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Dr Faiza Ikram, Asst. Prof. Physiology
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Adrenocortical Hormones
1
Dr Faiza
Assistant Professor of Physiology
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology,
ICMT, CHPE, DHPE (STMU)
MHPE (Riphah Int University)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Dr Faiza Ikram, Asst. Prof. Physiology
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0310-7990649
Adrenocortical Hormones
2
• Ch 78-Guyton and Hall textbook of medical physiology, 15th ed. Elsevier Health Sciences.
• Ch 20- Barrett, K. E. (2010). Ganong’s review of medical physiology, 25th ed
• Ch 19- Sherwood L. Human physiology: from cells to systems. Cengage learning; 9th ed.
• Ch 7- Costanzo LS. Costanzo Physiology E-Book. Board review series; 6th ed.
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• 15%
• Aldosterone
synthase
• Angiotensin II ,
K+
• 75%
• ACTH
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Cholesterol precursor (LDL, de novo from acetate)
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21,19,18-carbon steroids
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Aldosterone synthase
Aldosterone
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Cortisol
Half life: 60-90 min
90-95% bound form
Aldosterone
Half life: 20 min
60% bound form
Binding proteins
Globulin
Transcortin
Albumin
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Mineralocorticoids (Zona Glomerulosa)
• Aldosterone (Major)
• Regulation:
• ACTH
• Potassium
• plasma volume
• Sodium
• ANP
• Renin
• Permissive action: ACTH
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Apparent mineralocorticoid Excess
• licorice, which contains
glycyrrhetinic acid, may also
cause AME because of its
ability to block 11β-HSD2
enzyme activity
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Functions of Aldosterone
• Na reabsorption
• Fluid retention
• K excretion
• H excretion
• Principal cells, collecting ducts and tubules
• Colon
• Salivary and sweat glands
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• Hyperkalemia: Cardiac toxicity
• Hypokalemia: Transient muscle weakness , paralysis
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Hyperaldosteronism
• Increases Extracellular Fluid Volume
• Increases Arterial Pressure
• Small Effect on Plasma Sodium
Concentration
• Aldosterone Deficiency Causes
Hyponatremia
• Peripheral edema does not occur –
Aldosterone escape
• Aldosterone escape: pressure
natriuresis, diuresis
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Glucocorticoids (Zona Fasciculata & Reticularis)
• Cortisol /hydrocortisone (Major)
• Regulation:
• ACTH
• Stress
• Trauma
• Emotional Stimuli
• Diurnal variation
• Limbic system
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Cortisol
(stress
hormone)
Carbohydrate
metabolism
(Adrenal Diabetes)
Increases hepatic enzymes for conversion of amino acids to glucose
Metabolization of aminoacids from extrahepatic tissue specially muscles
Antagonized Insulin effect to inhibit hepatic gluconeogenesis
Decrease glucose utilization by cells-insulin resistence
Protein metabolism
(preferential effect)
Decrease synthesis, increase catabolism of extrahepatic proteins-muscle
weekness
Increase liver and plasma proteins
Enhanced transport of amino acids into hepatocytes
Fat metabolism Increase lipolysis in adipose tissue
Increase utilization of fatty acids for energy
Excess cortisol may cause obesity
Anti-inflammatory
effects (prevents and
resolves inflammation)
Stabilizes lysosomal membrane
Decreased migration and phagocytosis by white blood cells
Decreased lymphocyte production
Decreased interleukin 1 & phospholipase (Prostaglandins, leukotrienes)
Other effects Neutrophilia, lymphocytopenia, eosinopenia
Blocks inflammatory response to allergic reactions-inhibit histamine, serotonin
Permissive action on epinephrine, glucagon
• inhibit growth,
• decrease
growth
hormone
secretion
• induce PNMT
• decrease TSH
secretion
• Accelerate the
maturation of
