedly
enlarged, but internodular hyperplasia is invariably found.
Macronodular adrenal hyperplasia (MAH) is thought to result from
long-standing adrenal ACTH stimulation, which leads to autonomous
adrenal adenoma formation.
Therefore, as the adrenals in a patient with Cushing’s disease become
more hyperplastic, they secrete more cortisol for a given ACTH level,
which ultimately can lead to autosuppression.
The adenomas can be a trap for the unwary because they may be
mistaken for primary adrenal tumors.
38. Cortisol-Secreting Adrenal Adenoma
and Carcinoma
Excluding iatrogenic cases, adrenal adenomas are responsible for about 10%
to 15% of Cushing’s syndrome cases, and carcinomas for less than 5%.
Onset of clinical features is gradual in patients with adenomas, but it is often
rapid in adrenal carcinoma. In addition to the features of hypercortisolism,
patients may complain of loin or abdominal pain, and a tumor may be
palpable.
The tumor may secrete other steroids, such as androgens or mineralo-
corticoids.
Therefore, in females, there may be features of virilization, with hirsutism,
clitoromegaly, breast atrophy, deepening of the voice, temporal recession,
and severe acne.
Subclinical Cushing’s syndrome has been reported in up to 10% of patients
with adrenal “incidentalomas”
39. Primary Pigmented Nodular Adrenal
Hyperplasia and Carney’s Syndrome
About 100 cases of ACTH-independent Cushing’s syndrome
have been reported in association with bilateral, small,
pigmented adrenal nodules.
Pathologically, these nodules are usually 2 to 4 mm in diameter
(although they can be larger) and black or brown on cut section.
Adjacent adrenal tissue is atrophic, distinguishing this primary
pig- mented nodular adrenal hyperplasia (PPNAD) from MAH.
Presentation is with typical features of Cushing’s syndrome in
persons younger than 30 years of age .
Bilateral adrenalectomy is curative.
40. Carney’s complex
A familial autosomal dominant variant.
Mutations of the gene encoding the protein kinase
A (PKA) regulatory subunit type IA (PRKAR1A)
comprises mesenchymal tumors (especially atrial
myxomas), spotty skin pigmentation, peripheral
nerve tumors, and various other tumors including
breast lesions, testicular tumors, and GH-secreting
pituitary tumors.
41. McCune-Albright Syndrome
Here, fibrous dysplasia and cutaneous pigmentation may be
associated with pituitary, thyroid, adrenal, and gonadal
hyperfunction.
The most common manifestation is with sexual precocity and GH
excess, but Cushing’s syndrome has been reported.
The underlying abnormality is a somatic mutation in the α-subunit of
the stimulatory G protein, which is linked to adenyl cyclase.
The mutation results in constitutive activation of the G protein,
mimicking constant ACTH stimulation at the level of the adrenal.
ACTH levels are suppressed, and adrenal adenomas may occur.
42. Iatrogenic Cushing’s Syndrome
Development of the features of Cushing’s syndrome depends on the dose,
duration, and potency of the corti- costeroids used in clinical practice.
ACTH is rarely prescribed, but it will also result in cushingoid features if
administered long-term.
Some features, such as an increase in intraocular pressure, cataracts, benign
intracranial hypertension, aseptic necrosis of the femoral head,
osteoporosis, and pancreatitis, are more common in iatrogenic than
endogenous Cushing’s syndrome,
other features, notably hypertension, hirsutism, and oligomenorrhea/
amenorrhea, are less prevalent.
43. Cyclic Cushing’s Syndrome
Characterized by periods of excess cortisol production interspersed with
intervals of normal cortisol production
Some of these patients demonstrate a paradoxical rise in plasma ACTH and
cortisol when treated with dexamethasone, and occasionally a patient is
benefited by dopamine agonist (bromocriptine) or serotonin antagonist
(cyproheptadine) therapy.
Most patients have been thought to have pituitary- dependent disease, and
in many of these patients, basophil adenomas have been removed, with
long-term cure in some cases.
However, cortisol secretion may show some evidence of cyclicity in patients
with an ectopic source of ACTH.
44. Pseudo-Cushing’s Syndromes
defined as the presence of some or all of the clinical features
of Cushing’s syndrome together with some evidence for
hypercortisolism.
Resolution of the underlying cause results in disappearance of
the cushingoid state.
Causes: Alcoholism, Depression & Obesity.
45. Clinical manifestations
Cortisol levels in blood are normally elevated at 8 A.M. and
decrease to less than 50% by midnight except in infants and
young children in whom a diurnal rhythm is not always
established.
In patients with Cushing syndrome this circadian rhythm is lost,
and cortisol levels at midnight and 8 A.M. are usually
comparable.
Urinary excretion of free cortisol is increased. This is best
measured in a 24-hr urine sample and is expressed as a ratio of
micrograms of cortisol excreted per gram of creatinine.
Diagnosis
46.
47.
48. Dexamethasone is an exogenous steroid that provides negative
feedback to the pituitary to suppress the secretion of ACTH.
This steroid is unable to pass the blood brain barrier which allows this
test to assess a specific part of the hypothalamic-pituitary-adrenal axis.
Specifically, dexamethasone binds to glucocorticoid receptors in the
pituitary gland, which lies outside the blood brain barrier, resulting in
regulatory modulation
A single-dose dexamethasone suppression test is often helpful; a dose
of 25–30 μg/kg (maximum of 2 mg) given at 11 P.M. results in a plasma
cortisol level of less than 5 μg/dL at 8 A.M. the next morning in normal
individuals but not in patients with Cushing syndrome.
