Acromegaly is a disorder caused by an excessive production of growth hormone from the anterior pituitary gland, resulting in excessive growth of body tissues and other metabolic dysfunctions. Adult patients with acromegaly have the characteristic facial features of a large lower jaw, prominent forehead, and large hands and feet. This takes place after the growth plates are fused, distinguishing acromegaly from gigantism which occurs before fusion of growth plates.
Pituitary Tumor: In more than 95% of cases, the excessive growth hormone is caused by a pituitary tumor, usually a benign microadenoma of the pituitary gland.
Non-Pituitary Tumor: Tumors of the adrenals, lungs, and pancreas are implicated in a few cases. These tumors secrete growth hormone or growth hormone releasing Hormone (GH-RH).
Elevated levels of growth hormone stimulate the liver to produce Insulin-like growth factor-1 (IGF-1). Elevated levels of Insulin-like growth factor-1 stimulate the excessive growth of body tissues.
In about 95% of cases, acromegaly is associated to a pituitary microadenoma, while the remaining 5% are from non-pituitary ectopic sources of growth hormone or GH-RH. The common effect of the abnormal rise in growth hormone is the production of Insulin-like growth factor-1 (IGF-1) from the liver. The effect of IGF-1 on body tissues results in the multisystemic manifestation of acromegaly. IGF-1 also known as Somatomedin C is encoded by the IGF-1 gene on chromosome 12q23.2.
The pathologic effect of IGF-1 after fusion of the growth plates result in the acral growth spurts manifested as large hands and feet and a prominent jaw and forehead. It is clearly different from the linear size increase that occurs in gigantism in which the effect of elevated IGF-1 occurs before closure of the growth plate.
Acromegaly leads to elevated IGF-1 that affects the following pathways of metabolism:
IGF-1 is an insulin-like protein produced majorly in the liver. It is a single chain of 70 amino acids and three disulfide bridges with a molecular weight of approximately eight kilodaltons. IGF-1 level peaks around puberty, with low levels at extreme ages.
Synthetic IGF-1 analog is used in the treatment of growth disorders, for example, dwarfism.
IGF-1 almost always exists in the bound form. It is bound by the IGF-binding proteins (IGF-BPs), and the most abundant of them is IGFBP-3.
Nutrition also plays some role, as high protein intake tends to increase growth hormone and IGF-1 levels.
Acromegaly is usually a slow progressing disorder, with onset usually in the third or fourth decade of life. The presenting complaints include the following:
Signs upon physical examination include the following:
Visual field examination
GH suppression test:
Growth Hormone Releasing Hormone (GHRH) Levels
Skull x-ray: thickened calvaria, enlarged sella, long and thick mandibles, exaggerated ridges, dilated sinuses
Chest x-ray: barrel rib cage with long ribs
Hand x-ray: cortical thickening, ungal tufting, wide distal phalangeal bases, osteophytes and soft tissue hypertrophy
Minoxidil use has been associated with a condition characterized by facial features of acromegaly, but with normal growth hormone and IGF-1 blood levels. This condition is known as pseudoacromegaly.
Acromegaly is not a common disorder in North America, but when it presents, it is associated with a very high morbidity and mortality rates. Because the presentation of acromegaly is systemic, a multidisciplinary approach is necessary. In particular a cardiologist, oncologist, neurologist, and a pulmonologist should be involved as the disorder is associated with malignancies, adverse cardiac, CNS and pulmonary events. The mortality rates of patients with acromegaly are 3 times the general population, with most dying from respiratory and cardiac complications. These patients also develop several types of tumors including prostatic hypertrophy, uterine myomas, and skin tags. The overall outcome depends on whether the cause of acromegaly can be treated. even after surgical removal of a pituitary tumor, some patients may need treatment as a result of residual disease. The quality of life in these patients is poor.
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