Atlas of pathophysiology, 2 Edition

Part II - Disorders

Endocrine Disorders

Adrenal hypofunction

Adrenal hypofunction is classified as primary or secondary. Primary adrenal hypofunction or insufficiency (Addison's disease) originates within the adrenal gland and is characterized by the decreased secretion of mineralocorticoids, glucocorticoids, and androgens. It's defined as destruction of more than 90% of both adrenal glands and is usually caused by an autoimmune process. Addison's disease is relatively uncommon and can occur at any age and in both sexes. Secondary adrenal hypofunction is due to impaired pituitary secretion of adrenocorticotropin (ACTH) and is characterized by decreased glucocorticoid secretion.

With early diagnosis and adequate replacement therapy, the prognosis for adrenal hypofunction is good.

Clinical Tip

Adrenal crisis (Addisonian crisis) is a critical deficiency of mineralocorticoids and glucocorticoids that generally follows sepsis, trauma, surgery, omission of steroid therapy, or other acute physiologic stress. This medical emergency mandates immediate, vigorous treatment.


Primary hypofunction (Addison's disease)

·   Bilateral adrenalectomy

·   Hemorrhage into adrenal gland

·   Neoplasms

·   Tuberculosis, histoplasmosis, cytomegalovirus

·   Family history of autoimmune disease

Secondary hypofunction (glucocorticoid deficiency)

·   Hypopituitarism (causing decreased ACTH secretion)

·   Abrupt withdrawal of long-term corticosteroid therapy

·   Removal of an ACTH-secreting tumor

·   Pituitary injury by tumor or infiltrative or autoimmune process


Addison's disease is a chronic condition that results from partial or complete adrenal destruction. In most cases, cellular atrophy is limited to the cortex, although medullary involvement may occur, resulting in catecholamine deficiency.

ACTH acts primarily to regulate the adrenal release of glucocorticoids (primarily cortisol); mineralocorticoids, including aldosterone; and sex steroids that supplement those produced by the gonads. ACTH secretion is controlled by corticotropin-releasing hormone from the hypothalamus and by negative feedback control by the glucocorticoids.

Cortisol deficiency causes decreased liver gluconeogenesis. Glucose levels of patients on insulin may be dangerously low.

Aldosterone deficiency causes increased renal sodium loss and enhances potassium reabsorption. Sodium excretion causes a reduction in water volume that leads to hypotension.

Androgen deficiency may result in decreased hair growth in axillary and pubic areas, loss of erectile function, or decreased libido.

Signs and symptoms

Primary hypofunction

·   Weakness, fatigue

·   Nausea, vomiting, anorexia, weight loss

·   Conspicuous bronze color of the skin, especially on hands, elbows, and knees; darkening of scars

·   Cardiovascular abnormalities, including orthostatic hypotension, decreased cardiac size and output, and weak, irregular pulse

·   Decreased tolerance for even minor stress

·   Fasting hypoglycemia

·   Craving for salty food

Secondary hypofunction

·   Similar to primary hypofunction; differences include:

§  hyperpigmentation absent because ACTH and melanocyte-stimulating hormone levels are low

§  possibly normal blood pressure and electrolyte balance because aldosterone secretion is near normal

§  usually normal androgen secretion.

Addisonian crisis

·   Profound weakness and fatigue

·   Nausea, vomiting, dehydration

·   Hypotension

·   Confusion

Diagnostic test results

·   Blood test for plasma cortisol levels confirms adrenal insufficiency.

·   Metyrapone test is used to detect secondary adrenal hypofunction.

·   Rapid corticotropin stimulation test by I.V. or I.M. administration of cosyntropin, a synthetic form of corticotropin, after baseline sampling for cortisol and corticotropin (samples drawn for cortisol 30 and 60 minutes after injection), differentiates between primary and secondary adrenal hypofunction. A low corticotropin level indicates a secondary disorder. An elevated level is indicative of a primary disorder.

·   Laboratory studies reveal decreased plasma cortisol level (less than 10 mcg/dl in the morning; less in the evening); decreased serum sodium and fasting blood glucose levels.

·   Serum chemistry reveals increased serum potassium, calcium, and blood urea nitrogen levels.

·   Complete blood count shows elevated hematocrit; and increased lymphocyte and eosinophil counts.

·   X-rays show adrenal calcification if the cause is infectious.


Primary or secondary adrenal hypofunction

·   Lifelong corticosteroid replacement, usually with cortisone or hydrocortisone, which have a mineralocorticoid effect

·   I.V. hydrocortisone

Primary adrenal hypofunction

·   Oral fludrocortisone, a synthetic mineralocorticoid, to prevent dangerous dehydration, hypotension, hyponatremia, and hyperkalemia





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