Adrenal Disorders

Dr. Othman Al-Shboul Department of Physiology

Anatomy of the adrenal glands

aldosterone

cortisol

Sex hormones

Hormones of the Adrenal Cortex

1. Mineralocorticoids, mainly aldosterone 2. Glucocorticoids, primarily cortisol 3. Sex hormones, mainly dehydroepiandrosterone, a male sex hormone

Aldosterone

Aldosterone Effects
Site of aldosterone action is on the distal and collecting tubules of the kidney

i.

Promotes Na+ retention osmotic H2O retention increased ECF volumes increased blood pressure

ii. Enhances K+ elimination

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Regulation of Aldosterone Secretion

Aldosterone secretion is increased by:
Activation of the renin-angiotensin system Direct stimulation of the adrenal cortex by a rise in plasma K+ concentration

Regulation of Aldosterone Secretion

Na+ deprivation

Decreased ECF volume

Increase Plasma K+

Renin

Angiotensin II

Aldosterone

Cortisol

Cortisol Effects
i. Metabolic effects
stimulates hepatic gluconeogenesis inhibits glucose uptake and use by many tissues stimulates protein degradation in many tissues, especially muscle facilitates lipolysis
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Cortisol Effects
ii. Permissive actions

Permit the catecholamines to induce vasoconstriction

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Cortisol Effects
iii. Adaptation to stress
Stress is one of the major stimuli for increased cortisol secretion Increased pool of glucose, amino acids, and fatty acids is available for use in stressful situations

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Cortisol Effects
iv. Anti-inflammatory and immunosuppressive effects

o Pharmacological effect (at higher than normal concentrations) o Suppresses the bodys response to the disease o Useful in allergic disorders and organ transplant rejections o Precautions:
suppression of the normal inflammatory and immune responses negative-feedback effect (decreased ACTH adrenal atrophy) other side effects (high blood pressure, atherosclerosis)

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highest in the morning lowest at night

Control of Cortisol Secretion

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Abnormalities of Adrenocortical Secretion

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Abnormalities of adrenocortical secretion

i. Hypoadrenalism (Adrenal Insufficiency)-Addison's Disease

ii. Hyperadrenalism - Cushing's Syndrome iii. Primary Aldosteronism (Conn's Syndrome)

i.

Hypoadrenalism (Adrenal Insufficiency)Addison's Disease

Inability of the adrenal cortices to produce sufficient adrenocortical hormones

Primary adrenal insufficiency
Caused by primary atrophy (mostly due to autoimmunity) or injury (e.g. tuberculous destruction or cancer) of the adrenal cortices.

Secondary adrenal insufficiency

Secondary to impaired function of the pituitary gland and ACTH secretion
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i.

Hypoadrenalism (Adrenal Insufficiency)Addison's Disease

1. Mineralocorticoid Deficiency
Loss of sodium ions, chloride ions, and water in urine hyponatremia, decreased ECF volume shock Decreased renal secretion of K+ & H+ hyperkalemia, and mild acidosis

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i.

Hypoadrenalism (Adrenal Insufficiency)Addison's Disease

2. Glucocorticoid Deficiency
Disturbance of normal blood glucose concentration between meals Reduces mobilization of both proteins and fats from tissues depressing many other metabolic functions of the body Susceptibility to the deteriorating effects of different types of stresses (like infection)

Addisonian crisis: critical need for extra glucocorticoids and the associated severe debility in times of stress
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i.

Hypoadrenalism (Adrenal Insufficiency)Addison's Disease

3. Melanin pigmentation of mucus membrane and skin

Results from loss of cortisol ve feedback on hypothalamus increased ACTH & MSH secretion pigmentation

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MSH; Melanocyte Stimulating Hormone

i.

Hypoadrenalism (Adrenal Insufficiency)Addison's Disease

Treatment
Small quantities of mineralocorticoids and glucocorticoids are administered daily.

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ii.

Hyperadrenalism - Cushing's Syndrome

Hypersecretion by the adrenal cortex (mostly cortisol)

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ii.

Hyperadrenalism - Cushing's Syndrome

Causes:
1. Adenomas of the anterior pituitary that secrete large amounts of ACTH, which then causes adrenal hyperplasia and excess cortisol secretion, (most common cause). 2. Abnormal function of the hypothalamus that causes high levels of corticotropin-releasing hormone (CRH), which stimulates excess ACTH release. 3. Ectopic secretion" of ACTH by a tumor elsewhere in the body, such as an abdominal carcinoma
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ii.

Hyperadrenalism - Cushing's Syndrome

Causes:
4. Primary overproduction of cortisol by the adrenal glands (e.g., adenoma) o 25% of cases o Associated with reduced ACTH levels (cortisol feedback inhibition of ACTH secretion)
The dexamethasone test (synthetic glucocorticoid): large doses of dexamethasone leads to inhibition of ACTH in primary hyperadrenalism but not in pituitary adenomas

5.

When large amounts of glucocorticoids are administered over prolonged periods for therapeutic purposes
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ii.

Hyperadrenalism - Cushing's Syndrome

Signs and Symptoms:

o Buffalo torso; mobilization of fat from the lower part of the body, with concomitant extra deposition of fat in the thoracic and upper abdominal regions

o Edematous appearance of the face

o Acne and hirsutism o Moon face o Hypertension, presumably because of the mineralocorticoid effects of cortisol.

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ii.

Hyperadrenalism - Cushing's Syndrome

Signs and symptoms:

o Increased blood glucose concentration. o loss of protein from:
Muscles (severe weakness) Lymphoid tissues (suppressed immunity, leading to infections) Subcutaneous tissue (tear easily, purplish striae) Bones (severe osteoporosis)
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ii.

Hyperadrenalism - Cushing's Syndrome

Treatment:
o Surgical removal/ radiation of pituitary o Drugs that block steroidogenesis o Drugs that inhibit ACTH secretion o Bilateral partial (or even total) adrenalectomy, followed by administration of adrenal steroids to make up for any insufficiency that develops
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iii. Primary Aldosteronism (Conn's Syndrome)

Tumor of the zona glomerulosa cells secreting large amounts of aldosterone or hyperplastic adrenal cortices secrete aldosterone rather than cortisol

Signs and symptoms:

o Hypokalaemia, metabolic alkalosis, increased ECF volume and hypertension. o Occasional periods of muscle paralysis caused by the hypokalemia (depressant effect of low extracellular potassium concentration on action potential transmission by the nerve fibers)
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iii. Primary Aldosteronism (Conn's Syndrome)

Diagnosis:
Decreased plasma renin concentration

Na+ deprivation

Decreased ECF volume

Treatment:
Surgery Drugs against mineralocorticoid receptor
Renin

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The END
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