Growth Hormone Therapy: Who’s Going to Benefit From It?

It is commonly believed that only children can have growth hormone deficiency (GHD). But people can have GHD after they’ve stopped growing. Adult growth hormone deficiency (AGHD) occurs when the pituitary gland does not produce enough growth hormone (GH). In adults, GH is needed by the body to maintain lean muscle mass, healthy cholesterol levels, strong bones, and decreased body fat (especially around the waist).

What causes AGHD?

AGHD can be caused by damage to the pituitary gland or hypothalamus, which can result from:

  • pituitary tumors;
  • pituitary surgery;
  • radiation treatment (chemotherapy);
  • head injury;
  • congenital defects;
  • infection.

Damage to the pituitary gland or hypothalamus may impact the pituitary gland’s ability to produce enough GH.

What are the types of AGHD?

There are two types of AGHD:

  1. Childhood-onset AGHD — patients who were growth hormone deficient as children and continue to be so as adults.
  2. Adult-onset AGHD — patients with pituitary or hypothalamus disease, or who have had surgery, radiation treatment, or trauma and became growth hormone-deficient as adults.

In the United States, approximately 6,000 new cases of AGHD are diagnosed each year. AGHD is diagnosed by an endocrinologist or other qualified healthcare professional (HCP).

A person with AGHD can have a range of symptoms including:

  • increased body fat, especially in the abdomen;
  • reduced muscle mass;
  • fatigue;
  • decreased strength and exercise tolerance;
  • weight gain;
  • decreased spine bone mineral density.

You may be referred to an endocrinologist for an evaluation based on a physical exam, lab work, and your medical history.

The tests may include:

• a DEXA scan, which uses x-rays to scan your body and measure
bone mineral density as well as lean tissue;
• a physical exam;
• body mass index, a measure of body fat based on height and weight;
• insulin-like growth factor (IGF) levels and GH stimulation testing (stim testing).

A healthcare professional (HCP) will review the test results and discuss treatment options with you.

What is the growth hormone?

Growth hormone is produced by the somatotroph cells of the anterior pituitary. Its secretion is stimulated by growth hormone-releasing hormone and inhibited by somatostatin which is both produced by the hypothalamus.

Growth hormone secretion is pulsatile, and the amplitude of the pulses is greatest at night. Twenty-four-hour growth hormone secretion is maximal during puberty and declines gradually thereafter in both women and men.

Growth hormone acts by binding to receptors on liver cells and other cells. One growth hormone molecule binds to two receptor molecules on the target cell, initiating a cascade of events that results in the secretion of insulin-like growth factor I, which mediates many of the biological actions of growth hormone.

Some of the extracellular domain of the receptor is released into the serum, and approximately 50 percent of growth hormone in serum is bound to this part of the receptor. Despite its name, growth hormone has other actions in addition to promoting growth in children.

The goals of growth hormone therapy differ somewhat in adults and children. In adults, the goals are to restore normal body composition, improve muscle and cardiac function, normalize serum lipid concentrations, and improve the quality of life.

Growth Hormone Replacement Therapy in Adults

Growth hormone has been administered not only to adults of all ages with a growth hormone deficiency, but also to adults with catabolic illnesses, such as burn injuries, and to older adults with decreased growth hormone secretion.

Causes of Growth Hormone Deficiency in Adults

Over 90 percent of adults with growth hormone deficiency have overt pituitary disease, which is usually caused by a pituitary adenoma or by surgery or radiation therapy for a pituitary adenoma. Among patients with pituitary adenomas, those with a deficiency of one or more other pituitary hormones are also likely to have a growth hormone deficiency.

Diagnosis of Growth Hormone Deficiency

Growth hormone deficiency has been diagnosed primarily on the basis of subnormal growth hormone secretion in response to stimuli. In the United States, the Food and Drug Administration (FDA) has approved growth hormone therapy for adults only if there is evidence of hypothalamic or pituitary disease and a subnormal serum growth hormone response to one stimulation test.

The FDA has stipulated that the peak serum growth hormone concentration in response to hypoglycemia or another stimulus should be less than 5 μg per liter if measured by radioimmunoassay, or less than 2.5 μg per liter if measured by immunoradiometric assay.

The Growth Hormone Research Society has recommended that the diagnosis be based on a stimulated serum growth hormone value of fewer than 3 μg per liter during hypoglycemia, and this value is widely accepted as diagnostic in Europe.

Measurements of serum insulin-like growth factor I or insulin-like growth factor – binding protein 3, both of which are growth hormone-dependent, are not reliable indicators of growth hormone deficiency in adults.

Insulin-induced hypoglycemia is the preferred provocative stimulus because in patients with pituitary disease the response to this stimulus is more likely to be abnormal than are the responses to levodopa, arginine, growth hormone-releasing hormone, glucagon, and clonidine. However, the insulin test is contraindicated in patients with coronary artery disease, generalized debility, or seizure disorders.

The Dose of Growth Hormone

According to FDA recommendations, the starting dose of growth hormone in adults is 3 to 4 μg per kilogram given once daily by subcutaneous injection, with a maximal daily dose of 25 μg per kilogram for patients up to 35 years of age and 12.5 μg per kilogram for older patients.

These recommendations are based on clinical trials in which growth hormone was administered according to body weight. However, the Growth Hormone Research Society consensus conference has recommended a starting dose of 150 to 300 μg per day, regardless of body weight.

The goal of therapy is to restore the serum concentration of insulin-like growth factor I to the middle of the normal range for persons of the same sex and similar age. Initially, patients should be evaluated at one-to-two-month intervals by means of clinical observation and measurement of serum insulin-like growth factor I, and the dose of growth hormone should be adjusted as needed to maintain the target value for serum insulin-like growth factor I.

Other Uses of Growth Hormone in Adults

In 1996, growth hormone was approved by the FDA for the treatment of wasting or cachexia in patients with the acquired immunodeficiency syndrome (AIDS). This approval was based on evidence that growth hormone increased lean body mass and decreased fat mass in patients with AIDS.

The use of growth hormone has also been studied in small numbers of adults with other catabolic illnesses, including those associated with respiratory failure, burn injuries, recovery from surgery, congestive cardiomyopathy, liver transplantation, and renal failure.

The administration of growth hormone to elderly ambulatory patients resulted in changes in body composition similar to those that occur in adults with growth hormone deficiency. Short-term administration of growth hormone to increase strength and endurance in athletes is no more effective than training alone.

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