What is GHD?
What parts of the body are affected?
What are the symptoms of GHD?
Causes and risk factors of GHD
Diagnosis
Treatment
Human growth hormone replacement therapy
Glossary

What Is GHD?

Growth hormone deficiency (GHD) is a disorder in which the pituitary gland fails to produce or does not produce enough growth hormone, which is required to achieve normal growth. Deficiencies in growth hormone (GH) may affect both children and adults and can occur at any age. In children, GH is required to achieve normal growth. In adults of all ages, GH regulates the proper amounts of body fat, muscle, and bone. Adults with GHD either had GHD as a child or have a history of pituitary tumors or treatment by surgery or radiation.

What Parts of the Body Are Affected?

Musculoskeletal system: GH is important for building up bone strength. In children, GHD causes growth retardation, resulting in shorter stature. In adults with GHD, osteoporosis may develop. There is also a significant reduction in muscle size, strength, and performance in adults.

Cardiovascular system: Adult-acquired GHD patients have a higher risk of heart disease. Increased abdominal fat and high levels of cholesterol in the blood are risk factors for developing high blood pressure and heart disease.

Reproductive system: In children, GHD results in delayed puberty.

What Are The Symptoms of GHD?

The symptoms of GHD vary depending on whether the onset is in childhood or adulthood. In childhood onset GHD, symptoms may not be apparent at first; however, by 6 months of age growth retardation is obvious. Children with GHD typically look younger than other children of the same age and will be well below normal on both height and weight growth curves. Additionally, delayed tooth eruption, delayed puberty and significant increases of fat around the trunk of children with GHD may be observed. Anatomically-proportioned short stature and low-growth velocity in relation to age are also physical characteristics associated with childhood-onset GHD.

GHD in adults can cause an increase in fat tissue and a decrease in muscle mass. Other symptoms that may occur include the reduction of cardiac output and physical weakness that manifests itself as a form of lethargy and decreased sense of well being that is often attributed to old age.

Causes and Risk Factors of GHD

In healthy children and adults, the pituitary gland produces many necessary hormones for proper body functioning, including growth hormone. Consequently, when GH is absent or produced in inadequate levels, it is typically a result of a problem with the pituitary gland. Most commonly, patients with GHD may be born with the condition or acquire it well after birth as a result of either an abnormal pituitary gland or as a result of another disease or syndrome. Children who are born with GHD will continue to be affected into adulthood, though they may not experience symptoms after puberty. GHD is more prevalent in males than in females.

Adults may develop GHD during adolescence or in adulthood, often as a result of a disease such as cancer or an infection of the central nervous system that would cause the pituitary gland or hypothalamus to malfunction. In most cases, GHD is frequently a result of a pituitary disease, usually due to a pituitary tumor, surgery, or radiation therapy for the tumor. Other causes include trauma, infiltrative diseases such as sarcoidosis, tuberculosis, histiocytosis X, hemochromatosis, and lymphocytic hypophysitis

Other possible causes for hormone deficiency are from the insufficient release of GH stimulatory hormone from the hypothalamus, a decrease in insulin-like growth factor 1 (IGF-1), or defective receptors receiving the hormone in the body's cells. Defective receptor recognition of growth hormones is usually genetic. In these cases, high levels of GH are produced by the pituitary gland and circulate ineffectively through the blood. This can occur in individuals who do not have a family history of GHD.

Diagnosis

The following tests are conducted on both children and adults to accurately diagnose the presence of GHD

GH stimulation test. This test is a measure of plasma level of hGH after administrating the amino acid arginine and/or GH-releasing hormone (GHRH). The test is conducted in order to measure the ability of the pituitary to secrete GH in response to an appropriate stimulus. An IV is used to draw blood from a vein. Depending on the physicians' preference, either an arginine or GH-releasing hormone will be infused into the body. A normal peak value is at least 10 ng/mL; 5-10 ng/mL is indeterminate; 5 ng/mL is subnormal. A normal value rules out hGH deficiency. Failure of this test to raise hGH levels indicates malfunction in the release of GH from the pituitary gland.

Blood tests. Blood tests that reflect pituitary function, such as T4, Thyroid Stimulating Hormone (TSH), cortisol, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), and testosterone (in men) may be ordered to diagnose GHD. These tests are usually done prior to GH testing to make sure that they are normal and/or controlled with medication before GH testing is done.

• IGF-1 (Insulin-like growth factor-1) is a specific blood test often measured once during GH provocation testing and may be used by itself or with GH as a monitoring tool. Produced in the liver, IGF-1 mirrors GH excesses and deficiencies but its level is stable throughout the day - making it a useful indicator of average GH levels.

In children, testing for GHD occurs when other possibilities of short stature have been ruled out. To diagnose GHD, previous growth measurements are evaluated, a bone age (x-ray of a child's hand and wrist) is taken, and blood samples are assessed for possible thyroid hormone deficiencies. GH stimulation testing is usually conducted if the child has displayed symptoms of GHD to confirm the more subjective diagnosis criteria. Importantly, when GHD is diagnosed, it is critical to make sure that the other pituitary hormones are evaluated.

In adults, a GH stimulation test is necessary to document GH deficiency. The insulin tolerance test (ITT), arginine test, and GH-releasing hormone (GHRH) test are some examples of commonly used stimulation tests.