A low dose dexamethasone suppresses cortisol in individuals with no
pathology in endogenous cortisol production. A high dose
dexamethasone exerts negative feedback on pituitary ACTH producing
cells but not on ectopic ACTH producing cells or adrenal adenoma.
Dexamethasone suppression test
49. Low-dose DX suppression test
A normal result is decrease in cortisol levels upon
administration of low-dose dexamethasone.
Cushing's disease involve no change in cortisol on low-dose
dexamethasone, but inhibition of cortisol on high-dose
dexamethasone
50. Large dose DX suppression test
D.X 2mg q6h P.O 2 days
Urinary free cortisol reduced 50%: Cushing’s disease (Pituitary
adenoma)
Urinary free cortisol NOT reduced 50%:Adrenal tumor, carcinoma,
ectopic ACTH Syndrome
51. ACTH 25u intravenously 8h
2-5 fold increase in urinary free cortisol in Cushing’
s disease
Plasma cortisol and urinary free cortisol increase in
half of adrenal adenoma patients
No response in adrenal carcinoma
ACTH Stimulation test
52.
53. Etiology diagnose (especially for pituitary ACTH-dependent
or ectopic ACTH syndrome)
A newer approach is to combine a CRH stimulation test with
a dexamethasone suppression test(4mg ).
Method :
1 µg / kg of CRH is administered intravenously.
ACTH and cortisol levels are measured before CRH injection
and 15, 30, 45, 60, 90 and 120 minutes after injection.
A rise in the cortisol value of 20 percent or more above
basal level or a rise in the ACTH value of at least 50 percent
above basal level is considered evidence for an ACTH-
dependent lesion
CRH stimulation test
54. Etiology diagnose (especially for pituitary or adrenal)
Metyrapone (30mg/kg) P.O at midnight
Urinary 17-OHCS, Plasma ACTH,11-deoxycortisol more above
basal level : Cushing’s disease (Pituitary adenoma)
No response in adrenal carcinoma , tumor, ectopic ACTH
Syndrome
Metyrapone Test
55. Pituitary CT has a sensitivity of about 50% for identifying
microadenomas
MRI has increased sensitivity but is not 100% predictive
If diagnostic doubt need bilateral inferior petrosal sinus
sampling for ACTH
Adrenal ultrasonography---first choice
Abdominal CT will allow identification of adrenal pathology
Somatostatin scintigraphy to identify sites of ectopic hormone
production
Imaging diagnosis
56.
57.
58.
59. Cushing’ s disease:
Adrenal adenoma:
Adrenal carcinoma:
Ectopic ACTH Syndrome:
Chronic, moderate clinical features can be
suppressed by large dose test
Shorter course , mild features can NOT be
suppressed by large dose test
Acute onset, progressive course,
hyperandrogenic effect predominate,
palpable mass, low ACTH
Appear suddenly, progress rapidly, not typical
manifestation of Cushing’s syndrome,
hyperpigmentation, hypokalemia, high ACTH
Etiological diagnosis
60. Cushing’s disease
Transsphenoidal microadenomectomy
Pituitary radiation
Bilateral total adrenolectomy
Drugs
Adrenal adenoma and carcinoma
Surgical removal
Drugs ( mitotane, metyrapone, ketoconazole ) for nonresectable or
metastatic carcinoma
Ectopic ACTH Syndrome
Surgical removal of the ectopic tumor
Chemotherapy, radiotherapy
Drugs ( mitotane, metyrapone, ketoconazloe )
Treatment
61. Purpose
Correct metabolic abnormalities before
attempted surgical cure
Palliate surgically noncurable disease
Achieve remission in patients for whom
surgery is unlikely to achieve satisfactory
long term results
Medical therapy of Cushing’ s Disease
63. Glucocorticoid Resistance
A small number of patients have been described as having increased
cortisol secretion but without the stigmata of Cushing’s syndrome.
These patients are resistant to suppression of cortisol with low-dose
dexamethasone but respond to high doses.
ACTH levels are elevated and lead to increased adrenal production of
androgens and DOC. Therefore, these patients may present with the
features of androgen or mineralocorticoid excess, or both.
Treatment with a dose of dexamethasone (usually >3 mg/day)
adequate to suppress ACTH results in a fall in adrenal androgens and
often returns plasma potassium and blood pressure to normal levels.
Many of these patients have been found to have point mutations in
the steroid-binding domain of the GR, with consequent reduction of
glucocorticoid-binding affinity, but this is not invariable.
64. Prognosis of Cushing’s Syndrome
Studies carried out before the introduction of effective therapy
revealed that 50% of patients with untreated Cushing’s
syndrome died within 5 years, principally from vascular disease.
Even with modern management, an increased prevalence of
cardiovascular risk factors persists for many years after an
apparent “cure.”
Paradoxically, on correction of the hypercortisolism, patients
often feel worse.
Skin desquamation, steroid-withdrawal arthropathy, profound
lethargy, and mood changes may occur and can take several
weeks or months to resolve
65. o Features of Cushing’s syndrome disappear over a period of 2 to
12 months after treatment.
o Hypertension and diabetes mellitus improve, but, as with other
secondary causes, they may not resolve completely.
o The osteopenia of Cushing’s syndrome improves rapidly during
the first 2 years after treatment but resolves more slowly
thereafter.
o Vertebral fractures and osteonecrosis are irreversible, and
permanent deformity results. Visceral obesity and myopathy are
both reversible features.
o Reproductive and sexual func- tion return to normal within 6
months, provided that anterior pituitary function was not
compromised.
66.
ThankYou
References:
Harrison’s principles of Internal Medicine 19th Ed.
WilliamsTextbook of Endocrinology 12th Ed.
Ferri's ClinicalAdvisor 2015
Online Source – Pubmed Central