Growth Hormone Deficiency

Growth hormone deficiency is a rare but treatable condition where the body doesn’t produce enough of an essential hormone needed for growth in children and healthy metabolism in adults.

Table of contents

• What is growth hormone deficiency?
• The role of growth hormone in the body
• Types of growth hormone deficiency
• How common is this condition?
• Signs and symptoms
• Causes and risk factors
• How is it diagnosed?
• Treatment options
• Outlook and prognosis

What is growth hormone deficiency?

GHD, pituitary dwarfism, hyposomatotropism

Growth hormone deficiency (GHD) is a rare condition in which your pituitary gland doesn’t release enough growth hormone (also called GH or somatotropin). The condition can affect infants, children, and adults. In children, the most noticeable result is being shorter than expected with normal body proportions.^[1]

• Pituitary gland
• Hypothalamus
• Brain
• Liver
• Bones
• Muscles

Hormones are chemicals that coordinate different functions in your body by carrying messages through your blood to your organs, muscles, and other tissues. Your pituitary gland is a small, pea-sized gland located at the base of your brain below your hypothalamus. The front part of this gland, called the anterior lobe, makes growth hormone along with seven other hormones.^[1]

People with growth hormone deficiency may also have hypopituitarism, meaning they have a deficiency in other pituitary hormones as well. These can include antidiuretic hormone, follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, and adrenocorticotrophic hormone.^[1]

The role of growth hormone in the body

Growth hormone acts on many parts of the body to promote growth in children. It’s essential for normal growth, muscle and bone strength, and the way body fat is distributed.^[1] Growth hormone also helps control glucose (sugar) and lipid (fat) levels in the body.^[2]

Growth hormone works through a growth factor called insulin-like growth factor 1 (IGF-1). Growth hormone stimulates the liver to produce IGF-1 and release it into the bloodstream. IGF-1 then works at multiple tissues, like bone and cartilage, to promote growth. In addition, growth hormone produces IGF-1 locally at tissues such as bone and cartilage.^[2]

Once the growth plates in your bones have fused, growth hormone no longer increases height, but your body still needs it. After you’ve finished growing, growth hormone helps to maintain normal body structure and metabolism, including helping to keep your blood glucose levels within a healthy range.^[1] In adults, growth hormone plays a role in healthy muscle, how the body collects fat (especially around the stomach area), cholesterol levels, and bone density. It is also needed for normal brain function.^[11]

Types of growth hormone deficiency

There are three main types of growth hormone deficiency:^[1]

• Congenital GHD: This type is present from birth due to a genetic mutation (change) or structural issues in the baby’s brain. Some children with congenital growth hormone deficiency are found to have mutations (errors in the genes) that involve the development of the pituitary gland or growth hormone production and action. Genes that may be involved include GH1, GHRHR, or BTK.^[3] In certain instances, congenital growth hormone deficiency can also be seen as part of a syndrome that may affect the development of the middle of the face.^[2]
• Acquired GHD: Growth hormone deficiency is considered acquired if its onset is later in life as a result of damage to your pituitary gland. Children and adults can have acquired growth hormone deficiency.^[1]
• Idiopathic GHD: In the medical world, “idiopathic” means there’s no known cause. In about a third of cases, no cause is apparent.^[3]

Growth hormone deficiency is also categorized by the age of onset. It has different symptoms and processes for diagnosis if you’re a child or adult when the condition begins.^[1]

How common is this condition?