Treatment

The main goal for treating GHD in children is to restore hormones to a normal level and thereby enable the child to grow to a normal height. In adults, goals of treatment are to relieve fatigue and muscle weakness and also reverse metabolic abnormalities such as increased insulin production.

Surgery. If a pituitary tumor is the cause of hormone deficiencies, surgery may be the best option. Pituitary tumors and some of the abnormalities present at birth may require surgical removal of the tumor. If surgery cannot be accomplished safely, then radiation treatment may be considered.

Self care. GHD can result in a lack of energy and strength that can be regulated through healthy lifestyle practices. Patients are therefore encouraged to eat a balanced diet, get regular exercise, and plenty of rest.

Human Growth Hormone Replacement Therapy

In children, injections of recombinant human growth hormone (rhGH) are administered once GHD has been diagnosed. Most GHD patients receive daily injections to correct the low GH levels that exist in the body. For adults, individualized therapy is critical to reduce adverse events from GH. Factors such as age, sex, and estrogen levels significantly impact appropriate dosing regimens. Initial GH replacement should begin with low doses, and then be increased depending on patient response and IGF-1 levels.

The frequency of rhGH injections is believed to significantly impact quality of life for children and adults. It is estimated that a standard course of pediatric treatment for hGH lasts approximately 6 years, with more than 1,800 injections being administered over that period of time.

Outside of growth hormone deficiency, rhGH is also currently used to treat several other disorders, such as Turner syndrome, Prader Willi Syndrome, and short bowel syndrome.

• Turner syndrome is a genetic disorder affecting the DNA in women where there is a complete or partial absence of one of the two X chromosomes (normal female genetic makeup consists of 2 X chromosomes). Characteristics of this syndrome include short stature as well as endocrine and gynecological abnormalities. Treatment with rhGH is necessary to increase growth.
• Prader Willi Syndrome is a genetic disorder that affects children of both sexes. In this disorder, chromosome 15 is completely deleted as a result of a rare genetic anomaly. The resulting symptoms include short stature, poor muscle tone, and several other physical features. Food craving and insatiable appetite are also symptomatic of this syndrome, resulting in obesity. Treatment with rhGH accelerates growth and can decrease percent of body fat.
• Short bowel syndrome is a condition affecting people who have had half or more of their small intestine removed in order to treat Crohn's disease and less common conditions. Once the small intestine is removed, patients will experience dehydration and malnutrition. Patients are treated with rhGH to enhance nutritional absorption, body composition also improves.

Glossary

Abdominal fat
Fat tissue distributed in the midsection of the body that increases health risks

Adverse events
Unwanted experiences that occur during drug therapy not related to the drug

Arginine
A naturally occurring amino acid that is synthesized in the liver

Cholesterol
Fatty substance found in animal tissue and fat

Crohn's disease
Disease affecting the small intestine and colon

Chromosomes
Thread-like strands of DNA and protein carrying genes

DNA
Material inside cells that carries genetic information

Estrogen
Female hormone that stimulates development of secondary sex characteristics

Follicle-stimulating hormone
Hormone secreted from the pituitary gland that stimulates growth of eggs in females and sperm in males; works with luteinizing hormone

GH-releasing hormone
Hormone suspected in controlling body responses to growth hormone secretion

Growth hormones
Hormone secreted by the pituitary gland that controls growth (height) in children and adolescents

Hemochromatosis
Disorder that causes increased absorption of iron in the body and may reach toxic levels

High blood pressure
Increased pressure of the blood as it circulates through the body, leading to heart and kidney problems

Histiocytosis X
Abnormal increase of organ tissues, such as in the spleen, liver, lungs, bone marrow, and lymph nodes

Hypothalamus
Small structure at the base of the brain that regulates body functions, such as appetite and temperature

Insulin-like growth factor-1 (IGF-1)
Protein regulated by growth hormone that causes growth in the body

Insulin tolerance test
The gold standard for the evaluation of growth hormone reserves in the body

Liver
Organ that functions in the metabolism of protein, carbohydrate, and fat

Lymphocytic hypophysitis
Inflammation of the pituitary gland as a result of growth hormone deficiency

Luteinizing hormone
Hormone secreted from the pituitary gland that stimulates growth of eggs in females and sperm in males; works with follicle-stimulating hormone

Osteoporosis
Decrease in bone mass and density resulting in an increased risk of fracture

Pituitary gland
Gland located at the base of the brain that secretes hormones and regulates and controls other hormone-secreting glands

Pituitary disease
Any disease that affects the pituitary gland, and in turn affects hormone secretion

Radiation therapy
The use of ionizing radiation or radioactive substances to treat diseases

Receptors
Molecules located on the surfaces of cells that respond to hormones or other molecules of the body

Sarcoidosis
Inflammation of the lymph nodes and organs

Small intestine
Part of the digestive system where most of digestion occurs

T4
A blood test that helps determine thyroid function

Testosterone
Male hormone that stimulates development of secondary sex characteristics

Thyroid-stimulating hormone
Hormone formed in the pituitary gland that regulates the activity of the thyroid gland

Tuberculosis
Bacterial infection that mainly affects the lungs