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Pathophysiology 101-823 Unit 5 Common Health Problems

Endocrine Disorders Addison & Cushing Syndromes

Paul Anderson Fall 2008

Learning Objectives

Describe the causes, manifestations & treatment of Addison Syndrome & Cushing Syndrome. References: Porth, Esentials, Ch. 31 Porth, Pathophysiology, Ch. 42

Addison Disease - 1
Addison Disease is a rare Primary Adrenal Insufficiency Disorder in which the adrenal cortex is destroyed causing a deficiency of adrenal corticoid hormones & increased plasma levels of ACTH. CAUSES of Addison Disease include Autoimmune: most common form in developed countries. TB is most common cause where TB is prevalent. Viral Infections & Fungal Infections (especially histoplasmosis) e.g. with AIDS patients. Metastatic carcinomas

Functions of Aldosterone
Aldosterone is a mineralocorticoid secreted by the adrenal cortex. Aldosterone regulates sodium and potassium balance 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]

Addison Disease - Causes of Manifestations

Manifestations of Addison Disease only appear when about 90 % of the adrenal gland is destroyed. Manifestations of Addison Disease result from Lack of Aldosterone Lack of Glucocorticoids Elevated ACTH.

Addison Disease - Manifestations 1

Decreased Aldosterone causes: Hyponatremia Polyuria with loss of salt & H2O eventually may cause CV collapse & circulatory shock. Dehydration with polydipsia Orthostatic (postural) hypotension Decreased cardiac output Hyperkalemia Salt craving

Addison Disease - Manifestations 2

Decreased Glucocorticoids cause: 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 Weakness GI symptoms (anorexia, nausea, vomiting,

weight loss)


Addison Disease - Manifestations

Excess ACTH in Addison patients causes hyperpigmentation of the skin, gums, mouth from formation of a derivative of ACTH (Melanocyte Stimulating Hormone - MSH) that targets the skin. Signs of hyperpigmentation distinguishes Addison Disease (Primary Adrenal Insufficiency) from Secondary Adrenal Insufficiency due to lack of ACTH

(+) ACTH (+) -MSH

No effect on adrenal cortex

Addison Disease - Treatment

Addison Disease is a chronic disorder requiring lifelong hormone replacement therapy with higher doses given in times of stress. Hormones used are Oral hydrocortisone (glucocorticoid with some salt retention effects) & a mineralocorticoid (flurocortisone). Female patients may also be given an adrenal androgen to promote muscle mass, hemopoiesis & support sexual libido (all normal functions of adrenal androgens in females). Addison patients must be monitored carefully for signs of infection & hypoglycemia & need scheduled meals.

Cushing Syndrome
Cushing Syndrome refers to disorder causing hypersecretion of adrenal corticoid hormones from whatever cause. Cushing Syndrome if untreated produces serious morbidity, or death. There are 4 causes Pituitary hypersecretion of ACTH from a pituitary
tumor (classic Cushing Disease)

Adrenal hypersecretion of corticoid hormones

due to an adrenal tumor (benign or malignant)

Ectopic Cushing Syndrome from paraneoplastic

syndrome (secretion of ACTH from tumors e.g. small cell lung carcinoma).

Iatrogenic Cushing Syndrome from long term

glucocorticoid therapy.

Cushing Syndrome - Manifestations - 1

Manifestations in Cushing Syndrome are mainly due to excess glucocorticoids with exaggeration of cortisol actions (major glucocorticoid) & include: Buffalo hump, moon face & protruding abdomen from redistribution of body fat Muscle weakness & thin extremities from protein breakdown 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.

Cushing Syndrome - Manifestations - 2

Disturbed glucose metabolism with diabetes mellitus occuring in 20% of cases. Hypokalemia, Na retention & hypertension all from mineralocorticoid properties of glucocorticoids. Increased infections & diminished inflammatory & immune responses. Gastric ulceration & bleeding (cortisol stimulates gastric secretions) Hirsutism (body hair), acne & menstrual irregularities in females due to increased levels of androgens. Emotional lability (mild euphoria to psychotic behaviour).

Cushing Syndrome Manifestations

Moon face

Plethoric face Supraclavicular fat pads



Central Adiposity




Cushing Syndrome - Diagnosis & Treatment

Diagnosis involves determination of 24 hr cortisol levels in blood, saliva, urine to determine any late night cortisol increase. Plasma ACTH levels to determine cause of disorder (ACTH increased in ectopic source & in Cushing Disease. 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)