Porth's Essentials of Pathophysiology, 4e

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Disorders of Endocrine Control of Growth and Metabolism

C h a p t e r 3 2

The same pathology is responsible for dwarfism of the African pygmies. IGF-1 is now produced by recombi- nant DNA technology. Since GH produces its effects by promoting IGF-1 secretion, IGF-1 is an effective replace- ment therapy for Laron dwarfism, mimicking most of the effects ascribed to GH. 9 Growth Hormone Deficiency in Adults There are two categories of GH deficiency in adults: GH deficiency that was present in childhood, and GH deficiency that developed during adulthood, mainly as the result of hypopituitarism resulting from a pituitary tumor or its treatment. 15 Growth hormone levels also can decline with aging (described as the somatopause ), and there has been interest in the effects of declining GH levels in the elderly. 16 Growth hormone replacement obviously is important in the growing child; however, the role in adults (especially for the somatopause) is being assessed. The clinical features of adult GH deficiency include changes in body composition, such as a decrease in lean body mass and an increase in fat mass, hyperlipidemia, decreased bone mineral density, and reduced exercise capacity, and diminished sense of well-being. Growth hormone deficiency is associated with a cluster of cardio- vascular risk factors including central adiposity (associ- ated with increased visceral fat), insulin resistance, and dyslipidemia. 15 These features also are associated with the metabolic syndrome (see Chapter 33). In addition to these so-called traditional cardiovascular risk fac- tors, nontraditional cardiovascular risk factors (e.g., C-reactive protein [CRP], which is a marker of the inflammatory pathway) are also elevated. 17 Several recombinant human GH preparations have been approved for treatment of adults with diagnosed GH deficiency. The most common side effects of GH treatment in adults with hypopituitarism are periph- eral edema, arthralgias and myalgias, carpal tunnel syndrome, paresthesias, and decreased glucose tol- erance. 15 Side effects appear to be more common in people who are older, have greater weight, and are overtreated as determined by high serum IGF-1 levels during therapy. Just as there are children who are short for their age and gender, there also are children who are tall for their age and gender. 9,18 Normal variants of tall stature include genetic tall stature and constitutional tall stature. Children with exceptionally tall parents tend to be taller than children with shorter parents. The term constitu- tional tall stature is used to describe a child who is taller than his or her peers and is growing at a velocity that is within the normal range for bone age. Other causes of tall stature are genetic or chromosomal disorders such as Marfan syndrome or XYY syndrome (see Chapter 6). Endocrine causes of tall stature include sexual precocity because of early onset of estrogen and androgen secre- tion and excessive GH.  Tall Stature and Growth Hormone Excess in Children

Exceptionally tall children (i.e., genetic tall stat- ure and constitutional tall stature) can be treated with sex hormones—estrogens in girls and testosterone in boys—to effect early epiphyseal closure. Such treatment is undertaken only after full consideration of the risks involved. To be effective, such treatment must be insti- tuted 3 to 4 years before expected epiphyseal fusion. 9,18 Growth hormone excess occurring before puberty and the fusion of the epiphyses of the long bones results in gigantism 19 (Fig. 32-3). It usually develops when exces- sive secretion of GH by somatotrope adenomas leads to high levels of IGF-1, the mediator of excessive skeletal growth. Fortunately, the condition is rare because of early recognition and treatment of the adenoma. Growth Hormone Excess in Adults When GH excess occurs in adulthood or after the epiph- yses of the long bones have fused, it causes a condition called acromegaly (from the Greek words acros , mean- ing “end portion,” and megalos , meaning “large”),

FIGURE 32-3. Primary gigantism. A 22-year-old man with gigantism due to excess growth hormone is shown to the left of his identical twin. (From Gagel RF, McCutcheon IE. Images in clinical medicine. N Engl J Med. 1999;340:524. Copyright © 2003. Massachusetts Medical Society.)