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Adrenal Disease. Normal Anatomy and Physiology. Adrenal Disease. Objectives: 1. To increase students’ working knowledge of adrenal anatomy, physiology and pathology 2. To incorporate this working knowledge into patient assessment and clinical decision making. Adrenal glands: cortex
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Adrenal Disease Normal Anatomy and Physiology
Adrenal Disease Objectives: 1. To increase students’ working knowledge of adrenal anatomy, physiology and pathology 2. To incorporate this working knowledge into patient assessment and clinical decision making
Adrenal glands: cortex medulla
Adrenal: Normal Physiology Adrenal medulla: - ganglion of the sympathetic nervous system - secretes catecholamines: epinephrine and norepinephrine
Adrenal: Normal Physiology Adrenal medulla: Catecholamine (epinephrine and norepinephrine) secretion in response to sympathetic stimulation: fight or flight response
Adrenal: Normal Physiology Adrenal cortex: secretes steroid based hormones a. sex steroids b. mineralocorticoids c. glucocorticoids
Adrenal: Normal physiology • Sex steroids (testosterone) • supplemental to gonadal • production … not crucial to life
Adrenal: Normal physiology b. Mineralocorticoids: control of Na / K / H20 … blood pressure renin / angiotensin / aldosterone CRUCIAL TO LIFE
Adrenal: Normal physiology • Regulation of Renin / Angiotensin / Aldosterone • Renin secreted by JGA in response to BP or • chronic Na depletion • Renin catalyses the production of angiotensinI (a • decapeptide) from a circulating protein • 3. Angiotensin converting enzyme (ACE) in the lungs • cleaves off 2 more amino acids to form • AngiotensinII (an octapeptide)
Adrenal: Normal physiology • Renin / Angiotensin / Aldosterone • Angiotensin II : • is a potent vasoconstrictor and • it stimulates the release of aldosterone by the • adrenal cortex • Aldosterone acts on the collecting tubule to increase • the reabsorption of Na (and, therefore H2O)
Adrenal: Normal physiology • Glucocorticoids: • -control of CHO / protein / fat metabolism • -maintenance of vascular reactivity • -anti-inflammatory • -maintenance of homeostasis in response • to stress (surgery, infection, starvation, etc.) • CRUCIAL TO LIFE
Adrenal: Normal physiology • Glucocorticoids: control of • CHO / protein / fat metabolism • insulin antagonist ( serum glucose) • hepatic glucose output • initiates lipolysis and proteolysis • gluconeogenesis
Adrenal: Normal physiology • Glucocorticoids: • maintenance of vascular reactivity • “primes” blood vessels to respond • to catecholamine driven • vasoconstriction
Adrenal: Normal physiology • Glucocorticoids: anti-inflammatory • inhibits lysosome, prostaglandin, • eicosanoid, and cytokine release • inhibits endothelial cell adhesion
Adrenal: Normal physiology • Glucocorticoids: • maintenance of homeostasis in • response to physiologicstress • (surgery, infection, starvation, etc.)
H H H Adrenal: Normal physiology Steroid hormone mechanism of action: • 1. cell entry • 2. cytoplasmic • receptor binding • 3. migration to • nucleus • 4. DNA transcription • mRNA migration • to cytoplasm • 6. mRNA translation • 7. regulation of • receptor number • or activity 7 1 3 4 6 5 2
Adrenal: Normal physiology • Steroid mechanism of action: • requires multiple steps for effect • therefore, requires time to have • an effect … 2 to 4 hours
Adrenal: Normal physiology • Glucocorticoids: regulation • Normal diurnal variation (highest in AM): • Daily average of approximately 20 mg
Adrenal: Normal physiology • Glucocorticoids: regulation • Increased secretion in response to • physiologicstress (up to 200 mg) • Decreased secretion in response to • exogenous steroids, eg Prednisone
Adrenal: Normal physiology c. Glucocorticoids: regulation STRESS OR DECREASING CORTISOL EXOGENOUS STEROID OR INCREASING CORTISOL CRH = corticotropin releasing hormone hypothalamus CRH anterior pituitary ACTH cortisol adrenal cortex
Adrenal: Disease Hyperadrenalism Hypoadrenalism Patients taking or have taken oral steroids Will have 50 in 2000 patient practice
Adrenal: Disease (hyper) Hyperadrenalism: (Cushingoid) Cushing’s disease: excess of cortisol production (eg pituitary or adrenal tumour) with signs and symptoms of excess steroid
Adrenal: Disease (hyper) Hyperadrenalism: (Cushingoid) Cushing’s syndrome: Signs and symptoms of excess steroid secondary to chronic use
Adrenal: Disease (hyper) • Cushingoid side effects from excess • long term steroids: • adrenocortical suppression • weight gain, moon face, buffalo hump • abdominal striae, acne
