Tuesday, May 16, 2017

Acromegaly and Gigantism



Introduction
Chronic, progressive diseases, acromegaly and gigantism are marked by hormonal dysfunction and startling skeletal overgrowth. Acromegaly occurs after epiphyseal closure, causing bone thickening and transverse growth and visceromegaly. Gigantism begins before epiphyseal closure and causes proportional overgrowth of all body tissues. Although the prognosis depends on the causative factor, these disorders usually reduce life expectancy unless treated in a timely way.

Pathophysiology
Typically, oversecretion of human growth hormone (HGH) produces changes throughout the entire body, resulting in acromegaly and, when oversecretion occurs before puberty, gigantism. Somatotrope adenomas and, rarely, extrapyradimal pituitary lesions or other tumors may cause this oversecretion, but the cause of the tumors themselves remains unclear. Elevated HGH levels in more than one family member suggest a genetic cause.
The earliest sign of acromegaly is soft-tissue swelling of the extremities, which causes coarsening of the facial features. This rare form of hyperpituitarism occurs equally among men and women, usually between ages 30 and 50.

Signs and symptoms

Acromegaly develops slowly, whereas gigantism develops abruptly.

Acromegaly
Acromegaly commonly produces hyperdidrosis, arthropathy, carpal tunnel syndrome, proximal muscle weakness and fatigue, acanthosis nigricans and skin tags, and oily skin.
Hypersecretion of HGH produces cartilaginous and connective tissue overgrowth, resulting in a characteristic hulking appearance, with an enlarged supraorbital ridge and thickened ears and nose. Prognathism, projection of the jaw, becomes marked and may interfere with chewing. Laryngeal hypertrophy, paranasal sinus enlargement, and thickening of the tongue cause the voice to sound deep and hollow. Also, the fingers are thickened.
Coronary artery disease, cardiomyopathy with arrhythmias, left ventricular hypertrophy, decreased diastolic function, and hypertension occur in 30% of patients; upper airway obstruction with sleep apnea, in 60% of patients. Generalized visceromegaly occurs, including cardiomegaly, macroglossia, and thyroid gland enlargement.
Prolonged effects of excessive HGH secretion include barrel chest and kyphosis. Both gigantism and acromegaly may also cause signs of glucose intolerance and diabetes mellitus because of the insulin-antagonistic character of HGH.

Gigantism
Gigantism produces some of the same skeletal abnormalities seen in acromegaly. As the disease progresses, the pituitary tumor enlarges and invades normal tissue, resulting in the loss of other trophic hormones, such as thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and corticotropin, thus causing the target organ to stop functioning.

Diagnosis
Serum HGH levels measured by radioimmunoassay typically are elevated. However, because HGH secretion is pulsatile, the results of random sampling may be misleading. IGF-1 (somatomedin-C) levels offer a better screening alternative.
The glucose suppression test offers more reliable information. Glucose normally suppresses HGH secretion; therefore, a glucose infusion that doesn’t suppress the hormone level to below the accepted normal value of 2 ng/ml, when combined with characteristic signs and symptoms, strongly suggests hyperpituitarism.
In addition, skull X-rays, a computed tomography scan, arteriography, and magnetic resonance imaging determine the presence and extent of the pituitary lesion. Bone X-rays showing a thickening of the cranium (especially of frontal, occipital, and parietal bones) and of the long bones as well as osteoarthritis in the spine support this diagnosis.

Treatment

Overproduction of HGH is curbed through removal of the underlying tumor by cranial or transsphenoidal hypophysectomy or pituitary radiation therapy. With acromegaly, surgery is mandatory when a tumor causes blindness or another severe neurologic disturbance.
Postoperative therapy commonly requires replacement of thyroid and gonadal hormones and cortisone. Adjunctive treatment may include administration of lanreotide, bromocriptine, and octreotide, which inhibit HGH synthesis.

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