Atlas of pathophysiology, 2 Edition

Part II - Disorders

Endocrine Disorders

Growth hormone excess

Growth hormone (GH) excess that begins in adulthood (after epiphyseal closure) is called acromegaly. GH excess that's present before closure of the epiphyseal growth plates of the long bones causes pituitary gigantism. In both cases, the result is increased growth of bone, cartilage, and other tissues, as well as increased carbohydrate catabolism and protein synthesis. In gigantism, a proportional overgrowth of all body tissues before epiphyseal closure causes remarkable height increases—as much as 6″ (15 cm) a year. Acromegaly is rare; its prevalence is about 70 people per million in the United States, affecting men and women equally. GH excess is a slow but progressive disease that shortens life if untreated. Morbidity and mortality tend to be related to coronary artery disease and hypertension secondary to prolonged exposure to excessive growth hormone.

Age Alert

Most cases of acromegaly are diagnosed in the fourth and fifth decades, but the disease is usually present for years before diagnosis. Gigantism affects infants and children, causing them to reach as much as three times the normal height for their age. Affected adults may reach a height of more than 7½ (7.6 m).

Causes

Eosinophilic or mixed-cell adenomas of the anterior pituitary gland

Pathophysiology

A GH-secreting tumor creates an unpredictable GH secretion pattern, which replaces the usual peaks at 1 to 4 hours after the onset of sleep. Elevated GH and somatomedin levels stimulate growth of all tissues. In pituitary gigantism, the epiphyseal plates aren't closed, and so the excess GH stimulates linear growth. It also increases the bulk of bones and joints and causes enlargement of internal organs and metabolic abnormalities. In acromegaly, the excess GH increases bone density and width, and the proliferation of connective and soft tissues.

Signs and symptoms

Acromegaly

·   Soft-tissue thickening that causes enlargement of hands, feet, nose, mandible, supraorbital ridge, and ears

·   Severe headache, central nervous system impairment, bitemporal hemianopia (defective vision), loss of visual acuity, and blindness (if the intrasellar tumor compresses the optic chiasm or nerves)

·   Marked prognathism and malocclusion of teeth; may interfere with chewing

·   Laryngeal hypertrophy, paranasal sinus enlargement, thickening of the tongue—causing the voice to sound deep and hollow

·   Arrowhead appearance of distal phalanges on X-rays, thickened fingers

·   Sweating, oily skin, hypertrichosis, new skin tags (typical)

·   Irritability, hostility, various psychological disturbances

·   Bow legs, barrel chest, arthritis, osteoporosis, kyphosis

·   Glucose intolerance, clinical diabetes mellitus

·   Hypertension and arteriosclerosis (effects of prolonged excessive GH secretion)

·   Hypermetabolism

·   Weakness, arthralgia

Gigantism

·   Backache, arthralgia, arthritis

·   Excessive height

·   Headache, vomiting, seizure activity, visual disturbances, papilledema

·   Deficiencies of other hormone systems if GH-producing tumor destroys other hormone-secreting cells

·   Glucose intolerance and diabetes mellitus

Diagnostic test results

·   Laboratory studies reveal elevated plasma GH level measured by radioimmunoassay, the presence of somatomedin C, and elevated blood glucose levels.

·   Glucose suppression test confirms hyperpituitarism.

·   Skull X-rays, computed tomography scan, or magnetic resonance imaging show the presence and extent of pituitary lesion.

·   Bone X-rays show a thickening of the cranium (especially frontal, occipital, and parietal bones) and long bones, and osteoarthritis in the spine.

Treatment

·   Tumor removal by cranial or transphenoidal hypophysectomy or pituitary radiation therapy

·   Mandatory surgery for a tumor causing blindness or other severe neurologic disturbances

·   Postoperative replacement of thyroid, cortisone, and gonadal hormones

·   Bromocriptine and octreotide to inhibit GH synthesis

P.283

EFFECTS OF GROWTH HORMONE EXCESS

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