Adrenal: Disease (hyper) • Cushingoid side effects from excess • long term steroids: • hypertension, heart failure • osteoporosis, growth suppression • diabetes, impaired healing, peptic ulcers • depression, psychosis
Adrenal: Disease (hypo) • Adrenal insufficiency: • Primary: Addison’s disease (loss of • >90% of adrenal cortex) due to • autoimmune, hemorrhage, • infection, tumour, surgery, etc. • Cortisol and Aldosterone deficiency
Adrenal: Disease (hypo) • Adrenal insufficiency: • Secondary: hypothalamic or pituitary • disease or exogenous steroid causing • suppression of the hypothalamic / • pituitary axis leading to atrophy of the • adrenal cortex • Cortisol deficiency only
Adrenal: Pharmacology • b. Glucocorticoids: steroids indicated • for inflammatory conditions such as: • rheumatoid arthritis (RA) • systemic lupus erythematosis (SLE) • asthma • inflammatory bowel disease (IBD) • prevention of organ transplant rejection • many others
Adrenal: Pharmacology b. Glucocorticoids: equivalents Cortisol 20 mg = Prednisone 5 mg = Solumedrol 4 mg = Decadron .75 mg
Adrenal: Disease (hypo) c. Secondary Adrenal insufficiency: IS caused by chronic oral steroid use: > 5 mg of Prednisone / day (> 20 mg of cortisol) for > 2 wks within the last year IS NOTcaused by inhaled, nasal or topical steroid use
Adrenal: Disease (hypo) • c. Secondary Adrenal insufficiency: • Strategies used to minimize suppression: • minimize oral dosage to 20 mg/day • equivalent of cortisol or less • every other day dosing • tapering dosage to complete course
Adrenal: Disease (hypo) • d. Adrenal insufficiency: Problems • impaired CHO / protein / fat metabolism • hypoglycemia • hypovolemia / hyperkalemia / acidosis • hypotension
Adrenal: Disease (hypo) • d. Adrenal insufficiency: Signs and • symptoms • excess pigmentation • postural hypotension (dizziness) • muscular weakness • nausea, anorexia, weight loss
Adrenal: Disease (hypo) • d. Adrenal insufficiency: diagnosis • Signs and symptoms • Lab values: difficult to do and interpret • CRH stimulation • ACTH stimulation • 24 hour urine cortisol
Adrenal: Disease (hypo) • d. Adrenal insufficiency: treatment • Treat the cause (tumour / infection) • Hormone replacement: • mineralocorticoid • glucocorticoid
Adrenal: Pharmacology • d. For mineralocorticoid insufficiency: • fludrocortisone (Florinef) • 0.05 to 0.1 mg daily
Adrenal: Pharmacology • d. For glucocorticoid insufficiency: • Cortisol: 20 mg AM / 10 mg PM • Prednisone: 5 mg AM / 2.5 mg PM • (divided doses to reflect normal diurnal • cycle)
Adrenal: Crisis • e. Acute Adrenal insufficiency: crisis • medical emergency • inability to tolerate physiologic stress • acute refractory hypotension, diaphoresis • dehydration, dyspnea, hypothermia, • hypoglycemia, circulatory collapse, death • less likely with secondary AI
Adrenal: Crisis prevention • e. Acute Adrenal crisis prevention: • 1. Recognition of patient at risk: • Addison’s disease • Has taken suppressive dose • Is taking low suppressive dose • (Prednisone 10 mg or less)
Adrenal: Crisis prevention • e. Acute Adrenal crisis prevention: • 2. Supplement: day before / day of / day after • 100 mg cortisol = 20 mg Prednisone • or • double the existing dose if • 10 mg of Prednisone or less
Adrenal: Crisis treatment • e. Acute Adrenal crisis treatment: • Hydrocortisone 100 mg IV bolus • Hospital setting for fluid and electrolyte • replacement • Correction of hypoglycemia • Continued IV steroid
Adrenal: Dental concerns • Assess compliance with steroids • 2. Assess need for supplementation: • complexity of surgery versus • degree of adrenal suppression • 3. Discontinue Ketoconazole and • barbiturates if possible
Adrenal: Dental concerns 4. AM procedures 5. Anxiety reduction eg N2O / O2 6. Good intra- and post-op pain control avoid NSAIDs (Peptic ulcers) 7. Monitor blood pressure 8. Cushingoid patients prone to fractures
Thyroid Disease Normal Anatomy and Physiology
Thyroid Disease Objectives: 1. To increase students’ working knowledge of thyroid anatomy, physiology and pathology 2. To incorporate this working knowledge into patient assessment and clinical decision making
Thyroid gland:
Thyroid: Normal Physiology Thyroid gland produces 3 hormones: T3: triiodothyronine T4: thyroxine Calcitonin: controls Calcium levels in conjunction with parathyroid hormone and Vitamin D
Thyroid: Normal Physiology T3: triiodothyronine: more potent form of thyroid hormone … 20% formed by the thyroid, 80% by deiodination in the periphery T4: thyroxine: produced in the thyroid Thyroid hormone formation is iodine dependant
The Great Lakes area is endemically deficient in iodine, for this reason iodine is added to the table salt.