Abnormalities of Growth Hormone Secretion

Abnormalities of Growth Hormone Secretion

Panhypopituitarism. This term means decreased secretionof all the anterior pituitary hormones. The decrease in secretion may be congenital (present from birth), or it may occur suddenly or slowly at any time during life, most often resulting from a pituitary tumor that destroys the pituitary gland.

Dwarfism. Most instances of dwarfism result from gener-alized deficiency of anterior pituitary secretion (panhy-popituitarism) during childhood. In general, all the physical parts of the body develop in appropriate pro-portion to one another, but the rate of development is greatly decreased. A child who has reached the age of 10 years may have the bodily development of a child aged 4 to 5 years, and the same person at age 20 years may have the bodily development of a child aged 7 to 10 years.

A person with panhypopituitary dwarfism does not pass through puberty and never secretes sufficient quantities of gonadotropic hormones to develop adult sexual functions. In one third of such dwarfs, however, only growth hormone is deficient; these persons do mature sexually and occasionally reproduce. In one type of dwarfism (the African pygmy and the Lévi-Lorain dwarf), the rate of growth hormone secretion is normal or high, but there is a hereditary inability to form somatomedin C, which is a key step for the promotion of growth by growth hormone.

Treatment with Human Growth Hormone. Growth hor-mones from different species of animals are sufficiently different from one another that they will cause growth only in the one species or, at most, closely related species. For this reason, growth hormone prepared from lower animals (except, to some extent, from primates) is not effective in human beings. Therefore, the growth hormone of the human being is called human growthhormone to distinguish it from the others.

In the past, because growth hormone had to be pre-pared from human pituitary glands, it was difficult to obtain sufficient quantities to treat patients with growth hormone deficiency, except on an experimental basis. However, human growth hormone can now be synthe-sized by Escherichia coli bacteria as a result of success-ful application of recombinant DNA technology. Therefore, this hormone is now available in sufficient quantities for treatment purposes. Dwarfs who have pure growth hormone deficiency can be completely cured if treated early in life. Human growth hormone may prove to be beneficial in other metabolic disorders because of its widespread metabolic functions.

Panhypopituitarism in the Adult. Panhypopituitarism firstoccurring in adulthood frequently results from one of three common abnormalities. Two tumorous conditions, craniopharyngiomas or chromophobe tumors, may compress the pituitary gland until the functioning anterior pituitary cells are totally or almost totally destroyed. The third cause is thrombosis of the pituitary blood vessels. This abnormality occasionally occurs when a new mother develops circulatory shock after the birth of her baby.

The general effects of adult panhypopituitarism are (1) hypothyroidism, (2) depressed production of gluco-corticoids by the adrenal glands, and (3) suppressed secretion of the gonadotropic hormones so that sexual functions are lost. Thus, the picture is that of a lethargic person (from lack of thyroid hormones) who is gaining weight (because of lack of fat mobilization by growth, adrenocorticotropic, adrenocortical, and thyroid hor-mones) and has lost all sexual functions. Except for the abnormal sexual functions, the patient can usually be treated satisfactorily by administering adrenocortical and thyroid hormones.

Gigantism. Occasionally, the acidophilic, growthhormone–producing cells of the anterior pituitary gland become excessively active, and sometimes even aci-dophilic tumors occur in the gland. As a result, large quantities of growth hormone are produced. All body tissues grow rapidly, including the bones. If the condi-tion occurs before adolescence, before the epiphyses of the long bones have become fused with the shafts, height increases so that the person becomes a giant— up to 8 feet tall.

The giant ordinarily has hyperglycemia, and the beta cells of the islets of Langerhans in the pancreas are prone to degenerate because they become overactive owing to the hyperglycemia. Consequently, in about 10 per cent of giants, full-blown diabetes mellituseventu-ally develops.

In most giants, panhypopituitarism eventually devel-ops if they remain untreated, because the gigantism is usually caused by a tumor of the pituitary gland that grows until the gland itself is destroyed. This eventual general deficiency of pituitary hormones usually causes death in early adulthood. However, once gigantism is diagnosed, further effects can often be blocked by microsurgical removal of the tumor or by irradiation of the pituitary gland.

Acromegaly. If an acidophilic tumor occurs after adoles-cence—that is, after the epiphyses of the long bones have fused with the shafts—the person cannot grow taller, but the bones can become thicker and the soft tissues can continue to grow. This condition, shown in Figure 75–8, is known as acromegaly. Enlargement is especially marked in the bones of the hands and feet and in themembranous bones, including the cranium, nose, bosses on the forehead, supraorbital ridges, lower jawbone, and portions of the vertebrae, because their growth does not cease at adolescence. Consequently, the lower jaw protrudes forward, sometimes as much as half an inch, the forehead slants forward because of excess development of the supraorbital ridges, the nose increases to as much as twice normal size, the feet require size 14 or larger shoes, and the fingers become extremely thickened so that the hands are almost twice normal size. In addition to these effects, changes in the vertebrae ordinarily cause a hunched back, which is known clinically askyphosis. Finally, many soft tissue organs, such as the tongue, the liver, and especially the kidneys, become greatly enlarged.

Possible Role of Decreased Growth Hormone Secretion in Causing Changes Associated with Aging

In people who have lost the ability to secrete growth hormone, some features of the aging process accelerate. For instance, a 50-year-old person who has been without growth hormone for many years may have the appear-ance of a person aged 65. The aged appearance seems to result mainly from decreased protein deposition in most tissues of the body and increased fat deposition in its place. The physical and physiological effects are increased wrinkling of the skin, diminished rates of function of some of the organs, and diminished muscle mass and strength.

As one ages, the average plasma concentration of growth hormone in an otherwise normal person changes approximately as follows:

        Thus, it is highly possible that some of the normal aging effects result from diminished growth hormone secretion. In fact, multiple tests of growth hormone therapy in older people have demonstrated three important effects that suggest antiaging actions: (1) increased protein deposition in the body, especially in the muscles; (2) decreased fat deposits; and (3) a feeling of increased energy.