Porth's Essentials of Pathophysiology, 4e

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Endocrine System

U N I T 9

relieving the central mass effects; and improvement of adverse clinical features. 2 Pituitary tumors can be removed surgically using the transsphenoidal approach or, if that is not possible, a transfrontal craniotomy. Radiation therapy may be used, but remission (reduc- tion in GH levels) may not occur for several years after therapy. Somatostatin analogs (especially long-acting formu- lations of octreotide or lanreotide) produce feedback inhibition of GH and are effective in the medical man- agement of acromegaly. Dopamine agonists also reduce GH levels and have been used with some success. 2 Growth hormone analogs (e.g., pegvisomant) antago- nize the actions of GH by binding to GH receptors on the cell surfaces. These analogs produce symptom relief and normalize serum IGF-1 levels in most individuals with acromegaly. 2

which represents an exaggerated growth of the ends of the extremities (fingers, hands, and toes). The annual incidence of acromegaly is 3 to 4 cases per 1 million people, with a mean age at the time of diagnosis of 40 to 45 years. 2,20,21 The most common cause of acromegaly is GH-secreting adenomas, most of which are benign. 21 The disorder usually has an insidious onset, and symptoms often are present for a considerable period before a diagnosis is made. When the production of excessive GH occurs after the epiphyses of the long bones have closed, as in the adult, the person cannot grow taller, but the soft tissues continue to grow. Enlargement of the small bones of the hands and feet and of the mem- branous bones of the face and skull results in a pro- nounced enlargement of the hands and feet, a broad and bulbus nose, a protruding jaw, and a slanting forehead (Fig. 32-4). The teeth become splayed, caus- ing a disturbed bite and difficulty in chewing. The car- tilaginous structures in the larynx and respiratory tract also become enlarged, resulting in a deepening of the voice and tendency to develop bronchitis. Vertebral changes often lead to kyphosis, or hunchback. Bone overgrowth often leads to arthralgias and degenerative arthritis of the spine, hips, and knees. Virtually every organ of the body is increased in size. Enlargement of the heart and accelerated atherosclerosis may lead to an early death. The metabolic effects of excess levels of GH include disorders of fat and carbohydrate metabolism. Growth hormone causes increased release of free fatty acids from adipose tissue, leading to increased concentration of free fatty acids in body fluids. In addition, GH exerts multiple effects on carbohydrate metabolism, includ- ing decreased glucose uptake by tissues such as skeletal muscle and adipose tissue, increased glucose production by the liver, and increased insulin secretion. Each of these changes results in GH-induced insulin resistance (see Chapter 33). Impaired glucose tolerance occurs in as many as 50% to 70% of persons with acromegaly; overt diabetes mellitus subsequently can result. Other manifestations of acromegaly include exces- sive sweating with an unpleasant odor, oily skin, heat intolerance, moderate weight gain, muscle weakness and fatigue, menstrual irregularities, and decreased libido. Hypertension is relatively common. Sleep apnea syndrome is present in up to 90% of patients. The pathogenesis of the sleep apnea syndrome is obstructive in the majority of patients, due to increased pharyn- geal soft tissue accumulation. Paresthesias may develop because of nerve entrapment and compression caused by excess soft tissue and accumulation of subcutaneous fluid (especially carpal tunnel syndrome). Headaches are frequent. Temporal hemianopia (loss of vision for one half of the visual field) may occur as a result of the optic chiasm being impinged by a suprasellar growth of the tumor. The treatment goals for acromegaly focus on the correction of metabolic abnormalities and include nor- malization of the GH response to an oral glucose load; normalization of IGF-1 levels to age- and sex-matched control levels; removal or reduction of the tumor mass;

Somatotropic adenoma of pituitary

Acromegalic facies

Goiter

Cardiomegaly (hypertension)

Hyperostosis (thoracic vertebrae)

Barrel chest

Abnormal glucose tolerance secondary to insulin resistance

Male sexual dysfunction (or menstrual disorders in women)

Increased size (hands, feet)

Degenerative arthritis

Peripheral neuropathy

Thickened skin (hypertrophy of sebaceous and sweat glands)

FIGURE 32-4. Clinical manifestations of acromegaly.