Addison Cushingf08
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Transcript of Addison Cushingf08
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Unit 5
Common Health Problems
Endocrine Disorders
Addison & Cushing
Syndromes
Paul Anderson Fall 2008
Pathophysiology 101-823
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Learning Objectives
Describe the causes, manifestations& treatment of Addison Syndrome &Cushing Syndrome.
References:
Porth, Esentials, Ch. 31
Porth, Pathophysiology, Ch. 42
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Addison Disease - 1
CAUSES ofAddison Disease include
Autoimmune: most common form in developedcountries.
TB is most common cause where TB is prevalent.
Viral Infections &Fungal Infections (especiallyhistoplasmosis) e.g. with AIDS patients.
Metastatic carcinomas
Addison Disease is a rare Primary AdrenalInsufficiency Disorder in which the adrenal
cortex is destroyed causing a deficiency ofadrenal corticoid hormones & increased plasmalevels of ACTH.
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Functions of Aldosterone
Aldosterone is a mineralocorticoidsecretedby the adrenal cortex.
Aldosterone regulates sodium and potassiumbalance by causing the kidney to
- excrete potassium
- reabsorb sodium.
Aldosterone is secreted in response to
- low blood volume
- low blood pressure
- low blood [sodium]- high blood [potassium]
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Addison Disease - Causes of Manifestations
Manifestations ofAddison Disease
only appear when about 90 % of theadrenal gland is destroyed.
Manifestations of Addison Disease result
from Lack of Aldosterone
Lack of Glucocorticoids
Elevated ACTH.
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Addison Disease - Manifestations 1
Decreased Aldosterone causes:
Hyponatremia
Polyuria with loss of salt & H2Oeventually may cause CV collapse &circulatory shock.
Dehydration with polydipsia Orthostatic (postural) hypotension
Decreased cardiac output
Hyperkalemia
Salt craving
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Addison Disease - Manifestations 2
Decreased Glucocorticoidscause:
Hypoglycemia
Poor tolerance to stress(infections, trauma,surgery) causing an adrenal crisis with
hypoglycemia, hypotension & shock, lethargy,
weakness.Addison patients need a medical alert bracelet
Lethargy
WeaknessGI symptoms(anorexia, nausea, vomiting,weight loss)
fever
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Addison Disease - Manifestations
Excess ACTHin Addison patients causeshyperpigmentationof the skin, gums, mouth fromformation of a derivative of ACTH (Melanocyte
Stimulating Hormone - MSH) that targets the skin. Signs of hyperpigmentation distinguishes Addison
Disease (Primary Adrenal Insufficiency) fromSecondary Adrenal Insufficiency due to lack of ACTH
ACTH
(+)
(+)
-MSH
No effect on
adrenal cortex
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Addison Disease - Treatment
Addison Disease is a chronic disorder requiringlifelonghormone replacement therapy with higherdoses given in times of stress.
Hormones used are Oral hydrocortisone
(glucocorticoid with some salt retention effects) & amineralocorticoid (flurocortisone).
Female patients may also be given an adrenalandrogen to promote muscle mass, hemopoiesis &support sexual libido (all normal functions of
adrenal androgens in females).
Addison patients must be monitored carefully forsigns of infection & hypoglycemia & need scheduledmeals.
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Cushing Syndrome
Cushing Syndromerefers to disorder causinghypersecretion of adrenal corticoid hormones fromwhatever cause.
Cushing Syndrome if untreated produces seriousmorbidity, or death.
There are 4 causes
Pituitary hypersecretion of ACTHfrom a pituitarytumor (classic Cushing Disease)
Adrenal hypersecretion of corticoid hormonesdue to an adrenal tumor (benign or malignant)
Ectopic Cushing Syndromefrom paraneoplasticsyndrome (secretion of ACTH from tumors e.g. small cell
lung carcinoma).
Iatrogenic CushingSyndrome from long termglucocorticoid therapy.
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Cushing Syndrome - Manifestations - 1
Manifestations in Cushing Syndrome are
mainly due to excess glucocorticoids withexaggeration of cortisol actions(major
glucocorticoid) & include: Buffalo hump, moon face & protruding abdomen
from redistribution of body fat
Muscle weakness & thin extremities from proteinbreakdown with muscle wasting.
Thin parchment skin in arms, legs from protein &fat breakdown
Purple striae (stretch marks) on breasts, thighs,abdomen from protein & fat breakdown.
Osteoporosis & weak bones from protein breakdown
& Ca mobilisation.
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Cushing Syndrome - Manifestations - 2
Disturbed glucose metabolism with diabetes
mellitus occuring in 20% of cases.
Hypokalemia, Na retention & hypertension all frommineralocorticoid properties of glucocorticoids.
Increased infections & diminished inflammatory &immune responses.
Gastric ulceration & bleeding (cortisol stimulatesgastric secretions)
Hirsutism (body hair), acne & menstrual
irregularities in females due to increased levels ofandrogens.
Emotional lability (mild euphoria to psychotic
behaviour).
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Cushing
Syndrome -
Manifestations
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Moon face
ESR25-19
Plethoricface
(NO HIRSUTISM)Supra-
clavicularfat pads
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Central Adiposity
ESR25-20
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Bruising
ESR25-21
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Cushing Syndrome - Diagnosis & Treatment
Diagnosisinvolves
determination of24 hr cortisol levelsin blood, saliva,urine to determine any late night cortisol increase.
Plasma ACTH levels to determine cause of disorder(ACTH increased in ectopic source & in CushingDisease.
Treatment
Cushings disease:- trans-sphenoidal surgery
Cushings Syndrome -- resect ectopic site of ACTH secretion- adrenalectomy (+ steroid replacement)- anti-glucocorticoids (e.g. RU486) +
anti-androgens (e.g. flutamide)