surfactant in
the lungs-fetal
life
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Platelets 1,50,000 Raised
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Regulation of
Glucocorticoids
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POMC-Proopiomelanocortin
ACTH
MSH
Endorphin
ACTH has 1/30 MSH activity
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Adrenal Androgens
• Dehydroepiandrosterone (Major)
• Mostly conjugated to sulphate
• extra-adrenal tissues, some of the adrenal androgens are converted to
testosterone
• Required for female pubic and axillary haor growth
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Hypoadrenalism
Secondary hypoadrenalism Deficient ACTH (pituitary)
Tertiary hypoadrenalism Deficient CRH (Hypothalamus)
Primary adrenal insufficiency Addison disease
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26
Hypoadrenalism
Mineralocorticoid deficiency
Hyponatremia
Hyperkalemia
Acidosis
Hypovolemia-Shock
Glucocorticoid deficiency
Lack of glucose stabilization in stress
Addisonian crisis
Lack of vascular responsiveness to
epinephrine
High ACTH
Melanin pigmentation
(specially thin skin, mucous
membrane, lips, areola)
CNS-slow beta waves, irritability,
apprehension, lack of focus
Water intoxication risk
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Hyper-adrenalism
(Cushing
syndrome)
Conn’s disease Hyperaldosteronism
Hypernatremia,
hypokalemia, alkalosis,
muscle paralysis
Cushing syndrome
Secondary
hypoadrenalism /Cushing
disease
High ACTH (pituitary)
Tertiary hypoadrenalism
High CRH
(Hypothalamus/ectopic
source)
Primary hyperadrenalism High cortisol, low ACTH
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Dexamethasone suppression test
• Adrenal Cause: High Cortisol, Low ACTH
• Differentiate the cause of ACTH dependent Cushing syndrome
• Low Dose dexamethasone suppression test-
failure to reduce ACTH and cortisol
• High dose dexamethasone suppression test-
Pituitary cause: ACTH and cortisol decrease
Ectopic ACTH source: Cortisol and ACTH not supressed
Dr Faiza Ikram, Asst. Prof. Physiology
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29
Cushing
Disease/Syndrome
Increase glucose level Adrenal diabetes
Fat redistribution and water
retention
Buffalo like torso
Moon Face
Facial plethora
Pot like abdomen
Protein catabolism
Muscle weakness
Abdominal purplish striae
Poor wound healing
Thin skin
Bruisability
Osteoporosis
Excess androgens
Hirsutism
Virilization
Acne
CNS-slow beta waves,
irritability, apprehension, lack
of focus
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Treatment Options (Figure out which suits what)
• Exogenous Cortisol
• ACE inhibitors
• Block steroidogenesis- metyrapone, ketoconazole, and
aminoglutethimide
• inhibit ACTH secretion, such as serotonin antagonists and GABA
transaminase inhibitors
• Aldosterone antagonists
• Exogenous ACTH
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Adrenogenital
Syndrome
Prepubertal males Precocious pseudo puberty
Females-Adrenogenital syndrome
Virilization- beard, hoarse voice,
baldness, masculine distribution of
hair
Skin and muscles develop masculine
characters
Genital changes-clitoris hypertrophy
to resemble penis
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21β-Hydroxylase deficiency
17α-Hydroxylase deficiency
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Inc Aldosterone,
Cortisol,
Androgens
Inc Cortisol,
Androgens
Sec adrenal
hyperplasia)
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Adrenal Medulla
• 20% norepinephrine
• 80% epinephrine
• Pheochromocytoma
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Dr Faiza Ikram, Asst. Prof. Physiology 43
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Thank You
• Ch 78-Guyton and Hall textbook of medical physiology, 15th ed. Elsevier Health Sciences.
• Ch 20- Barrett, K. E. (2010). Ganong’s review of medical physiology, 25th ed
• Ch 19- Sherwood L. Human physiology: from cells to systems. Cengage learning; 9th ed..
• Ch 7- Costanzo LS. Costanzo Physiology E-Book. Board review series; 6th ed.