Growth hormone deficiency is a rare condition. About 1 in 4,000 to 10,000 children have growth hormone deficiency.^[1] The genetic forms of this disease are estimated to affect about 1 in 7,000 people.^[3] Approximately 1 in every 10,000 people have adult-onset growth hormone deficiency.^[1] Most types occur equally in males and females, though males are more often diagnosed.^[3]

Signs and symptoms

The signs and symptoms of growth hormone deficiency vary based on what age you are at the onset of the condition.^[1]

In infants and children

Growth hormone deficiency in infants and children results in poor growth. The main sign of growth hormone deficiency in children is slow height growth each year after a child’s third birthday. This means they grow less than about 1.4 inches in height a year. If your child is less than the third percentile in height for a child of his age, that can be a red flag for growth hormone deficiency.^[4]

Growth rates vary considerably from child to child. But measured in height, average “normal” growth is often described as: 0-12 months, about 10 inches a year; 1-2 years, about 5 inches a year; 2-3 years, about 3½ inches a year; and 3 years to puberty, about 2 to 2½ inches a year.^[4]

Other symptoms of growth hormone deficiency in children and infants include:^[1]

• A younger-looking face than what’s expected for their age
• Impaired hair and nail growth
• Delayed tooth development
• A chubby body build
• A prominent forehead
• An underdeveloped bridge of the nose
• Delayed puberty or absence of puberty
• Slower muscular development

Severe prenatal deficiency of growth hormone, as occurs in congenital hypopituitarism, has little effect on fetal growth. However, prenatal and congenital deficiency can reduce the size of a male’s penis. Besides small penis size in males, additional consequences of severe deficiency in the first days of life can include low blood sugar and exaggerated jaundice.^[3]

Growth is not as severely affected in growth hormone deficiency as in untreated hypothyroidism, but growth at about half the usual velocity for age is typical. It tends to be accompanied by delayed physical maturation so that bone maturation and puberty may be several years delayed. When severe growth hormone deficiency is present from birth and never treated, adult heights can be as short as 48–65 inches (120–170 cm).^[3]

Growth hormone deficiency has no effect on a child’s intelligence.^[4]

In adults

A person who has too little adult growth hormone will have symptoms that include:^[11]

• A higher level of body fat, especially around the waist
• Decreased muscle mass and strength
• Less stamina and ability to exercise without taking a rest
• Reduced bone density and a tendency to have more bone fractures as they get older
• Anxiety and depression
• Decreased sexual function and interest
• Fatigue (lower-than-normal energy levels)
• Feelings of being isolated from other people
• Greater sensitivity to heat and cold
• Changes in cholesterol levels
• Trouble concentrating or lack of interest in doing things

Some research suggests that there are additional complications from growth hormone deficiency, including decreased bone mineral density, increased cardiovascular risk factors, and decreased energy level.^[4]

Causes and risk factors

Often, doctors don’t know why a child has growth hormone deficiency. When a cause is found, it’s often related to problems with the pituitary gland or with the brain around the pituitary gland.^[7]

A lack of growth hormone is usually caused by damage to the pituitary gland or the hypothalamus, a part of the brain that controls the pituitary gland.^[11]

Congenital causes

Congenital growth hormone deficiency can occur if there are mutations in genes for factors that are important in pituitary gland development, or in receptors and factors (including growth hormone) along the growth hormone pathway. To date, however, the cause of most of these cases is unknown.^[4]

Acquired causes

Growth hormone deficiency may develop during childhood or adulthood (acquired growth hormone deficiency) after any process that can damage the pituitary gland or the surrounding brain area. Causes of acquired growth hormone deficiency include:^[2]

• Brain tumor in the hypothalamus or pituitary
• Surgery to the pituitary gland or brain
• Severe brain injury or head trauma
• Radiation therapy for cancers, if the treatment field includes the hypothalamus and pituitary
• Diseases that infiltrate the hypothalamus or its connection to the pituitary gland, such as histiocytosis
• An autoimmune condition called lymphocytic hypophysitis
• Problems with the blood supply to the pituitary gland
• Chronic inflammation of the pituitary called hypophysitis, which can be seen after treatment with certain cancer medications

In all these cases, the individual may have additional deficiencies of other pituitary hormones.^[2]

How is it diagnosed?

