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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)

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