Biology of Disease

an inactive form called preprogrowth hormone that is hydrolyzed in several

enzyme-catalyzed reactions to give active GH prior to its secretion. A number

of factors, such as sleep, amino acids, exercise and stress stimulate GHRH

release from the hypothalamus and that, in turn, stimulates GH secretion.

Hyperglycemia stimulates the secretion of somatostatin from the hypo-

thalamus and this inhibits the secretion of GH. Increasing concentrations of

serum GH and IGF-I exert a negative feedback effect that prevents further

release of GH (Figure 7.14 (B)). The rate of adult secretion varies but is

generally about 1.4 mg daily and occurs in pulses with the largest amounts

being released during sleep.

The clinical features resulting from an excess or deficiency of GH depend on

the age of the person. A deficiency during childhood leads to a stunted growth

called dwarfism (Figure 7.15 (A)) and therefore requires early detection.

However, GH deficiency is a rare cause of dwarfism and other causes, for

example thyroid deficiency or inadequate nutrition, need to be excluded first.

The commonest causes of GH deficiency are nonendocrine tumors that affect

the pituitary gland or hypothalamus. Growth hormone deficiency may also be

a consequence of generalized pituitary disease or a congenital defect leading

to a deficient production of GHRH. Whatever the cause, the major clinical

feature is stunted growth, well below that expected for a child of comparable

age, with a short height, immature face and skeleton as revealed by radiological

investigations. Clinical signs of other anterior pituitary hormone deficiencies

may be evident.

The most common cause of excessive GH release is a GH secreting pituitary

tumor or adenoma (Chapter 17). Although these are benign, they are not

subject to normal control and continually release large amounts of GH. The

X]VeiZg,/ DISORDERS OF THE ENDOCRINE SYSTEM

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Figure 7.15 Photographs showing one of the authors beside (A) a dwarf

and (B) a person with combined gigantism and acromegaly.