Disorders Treated With Genentech's Growth Hormone Products Genentech's recombinant growth hormone portfolio of products is available for the treatment of five disease indications. Below are descriptions of the five diseases.

Patients being treated with growth hormone (GH) should be informed of the potential benefits and risks associated with growth hormone therapy. Please see the full prescribing information for additional safety information.

Pediatric Growth Hormone Deficiency In children, growth hormone (GH) plays a critical role in stimulating body growth and development. Growth hormone travels from the pituitary gland to the liver to generate IGF-I, which promotes growth. Growth hormone also acts on the cartilage and causes it to grow and turn into bone. Moreover, GH helps build muscle and break down fats.

In some children, however, the pituitary gland fails to produce any GH, or secretes inadequate amounts of the hormone. These children have a condition known as pediatric growth hormone deficiency (PGHD).

What causes PGHD? PGHD results when the production of GH is disrupted, sometimes from damage to the hormone-secreting pituitary gland or from damage to the hypothalamus, which controls the pituitary. This damage can be genetic, developmental, or acquired secondarily to disorders such as a tumor, trauma, irradiation or infection. Although PGHD is uncommon, affecting only approximately 20,000 children nationwide, it may occur at any time during infancy or childhood.

What are the symptoms of PGHD? A major sign of PGHD is a marked slowing of growth, usually fewer than two inches a year. These children often "fall off" the growth curve when plotted on a growth chart at their annual physical exam. Some children also may be overweight for their height and/or have problems with low blood sugar. However, unlike many other conditions involving short stature, most children with GH deficiency are short but appear quite normal otherwise, with typical body proportions, such as arm and leg length.

How is PGHD diagnosed? Doctors diagnose PGHD through special blood tests that detect GH in the blood. If the tests reveal a deficiency in GH, doctors may prescribe regular injections of GH until the child reaches an adult height in the normal range or until the growing ends of the bones fuse — usually at the end of puberty — preventing further growth. At that time, the patient will need to be re-tested to determine if GHD is persisting.

Adult Growth Hormone Deficiency Even after growth has stopped, a healthy body will continue to produce GH. Medical research indicates that adults need adequate levels of this hormone to maintain healthy body composition and metabolism. GH produced by the body plays an important role in maintaining the ratio of body fat to lean mass, "bad" to "good" cholesterol levels, and proper bone-mineral density.

What is AGHD? As in pediatric GH deficiency, adult GH deficiency (AGHD) occurs when the pituitary gland, which controls the level of many hormones in the body, does not secrete enough GH. When this happens, it may be necessary to replace the growth hormone that the gland is not providing.

In the United States, approximately three in 10,000 adults suffer from GH deficiency. Generally, AGHD patients can be divided into two groups: those who were GH-deficient as children and continue to be so as adults, and those who develop GH deficiency as adults.

What is childhood-onset AGHD? When adult growth hormone deficiency is the continuation of a disorder that began in infancy or childhood, the condition is known as childhood-onset AGHD. Although some children with GH deficiency eventually may gain the ability to secrete a sufficient amount of GH with time, scientific evidence suggests that many adults who were GH-deficient as children and continue to be as adults may need GH therapy into adulthood in order to have enough GH to meet metabolic demands as adults.

What is adult-onset AGHD? Some people with adult growth hormone deficiency were not GH-deficient as children. These people are said to have adult-onset GH deficiency.

The usual cause of adult-onset GH deficiency is hypopituitarism, a condition in which the pituitary gland does not produce one or more of its hormones or does not produce enough of these hormones. This condition may occur because of a loss of function of the pituitary gland or hypothalamus (a part of the brain that contains hormones that control the pituitary gland). When adult-onset GH deficiency is caused by hypopituitarism, the pituitary gland does not produce enough growth hormone.

What causes hypopituitarism? Tumors can injure the pituitary gland or hypothalamus, preventing it from functioning properly. Radiation, surgery, infections (e.g., meningitis), or various other conditions can also cause damage to the pituitary gland or hypothalamus, resulting in hypopituitarism. Hypopituitarism can also cause pediatric growth hormone deficiency.

What is panhypopituitarism? The pituitary gland produces several types of hormones in addition to growth hormone. When there is little or no production of all of the pituitary hormones, the condition is called panhypopituitarism. Panhypopituitarism can also cause pediatric growth hormone deficiency.

What are the symptoms of AGHD? Signs and symptoms of adult GH deficiency may include:

• Increased body fat, especially around the abdomen
• Decreased muscle mass, which can result in reduced strength or physical performance
• Lower bone-mineral content, which increases the likelihood of fractures
• Predisposition to atherosclerosis (hardening of the arteries)
• Feelings of depressed mood, emotional instability, social isolation, and/or anxiety

Growth Failure Due to Chronic Renal Insufficiency The kidneys have a number of important functions, such as the removal of wastes and extra fluid from the body. Kidneys also regulate the amounts of nutrients, such as calcium and vitamin D, which are involved in the growth process.

What is CRI? In chronic renal insufficiency (CRI), the kidneys slowly lose their ability to function normally. This means that they lose the ability to excrete wastes, concentrate urine, and conserve salt and water. The kidneys' role in the growth process is also compromised, which can lead to growth failure. Approximately 3,000 children in the United States suffer from CRI.

How does CRI impact growth? CRI can impact growth because, with this condition, the kidney does not produce enough vitamin D and, as a result, bones do not grow normally. Additionally, waste indirectly in the blood resulting from CRI disrupts the way growth hormone functions. Consequently, the growth process is interrupted. GH treatment is used to improve this growth process.

What are the symptoms of CRI? Often, the signs and symptoms of CRI aren't evident until after serious damage has occurred. As CRI progresses, the kidneys may fail to the point where either kidney dialysis (a medical procedure used to remove waste products from the bloodstream) or kidney transplantation becomes necessary to keep the patient alive. Although a kidney transplant can return a child's growth process to normal, by that time, growth potential may already have been lost. That is why GH therapy prior to kidney transplantation is an important component of the treatment strategy for CRI.

Short Stature Associated with Turner Syndrome Turner syndrome (TS), a condition that affects girls, occurs in approximately one in 2,500 live female births worldwide. The hallmarks of Turner syndrome are short stature and underdeveloped ovaries. Although there is no cure for Turner syndrome, its symptoms may be minimized with the proper treatment.

What causes TS? Turner syndrome results from a chromosomal disorder present since birth. Normally, girls have two X chromosomes (the sex chromosomes), but girls with Turner syndrome do not. They are missing part or all of one of the X chromosomes.

As a result, girls with this condition may exhibit certain physical abnormalities, particularly short stature. Other physical characteristics of individuals with Turner syndrome can include a short, thick neck; arms that turn out slightly at the elbows; and a low hairline at the back of the head.

Idiopathic Short Stature Idiopathic short stature (ISS) is defined by a height of SDS < -2.25 and is associated with growth rates unlikely to permit attainment of adult height in the normal range in pediatric patients whose epiphyses are not closed and for whom diagnostic evaluation excludes other causes associated with short stature that should be observed or treated by other means.