Doctors check kids’ height during regular checkups. Over time, doctors can see how fast kids grow. If a child is growing much slower than most other kids the same age, this is called growth failure.^[7]

If your child has growth failure or short stature, even without any other signs or symptoms, your doctor might send you to a pediatric endocrinologist, who specializes in children’s growth and hormones. The endocrinologist will ask about your child’s growth and will do a careful exam.^[7]

If a person has had surgery, an injury, or a history of pituitary disorders, a doctor or endocrinologist (a specially trained physician who focuses on the health of hormone-secreting glands) will check for adult growth hormone deficiency.^[11]

Blood tests

The doctor will order some tests to look for growth hormone deficiency. There are no easy tests to measure growth hormone levels. Growth hormone is made in short bursts, mostly overnight. At other times, levels may be undetectable. This makes testing for it hard, because there is no way to know when the bursts will happen. So instead, doctors look at the levels of two proteins that have more stable levels and are markers of growth hormone function: IGF-I (insulin-like growth factor I) and IGFPB-3 (insulin-like growth factor binding protein). They may also check for any other causes of short stature that are not related to growth hormone.^[7]

Growth hormone in adults is absorbed quickly by tissues from the blood as it circulates. As a result of this, a blood test given to a healthy person will show low levels of growth hormone. Endocrinologists instead check the pituitary gland’s response when it is stimulated to produce growth hormone. These growth hormone stimulation tests are done in an outpatient setting and take about two to three hours. You will be asked not to eat before the test.^[11]

Other tests

Bone age X-rays are X-rays of one of your child’s hands and wrists. An expert compares them to X-rays of what’s typical for that age.^[7]

If there is a known disorder or problem with the pituitary gland, the doctor will probably order a magnetic resonance imaging (MRI) scan before any treatment is done. This allows the doctor to more accurately monitor how treatment is affecting the tumor.^[11]

Treatment options

Treatment is by growth hormone replacement using synthetic human growth hormone.^[3] Growth hormone is given as daily injections under the skin. When dosed appropriately, growth hormone replacement therapy is well tolerated, with a low incidence of side effects, and improves most of the alterations observed in growth hormone deficiency.^[20]

Treatment in children

With early detection and treatment, many children with growth hormone deficiency can reach a normal height.^[4] Growth hormone replacement therapy helps with bone growth, affects how well the heart and blood vessels work, helps the body use fat and make muscle, strengthens bones, and supports overall health throughout life.^[2]

Treatment in adults

Once adult growth hormone deficiency has been confirmed, treatment improves most of the alterations observed in growth hormone deficiency. Beneficial effects on body composition (muscle and fat distribution), exercise capacity, bone density, cholesterol levels, and quality of life have been demonstrated.^[20] However, beneficial effects on mortality, cardiovascular events, and fracture rates remain to be conclusively demonstrated.^[20]

Side effects

The potential of growth hormone to act as a growth promoter has resulted in concern over the possibility of increased new tumors or recurrence of pre-existing malignancies in individuals treated with growth hormone. Though studies of adults who received growth hormone replacement therapy in childhood have produced conflicting reports in this regard, long-term surveillance of adult growth hormone replacement therapy has not demonstrated increased cancer risk or mortality.^[20]

Outlook and prognosis

For children

With early detection and treatment, many children with growth hormone deficiency can reach a normal height.^[4] Growth is not as severely affected in growth hormone deficiency as in untreated hypothyroidism, but growth at about half the usual velocity for age is typical before treatment. When severe growth hormone deficiency is present from birth and never treated, adult heights can be as short as 48–65 inches (120–170 cm).^[3]

For adults

Deficiency of growth hormone in adults results in a syndrome characterized by decreased muscle mass and exercise capacity, increased visceral fat, impaired quality of life, unfavorable alterations in lipid profile and markers of cardiovascular risk, decrease in bone mass and integrity, and increased mortality.^[20] When dosed appropriately, growth hormone replacement therapy improves most of these alterations, although beneficial effects on mortality, cardiovascular events, and fracture rates remain to be conclusively demonstrated.^[20]